User:Y-S.Ko/free study/Medical

internal medicine

Harrison Internal Meidicine 21st edition

part 1 the profession of medicine.
- 1 the practice of medicine
  - enduring values of the medical profession.
  - the science and art of medicine.
  - clinical skills.
    - history-taking
    - physical examination
    - diagnostic studies
  - management of patient care
    - team-based care.
    - the dichotomy of inpatient and outpatient internal medicine.
    - mitigating the stress of acute illness
    - medical decision-making
    - practice guidelines.
    - precision medicine
    - evaluation of outcomes .
    - errors in the delivery of health care.
    - electronic medical records .
  - the patient–physician relationship
    - informed consent
    - approach to grave prognoses and death.
    - maintaining humanism and professionalism
  - expanding frontiers in medical practice.
    - the era of “omics” .
    - the globalization of medicine.
    - medicine on the internet
    - public expectations and accountability
    - medical ethics and new technologies.
    - learning medicine.
    - the physician as perpetual student .
    - the physician as citizen .
    - research, teaching, and the practice of medicine
  - further reading.
- 2 promoting good health.
  - goals and approaches to prevention
  - health promotion
  - prioritizing prevention strategies
  - prevention and health promotion across the life course
    - periodic health evaluations.
    - healthy behaviors and lifestyles
    - healthy eating patterns.
    - physical activity.
    - sleep hygiene.
    - weight management.
    - tobacco cessation.
  - vaccination.
  - mental health and addiction.
    - alcohol and opioids.
  - accidents and suicide.
  - approach to the patient.
  - further reading.
- 3 vaccine opposition and hesitancy
  - vaccine coverage and outbreaks
    - north america.
    - outside north america.
  - factors in vaccine hesitancy
  - social and cultural trends
    - individualized health care
    - parenting trends
    - traditional media.
    - the internet and social media.
  - approach to the patient.
  - other considerations during clinical encounters.
    - missed opportunities
    - adverse events following vaccination
    - addressing inequities in vaccine access.
    - further communication with patients who refuse vaccines.
  - conclusion
  - focus: covid-19 vaccine hesitancy.
    - past experience with new vaccines.
    - specific concerns about covid-19 vaccines.
    - social and cultural trends
    - tips for discussion of covid-19 vaccines
  - further reading.
- 4 decision-making in clinical medicine
  - brief introduction to clinical reasoning
    - clinical expertise
    - intuitive versus analytic reasoning.
  - diagnostic versus therapeutic decision-making.
  - nonclinical influences on clinical decision-making
    - factors related to practice style.
    - practice setting factors
    - payment systems.
  - interpretation of diagnostic tests
  - diagnostic testing: measures of test accuracy.
  - measures of disease probability and bayes’ rule.
  - applications to diagnostic testing in cad.
  - statistical prediction models.
  - formal decision support tools.
    - decision support systems
    - decision analysis.
  - diagnosis as an element of quality of care
  - evidence-based medicine.
    - sources of evidence: clinical trials and registries.
    - meta-analysis.
    - clinical practice guidelines
  - conclusions.
  - further reading.
- 5 precision medicine and clinical care
  - disease nosology and precision medicine.
  - requirements for precision medicine.
  - examples of precision medicine applications.
  - the future of precision medicine
  - further reading.
- 6 screening and prevention of disease.
  - basic principles of screening.
  - methods of measuring health benefits
  - assessing the harms of screeningand prevention
  - weighing the benefits and harms.
  - counseling on healthy behaviors.
  - implementing disease prevention and screening.
  - further reading.
- 7 global diversity of health system financing and delivery
  - financing individual patient careservices in developed countries
    - total health expenditures.
    - tax-funded systems
    - social insurance–funded systems.
    - the united states.
  - delivering individual patient careservices in developed countries.
    - hospital services.
    - primary care services.
    - access to elective specialist care
    - long-term care services.
  - pharmaceuticals.
  - governance and regulation.
  - future challenges.
  - financing and providing health services in developing countries.
  - further reading.
- 8 the safety and quality of health care.
  - safety in health care.
    - safety theory and systems theory
    - factors that increase the likelihood of errors
    - the frequency of adverse events in health care
    - prevention strategies.
    - the national safety picture.
    - measurement of safety.
    - conclusions about safety
  - quality in health care
    - quality theory
    - factors relating to quality.
    - data about the current state of quality.
    - strategies for improving quality and performance
    - national state of quality measurement.
    - public reporting
    - pay-for-performance.
  - conclusions.
  - further reading.
- 9 diagnosis: reducing errors and improving quality
  - emergence of diagnosis error as an important patient safety issue.
  - new ways to think about diagnosis and diagnostic errors.
  - uncertainty in diagnosis
  - don’t miss diagnoses and red flags
  - diagnostic pitfalls.
  - diagnosis safety culture
  - health information technology and the future of diagnosis.
  - diagnosis of diagnosis errors and safety: practical conclusions.
  - further reading.
- 10 racial and ethnic disparities in health care.
  - nature and extent of disparities
  - root causes of disparities
    - race, racism, and health
  - social determinantsof health
    - health system factors.
    - provider-level factors
    - patient-level factors.
  - key recommendations to address racial/ethnic disparities in health care.
    - health system interventions.
    - provider interventions
    - patient interventions.
    - general recommendations.
  - implications for clinical practice
  - conclusion
  - further reading.
- 11 ethical issues in clinical medicine
  - approaches to ethical problems
    - ethical principles
      - respecting patients.
      - beneficence or acting in patients’ best interests.
      - acting justly.
    - virtue ethics.
    - professional oaths and codes
    - personal values.
  - ethically complex professionalissues for physicians.
    - claims of conscience
    - physician as gatekeeper.
    - moral distress
    - occupational risks and burdens
    - use of social media and patient portals.
  - conflicts of interest.
    - financial incentives
    - relationships with pharmaceutical companies.
    - learning clinical skills
    - response to medical errors
    - physician impairment
  - ethical issues in clinical research.
  - emerging technologies.
  - global considerations.
    - international research
    - international clinical experiences
  - conclusion
  - further reading.
- 12 palliative and end-of-life care
  - epidemiology
    - causes of death.
    - site of death.
  - hospice and the palliative care framework.
    - assessment and care planning
      - comprehensive assessment
      - communication.
      - continuous goal assessment
      - advance care planning.
  - interventions.
    - physical symptoms and their management
      - pain .
      - constipation
      - untitled
      - dyspnea.
      - fatigue.
    - palliative sedation.
  - psychological symptoms and their management.
    - depression
    - delirium
    - insomnia
  - social needs and their management.
    - financial burdens.
    - relationships.
    - family caregivers.
  - existential needs and their management
  - managing the last stages
    - palliative care services: how and where.
    - withdrawing and withholding life-sustaining treatment.
    - futile care.
    - euthanasia and physician-assisted suicide.
    - care during the last hours
  - further reading.
part 2 cardinal manifestations and presentation of diseases.
- section 1 pain
  - 13 pain: pathophysiology and management.
    - the pain sensory system.
      - peripheral mechanisms.
        the primary afferent nociceptor.
        
        sensitization
        
        nociceptor-induced inflammation.
      - central mechanisms
        the spinal cord and referred pain.
        
        ascending pathways for pain.
      - pain modulation.
      - neuropathic pain
        sympathetically maintained pain
    - treatment: acute pain.
      - aspirin, acetaminophen, and nonsteroidalanti-inflammatory agents (Nsaids).
      - opioid analgesics.
    - chronic pain
      - treatment: chronic pain.
        antidepressant medications
        
        anticonvulsants and antiarrhythmics.
        
        cannabinoids
        
        chronic opioid medication.
        
        treatment of neuropathic pain.
    - further reading.
  - 14 chest discomfort.
    - epidemiology and natural history
    - causes of chest discomfort
      - myocardial ischemia/injury
        characteristics of ischemic chest discomfort
        
        mechanisms of cardiac pain
      - other cardiopulmonary causes
        pericardial and other myocardial diseases.
        
        diseases of the aorta
        
        pulmonary conditions
        
        other pulmonary parenchymal, pleural, or vascular disease.
      - noncardiopulmonary causes.
        gastrointestinal conditions.
        
        musculoskeletal and other causes
        
        emotional and psychiatric conditions
    - approach to the patient: chest discomfort.
      - history.
      - physical examination
      - electrocardiography.
      - chest radiography.
      - cardiac biomarkers
      - integrative decision-aids.
      - coronary and myocardial stress imaging
      - exercise electrocardiography
      - other noninvasive studies.
    - critical pathways for acute chest discomfort
    - outpatient evaluation of chest discomfort.
    - further reading.
  - 15 abdominal pain.
    - some mechanisms of pain originating in the abdomen
      - inflammation of the parietal peritoneum.
      - obstruction of hollow viscera.
      - vascular disturbances.
      - abdominal wall
    - referred pain in abdominal disease
    - metabolic abdominal crises
    - immunocompromise
    - neurogenic causes.
    - approach to the patient: abdominal pain.
    - further reading.
  - 16 headache.
    - general principles
    - anatomy and physiology of headache
    - clinical evaluation of acute, new-onset headache
    - secondary headache
      - meningitis
      - intracranial hemorrhage.
      - brain tumor.
      - temporal arteritis
      - glaucoma
    - primary headache disorders
      - chronic daily or near-daily headache
      - approach to the patient: chronic daily headache.
        management of medically intractable disabling primary headache
        
        medication-related and medication-overuse headache
        
        new daily persistent headache.
    - primary care and headachemanagement.
  - 17 back and neck pain.
    - anatomy of the spine
    - approach to the patient: back pain
      - types of back pain
      - examination.
      - laboratory, imaging, and emg studies
    - causes of back pain.
      - lumbar disk disease.
      - degenerative conditions.
      - spondylosis and spondylolisthesis.
      - neoplasms.
      - infections/inflammation.
      - trauma
        sprains and strains.
        
        traumatic vertebral fractures.
      - metabolic causes
        osteoporosis and osteosclerosis.
      - autoimmune inflammatory arthritis.
      - congenital anomalies of the lumbar spine
      - referred pain from visceral disease.
        low thoracic or lumbar pain with abdominal disease
        
        sacral pain with gynecologic and urologic disease.
      - other causes of back pain.
        postural back pain
        
        idiopathic
      - global considerations.
    - treatment: back pain
      - acute low back pain without radiculopathy.
      - chronic low back pain without radiculopathy.
      - low back pain with radiculopathy
    - pain in the neck and shoulder.
      - trauma to the cervical spine
      - cervical disk disease.
      - cervical spondylosis
      - other causes of neck pain.
      - thoracic outlet syndromes.
      - brachial plexus and nerves
      - shoulder
      - global considerations.
    - treatment: neck pain without radiculopathy
    - treatment: neck pain with radiculopathy.
    - further reading.
- section 2 alterations in body temperature.
  - 18 fever
    - fever versus hyperthermia.
    - pathogenesis of fever.
      - pyrogens
      - pyrogenic cytokines.
      - elevation of the hypothalamic set point by cytokines
      - production of cytokines in the cns
    - approach to the patient: fever
      - history and physical examination
      - laboratory tests
      - fever in patients receiving anticytokine therapy
    - treatment: fever
      - the decision to treat fever.
      - anticytokine therapy to reduce fever in autoimmune and autoinflammatory diseases
      - mechanisms of antipyretic agents
      - regimens for the treatment of fever.
  - 19 fever and rash.
    - approach to the patient: fever and rash.
      - physical examination
    - classification of rash
    - centrally distributed maculopapulareruptions
    - peripheral eruptions
    - confluent desquamativeerythemas.
    - vesiculobullous or pustular eruptions.
    - urticaria-like eruptions
    - nodular eruptions.
    - purpuric eruptions
    - eruptions with ulcers or eschars
    - further reading.
  - 20 fever of unknown origin
    - definition
    - etiology and epidemiology.
    - differential diagnosis
    - approach to the patient: fever of unknown origin
      - first-stage diagnostic tests
      - later-stage diagnostic tests
      - second opinion in an expert center
    - treatment: fever of unknown origin
      - antibiotics and antituberculous therapy.
      - colchicine, nonsteroidal anti-inflammatorydrugs, and glucocorticoids
      - interleukin 1 inhibition
    - prognosis.
    - further reading.
- section 3 nervous system dysfunction
  - 21 syncope
    - epidemiology and natural history
    - pathophysiology.
    - classification
      - neurally mediated syncope.
        classification of neurally mediated syncope.
        
        features of neurally mediated syncope.
      - treatment: neurally mediated syncope
      - orthostatic hypotension.
        causes of neurogenic orthostatic hypotension
      - treatment: orthostatic hypotension
      - cardiac syncope.
        arrhythmias
        
        structural disease
      - treatment: cardiac syncope
      - approach to the patient: syncope
        differential diagnosis
        
        initial evaluation
    - further reading.
  - 22 dizziness and vertigo
    - approach to the patient: dizziness
      - history.
      - examination.
      - ancillary testing.
    - differential diagnosis and treatment
    - acute prolonged vertigo (Vestibular neuritis).
    - benign paroxysmal positional vertigo
    - vestibular migraine.
    - ménière’s disease.
    - vestibular schwannoma.
    - bilateral vestibular hypofunction.
    - central vestibular disorders
    - psychosomatic and functional dizziness
    - treatment: vertigo
    - further reading.
  - 23 fatigue
    - epidemiology and global considerations
    - differential diagnosis
      - psychiatric disease.
      - neurologic disease
      - sleep disorders.
      - endocrine disorders.
      - liver and kidney disease
      - obesity.
      - physical inactivity.
      - malnutrition
      - infection.
      - drugs.
      - cardiovascular and pulmonary disorders .
      - malignancy
      - hematologic disorders.
      - immune-mediated disorders.
      - pregnancy.
      - disorders of unclear cause
    - approach to the patient: fatigue
    - treatment: fatigue
    - prognosis.
    - further reading.
  - 24 neurologic causes of weakness and paralysis
    - pathogenesis
      - upper motor neuron weakness.
      - lower motor neuron weakness.
      - neuromuscular junction weakness.
      - myopathic weakness
      - psychogenic weakness
    - distribution of weakness
      - hemiparesis
      - paraparesis.
      - quadriparesis or generalized weakness.
      - monoparesis.
      - distal weakness.
      - proximal weakness.
      - weakness in a restricted distribution.
    - further reading.
  - 25 numbness, tingling, and sensory loss.
    - positive and negative symptoms
    - terminology.
    - anatomy of sensation
    - approach to the patient: clinical examination of sensation
      - primary sensation.
      - cortical sensation
      - quantitative sensory testing
      - electrodiagnostic studies and nerve biopsy
    - localization of sensory abnormalities.
      - nerve and root
      - spinal cord.
      - brainstem.
      - thalamus
      - cortex
      - focal sensory seizures
      - psychogenic symptoms
    - treatment.
  - 26 gait disorders, imbalance, and falls.
    - prevalence, morbidity,and mortality.
    - anatomy and physiology
    - disorders of gait.
      - cautious gait.
      - stiff-legged gait.
      - parkinsonism, freezing gait, and other movement disorderss
      - frontal gait disorder.
      - cerebellar gait ataxia
      - sensory ataxia
      - neuromuscular disease.
      - toxic and metabolic disorders.
      - functional gait disorder
    - approach to the patient: slowly progressive disorder of gait
    - disorders of balance
      - definition, etiology, and manifestations
      - falls.
      - risk factors for falls
      - assessment of the patient with falls
        history.
        
        physical examination
        
        fall patterns.
      - treatment: interventions to reduce the risk of falls and injury.
    - further reading.
  - 27 confusion and delirium.
    - clinical features of delirium.
    - risk factors
    - epidemiology
    - pathogenesis
    - approach to the patient: delirium.
      - history.
      - physical examination
      - etiology
      - laboratory and diagnostic evaluation
    - treatment: delirium.
    - prevention
    - further reading.
  - 28 coma.
    - the anatomy and physiology of coma
      - coma due to cerebral mass lesions and herniation syndromes
      - coma due to metabolic, drug, and toxic disorders
      - epileptic coma
      - coma due to widespread structural damage to the cerebral hemispheres
    - approach to the patient: coma.
      - history.
      - general physical examination
      - neurologic examination
      - level of arousal
      - brainstem reflexes
    - laboratory studies and imaging
    - differential diagnosis of coma
    - brain death.
    - treatment: coma.
    - prognosis.
    - further reading.
  - 29 dementia.
    - functional anatomy of thedementias
      - the causes of dementia
    - approach to the patient: dementias
      - history.
      - physical and neurologic examination.
      - cognitive and neuropsychiatric examination
      - laboratory tests
    - global considerations.
    - treatment: dementia.
  - 30 aphasia, memory loss, and other cognitive disorders
    - the left perisylvian network for language and aphasias
      - clinical examination
        wernicke’s aphasia
        
        broca’s aphasia.
        
        conduction aphasia
        
        transcortical aphasias: fluent and nonfluent
        
        global and isolation aphasias.
        
        anomic aphasia
        
        pure word deafness
        
        pure alexia without agraphia
        
        apraxia and aphemia.
        
        gerstmann’s syndrome
        
        pragmatics and prosody
        
        subcortical aphasia.
        
        agrammatic ppa
        
        semantic ppa .
        
        logopenic ppa.
    - the parietofrontal network for spatial orientation
      - hemispatial neglect.
        clinical examination
      - bálint’s syndrome, simultanagnosia, dressing apraxia, construction apraxia, and route-finding impairments.
        causes of spatial disorientation and the posterior cortical atrophy syndrome
    - the occipitotemporal network forface and object recognition.
      - causes and relation to semantic dementia
    - limbic network for explicit memory and amnesia
      - clinical examination
      - causes, including alzheimer’s disease.
    - the prefrontal network for executive function and behavior
      - clinical examination
      - causes: trauma, neoplasm, and frontotemporal dementia.
    - caring for patients with deficits of higher cerebral function.
      - pharmacologic and nonpharmacologic interventions
    - further reading.
  - 31 sleep disorders
    - physiology of sleep and wakefulness.
      - organization of human sleep.
      - wake and sleep are regulated by brain circuits
      - sleep-wake cycles are driven by homeostatic, allostatic, and circadian inputs.
      - physiology of circadian rhythmicity.
      - behavioral and physiologic correlates of sleep states and stages
    - disorders of sleep and wakefulness
      - approach to the patient: sleep disorders
      - evaluation of daytime sleepiness
      - insufficient sleep
      - sleep apnea syndromes.
      - narcolepsy
        diagnosis.
        
        treatment: narcolepsy.
      - evaluation of insomnia
        psychophysiological factors.
        
        inadequate sleep hygiene
        
        psychiatric conditions
        
        medications and drugs of abuse
        
        medical conditions
        
        neurologic disorders
      - treatment: insomnia.
        treatment of medical and psychiatric disease
        
        improve sleep hygiene.
        
        cognitive behavioral therapy
        
        medications for insomnia
      - restless legs syndrome
      - periodic limb movement disorder.
      - parasomnias.
        sleepwalking (Somnambulism).
        
        sleep terrors.
        
        sleep enuresis
        
        sleep bruxism.
        
        rem sleep behavior disorder (Rbd).
      - circadian rhythm sleep disorders
        delayed sleep-wake phase disorder.
        
        advanced sleep-wake phase disorder
        
        non-24-h sleep-wake rhythm disorder.
        
        shift-work disorder.
        
        treatment: shift-work disorder
        
        jet lag disorder
      - medical implications of circadianrhythmicity
    - further reading.
- section 4 disorders of eyes, ears, nose, and throat.
  - 32 disorders of the eye.
    - the human visual system.
    - clinical assessment of visual function
      - refractive state
      - visual acuity.
      - pupils
      - eye movements and alignment.
      - stereopsis
      - color vision
      - visual fields.
    - disorders.
      - red or painful eye
        corneal abrasions
        
        subconjunctival hemorrhage
        
        pinguecula
        
        blepharitis.
        
        dacryocystitis .
        
        conjunctivitis
        
        allergic conjunctivitis.
        
        keratoconjunctivitis sicca
        
        keratitis.
        
        herpes simplex .
        
        herpes zoster
        
        episcleritis .
        
        anterior uveitis
        
        posterior uveitis.
        
        acute angle-closure glaucoma
        
        endophthalmitis.
      - transient or sudden visual loss.
        amaurosis fugax.
        
        anterior ischemic optic neuropathy (Aion).
        
        posterior ischemic optic neuropathy.
        
        optic neuritis
      - leber’s hereditary optic neuropathy.
        toxic optic neuropathy
        
        papilledema.
        
        optic disc drusen.
        
        vitreous degeneration.
        
        retinal detachment
        
        classic migraine
        
        transient ischemic attacks
        
        stroke
        
        factitious (Functional, nonorganic) Visual loss.
      - chronic visual loss.
        cataract .
        
        glaucoma .
        
        macular degeneration .
        
        central serous chorioretinopathy
        
        diabetic retinopathy
        
        retinitis pigmentosa
        
        epiretinal membrane.
        
        melanoma and other tumors
      - proptosis.
        graves’ ophthalmopathy
        
        orbital pseudotumor.
        
        orbital cellulitis
        
        tumors
        
        carotid cavernous fistulas
      - ptosis
        blepharoptosis
        
        mechanical ptosis.
        
        aponeurotic ptosis .
        
        myogenic ptosis.
        
        neurogenic ptosis
      - double vision (Diplopia)
        myasthenia gravis.
        
        oculomotor nerve
        
        trochlear nerve.
        
        abducens nerve
        
        multiple ocular motor nerve palsies.
        
        supranuclear disorders of gaze
        
        horizontal gaze.
        
        vertical gaze
        
        nystagmus
        
        opsoclonus
    - further reading.
  - 33 disorders of smell and taste.
    - anatomy and physiology
      - olfactory system .
      - taste system
    - disorders of olfaction
    - disorders of taste
    - clinical evaluation.
    - treatment and management
    - further reading.
  - 34 disorders of hearing.
    - physiology of hearing.
    - disorders of the sense of hearing.
      - conductive hearing loss
      - sensorineural hearing loss
      - noise-induced hearing loss
      - tinnitus .
    - genetic causes of hearing loss
    - approach to the patient: disorders of the sense of hearing
    - laboratory assessment of hearing
      - audiologic assessment.
      - evoked responses
      - imaging studies.
    - treatment: disorders of the sense of hearing
    - prevention
    - further reading.
  - 35 upper respiratory symptoms, including earache, sinus symptoms, and sore throat.
    - upper respiratory infections
      - improving ambulatory antibiotic prescribing.
      - ambulatory antibiotic stewardship.
    - nonspecific upper respiratory infection (“the common cold”).
      - definition and etiology.
      - symptoms and signs
      - treatment: nonspecific upper respiratory infection
    - ear pain
      - otitis externa
        etiology and clinical manifestations
        
        malignant otitis externa
        
        treatment: otitis externa.
      - acute otitis media
        epidemiology and etiology
        
        symptoms and signs
        
        treatment: acute otitis media.
      - otitis media with effusion
        definition and etiology.
        
        symptoms and signs .
        
        treatment: otitis media with effusion.
      - acute mastoiditis.
        etiology
        
        symptoms and signs
        
        evaluation
        
        evaluation
        
        differential diagnosis
        
        treatment: mastoiditis
    - sinus symptoms
      - acute sinusitis.
        definition and etiology.
        
        symptoms and signs
        
        complications
        
        treatment: acute sinusitis
      - chronic sinusitis.
        definition and etiology.
        
        symptoms and signs
        
        evaluation .
        
        treatment: chronic sinusitis
    - sore throat and neck pain.
      - streptococcal pharyngitis.
        evaluation
        
        complications.
        
        treatment: streptococcal pharyngitis
      - nonstreptococcal pharyngitis
        acute infectious mononucleosis
        
        other bacterial pharyngitis
      - head and neck abscesses.
      - epiglottitis
      - laryngitis
    - further reading.
  - 36 oral manifestations of disease.
    - diseases of the teeth and periodontal structures
      - dental caries, pulpal and periapical disease, and complications.
      - periodontal disease.
      - prevention of tooth decay and periodontal infection.
      - developmental and systemic disease affecting the teeth and periodontium.
    - diseases of the oral mucosa.
      - infections
      - pigmented lesions.
      - dermatologic diseases
      - diseases of the tongue
      - hiv disease and aids
      - ulcers
      - hematologic and nutritional disease.
    - nondental causes of oral pain.
      - diseases of the salivary glands.
        dental care for medically complex patients
        
        halitosis.
        
        aging and oral health.
    - further reading.
- section 5 alterations in circulatory and respiratory functions
  - 37 dyspnea
    - definition
    - epidemiology
    - mechanisms underlying dyspnea.
    - assessing dyspnea.
    - differential diagnosis
    - approach to the patient.
    - treatment.
  - 38 cough
    - cough mechanism.
    - impaired cough
    - symptomatic cough.
    - assessment of chronic cough.
    - chronic cough with a normal chest radiograph
    - global considerations.
    - symptom-based treatment of cough
    - further reading.
  - 39 hemoptysis.
    - anatomy and physiology of hemoptysis
    - etiology
      - infections
      - vascular
      - malignancy
      - mechanical and other causes.
    - evaluation and management.
      - history.
      - physical examination
      - diagnostic studies .
      - interventions.
    - further reading.
  - 40 hypoxia and cyanosis.
    - hypoxia.
      - responses to hypoxia
        effects on the central nervous system.
        
        effects on the cardiovascular system
      - causes of hypoxia.
        respiratory hypoxia.
        
        hypoxia secondary to high altitude
        
        hypoxia secondary to right-to-left extrapulmonary shunting
        
        anemic hypoxia
        
        carbon monoxide (Co) Intoxication.
        
        circulatory hypoxia.
        
        specific organ hypoxia
        
        increased o2 requirements.
        
        improper oxygen utilization.
      - adaptation to hypoxia.
    - cyanosis
      - differential diagnosis
        central cyanosis
        
        peripheral cyanosis.
      - approach to the patient.
    - clubbing
    - further reading.
  - 41 edema
    - plasma and interstitial fluid exchange
      - reduction of effective arterial volume
      - renal factors and the reninangiotensin-aldosterone system.
      - arginine vasopressin
      - endothelin-1
      - natriuretic peptides
      - clinical causes of edema
      - generalized edema.
        heart failure.
        
        edema of renal disease
        
        nephrotic syndrome and other hypoalbuminemic states.
        
        hepatic cirrhosis.
        
        drug-induced edema
        
        edema of nutritional origin.
      - localized edema.
        other causes of edema.
      - distribution of edema.
    - approach to the patient.
    - further reading.
  - 42 approach to the patient with a heart murmur
    - duration and character
    - intensity.
    - location and radiation
    - systolic heart murmurs
      - early systolic murmurs
      - midsystolic murmurs
      - late systolic murmurs
      - holosystolic murmurs
    - diastolic heart murmurs.
      - early diastolic murmurs.
      - mid-diastolic murmurs
    - continuous murmurs
    - dynamic auscultation
      - respiration.
      - alterations of systemic vascular resistance.
      - changes in venous return .
      - post-premature ventricular contraction
    - the clinical context
    - echocardiography
    - other cardiac testing.
    - integrated approach.
    - further reading.
  - 43 palpitations.
    - approach to the patient.
    - further reading.
- section 6 alterations in gastrointestinal function
  - 44 dysphagia
    - physiology of swallowing
    - pathophysiology of dysphagia
    - approach to the patient.
    - further reading.
  - 45 nausea, vomiting, and indigestion
    - nausea and vomiting.
      - mechanisms
        coordination of emesis .
        
        activators of emesis
      - differential diagnosis
        intraperitoneal disorders.
        
        extraperitoneal disorders.
        
        medications and metabolic disorders.
      - approach to the patient: nausea and vomiting
      - treatment: nausea and vomiting
    - indigestion.
      - mechanisms
        gastroesophageal reflux.
        
        gastric motor dysfunction.
        
        visceral afferent hypersensitivity
        
        immune activation
        
        other factors
      - differential diagnosis
        gastroesophageal reflux disease.
        
        functional dyspepsia
        
        ulcer disease.
        
        malignancy
        
        other causes
      - approach to the patient: indigestion
      - treatment: indigestion
        lifestyle, diet, and nonmedication recommendations
        
        acid-suppressing or -neutralizing medications.
        
        helicobacter pylori eradication.
        
        agents that modify gastrointestinal motor activity
        
        antidepressants.
        
        other options.
    - further reading.
  - 46 diarrhea and constipation
    - normal physiology.
      - neural control
      - intestinal fluid absorption and secretion.
      - small-intestinal motility.
      - ileocolonic storage and salvage.
      - colonic motility and tone.
      - colonic motility after meal ingestion.
      - defecation
    - diarrhea
      - definition
      - acute diarrhea
        infectious agents.
        
        other causes .
        
        approach to the patient.
        
        treatment.
      - chronic diarrhea
        secretory causes
        
        osmotic causes .
        
        steatorrheal causes.
        
        inflammatory causes.
        
        dysmotility causes .
        
        factitial causes
        
        approach to the patient.
        
        treatment.
    - constipation
      - definition
      - causes
      - approach to the patient.
      - investigation of severe constipation
        measurement of colonic transit
        
        anorectal and pelvic floor tests .
      - treatment.
    - further reading.
  - 47 unintentional weight loss
    - physiology of weight regulation withaging.
    - causes of unintentional weight loss.
    - assessment
    - treatment.
    - further reading.
  - 48 gastrointestinal bleeding
    - sources of gastrointestinal bleeding
      - upper gastrointestinal sources of bleeding
      - small-intestinal sources of bleeding
      - colonic sources of bleeding
    - approach to the patient.
      - initial assessment
      - differentiation of ugib from lgib.
      - evaluation and management of ugib.
      - evaluation and management of lgib
      - evaluation and management of small-intestinal or obscure gib
      - positive fecal occult blood test
    - further reading.
  - 49 jaundice.
    - production and metabolism of bilirubin
    - measurement of serum bilirubin
    - measurement of urine bilirubin
    - approach to the patient.
      - isolated elevation of serum bilirubin.
      - elevation of serum bilirubin with other liver test abnormalities
    - global considerations.
    - further reading.
  - 50 abdominal swelling and ascites.
    - abdominal swelling
      - causes
      - approach to the patient.
      - imaging and laboratory evaluation.
    - ascites.
      - pathogenesis in the presence of cirrhosis.
      - pathogenesis in the absence of cirrhosis
      - causes
      - evaluation
      - treatment.
      - complications.
    - further reading.
- section 7 alterations in renal and urinary tract function.
  - 51 interstitial cystitis/bladder pain syndrome
    - definition
    - etiology and pathogenesis.
      - infection and the urinary microbiota
      - autoimmunity
      - inflammation
      - urothelial dysfunction
        urothelial permeability and the glycosaminoglycan layer.
        
        antiproliferative factor
      - pelvic organ crosstalk
      - neurobiologic contributions and central sensitization.
    - epidemiology
    - clinical manifestations.
    - approach to the patient.
    - diagnosis.
      - history and physical (Including frequency/volume charts)
      - symptom scores
      - urine studies.
      - imaging, cystoscopy, and urodynamics
      - intravesical anesthetic bladder challenge and hydrodistension.
    - treatment: clinical phenotyping.
    - conservative measures.
    - medical therapies.
    - surgical therapies
    - complications and prognosis.
    - global considerations.
    - further reading.
  - 52 azotemia and urinary abnormalities.
    - azotemia
      - assessment of gfr.
      - approach to the patient.
        prerenal failure
        
        postrenal azotemia
        
        intrinsic renal disease.
        
        oliguria and anuria.
    - abnormalities of the urine
      - proteinuria.
      - hematuria, pyuria, and casts
    - abnormalities of urine volume.
      - polyuria
  - 53 fluid and electrolyte disturbances.
    - sodium and water
      - composition of body fluids
      - hypovolemia.
        etiology
        
        diagnostic evaluation.
        
        treatment.
    - sodium disorders
      - hyponatremia
        hypovolemic hyponatremia
        
        hypervolemic hyponatremia.
        
        euvolemic hyponatremia
        
        low solute intake and hyponatremia
        
        clinical features of hyponatremia.
        
        diagnostic evaluation of hyponatremia.
        
        treatment.
      - hypernatremia.
        etiology
        
        clinical features.
        
        diagnostic approach
        
        treatment.
    - potassium disorders.
      - hypokalemia.
        redistribution and hypokalemia
        
        nonrenal loss of potassium
        
        renal loss of potassium.
        
        magnesium deficiency and hypokalemia
        
        clinical features.
        
        treatment.
      - hyperkalemia
        pseudohyperkalemia .
        
        redistribution and hyperkalemia.
        
        hyperkalemia caused by excess intake or tissue necrosis.
        
        hypoaldosteronism and hyperkalemia
        
        renal disease and hyperkalemia
        
        medication-associated hyperkalemia
        
        clinical features.
        
        diagnostic approach.
        
        treatment.
  - 54 hypercalcemia and hypocalcemia.
    - hypercalcemia.
      - etiology
      - clinical manifestations.
      - diagnostic approach.
      - treatment.
    - hypocalcemia
      - etiology
      - clinical manifestations.
      - diagnostic approach.
      - treatment.
      - global considerations.
    - further reading.
  - 55 acidosis and alkalosis.
    - normal acid-base homeostasis
    - diagnosis of general types of disturbances
      - simple acid-base disorders
      - mixed acid-base disorders.
    - approach to the patient: acid-base disorders
    - metabolic acidosis
      - treatment.
      - high-anion gap acidoses.
        approach to the patient.
        
        lactic acidosis.
        
        ketoacidosis
        diabetic ketoacidosis (Dka).
        
        alcoholic ketoacidosis (Aka)
        
        drug- and toxin-induced acidosis
        salicylates
        
        alcohols
        
        ethylene glycol.
        
        methanol
        
        propylene glycol
        
        isopropyl alcohol.
        
        pyroglutamic acid.
        
        chronic kidney disease
      - non–anion gap metabolic acidoses
        treatment.
    - metabolic alkalosis.
      - etiology and pathogenesis.
      - differential diagnosis
      - metabolic alkalosis associated with ecfv contraction, k+ depletion, and secondary hyperreninemic hyperaldosteronism.
        gastrointestinal origin.
        
        renal origin
        diuretics.
        
        solute losing disorders: bartter’s syndrome and gitelman’s syndrome.
        
        non-reabsorbable anions and magnesium deficiency
        
        potassium depletion.
        
        after treatment of lactic acidosis or ketoacidosis
        
        posthypercapnia
      - metabolic alkalosis associated with ecfv expansion, hypertension, and mineralocorticoid excess
        symptoms
        
        treatment.
    - respiratory acidosis
    - respiratory alkalosis.
- section 8 alterations in the skin.
  - 56 approach to the patient with a skin disorder.
    - description of primary skin lesions.
    - description of secondary skin lesions.
    - common dermatologic terms.
    - selected common dermatologic conditions.
    - approach to the patient.
    - diagnostic techniques.
      - skin biopsy.
      - koh preparation.
      - tzanck smear
      - diascopy
      - dermoscopy
      - wood’s light
      - patch tests
    - further reading.
  - 57 eczema, psoriasis, cutaneous infections, acne, and other common skin disorders.
    - eczema and dermatitis.
      - atopic dermatitis.
      - lichen simplex chronicus
      - contact dermatitis
      - hand eczema.
      - nummular eczema.
      - asteatotic eczema.
      - stasis dermatitis and stasis ulceration.
      - seborrheic dermatitis.
    - papulosquamous disorders
      - psoriasis.
      - lichen planus.
      - pityriasis rosea
    - cutaneous infections .
      - impetigo, ecthyma, and furunculosis.
      - erysipelas and cellulitis.
      - dermatophytosis.
      - tinea (Pityriasis) Versicolor.
      - candidiasis.
      - warts.
      - herpes simplex
      - herpes zoster.
    - acne
      - acne vulgaris.
      - acne rosacea
    - skin diseases and smallpox vaccination
    - further reading.
  - 58 skin manifestations of internal disease
    - papulosquamous skin lesions.
    - erythroderma
    - alopecia
    - figurate skin lesions.
    - acne
    - pustular lesions
    - telangiectasias.
    - hypopigmentation
    - hyperpigmentation.
    - vesicles/bullae.
    - urticaria.
    - papulonodular skin lesions
      - white lesions.
      - skin-colored lesions
      - pink lesions
      - yellow lesions
      - red lesions.
      - red-brown lesions.
      - blue lesions
      - violaceous lesions
      - purple lesions
      - brown and black lesions.
      - cutaneous metastases
    - purpura.
    - ulcers
    - fever and rash
    - further reading.
  - 59 immunologically mediated skin diseases.
    - autoimmune cutaneous diseases.
      - pemphigus vulgaris
      - pemphigus foliaceus.
      - paraneoplastic pemphigus
      - bullous pemphigoid
      - pemphigoid gestationis
      - dermatitis herpetiformis
      - linear iga disease
      - epidermolysis bullosa acquisita.
      - mucous membrane pemphigoid
    - autoimmune systemic diseases with prominent cutaneous features
      - dermatomyositis.
      - lupus erythematosus.
      - scleroderma and morphea.
    - further reading.
  - 60 cutaneous drug reactions.
    - use of prescription drugs in theunited states.
    - incidence of cutaneous reactions
    - pathogenesis of drug reactions
      - nonimmunologic drug reactions.
      - immunologic drug reactions
        immediate reactions.
        
        immune complex–dependent reactions
        
        delayed hypersensitivity
      - genetic factors and cutaneous drug reactions
      - global considerations.
    - clinical presentation of cutaneous drug reactions.
      - nonimmune cutaneous reactions.
        exacerbation or induction of dermatologic diseases
        
        photosensitivity eruptions .
        
        pigmentation changes
        
        warfarin necrosis of skin.
        
        drug-induced hair disorders.
        
        drug-induced nail disorders.
        
        toxic erythema of chemotherapy and other chemotherapy reactions.
      - immune cutaneous reactions: common
        maculopapular eruptions.
        
        pruritus
        
        urticaria/angioedema/anaphylaxis
        
        anaphylactoid reactions.
        
        irritant/allergic contact dermatitis
        
        fixed drug eruptions
      - immune cutaneous reactions: rare and severe.
        drug-induced hypersensitivity syndrome
        
        stevens-johnson syndrome and toxic epidermal necrolysis.
        
        pustular eruptions
        
        overlap hypersensitivity syndromes
        
        vasculitis
    - management of the patient with suspected drug eruption
      - early diagnosis of severe eruptions.
      - confirmation of drug reaction.
      - what drug(S) To suspect and withdraw
      - recommendation for future use of drugs
      - cross-sensitivity.
      - role of testing for causality and drug rechallenge
      - reporting.
    - further reading.
  - 61 photosensitivity and other reactions to sunlight.
    - solar radiation.
      - uv radiation (Uvr) And skin structure andfunction.
        molecular targets for uvr-induced skin effects .
        
        cutaneous optics and chromophores.
        
        acute effects of sun exposure.
        
        chronic effects of sun exposure: nonmalignant.
        
        chronic effects of sun exposure: malignant
        
        photoimmunology.
      - photosensitivity diseases.
        polymorphous light eruption.
        
        phototoxicity and photoallergy
        
        porphyria.
    - photoprotection.
    - phototherapy and photochemotherapy
    - further reading.
- section 9 hematologic alterations.
  - 62 interpreting peripheral blood smears.
    - normal peripheral blood smear.
    - reticulocyte count preparation
    - hypochromic microcytic anemia of iron deficiency
    - iron deficiency anemia next to normal red blood cells.
    - polychromatophilia
    - macrocytosis
    - hypersegmented neutrophils
    - spherocytosis.
    - rouleaux formation
    - red cell agglutination
    - fragmented red cells
    - sickle cells
    - target cells
    - elliptocytosis
    - stomatocytosis
    - acanthocytosis
    - howell-jolly bodies.
    - teardrop cells and nucleated red blood cells characteristic of myelofibrosis
    - myelofibrosis of the bone marrow
    - reticulin stain of marrow myelofibrosis.
    - stippled red cell in lead poisoning.
    - heinz bodies
    - giant platelets.
    - normal granulocytes.
    - normal monocytes
      - normal eosinophils.
      - normal basophil
    - pelger-hüet anomaly.
    - döhle body
    - chédiak-higashi disease.
  - 63 anemia and polycythemia
    - hematopoiesis and the physiologicbasis of red cell production.
    - anemia
      - clinical presentation of anemia.
      - approach to the patient.
        laboratory evaluation.
        peripheral blood smear
        
        reticulocyte count .
        
        tests of iron supply and storage
        
        bone marrow examination.
        
        other laboratory measurements.
      - definition and classification of anemia.
        initial classification of anemia
        
        hypoproliferative anemias.
        
        maturation disorders
        
        blood loss/hemolytic anemia.
      - treatment.
    - polycythemia
    - further reading.
  - 64 disorders of granulocytes and monocytes
    - neutrophils.
      - maturation
      - marrow release andcirculating compartments
      - neutrophil abnormalities
        neutropenia.
        
        hereditary neutropenias.
        
        neutrophilia
        
        abnormal neutrophil function .
    - mononuclear phagocytes
      - disorders of the mononuclearphagocyte system
    - eosinophils.
      - eosinophilia
      - eosinopenia.
    - hyperimmunoglobulin e–recurrent infection syndrome
    - laboratory diagnosis and management.
    - further reading.
  - 65 bleeding and thrombosis
    - steps of normal hemostasis
      - platelet plug formation.
      - fibrin clot formation.
    - antithrombotic mechanisms.
      - the fibrinolytic system.
    - approach to the patient.
      - clinical presentation.
        history of bleeding.
        
        prohemorrhagic effects of medications and dietary supplements.
        
        underlying systemic diseases that cause or exacerbate a bleeding tendency.
      - history of thrombosis.
      - laboratory evaluation.
        screening assays
        
        mixing studies
        
        specific factor assays
        
        testing for antiphospholipid antibodies.
        
        other coagulation tests
        
        laboratory testing for thrombophilia
        
        measures of platelet function.
    - further reading.
  - 66 enlargement of lymph nodes and spleen
    - lymphadenopathy.
    - splenomegaly
    - splenectomy.
    - further reading.
part 3 pharmacology
- 67 principles of clinical pharmacology
  - global considerations.
  - indications for drug therapy: risk versus benefit.
    - adverse effects.
    - therapeutic index.
  - principles of pharmacokinetics
    - absorption and bioavailability
    - drug transport
    - drug metabolism.
    - plasma half-life
    - drug distribution.
    - drug elimination
    - active drug metabolites.
    - the concept of high-risk pharmacokinetics.
    - principles of pharmacodynamics
    - principles of dose selection
  - effects of disease on drug concentration and response.
    - renal disease.
    - liver disease.
    - heart failure and shock.
    - drug use in the elderly.
    - drug use in children
  - interactions between drugs
  - adverse drug reactions
    - scope of the problem
    - toxicity unrelated to a drug’s primarypharmacologic activity
      - acetaminophen.
      - immunologic reactions.
    - diagnosis and treatment of adverse drug reactions.
  - the drug development process
  - summary.
  - further reading.
- 68 pharmacogenomics.
  - principles of genetic variation and drug response
    - types of genetic variants influencing drug response.
    - candidate gene approaches.
    - genome-wide association studies.
  - genetic variants affecting pharmacokinetics.
    - cyp3a.
    - cyp2d6
    - cyp2c19.
    - cyp2c9
    - dpyd
    - transferase variants
    - transporter variants
  - genetic variants affecting pharmacodynamics.
    - immunologically mediated drug reactions.
    - tumor and infectious agent genomes
  - incorporating pharmacogenetic information into clinical practice
    - point of care versus preemptive approaches
    - challenges
    - developing evidence that pharmacogenetic testing alters drug outcomes.
  - genetics and drug development.
    - finding protective alleles can identify drug targets
    - cancer
    - using multiple data types.
  - summary.
  - further reading.
part 4 oncology and hematology
- section 1 neoplastic disorders
  - 69 approach to the patient with cancer
    - the magnitude of the problem
    - patient management
      - diagnosis.
      - defining the extent of disease andthe prognosis.
      - making a treatment plan.
      - management of disease and treatmentcomplications
    - long-term follow-up/latecomplications.
      - supportive care.
        pain
        
        nausea
        
        effusions.
        
        nutrition.
        
        psychosocial support .
        
        death and dying.
        
        end-of-life decisions.
    - further reading.
  - 70 prevention and early detection of cancer.
    - education and healthful habits
      - smoking cessation.
      - physical activity.
      - diet modification.
      - energy balance
      - un avoidance
    - cancer chemoprevention
      - chemoprevention of cancers of the upper aerodigestive tract.
      - chemoprevention of colon cancer.
      - chemoprevention of breast cancer
      - chemoprevention of prostate cancer
      - vaccines and cancer prevention
    - surgical prevention of cancer.
    - cancer screening
      - the accuracy of screening.
      - potential biases of screening tests.
      - potential drawbacks of screening
      - assessment of screening tests.
      - screening for specific cancers
        breast cancer
        
        cervical cancer
        
        colorectal cancer.
        
        lung cancer.
        
        ovarian cancer
        
        prostate cancer.
        
        skin cancer.
    - further reading.
  - 71 cancer genetics
    - cancer is a genetic disease.
    - historical perspective
    - the clonal origin and multistep nature of cancer
    - two types of cancer genes: oncogenes and tumor-suppressor genes.
    - oncogenes in human cancer.
    - mechanisms of oncogene activation.
      - point mutation
      - dna amplification.
      - chromosomal rearrangement.
    - chromosomal instability in solid tumors.
    - tumor-suppressor gene inactivation in cancer
    - familial cancer syndromes.
    - genetic testing for familial cancer.
    - viruses in human cancer.
    - cancer genomes
    - tumor heterogeneity.
    - personalized cancer detection and treatment.
    - the future
    - further reading.
  - 72 cancer cell biology
    - cancer cell biology.
    - cancer as an organ that ignores its niche.
    - cell cycle checkpoints
    - cellular senescence.
    - signal transduction pathways in cancer cells
    - cancer-specific genetic changes and synthetic lethality.
    - epigenetic influences on cancer gene transcription
    - apoptosis and other mechanisms of cell death
    - metastasis
    - cancer stem cells.
    - plasticity and resistance.
    - cancer metabolism.
    - tumor microenvironment, angiogenesis, and immune evasion
    - obesity and cancer
    - mechanisms of tumor vessel formation
    - antiangiogenic therapy
    - evasion of the immune system by cancers.
    - summary.
    - further reading.
  - 73 principles of cancer treatment.
    - cancer presentation.
      - detection of a cancer.
      - establishing a cancer diagnosis.
      - cancer staging
    - cancer treatment
    - localized cancer treatments.
      - surgery.
      - radiation.
      - other localized cancer treatments.
    - systemic cancer treatments
      - systemic cancer therapy overview
        general principles .
        
        strategies in systemic cancer management
      - cancer biologic therapy.
        antibody-mediated therapeutic approaches
        
        nontargeted immunomodulators
        
        cytokines.
        
        t cell–mediated therapies.
        
        oncolytic viruses
      - cancer cytotoxic therapy
        dna-interactive agents
        
        antitumor antibiotics and topoisomerase poisons.
        
        antimetabolites.
        
        mitotic spindle inhibitors
      - cancer molecular targeted therapy.
        hormone receptor–directed therapy.
        
        non-receptor-linked tyrosine kinase antagonists.
        
        receptor-linked tyrosine kinase antagonists.
        
        ras/raf/mek antagonists.
        
        multikinase inhibitors
        
        cyclin-dependent kinase inhibitors
        
        protein homeostasis modulators
        
        chromatin-modifying agents
        
        cancer cell metabolism modulators.
        
        dna repair pathway modulators.
        
        miscellaneous targeted therapies
      - systemic radiation therapy
    - resistance to cancer treatments.
    - supportive care during cancer treatment.
      - myelosuppression
      - nausea and vomiting.
      - diarrhea
      - mucositis.
      - alopecia
      - gonadal dysfunction and pregnancy.
      - palliative and supportive care
    - further reading.
  - 74 infections in patients with cancer.
    - system-specific syndromes.
      - skin-specific syndromes.
      - catheter-related infections.
      - gastrointestinal tract–specificsyndromes
      - central nervous system–specific syndromes.
      - pulmonary infections
      - cardiovascular infections.
      - endocrine syndromes.
      - musculoskeletal infections
      - renal and ureteral infections.
    - abnormalities that predispose to infection
      - the lymphoid system.
      - the hematopoietic system
    - treatment.
      - antibacterial therapy.
      - antifungal therapy
      - antiviral therapy.
      - other therapeutic modalities
    - prevention of infection in cancer patients
      - effect of the environment.
      - physical measures.
      - immunoglobulin replacement
      - sexual practices
      - antibiotic prophylaxis
      - vaccination of cancer patients
    - in memoriam.
    - further reading.
    - website.
  - 75 oncologic emergencies
    - structural-obstructive oncologicemergencies.
      - superior vena cava syndrome.
      - pericardial effusion/tamponade
      - intestinal obstruction
      - urinary obstruction.
      - malignant biliary obstruction.
      - spinal cord compression.
      - increased intracranial pressure.
      - neoplastic meningitis.
      - seizures
      - pulmonary and intracerebral leukostasis.
      - hemoptysis
      - airway obstruction
    - metabolic emergencies.
      - hypercalcemia.
      - syndrome of inappropriate secretion of antidiuretic hormone.
      - lactic acidosis.
      - hypoglycemia
      - adrenal insufficiency.
    - treatment-related emergencies.
      - tumor lysis syndrome
      - human antibody infusion reactions.
      - hemolytic-uremic syndrome.
      - neutropenia and infection.
      - pulmonary infiltrates.
      - neutropenic enterocolitis.
      - hemorrhagic cystitis
      - hypersensitivity reactions to antineoplastic drugs
    - further reading.
  - 76 cancer of the skin.
    - melanoma
      - risk factors and epidemiology.
      - global considerations.
      - genetic susceptibility to melanoma
      - prevention and early detection
      - diagnosis.
      - classification and pathogenesis.
      - prognostic factors
      - staging.
      - treatment: melanoma.
      - treatment: metastatic disease.
    - nonmelanoma skin cancers
      - pathophysiology and etiology
      - clinical presentation.
      - natural history.
      - treatment.
      - prevention
      - other nonmelanoma cutaneous malignancies
    - further reading.
  - 77 head and neck cancer.
    - incidence and epidemiology
    - etiology and genetics.
    - histopathology, carcinogenesis, and molecular biology.
    - clinical presentation and differential diagnosis
    - treatment.
    - salivary gland tumors.
    - further reading.
  - 78 neoplasms of the lung
    - epidemiology
      - risk factors
      - pathology.
      - immunohistochemistry
      - molecular pathogenesis
    - early detection and screening.
    - clinical manifestations.
    - diagnosing lung cancer
    - staging lung cancer.
      - anatomic staging of patients with lung cancer.
      - staging system for non-small-cell lung cancer.
      - staging system for small-cell lung cancer.
      - physiologic staging.
    - treatment: non-small-cell lung cancer.
      - occult and stage 0 carcinomas.
      - solitary pulmonary nodule and “ground-glass” opacities
      - management of stages i and ii nsclc.
      - management of stage iii nsclc.
      - management of metastatic nsclc
    - treatment: small-cell lung cancer.
      - surgery for limited-disease small-cell lung cancer
      - chemotherapy
      - thoracic radiation therapy
      - prophylactic cranial irradiation
    - thymic tumors.
      - clinical manifestations.
      - staging.
      - treatment.
    - covid-19 and lung cancer
    - summary.
    - further reading.
  - 79 breast cancer
    - introduction and background.
    - epidemiology and risk factors.
    - prevention of breast cancer.
    - screening for breast cancer.
    - evaluation of breast masses.
      - palpable breast masses
      - abnormal mammogram
      - breast masses in pregnancy or lactation.
    - pathologic findings of the breast.
      - benign breast histopathology
      - noninvasive breast neoplasms
        ductal carcinoma in situ
        
        lobular carcinoma (Neoplasia) In situ.
      - invasive breast cancers.
    - staging and diagnostic considerations.
    - treatment.
      - general considerations
      - local (Primary) Treatments
      - adjuvant systemic therapies.
      - stage iii breast cancer.
      - simultaneous new primary with detectable metastases.
      - breast cancer survivorship issues.
      - metastatic disease
      - systemic treatments for metastatic breast cancer
      - breast cancer in pregnancy
      - male breast cancer
    - further reading.
  - 80 upper gastrointestinal tract cancers.
    - esophageal cancer.
      - incidence and causative factors.
      - screening and surveillance of higher risk groups
      - genomic alterations.
      - presenting symptoms.
      - staging.
      - treatment.
    - tumors of the stomach.
    - gastric lymphomas.
    - uncommon tumors of the esophagus and stomach
      - neuroendocrine tumors.
      - gastrointestinal stromal tumors.
      - small-bowel neoplasms.
      - small-bowel gastrointestinal stromal tumors.
      - carcinoid (Neuroendocrine) Tumors of the small bowel
      - benign neoplasms of the small bowel.
    - further reading.
  - 81 lower gastrointestinal cancers.
    - colorectal cancer.
      - incidence.
      - polyps and molecular pathogenesis.
      - etiology and risk factors.
      - hereditary factors and syndromes
      - inflammatory bowel disease
      - other high-risk conditions
      - primary prevention
      - screening.
      - clinical features.
      - treatment.
    - cancers of the anus.
  - 82 tumors of the liver and biliary tree.
    - hepatocellular carcinoma
      - epidemiology and risk factors.
      - molecular pathogenesis
      - prevention and early detection
      - treatment.
      - surgical therapies
      - locoregional therapies
      - systemic therapies
    - cholangiocarcinoma
      - epidemiology, risk factors, and molecular traits
      - intrahepatic cholangiocarcinoma.
      - treatment.
      - extrahepatic cholangiocarcinoma.
      - gallbladder cancer
    - other malignant liver tumors
      - fibrolamellar hepatocellular carcinoma
      - hepatoblastoma
    - benign liver tumors.
    - further reading.
  - 83 pancreatic cancer
    - epidemiology
    - risk factors
    - pathology and molecular consideration.
    - clinical features.
    - diagnostic workup.
    - important immediate considerations in patient care
    - clinical staging
    - treatment.
    - future directions.
    - further reading.
  - 84 gastrointestinal neuroendocrine tumors.
    - incidence and prevalence
    - histologic classification and molecular features
    - clinical presentation and management of localized pancreatic neuroendocrine tumors
      - gastrinoma
      - insulinoma
      - glucagonoma.
      - somatostatinoma.
      - vipoma
      - other secretory pancreatic nets.
      - pancreatic nets arising in the setting ofmen 1
      - nonfunctioning pancreatic nets
    - clinical presentation and management of localized extrapancreatic gastrointestinal neuroendocrine tumors
      - gastric nets
      - nets of the small intestine.
      - nets of the appendix
      - rectal nets.
    - clinical presentation, diagnosis, and evaluation of patients with metastatic neuroendocrine tumors
    - management of symptoms of hormone hypersecretion and the carcinoid syndrome.
      - diagnosis and treatment of the carcinoid syndrome.
      - carcinoid crisis
      - carcinoid heart disease.
    - hepatic-directed therapy for metastatic nets
    - systemic treatment to control tumor growth
      - somatostatin analogues
      - peptide receptor radioligand therapy
      - alkylating agents.
    - small-molecule tyrosine kinase inhibitors.
      - mtor inhibitors.
      - other systemic treatments for controlof tumor growth
      - systemic therapy for high-gradeneuroendocrine carcinoma.
    - further reading.
  - 85 renal cell carcinoma.
    - epidemiology
    - pathology and genetics
    - clinical presentation.
    - staging and prognosis.
    - treatment.
    - global considerations.
    - further reading.
  - 86 cancer of the bladder and urinary tract
    - global considerations.
    - introduction
    - clinical epidemiology and risk factors
    - clinical presentation and diagnosticworkup
    - histology.
    - molecular biology.
    - staging and outcomes by stage.
    - treatment approaches
    - further reading.
  - 87 benign and malignant diseases of the prostate
    - anatomy and pathology.
    - prostate cancer.
      - epidemiology
      - diagnosis and treatment by clinical state.
      - treatment.
    - benign disease
      - benign prostatic hyperplasia
    - further reading.
  - 88 testicular cancer
    - incidence.
    - global considerations.
    - epidemiology
    - biology.
    - pathology.
    - initial presentation
      - signs and symptoms
      - physical examination .
      - diagnostic testing
      - serum tumor markers.
    - initial management
      - inguinal orchiectomy
      - staging.
    - stage-based management
      - stage i.
      - stage ii
      - stage iii.
      - chemotherapy
      - postchemotherapy surgery
    - relapsed disease
    - extragonadal gcts.
    - testicular non–germ cell tumors.
    - survivorship and late effects.
    - further reading.
  - 89 gynecologic malignancies.
    - ovarian cancer
      - incidence and pathology.
      - ovarian cancer of epithelial origin.
        epidemiology
        
        genetics and pathogenesis.
        
        screening.
        
        treatment.
      - uncommon ovarian tumors.
        low malignant potential tumors (Borderline tumors)
        
        stromal tumors
        
        germ cell tumors of the ovary.
    - fallopian tube cancer.
    - cervical cancer.
      - etiology and genetics.
      - hpv infection and prevention
      - clinical presentations
    - uterine cancer
      - epidemiology
      - pathology.
      - clinical presentation.
      - treatment.
    - gestational trophoblastic tumors
      - risk factors
      - presentation of invasive trophoblastic disease
      - treatment: invasive trophoblastic disease.
  - 90 primary and metastatic tumors of the nervous system
    - approach to the patient.
    - treatment: brain tumors.
    - primary brain tumors
      - epidemiology
      - molecular pathogenesis
    - intrinsic “malignant” tumors
      - diffuse gliomas.
      - astrocytomas
      - oligodendroglioma.
      - ependymomas.
      - other less common gliomas.
      - primary central nervous system lymphoma.
      - medulloblastomas
      - pineal region tumors
    - extrinsic “benign” tumors.
      - meningiomas.
      - schwannomas.
      - pituitary tumors
      - craniopharyngiomas
      - other benign tumors.
        dysembryoplastic neuroepithelial tumors (Dnts)
        
        epidermoid cysts
        
        dermoid cysts.
        
        colloid cysts.
    - neurocutaneous syndromes (Phakomatoses).
      - neurofibromatosis type 1 (Von recklinghausen’s disease).
      - neurofibromatosis type 2
      - tuberous sclerosis (Bourneville disease)
    - tumors metastatic to the brain
      - diagnosis of metastases.
      - treatment.
    - leptomeningeal metastases.
      - clinical features.
      - laboratory and imaging diagnosis
      - treatment.
    - epidural metastasis.
      - clinical features.
      - diagnosis.
      - treatment.
    - neurologic toxicity of therapy
      - toxicity from radiotherapy
      - toxicity from chemotherapy
    - further reading.
  - 91 soft tissue and bone sarcomas and bone metastases
    - soft tissue sarcomas
      - incidence.
      - epidemiology
      - genetic considerations
      - classification
      - diagnosis.
      - staging and prognosis.
      - treatment.
    - bone sarcomas.
      - incidence and epidemiology
      - classification
      - osteosarcoma
      - chondrosarcoma
      - ewing’s sarcoma.
    - tumors metastatic to bone.
    - further reading.
  - 92 carcinoma of unknown primary.
    - cup biology.
    - approach to the patient.
    - role of serum tumor markers and cytogenetics
    - role of imaging studies.
    - role of pathologic studies
      - light microscopy evaluation
      - role of ihc analysis
      - role of cancer classifier molecular profiling.
      - role of next-generation sequencing
    - treatment.
      - general considerations
      - treatment of favorable cup subsets
        women with isolated axillary adenopathy.
        
        women with peritoneal carcinomatosis
        
        poorly differentiated carcinoma with midline adenopathy.
        
        neuroendocrine cancer.
        
        squamous cell carcinoma presenting as neck adenopathy.
        
        solitary metastatic sites.
        
        men with blastic skeletal metastases and elevated psa.
      - management of disseminated cup
    - summary.
    - further reading.
  - 93 paraneoplastic syndromes: endocrinologic/hematologic.
    - endocrine paraneoplastic syndromes
      - hypercalcemia caused by ectopic production of pthrp.
      - ectopic vasopressin: tumor-associated syndrome of inappropriate antidiuretic hormone
      - cushing’s syndrome caused by ectopic acth production
      - tumor-induced hypoglycemia caused by excess production of insulin-like growth factor type ii
      - human chorionic gonadotropin
      - oncogenic osteomalacia
      - consumptive hypothyroidism
    - hematologic syndromes.
      - erythrocytosis
      - granulocytosis
      - thrombocytosis
      - eosinophilia
      - thrombophlebitis and deep venous thrombosis.
    - miscellaneous remote effects ofcancer.
    - further reading.
  - 94 paraneoplastic neurologic syndromes and autoimmune encephalitis
    - pathogenesis
    - approach to the patient: paraneoplastic neurologic disorders
    - specific paraneoplastic neurologic syndromes
      - paraneoplastic encephalomyelitis and focal encephalitis with antibodies against intracellular neuronal proteins.
      - encephalitides with antibodies to cell-surface or synaptic proteins
      - paraneoplastic cerebellar degeneration
      - paraneoplastic opsoclonus-myoclonus syndrome
      - paraneoplastic syndromes of the spinal cord.
      - paraneoplastic stiff-person syndrome
      - paraneoplastic sensory neuronopathy or dorsal root ganglionopathy.
      - paraneoplastic peripheral neuropathies
      - lambert-eaton myasthenic syndrome.
      - myasthenia gravis.
      - polymyositis-dermatomyositis
      - immune-mediated necrotizing myopathy
      - paraneoplastic visual syndromes.
    - further reading.
  - 95 cancer survivorship and the long-term impact of cancer and its treatment.
    - cardiovascular dysfunction
    - pulmonary dysfunction.
    - immune system dysfunction.
    - reproductive and endocrine dysfunction
    - neurologic dysfunction
    - hepatic and gastrointestinal dysfunction
    - renal and bladder dysfunction.
    - psychological dysfunction and socioeconomic impact of survivorship
    - cancer survivorship care plans
    - outlook.
    - further reading.
- section 2 hematopoietic disorders.
  - 96 hematopoietic stem cells.
    - cardinal functions of hematopoietic stem cells
      - developmental biology of hematopoieticstem cells
      - mobility of hematopoietic stem cells
      - hematopoietic stem cell microenvironment
      - excess capacity of hematopoietic stem cells.
      - hematopoietic stem cell differentiation.
      - self-renewal
    - cancer is similar to an organ with self-renewing capacity.
    - what else can hematopoietic stem cells do?
    - stem cells as targets of gene therapy.
    - further reading.
  - 97 iron deficiency and other hypoproliferative anemias
    - iron metabolism.
      - the iron cycle in humans
      - nutritional iron balance
    - iron-deficiency anemia
      - stages of iron deficiency.
      - causes of iron deficiency.
      - clinical presentation of iron deficiency
      - laboratory iron studies.
      - differential diagnosis
      - treatment.
    - other hypoproliferative anemias.
      - anemia of acute and chronic inflammation/infection (Ai).
      - anemia of chronic kidney disease (Ckd)
      - anemia in hypometabolic states
      - anemia in aging.
      - treatment: hypoproliferative anemias
    - further reading.
  - 98 disorders of hemoglobin
    - hemoglobin
      - developmental biology.
      - globin gene clusters
      - hemoglobin structure
      - hemoglobin function.
      - globin gene switching.
    - diagnosis of hemoglobin disorders.
    - sickle cell disease.
      - origin, spread, and epidemiology
      - pathophysiology.
      - diagnosis.
      - complications.
      - sickle cell trait (Carriers, or simple heterozygosity for the hbs gene).
      - treatment, screening, counseling, and antenatal diagnosis.
    - thalassemia.
    - β thalassemia.
      - epidemiology
      - classification
      - diagnosis.
      - complications.
      - management, screening, counseling,and antenatal diagnosis.
    - α thalassemia.
      - epidemiology
      - classification
      - pathophysiology.
      - diagnosis.
      - complications.
      - management, screening, counseling, and antenatal diagnosis
    - other hemoglobinopathies of clinical importance.
      - m hemoglobins.
      - unstable hemoglobins
      - hemoglobins with high oxygen affinity and low oxygen affinity.
      - acquired disorders of hemoglobin
    - further reading.
  - 99 megaloblastic anemias
    - cobalamin.
      - dietary sources and requirements
      - absorption
      - transport.
    - folate
      - dietary folate
      - absorption
      - transport.
      - biochemical functions.
    - biochemical basis of megaloblastic anemia.
    - clinical features.
    - hematologic findings
      - peripheral blood
      - bone marrow.
      - chromosomes.
      - ineffective hematopoiesis.
    - causes of cobalamin deficiency
      - inadequate dietary intake.
      - gastric causes of cobalamin malabsorption.
      - juvenile pernicious anemia
      - congenital intrinsic factor deficiency or functional abnormality
      - gastrectomy.
      - food cobalamin malabsorption
      - intestinal causes of cobalamin malabsorption
      - abnormalities of cobalamin metabolism.
    - causes of folate deficiency.
      - nutritional.
      - malabsorption.
      - excess utilization or loss
      - antifolate drugs
      - congenital abnormalities of folate metabolism.
    - diagnosis of cobalamin and folate deficiencies
    - treatment.
    - megaloblastic anemia not due to cobalamin or folate deficiency or altered metabolism
  - 100 hemolytic anemias.
    - definitions.
    - general clinical and laboratoryfeatures.
    - general pathophysiology.
    - inherited hemolytic anemias.
      - hemolytic anemias due to abnormalities of the membranecytoskeleton complex
        hereditary spherocytosis
        
        hereditary elliptocytosis.
      - channelopathies.
      - enzyme abnormalities .
        abnormalities of the glycolytic pathway.
        pyruvate kinase deficiency
        
        other glycolytic enzyme abnormalities.
        
        abnormalities of redox metabolism.
        glucose-6-phosphate dehydrogenase (G6pd) Deficiency.
        
        other abnormalities of the redox system.
        
        pyrimidine 5’-nucleotidase (P5n) Deficiency.
      - familial (Atypical) Hemolytic-uremic syndrome (Ahus)
    - acquired hemolytic anemia.
      - mechanical destruction of red cells.
      - infection.
      - immune hemolytic anemias .
        autoimmune hemolytic anemia, warm type (Waiha: for simplicity we will use the acronym aiha).
        
        paroxysmal cold hemoglobinuria (Pch)
        
        cold agglutinin disease.
      - hemolytic anemia from toxic agents and drugs
      - paroxysmal nocturnal hemoglobinuria (Pnh).
    - further reading.
  - 101 anemia due to acute blood loss
    - treatment.
    - further reading.
  - 102 bone marrow failure syndromes including aplastic anemia and myelodysplasia
    - aplastic anemia.
      - definition
      - epidemiology
      - etiology
      - pathophysiology.
      - clinical features.
      - laboratory studies
      - diagnosis.
      - prognosis.
      - treatment.
    - pure red cell aplasia.
      - definition and differential diagnosis.
      - clinical associations and etiology
      - persistent parvovirus b19 infection.
      - treatment.
    - myelodysplastic syndromes.
      - definition
      - epidemiology
      - etiology and pathophysiology
      - clinical features.
      - laboratory studies
      - differential diagnosis
      - prognosis.
      - treatment.
    - myelophthisic anemias.
    - further reading.
  - 103 polycythemia vera and other myeloproliferative neoplasms
    - polycythemia vera.
      - etiology
      - clinical features.
      - diagnosis.
      - complications.
      - treatment.
    - primary myelofibrosis.
      - etiology
      - clinical features.
      - diagnosis.
      - complications.
      - treatment.
    - essential thrombocytosis
      - etiology
      - clinical features.
      - diagnosis.
      - complications.
      - treatment.
    - further reading.
  - 104 acute myeloid leukemia
    - incidence.
    - etiology
    - classification
    - prognostic factors
    - clinical presentation.
      - symptoms
      - physical findings.
      - hematologic findings .
      - pretreatment evaluation.
    - treatment.
      - induction chemotherapy
      - postremission therapy.
      - supportive care.
      - treatment for refractory or relapsed aml
      - treatment of acute promyelocytic leukemia.
    - further reading.
  - 105 chronic myeloid leukemia
    - incidence and epidemiology
    - etiology
    - pathophysiology.
    - clinical presentation.
      - symptoms
      - physical findings
      - hematologic and marrow findings
      - cytogenetic and molecular findings
      - findings in cml transformation
    - prognosis and cml course
    - treatment.
    - global aspects of cml.
    - further reading.
  - 106 acute lymphoid leukemia.
    - incidence and age.
    - etiology
    - congenital disorders
    - infectious agents.
    - diagnosis and classification
    - peripheral blood
    - bone marrow examination.
    - lumbar puncture.
    - morphologic subtypes in all.
    - immunologic subtypes
    - cytogenetic and molecular analysis
    - minimal residual disease
    - molecular response after induction therapy and impact on outcome
    - prognostic factors, risk stratification, and mrd
    - treatment principles
      - pre-phase therapy.
      - induction therapy.
      - postremission consolidation.
      - maintenance therapy.
    - treatment of all patients according to age
    - prophylaxis and treatment of central nervous system leukemia
    - stem cell transplantation.
    - pediatric-inspired therapies for adolescents and young adults.
    - adult all.
    - elderly all.
    - targeted therapies
    - tyrosine kinase inhibitors in philadelphia-positive all.
    - immunotherapeutic approaches
      - anti-cd20.
      - anti-cd22.
      - anti-cd19.
      - car-t cells.
      - toxicities of immunotherapies.
    - treatment of t-all
    - conclusion and future directions
    - further reading.
  - 107 chronic lymphocytic leukemia
    - epidemiology
    - biology and pathophysiology.
      - cell of origin
      - b-cell receptor signaling in cll
      - cytogenetic abnormalities.
      - gene mutations and mir alterations
      - immunology
    - clinical presentation and diagnosisof cll.
    - monoclonal b-cell lymphocytosis.
    - complications of cll
      - infections
      - secondary malignancies
      - autoimmune complications
      - richter’s transformation
    - workup of cll and approach to therapy.
      - workup and staging
      - staging.
      - criteria for the initiation of therapy
      - initial therapy for cll.
        btk inhibitors
        
        bcl2 inhibitor
        
        pi3k inhibitors.
        
        chemoimmunotherapy
      - therapy of relapsed cll.
      - assessing response to therapy and minimal residual disease in cll.
    - conclusion
    - further reading.
  - 108 non-hodgkin’s lymphoma
    - epidemiology and etiology.
    - immunology
    - approach to the patient.
    - clinical features, treatment, and prognosis of specific nhl.
      - mature b-cell neoplasms.
        burkitt’s lymphoma
        
        diffuse large b-cell lymphoma.
        
        follicular lymphoma.
        
        marginal zone lymphoma
        
        lymphoplasmacytic lymphoma
        
        mantle cell lymphoma
      - mature (Peripheral) T cell disorders
        mycosis fungoides.
        
        peripheral t-cell lymphoma, not otherwise specified.
        
        angioimmunoblastic t-cell lymphoma
        
        anaplastic large-cell lymphoma
        
        other ptcl subtypes.
        
        adult t-cell leukemia/lymphoma .
        
        extranodal nk/t-cell lymphoma, nasal type.
    - further reading.
  - 109 hodgkin’s lymphoma
    - epidemiology and etiology.
    - approach to the patient.
    - treatment.
    - further reading.
  - 110 less common lymphoid and myeloid malignancies.
    - rare lymphoid malignancies
      - mature b-cell neoplasms.
        b-cell prolymphocytic leukemia (B-pll)
        
        splenic marginal zone lymphoma (Smzl).
        
        hairy cell leukemia.
        
        nodal marginal zone b cell lymphoma.
        
        mediastinal (Thymic) Large b-cell lymphoma
        
        intravascular large b-cell lymphoma.
        
        primary effusion lymphoma.
        
        lymphomatoid granulomatosis.
      - mature t-cell and nk cell neoplasms.
        t-cell prolymphocytic leukemia
        
        t-cell large granular lymphocytic leukemia
        
        aggressive nk cell leukemia.
        
        extranodal nk/t-cell lymphoma, nasal type.
        
        enteropathy-type t-cell lymphoma
        
        hepatosplenic t-cell lymphoma.
        
        subcutaneous panniculitis-like t-cell lymphoma
        
        blastic nk cell lymphoma
        
        primary cutaneous cd30+ t-cell lymphoma.
        
        angioimmunoblastic t-cell lymphoma
    - rare myeloid malignancies.
      - chronic neutrophilic leukemia.
      - atypical chronic myeloid leukemia.
      - chronic myelomonocytic leukemia.
      - juvenile myelomonocytic leukemia
      - mds/mpn, unclassifiable (Mds/mpn-u).
      - mds/mpn with ring sideroblasts and thrombocytosis (Mds/mpn-rs-t)
      - myeloproliferative neoplasm, unclassifiable (Mpn-u).
      - myeloid neoplasms with germline predisposition
      - transient myeloproliferative disorder (Tmd).
      - primary eosinophilia
      - mastocytosis
      - dendritic and histiocytic neoplasms.
    - further reading.
  - 111 plasma cell disorders.
    - multiple myeloma
      - definition
      - etiology
      - incidence and prevalence
      - global considerations.
      - pathogenesis and clinical manifestations
      - diagnosis and staging.
      - prognosis.
      - treatment.
    - waldenström’s macroglobulinemia.
    - poems syndrome
    - heavy chain diseases
      - gamma heavy chain disease (Franklin’s disease)
      - alpha heavy chain disease (Seligmann’s disease).
      - mu heavy chain disease
    - further reading.
  - 112 amyloidosis.
    - general principles
    - al amyloidosis
      - etiology and incidence
      - pathology and clinical features
      - diagnosis
      - staging system and risk stratification
      - treatment
    - aa amyloidosis
      - etiology and incidence
      - pathology and clinical features.
      - treatment.
    - attr and af amyloidosis.
    - aβ2m amyloidosis
    - therapeutic frontiers.
    - summary.
    - further reading.
  - 113 transfusion therapy and biology.
    - blood components
    - blood group antigens and antibodies.
    - clinical indications and efficacy assessment of blood components
    - adverse reactions to blood components.
      - immune-mediated adverse reactions.
        hemolytic transfusion adverse reactions.
        
        febrile nonhemolytic transfusion reaction.
        
        allergic reactions
        
        graft-versus-host disease.
        
        transfusion-related acute lung injury.
        
        posttransfusion purpura.
        
        alloimmunization/platelet refractoriness
        
        immunomodulation
      - nonimmunologic transfusion adversereactions.
        fluid overload
        
        massive transfusion-associated reactions/electrolyte and cold toxicity reactions
        
        iron overload
        
        hypotensive reactions
        
        adverse transfusion reactions of uncertain imputability.
      - infectious adverse reactions
    - alternatives and perspectives.
    - further reading.
  - 114 hematopoietic cell transplantation
    - the hematopoietic stem cell.
    - categories of hematopoietic celltransplantation.
    - the transplant preparative regimen
      - the transplant procedure
      - engraftment and immune reconstitution.
      - complications following hematopoietic cell transplantation
        early direct chemoradiotoxicities.
        
        late direct chemoradiotoxicities
        
        graft failure.
        
        graft-versus-host disease.
        
        infection.
    - treatment.
      - immunodeficiency disorders
      - aplastic anemia.
      - hemoglobinopathies
      - other nonmalignant diseases.
      - acute leukemia
      - chronic leukemia
      - myelodysplasia and myeloproliferativedisorders
      - lymphoma
      - myeloma.
      - solid tumors
      - posttransplant relapse
    - further reading.
- section 3 disorders of hemostasis.
  - 115 disorders of platelets and vessel wall
    - the platelet
    - the vessel wall.
    - disorders of platelets
      - thrombocytopenia
        approach to the patient.
        
        infection-induced thrombocytopenia
        
        drug-induced thrombocytopenia.
        
        heparin-induced thrombocytopenia
        
        immune thrombocytopenic purpura.
        
        inherited thrombocytopenia
      - thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome.
        thrombotic thrombocytopenic purpura.
        
        hemolytic-uremic syndrome.
      - thrombocytosis
      - qualitative disorders of platelet function
        inherited disorders of platelet function
        
        acquired disorders of platelet function.
      - von willebrand disease
    - disorders of the vessel wall
      - metabolic and inflammatory disorders
      - inherited disorders of the vessel wall
    - further reading.
  - 116 coagulation disorders.
    - hemophilia a and b
    - factor xi deficiency
    - rare bleeding disorders.
    - familial multiple coagulation deficiencies
    - disseminated intravascular coagulation
    - vitamin k deficiency
    - coagulation disorders associated with liver failure.
    - further reading.
  - 117 arterial and venous thrombosis
    - overview of thrombosis
    - arterial thrombosis.
      - overview of arterialthrombosis
      - arterial thrombosisand vascular disease.
      - the platelet
      - the role of platelets and thrombosis ininflammation.
        genetics of arterial thrombosis
    - venous thrombosis.
      - overview of venous thrombosis.
      - deep-venous thrombosis and pulmonary embolism.
      - overview of the coagulation cascade and its role in venous thrombosis.
      - risk factors for venous thrombosis
      - genetics of venous thrombosis.
      - fibrinolysis and thrombosis.
    - the distinction between arterial and venous thrombosis
    - further reading.
  - 118 antiplatelet, anticoagulant, and fibrinolytic drugs.
    - antiplatelet drugs
      - role of platelets in arterial thrombosis
      - aspirin.
      - adp receptor antagonists
      - dipyridamole
      - gp iib/iiia receptor antagonists
      - vorapaxar.
    - anticoagulants
      - parenteral anticoagulants.
        heparin.
        
        low-molecular-weight heparin
        
        fondaparinux
        
        parenteral direct thrombin inhibitors.
      - oral anticoagulants.
        warfarin
        
        direct oral anticoagulants
    - fibrinolytic drugs
      - role of fibrinolytic therapy
      - mechanism of action.
      - streptokinase.
      - anistreplase
      - urokinase.
      - alteplase.
      - tenecteplase
      - reteplase.
    - conclusions and future directions.
    - further reading.
part 5 infectious diseases
- section 1 basic considerations in infectious diseases.
  - 119 approach to the patient with an infectious disease
    - historical perspective
    - global considerations.
    - understanding the microbiota
    - when to consider an infectious etiology.
    - approach to the patient.
    - perspective.
    - further reading.
  - 120 molecular mechanisms of microbial pathogenesis
    - entry into the human host.
    - establishment of infection
      - niche.
      - attachment
      - replicative niche.
    - survival in the vacuole.
      - type iii secretion systems
      - type iv secretion systems.
      - other secretion systems.
    - survival in the cytosol.
      - nutrient acquisition
      - cellular trafficking
    - avoidance of innate immune responses
      - complement
      - lysosomes.
      - antimicrobial peptides
      - oxidative burst.
      - neutrophil extracellular traps
      - pattern recognition receptors and their evasion.
      - inhibition of adaptive immune responses.
      - bacterial cytotoxins
      - tissue damage and pathogen dissemination
      - competition with commensal microbes
    - summary
    - further reading
  - 121 microbial genomics and infectious disease
    - microbial diagnostics
      - historical limitations and progress through genetic approaches
      - organism identification
      - pathogen discovery
      - antibiotic resistance
      - host-based diagnostics
    - therapeutics
      - genomic diagnostics informing therapeutics
      - genomics in drug and vaccine development
    - epidemiology of infectious diseases
      - transmission networks
      - origins and dynamics of pathogen spread
      - epidemic potential
      - pathogen evolution
    - global considerations
    - genomics and the covid-19 pandemic
    - summary
    - further reading
  - 122 approach to the acutely ill infected febrile patient
    - approach to the patient
    - treatment
    - specific presentations
    - sepsis without an obvious focus of primary infection
      - septic shock
      - overwhelming infection in asplenic patients
      - babesiosis
      - other sepsis syndromes
    - sepsis with skin manifestations
      - meningococcemia
      - rocky mountain spotted fever and other rickettsial diseases
      - purpura fulminans
      - ecthyma gangrenosum
      - other infections associated with rash
      - erythroderma
      - viral hemorrhagic fevers
    - sepsis with a soft tissue/muscle primary focus
      - necrotizing fasciitis
      - clostridial myonecrosis
    - neurologic infections with or without septic shock
      - bacterial meningitis
      - suppurative intracranial infections
      - brain abscess
      - cerebral malaria
      - intracranial and spinal epidural abscesses
    - other focal syndromes with afulminant course
      - rhinocerebral mucormycosis
      - acute bacterial endocarditis
      - inhalational anthrax
      - viral respiratory tract illness
      - avian and swine influenza
      - sars, covid-19, and mers
      - hantavirus pulmonary syndrome
      - clostridioides difficile infection
    - summary
    - further reading
  - 123 immunization principles and vaccine use
    - vaccine impact
      - direct and indirect effects
      - control, elimination, and eradication of vaccine-preventable diseases
      - outbreak detection and control
      - enhancing immunization in adults
    - immunization practice standards
      - deciding whom to vaccinate
      - assessing contraindications and precautions
      - history of immediate hypersensitivity to a vaccine component
      - pregnancy
      - immunosuppression
    - vaccine information statements
    - storage and handling
    - administration of vaccines
    - maintenance of vaccine records
    - vaccine safety monitoring and adverse event reporting
      - prelicensure evaluations of vaccine safety
      - postlicensure monitoring of vaccine safety
    - consumer access to and demand for immunization
    - strategies for providers and health care facilities
      - recommendation from the provider
      - system supports
      - immunization requirements
      - vaccination of health care staff
    - vaccination in nonmedical settings
    - performance monitoring
    - future trends
    - further reading
  - 124 health recommendations for international travel
    - epidemiology of travel-related conditions
    - general approach to advising international travelers
    - immunizations for travelers
      - immunizations for travelersto most destinations
      - immunizations for certainregions or situations
    - prevention of arthropod-borne infections
      - malaria prevention
      - prevention of other arthropod-borne infections
    - gastrointestinal illness
    - prevention of other travel-related problems
      - activity-specific infection risks
      - venous thromboembolism
      - altitude illness
      - jet lag
      - injuries
    - travelers with preexisting medical conditions
      - immunocompromised travelers
      - hiv-infected travelers
      - pregnant travelers
      - travelers with severe allergies
    - other pre-travel preparations
      - travel health kits
      - traveling with prescription medications
      - health care overseas and travel health insurance
    - special travel populations
    - post-travel medical care
    - outbreaks and emerging infectious diseases
    - further reading
  - 125 climate change and infectious disease
    - overview
      - greenhouse gases
      - temperature
      - precipitation
      - hurricanes
      - sea level rise
      - el niño southern oscillation
      - population migration and conflict
    - effects of climate change on infectious disease
      - vector-borne disease
        malaria
        
        dengue
        
        other arbovirus infections
        
        lyme disease
      - waterborne disease
        combined sewer systems
        
        rising temperatures and vibrio species
    - climate change, population displacement, and infectious disease epidemics
    - a broader view of climate change and health
    - further reading
- section 2 clinical syndromes: community-acquired infections
  - 126 pneumonia
    - definition
    - pathophysiology
    - pathology
    - community-acquired pneumonia
      - etiology
      - epidemiology
      - clinical manifestations
      - diagnosis
      - treatment
      - prognosis
      - prevention
    - ventilator-associated pneumonia
      - etiology
      - epidemiology
      - clinical manifestations
      - diagnosis
      - treatment
      - prognosis
      - prevention
    - hospital-acquired pneumonia
    - global impact
    - further reading
  - 127 lung abscess
    - etiology
    - epidemiology
    - pathogenesis
    - pathology and microbiology
    - clinical manifestations
    - differential diagnosis
    - diagnosis
    - treatment
    - complications
    - prognosis and prevention
    - approach to the patient
    - further reading
  - 128 infective endocarditis
    - etiology
    - pathogenesis
    - clinical manifestations
    - diagnosis
    - treatment
    - outcome
    - prevention
    - further reading
  - 129 infections of the skin, muscles, and soft tissues
    - anatomic relationships: clues to the diagnosis of soft tissue infections
    - infections associated with vesicles
    - infections associated with bullae
    - infections associated with crusted lesions
    - folliculitis
    - papular and nodular lesions
    - ulcers with or without eschars
    - erysipelas
    - cellulitis
    - necrotizing fasciitis
    - myositis and myonecrosis
    - diagnosis
    - treatment
    - further reading
  - 130 infectious arthritis
    - approach to the patient
    - acute bacterial arthritis
      - pathogenesis
      - microbiology
      - nongonococcal bacterial arthritis
      - gonococcal arthritis
    - spirochetal arthritis
      - lyme disease
      - syphilitic arthritis
    - mycobacterial arthritis
    - fungal arthritis
    - viral arthritis
    - untitled
    - postinfectious or reactive arthritis
    - infections in prosthetic joints
    - further reading
  - 131 osteomyelitis
    - classification
    - vertebral osteomyelitis
      - pathogenesis
      - epidemiology
      - microbiology
      - clinical manifestations
      - diagnosis
      - treatment
      - complications
      - global considerations
    - osteomyelitis in long bones
      - pathogenesis
      - epidemiology
      - microbiology
      - clinical manifestations
      - diagnosis
      - treatment
      - complications
      - global considerations
    - periprosthetic joint infection
      - pathogenesis
      - epidemiology
      - microbiology
      - classification and clinical manifestations
      - diagnosis
      - treatment
      - prevention of hematogenous infection
      - global considerations
    - sternal osteomyelitis
      - pathogenesis
      - epidemiology
      - microbiology
      - clinical manifestations
      - diagnosis
      - treatment
      - prognosis
      - global considerations
    - foot osteomyelitis
      - pathogenesis
      - epidemiology
      - risk factors
      - microbiology
      - diagnosis
      - treatment
      - global considerations
    - further reading
  - 132 intraabdominal infections and abscesses
    - peritonitis
      - primary (Spontaneous) Bacterial peritonitis
      - secondary peritonitis
      - peritonitis in patients undergoing continuous ambulatory peritoneal dialysis
      - tuberculous peritonitis
    - intraabdominal abscesses
      - intraperitoneal abscesses
        pathogenesis and immunity
        
        clinical presentation
        
        diagnosis
        
        treatment
      - visceral abscesses
        liver abscesses
        
        splenic abscesses
        
        perinephric and renal abscesses
        
        psoas abscesses
        
        pancreatic abscesses
      - further reading
  - 133 acute infectious diarrheal diseases and bacterial food poisoning
    - pathogenic mechanisms
      - inoculum size
      - adherence
      - toxin production
      - invasion
    - host defenses
      - intestinal microbiota
      - gastric acid
      - intestinal motility
      - intestinal mucin
      - immunity
      - genetic determinants
    - approach to the patient
    - epidemiology
      - travel history
      - location
      - age
      - host immune status
      - bacterial food poisoning
      - laboratory evaluation
    - treatment
    - prophylaxis
    - further reading
  - 134 clostridioides difficile infection, including pseudomembranous colitis
    - definition
    - etiology and epidemiology
    - pathology and pathogenesis
    - global considerations
    - clinical manifestations
    - diagnosis
    - treatment
    - prognosis
    - prevention and control
    - further reading
  - 135 urinary tract infections, pyelonephritis, and prostatitis
    - definitions
    - epidemiology and risk factors
    - etiology
    - pathogenesis
    - approach to the patient
    - diagnostic tools
    - diagnostic approach
    - treatment
    - prevention of recurrent uti in women
    - prognosis
    - further reading
  - 136 sexually transmitted infections: overview and clinical approach
    - classification and epidemiology
    - management of common sexually transmitted disease (Std) Syndromes
      - urethritis in men
      - epididymitis
      - urethritis and the urethral syndrome in women
      - vulvovaginal infections
        abnormal vaginal discharge
        
        vaginal trichomoniasis
        
        bacterial vaginosis
        
        vulvovaginal pruritus, burning, or irritation
        
        other causes of vaginal discharge or vaginitis
      - mucopurulent cervicitis
      - cervical ectopy
      - pelvic inflammatory disease
        etiology
        
        epidemiology
        
        clinical manifestations
        
        diagnosis
        
        treatment
        
        prognosis
        
        prevention
      - ulcerative genital or perianal lesions
      - proctitis, proctocolitis, enterocolitis, and enteritis
    - prevention and control of stis
    - sti risk assessment
    - further reading
  - 137 encephalitis
    - definition
    - clinical manifestations
    - etiology
    - laboratory diagnosis
    - csf polymerase chain reaction
    - differential diagnosis
    - treatment
    - sequelae
    - chronic encephalitis
      - progressive multifocal leukoencephalopathy
      - subacute sclerosing panencephalitis
      - progressive rubella panencephalitis
    - further reading
  - 138 acute meningitis
    - bacterial meningitis
    - viral meningitis
    - subacute meningitis
    - further reading
  - 139 chronic and recurrent meningitis
    - clinical pathophysiology
    - approach to the patient: chronic meningitis
    - the immunosuppressed patient
    - further reading
  - 140 brain abscess and empyema
    - brain abscess
      - definition
      - epidemiology
      - etiology
      - pathogenesis and histopathology
      - clinical presentation
      - diagnosis
      - differential diagnosis
      - treatment
      - prognosis
    - nonbacterial causes of infectious focal cns lesions
      - etiology
      - clinical presentation
      - diagnosis
      - treatment
    - subdural empyema
      - epidemiology
      - etiology
      - pathophysiology
      - clinical presentation
      - diagnosis
      - differential diagnosis
      - treatment
      - prognosis
    - cranial epidural abscess
      - etiology and pathophysiology
      - clinical presentation
      - diagnosis
      - treatment
      - prognosis
    - suppurative thrombophlebitis
      - definition
      - anatomy and pathophysiology
      - clinical manifestations
      - diagnosis
      - treatment
    - further reading
  - 141 infectious complications of bites
    - dog bites
    - cat bites
    - other animal bites
    - human bites
    - approach to the patient
    - treatment
    - further reading
- section 3 clinical syndromes: health care–associated infections
  - 142 infections acquired in health care facilities
    - organization, responsibilities, and scrutiny of health care–associated infection programs
    - surveillance
    - epidemiologic basis and general measures for prevention and control
    - nosocomial and device-relatedinfections
      - urinary tract infections
      - pneumonia
      - surgical-site (Wound) Infections
      - infections related to vascular access and monitoring
    - isolation techniques
    - epidemic and emerging problems
      - viral respiratory infections: coronavirus epidemics and pandemic influenza
      - other emerging viral pathogens
      - nosocomial diarrhea
      - chickenpox
      - mycobacteria
      - group a streptococcal infections
      - fungal infections
      - legionellosis
    - antibiotic-resistant bacteria: surveillance, control, and antibiotic and diagnostic stewardship
    - bioterrorism and other surge-event preparedness
    - employee health service issues
    - further reading
  - 143 infections in transplant recipients
    - pretransplantation evaluation
      - the donor
      - the recipient
      - the recipient
      - the donor cells/organ
    - infections in hematopoietic stem cell transplant recipients
      - bacterial infections
      - fungal infections
      - parasitic infections
      - viral infections
      - global considerations
      - kidney transplantation
      - heart transplantation
      - lung transplantation
      - liver transplantation
      - pancreas transplantation
      - composite-tissue transplantation
      - miscellaneous infections in solid organ transplantation
      - vaccination of transplant recipients
    - in memoriam
    - further reading
- section 4 therapy for bacterial diseases
  - 144 treatment and prophylaxis of bacterial infections
    - mechanisms of action
      - inhibition of cell wall synthesis
        β-lactams
        
        glycopeptides and lipoglycopeptides
        
        bacitracin (Topical) And fosfomycin
      - inhibition of protein synthesis
        aminoglycosides
        
        tetracyclines
        
        macrolides and ketolides
        
        lincosamides
        
        streptogramins
        
        chloramphenicol
        
        oxazolidinones
        
        pleuromutilins
        
        mupirocin
      - inhibition of bacterial metabolism
        sulfonamides
        
        trimethoprim
      - inhibition of dna and rna synthesis or activity
        quinolones
        
        rifamycins
        
        nitrofurantoin
        
        metronidazole
      - disruption of membrane integrity
        polymyxins
        
        daptomycin
    - pharmacokinetics and pharmacodynamics
      - pharmacokinetics
      - pharmacodynamics
    - approach to therapy
      - empirical and directed therapy
      - site of infection
      - host factors
      - duration of therapy
      - failure of therapy
      - expert guidance
    - clinical use of antibacterial agents
      - β-lactams
      - glycopeptides and lipoglycopeptides
      - lipopeptides
      - aminoglycosides
      - macrolides and ketolides
      - clindamycin
      - tetracyclines
      - trimethoprim-sulfamethoxazole
      - fluoroquinolones
      - rifamycins
      - metronidazole
      - oxazolidinones
      - pleuromutilins
      - nitrofurantoin
      - polymyxins
      - quinupristin-dalfopristin
      - fosfomycin
      - chloramphenicol
    - approach to prophylaxis of infection
    - antimicrobial stewardship
    - further reading
  - 145 bacterial resistance to antimicrobial agents
    - definition of resistance
    - mechanisms of resistance
      - β-lactams
      - glycopeptides and lipoglycopeptides
      - aminoglycosides
      - tetracyclines
      - macrolides, ketolides, lincosamides, and streptogramins
      - chloramphenicol
      - oxazolidinones
      - pleuromutilins
      - mupirocin
      - sulfonamides and trimethoprim
      - quinolones
      - rifampin and rifabutin
      - metronidazole
      - nitrofurantoin
      - polymyxins
      - daptomycin
    - epidemiology of resistance and reduction of its occurrence
    - further reading
- section 5 diseases caused by gram-positive bacteria
  - 146 pneumococcal infections
    - microbiology
      - etiologic agent
      - virulence factors
    - epidemiology
      - serotype distribution
      - nasopharyngeal carriage
      - invasive disease and pneumonia
      - antibiotic resistance
    - pathogenesis
    - host defense mechanisms
      - innate immunity
      - acquired immunity
    - approach to the patient
    - clinical manifestations
      - pneumonia
      - meningitis
      - other invasive syndromes
      - noninvasive syndromes
    - treatment
    - prevention
      - capsular polysaccharide vaccines
      - polysaccharide–protein conjugate vaccines
      - other prevention strategies
    - global health
    - further reading
    - websites
  - 147 staphylococcal infections
    - microbiology and taxonomy
    - s. Aureus infections
      - epidemiology
      - pathogenesis
      - diagnosis
      - clinical syndromes
    - non–s. Aureus staphylococcal infections
      - pathogenesis
      - diagnosis
      - clinical syndromes
      - treatment
      - prevention
    - further reading
  - 148 streptococcal infections
    - group a streptococci
      - pathogenesis
      - clinical manifestations
        pharyngitis
        
        bacteriologic treatment failure and the asymptomatic carrier state
        
        scarlet fever
        
        skin and soft tissue infections
        
        impetigo (Pyoderma)
        
        cellulitis
        
        deep soft-tissue infections
        
        pneumonia and empyema
        
        bacteremia, puerperal sepsis, and streptococcal toxic shock syndrome
      - prevention
    - streptococci of groups c and g
    - group b streptococci
    - nonenterococcal group d streptococci
    - viridans and other streptococci
      - viridans streptococci
      - abiotrophia and granulicatella species (Nutritionally variant streptococci)
      - other streptococci
    - further reading
  - 149 enterococcal infections
    - microbiology and taxonomy
    - pathogenesis
    - epidemiology
    - clinical syndromes
      - urinary tract infection and prostatitis
      - bacteremia and endocarditis
      - meningitis
      - intraabdominal, pelvic, and soft tissue infections
      - other infections
    - treatment
    - further reading
  - 150 diphtheria and other corynebacterial infections
    - diphtheria
      - etiology
      - epidemiology
      - pathogenesis and immunology
      - approach to the patient
      - clinical manifestations
        respiratory diphtheria
        
        cutaneous diphtheria
        
        infections due to non-diphtheriae corynebacterium species and nontoxigenic c. Diphtheriae
        
        other clinical manifestations
      - complications
      - diagnosis
      - treatment
        diphtheria antitoxin
        
        antimicrobial therapy
        
        management strategies
      - prognosis
      - prevention
        vaccination
        
        prophylaxis administration to contacts
    - other corynebacterial and rhodococcus infections
      - microbiology and laboratory diagnosis
      - epidemiology
      - clincal manifestations
        c. Ulcerans
        
        c. Pseudotuberculosis
        
        c. Jeikeium (Group jk)
        
        c. Urealyticum (Group d2)
        
        c. Minutissimum (Erythrasma)
        
        other nondiphtherial corynebacteria
        
        rhodococcus
        
        arcanobacteria
    - further reading
  - 151 listeria monocytogenes infections
    - microbiology
    - pathogenesis
    - immune response
    - epidemiology
    - clinical manifestations
    - diagnosis
    - treatment
    - prevention
    - further reading
  - 152 tetanus
    - definition
    - etiology
    - epidemiology
    - pathogenesis
    - approach to the patient
    - clinical manifestations
    - diagnosis
    - treatment
    - prognosis
    - prevention
    - further reading
    - websites
  - 153 botulism
    - etiology and pathogenesis
    - epidemiology
    - clinical manifestations
    - clinical diagnosis and laboratory confirmation
    - treatment
    - prevention
    - global considerations
    - further reading
  - 154 gas gangrene and other clostridial infections
    - etiologic agent
    - epidemiology and transmission
    - clinical syndromes
      - clostridial wound contamination
      - polymicrobial infections involving clostridia
      - enteric clostridial infections
      - clostridial bacteremia
      - clostridial skin and soft tissue infections
        clostridial myonecrosis (Gas gangrene)
        
        toxic shock syndrome
        
        other clostridial skin and soft tissue infections
    - further reading
- section 6 diseases caused by gram-negative bacteria
  - 155 meningococcal infections
    - definition
    - etiology and microbiology
    - epidemiology
      - patterns of disease
      - factors associated with disease risk and susceptibility
    - pathogenesis
    - clinical manifestations
      - rash
      - meningitis
      - septicemia
      - chronic meningococcemia
      - postmeningococcal reactive disease
    - diagnosis
    - treatment
    - complications
    - prognosis
    - prevention
      - polysaccharide vaccines
      - conjugate vaccines
      - vaccines based on subcapsular antigens
    - management of contacts
    - further reading
  - 156 gonococcal infections
    - definition
    - microbiology
    - epidemiology
    - pathogenesis, immunology, and antimicrobial resistance
      - outer-membrane proteins
      - lipooligosaccharide
      - host factors
      - gonococcal resistance to antimicrobial agents
    - clinical manifestations
      - gonococcal infections in men
      - gonococcal infections in women
      - anorectal gonorrhea
      - pharyngeal gonorrhea
      - ocular gonorrhea in adults
      - gonorrhea in pregnant women, neonates, and children
      - gonococcal arthritis
      - gonococcal infections in hiv-infected persons
    - laboratory diagnosis
    - treatment
    - prevention and control
      - further reading
  - 157 haemophilus and moraxella infections
    - haemophilus influenzae
      - microbiology
      - epidemiology and transmission
      - pathogenesis
      - immune response
      - clinical manifestations
        hib
        
        nontypable h. Influenzae
      - diagnosis
      - treatment
      - prevention
        vaccination
        
        chemoprophylaxis
    - haemophilus ducreyi
      - microbiology
      - epidemiology and prevalence
      - clinical manifestations and differential diagnosis
      - diagnosis
      - treatment
    - moraxella catarrhalis
      - microbiology
      - epidemiology
      - pathogenesis
      - clinical manifestations
      - diagnosis
      - treatment
      - further reading
  - 158 infections due to the hacek group and miscellaneous gram-negative bacteria
    - the hacek group
    - other fastidious gram-negative bacteria
    - other gram-negative bacteria
    - miscellaneous organisms
  - 159 legionella infections
    - pathogen and pathogenicity
    - epidemiology
    - clinical presentations
      - legionella pneumonia
      - pontiac fever
      - extrapulmonary disease
    - diagnosis
      - radiologic findings
      - laboratory diagnostics
    - treatment
    - outcomes
    - prevention
    - further reading
  - 160 pertussis and other bordetella infections
    - microbiology
    - epidemiology
    - pathogenesis
    - immunity
    - clinical manifestations
    - complications
    - diagnosis
    - differential diagnosis
    - treatment
    - prevention
    - further reading
  - 161 diseases caused by gram-negative enteric bacilli
    - general features and principles
      - epidemiology
      - structure and function
      - pathogenesis
      - infectious syndromes
      - diagnosis
      - treatment
      - prevention
    - escherichia coli infections
      - commensal strains
      - extraintestinal pathogenic strains
      - intestinal pathogenic strains
    - klebsiella infections
      - infectious syndromes
      - diagnosis
      - treatment
    - proteus infections
      - infectious syndromes
      - diagnosis
      - treatment
    - enterobacter and cronobacter infections
      - infectious syndromes
      - diagnosis
      - treatment
    - serratia infections
      - infectious syndromes
      - diagnosis
      - treatment
    - citrobacter infections
      - infectious syndromes
      - diagnosis
      - treatment
    - morganella and providencia infections
      - infectious syndromes
      - diagnosis
      - treatment
    - edwardsiella infections
      - infectious syndromes
      - diagnosis
      - treatment
    - infections caused by miscellaneous genera
    - further reading
  - 162 acinetobacter infections
    - definition
    - etiology and epidemiology
    - pathogenesis
    - clinical manifestations
      - pneumonia
      - bloodstream infections
      - skin and soft tissue infections
      - urinary tract infections
      - meningitis
      - other miscellaneous infections
    - treatment
    - complications and prognosis
    - infection control and prevention
    - further reading
  - 163 helicobacter pylori infections
    - etiologic agent
    - epidemiology
    - pathology and pathogenesis
    - clinical manifestations
    - peptic ulcer disease
    - diagnosis
    - treatment
    - prevention
    - further reading
  - 164 infections due to pseudomonas, burkholderia, and stenotrophomonas species
    - pseudomonas aeruginosa
      - epidemiology
      - laboratory features
      - pathogenesis
      - clinical manifestations
        bacteremia
        
        acute pneumonia
        
        chronic respiratory tract infections
        
        endovascular infections
        
        bone and joint infections
        
        central nervous system (Cns) Infections
        
        eye infections
        
        ear infections
        
        urinary tract infections
        
        skin and soft tissue infections
        
        infections in febrile neutropenic patients
        
        infections in patients with aids
        
        gastrointestinal infections
        
        multidrug-resistant infections
    - burkholderia species
      - burkholderia cepacia complex
      - burkholderia pseudomallei
      - burkholderia mallei
    - stenotrophomonas maltophilia
    - further reading
  - 165 salmonellosis
    - etiology
    - pathogenesis
    - enteric (Typhoid) Fever
    - nontyphoidal salmonellosis
    - further reading
  - 166 shigellosis
    - etiologic agent
    - epidemiology
    - pathogenesis and pathology
    - clinical manifestations
    - laboratory diagnosis
    - treatment
    - prevention
    - further reading
  - 167 infections due to campylobacter and related organisms
    - definition
    - etiology
    - epidemiology
    - pathology and pathogenesis
    - clinical manifestations
    - complications
    - diagnosis
    - differential diagnosis
    - treatment
    - prognosis
    - further reading
  - 168 cholera and other vibrioses
    - cholera
      - definition
      - microbiology and epidemiology
      - pathogenesis
      - clinical manifestations
      - diagnosis
      - treatment
      - prevention
    - other vibrio species
      - species associated primarily with gastrointestinal illness
        v. Parahaemolyticus
        
        non-o1/o139 (Noncholera) V. Cholerae
      - species associated primarily with soft tissue infection or bacteremia
        v. Vulnificus
        
        v. Alginolyticus
    - further reading
  - 169 brucellosis
    - definition
    - etiologic agents
    - epidemiology
    - immunity and pathogenesis
    - clinical features
    - diagnosis
    - treatment
    - prognosis and follow-up
    - prevention
    - further reading
  - 170 tularemia
    - definition
    - francisella species, subspecies, and clades
    - epidemiology
      - geographic distribution
      - reservoirs and modes of transmission
      - at-risk exposures and populations
      - natural cycles of f. Tularensis
    - pathogenesis
    - clinical manifestations
      - severe type a tularemia
      - more common presentations of tularemia
    - diagnosis
      - nonspecific biologic findings
      - radiologic findings
      - clinical samples
      - serologic diagnosis
      - culture-based diagnosis
      - molecular diagnosis
      - optimized diagnostic strategy
    - treatment
      - antibiotic therapy
      - surgical treatment
    - prognosis
    - prevention
      - lack of human-to-human transmission
      - exposure prevention
      - postexposure prophylaxis
      - vaccination
    - further reading
  - 171 plague and other yersinia infections
    - plague
      - etiology
      - epidemiology
      - global features
      - pathogenesis
      - clinical manifestations
      - laboratory diagnosis
      - treatment
      - prevention
    - yersiniosis
      - epidemiology
      - pathogenesis
      - clinical manifestations
      - postinfective phenomena
      - laboratory diagnosis
      - treatment
      - prevention and control
    - further reading
  - 172 bartonella infections, including cat-scratch disease
    - cat-scratch disease
      - definition and etiology
      - epidemiology
      - pathogenesis
      - clinical manifestations and prognosis
      - diagnosis
      - treatment
      - prevention
    - trench fever and chronic bacteremia
      - definition and etiology
      - epidemiology
      - clinical manifestations
      - diagnosis
      - treatment
    - bartonella endocarditis
      - definition and etiology
      - epidemiology
      - clinical manifestations
      - diagnosis
      - treatment
    - bacillary angiomatosis and peliosis
      - definition and etiology
      - epidemiology
      - clinical manifestations
      - pathology
      - diagnosis
      - treatment
      - prevention
    - carrión’s disease (Oroya fever and verruga peruana)
      - definition and etiology
      - epidemiology and prevention
      - pathogenesis
      - clinical manifestations
      - diagnosis and approach to the patient
      - treatment
      - complications and prognosis
    - further reading
  - 173 donovanosis
    - etiology
    - epidemiology
    - clinical features
    - diagnosis
    - treatment
    - control and prevention
    - further reading
- section 7 miscellaneous bacterial infections
  - 174 nocardiosis
    - epidemiology
    - pathology and pathogenesis
    - clinical manifestations
      - respiratory tract disease
      - extrapulmonary disease
      - disease following transcutaneous inoculation
      - eye infections
    - diagnosis
    - treatment
    - further reading
  - 175 actinomycosis
    - etiologic agents
    - epidemiology
    - pathogenesis and pathology
    - clinical manifestations
      - oral–cervicofacial disease
      - thoracic disease
      - abdominal disease
      - pelvic disease
      - central nervous system disease
      - musculoskeletal and soft tissue infection
      - disseminated disease
    - diagnosis
    - treatment
    - further reading
  - 176 whipple’s disease
    - etiologic agent
    - epidemiology
    - pathogenesis and pathology
    - clinical manifestations
      - asymptomatic colonization/carriage
      - acute infection
      - chronic infection
    - diagnosis
    - treatment
    - further reading
  - 177 infections due to mixed anaerobic organisms
    - historical perspective
    - differences between anaerobic and aerobic organisms
    - anaerobes of the human microbiota
    - anaerobes and human health
    - etiology
    - pathogenesis
    - approach to the patient
    - epidemiology
    - clinical manifestations
      - anaerobic infections of the mouth, head, and neck
      - central nervous system (Cns) Infections
      - pleuropulmonary infections
      - intraabdominal infections
      - pelvic infections
      - skin and soft tissue infections
      - bone and joint infections
      - bacteremia
      - endocarditis
    - diagnosis
    - treatment
      - antibiotic therapy and resistance
      - failure of therapy
    - further reading
- section 8 mycobacterial diseases
  - 178 tuberculosis
    - etiologic agent
    - epidemiology
    - pathogenesis and immunity
      - infection and macrophage invasion
      - virulence of tubercle bacilli
      - innate resistance to infection
      - the host response, granuloma formation, and “latency”
      - macrophage-activating response
      - delayed-type hypersensitivity
      - role of macrophages and monocytes
      - role of t lymphocytes
      - mycobacterial lipids and proteins
      - skin-test reactivity
    - clinical manifestations
      - pulmonary tb
        primary disease
        
        postprimary (Adult-type) Disease
      - extrapulmonary tb
        lymph node tb (Tuberculous lymphadenitis)
        
        pleural tb
        
        tb of the upper airways
        
        genitourinary tb
        
        skeletal tb
        
        tb of the central nervous system (Cns) Accounts for ~5% of extrapulmonary cases in figure 178-9 mri of culture-confirmed renal tuberculosis. T2-weighted coronary plane: coronal sections showing several renal lesions in both the cortical and the medullary tissues of the right kidney. (Courtesy of dr. Alberto matteelli, department
        
        gastrointestinal tb
        
        pericardial tb (Tuberculous pericarditis)
        
        miliary or disseminated tb
        
        less common extrapulmonary forms
        
        post-tb complications
        
        hiv-associated tb
    - diagnosis
      - nucleic acid amplification technology
      - afb microscopy
      - mycobacterial culture
      - drug susceptibility testing
      - radiographic procedures
      - additional diagnostic procedures
      - serologic and other diagnostic tests for active tb
      - biomarkers
      - diagnosis of m. Tuberculosis infection
        tuberculin skin testing
        
        ifn-γ release assays
    - treatment
      - drugs
      - regimens
      - patient care and support
      - monitoring treatment response and drug toxicity
      - treatment failure and relapse
      - drug-resistant tb
      - hiv-associated tb
      - special clinical situations
    - prevention
      - bcg vaccination
      - tb preventive treatment (Tpt)
      - principles of tb control
    - further reading
    - websites
  - 179 leprosy
    - etiology
      - ultrastructural characteristics of m. Leprae
      - genome of m. Leprae
      - culture difficulties
      - immunologic properties of m. Leprae
      - mycobacterium lepromatosis
    - epidemiology
      - incidence, prevalence, and disability
      - sex, age, and geographic distribution
      - transmission
      - reservoirs of infection
      - incubation period, the role of contacts, and genetic susceptibility
    - pathogenesis
      - ridley-jopling classification of leprosy
      - who simplified clinical classification of leprosy
    - clinical manifestations
      - indeterminate leprosy (Il)
      - tuberculoid (Tt) Leprosy
      - borderline tuberculoid (Bt) Leprosy
      - mid-borderline (Bb) Leprosy
      - borderline lepromatous (Bl) Leprosy
      - lepromatous (Ll) Leprosy
      - primary neuritic leprosy
    - leprosy reactions
      - type 1 leprosy reaction (T1r)
      - type 2 leprosy reaction (T2r)
      - lucio’s phenomenon
      - nerve function impairment, neuritis, and disfigurement
    - diagnosis
      - clinical diagnosis
      - diagnostic tools
        testing of skin sensation
        
        slit-skin smear
        
        skin biopsy
        
        pgl-1 antibody test
        
        lepromin test
        
        gene amplification (Pcr) Technique
      - differential diagnosis
      - diagnostic tools for nerve function impairment
        touch sensation testing
        
        voluntary muscle testing
        
        nerve conduction tests
        
        ultrasound testing of nerves
        
        other tests of peripheral nerve function
    - treatment
      - treatment of leprosy
      - treatment of leprosy reactions
      - treatment and prognosis of nerve function impairment
      - treatment of (Neuropathic) Pain
      - disease management during treatment
    - rehabilitation and social aspects
      - physical rehabilitation
      - mental and social support
    - prevention and control
      - interruption of transmission and novel preventive strategies
      - vaccines against leprosy
      - postexposure chemoprophylaxis
      - “zero leprosy”
    - further reading
  - 180 nontuberculous mycobacterial infections
    - epidemiology
    - pathobiology
    - clinical manifestations
      - disseminated disease
      - pulmonary disease
      - cervical lymph nodes
      - skin and soft tissue disease
    - diagnosis
    - prevention
    - treatment
    - prognosis
    - global considerations
    - further reading
  - 181 antimycobacterial agents
    - tuberculosis
      - general principles
      - first-line antituberculosis drugs
        isoniazid
        
        rifampin
        
        pyrazinamide
        
        ethambutol
      - other rifamycin drugs
        rifabutin
        
        rifapentine
      - second-line antituberculosis drugs
        group a
        fluoroquinolones
        
        diarylquinolines
        
        oxazolidinones
        
        group b
        clofazimine
        
        cycloserine
        
        group c
        nitroimidazoles
        
        amoxicillin-clavulanate and carbapenems
        
        aminoglycosides
        
        ethionamide
        
        para-aminosalicylic acid
      - drugs in development
    - nontuberculous mycobacteria
      - therapeutic considerations forspecific ntm
        slowly growing mycobacteria
        
        rapidly growing mycobacteria
      - drugs for the treatment of ntm
        azithromycin
        
        amikacin liposome inhalation suspension (Alis)
        
        imipenem
        
        cefoxitin
        
        newer drugs
    - conclusion
    - further reading
- section 9 spirochetal diseases
  - 182 syphilis
    - definition
    - etiology
    - transmission and epidemiology
      - syphilis in the united states
      - global syphilis
    - natural course and pathogenesis ofuntreated syphilis
    - clinical manifestations
      - primary syphilis
      - secondary syphilis
      - latent syphilis
      - reinfection syphilis
      - involvement of the cns
      - other manifestations of late syphilis
      - congenital syphilis
    - laboratory examinations
      - demonstration of the organism
      - serologic tests for syphilis
      - evaluation for neurosyphilis
      - evaluation of hiv-infected patients for syphilis
    - treatment
      - treatment of acquired syphilis
      - evaluation and management of congenital syphilis
      - jarisch-herxheimer reaction
      - follow-up evaluation of responses to therapy
    - immunity to syphilis
    - further reading
  - 183 endemic treponematoses
    - epidemiology
    - microbiology
    - clinical features
    - diagnosis
    - treatment
    - control
    - further reading
  - 184 leptospirosis
    - etiologic agent
    - epidemiology
    - pathogenesis
    - clinical manifestations
    - diagnosis
    - differential diagnosis
    - treatment
    - prognosis
    - prevention
    - further reading
  - 185 relapsing fever and borrelia miyamotoi disease
    - etiologic agent
    - epidemiology
    - pathogenesis and immunity
    - clinical manifestations
    - diagnosis
    - differential diagnosis
    - treatment
    - prognosis
    - prevention
    - further reading
  - 186 lyme borreliosis
    - definition
    - etiologic agent
    - epidemiology
    - pathogenesis and immunity
    - clinical manifestations
      - early infection: stage 1 (Localized infection)
      - early infection: stage 2 (Disseminated infection)
      - late infection: stage 3 (Persistent infection)
      - post-lyme syndrome (Chronic lyme disease)
    - diagnosis
    - differential diagnosis
    - treatment
    - prognosis
    - reinfection
    - prevention
    - further reading
- section 10 diseases caused by rickettsiae, mycoplasmas, and chlamydiae
  - 187 rickettsial diseases
    - tick-, mite-, louse-, and flea-borne rickettsioses
      - rocky mountain spotted fever
      - mediterranean spotted fever (Boutonneuse fever), african tick-bite fever, and other tick-borne spotted fevers
      - rickettsialpox
      - flea-borne spotted fever
      - epidemic (Louse-borne) Typhus
      - endemic murine typhus
      - scrub typhus
    - ehrlichioses and anaplasmosis
      - human monocytotropic ehrlichiosis
      - ewingii ehrlichiosis and ehrlichia muris eauclairensis infections
        “candidatus neoehrlichia mikurensis”infection
      - human granulocytotropic anaplasmosis
    - q fever
    - further reading
  - 188 infections due to mycoplasmas
    - mycoplasma pneumoniae
    - urogenital mycoplasmas
  - 189 chlamydial infections
    - etiologic agents
    - biology, growth cycle, and pathogenesis
    - c. Trachomatis infections
      - genital infections
      - trachoma
    - psittacosis
    - c. Pneumoniae infections
    - further reading
- section 11 viral diseases: general considerations
  - 190 principles of medical virology
    - virus structure
    - classification of viruses
    - viral replication in cells
    - viral effects on the host cell
    - host antiviral responses and viral antagonistic mechanisms
    - molecular epidemiology of viruses
    - detection and quantification of viruses
    - detection of virus-specific antibodies
    - immunization against viral diseases
    - antiviral therapeutics
    - summary
  - 191 antiviral chemotherapy, excluding antiretroviral drugs
    - antiviral drugs for herpesvirus infections
    - antiviral drugs for respiratory virus infections
    - antiviral drugs for human papillomavirus and poxvirus infections
    - investigational antiviral drugs for picornavirus
    - antiviral drugs for hepatitis b virus infection
    - antiviral drugs for hepatitis c infection
    - further reading
- section 12 infections due to dna viruses
  - 192 herpes simplex virus infections
    - definition
    - etiologic agent
    - pathogenesis
    - immunity
    - epidemiology
    - clinical spectrum
    - diagnosis
    - treatment
    - prevention
    - further reading
  - 193 varicella-zoster virus infections
    - definition
    - etiology
    - pathogenesis and pathology
      - primary infection
      - recurrent infection
    - epidemiology and clinical manifestations
      - chickenpox
      - herpes zoster
    - differential diagnosis
    - laboratory findings
    - treatment
    - prevention
    - further reading
  - 194 epstein-barr virus infections, including infectious mononucleosis
    - definition
    - epidemiology
    - pathogenesis
    - clinical manifestations
    - diagnosis
    - treatment
    - prevention
    - further reading
  - 195 cytomegalovirus and human herpesvirus types 6, 7, and 8
    - cytomegalovirus
      - definition
      - epidemiology
      - pathogenesis
      - pathology
      - clinical manifestations
      - diagnosis
      - prevention
      - treatment
    - human herpesvirus (Hhv) Types 6, 7, and 8
      - hhv-6 and hhv-7
      - hhv-8
    - further reading
  - 196 molluscum contagiosum, monkeypox, and other poxvirus infections
    - poxviruses
      - definition and etiology
      - epidemiology
      - pathogenesis
      - approach to the patient
      - clinical manifestations
      - diagnosis
      - treatment
      - complications
      - prognosis
      - prevention
    - select poxvirus infections
      - molluscum contagiosum
      - monkeypox virus
      - other poxvirus infections of humans
    - further reading
  - 197 parvovirus infections
    - parvovirus b19
      - definition
      - epidemiology
      - pathogenesis
      - clinical manifestations
        erythema infectiosum
        
        polyarthropathy syndrome
        
        transient aplastic crisis
        
        pure red cell aplasia/chronic anemia
        
        hydrops fetalis
        
        unusual manifestations
      - diagnosis
      - treatment
      - prevention
    - human tetraparvoviruses (Parv4/5)
      - definition
      - epidemiology
        clinical manifestations
    - human bocaparvoviruses
      - definition
      - epidemiology
      - clinical manifestations
    - human protoparvoviruses
      - definition
      - epidemiology
      - clinical manifestations
    - further reading
  - 198 human papillomavirus infections
    - pathogenesis
    - the natural history of hpv-associated malignancy
    - the effects of hiv on hpv associated disease
    - clinical manifestations of hpv infection
    - prevention of hpv infection and disease
    - screening for hpv-associated cancer
    - treatment
    - counseling patients regarding hpv disease
    - further reading
- section 13 infections due to dna and rna respiratory viruses
  - 199 common viral respiratory infections, including covid-19
    - anatomic sites in the humanrespiratory tract
    - disease syndromes
    - etiologic agents
      - respiratory viruses causing disease in immunocompetent hosts
      - respiratory viruses causing disease in immunocompromised hosts
      - specific viral causes of respiratory disease
        orthomyxoviridae: influenza viruses
        
        pneumoviridae
        
        paramyxoviridae
        
        picornaviridae
        
        adenoviridae
        
        coronaviridae
        
        covid-19
        
        herpesviridae
        
        parvoviridae: human bocavirus
        
        retroviridae: hiv
        
        papovaviridae: polyomaviruses
    - epidemiology
      - age
      - season
      - risk factors for disease
      - transmission
    - approach to the patient
    - clinical manifestations
    - diagnosis
    - treatment
    - complications: co-infections
    - prevention
      - vaccines
      - passive protection with immunotherapy
      - isolation procedures, personal protective equipment, and hand washing
    - global considerations
      - hendra and nipah viruses
      - bunyaviridae: hantavirus
    - summary
    - further reading
  - 200 influenza
    - definition
    - etiologic agents
    - epidemiology
    - pathogenesis and immunity
    - clinical manifestations
    - complications
    - laboratory findings and diagnosis
    - differential diagnosis
    - immunization
    - treatment
    - further reading
- section 14 infections due to human immunodeficiency virus and other human retroviruses
  - 201 the human retroviruses
    - structure and life cycle
    - human t-cell lymphotropic virus
      - biology and molecular biology
      - features of htlv-1 infection
      - features of htlv-2 infection
    - human immunodeficiency virus
    - further reading
  - 202 human immunodeficiency virus disease: aids and related disorders
    - definition
    - etiologic agent
      - morphology of hiv
      - replication cycle of hiv
      - hiv genome
      - molecular heterogeneity of hiv-1
    - transmission
      - sexual transmission
      - transmission through injection drug use
      - transmission by transfused blood and blood products
      - occupational transmission of hiv: health care workers, laboratory workers, and the health care setting
      - mother-to-child transmission of hiv
      - transmission of hiv by other body fluids
    - epidemiology
      - hiv infection and aids worldwide
      - hiv infection in the united states
    - pathophysiology and pathogenesis
      - early events in hiv infection: primary infection and initial dissemination of virus
      - establishment of chronic infection
      - advanced hiv disease
      - long-term survivors, long-term nonprogressors, and elite controllers
      - lymphoid organs and hiv pathogenesis
      - the role of immune activation and inflammation in hiv pathogenesis
      - cytokines and other soluble factors in hiv pathogenesis
      - lymphocyte turnover in hiv infection
      - the role of viral receptors and co-receptors in hiv pathogenesis
      - cellular targets of hiv
      - qualitative and quantitative abnormalities of mononuclear cells
      - genetic factors in hiv-1 and aids pathogenesis
      - neuropathogenesis in hiv disease
      - pathogenesis of kaposi’s sarcoma
    - immune response to hiv
      - humoral immune response
      - cellular immune response
    - diagnosis and laboratory monitoring of hiv infection
      - diagnosis of hiv infection
      - laboratory monitoring of patients with hiv infection
      - acute hiv infection
      - the asymptomatic stage—clinical latency
      - symptomatic disease
        diseases of the respiratory system
        
        diseases of the cardiovascular system
        
        diseases of the oropharynx and gastrointestinal system
        
        hepatobiliary diseases
        
        diseases of the kidney and genitourinary tract
        
        diseases of the endocrine system and metabolic disorders
        
        immunologic and rheumatologic diseases
        
        immune reconstitution inflammatory syndrome (Iris)
        
        diseases of the hematopoietic system
        
        dermatologic diseases
        
        neurologic diseases
        
        ophthalmologic diseases
        
        additional disseminated infections and wasting syndrome
        
        neoplastic diseases
    - idiopathic cd4+ t lymphocytopenia
    - treatment
      - general principles of patient management
      - antiretroviral therapy
      - principles of therapy
    - hiv and the health care worker
    - hiv prevention
    - further reading
- section 15 infections due to rna viruses
  - 203 viral gastroenteritis
    - human caliciviruses
    - rotavirus
    - other viral agents of gastroenteritis
  - 204 enterovirus, parechovirus, and reovirus infections
    - enteroviruses
      - classification and characterization
      - pathogenesis and immunity
      - epidemiology
      - clinical features
        poliovirus infection
        paralytic poliomyelitis
        
        vaccine-associated poliomyelitis
        
        postpolio syndrome
        
        other enteroviruses
        nonspecific febrile illness (Summer grippe)
        
        generalized disease of the newborn
        
        aseptic meningitis and encephalitis
        
        acute flaccid myelitis
        
        pleurodynia (Bornholm disease)
        
        myocarditis and pericarditis
        
        exanthems
        
        hand-foot-and-mouth disease
        
        herpangina
        
        acute hemorrhagic conjunctivitis
        
        other manifestations
      - diagnosis
      - treatment
      - prevention and eradication of poliovirus
    - parechoviruses
    - reoviruses
    - further reading
  - 205 measles (Rubeola)
    - definition
    - global considerations
    - etiology
    - epidemiology
    - pathogenesis
    - immune responses
    - approach to the patient
    - clinical manifestations
    - differential diagnosis
    - diagnosis
    - treatment
    - complications
    - prognosis
    - prevention
    - prospects for measles eradication
    - further reading
  - 206 rubella (German measles)
    - etiology
    - pathogenesis and pathology
    - epidemiology
    - clinical features
      - acquired rubella
      - congenital rubella syndrome
    - diagnosis
      - acquired rubella
      - congenital rubella syndrome
      - rubella diagnosis in pregnant women
    - treatment
    - prevention
    - further reading
  - 207 mumps
    - etiologic agent
    - epidemiology
    - pathogenesis
    - clinical manifestations
    - differential diagnosis
    - laboratory diagnosis
    - treatment
    - prevention
    - further reading
  - 208 rabies and other rhabdovirus infections
    - rabies
      - etiologic agent
      - epidemiology
      - pathogenesis
      - clinical manifestations
        prodromal features
        
        encephalitic rabies
        
        paralytic rabies
      - laboratory investigations
      - diagnosis
      - differential diagnosis
      - treatment
      - prognosis
      - prevention
    - other rhabdoviruses
      - other lyssaviruses
      - vesicular stomatitis virus
    - further reading
  - 209 arthropod-borne and rodent-borne virus infections
    - etiology
      - amarillovirales: flaviviridae
      - articulavirales: orthomyxoviridae
      - bunyavirales: arenaviridae
      - bunyavirales: hantaviridae, nairoviridae, peribunyaviridae, and phenuiviridae
      - martellivirales: togaviridae
      - mononegavirales: rhabdoviridae
      - reovirales: reoviridae
    - epidemiology
    - diagnosis
    - clinical disease syndromes
      - arthritis and rash
      - encephalitis
      - fever and myalgia
      - pulmonary disease
      - viral hemorrhagic fever
    - further reading
    - website
  - 210 ebolavirus and marburgvirus infections
    - etiology
    - epidemiology
    - pathogenesis
    - clinical manifestations
    - diagnosis
    - treatment
    - complications
    - prognosis
    - control and prevention
    - further reading
- section 16 fungal infections
  - 211 pathogenesis, diagnosis, and treatment of fungal infections
    - definition and etiology
    - pathogenesis
    - diagnosis
    - antifungal drugs
    - amphotericin b
    - azoles
    - echinocandins
    - flucytosine (5-fluorocytosine)
    - griseofulvin and terbinafine
    - topical antifungal agents
    - further reading
  - 212 histoplasmosis
    - etiology
    - epidemiology
    - pathogenesis and pathology
    - clinical manifestations
    - diagnosis
    - treatment
    - further reading
  - 213 coccidioidomycosis
    - definition and etiology
    - epidemiology
    - pathogenesis, pathology, and immune response
    - clinical and laboratory manifestations
    - diagnosis
    - treatment
    - prevention
    - further reading
  - 214 blastomycosis
    - definition
    - etiology
    - epidemiology
    - pathogenesis
    - approach to the patient
    - clinical manifestations
    - diagnosis
    - treatment
    - prognosis
    - prevention
    - further reading
  - 215 cryptococcosis
    - definition and etiology
    - epidemiology
    - pathogenesis
    - approach to the patient
    - clinical manifestations
    - diagnosis
    - treatment
    - prognosis and complications
    - immune reconstitution inflammatory syndrome
    - prevention
    - further reading
  - 216 candidiasis
    - epidemiology
    - pathogenesis
    - clinical manifestations
      - mucocutaneous candidiasis
      - deeply invasive candidiasis
    - diagnosis
    - treatment
    - prophylaxis
    - further reading
  - 217 aspergillosis
    - epidemiology and ecology
    - risk factors and pathogenesis
    - clinical features and approach to the patient
      - invasive pulmonary aspergillosis
      - invasive sinusitis
      - tracheobronchitis
      - aspergillus bronchitis
      - disseminated aspergillosis
      - cerebral aspergillosis
      - endocarditis
      - cutaneous aspergillosis
      - chronic pulmonary aspergillosis
      - aspergilloma
      - aspergillus nodule
      - chronic aspergillus sinusitis
      - allergic bronchopulmonary aspergillosis
      - severe asthma with fungal sensitization (Safs)
      - allergic fungal rhinosinusitis
      - superficial aspergillosis
    - diagnosis
      - acute invasive aspergillosis
      - chronic aspergillosis
      - abpa, safs, and allergic aspergillus sinusitis
    - treatment
    - prophylaxis
    - outcome
    - further reading
  - 218 mucormycosis
    - etiology
    - pathogenesis
    - epidemiology
    - clinical manifestations
      - rhino-orbital-cerebral disease
      - pulmonary disease
      - cutaneous disease
      - gastrointestinal disease
      - disseminated and miscellaneous forms of disease
    - diagnosis
    - differential diagnosis
    - treatment
    - prognosis
    - further reading
  - 219 less common systemic mycoses and superficial mycoses
    - endemic mycoses (Dimorphic fungi)
      - sporotrichosis
      - paracoccidioidomycosis
      - talaromycosis (Penicilliosis)
    - phaeohyphomycoses
    - opportunistic fungal infections
      - fusariosis
      - scedosporiosis and lomentosporiosis
      - trichosporonosis
    - superficial cutaneous infections
      - yeast infections
      - dermatophyte (Mold) Infections
    - further reading
  - 220 pneumocystis infections
    - definition and description
    - epidemiology
    - pathogenesis and pathology
    - clinical features
    - diagnosis
    - course and prognosis
    - treatment
    - prevention
    - further reading
- section 17 protozoal and helminthic infections: general considerations
  - 221 introduction to parasitic infections
    - helminthic infections
      - flatworms
      - roundworms
    - protozoal infections
      - intestinal protozoa
      - free-living amoebas
      - blood and tissue protozoans
    - approach to the patient
    - further reading
  - 222 agents used to treat parasitic infections
- section 18 protozoal infections
  - 223 amebiasis and infection with free-living amebae
    - amebiasis
      - definition
      - life cycle and transmission
      - epidemiology
      - pathogenesis and pathology
      - clinical syndromes
        intestinal amebiasis
        
        amebic liver abscess
        
        complications of amebic liver abscess
        
        involvement of other extraintestinal sites
      - diagnostic tests
        laboratory diagnosis
        
        radiographic studies
        
        differential diagnosis
      - treatment
      - prevention
    - infection with free-living amebae
      - epidemiology
      - naegleria infections
      - acanthamoeba infections
      - balamuthia infections
    - further reading
  - 224 malaria
    - etiology and pathogenesis
    - pathophysiology
      - erythrocyte changes
      - host response
    - clinical features
      - severe falciparum malaria
      - malaria in pregnancy
      - malaria in children
      - transfusion malaria
    - chronic complications of malaria
      - hyperreactive malarial splenomegaly
      - quartan malarial nephropathy
      - burkitt’s lymphoma and epstein-barr virus infection
    - treatment
    - global considerations
    - malaria prevention
      - personal protection against malaria
      - chemoprophylaxis
    - further reading
  - 225 babesiosis
    - etiology, epidemiology, and modes of transmission
    - clinical manifestations
    - pathogenesis
    - treatment
    - prevention
    - further reading
  - 226 leishmaniasis
    - etiology and life cycle
    - epidemiology
    - visceral leishmaniasis
    - cutaneous leishmaniasis
    - mucosal leishmaniasis
    - prevention of leishmaniasis
    - further reading
  - 227 chagas disease and african trypanosomiasis
    - chagas disease (American trypanosomiasis)
      - definition
      - transmission
      - epidemiology
      - pathology
      - clinical manifestations
      - approach to the patient
      - diagnosis and staging
      - treatment
      - prevention
      - global considerations
    - human african trypanosomiasis (Sleeping sickness)
      - definition
      - epidemiology
      - pathology and pathogenesis
      - approach to the patient
      - clinical manifestations
      - diagnosis
      - treatment
      - prognosis
      - global considerations
  - 228 toxoplasma infections
    - definition
    - etiology
    - epidemiology
    - transmission
    - pathogenesis
    - pathology
    - host immune response
    - clinical manifestations
    - diagnosis
    - treatment
    - prevention
  - 229 protozoal intestinal infections and trichomoniasis
    - protozoal infections
      - giardiasis
      - cryptosporidiosis
      - cystoisosporiasis
      - cyclosporiasis
      - microsporidiosis
      - other intestinal protozoa
    - trichomoniasis
- section 19 helminthic infections
  - 230 introduction to helminthic infections
    - nematodes
    - cestodes
    - trematodes
    - conclusion
  - 231 trichinellosis and other tissue nematode infections
    - trichinellosis
    - visceral and ocular larva migrans
    - cutaneous larva migrans
    - angiostrongyliasis
    - gnathostomiasis
  - 232 intestinal nematode infections
    - ascariasis
    - hookworm
    - strongyloidiasis
    - trichuriasis
    - enterobiasis (Pinworm)
    - trichostrongyliasis
    - anisakiasis
    - capillariasis
    - abdominal angiostrongyliasis
  - 233 filarial and related infections
    - lymphatic filariasis
    - tropical pulmonary eosinophilia
    - onchocerciasis
    - loiasis
    - streptocerciasis
    - mansonella perstans infection
    - mansonella ozzardi infection
    - zoonotic filarial infections
    - dracunculiasis (Guinea worm infection)
  - 234 schistosomiasis and other trematode infections
    - approach to the patient
    - schistosomiasis
      - etiology
      - epidemiology
      - pathogenesis
      - clinical features
      - diagnosis
      - treatment
      - prevention and control
    - food-borne trematode infections
      - liver flukes
      - intestinal flukes
      - lung flukes
      - treatment
      - control and prevention
  - 235 cestode infections
    - taeniasis saginata and taeniasis asiatica
    - taeniasis solium and cysticercosis
    - echinococcosis
    - hymenolepiasis nana
    - hymenolepiasis diminuta
    - diphyllobothriasis
    - dipylidiasis
    - sparganosis
    - coenurosis
part 6 disorders of the cardiovascular system
- section 1 introduction to cardiovascular disorders
  - 236 approach to the patient with possible cardiovascular disease
    - the magnitude of the problem
    - natural history
    - cardiac symptoms
    - diagnosis
    - family history
    - assessment of functional impairment
    - electrocardiogram
    - assessment of the patient with a heart murmur
    - pitfalls in cardiovascular medicine
    - disease prevention and management
  - 237 basic biology of the cardiovascular system
    - developmental biology of thecardiovascular system
    - the blood vessel
      - vascular ultrastructure
      - vascular cell biology
      - arteriogenesis and angiogenesis
    - cellular basis of cardiac contraction
      - cardiac ultrastructure
      - the contractile process
      - cardiac activation
    - control of cardiac performance and output
      - the role of muscle length (Preload)
      - cardiac performance
      - ventricular afterload
      - exercise
    - assessment of cardiac function
      - diastolic function
      - cardiac metabolism
      - regenerating cardiac tissue
  - 238 epidemiology of cardiovascular disease
    - the epidemiologic transition
    - patterns in the epidemiologic transition
    - global trends in cardiovascular disease
    - risk factors
      - behavioral risk factors
      - metabolic risk factors
      - genetic risk factors
    - summary
- section 2 diagnosis of cardiovascular disorders
  - 239 physical examination of the cardiovascular system
    - the general physical examination
      - skin
      - head and neck
      - chest
      - abdomen
      - extremities
    - cardiovascular examination
      - jugular venous pressure and waveform
      - assessment of blood pressure
      - arterial pulse
    - cardiac auscultation
      - heart sounds
      - systolic sounds
      - diastolic sounds
      - cardiac murmurs
      - diastolic murmurs
      - continuous murmur
      - dynamic auscultation
      - prosthetic heart valves
      - pericardial disease
  - 240 electrocardiography
    - electrophysiologic background
    - ecg waveforms and intervals
    - ecg leads
    - genesis of the normal ecg
    - major ecg abnormalities
      - cardiac enlargement and hypertrophy
      - bundle branch blocks and related patterns
      - myocardial ischemia and infarction
      - metabolic factors and drug effects
      - nonspecific st-t changes and low qrs voltage
      - electrical alternans syndromes
    - clinical interpretation of the ecg
    - computerized electrocardiography
  - 241 noninvasive cardiac imaging: echocardiography, nuclear cardiology, and magnetic resonance/computed tomography imaging
    - principles of multimodality cardiac imaging
      - echocardiography
      - radionuclide imaging
      - cardiac computed tomography
      - cardiac magnetic resonance
    - assessment of cardiac structure and function
      - assessment of left ventricular systolic function
      - assessment of left ventricular diastolic function
      - assessment of right ventricular function
    - patient safety considerations
      - radiation exposure
      - contrast agents
      - safety considerations of cmr in patients with pacemakers and defibrillators
    - patient-centered applications of cardiac imaging
      - coronary artery disease
      - valvular heart disease
      - myocardial infarction and heart failure
      - pericardial disease
      - cardiac thrombus and mass
      - role of imaging in infectious and inflammatory disease
      - evaluation of common congenital abnormalities in the adult
  - 242 diagnostic cardiac catheterization and coronary angiography
    - cardiac catheterization
      - indications, risks, and preproceduremanagement
      - technique
      - hemodynamics
      - ventriculography and aortography
      - cinefluoroscopy of prosthetic mechanical valves
    - coronary angiography
- section 3 disorders of rhythm
  - 243 principles of clinical cardiac electrophysiology
    - historical perspective
    - cellular electrophysiology
    - normal cardiac impulse propagation
    - mechanisms of cardiac arrhythmias
    - care of the arrhythmia patient
  - 244 the bradyarrhythmias: disorders of the sinoatrial node
    - structure and physiology of the sa node
    - diagnosis of sa nodal disease
    - sa nodal dysfunction subtypes
    - treatment
  - 245 the bradyarrhythmias: disorders of the atrioventricular node
    - structure and physiology of the av node
    - electrocardiographic definitions of av conduction block
    - etiology of av conduction disease
    - diagnostic testing
    - treatment
  - 246 approach to supraventricular tachyarrhythmias
    - clinical presentation
  - 247 physiologic and nonphysiologic sinus tachycardia
    - physiologic sinus tachycardia
    - nonphysiologic sinus tachycardia
  - 248 focal atrial tachycardia
  - 249 paroxysmal supraventricular tachycardias
    - atrioventricular nodal reentry tachycardia
    - junctional tachycardia
    - accessory pathways and the wolff-parkinson-white syndrome
    - atrioventricular reciprocating tachycardia
    - preexcited tachycardias
    - management of patients with accessory pathways
    - treatment
  - 250 common atrial flutter and macroreentrant and multifocal atrial tachycardias
    - atrial flutter
    - multifocal atrial tachycardia
  - 251 atrial fibrillation
    - pathophysiology and epidemiology
    - clinical presentation and manifestations
    - treatment
    - risk factors for and lifestyle impact on atrial fibrillation
  - 252 approach to ventricular arrhythmias
    - types of vas
    - clinical manifestations
    - evaluation of patients with documented or suspected ventricular arrhythmias
    - arrhythmia surgery
  - 253 premature ventricular contractions, nonsustained ventricular tachycardia, and accelerated idioventricular rhythm
    - premature ventricular contractions and non-sustained vt
    - pvcs and nsvt during acute illness
    - pvcs and nsvt in patients without heart disease
    - treatment of idiopathic arrhythmias
    - pvcs and nsvt associated with acute coronary syndromes
    - pvcs and nsvt associated with depressed ventricular function and heart failure
    - pvc and nsvt associated with other cardiac diseases
    - pvc-induced ventricular dysfunction
    - accelerated idioventricular rhythms
    - future directions
  - 254 sustained ventricular tachycardia
    - diagnosis
    - treatment and prognosis
    - sustained monomorphic vt in specific diseases
    - arrhythmogenic right ventricular cardiomyopathy
    - adult congenital heart disease
    - bundle branch reentry vt
    - idiopathic monomorphic vt
    - management of idiopathic vt
    - future directions
  - 255 polymorphic ventricular tachycardia and ventricular fibrillation
    - polymorphic ventricular tachycardia
    - polymorphic vt associated with acute myocardial infarction/ischemia
    - repolarization abnormalities and genetic arrhythmia syndromes
      - acquired long qt syndrome
      - congenital long qt syndrome
      - short qt syndrome
      - brugada syndrome
      - early repolarization syndrome
      - catecholaminergic polymorphic vt
      - hypertrophic cardiomyopathy
      - genetic dilated cardiomyopathies
      - ventricular fibrillation
    - future directions
  - 256 electrical storm and incessant ventricular tachycardia
    - electrical storm
    - incessant vt
    - management of patients presenting with icd shocks
    - management of the patient with electrical storm
- section 4 disorders of the heart, muscles, valves, and pericardium
  - 257 heart failure: pathophysiology and diagnosis
    - clinical definitions, epidemiology, and phenotypes
      - definitions
      - epidemiology
      - phenotypes and causes
    - pathophysiology
      - progressive disease
      - mechanisms of disease progression
      - cardiorenal and abdominal interactions
      - gut congestion, the microbiome, and inflammation
      - high-output states
    - evaluation
      - history
      - physical examination
      - diagnosis
    - comorbidities
      - diabetes
      - sleep apnea
      - obesity
      - depression
    - differential diagnosis
  - 258 heart failure: management
    - heart failure with preserved ejection fraction
      - general principles
      - clinical trials in hfpef
      - novel targets
      - clinical guiding principles
    - acute decompensated heart failure
      - general principles
      - volume management
      - vasoactive therapy
      - inotropic therapy
      - other therapies for adhf
      - clinical guiding principles
    - heart failure with reduced ejection fraction
      - neurohormonal antagonism
      - mineralocorticoid receptor antagonists
      - raas therapy and neurohormonal “escape”
      - alternative vasodilators
      - novel neurohormonal antagonists
      - heart rate modification
      - sglt-2 inhibition
      - soluble guanylyl cyclase stimulation
      - myosin activation
      - digoxin
      - oral diuretics
      - calcium channel antagonists
      - anti-inflammatory therapy
      - hmg-coa reductase inhibitors (Statins)
      - anticoagulation and antiplatele ttherapy
      - fish oil
      - micronutrients
      - enhanced external counterpulsation
      - exercise
      - management of selected comorbidity
      - neuromodulation using device therapy
      - cardiac contractility modulation
    - cardiac resynchronization therapy
    - sudden cardiac death prevention in heart failure
    - surgical therapy in heart failure
    - cellular and gene-based therapy
    - disease management and supportive care
    - global considerations
  - 259 cardiomyopathy and myocarditis
    - definition and classification
    - general presentation
      - genetic causes of cardiomyopathy
    - dilated cardiomyopathy
      - myocarditis
      - infective myocarditis
      - specific viruses implicated in myocarditis
      - therapy of viral myocarditis
      - other infectious causes
      - noninfective myocarditis
      - peripartum cardiomyopathy
      - toxic cardiomyopathy
      - metabolic causes of cardiomyopathy
      - familial dilated cardiomyopathy
      - takotsubo cardiomyopathy
      - idiopathic dcm
    - overlapping types of cardiomyopathy
      - disorders of metabolic pathways
    - restrictive cardiomyopathy
      - nfiltrative disease
      - fibrotic restrictive cardiomyopathy
      - endomyocardial disease
    - hypertrophic cardiomyopathy
      - diagnosis
      - treatment
      - prognosis
    - global perspectives
  - 260 cardiac transplantation and prolonged assisted circulation
    - cardiac transplantation
      - candidates for cardiac transplantation
      - principles of donor recovery and allocation
      - surgery for cardiac transplantation
      - cardiac allograft rejection and immunosuppression
      - late complications after cardiac transplantation
    - prolonged assisted circulation
      - left ventricular assist systems and clinical trials
      - management of lvas and their complications
      - novel devices
      - total artificial heart
    - global considerations
  - 261 aortic stenosis
    - global burden of valvular heart disease
    - etiology and pathogenesis
    - bicuspid aortic valve disease
    - other forms of obstruction to left ventricular outflow
    - pathophysiology
    - symptoms
    - physical findings
    - laboratory examination
    - treatment
  - 262 aortic regurgitation
    - etiology
    - pathophysiology
    - history
    - physical findings
    - laboratory examination
    - treatment
  - 263 mitral stenosis
    - etiology and pathology
    - pathophysiology
    - symptoms
    - physical findings
    - laboratory examination
    - differential diagnosis
    - cardiac catheterization
    - treatment
  - 264 mitral regurgitation
    - etiology
    - pathophysiology
    - symptoms
    - physical findings
    - laboratory examination
    - treatment
  - 265 mitral valve prolapse
    - clinical features
    - laboratory examination
    - treatment
  - 266 tricuspid valve disease
    - tricuspid stenosis
    - tricuspid regurgitation
  - 267 pulmonic valve disease
    - pulmonic stenosis
    - pulmonic regurgitation
  - 268 multiple and mixed valvular heart disease
    - pathophysiology
    - symptoms
    - physical findings
    - laboratory examination
    - treatment
  - 269 congenital heart disease in the adult
    - prevalence
    - the changing landscape of adult chd
    - special considerations for the achdpatient
    - congenital terminology, development, and genetics
    - specific chd lesions
      - dilated right heart
      - atrial septal defect
      - partial anomalous pulmonary venous return
      - ebstein anomaly
      - shunt lesions causing left heart dilation
      - ventricular septal defects
      - patent ductus arteriosus
    - moderate and complex chd
      - tetralogy of fallot
      - transposition of the great arteries
      - coarctation of the aorta
      - single ventricle physiology
    - unrepaired cyanotic chd
      - eisenmenger syndrome
      - the role of palliative care in achd
    - global considerations
  - 270 pericardial disease
    - normal functions of the pericardium
    - acute pericarditis
    - cardiac tamponade
    - viral or idiopathic acute pericarditis
    - chronic pericardial effusions
    - chronic constrictive pericarditis
  - 271 atrial myxoma and other cardiac tumors
    - primary tumors
      - clinical presentation
      - myxoma
      - other benign tumors
      - malignant tumors
    - tumors metastatic to the heart
  - 272 cardiac trauma
    - cardiac trauma
    - blunt cardiac injury
    - penetrating cardiac injury
- section 5 coronary and peripheral vascular disease
  - 273 ischemic heart disease
    - epidemiology and global trends
    - pathophysiology
    - coronary atherosclerosis
    - stable angina pectoris
    - coronary revascularization
    - asymptomatic (Silent) Ischemia
  - 274 non-st-segment elevation acute coronary syndrome (Non-st-segment elevation myocardial infarction and unstable angina)
    - pathophysiology
    - clinical presentation
    - treatment
    - long-term management
    - prinzmetal’s variant angina
    - global considerations
  - 275 st-segment elevation myocardial infarction
    - pathophysiology: role of acute plaque rupture
    - clinical presentation
    - laboratory findings
      - electrocardiogram
      - serum cardiac biomarkers
      - cardiac imaging
    - initial management
    - management in the emergency department
    - control of discomfort
    - management strategies
    - limitation of infarct size
    - hospital phase management
    - pharmacotherapy
    - complications and their management
  - 276 percutaneous coronary interventions and other interventional procedures
    - technique
    - success and complications
    - indications
    - other interventional techniques
    - conclusion
  - 277 hypertension
    - epidemiology
    - mechanisms of hypertension
    - pathologic consequences of hypertension
    - defining hypertension
    - clinical disorders of hypertension
    - monogenic hypertension
    - approach to the patient
    - treatment
  - 278 renovascular disease
    - mechanisms of vascular injury and hypertension
    - diagnosis of renovascular disease
    - treatment
    - atheroembolic renal disease
    - thromboembolic renal disease
    - microvascular injury associated with hypertension
      - arteriolonephrosclerosis
  - 279 deep-venous thrombosis and pulmonary thromboembolism
    - epidemiology
    - pathophysiology
    - classification of pulmonary embolism and deep-venous thrombosis
    - diagnosis
    - treatment: deep-venous thrombosis
    - treatment: pulmonary embolism
    - prevention of vte
  - 280 diseases of the aorta
    - congenital anomalies of the aorta
    - aortic aneurysm
      - etiology
      - thoracic aortic aneurysms
      - abdominal aortic aneurysms
    - acute aortic syndromes
      - clinical manifestations
      - treatment
    - chronic atherosclerotic occlusive disease
    - acute aortic occlusion
    - aortitis
      - takayasu’s arteritis
      - giant cell arteritis
      - rheumatic aortitis
      - idiopathic aortitis
      - infective aortitis
  - 281 arterial diseases of the extremities
    - peripheral artery disease
    - fibromuscular dysplasia
    - thromboangiitis obliterans
    - vasculitis
    - acute limb ischemia
    - atheroembolism
    - thoracic outlet compression syndrome
    - popliteal artery entrapment
    - popliteal artery aneurysm
    - arteriovenous fistula
    - raynaud’s phenomenon
    - acrocyanosis
    - livedo reticularis
    - pernio (Chilblains)
    - erythromelalgia
    - frostbite
  - 282 chronic venous disease and lymphedema
    - chronic venous disease
      - venous anatomy
      - pathophysiology of chronic venous disease
      - clinical presentation
      - differential diagnosis
      - classification of chronic venous disease
      - diagnostic testing
      - treatment
    - lymphedema
      - lymphatic anatomy
      - etiology
      - clinical presentation
      - differential diagnosis
      - diagnostic testing
      - treatment
  - 283 pulmonary hypertension
    - pathobiology
    - pathophysiology
    - diagnosis
    - pulmonary hypertension classification
    - other disorders affecting the pulmonary vasculature
    - pharmacologic treatment of pah
    - approach to pah treatment
    - unmet and future research needs in pulmonary hypertension
part 7 disorders of the respiratory system
- section 1 diagnosis of respiratory disorders
  - 284 approach to the patient with disease of the respiratory system
    - history
      - dyspnea and cough
      - additional symptoms
      - additional history
    - physical examination
    - diagnostic evaluation
      - pulmonary function testing
      - chest imaging
    - further studies
  - 285 disturbances of respiratory function
    - ventilation
      - volume-related mechanical properties—statics
      - flow-related mechanical properties—dynamics
      - the work of breathing
      - adequacy of ventilation
    - gas exchange
      - diffusion
      - ventilation/perfusion heterogeneity
    - pathophysiology
      - ventilatory restriction due to increased elastic recoil—example: idiopathic pulmonary fibrosis
      - ventilatory restriction due to chest wall abnormality—example: moderate obesity
      - ventilatory restriction due to reduced muscle strength—example: myasthenia gravis
      - airflow obstruction due to decreased airway diameter—example: acute asthma
      - airflow obstruction due to decreased elastic recoil—example: severe emphysema
    - functional measurements
      - measurement of ventilatory function
      - measurement of gas exchange
      - arterial blood gases
  - 286 diagnostic procedures in respiratory disease
    - bedside pleural procedures
      - thoracentesis
      - closed pleural biopsy
    - thoracic surgical procedures
      - thoracoscopy and thoracotomy
      - mediastinoscopy and mediastinotomy
    - bronchoscopy
      - bronchoalveolar lavage
      - brushing and endobronchial biopsy
      - transbronchial biopsy including cryobiopsy
      - transbronchial needle aspiration
      - endobronchial ultrasound-guided transbronchial needle aspiration
      - guided peripheral bronchoscopy
      - robotic bronchoscopy
    - medical imaging
      - chest x-ray
      - computed tomography
      - magnetic resonance imaging
      - positron emission tomography
      - artificial intelligence/deep learning
    - transthoracic needle aspiration
    - miscellaneous testing
      - sputum testing
      - exhaled breath condensate
      - sweat testing
      - allergy testing
- section 2 diseases of the respiratory system
  - 287 asthma
    - manifestations
    - epidemiology
    - the pathway to the development of asthma
    - pathophysiology
      - mechanisms leading to acute and chronic airway obstruction
      - airway inflammation (Type 2 and non–type 2 inflammation)
      - mediators
    - etiologic mechanisms, risk factors, triggers, and complicating comorbidities
      - heritable predisposition
      - exposures and risk factors
      - triggers of airway narrowing
      - comorbidities
    - diagnosis and evaluation
      - approach
      - primary assessment tools for establishing a diagnosis
      - adjunctive assessment tools
      - additional evaluation in severe/poorly responsive asthma
    - treatment: asthma
      - goals of asthma therapy and assessment of control
      - medications
    - approach to the patient
    - treatment: asthma attacks
    - special considerations
      - high-risk asthma patients
      - exercise-induced symptoms
      - pregnancy
      - aspirin-exacerbated respiratory disease
      - severe asthma
      - elderly patients with asthma
      - asthma-copd overlap
  - 288 hypersensitivity pneumonitis and pulmonary infiltrates with eosinophilia
    - hypersensitivity pneumonitis
      - introduction and definition
      - offending antigens
      - pathophysiology
      - clinical presentation
      - diagnosis
      - differential diagnosis
      - treatment
      - global considerations
    - pulmonary infiltrates with eosinophilia
      - classifying pulmonary infiltrates with eosinophilia and general approach
      - pathophysiology
      - acute eosinophilic pneumonia
      - eosinophilic granulomatosis with polyangiitis (Egpa)
      - hypereosinophilic syndromes
      - allergic bronchopulmonary aspergillosis
      - infectious processes
      - drugs and toxins
    - global considerations
  - 289 occupational and environmental lung disease
    - history and exposure assessment
    - laboratory tests
    - determinants of inhalational exposure
    - occupational exposures and pulmonary disease
      - asbestos-related diseases
      - silicosis
      - coal worker’s pneumoconiosis (Cwp)
      - chronic beryllium disease
      - other metals
      - other inorganic dusts
      - organic dusts
      - toxic chemicals
      - occupational respiratory carcinogens
      - assessment of disability
    - general environmental exposures
      - outdoor air pollution
      - indoor exposures
  - 290 bronchiectasis
    - etiology
    - epidemiology
    - pathogenesis and pathology
    - clinical manifestations
    - diagnosis
    - approach to the patient
    - treatment
    - complications
    - prognosis
    - prevention
  - 291 cystic fibrosis
    - clinical features
    - pathogenesis
    - molecular genetics
    - diagnosis
    - complexity of a cf phenotype
    - cftr modulators
    - therapeutics directed toward cf sequelae
    - cf quality improvement
    - global considerations
  - 292 chronic obstructive pulmonary disease
    - pathogenesis
    - pathophysiology
    - risk factors
    - natural history
    - clinical presentation
    - treatment
  - 293 interstitial lung disease
    - diagnostic approach
      - history
      - physical examination
      - laboratory studies
      - pulmonary function tests
      - chest imaging studies
      - lung biopsy
      - individual forms of ild
    - idiopathic interstitial pneumonias
      - idiopathic pulmonary fibrosis
      - nonspecific interstitial pneumonia
      - smoking-related ild
      - cryptogenic organizing pneumonia
    - acute or subacute iips
      - acute interstitial pneumonia (Hamman-rich syndrome)
      - acute exacerbations of iips
    - ild associated with connective tissue disease
      - systemic sclerosis
      - rheumatoid arthritis
      - dermatomyositis/polymyositis
      - granulomatous ilds
      - genetics and ild
    - global considerations
  - 294 disorders of the pleura
    - pleural effusion
    - pneumothorax
  - 295 disorders of the mediastinum
    - mediastinal masses
    - acute mediastinitis
    - chronic mediastinitis
    - pneumomediastinum
  - 296 disorders of ventilation
    - definition and physiology
    - hypoventilation
    - hypoventilation syndromes
    - hyperventilation
  - 297 sleep apnea
    - obstructive sleep apnea/hypopnea syndrome
  - 298 lung transplantation
    - end-stage lung disease and indicationsfor lung transplantation
    - contraindications to lung transplantation
    - lung transplant candidate management
    - donor considerations
    - procurement operation
    - recipient operation and early posttransplant considerations
    - long-term management of lung transplant recipients
  - 299 interventional pulmonary medicine
    - diagnostic bronchoscopy
      - endobronchial ultrasound
      - peripheral bronchoscopy
    - therapeutic bronchoscopy
      - central airway obstruction
      - ablative therapies for cao
      - bronchoplasty
      - airway stenting
      - endobronchial intratumoral chemotherapy
      - ablative therapies for early-stage lung cancer
      - bronchoscopic therapies for asthma
      - bronchoscopic therapies for chronic obstructive pulmonary disease
      - bronchoscopic lung volume reduction
      - targeted lung denervation
      - pleural interventions
      - pneumothorax and persistent air leak
    - summary
part 8 critical care medicine
- section 1 respiratory critical care
  - 300 approach to the patient with critical illness
    - assessment of illness severity
    - shock
    - respiratory failure
    - care of the mechanically ventilated patient
    - multiorgan system failure
    - monitoring in the icu
    - prevention of complications of critical illness
    - neurologic dysfunction in critically ill patients
  - 301 acute respiratory distress syndrome
    - etiology
    - clinical course and pathophysiology
      - exudative phase
      - proliferative phase
      - fibrotic phase
    - treatment
      - general principles
      - management of mechanical ventilation
      - other strategies in mechanical ventilation
      - fluid management
      - neuromuscular blockade
      - glucocorticoids
      - other therapies
      - recommendations
    - prognosis
      - mortality
      - functional recovery in ards survivors
  - 302 mechanical ventilatory support
    - principles of mechanical ventilation
    - mechanical ventilation modes
    - strategies to optimize gas exchange on mechanical ventilation
    - complications of mechanical ventilation
    - liberation from mechanical ventilation
    - extracorporeal gas exchange
- section 2 shock and cardiac arrest
  - 303 approach to the patient with shock
    - pathophysiology of shock
    - classification of shock
      - distributive shock
      - cardiogenic shock
      - hypovolemic shock
      - obstructive shock
      - mixed shock
      - undifferentiated shock
    - stages of shock
    - evaluation of the patient with shock
    - initial treatment of shock
    - oxygenation and ventilation support
  - 304 sepsis and septic shock
    - introduction and definitions
    - etiology
    - epidemiology
    - pathogenesis
    - approach to the patient
    - clinical manifestations
    - diagnosis
    - treatment
    - prognosis
    - prevention
  - 305 cardiogenic shock and pulmonary edema
    - cardiogenic shock
    - pulmonary edema
  - 306 cardiovascular collapse, cardiac arrest, and sudden cardiac death
    - overview and definitions
    - epidemiology
    - causes of sudden cardiac death
    - management of cardiac arrest
- section 3 neurologic critical care
  - 307 nervous system disorders in critical care
    - pathophysiology
    - approach to the patient
    - critical care disorders of the cns
    - treatment
    - postcardiac bypass brain injury
    - metabolic encephalopathies
    - sepsis-associated encephalopathy
    - osmotic demyelination syndrome (Central pontine myelinolysis)
    - wernicke’s disease
    - hyperperfusion disorders (Posterior reversible encephalopathy syndrome)
    - post–solid organ transplant brain injury
    - cns complications of checkpoint inhibitor and chimeric antigen receptor t-cell therapy
    - critical care disorders of the peripheral nervous system
part 9 disorders of the kidney and urinary tract
- 308 approach to the patient with renal disease or urinary tract disease
  - nephritic syndromes
    - glomerulonephritis
    - proteinuric states and nephrotic syndrome
  - hematuria and lower urinary tract syndromes
  - acute kidney injury
  - chronic kidney disease and the uremic syndrome
- 309 cell biology and physiology of the kidney
  - embryologic development
  - determinants and regulation of glomerular filtration
  - mechanisms of renal tubular transport
  - loop of henle
  - distal convoluted tubule
  - collecting duct
  - hormonal regulation of sodium and water balance
- 310 acute kidney injury
  - epidemiology
  - etiology and pathophysiology
    - prerenal azotemia
    - intrinsic aki
      - sepsis-associated aki
      - ischemia-associated aki
      - nephrotoxin-associated aki
    - postrenal aki
  - diagnostic evaluation
    - history and physical examination
    - urine findings
    - blood laboratory findings
    - renal failure indices
    - radiologic evaluation
    - kidney biopsy
    - novel biomarkers
  - complications of aki
    - uremia
    - hypervolemia and hypovolemia
    - hyponatremia
    - hyperkalemia
    - acidosis
    - hyperphosphatemia and hypocalcemia
    - bleeding
    - infections
    - cardiac complications
    - malnutrition
    - prevention and treatment of aki
    - supportive measures for aki
  - outcome and prognosis
- 311 chronic kidney disease
  - pathophysiology of ckd
  - identification of risk factors and staging of ckd
  - etiology and epidemiology
  - pathophysiology and biochemistry of uremia
  - clinical and laboratory manifestations of ckd and uremia
    - fluid, electrolyte, and acid-base disorders
      - sodium and water homeostasis
      - potassium homeostasis
      - metabolic acidosis
    - disorders of calcium and phosphate metabolism
      - bone manifestations of ckd
      - calcium, phosphorus, and the cardiovascular system
      - other complications of abnormal mineral metabolism
    - cardiovascular abnormalities
      - vascular disease
      - heart failure
      - pericardial disease
    - hematologic abnormalities
      - anemia
      - abnormal hemostasis
    - neuromuscular abnormalities
    - gastrointestinal and nutritional abnormalities
    - ndocrine-metabolic disturbances
    - dermatologic abnormalities
  - evaluation and management ofpatients with ckd
    - initial approach
    - establishing the diagnosis and etiology of ckd
  - treatment
  - implications for global health
- 312 dialysis in the treatment of kidney failure
  - treatment options for patients with eskd
  - hemodialysis
    - the dialyzer
    - dialysate
    - blood delivery system
    - dialysis access
    - goals of dialysis
    - complications during hemodialysis
  - peritoneal dialysis
    - forms of peritoneal dialysis
    - access to the peritoneal cavity
    - complications during peritoneal dialysis
  - long-term outcomes in eskd
  - global perspective
- 313 transplantation in the treatment of renal failure
  - recent activity and results
  - recipient evaluation
  - tissue typing and clinical immunogenetics
  - donor evaluation
  - immunology of rejection
  - immunosuppressive treatment
  - clinical course and management of the recipient
  - malignancy
- 314 glomerular diseases
  - pathogenesis of glomerular disease
  - progression of glomerular disease
  - approach to the patient
  - renal pathology
  - acute nephritic syndromes
    - poststreptococcal glomerulonephritis
    - subacute bacterial endocarditis
    - lupus nephritis
    - antiglomerular basement membrane disease
    - iga nephropathy
    - anca small-vessel vasculitis
      - granulomatosis with polyangiitis
      - microscopic polyangiitis
      - churg-strauss syndrome
    - c3 glomerulopathies
    - membranoproliferative glomerulonephritis
    - mesangioproliferative glomerulonephritis
  - nephrotic syndrome
    - minimal change disease
    - focal segmental glomerulosclerosis
    - membranous glomerulonephritis
    - diabetic nephropathy
    - glomerular deposition diseases
    - fabry’s disease
  - pulmonary-renal syndromes
  - basement membrane syndromes
    - anti-gbm disease
    - alport’s syndrome
    - thin basement membrane disease
    - nail-patella syndrome
    - glomerular-vascular syndromes
  - atherosclerotic nephropathy
    - hypertensive nephrosclerosis
    - cholesterol emboli
    - sickle cell disease
    - thrombotic microangiopathies
    - antiphospholipid antibody syndrome
  - global considerations
    - infectious disease–associated syndromes
- 315 polycystic kidney disease and other inherited disorders of tubule growth and development
  - autosomal dominant polycystic kidney disease
  - autosomal recessive polycystic kidney disease
  - other diseases characterized bylarge kidney cysts
    - tuberous sclerosis
    - von hippel-lindau disease
  - other inherited diseases of tubulegrowth and development
  - nephronophthisis
  - karyomegalic tubulointerstitial nephritis
  - medullary sponge kidney
  - congenital abnormalities of the kidney and urinary tract
  - mitochondrial disease
  - diagnostic considertions
  - global considerations
- 316 tubulointerstitial diseases of the kidney
  - acute interstitial nephritis
    - allergic interstitial nephritis
    - sjögren’s syndrome
    - tubulointerstitial nephritis with uveitis
    - systemic lupus erythematosus
    - granulomatous interstitial nephritis
    - igg4-related systemic disease
    - ain associated with the use of immune checkpoint inhibitors
    - idiopathic ain
    - infection-associated ain
    - crystal deposition disorders and obstructive tubulopathies
    - light chain cast nephropathy
    - lymphomatous infiltration of the kidney
  - chronic tubulointerstitial diseases
    - vesicoureteral reflux and reflux nephropathy
    - sickle cell nephropathy
    - tubulointerstitial abnormalities associated with glomerulonephritis
    - analgesic nephropathy
    - aristolochic acid nephropathy
    - karyomegalic interstitial nephritis
    - lithium-associated nephropathy
    - calcineurin inhibitor nephrotoxicity
    - heavy metal (Lead) Nephropathy
  - metabolic disorders
    - chronic uric acid nephropathy
    - hypercalcemic nephropathy
    - hypokalemic nephropathy
  - global perspective
- 317 vascular injury to the kidney
  - thrombotic microangiopathy
  - hemolytic-uremic syndrome/thromboticthrombocytopenic purpura
  - hematopoietic stem cell transplantation–associated thrombotic microangiopathy
  - hiv-related thrombotic microangiopathy
  - radiation nephropathy
  - scleroderma (Progressive systemic sclerosis)
  - antiphospholipid syndrome
  - hellp syndrome
  - sickle cell nephropathy
  - renal vein thrombosis
- 318 nephrolithiasis
  - epidemiology
  - associated medical conditions
  - pathogenesis
  - risk factors
  - approach to the patient
  - recommendations for specific stone types
  - long-term follow-up
- 319 urinary tract obstruction
  - etiology
  - clinical features and pathophysiology
  - diagnosis
  - treatment
  - prognosis
  - postobstructive diuresis
- 320 interventional nephrology
  - history
  - physiology and pathophysiology of dialysis access
  - arteriovenous grafts and fistulas
  - approach to the patient
part 10 disorders of the gastrointestinal system
- section 1 disorders of the alimentary tract
  - 321 approach to the patient with gastrointestinal disease
    - anatomic considerations
    - functions of the gi tract
    - extrinsic modulation of gut function
    - overview of gi diseases
      - classification of gi diseases
        impaired digestion and absorption
        
        altered secretion
        
        altered gut transit
        
        immune dysregulation
        
        impaired gut blood flow
        
        neoplastic degeneration
        
        disorders without obvious organic abnormalities
        
        genetic influences
      - symptoms of gi disease
        abdominal pain
        
        heartburn
        
        nausea and vomiting
        
        altered bowel habits
        
        gi bleeding
        
        jaundice
        
        other symptoms
    - evaluation of the patient with gi disease
      - history
      - physical examination
      - tools for patient evaluation
    - treatment
  - 322 gastrointestinal endoscopy
    - endoscopic procedures
      - upper endoscopy
      - colonoscopy
      - flexible sigmoidoscopy
      - small-bowel endoscopy
      - endoscopic retrograde cholangiopancreatography
      - endoscopic ultrasound
      - natural orifice transluminal endoscopic surgery
      - endoscopic resection and closure techniques
    - risks of endoscopy
    - urgent endoscopy
      - acute gastrointestinal hemorrhage
      - gastrointestinal obstruction andpseudoobstruction
      - acute biliary obstruction
    - elective endoscopy
      - dyspepsia
      - gastroesophageal reflux disease
      - peptic ulcer
      - nonulcer dyspepsia
      - dysphagia
      - endoscopic treatment of obesity
      - treatment of malignancies
      - anemia and occult blood in the stool
      - colorectal cancer screening
      - diarrhea
      - minor hematochezia
      - pancreatitis
      - cancer staging
    - open-access endoscopy
  - 323 diseases of the esophagus
    - esophageal structure and function
    - symptoms of esophageal disease
    - diagnostic studies
      - endoscopy
      - radiography
      - endoscopic ultrasound
      - esophageal manometry
      - reflux testing
    - structural disorders
      - hiatal hernia
      - rings and webs
      - diverticula
      - tumors
    - congenital anomalies
    - esophageal motility disorders
      - achalasia
      - diffuse esophageal spasm
      - nonspecific manometric findings
    - gastroesophageal reflux disease
      - pathophysiology
      - symptoms
      - differential diagnosis
      - complications
      - treatment
      - eosinophilic esophagitis
    - infectious esophagitis
      - candida esophagitis
      - herpetic esophagitis
      - cytomegalovirus
    - mechanical trauma and iatrogenic injury
      - esophageal perforation
      - mallory-weiss tear
      - radiation esophagitis
      - corrosive esophagitis
      - pill esophagitis
      - foreign bodies and food impaction
    - esophageal manifestations of systemic disease
      - scleroderma and connectivetissue disorders
      - dermatologic diseases
  - 324 peptic ulcer disease and related disorders
    - peptic ulcer disease
      - gastric physiology
      - pathophysiologic basis of pud
      - clinical features
      - treatment
    - related conditions
      - zollinger-ellison syndrome
      - stress-related mucosal injury
      - gastritis
      - ménétrier’s disease
  - 325 disorders of absorption
    - overview: nutrient digestionand absorption
      - specific nutrients
      - luminal phase of digestion
      - mucosal phase of digestion and absorption
    - intestinal mucosal disorders
      - disorders of enterocyte carbohydrate transporters and enzyme deficiencies
      - intestinal mucosal disorders that result in malabsorption of multiple nutrients
      - whipple’s disease
      - tropical sprue
    - short-bowel syndrome
      - overview
      - disorders of post-mucosal absorption
    - protein-losing enteropathy
    - approach to the patient
    - summary
  - 326 inflammatory bowel disease
    - global considerations: epidemiology
    - global considerations: ibd phenotypes
    - etiology and pathogenesis
      - genetic considerations
      - commensal microbiota and ibd
      - defective immune regulation in ibd
      - the inflammatory cascade in ibd
    - pathology
      - ulcerative colitis: macroscopic features
      - ulcerative colitis: microscopic features
      - crohn’s disease: macroscopic features
      - crohn’s disease: microscopic features
    - clinical presentation
      - ulcerative colitis
      - crohn’s disease
    - differential diagnosis of uc and cd
      - infectious diseases
      - noninfectious diseases
      - the atypical colitides
    - extraintestinal manifestations
      - dermatologic
      - rheumatologic
      - ocular
      - hepatobiliary
      - urologic
      - metabolic bone disorders
      - thromboembolic disorders
      - other disorders
    - treatment
      - 5-asa agents
      - glucocorticoids
      - antibiotics
      - azathioprine and mercaptopurine
      - methotrexate
      - cyclosporine
      - tacrolimus
      - biologic therapies
      - anti-integrins
      - small molecules
      - ozanimod
      - nutritional therapies
      - surgical therapy
    - ibd and pregnancy
    - cancer in ibd
      - ulcerative colitis
      - crohn’s disease
      - management of dysplasia and cancer
    - covid-19 and ibd
  - 327 irritable bowel syndrome
    - clinical features
    - pathophysiology
    - approach to the patient
    - treatment
  - 328 diverticular disease and common anorectal disorders
    - diverticular disease
    - common diseases of the anorectum
      - rectal prolapse (Procidentia)
      - fecal incontinence
      - hemorrhoidal disease
      - anorectal abscess
      - fistula in ano
      - anal fissure
  - 329 mesenteric vascular insufficiency
    - intestinal ischemia
      - incidence and epidemiology
      - anatomy and pathophysiology
      - presentation, evaluation, and management
  - 330 acute intestinal obstruction
    - epidemiology
    - pathophysiology
    - history and physical findings
    - laboratory and imaging studies
    - treatment
  - 331 acute appendicitis and peritonitis
    - acute appendicitis
      - incidence and epidemiology
      - pathogenesis of appendicitis and appendiceal perforation
      - clinical manifestations
      - laboratory testing
      - imaging
      - special patient populations
      - treatment
    - acute peritonitis
      - etiology
      - clinical features
      - therapy and prognosis
- section 2 nutrition
  - 332 nutrient requirements and dietary assessment
    - essential nutrient requirements
      - energy
      - protein
      - fat and carbohydrate
      - water
      - other nutrients
    - dietary reference intakes and rdas
      - estimated average requirement (Ear)
      - recommended dietary allowances
      - adequate intake (Ai)
      - tolerable upper levels (Ul)
      - chronic disease risk reduction intake (Cdrr)
      - acceptable macronutrient distribution ranges (Amdrs)
    - factors altering nutrient needs
      - physiologic factors
      - dietary composition
      - route of intake
      - disease
    - dietary assessment
      - acute-care settings
      - ambulatory settings
    - nutritional status assessment
    - global considerations
  - 333 vitamin and trace mineral deficiency and excess
    - vitamins
      - thiamine (Vitamin b1)
      - riboflavin (Vitamin b2)
      - niacin (Vitamin b3)
      - pyridoxine (Vitamin b6)
      - folate (Vitamin b12)
      - vitamin c
      - biotin
      - pantothenic acid (Vitamin b5)
      - choline
      - flavonoids
      - vitamin a
      - vitamin d
      - vitamin e
      - vitamin k
    - minerals
      - calcium
      - zinc
      - copper
      - selenium
      - chromium
      - magnesium
      - fluoride, manganese, and ultratrace elements
  - 334 malnutrition and nutritional assessment
    - malnutrition syndromes
    - nutrition assessment
  - 335 enteral and parenteral nutrition
    - nutritional physiology
    - macronutrient malnutrition syndromes
    - nutritional diagnosis
    - specialized nutritional support
    - approach to the patient
- section 3 liver and biliary tract disease
  - 336 approach to the patient with liver disease
    - liver structure and function
    - liver diseases
      - clinical history
      - physical examination
      - diagnosis of liver disease
      - grading and staging of liver disease
      - nonspecific issues in the management of patients with liver disease
  - 337 evaluation of liver function
    - serum bilirubin
    - serum enzymes
    - serum albumin
    - serum globulins
    - coagulation factors
    - other diagnostic tests
    - use of liver tests
    - global considerations
  - 338 the hyperbilirubinemias
    - bilirubin metabolism
    - extrahepatic aspects of bilirubin disposition
    - disorders of bilirubin metabolism leading to unconjugated hyperbilirubinemia
      - increased bilirubin production
      - decreased hepatic bilirubin clearance
      - hereditary defects in bilirubin conjugation
    - disorders of bilirubin metabolism leading to mixed or predominantly conjugated hyperbilirubinemia
      - familial defects in hepaticexcretory function
  - 339 acute viral hepatitis
    - virology and etiology
      - hepatitis a
      - hepatitis b
      - hepatitis d
      - hepatitis c
      - hepatitis e
    - pathogenesis
      - hepatitis b
      - hepatitis c
      - hepatitis a and e
    - extrahepatic manifestations
    - pathology
    - epidemiology and global features
      - hepatitis a
      - hepatitis b
      - hepatitis d
      - hepatitis c
      - hepatitis e
    - clinical and laboratory features
      - symptoms and signs
      - laboratory features
    - prognosis
    - complications and sequelae
    - differential diagnosis
    - treatment
    - prophylaxis
      - hepatitis a
      - hepatitis b
      - hepatitis d
      - hepatitis c
      - hepatitis e
  - 340 toxic and drug-induced hepatitis
    - drug metabolism
    - liver injury caused by drugs
    - treatment: toxic and drug-induced hepatic disease
    - acetaminophen hepatotoxicity (Direct toxin)
    - isoniazid hepatotoxicity (Toxic and idiosyncratic reaction)
    - sodium valproate hepatotoxicity (Toxic and idiosyncratic reaction)
    - nitrofurantoin hepatotoxicity (Idiosyncratic reaction)
    - amoxicillin-clavulanate hepatotoxicity (Idiosyncratic mixed reaction)
    - amiodarone hepatotoxicity (Toxic and idiosyncratic reaction)
    - anabolic steroids (Cholestatic reaction)
    - trimethoprim-sulfamethoxazole hepatotoxicity (Idiosyncratic reaction)
    - hmg-coa reductase inhibitors (Statins) (Idiosyncratic mixed hepatocellular and cholestatic reaction)
    - alternative and complementary medicines (Idiosyncratic hepatitis, steatosis)
    - checkpoint inhibitor and other immunotherapies for cancer
    - highly active antiretroviral therapy for hiv infection (Mitochondrial toxic, idiosyncratic, steatosis; hepatocellular,cholestatic, and mixed)
  - 341 chronic hepatitis
    - classification of chronic hepatitis
      - classification by cause
      - classification by grade
      - classification by stage
    - chronic viral hepatitis
      - chronic hepatitis b
      - chronic hepatitis c
    - autoimmune hepatitis
      - definition
      - immunopathogenesis
      - clinical features
      - diagnostic criteria
      - differential diagnosis
      - treatment
  - 342 alcohol-associated liver disease
    - epidemiology
    - pathogenesis
    - risk factors for progression of ald
    - clinical features
    - laboratory findings
    - diagnosis
    - treatment
  - 343 nonalcoholic fatty liver diseases and nonalcoholic steatohepatitis
    - incidence, prevalence, and natural history
    - pathogenesis
    - diagnosis
    - clinical features of nafld
    - treatment of nafld
      - global health considerations
  - 344 cirrhosis and its complications
    - alcohol-associated cirrhosis
    - cirrhosis due to chronic viral hepatitis b or c
    - cirrhosis from autoimmune hepatitis and nonalcoholic fatty liver disease
    - biliary cirrhosis
    - primary biliary cholangitis
    - primary sclerosing cholangitis
    - cardiac cirrhosis
    - other types of cirrhosis
    - major complications of cirrhosis
      - portal hypertension
      - portal hypertensive gastropathy
      - splenomegaly and hypersplenism
      - ascites
      - spontaneous bacterial peritonitis
      - hepatorenal syndrome
      - hepatic encephalopathy
      - liver-lung syndromes
      - malnutrition in cirrhosis
      - abnormalities in coagulation
      - bone disease in cirrhosis
      - hematologic abnormalities in cirrhosis
  - 345 liver transplantation
    - indications
    - contraindications
    - technical considerations
    - postoperative course and management
    - outcome
  - 346 diseases of the gallbladder and bile ducts
    - physiology of bile production and flow
      - bile secretion and composition
      - the bile acids
      - enterohepatic circulation
      - gallbladder and sphincteric functions
    - diseases of the gallbladder
      - congenital anomalies
      - gallstones
      - acute and chronic cholecystitis
      - the hyperplastic cholecystoses
    - diseases of the bile ducts
      - congenital anomalies
      - choledocholithiasis
      - trauma, strictures, and hemobilia
      - extrinsic compression of the bile ducts
      - hepatobiliary parasitism
      - sclerosing cholangitis
- section 4 disorders of the pancreas
  - 347 approach to the patient with pancreatic disease
    - general considerations
    - tests useful in the diagnosis of pancreatic disease
    - tests of exocrine pancreatic function
  - 348 acute and chronic pancreatitis
    - biochemistry and physiology of pancreatic exocrine secretion
      - general considerations
      - regulation of pancreatic secretion
      - water and electrolyte secretion
      - enzyme secretion
      - autoprotection of the pancreas
      - enteropancreatic axis and feedback inhibition
    - acute pancreatitis
      - general considerations
      - etiology and pathogenesis
      - activation of pancreatic enzymes in the pathogenesis of acute pancreatitis
      - approach to the patient
      - laboratory data
      - diagnosis
      - clinical course, definitions, and classifications
      - acute pancreatitis management
      - recurrent acute pancreatitis
      - pancreatitis in patients with aids
    - chronic pancreatitis and exocrine pancreatic insufficiency
      - pathophysiology
      - etiologic considerations
      - autoimmune pancreatitis
      - treatment
      - hereditary pancreatitis
      - pancreatic endocrine tumors
    - other conditions
      - annular pancreas
      - pancreas divisum
      - macroamylasemia
part 11 immune-mediated, inflammatory, and rheumatologic disorders
- section 1 the immune system in health and disease
  - 349 introduction to the immune system
    - definitions
    - introduction
    - the innate immune system
    - pattern recognition
    - effector cells of innate immunity
      - monocytes-macrophages
      - dendritic cells
      - innate lymphoid cells
      - neutrophils, eosinophils, and basophils
      - the complement system
    - cytokines
    - the adaptive immune system
      - t cells
      - humoral mediators of adaptive immunity: immunoglobulins
    - cellular interactions in regulation of normal immune responses
    - immune tolerance and autoimmunity
    - the cellular and molecular control of programmed cell death
    - mechanisms of immune-mediated damage to microbes or host tissues
    - clinical evaluation of immune function
    - immunotherapy
  - 350 mechanisms of regulation and dysregulation of the immune system
    - definitions
    - introduction
    - mechanisms of regulation of t-cell activation
    - checkpoint inhibitiontherapy for cancer
    - chimeric antigen receptor t cells
    - mechanisms of immunedysregulation in autoimmunedisease
    - immune dysregulation in aging
  - 351 primary immune deficiency diseases
    - diagnosis of primary immunodeficiencies
    - primary immunodeficiencies of the innate immune system
      - severe congenital neutropenia
      - asplenia
      - gata2 deficiency
      - leukocyte adhesion deficiency
      - chronic granulomatous diseases
      - mendelian susceptibility to mycobacterial disease
      - toll-like receptor (Tlr) Pathway deficiencies
      - complement deficiency
    - primary immunodeficiencies of the adaptive immune system
      - t lymphocyte deficiencies
        severe combined immunodeficiencies
        
        thymic defects
        
        omenn syndrome
        
        functional t-cell defects
        
        t-cell primary immunodeficiencies with dna repair defects
        
        t-cell primary immunodeficiencies with hyper-ige
        
        autosomal dominant hyper-ige syndrome
        
        cartilage hair hypoplasia
        
        cd40 ligand and cd40 deficiencies
        
        wiskott-aldrich syndrome
      - b lymphocyte deficiencies
        agammaglobulinemia
        
        hyper-igm (Higm) Syndromes
        
        common variable immunodeficiency
        
        selective ig isotype deficiencies
        
        selective antibody deficiency to polysaccharide antigens
        
        immunoglobulin replacement
    - primary immunodeficiencies affecting regulatory pathways
      - hemophagocytic lymphohistiocytosis
      - autoimmune lymphoproliferative syndrome
      - colitis, autoimmunity, and primary immunodeficiencies
    - conclusion
- section 2 disorders of immune-mediated injury
  - 352 urticaria, angioedema, and allergic rhinitis
    - introduction
    - urticaria and angioedema
      - definition
      - predisposing factors and etiology
      - clinical presentation and pathophysiology
      - treatment
    - allergic rhinitis
      - definition
      - predisposing factors and etiology
      - pathophysiology and manifestations
      - diagnosis
      - treatment
  - 353 anaphylaxis
    - background
    - clinical manifestations
    - pathophysiology
    - predisposing factors and mechanisms
    - diagnosis
    - treatment
    - prevention
  - 354 mastocytosis
    - definition and epidemiology
    - classification and pathophysiology
    - clinical manifestations
    - diagnosis and differential diagnosis
    - treatment
  - 355 autoimmunity and autoimmune diseases
    - mechanisms of autoimmunity
    - genetic considerations
    - immunopathogenic mechanisms in autoimmune diseases
    - autoimmune diseases
    - organ-specific versus systemic autoimmune diseases
    - treatment
  - 356 systemic lupus erythematosus
    - definition and prevalence
    - pathogenesis and etiology
    - interpretation of clinical manifestations
    - laboratory tests
    - conservative therapies for management of non-life-threatening disease
    - patient outcomes, prognosis, and survival
    - drug-induced lupus
  - 357 antiphospholipid syndrome
    - definitions
    - epidemiology
    - pathogenesis
    - clinical manifestations and laboratory findings
    - diagnosis and differential diagnosis
    - treatment
  - 358 rheumatoid arthritis
    - introduction
    - clinical features
    - epidemiology
    - genetic considerations
    - environmental factors
    - pathology
    - pathogenesis
    - diagnosis
    - laboratory features
    - clinical course
    - treatment
    - approach to the patient
    - global challenges
    - summary
  - 359 acute rheumatic fever
    - global considerations
    - epidemiology
    - pathogenesis
    - clinical features
    - treatment
    - prognosis
    - prevention
  - 360 systemic sclerosis (Scleroderma) And related disorders
    - definition and classification
    - incidence and prevalence
    - genetic contribution to disease pathogenesis
    - environmental and occupational exposures
    - pathogenesis
    - pathology
    - clinical features
    - organ involvement
    - management of systemic sclerosis
    - treatment
    - course
    - prognosis
    - localized scleroderma
    - mixed connective tissue disease
    - eosinophilic fasciitis (Diffuse fasciitis with eosinophilia)
  - 361 sjögren’s syndrome
    - definition, incidence, and prevalence
    - pathogenesis
    - clinical manifestations
    - diagnosis and differential diagnosis
    - treatment
  - 362 spondyloarthritis
    - ankylosing spondylitis and axial spondyloarthritis
    - reactive arthritis
    - psoriatic arthritis
    - ibd-associated arthritis
    - sapho syndrome
  - 363 the vasculitis syndromes
    - definition
    - classification
    - pathophysiology and pathogenesis
    - approach to the patient
    - granulomatosis with polyangiitis
    - microscopic polyangiitis
    - eosinophilic granulomatosis with polyangiitis (Churg-strauss)
    - polyarteritis nodosa
    - giant cell arteritis and polymyalgia rheumatica
    - takayasu arteritis
    - iga vasculitis (Henoch-schönlein)
    - cryoglobulinemic vasculitis
    - single-organ vasculitis
    - idiopathic cutaneous vasculitis
    - primary central nervous system vasculitis
    - behçet’s disease
    - cogan’s syndrome
    - kawasaki’s disease
    - polyangiitis overlap syndromes
    - secondary vasculitis
  - 364 behçet syndrome
    - diagnosis
    - pathogenesis
    - clinical presentation
    - treatment
  - 365 inflammatory myopathies
    - diagnostic approach and differential diagnosis
    - specific disorders
      - dermatomyositis
      - polymyositis
      - overlap syndromes
      - immune-mediated necrotizing myopathy
      - antisynthetase syndrome
      - inclusion body myositis
    - treatment of the im
      - general guidelines for use ofspecific immunotherapies
      - second-line therapies
    - myositis associated with checkpoint inhibitors
    - myositis associated with covid-19 infection
    - global issues
  - 366 relapsing polychondritis
    - pathology and pathophysiology
    - clinical manifestations
    - laboratory findings and diagnostic imaging
    - diagnosis
    - treatment
    - patient outcome, prognosis, and survival
  - 367 sarcoidosis
    - definition
    - etiology
      - incidence, prevalence, and global impact
      - pathophysiology and immunopathogenesis
      - clinical manifestations
      - lung
      - skin
      - eye
      - liver
      - bone marrow and spleen
      - calcium metabolism
      - renal disease
      - nervous system
      - cardiac
      - musculoskeletal system
      - other organ involvement
      - complications
    - laboratory findings
    - diagnosis
    - prognosis
    - treatment
  - 368 igg4-related disease
    - clinical features
    - serologic findings
    - epidemiology
    - pathology
    - pathophysiology
    - treatment
  - 369 familial mediterranean fever and other hereditary autoinflammatory diseases
    - background and pathophysiology
    - acute attacks
    - amyloidosis
    - diagnosis
    - treatment: familial mediterranean fever
    - other hereditary recurrent fevers
      - tnf receptor–associated periodic syndrome
      - hyperimmunoglobulinemia d with periodic fever syndrome (Also known as mevalonate kinase deficiency)
      - nlrp3-associated autoinflammatory disease (Also known as the cryopyrinopathies or cryopyrin-associated periodic syndromes)
      - periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis
    - other inherited autoinflammatory diseases
    - global considerations
- section 3 disorders of the joints and adjacent tissues
  - 370 approach to articular and musculoskeletal disorders
    - articular versus nonarticular
    - inflammatory versus noninflammatory disorders
    - rheumatologic evaluation of the elderly
    - rheumatologic evaluation of the hospitalized patient
    - physical examination
    - approach to regional rheumatic complaints
    - telehealth musculoskeletal evaluation
    - laboratory investigations
    - diagnostic imaging in joint diseases
  - 371 osteoarthritis
    - global considerations
    - definition
    - joint protective mechanisms and their failure
    - risk factors
    - pathology
    - sources of pain
    - clinical features
    - treatment
  - 372 gout and other crystal-associated arthropathies
    - gout
    - calcium pyrophosphate deposition disease
    - calcium apatite deposition disease
    - caox deposition disease
  - 373 fibromyalgia
    - definition
    - epidemiology
    - clinical manifestations
    - differential diagnosis
    - laboratory or radiographic testing
    - approach to the patient
    - treatment
  - 374 arthritis associated with systemic disease, and other arthritides
    - arthritis associated with systemic disease
      - arthropathy of acromegaly
      - arthropathy of hemochromatosis
      - hemophilic arthropathy
      - arthropathies associated with hemoglobinopathies
      - musculoskeletal disorders associated with hyperlipidemia
    - other arthritides
      - neuropathic joint disease
      - hypertrophic osteoarthropathy and clubbing
      - complex regional pain syndrome
      - tietze syndrome and costochondritis
      - myofascial pain syndrome
      - neoplasias and arthritis
  - 375 periarticular disorders of the extremities
    - bursitis
    - rotator cuff tendinitis and impingement syndrome
    - calcific tendinitis
    - bicipital tendinitis and rupture
    - de quervain’s tenosynovitis
    - patellar tendinitis
    - drug-induced tendinopathies
    - iliotibial band syndrome
    - adhesive capsulitis
    - lateral epicondylitis
    - medial epicondylitis
    - plantar fasciitis
part 12 endocrinology and metabolism
- section 1 endocrinology
  - 376 approach to the patient with endocrine disorders
    - scope of endocrinology
    - pathologic mechanisms of endocrine disease
      - causes of hormone excess
      - causes of hormone deficiency
      - hormone resistance
      - clinical evaluation of endocrine disorders
      - hormone measurements and endocrine testing
      - screening and assessment of common endocrine disorders
  - 377 mechanisms of hormone action
    - classes of hormones
      - hormone and receptor families
      - hormone synthesis and processing
      - hormone secretion, transport, and degradation
      - hormone action through receptors
      - membrane receptors
      - nuclear receptors
      - maintenance of homeostasis
      - reproduction
    - hormonal feedback regulatory systems
      - paracrine and autocrine control
      - hormonal rhythms
  - 378 physiology of anterior pituitary hormones
    - anatomy and development
    - anterior pituitary hormones
      - prolactin
      - growth hormone
      - adrenocorticotropic hormone
      - gonadotropins: fsh and lh
      - thyroid-stimulating hormone
  - 379 hypopituitarism
    - developmental causes of hypopituitarism
    - hypothalamic endocrine dysfunction
      - kallmann syndrome
      - bardet-biedl syndrome
      - leptin and leptin receptor mutations
      - prader-willi syndrome
    - acquired hypopituitarism
      - hypothalamic infiltration disorders
      - inflammatory lesions
      - cranial irradiation
      - lymphocytic hypophysitis
      - immunotherapy and hypophysitis
      - pituitary apoplexy
      - empty sella
    - presentation and diagnosis
    - laboratory investigation
    - treatment
    - disorders of growth and development
    - adult gh deficiency
    - acth deficiency
    - gonadotropin deficiency
    - diabetes insipidus
  - 380 pituitary tumor syndromes
    - hypothalamic, pituitary, and other sellar masses
    - evaluation of sellar masses
    - sellar masses
    - pituitary adenomas and hypersecretion syndromes
    - hyperprolactinemia
    - galactorrhea
    - prolactinoma
    - acromegaly
    - cushing’s disease (Acth-producing adenoma)
    - nonfunctioning and gonadotropin-producing pituitary adenomas
    - tsh-secreting adenomas
    - aggressive adenomas
  - 381 disorders of the neurohypophysis
    - vasopressin
    - thirst
    - oxytocin
    - deficiencies of avp secretion and action
      - diabetes insipidus
      - hypodipsic hypernatremia
      - inappropriate antidiuresis
    - global perspectives
  - 382 thyroid gland physiology and testing
    - anatomy and development
    - thyroid hormone synthesis, metabolism, and action
      - thyroid hormone synthesis
      - thyroid function in pregnancy
      - thyroid hormone transport and metabolism
      - thyroid hormone action
    - physical examination
    - laboratory evaluation
  - 383 hypothyroidism
    - congenital hypothyroidism
    - autoimmune hypothyroidism
    - other causes of hypothyroidism
    - treatment
  - 384 hyperthyroidism and other causes of thyrotoxicosis
    - thyrotoxicosis
      - graves’ disease
      - other causes of thyrotoxicosis
      - acute thyroiditis
      - subacute thyroiditis
      - silent thyroiditis
      - drug-induced thyroiditis
      - chronic thyroiditis
    - sick euthyroid syndrome (Nonthyroidal illness)
    - amiodarone effects on thyroid function
  - 385 thyroid nodular disease and thyroid cancer
    - goiter and thyroid nodular disease
    - diffuse nontoxic (Simple) Goiter
    - nontoxic multinodular goiter
    - toxic multinodular goiter
    - hyperfunctioning solitary nodule
    - benign lesions
    - thyroid cancer
      - classification
      - pathogenesis and genetic basis
      - well-differentiated thyroid cancer
      - anaplastic and other forms of thyroid cancer
      - medullary thyroid carcinoma
  - 386 disorders of the adrenal cortex
    - adrenal anatomy and development
    - regulatory control of steroidogenesis
    - steroid hormone synthesis, metabolism, and action
    - cushing’s syndrome
    - mineralocorticoid excess
    - approach to the patient: incidentally discovered adrenal mass
    - adrenocortical carcinoma
    - adrenal insufficiency
    - congenital adrenal hyperplasia
  - 387 pheochromocytoma
    - epidemiology
    - etiology and pathogenesis
    - clinical features
    - diagnosis
    - treatment
    - metastatic pheochromocytoma
      - pheochromocytoma in pregnancy
    - pheochromocytoma-associated syndromes
    - genetic screening of patients with pheochromocytoma or paraganglioma
  - 388 multiple endocrine neoplasia syndromes
    - multiple endocrine neoplasia type 1
    - multiple endocrine neoplasia type 2 and type 3
    - multiple endocrine neoplasia type 4
    - hyperparathyroidism-jaw tumor syndrome
    - von hippel–lindau disease
    - neurofibromatosis
    - carney complex
    - cowden’s syndrome
    - mccune-albright syndrome
  - 389 autoimmune polyendocrine syndromes
    - aps-1
    - aps-2
    - immune checkpoint inhibitor–induced endocrine autoimmunity
    - ipex
    - thymic tumors
    - anti-insulin receptor antibodies
    - insulin autoimmune syndrome (Hirata’s syndrome)
    - poems syndrome
    - other disorders
    - global considerations
- section 2 sex- and gender-based medicine
  - 390 sex development
    - sex development
    - disorders of chromosomal sex
      - klinefelter syndrome (47,xxy)
      - turner syndrome (Gonadal dysgenesis; 45,x)
      - 45,x/46,xy mosaicism
      - ovotesticular dsd
    - disorders of gonadal and phenotypic sex
      - 46,xy dsd
      - other disorders affecting 46,xy males
      - 46,xx dsd
      - global considerations
    - other disorders affecting 46,xx females
  - 391 disorders of the testes and male reproductive system
    - development and structureof the testis
    - normal male pubertal development
    - regulation of testicular function
      - regulation of the hypothalamic-pituitary-testis axis in adult man
      - the leydig cell: androgen synthesis
      - the seminiferous tubules: spermatogenesis
    - clinical and laboratory evaluation of male reproductive function
      - history and physical examination
      - gonadotropin and inhibin measurements
      - testosterone assays
      - semen analysis
      - testicular biopsy
    - disorders of sexual differentiation
    - disorders of puberty
      - precocious puberty
      - delayed puberty
    - disorders of the male reproductive axis during adulthood
      - hypogonadotropic hypogonadism
      - primary testicular causes of hypogonadism
      - androgen insensitivity syndromes
    - gynecomastia
    - aging-related changes in male reproductive function
    - approach to the patient: androgen deficiency
    - treatment: androgen deficiency
    - approach to the patient: androgenic-anabolic steroids use
  - 392 disorders of the female reproductive system
    - development of the ovary and early follicular growth
    - development of a mature follicle
    - regulation of ovarian function
      - hypothalamic and pituitary secretion
      - ovarian steroids
      - ovarian peptides
    - hormonal integration of the normal menstrual cycle
      - the follicular phase
      - the luteal phase
    - clinical assessment of ovarian function
    - puberty
      - normal pubertal development in girls
      - disorders of puberty
        precocious puberty
        
        delayed puberty
  - 393 menstrual disorders and pelvic pain
    - menstrual disorders
      - definition and prevalence
      - primary amenorrhea
      - secondary amenorrhea or oligomenorrhea
      - disorders of the uterus or outflow tract
      - disorders of ovulation
        hypogonadotropic hypogonadism
        
        hypergonadotropic hypogonadism
        
        polycystic ovarian syndrome
    - pelvic pain
      - acute pelvic pain
      - chronic pelvic pain
  - 394 hirsutism
    - defining hirsutism
    - hair follicle growth and differentiation
    - clinical assessment
    - hormonal evaluation
    - treatment
  - 395 menopause and postmenopausal hormone therapy
    - perimenopause
      - physiology
      - diagnostic tests
      - symptoms
      - treatment
    - menopause and postmenopausal ht
      - benefits and risks of postmenopausal ht
      - approach to the patient
  - 396 infertility and contraception
    - infertility
      - etiology
      - fertility evaluation
      - counseling and treatment
      - psychological aspects of infertility
    - contraception
      - types of contraception
      - contraception counseling
  - 397 sexual dysfunction
    - male sexual dysfunction
      - physiology of male sexual response
      - erectile dysfunction
      - treatment
    - female sexual dysfunction
      - epidemiology
      - physiology of the female sexual response
      - approach to the patient
      - treatment
  - 398 women’s health
    - disease risk: reality and perception
    - sex differences in health and disease
    - summary
  - 399 men’s health
    - aging-related changes in male reproductive function
    - approach to the patient: older men with age-related decline in testosterone
    - age-related changes in fecundity
      - sexual dysfunction
      - muscle dysmorphia syndrome in men—a form of body image disorder
      - aas abuse by athletes and recreational bodybuilders
      - luts in men
      - medical complications of prostate cancer therapy
      - medical complications of adt
      - prevention of sexually transmitted diseases
    - sex differences in covid-19 disease outcomes
  - 400 lesbian, gay, bisexual, and transgender (Lgbt) Health
    - understanding lgbt health disparities
    - creating positive health experiences for lgbt patients
    - future direction in lgbt health
- section 3 obesity, diabetes mellitus, and metabolic syndrome
  - 401 pathobiology of obesity
    - definition of obesity and overweight
    - epidemiology
    - physiologic regulation of energy balance
    - the physiology of nutrient storage in adipose tissue
    - the causes of obesity: an interaction of genes and environment
    - the relative roles of excess intake and lower energy expenditure in conferring biologic predisposition
    - environmental factors predisposing to obesity
    - why doesn’t leptin prevent obesity?
    - single-gene disorders leading to obesity
    - classical syndromic disorders
    - disorders of leptin-melanocortin signaling
    - genetic subtypes of obesity associated with neurobehavioral abnormalities
    - obesity secondary to other disorders
    - adverse consequences of obesity
    - conclusion
  - 402 evaluation and management of obesity
    - evaluation
    - treatment
  - 403 diabetes mellitus: diagnosis, classification, and pathophysiology
    - classification
    - epidemiology and global considerations
    - diagnosis
    - regulation of glucose homeostasis
    - pathogenesis
    - genetically defined, monogenic forms of dm related to reduced insulin secretion
    - approach to the patient
  - 404 diabetes mellitus: management and therapies
    - overall goals
    - ongoing aspects of comprehensive diabetes care
      - lifestyle management in diabetes care
      - diabetes self-management education and support (Dsmes)
      - nutrition therapy
      - physical activity
      - psychosocial care
      - monitoring the level of glycemic control
        self-monitoring of blood glucose
        
        continuous glucose monitoring
        
        assessment of long-term glycemic control
    - pharmacologic treatment of diabetes
      - establishment of target level ofglycemic control
      - type 1 diabetes mellitus
        general aspects
        
        intensive management
        
        insulin preparations
        
        insulin regimens
        
        other agents that improve glucose control
      - type 2 diabetes mellitus
        general aspects
        
        glucose-lowering agents
      - other therapies for diabetes
      - emerging therapies
    - adverse effects of therapy for dm
    - acute disorders related to severe hyperglycemia
      - diabetic ketoacidosis
      - hyperglycemic hyperosmolar state
    - management of diabetes in a hospitalized patient
    - special considerations in dm
  - 405 diabetes mellitus: complications
    - glycemic control and complications
    - mechanisms of complications
    - ophthalmologic complications of diabetes mellitus
    - renal complications of diabetes mellitus
    - neuropathy and diabetes mellitus
    - gastrointestinal/genitourinary dysfunction
    - cardiovascular morbidity and mortality
    - lower extremity complications
    - infections
    - dermatologic manifestations
  - 406 hypoglycemia
    - systemic glucose balance and glucose counterregulation
    - hypoglycemia in diabetes
    - hypoglycemia without diabetes
    - accidental, surreptitious, or malicious hypoglycemia
    - inborn errors of metabolism causing hypoglycemia
    - approach to the patient
  - 407 disorders of lipoprotein metabolism
    - lipoprotein structureand metabolism
      - transport of intestinally derived dietary lipids by chylomicrons
      - transport of hepatically derived lipids by vldl and ldl
      - hdl metabolism and reverse cholesterol transport
    - screening
    - disorders associated with elevated apob-containing lipoproteins
      - severe hypertriglyceridemia
      - hypercholesterolemia (Elevated ldl-c)
      - mixed hyperlipidemia (Elevated tg and ldl-c)
      - secondary contributors to elevated levels of apob-containing lipoproteins
    - disorders associated with reduced apob-containing lipoproteins
      - abetalipoproteinemia
      - familial hypobetalipoproteinemia (Fhbl)
      - familial pcsk9 deficiency
      - familial combined hypolipidemia
    - disorders associated with reduced high-density lipoproteins
      - primary (Genetic) Causes of low hdl-c
        gene deletions and missense mutations in apoa1
        
        tangier disease (Abca1 deficiency)
        
        familial lcat deficiency
        
        primary hypoalphalipoproteinemia
      - secondary factors that reduce hdl-c levels
        hypertriglyceridemia
        
        very-low-fat diet
      - sedentary lifestyle and obesity
    - approach to the patient
    - treatment: severe hypertriglyceridemia
    - treatment: hypercholesterolemia (Elevated ldl-cwith or without elevated tg)
  - 408 the metabolic syndrome
    - global health/epidemiology
    - risk factors
    - etiology
    - clinical features
    - diagnosis
    - treatment
- section 4 disorders of bone and mineral metabolism
  - 409 bone and mineral metabolism in health and disease
    - bone structure and metabolism
    - calcium metabolism
    - phosphorus metabolism
    - magnesium metabolism
    - vitamin d
  - 410 disorders of the parathyroid gland and calcium homeostasis
    - introduction
    - pth
    - pthrp
    - calcitonin
    - hypercalcemia
      - introduction
      - primary hyperparathyroidism
      - other parathyroid causes of hypercalcemia
      - genetic disorders causing hyperparathyroidism-like syndromes
      - malignancy-related hypercalcemia
      - vitamin d–related hypercalcemia
      - high-bone-turnover states
      - renal failure–associated hypercalcemia
      - other causes of hypercalcemia
      - differential diagnosis of hypercalcemia
      - treatment
    - hypocalcemia
      - pathophysiology
      - classification of hypocalcemia
      - pth absent
      - pth ineffective
      - pth overwhelmed
      - differential diagnosis
  - 411 osteoporosis
    - definition
    - epidemiology
    - pathophysiology
      - bone remodeling
      - calcium nutrition
      - vitamin d
      - estrogen status
      - physical activity
      - chronic diseases
      - medications
      - smoking
      - other potential factors
    - diagnosis
      - measurement of bone mass
      - indications for bone mass measurement
      - vertebral imaging
    - approach to the patient
    - treatment
      - management of patients with fractures
      - management of the underlying disease
        risk factor reduction
        
        nutritional recommendations
        
        exercise
      - pharmacologic treatment of osteoporosis
        antiresorptive agents
        
        anabolic agents
      - other pharmacologic agents not approved in the united states
      - nonpharmacologic approaches
      - treatment monitoring
    - glucocorticoid-induced osteoporosis
      - pathophysiology
      - evaluation of the patient
      - prevention
      - treatment
  - 412 paget’s disease and other dysplasias of bone
    - paget’s disease of bone
      - epidemiology
      - etiology
      - pathophysiology
      - clinical manifestations
      - diagnosis
      - treatment
    - sclerosing bone disorders
      - osteopetrosis
      - pyknodysostosis
      - progressive diaphyseal dysplasia
      - hyperostosis corticalis generalisata
      - melorheostosis
      - osteopoikilosis
      - hepatitis c–associated osteosclerosis
    - disorders associated with defective mineralization
      - hypophosphatasia
      - axial osteomalacia
      - fibrogenesis imperfecta ossium
    - fibrous dysplasia and mccune-albright syndrome
    - other dysplasias of bone and cartilage
      - pachydermoperiostosis
      - osteochondrodysplasias
    - extraskeletal (Ectopic) Calcification and ossification
      - metastatic calcification
      - tumoral calcinosis
      - dystrophic calcification
      - ectopic ossification
      - fibrodysplasia ossificans progressiva
- section 5 disorders of intermediary metabolism
  - 413 heritable disorders of connective tissue
    - classification of connective tissue disorders
    - specific disorders
      - osteogenesis imperfecta
      - hlers-danlos syndromes
      - chondrodysplasias
      - heritable thoracic aortic aneurysm disease
  - 414 hemochromatosis
    - definition
    - prevalence
    - genetic basis
    - pathophysiology and the role of hepcidin
    - clinical manifestations
    - diagnosis
    - screening for hemochromatosis
    - treatment
    - prognosis
    - role of hfe mutations in other liver diseases
    - global considerations
  - 415 wilson’s disease
    - history of wilson’s disease
    - phenotypes
      - clinical
      - biochemical
      - molecular
    - diagnosis
    - treatment
    - future outlook
  - 416 the porphyrias
    - the porphyrias: introduction
    - global considerations
    - heme biosynthesis
    - regulation of heme biosynthesis
    - classification of the porphyrias
    - diagnosis of porphyria
    - the hepatic porphyrias
      - ala-dehydratase-deficient porphyria
      - acute intermittent porphyria
      - porphyria cutanea tarda
      - hereditary coproporphyria
      - variegate porphyria
    - the erythropoietic porphyrias
      - x-linked sideroblastic anemia
      - congenital erythropoietic porphyria
      - erythropoietic protoporphyria
  - 417 disorders of purine and pyrimidine metabolism
    - uric acid metabolism
    - hyperuricemia
    - evaluation
    - complications
    - hyperuricemia and metabolic syndrome
    - hypouricemia
    - selected inborn errors of purine and pyrimidine metabolism
    - purine disorders
    - pyrimidine disorders
  - 418 lysosomal storage diseases
    - pathogenesis
    - selected disorders
      - tay-sachs disease
      - fabry disease
      - gaucher disease
      - niemann-pick diseases
      - mucopolysaccharidoses
      - pompe disease
      - lysosomal acid lipase deficiency
      - krabbe disease
        neuronal ceroid lipofuscinosis type 2 (Ncl2 or cln2)
  - 419 glycogen storage diseases and other inherited disorders of carbohydrate metabolism
    - selected liver glycogenoses
      - disorders with hepatomegaly and hypoglycemia
        type i gsd (Glucose-6-phosphatase or translocase deficiency, von gierke disease)
        
        type iii gsd (Debrancher deficiency, limit dextrinosis)
        
        type ix gsd (Liver phosphorylase kinase deficiency)
        
        type iv gsd (Branching enzyme deficiency, amylopectinosis,polyglucosan disease, or andersen disease)
        
        other liver glycogenoses with hepatomegaly and hypoglycemia
    - selected muscle glycogenoses
      - disorders with muscle-energyimpairment
        type v gsd (Muscle phosphorylase deficiency, mcardle disease)
        
        type ix gsd (Muscle phosphorylase kinase deficiency)
      - disorders with progressive skeletalmuscle myopathy and/or cardiomyopathy
        pompe disease, type ii gsd (Acid α-1,4 glucosidase deficiency)
    - selected disorders of galactose metabolism
    - selected disorders of fructose metabolism
    - global considerations
  - 420 inherited disorders of amino acid metabolism in adults
    - the hyperphenylalaninemias
    - the homocystinurias (Hyperhomocysteinemias)
    - alkaptonuria
    - urea cycle defects
  - 421 inherited defects of membrane transport
    - cystinuria
    - lysinuric protein intolerance
    - citrullinemia type 2 (Citrin deficiency)
    - hartnup disease
    - cystinosis
part 13 neurologic disorders
- section 1 diagnosis of neurologic disorders
  - 422 approach to the patient with neurologic disease
    - the neurologic method
      - define the anatomy
      - identify the pathophysiology
    - the neurologic history
    - the neurologic examination
      - mental status examination
      - cranial nerve examination
      - motor examination
      - reflex examination
      - sensory examination
      - coordination examination
      - gait examination
    - neurologic diagnosis
  - 423 neuroimaging in neurologic disorders
    - computed tomography
    - magnetic resonance imaging
    - magnetic resonance angiography
    - echo-planar mri
    - arterial spin labeling
    - magnetic resonance neurography
    - positron emission tomography
    - myelography
    - spine interventions
    - angiography
    - interventional neuroradiology
  - 424 pathobiology of neurologic diseases
    - neuroimmunology and neuroinflammation
      - oligodendrocytes and myelin
      - microglia and macrophages
      - astrocytes
    - lymphatics of the central nervous system
    - microbiota and neurologic disease
    - pathologic proteins, prions, and neurodegeneration
      - protein aggregation and cell death
      - prions and neurodegenerative diseases
      - neural stem cell biology
      - organoids
      - brain development and developmental disorders: microcephaly and lissencephaly
      - acquired neurodevelopmental disorders: zika
      - neurodevelopmental disorders: autism and schizophrenia
      - alzheimer’s disease
      - cell type disorders: als and huntington’s disease
      - amyotrophic lateral sclerosis
      - huntington’s disease
    - future perspectives
- section 2 diseases of the central nervous system
  - 425 seizures and epilepsy
    - classification of seizures
      - focal onset seizures
      - evolution of focal seizures togeneralized seizures
      - generalized onset seizures
    - epilepsy syndromes
      - juvenile myoclonic epilepsy
      - lennox-gastaut syndrome
      - mesial temporal lobe epilepsy syndrome
    - the causes of seizures and epilepsy
    - basic mechanisms
      - mechanisms of seizure initiation and propagation
      - mechanisms of epileptogenesis
      - genetic causes of epilepsy
      - mechanisms of action of antiseizure drugs
    - approach to the patient
      - seizure
      - history and examination
      - laboratory studies
      - electrophysiologic studies
      - brain imaging
      - genetic testing
    - differential diagnosis of seizures
      - syncope
      - psychogenic seizures
    - treatment
      - treatment of underlying conditions
      - avoidance of precipitating factors
      - antiseizure drug therapy
      - initiation and monitoring of therapy
      - when to discontinue therapy
      - treatment of refractory epilepsy
      - surgical treatment of refractory epilepsy
    - status epilepticus
    - beyond seizures: other management issues
      - epilepsy comorbidities
      - mortality of epilepsy
      - psychosocial issues
      - employment, driving, and other activities
    - special issues related to women and epilepsy
      - catamenial epilepsy
      - pregnancy
      - contraception
        breast-feeding
  - 426 introduction to cerebrovascular diseases
    - approach to the patient
    - stroke syndromes
      - stroke within the anterior circulation
      - stroke within the posterior circulation
    - imaging studies
      - ct scans
      - mri
      - cerebral angiography
      - ultrasound techniques
      - perfusion techniques
  - 427 ischemic stroke
    - pathophysiology of ischemic stroke
    - treatment
    - etiology of ischemic stroke
    - small-vessel stroke
    - less common causes of stroke
    - transient ischemic attacks
  - 428 intracranial hemorrhage
    - diagnosis
    - emergency management
    - intracerebral hemorrhage
      - hypertensive ich
      - lobar hemorrhage
      - other causes of ich
      - laboratory and imaging evaluation
      - treatment
    - vascular anomalies
      - congenital vascular malformations
      - acquired vascular lesions
  - 429 subarachnoid hemorrhage
    - saccular (“berry”) Aneurysm
      - pathophysiology
      - clinical manifestations
      - delayed neurologic deficits
      - laboratory evaluation and imaging
    - treatment
  - 430 migraine and other primary headache disorders
    - migraine
      - pathogenesis
      - diagnosis and clinical features
      - treatment
        nonpharmacologic management
        
        acute attack therapies for migraine
        
        5-ht1b/1d receptor agonists—triptans
        
        calcitonin gene-related peptide (Cgrp) Receptor antagonists—gepants
        
        5-ht1f receptor agonists—ditans
        
        dopamine receptor antagonists
        
        other options for acute migraine
        
        medication-overuse headache
        
        preventive treatments for migraine
    - tension-type headache
    - trigeminal autonomic cephalalgias (Tacs), including cluster headache
    - paroxysmal hemicrania
    - sunct/suna
    - hemicrania continua
    - other primary headache disorders
      - primary cough headache
      - primary exercise headache
      - primary headache associated with sexual activity
      - primary thunderclap headache
      - cold-stimulus headache
      - external pressure headache
      - primary stabbing headache
      - nummular headache
      - hypnic headache
      - new daily persistent headache
  - 431 alzheimer’s disease
    - alzheimer’s disease
      - clinical manifestations
      - diagnosis
      - epidemiology
      - pathology
      - genetic considerations
      - treatment
        patient and caregiver education
        
        neurotransmitter-based therapies
        
        therapies targeting amyloid-β
        
        additional therapies
        
        experimental therapies
    - other causes of dementia
  - 432 frontotemporal dementia
    - clinical manifestations
    - genetic considerations
    - neuropathology
    - pathogenesis
    - treatment
    - progressive supranuclear palsy syndrome
    - corticobasal syndrome
  - 433 vascular dementia
    - global considerations
    - subtypes of cerebrovascular disease associated with vcid
      - large cerebral strokes
      - cerebral small-vessel disease
      - role of accompanying brain pathologies
    - approach to the patient
    - treatment
  - 434 dementia with lewy bodies
    - clinical manifestations
    - pathology
    - pathogenesis
    - laboratory features
    - treatment
  - 435 parkinson’s disease
    - parkinson’s disease and related disorders
    - diagnosis and differential diagnosis
    - etiology and pathogenesis
    - pathophysiology of pd
    - treatment
      - levodopa
      - dopamine agonists
      - mao-b inhibitors
      - comt inhibitors
      - other medical therapies
      - on-demand therapies for “off” periods
      - neuroprotection
      - surgical treatment
      - other experimental therapies for pd
      - management of the nonmotor and nondopaminergic features of pd
      - nonpharmacologic therapy
      - current management of pd
  - 436 tremor, chorea, and other movement disorders
    - hyperkinetic movement disorders
    - tremor
      - clinical features
      - essential tremor
      - etiology and pathophysiology
      - treatment
    - dystonia
      - clinical features
      - isolated dystonias
        focal, multifocal, and segmental dystonia
        
        generalized dystonia
      - combined dystonias
      - complex dystonias
      - pathophysiology of dystonia
      - treatment
    - choreas
      - huntington’s disease
      - huntington’s disease-like disorders
      - other choreas
      - ballism/hemiballismus
    - tics
      - tourette’s syndrome
    - myoclonus
    - drug-induced movement disorders
      - acute
      - subacute
      - tardive syndromes
    - paroxysmal dyskinesias
    - restless legs syndrome
    - other disorders that may present with a combination of parkinsonism and hyperkinetic movements
      - wilson’s disease
      - neurodegeneration with brain iron accumulation
    - functional (Psychogenic) Disorders
  - 437 amyotrophic lateral sclerosis and other motor neuron diseases
    - amyotrophic lateral sclerosis (Als)
      - pathology
      - clinical manifestations
      - epidemiology
      - familial als
      - differential diagnosis
      - pathogenesis
      - treatment
    - other motor neuron diseases
      - selected lower motor neuron disorders
        x-linked spinobulbar muscular atrophy (Kennedy’s disease)
        
        adult tay-sachs disease
        
        spinal muscular atrophy
        
        multifocal motor neuropathy with conduction block
        
        other forms of lower motor neuron disease
      - selected disorders of the upper motor neuron
        primary lateral sclerosis
        
        hereditary spastic paraplegia
  - 438 prion diseases
    - spectrum of prp prion diseases
    - sporadic and inheritedprp prion diseases
    - acquired prp prion diseases
    - different prions causing other neurodegenerative diseases
  - 439 ataxic disorders
    - approach to the patient
    - the inherited ataxias
      - autosomal dominant ataxias
      - sca1
      - sca2
      - machado-joseph disease/sca3
      - sca6
      - sca7
      - sca8
      - dentatorubropallidoluysian atrophy
      - episodic ataxia
      - autosomal recessive ataxias
        friedreich’s ataxia
        
        ataxia telangiectasia
      - mitochondrial ataxias
      - genetic diagnostic laboratories
    - global features
  - 440 disorders of the autonomic nervous system
    - anatomic organization
    - clinical evaluation
      - classification
      - symptoms of autonomic dysfunction
    - approach to the patient: orthostatic hypotension and other ans disorders
    - specific syndromes of ans dysfunction
      - multiple-system atrophy
      - spinal cord
      - peripheral nerve and neuromuscular junction disorders
      - pure autonomic failure (Paf)
      - postural orthostatic tachycardia syndrome (Pots)
      - inherited disorders
      - primary focal hyperhidrosis
      - acute sympathetic overactivity syndromes
      - miscellaneous and controversial autonomic syndromes
      - complex regional pain syndromes (Crps)
      - treatment: autonomic failure
  - 441 trigeminal neuralgia, bell’s palsy, and other cranial nerve disorders
    - facial pain or numbness
      - anatomic considerations
      - trigeminal neuralgia (Tic douloureux)
      - trigeminal neuropathy
    - facial weakness
      - anatomic considerations
      - bell’s palsy
      - other motor disorders of the face
    - other cranial nerve disorders
      - glossopharyngeal neuralgia
      - dysphagia and dysphonia
      - neck weakness
      - tongue paralysis
    - multiple cranial nerve palsies
  - 442 diseases of the spinal cord
    - approach to the patient
    - acute and subacute spinal cord diseases
      - approach to the patient: compressive and noncompressive myelopathy
      - compressive myelopathies
        neoplastic spinal cord compression
        
        spinal epidural abscess
        
        spinal epidural hematoma
        
        hematomyelia
        
        acute spondylytic myelopathy
      - noncompressive myelopathies
        spinal cord infarction
        
        inflammatory and immune myelopathies (Myelitis)
        
        high-voltage electrical injury
    - chronic myelopathies
      - spondylotic myelopathy
      - vascular malformations of the cord and dura
      - retrovirus-associated myelopathies
    - syringomyelia
      - treatment: syringomyelia
      - chronic myelopathy of multiple sclerosis
      - subacute combined degeneration (Vitamin b12 deficiency)
      - hypocupric myelopathy
      - tabes dorsalis
      - hereditary spastic paraplegia
    - primary lateral sclerosis
      - adrenomyeloneuropathy
      - cancer-related syndromes
      - other chronic myelopathies
    - rehabilitation of spinal cord disorders
  - 443 concussion and other traumatic brain injuries
    - introduction
    - definition and classification
    - tbi types and pathologies
    - skull fracture, extra-axial hematoma, contusion, and axonal injury
    - epidural and subdural hematomas
      - epidural hematoma
      - acute subdural hematoma
      - chronic subdural hematoma
    - traumatic subarachnoid hemorrhage
      - contusion
      - axonal injury
    - cranial nerve injuries
    - eizures
    - clinical syndromes and treatment of head injury
      - concussion/mild tbi
      - sport-related concussion
      - postconcussive states
      - injury of intermediate severity
      - severe injury
      - long-term outcomes in tbi
  - 444 multiple sclerosis
    - clinical manifestations
    - ancillary symptoms
    - disease course
    - epidemiology
    - genetic considerations
    - pathogenesis
      - pathology
        demyelination
        
        neurodegeneration
      - physiology
      - immunology
      - autoreactive t lymphocytes
      - humoral autoimmunity
    - diagnosis
      - diagnostic tests
        magnetic resonance imaging
        
        evoked potentials
        
        cerebrospinal fluid
      - differential diagnosis
    - prognosis
    - effect of pregnancy
    - treatment
      - acute attacks or initial demyelinating episodes
      - disease-modifying therapies for relapsing forms of ms (Rms, spms with exacerbations)
    - frequently used agents for rms
      - anti-cd20 monoclonal antibodies (Highly effective)
      - natalizumab (Highly effective)
      - s1p receptor modulators (Moderately effective)
      - dimethyl fumarate (Moderately effective)
      - glatiramer acetate (Modestly effective)
      - interferon β (Modestly effective)
    - less commonly used agents for rms
      - teriflunomide (Modestly effective)
      - cladribine (Moderately effective)
      - alemtuzumab (Highly effective)
      - mitoxantrone hydrochloride (Highly effective)
    - decision-making for treatment of rms
    - disease-modifying therapies for progressive ms
      - spms
      - ppms
      - off-label treatment options for rms and spms
      - promising experimental therapies
    - other therapeutic claims
    - symptomatic therapy
    - clinical variants of ms
    - acute disseminated encephalomyelitis (Adem)
      - clinical manifestations
      - diagnosis
      - treatment
    - glial fibrillary acidic protein (Gfap) Autoimmunity
  - 445 neuromyelitis optica
    - introduction
    - immunology
    - clinical course
    - global considerations
    - associated conditions
    - treatment
    - myelin oligodendrocyte glycoprotein-antibody-associated disease (Mogad)
- section 3 nerve and muscle disorders
  - 446 peripheral neuropathy
    - general approach
      - information from the history and physical examination: seven key questions
      - pattern recognition approach to neuropathic disorders
      - electrodiagnostic studies
      - other important laboratory information
      - nerve biopsies
      - skin biopsies
    - specific disorders
      - hereditary neuropathies
      - cmt1
      - cmt2
      - cmtdi
      - cmt3
      - cmt4
      - cmt1x
      - hereditary neuropathy with liability to pressure palsies (Hnpp)
      - hereditary neuralgic amyotrophy (Hna)
      - hereditary sensory and autonomic neuropathy (Hsan)
    - other hereditary neuropathies
      - fabry’s disease
      - adrenoleukodystrophy/adrenomyeloneuropathy
      - refsum’s disease
      - tangier disease
      - porphyria
      - familial amyloid polyneuropathy
    - acquired neuropathies
      - primary or al amyloidosis
      - diabetic neuropathy
      - hypothyroidism
      - sjögren’s syndrome
      - rheumatoid arthritis
      - systemic lupus erythematosus
      - systemic sclerosis (Scleroderma)
      - mixed connective tissue disease (Mctd)
      - sarcoidosis
      - hypereosinophilic syndrome
      - celiac disease (Gluten-induced enteropathy or nontropical sprue)
      - inflammatory bowel disease
      - uremic neuropathy
      - chronic liver disease
      - critical illness polyneuropathy
      - leprosy (Hansen’s disease)
      - lyme disease
      - diphtheritic neuropathy
      - covid-19
      - human immunodeficiency virus
      - herpes varicella-zoster virus
      - cytomegalovirus
      - epstein-barr virus
      - hepatitis viruses
    - neuropathies associated with malignancy
      - paraneoplastic sensory neuronopathy/ganglionopathy
      - neuropathy secondary to tumor infiltration
      - neuropathy as a complication of bone marrow transplantation
      - lymphoma
      - multiple myeloma
      - neuropathies associated with monoclonal gammopathy of uncertain significance
    - other toxic neuropathies
      - chloroquine and hydroxychloroquine
      - amiodarone
      - colchicine
      - thalidomide
      - pyridoxine (Vitamin b6) Toxicity
      - isoniazid
      - antiretroviral agents
      - hexacarbons (N-hexane, methyl n-butyl ketone)/glue sniffer’s neuropathy
      - lead
      - mercury
      - thallium
      - arsenic
    - nutritional neuropathies
      - cobalamin (Vitamin b12)
      - thiamine deficiency
      - vitamin e deficiency
      - vitamin b6 deficiency
      - pellagra (Niacin deficiency)
      - copper deficiency
      - neuropathy associated with gastric surgery
    - cryptogenic (Idiopathic) Sensory and sensorimotor polyneuropathy
    - mononeuropathies/plexopathies/radiculopathies
      - median neuropathy
      - ulnar neuropathy at the elbow— “cubital tunnel syndrome”
      - radial neuropathy
      - lateral femoral cutaneous neuropathy (Meralgia paresthetica)
      - femoral neuropathy
      - sciatic neuropathy
    - peroneal neuropathy
    - radiculopathies
    - plexopathies
      - brachial plexus
      - lumbosacral plexopathies
      - recurrent neoplastic disease or radiation-induced plexopathy
      - evaluation and treatment of plexopathies
  - 447 guillain-barré syndrome and other immune-mediated neuropathies
    - guillain-barré syndrome
      - clinical manifestations
      - antecedent events
      - immunopathogenesis
      - pathophysiology
      - laboratory features
      - diagnosis
      - treatment
      - prognosis and recovery
    - chronic inflammatory demyelinating polyneuropathy
      - clinical manifestations
      - diagnosis
      - pathogenesis
      - treatment
    - multifocal motor neuropathy
    - neuropathies with monoclonal gammopathy
      - multiple myeloma
      - monoclonal gammopathy of undetermined significance
    - vasculitic neuropathy
    - anti-hu paraneoplastic neuropathy
  - 448 myasthenia gravis and other diseases of the neuromuscular junction
    - pathophysiology
    - clinical features
    - diagnosis and evaluation
      - ice-pack test
      - autoantibodies associated with mg
      - electrodiagnostic testing
      - anticholinesterase test
      - pulmonary function tests
      - differential diagnosis
      - search for associated conditions
    - treatment
      - anticholinesterase medications
      - thymectomy
      - immunotherapy
      - plasmapheresis and intravenous immunoglobulin
      - investigational treatments
      - management of myasthenic crisis
      - drugs to avoid in myasthenic patients
    - patient assessment
    - prognosis
    - global issues
  - 449 muscular dystrophies and other muscle diseases
    - clinical features
      - muscle weakness
      - muscle pain (Myalgias), cramps, and stiffness
      - muscle enlargement and atrophy
    - laboratory evaluation
      - serum enzymes
      - electrodiagnostic studies
      - imaging studies
      - genetic testing
      - forearm exercise test
      - muscle biopsy
    - hereditary myopathies
      - duchenne and becker musculardystrophy (Dmd and bmd)
      - limb-girdle muscular dystrophy
      - emery-dreifuss muscular dystrophy
      - myotonic dystrophy
      - facioscapulohumeral (Fshd) Muscular dystrophy
      - oculopharyngeal dystrophy (Opmd)
      - distal myopathies/dystrophies
    - disorders of muscle energy metabolism
      - glycogen storage and glycolytic defects
      - lipid as an energy source and associated defects
    - mitochondrial myopathies
      - kearns-sayre syndrome (Kss)
      - progressive external ophthalmoplegia (Peo)
      - myoclonic epilepsy with ragged red fibers (Merrf)
      - mitochondrial myopathy, encephalopathy, lactic acidosis,and stroke-like episodes (Melas)
      - mitochondrial dna depletion syndromes
    - disorders of muscle membrane excitability
      - calcium channel disorders of muscle
        hypokalemic periodic paralysis (Hypokpp)
      - sodium channel disorders of muscle
        hyperkalemic periodic paralysis (Hyperkpp)
        
        paramyotonia congenita
      - potassium channel disorders
        andersen-tawil syndrome
      - chloride channel disorders
    - endocrine and metabolic myopathies
      - thyroid disorders
      - parathyroid disorders
      - adrenal disorders
      - pituitary disorders
      - diabetes mellitus
    - myopathies of systemic illness
    - drug-induced or toxic myopathies
      - myopathy from lipid-lowering agents
      - glucocorticoid-related myopathies
      - other drug-induced myopathies
    - global issues
- section 4 myalgic encephalomyelitis/chronic fatigue syndrome
  - 450 myalgic encephalomyelitis/chronic fatigue syndrome
    - epidemiology
    - risk factors and pathophysiology
    - approach to the patient
      - diagnosis
      - differential diagnosis and comorbid conditions
      - management
      - course and prognosis
- section 5 psychiatric and addiction disorders
  - 451 biology of psychiatric disorders
    - neurogenetics
    - signal transduction
    - systems neuroscience
    - neuroinflammation
    - conclusions
  - 452 psychiatric disorders
    - global considerations
    - anxiety disorders
      - panic disorder
      - generalized anxiety disorder
      - phobic disorders
      - stress disorders
      - obsessive-compulsive disorder
    - mood disorders
      - depression in association with medical illness
      - depressive disorders
      - bipolar disorder
    - somatic symptom disorder
    - feeding and eating disorders
      - clinical manifestations
      - pica
      - rumination disorder
      - avoidant/restrictive food intake disorder
      - anorexia nervosa
        bulimia nervosa
      - binge-eating disorder
    - personality disorders
      - clinical manifestations
      - etiology and pathophysiology
      - treatment
    - schizophrenia
      - clinical manifestations
      - differential diagnosis
      - epidemiology and pathophysiology
      - treatment
    - assessment and evaluation of violence
  - 453 alcohol and alcohol use disorders
    - pharmacology and nutritional impact of ethanol
    - behavioral effects, tolerance, and withdrawal
    - the effects of ethanol on organ systems
      - nervous system
      - the gastrointestinal system
      - cancer
      - hematopoietic system
      - cardiovascular system
      - genitourinary system changes, sexual functioning, and fetal development
      - other effects
    - alcohol use disorders
      - definitions and epidemiology
      - genetics
      - natural history
      - treatment
      - identification of patients with alcohol use disorders
    - treatment
      - acute intoxication
      - intervention
      - alcohol withdrawal
      - helping individuals with alcohol use disorders to stop drinking: the rehabilitation phase
    - global considerations
  - 454 nicotine addiction
    - disease manifestations of cigarette smoking
      - cardiovascular diseases
      - cancer
      - respiratory disease
      - pregnancy
      - other conditions
      - environmental tobacco smoke
    - pharmacologic interactions
    - other forms of tobacco use
    - electronic cigarettes
    - lower tar and nicotine cigarettes
    - cessation
    - physician intervention
    - prevention
  - 455 marijuana and marijuana use disorders
    - pharmacologic effects
    - cannabis pharmacokinetics
    - harmful effects
    - therapeutic potential
  - 456 opioid-related disorders
    - neurobiology
    - pharmacology
    - treatment
    - prevention
  - 457 cocaine, other psychostimulants, and hallucinogens
    - psychostimulants
      - cocaine
      - methamphetamine
      - mdma and cathinones
      - prescribed psychostimulants
      - psychostimulant clinical manifestations
      - diagnosis
      - treatment
    - hallucinogens
    - emerging drugs
    - substance use and mental health
    - global considerations
    - future directions
part 14 poisoning, drug overdose, and envenomation
- 458 heavy metal poisoning
  - arsenic
  - cadmium
  - lead
  - mercury
- 459 poisoning and drug overdose
  - epidemiology
  - diagnosis
    - history
    - physical examination and clinical course
    - laboratory assessment
  - treatment
    - general principles
    - supportive care
    - prevention of poison absorption
    - enhancement of poison elimination
    - administration of antidotes
    - prevention of reexposure
  - specific toxic syndromes and poisonings
  - global considerations
- 460 disorders caused by venomous snakebites and marine animal exposures
  - venomous snakebite
    - epidemiology
    - snake anatomy/identification
    - venoms and clinical manifestations
    - treatment
    - morbidity and mortality
    - global considerations
  - marine envenomations
    - invertebrates
      - cnidarians
      - sea sponges
      - annelid worms
      - sea urchins
      - starfish
      - sea cucumbers
      - cone snails
      - octopuses
    - vertebrates
      - stingrays
      - stonefish
      - lionfish
      - platypuses
    - treatment
    - approach to the patient
    - sources of antivenoms and other assistance
  - marine poisonings
    - histamine (Scombroid) Fish poisoning
    - ciguatera
    - paralytic shellfish poisoning
    - amnesic shellfish poisoning
    - diarrhetic shellfish poisoning
- 461 ectoparasite infestations and arthropod injuries
  - scabies
  - chiggers and other biting mites
  - tick bites and tick paralysis
  - louse infestation (Pediculiasis and pthiriasis)
  - myiasis (Fly infestation)
  - pentastomiasis
  - leech infestations
  - spider bites
    - recluse spider bites and necrotic arachnidism
    - widow spider bites
    - tarantulas and other spiders
  - scorpion stings
  - hymenoptera stings
    - bee and wasp stings
  - stinging ants
  - dipteran (Fly and mosquito) Bites
  - flea bites
  - hemipteran/heteropteran (True bug) Bites
  - centipede bites and millipede dermatitis
  - caterpillar stings and dermatitis
  - beetle vesication and dermatitis
  - delusional infestations
part 15 disorders associated with environmental exposures
- 462 altitude illness
  - epidemiology
  - physiology
  - genetics
  - acute mountain sickness and high-altitude cerebral edema
  - high-altitude pulmonary edema
  - other high-altitude problems
  - preexisting medical issues
  - chronic mountain sickness and high-altitude pulmonary hypertension in highlanders
- 463 hyperbaric and diving medicine
  - what is hyperbaricand diving medicine?
  - mechanisms of hyperbaric oxygen
  - adverse effects of therapy
    - barotrauma
    - oxygen toxicity
  - contraindications to hyperbaric oxygen
  - indications for hyperbaric oxygen
  - late radiation tissue injury
  - selected problem wounds
  - carbon monoxide poisoning
  - current controversies in hyperbaric medicine
  - diving medicine
    - introduction
    - breathing equipment
    - suitability for diving
  - barotrauma
  - decompression sickness
  - treatment
- 464 hypothermia and peripheral cold injuries
  - hypothermia
    - causes
    - thermoregulation
    - clinical presentation
    - diagnosis and stabilization
    - rewarming strategies
    - treatment
  - frostbite
    - clinical presentation
    - treatment
- 465 heat-related illnesses
  - thermoregulation
  - predisposing factors and differential diagnosis
  - minor heat-emergency syndromes
  - heat cramps
  - heat exhaustion
  - heatstroke
  - cooling strategies
  - resuscitation
  - disposition
part 16 genes, the environment, and disease
- 466 principles of human genetics
  - impact of genetics and genomics on medical practice
  - the human genome
    - structure of the human genome
    - replication of dna and mitosis
    - assortment and segregation of genes during meiosis
  - regulation of gene expression
    - regulation by transcription factors
    - epigenetic regulation of gene expression
  - transmission of genetic disease
    - origins and types of mutations
    - functional consequences of mutations
    - genotype and phenotype
    - chromosomal disorders
    - monogenic mendelian disorders
    - exceptions to simple mendelian inheritance patterns
    - complex genetic disorders
    - linkage and association studies
  - approach to the patient
- 467 the practice of genetics in clinical medicine
  - applications of molecular genetics in clinical medicine
  - common adult-onset genetic disorders
    - inheritance patterns
    - family history
  - genetic testing for adult-onset disorders
    - methodologic approaches to genetic testing
    - direct-to-consumer genetic testing
    - informed consent
    - follow-up care after testing
  - therapeutic interventions based on genetic risk for disease
- 468 mitochondrial dna and heritable traits and diseases
  - mitochondrial dna structure and function
    - maternal inheritance and lack of recombination
    - multiple copy number (Polyploidy), high mutation rate, heteroplasmy, and mitotic segregation
    - homoplasmic variants and human mtdna phylogeny
  - mitochondrial dna disease
    - overview of clinical and pathologic features of human mtdna disease
    - mtdna disease presentations
    - the investigation of suspected mtdna disease
  - impact of homoplasmic sequence variation on heritable traits and disease
  - impact of acquired somatic mtdna mutation on human health and disease
  - prospects for clinical management of mtdna disease
    - treatment of mtdna disorders
  - genetic counseling, prenatal diagnosis, and pgd in mtdna disorders
    - prevention of mitochondrial disease inheritance by assisted reproductive technologies
- 469 telomere disease
  - definition
  - disease mechanism
  - genetics
  - clinical manifestations
  - telomere length measurement
  - genetic testing
  - treatment
- 470 gene- and cell-based therapy in clinical medicine
  - gene transfer for genetic disease
    - immunodeficiency disorders: proof of principle for ex vivo gene transfer
    - transfusion-dependent thalassemia: extension of principle
    - neurodegenerative diseases: broadening of principle
  - long-term expression in genetic disease: in vivo gene transfer with recombinant adeno-associated viral vectors
    - first licensed product
    - retinal gene therapy
    - spinal muscular atrophy type 1
  - gene therapy for cancer
    - modifying the cancer
    - modifying the host
    - combination approaches—modification of host and tumor by virotherapy
    - other approaches
  - summary
- 471 the human microbiome
  - historical perspective
  - a primer on taxonomy
  - the microbiota and human health
  - the microbiota and disease
  - mechanisms of microbiome-mediated effects
  - moving microbiome science from bench to bedside
  - perspective
part 17 global medicine
- 472 global issues in medicine
  - why global health?
  - a brief history of global health institutions
  - the economics of global health
  - mortality and the global burden of disease
    - global mortality
    - health and wealth
    - risk factors for disease burden
    - hiv infection/aids
    - tuberculosis
    - tuberculosis and aids as chronic diseases: lessons learned
    - malaria
    - ebola
    - covid-19
    - “noncommunicable” chronic diseases
    - mental and neurologic health
  - conclusion: toward a science of implementation
- 473 emerging and reemerging infectious diseases
  - the concept of emerging infectious diseases
  - examples of emerging infectious diseases
    - west nile virus
    - dengue virus
    - ebola and marburg viruses
    - zika virus
    - sars-cov-2
    - poliovirus
    - measles virus
  - control of emerging infectious diseases
- 474 primary care and global health
  - primary care and primary health care
  - health challenges in low- and middle-income countries
  - primary health care in the twenty-first century
  - experiences with primary care in low- and middle-income countries
  - conclusion
- 475 health effects of climate change
  - effects of climate change on health
    - air pollution and synergistic effects
    - heat-related illnesses
    - natural disasters, coastal flooding, and displacement
    - food security and ocean resources
    - infections and diarrheal disease
  - potential solutions
  - conclusions
part 18 aging
- 476 biology of aging
  - aging
  - evolutionary theories of aging
  - the hallmarks of aging
    - genomic instability
    - telomere attrition
    - epigenetic alterations
    - loss of proteostasis
    - deregulated nutrient sensing
    - mitochondrial dysfunction
    - cellular senescence
    - stem cell exhaustion
    - altered intracellular communication and inflammation
  - geroscience and the relationship between aging and disease
  - strategies that increase health span and delay aging
    - caloric restriction
    - periodic fasting
    - pharmacologic interventions to delay aging and increase life span
    - exercise and physical activity
    - hormesis
  - conclusions
- 477 caring for the geriatric patient
  - aging and geriatric care
    - demographics of aging and its implications for geriatric care
    - implications of the aging population for health care systems and system-based practice
    - models of geriatric care
    - interprofessional teams and co-managed care
    - age-friendly health systems
  - fundamentals of geriatric care
    - person-centered care
    - evaluation of the geriatric patient
    - prevention in older adults
  - treatment of common diseases in the geriatric population
    - hypertension
    - diabetes
    - hyperlipidemia
    - osteoarthritis
    - cancer
    - anemia
  - geriatric syndromes and conditions
    - falls
    - polypharmacy
    - cognitive impairment: delirium and dementia
    - urinary incontinence and overactive bladder
    - sleep disorders
    - frailty
    - elder abuse and neglect
    - severe acute respiratory syndrome corona virus (Sars-cov-2) Infection and covid-19 disease
  - end-of-life and palliative care
part 19 consultative medicine
- 478 approach to medical consultation
  - responsibilities of the requestingclinician
  - responsibilities of the consultant
  - responsibilities of health systems, hospitals, and medical organizations
  - special issues in medical consultation
    - curbside consults
    - advice
    - second opinions
    - consults involving advanced practice providers
    - consultation involving telemedicine
- 479 medical disorders during pregnancy
  - hypertension
    - preeclampsia
    - gestational hypertension
    - treatment
    - chronic hypertension
  - renal disease
  - cardiac disease
    - valvular heart disease
    - congenital heart disease
    - aortopathy
    - cardiac complications in pregnancy
  - endocrine and metabolic disorders
    - diabetes mellitus
    - gestational diabetes
    - treatment: diabetes mellitus in pregnancy
    - treatment: gestational diabetes
    - obesity
    - thyroid disease
    - treatment: hyperthyroidism
    - treatment: hypothyroidism
  - hematologic disorders
    - deep venous thrombosis and pulmonary embolism
    - neoplasia
  - neurologic disorders
  - gastrointestinal and liver disease
  - infections
    - bacterial infections
    - viral infections
    - vaccinations
  - maternal mortality
  - summary
- 480 medical evaluation of the surgical patient
  - evaluation of intermediate- and high-risk patients
  - preoperative cardiac risk assessment
    - preoperative noninvasive cardiac testing for risk stratification
    - risk modification: preventive strategies to reduce cardiac risk
  - preoperative pulmonary risk assessment
  - perioperative management and prophylaxis
    - diabetes mellitus
    - infective endocarditis
    - aortic stenosis
    - venous thromboembolism
part 20 frontiers
- 481 behavioral economics and health
  - concepts of classical economics and how they differ from behavioral economics
  - using behavioral economics to promote self-beneficial health behaviors
    - loss aversion and framing effects
    - loss aversion and overoptimism
    - peanuts effects
  - present-biased preferences
    - nonlinear probability weighting
    - regret aversion
    - defaults
    - the rational-world bias
  - applications
    - weight loss
    - medication adherence
    - the 5000 hours problem
  - reflections on sars-cov-2
  - future perspectives
- 482 complementary and integrative therapies and practices
  - definitions and scope
  - patterns of use
  - categories of complementary and integrative health therapies and practices based on primary therapeutic input
    - primary dietary input
      - pain
      - anxiety
      - rheumatoid arthritis
      - irritable bowel syndrome
      - depression
      - smoking cessation
      - eye disease
      - multiple sclerosis
      - other conditions
      - general health and wellness
      - challenges
      - regulation
      - inherent toxicity
      - herb-drug interactions
    - primary psychological and physical input
      - primary psychological input
      - primary physical input
      - combined psychological and physical input
  - multimodal therapies and systems
    - naturopathy
    - chiropractic
    - osteopathic medicine
    - homeopathy
    - research challenges
  - therapeutic output—systems impacted and challenges of mechanistic research
  - patient and provider resources
  - summary
- 483 the role of epigenetics in disease and treatment
  - the biochemical bases of epigenetics
  - epigenetics in development and differentiation
  - epigenetics of metabolism
  - cancer epigenetics
  - epigenetics of aging
  - epigenetics of the brain and behavior
  - epigenetic influences on infection, immunity, and inflammation
  - conclusions
- 484 applications of stem cell biology in clinical medicine
  - general strategies for stem cell replacement
  - sources of stem cells for tissue repair
    - embryonic stem cells
    - induced pluripotent stem cells
    - umbilical-cord stem cells
    - organ-specific multipotent stem cells
  - disease-specific applications of stem cells
    - ischemic heart disease and cardiomyocyte regeneration
    - diabetes
    - nervous system
    - liver
    - other organ systems and the future
  - ethical issues
- 485 the role of circadian biology in health and disease
  - basic evolution and structure of the circadian system
  - molecular organization of the mammalian circadian clock
  - anatomic organization of the circadian clock network
  - entrainment and measurement of the circadian system
  - primary pathologies of the circadian system
  - role of the clock system in physiology
- 486 network medicine: systems biology in health and disease
  - properties of complex biologic systems
  - applications of systems biology to pathobiology
  - systems pathobiology and human disease classification: network medicine
- 487 emerging neurotherapeutic technologies
  - introduction
  - technologies to harness plasticity
    - robotics
    - virtual and augmented reality
    - neurogaming
  - neuroimaging
    - neuroimaging of connectivity
    - closed-loop neuroimaging
  - noninvasive brain stimulation
  - implantable neural interfaces including brain–machine interfaces
    - implantable devices for neuromodulation
    - brain–machine interfaces for paralysis
- 488 machine learning and augmented intelligence in clinical medicine
  - concepts of machine learning
    - types of machine learning
    - modern medical machine learning
    - practical concepts in training a modern machine-learning model
  - applications of modern machine learning to clinical medicine
    - computer vision
    - natural language processing
    - other applications
  - machine learning and precision medicine: deeper representations of patient state
  - conclusion
- 489 metabolomics
  - approaches and sampling considerations
    - untargeted and targeted metabolomics
      - untargeted metabolomics
      - targeted metabolomics
    - sampling considerations
  - metabolomics technologies
    - nuclear magnetic resonance
    - chromatography/mass spectrometry
      - sample preparation
      - chromatography
      - mass spectrometry
  - current clinical applications
    - magnetic resonance spectroscopy
    - newborn screening programs
    - metabolite measurements in children and adults
  - emerging and experimental clinical applications
    - metabolites as biomarkers of disease
    - refining diagnosis and prediction of drug susceptibility
    - pharmacometabolomics
  - emerging technologies
    - mass spectrometry imaging
    - improving untargeted metabolomics
  - summary
- 490 circulating nucleic acids as liquid biopsies and noninvasive disease biomarkers
  - cell-free dna in oncology
    - early cancer detection
    - noninvasive tumor genotyping
    - biologic considerations
    - pretreatment tumor burden
    - monitoring response to treatment
    - minimal residual disease
    - technical considerations
  - cell-free dna in transplantation
    - noninvasive detection of acute allograft rejection
    - monitoring microbial diversity and infection after transplantation
    - monitoring host immunity
  - cell-free dna in prenatal medicine
    - noninvasive prenatal testing for fetal aneuploidy
    - noninvasive prenatal screening versus noninvasive prenatal diagnosis versus noninvasive prenatal testing
    - dependence on fetal fraction
    - nipt in multiple gestations
    - nipt for fetal microdeletion/duplication syndromes
    - whole genome nipt and single-gene disorders
    - nipt using cell-free rna
    - nipt detecting maternal malignancy
    - beyond next-generation sequencing
  - summary
- 491 protein folding disorders
  - protein quality control mechanisms
  - cell stress responses: sensors and regulators of protein damage
  - organismal proteostasis in aging and disease
  - properties of protein folding diseases
    - disorders that enhance misfolding and cause premature degradation (Cystic fibrosis)
    - disorders that induce toxic aggregates and loss of function (Aat deficiency)
    - interactions with pn components that change conformation, stability, or function (Cancer)
    - strongly enhanced aggregation propensity and amyloid formation (Alzheimer’s disease, parkinson’s disease, amyotrophic lateral sclerosis, huntington’s disease, type 2 diabetes mellitus)
    - secreted aggregated and amyloid species causing systemic amyloidosis
    - native proteins prone to aggregate when the cellular environment is altered by stress and aging
    - infectious diseases and imbalanced cell stress responses in aging
- 492 novel approaches to diseases of unknown etiology
  - the undiagnosed disease state
    - the meaning and context of a diagnosis
    - undiagnosed rare diseases
    - the effect of the undiagnosed disease state on the patient
  - approach to challenging diseases of unknown etiology
    - comprehensive data collection
    - validation of subjective and objective findings
    - periodic reevaluation
    - genomics
    - exposome
    - engagement of research approaches
    - challenges
  - conclusion