Early methods of determining the truth simply relied on the size of association. Modern approaches used Koch’s postulates for infectious disease and the Bradford-Hill criteria for chronic disease. In the latter, documentation of an association between risk factor and disease is a “gateway” criterion, but it is in identifying an association that bias can be most disruptive. The most recent additions to searching for truth are derived from paradigms of evidence-based medicine: systematic reviewing and meta-analysis, and most recently a GRADE assessment. Current levels for determining statistical significance are not fit for purpose and a stricter level is proposed.

1. Engraftment syndrome (ES) is a common complication of HSCT.

2. ES is characterized by a constellation of symptoms, including fever, rash, and pulmonary infiltrates, which occur around the time of neutrophil recovery.

3. Prompt recognition and treatment with corticosteroids are essential to mitigate the cytokine inflammatory response.

4. The differential diagnosis of ES should consider infections and acute graft-versus-host disease (GVHD), requiring careful clinical assessment.

5. Distinguishing features of ES from GVHD include early time of presentation, fluid retention and pulmonary edema.

Antipsychotics effective for schizophrenia approved prior to 2024 shared the common mechanismof postsynaptic dopamine D2 receptor antagonism or partial agonism. Positive psychosis symptoms correlate with excessive presynaptic dopamine turnover and release, yet this postsynaptic mechanism improved positive symptoms only in some patients, and with concomitant risk for off-target motor and endocrine adverse effects; moreover, these agents showed no benefit for negative symptoms and cognitive dysfunction. The sole exception was data supporting cariprazine’s superiority to risperidone for negative symptoms. The muscarinic M1/M4 agonist xanomeline was approved in September 2024 and represents the first of a new antipsychotic class. This novel mechanism improves positive symptoms by reducing presynaptic dopamine release. Xanomeline also lacks anyD2 receptor affinity and is not associated with motor or endocrine side effects. Of importance, xanomeline treated patients with higher baseline levels of cognitive dysfunction in clinical trials data saw cognitive improvement, a finding likely related to stimulation of muscarinicM1 receptors. Treatment resistance is seen in one-third of schizophrenia patients. These individuals do not have dopamine dysfunction underlying their positive symptoms, and therefore show limited response to antipsychotics that target dopamine neurotransmission. Clozapine remains the only medication with proven efficacy for resistant schizophrenia, and with unique benefits for persistent impulsive aggression and suicidality. New molecules are being studied to address the array of positive, negative and cognitive symptoms of schizophrenia; however, until their approval, clinicians must be familiar with currently available agents and be adept at prescribing clozapine.

1. It is important to have a high index of suspicion for malignant spinal cord compression (MSCC) in patients who have a history of cancer and present with back pain. In the absence of neurologic symptoms or deficit, close follow up and outpatient imaging is indicated.

2. Pain is the most common symptom of MSCC and is present in 95% of cases.

3. Red flags of MSCC include extremity weakness, difficulty walking, loss of sensation, bowel or bladder dysfunction, thoracic or cervical pain, pain increased with straining, and pain that is worse at night.

4. MRI of the entire spine is indicated for accurate diagnosis and treatment of MSCC.

5. Treatment includes Dexamethasone IV bolus followed by maintenance dosing and radiation therapy with or without surgical decompression.

Schizophrenia spectrum disorders are brain diseases that are developmental dementias (dementiapraecox). Their pathology begins in utero with psychosis most commonly becoming evident in adolescence and early adulthood. It is estimated they afflict the U.S. population at a prevalence rate of approximately 0.8%. Genetic studies indicate that these brain diseases are about 80% determined by genes and about 20%determined by environmental risk factors. Inheritance is polygenic with some 270 gene loci having been identified as contributing to the risk for schizophrenia. Interestingly, many of the identified gene loci and gene polymorphisms are involved in brain formation and maturation. The identified genetic and epigenetic risks give rise to a brain in which neuroblastsmigrate abnormally, assume abnormal locations and orientations, and are vulnerable to excessive neuronal and synaptic loss, resulting in overt psychotic illness. The illness trajectory of schizophrenia then is one of loss of brain mass related to the number of active psychotic exacerbations and the duration of untreated illness. In this context, molecules such as dopamine, glutamate, and serotonin play critical roles with respect to positive, negative, and cognitive domains of illness. Acutely, antipsychotics ameliorate active psychotic illness, especially positive signs and symptoms. The long-term effects of antipsychotic medications have been debated; however, the bulk of imaging data suggest that antipsychotics slow but do not reverse the illnesstrajectory of schizophrenia. Long-acting injectable antipsychotics (LAI) appear superior in this regard. Clozapine remains the “gold standard” in managing treatment-resistant schizophrenia.

1. Sinusoidal obstructive syndrome (SOS)/Veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic stem cell transplant (HSCT) and chemotherapy treatment that can cause multi-organ failure, including pulmonary and renal dysfunction.

2. Suspect SOS/VOD in patients with recent stem cell transplant or chemotherapy presenting with hepatomegaly, ascites, and weight gain.

3. SOS/VOD diagnostic criteria is separated into classic and late onset SOS/VOD, which involves the presence of hyperbilirubinemia plus two or more findings of ascites, weight gain, and right upper quadrant abdominal pain.

4. Management of fluid status is critical and should be started before diagnosis is confirmed

5. Defibrotide is potentially lifesaving. Unless SOS/VOD is mild, begin this mediation when more than two diagnostic criteria are present.

1. It is important for the provider to maintain a high index of suspicion for those at risk for tumor lysis syndrome (TLS), which includes a large tumor burden, high proliferation rate, pre-existing kidney dysfunction and certain types of cancer such as Burkett lymphoma and acute leukemias.

2. The best form of treatment includes preventive measures with aggressive hydration and urate-lowering agents.

3. In established TLS, in addition to hydration, the use of rasburicase and correction of any electrolyte derangements are key to present complications and preserve renal function.

4. A coordinated approach between the oncologist, nephrologist, and critical care specialists is required to provide effective management.

5. Educating patients and caregivers about the signs and symptoms of TLS is important for early detection and prompt treatment, especially in outpatient settings.

1. Bispecific T-cell engaging Antibody (BsABs) treatments can cause cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) similar to CAR-T, but current data suggests reduced overall severity with grade 3+ events from BsABs being rare.

2. Most CRS/ICANS events associated with BsAB treatment occur within one week after the initial dose or during step-up dosing periods.

3. Grading the severity of the adverse event is critical to appropriate management and disposition. This includes performing an immune effector cell-associated encephalopathy (ICE) score assessment for neurotoxicity cases.

4. The mainstay management for CRS are tocilizumab and steroids, whereas the management for ICANS is high dose steroids since tocilizumab does not cross the blood-brain barrier.

5. Even low grade CRS/ICANS requires discussion with an oncologist given that these treatments are administered in a step-up dose and may or may not be held.

1. Stridor denotes severe airway obstruction with impending respiratory failure that requires immediate evaluation and treatment, regardless of oxygenation level.

2. Obstruction may arise at the level of the pharynx, hypopharynx, epiglottis, larynx, subglottic region or trachea.

3. Regardless of the precise cause, begin therapy with IV corticosteroids and nebulized racemic epinephrine while completing the diagnostic work up. If head and neck cancer is suspected, administering steroids to reduce edema may allow time to organize airway management in a more controlled setting.

4. Keeping both the patient and staff calm is also important in maintaining the airway.

5. If intubation or emergent surgical airway is necessary defer to the most experienced personnel.

Participating in research incurs its own risk for bias in research subjects themselves. The classic Milgram studies on obedience to authority are discussed as classic studies of response bias. Methods for unbiased questionaire design, especially for sensitive topics, are reviewed. The iconic Hawthorne studies are considered and the impact of litigation on study subjects is described. Pretest sensitization occurs when preliminary screening tests for study eligibility interact with the study’s primary intervention. Informative presence bias results from research subjects having multiple contacts with the health care system from which they are recruited.

1. Radiation therapy is a crucial treatment method for various cancers, used alone or with chemotherapy and surgery.

2. Radiation-Induced Oral Mucositis (RIOM) is the most common and significant side effect, which worsens with higher doses delivered over a shorter period of time.

3. Radiation Proctitis is a common side effect, characterized by inflammation of the rectal mucosa due to radiation. Acute proctitis usually appears within three months of starting therapy and can last up to six months, potentially progressing to chronic proctitis after therapy.

4. Acute Radiation-Induced Esophagitis (ARIE) symptoms usually arise within the first two months of radiotherapy and adversely affect the quality of life, often causing unplanned pauses in treatment and lessening therapy effectiveness.

5. Radiation-induced pneumonitis is a significant concern in patients receiving radiation for lung, breast, and lymphoma cancers, and in those undergoing total body irradiation for bone marrow transplants with systemic glucocorticoids being the preferred treatment that can lead to symptom relief and radiographic improvement although relapse is possible post-treatment.

Anosognosia, a term that denotes a lack of insight into one’s own condition, is a defining characteristic of many psychotic illnesses. As a result, generations of psychiatrists have pursued a paternalistic approach to care. Yet in the past century, the overall trend in patient care has been toward autonomy. What does it mean to respect the autonomy of patients whose lack of insight may bring them harm ? This chapter will explore these questions through each of the four principles generally employed in bioethical analysis: beneficence, nonmaleficence, justice, and autonomy. Each will have an illustrative case study and explore how anosognosia can further complicate already perplexing ethical scenarios.

This chapter explores the transformative potential of early intervention in schizophrenia, emphasizing its role in improving clinical, functional, and social outcomes. Through the poignant case of “Roger,” a man whose life was marked by untreated psychosis, homelessness, and missed opportunities for care, the chapter illustrates the consequences of delayed treatment and fragmented systems. It reviews epidemiological data, the importance of reducing the duration of untreated psychosis (DUP), and the neurobiological rationale for early-phase treatment. Models such as Coordinated Specialty Care (CSC), EPPIC, and Assertive Community Treatment (ACT) are discussed as effective frameworks for delivering comprehensive, multidisciplinary care. The chapter also addresses barriers to early intervention—including stigma, misdiagnosis, access limitations, and systemic inequities—and advocates for integrated, culturally responsive, and person-centered approaches. Ultimately, it calls for a shift in healthcare systems to prioritize early identification and treatment as a moral and clinical imperative.

1. Acute kidney injury (AKI) is common in patients with cancer and can lead to increased morbidity and mortality.

2. Presenting symptoms for acute renal failure (ARF) depend on the etiology and may be asymptomatic. A detailed history including type of cancer, current and past treatments can help elucidate the etiology.

3. Oncology patients can have AKI for many reasons; both cancers and their treatments are often associated with multiple different mechanisms of kidney injury.

4. Management of AKI includes treating the suspected underlying etiology.

5. Prompt involvement of a multidisciplinary team including Oncologists and Nephrologists may be necessary.