Immune checkpoint inhibitor-induced diarrhea and colitis: an overview.

Immune checkpoint inhibitors (ICIs) have emerged as an integral component of the management of various cancers and have contributed to significant improvements in overall survival. Most available ICIs target anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4), and anti-programmed cell death 1/programmed cell death ligand 1 (anti-PD1/PDL1). Gastrointestinal immune-related adverse events remain a common complication of ICIs. The predominant manifestations include diarrhea and colitis, which often manifest concurrently as immune-mediated diarrhea and colitis (IMDC). Risk factors for developing these side effects include baseline gut microbiota, preexisting autoimmune disorders, such as inflammatory bowel disease, and type of neoplasm. The hallmark symptom of colitis is diarrhea which may be accompanied by mucus or blood in stools. Patients may also experience abdominal pain, fever, vomiting, and nausea. If not treated rapidly, ICI-induced colitis can lead to serious life-threatening complications. Current management is based on corticosteroids as first-line, and immunosuppressants like infliximab or vedolizumab for refractory cases. Microbiota transplantation and specific cytokines and lymphocyte replication inhibitors are being investigated. Optimal patient care requires maintaining a balance between treatment toxicity and efficacy, hence the aim of this review is to enhance readers' comprehension of the gastrointestinal adverse events associated with ICIs, particularly IMDC. In addition to identifying the risk factors, we discuss the incidence, clinical presentation, workup, and management options of IMDC.

Association of emergency department admission and early inpatient palliative care consultation with hospital mortality in a comprehensive cancer center.

PURPOSE: Consultation to palliative care (PC) services in hospitalized patients is frequently late after admission to a hospital. The purpose of this study is to examine the association of in-hospital mortality and timing of palliative care consultation in cancer patients admitted through the emergency department (ED) of MD Anderson Cancer Center. METHODS: Institutional databases were queried for unique medical admissions over a period of 1 year. Primary cancer type, ED versus direct admission, length of stay (LOS), presenting symptoms, and in-hospital mortality were reviewed; patient data were analyzed, and risk factors for in-hospital mortality were identified. The association of early palliative care consultation (within 3 days of admission) with these outcomes was studied. Descriptive statistics and multivariate logistic regression model were used. RESULTS: Equal numbers of patients were admitted directly versus through the ED (7598 and 7538 respectively). However, of all patients who died in the hospital, 990 (88%) were admitted through the ED, compared with 137 admitted directly (P < 0.001). Patients who died in the hospital had longer median LOS compared with patients who were discharged alive (11 vs. 4 days, respectively, P < 0.001). Early palliative care consultation was associated with decreased mortality, compared with late consultation (P < 0.001). Chief complaints of respiratory problems, neurologic issues, or fatigue/weakness were significantly associated with in-hospital mortality. CONCLUSION: We found an association between ED admission and hospital mortality. Decedent cancer patients had a prolonged LOS, and early palliative care consultation for terminally ill symptomatic patients may prevent in-hospital mortality and improve quality of cancer care.

Is there coronary artery disease in the cancer patient who manifests with chest pain, shortness of breath and/or tachycardia? A retrospective observational cohort.

OBJECTIVE: Cancer therapies lead to chest pain (CP), shortness of breath (SOB), and/or tachydysrhythmias (TACH Y) requiring cardiac risk stratification including coronary computed tomographic angiography (CCTA). We posit that cancer patients with CP, SOB and/or TACH Y have greater odds of having coronary artery disease (CAD) identified by CCTA than those that do not. METHODS: Eligibility for this IRB-approved retrospective observational cohort included those with cancer that had CCTA performed. Groups were stratified with and without CP, SOB, and/or TACH Y. Electronic medical records were mined for appropriate CPT codes from 01012010 to 08312013. Demographics, cancer type, and clinical outcomes were obtained. Standard t tests, odds ratios, and frequencies were used. RESULTS: Of 176 participants identified; 84 were male (48 %) and 118 were Caucasian (67 %). Of those, 100/176 (57 %) had CP, SOB, and/or TACH Y; 72/100 (72 %) had CP; 10/100 (10 %) had TACH Y; and 18/100 (18 %) had SOB. Of the 72 with CP, 40 (56 %) had CAD; of the 10 with TACH Y, 6 (60 %) had CAD; of the 18 with SOB, and 10 (56 %) had CAD. Thus, a 2.6-fold increased odds of having CAD (56/100 = 56 %) compared to 25/76 (33 %) in the group with cancer without CP, SOB, and/or TACH Y (95 % CI = 1.40 to 4.83; p = 0.003). CONCLUSION: Cancer patients with CP, SOB, and/or TACH Y have a 2.6-fold increased odds of having CAD compared to cancer patients without CP, SOB, and/or TACH Y (95 % CI = 1.40 to 4.83; p = 0.003).

Towards full recovery with lurasidone: effective doses in the treatment of agitation, affective, positive, and cognitive symptoms in schizophrenia and of dual psychosis.

The management of schizophrenia necessitates a comprehensive treatment paradigm that considers individual patient nuances and the efficacy of lurasidone in addressing schizophrenia symptoms, particularly at elevated dosages. Numerous randomized trials have affirmed the efficacy of lurasidone across various dimensions of schizophrenia, demonstrating marked enhancements in positive, negative and cognitive symptoms compared to a placebo. In addition, lurasidone exhibits potential in ameliorating agitation amongst acutely ill patients, showcasing greater efficacy at higher doses. However, despite the favourable outcomes observed with higher lurasidone doses, routine clinical practice often opts for lower doses, potentially limiting its maximal therapeutic impact. Furthermore, lurasidone also shows efficacy in reducing post-psychotic depression in dual psychosis. Moreover, practical insights into lurasidone usage encompass swift dose escalation within a 1-5-day span and recommended combination strategies with other medications such as benzodiazepines for insomnia or agitation, beta-blockers for akathisia, and antihistamines or antimuscarinic drugs for patients transitioning rapidly from antipsychotics with substantial antihistamine and/or anticholinergic effects. Finally, a series of clinical cases is presented, highlighting benefits of lurasidone in terms of cognitive function, functional recovery and other therapeutic aspects for the management of schizophrenia.

Translating NIA-AA criteria into usual practice: Report from the ReDeMa Project.

INTRODUCTION: Biomarker-informed criteria were proposed for the diagnosis of Alzheimer's disease (AD) by the National Institute on Aging and the Alzheimer's Association (NIA-AA) in 2011; however, the adequacy of this criteria has not been sufficiently evaluated. METHODS: ReDeMa (Red de Demencias de Madrid) is a regional cohort of patients attending memory and neurology clinics. Core cerebrospinal fluid biomarkers were obtained, NIA-AA diagnostic criteria were considered, and changes in diagnosis and management were evaluated. RESULTS: A total of 233 patients were analyzed (mean age 70 years, 50% women, 73% AD). The diagnostic language was modified significantly, with a majority assumption of NIA-AA definitions (69%). Confidence in diagnosis increased from 70% to 92% (p < 0.0005) and management was changed in 71% of patient/caregivers. The influence of neurologist's age or expertise on study results was minimal. DISCUSSION: The NIA-AA criteria are adequate and utile for usual practice in memory and neurology clinics, improving diagnostic confidence and significantly modifying patient management. HIGHLIGHTS: Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers increase diagnostic certainty regardless of the neurologist.AD CSF biomarkers lead to changes in disease management .Biomarker-enriched, 2011 NIA-AA diagnostic criteria are adequate for usual practice.

Characteristics and Outcomes of Patients with Cancer Pain Placed in an Emergency Department Observation Unit.

Pain remains an undertreated complication of cancer, with poor pain control decreasing patients' quality of life. Traditionally, patients presenting to an emergency department with pain have only had two dispositions available to them: hospitalization or discharge. A third emerging healthcare environment, the emergency department observation unit (EDOU), affords patients access to a hospital's resources without hospitalization. To define the role of an EDOU in the management of cancer pain, we conducted a retrospective study analyzing patients placed in an EDOU with uncontrolled cancer pain for one year. Patient characteristics were summarized using descriptive statistics and predictors of disposition from the EDOU and were identified with univariate and multivariate analyses. Most patients were discharged home, and discharged patients had low 72-hour revisit and 30-day mortality rates. Significant predictors of hospitalization were initial EDOU pain score (odds ratio (OR) = 1.12; 95% CI 1.06−1.19; p < 0.001) and supportive care (OR = 2.04; 95% CI 1.37−3.04; p < 0.001) or pain service (OR = 2.67; 95% CI 1.63−4.40; p < 0.001) consultations. We concluded that an EDOU appears to be the appropriate venue to care for a subsegment of patients presenting to an emergency department with cancer pain, with patients receiving safe care as well as appropriate consultation and admission when indicated.

Relationships between social withdrawal and facial emotion recognition in neuropsychiatric disorders.

BACKGROUND: Emotion recognition constitutes a pivotal process of social cognition. It involves decoding social cues (e.g., facial expressions) to maximise social adjustment. Current theoretical models posit the relationship between social withdrawal factors (social disengagement, lack of social interactions and loneliness) and emotion decoding. OBJECTIVE: To investigate the role of social withdrawal in patients with schizophrenia (SZ) or probable Alzheimer's disease (AD), neuropsychiatric conditions associated with social dysfunction. METHODS: A sample of 156 participants was recruited: schizophrenia patients (SZ; n = 53), Alzheimer's disease patients (AD; n = 46), and two age-matched control groups (SZc, n = 29; ADc, n = 28). All participants provided self-report measures of loneliness and social functioning, and completed a facial emotion detection task. RESULTS: Neuropsychiatric patients (both groups) showed poorer performance in detecting both positive and negative emotions compared with their healthy counterparts (p < .01). Social withdrawal was associated with higher accuracy in negative emotion detection, across all groups. Additionally, neuropsychiatric patients with higher social withdrawal showed lower positive emotion misclassification. CONCLUSIONS: Our findings help to detail the similarities and differences in social function and facial emotion recognition in two disorders rarely studied in parallel, AD and SZ. Transdiagnostic patterns in these results suggest that social withdrawal is associated with heightened sensitivity to negative emotion expressions, potentially reflecting hypervigilance to social threat. Across the neuropsychiatric groups specifically, this hypervigilance associated with social withdrawal extended to positive emotion expressions, an emotional-cognitive bias that may impact social functioning in people with severe mental illness.

Personalized Repetitive Transcranial Magnetic Stimulation for Primary Progressive Aphasia.

BACKGROUND: Primary progressive aphasia (PPA) is a neurodegenerative syndrome for which no effective treatment is available. OBJECTIVE: We aimed to assess the effect of repetitive transcranial magnetic stimulation (rTMS), using personalized targeting. METHODS: We conducted a randomized, double-blind, pilot study of patients with PPA receiving rTMS, with a subgroup of patients receiving active- versus control-site rTMS in a cross-over design. Target for active TMS varied among the cases and was determined during a pre-treatment phase from a list of potential regions. The primary outcome was changes in spontaneous speech (word count). Secondary outcomes included changes in other language tasks, global cognition, global impression of change, neuropsychiatric symptoms, and brain metabolism using FDG-PET. RESULTS: Twenty patients with PPA were enrolled (14 with nonfluent and 6 with semantic variant PPA). For statistical analyses, data for the two variants were combined. Compared to the control group (n = 7), the group receiving active-site rTMS (n = 20) showed improvements in spontaneous speech, other language tasks, patient and caregiver global impression of change, apathy, and depression. This group also showed improvement or stabilization of results obtained in the baseline examination. Increased metabolism was observed in several brain regions after the therapy, particularly in the left frontal and parieto-temporal lobes and in the precuneus and posterior cingulate bilaterally. CONCLUSION: We found an improvement in language, patient and caregiver perception of change, apathy, and depression using high frequency rTMS. The increase of regional brain metabolism suggests enhancement of synaptic activity with the treatment. TRIAL REGISTRATION: NCT03580954 (https://clinicaltrials.gov/ct2/show/NCT03580954).

Methotrexate-induced leukoencephalopathy presenting as stroke in the emergency department.

Methotrexate-induced leukoencephalopathy is to be considered as a potential etiology in any patient presenting with stroke-like symptoms after receiving methotrexate. One of our cases suggests that the method of administration of the methotrexate can be IV or intrathecal and still results in leukoencephalopathy.

Association of body composition with outcome of docetaxel chemotherapy in metastatic prostate cancer: a retrospective review.

BACKGROUND: Docetaxel, a lipophilic drug, is indicated for castration-resistant metastatic prostate cancer. Most men with such disease would have had androgen-deprivation therapy, which decreases muscle and increases body fat. Obesity and body composition changes may influence the outcomes of docetaxel therapy. METHODS: We conducted a retrospective review of 333 patients with metastatic prostate cancer treated with docetaxel at a comprehensive cancer center between October 7, 2004 and December 31, 2012. Body composition parameters were measured based on the areas of muscle and adipose tissues in the visceral and subcutaneous compartments on CT images at L3-4 levels. Dose calculations, toxicity and adverse reaction profiles, and overall survival were analyzed. RESULTS: Obese patients were younger at the diagnosis of prostate cancer and had a shorter duration from diagnosis to docetaxel therapy. Analysis of body composition found that a high visceral fat-to-subcutaneous fat area ratio (VSR) was associated with poor prognosis but a high visceral fat-to-muscle area ratio (VMR) and high body mass index were associated with increased duration from starting docetaxel to death, allowing such men to catch up with patients with normal body mass index in overall survival from cancer diagnosis to death. Cox proportional hazard regression showed that age ≥65 years, high VSR, abnormal serum alkaline phosphatase, and >10% reduction of initial dosage were significant predictors of shorter time between starting docetaxel and death, and that high VMR, obesity, and weekly regimens were significant predictors of longer survival after docetaxel. CONCLUSION: Obese and overweight patients may benefit more from weekly docetaxel regimens using the reference dosage of 35 mg/m2 without empirical dosage reduction.

Low tissue oxygen saturation at emergency center triage is predictive of intensive care unit admission.

PURPOSE: Timely recognition of critical patients by emergency center triage is an ongoing challenge. Peripheral tissue oxygen saturation (StO2) measurement has been used to monitor shock patients' responses to resuscitation. Interest has developed in evaluating StO2 as a triage tool, but limited studies have addressed critically ill patients. MATERIAL AND METHODS: This is a single-center, retrospective study of 158 emergent cancer patients with hypotension and/or modified systemic inflammatory response syndrome who underwent StO2 spot measurement at triage. RESULTS: Of the 57 patients with StO2 less than 70%, 17 went to the intensive care unit (ICU), whereas only 14 of the 101 patients with StO2 of 70% to 89% (P = .01) went to the ICU. There was no significant difference in non-ICU hospital admission or mortality between the 2 groups. The odds ratio of ICU admission for patients with StO2 less than 70% relative to those with StO2 of 70% to 89% was 2.64 (95% confidence interval, 1.18-5.87) and 2.87 (95% confidence interval, 1.23-6.66) when adjusted for mean arterial pressure, pulse, and temperature. CONCLUSIONS: In this patient population, an StO2 less than 70% significantly increased the risk of ICU admission. Tissue oxygen saturation at triage identifies critical patients who may not be recognized by vital signs alone. Tissue oxygen saturation measurement could help providers make earlier decisions regarding hospital resource allocation.