NCCN Guidelines® Insights: Management of Immunotherapy-Related Toxicities, Version 2.2024.

The NCCN Guidelines for the Management of Immunotherapy-Related Toxicities are intended to provide oncology practitioners with guidance on how to manage the wide-ranging and potentially fatal toxicities that may occur with cancer immunotherapy. The guidelines address immune-related adverse events related to immune checkpoint inhibitors, CAR T-cell therapies, and lymphocyte engagers (which include T-cell-engaging bispecific antibodies). These NCCN Guidelines Insights highlight recent guideline updates pertaining to the management of emerging toxicities related to cancer immunotherapy.

Recommendations for Clinicians, Technologists, and Healthcare Organizations on the Use of Generative Artificial Intelligence in Medicine: A Position Statement from the Society of General Internal Medicine.

Generative artificial intelligence (generative AI) is a new technology with potentially broad applications across important domains of healthcare, but serious questions remain about how to balance the promise of generative AI against unintended consequences from adoption of these tools. In this position statement, we provide recommendations on behalf of the Society of General Internal Medicine on how clinicians, technologists, and healthcare organizations can approach the use of these tools. We focus on three major domains of medical practice where clinicians and technology experts believe generative AI will have substantial immediate and long-term impacts: clinical decision-making, health systems optimization, and the patient-physician relationship.

Functional organization and natural scene responses across mouse visual cortical areas revealed with encoding manifolds.

A challenge in sensory neuroscience is understanding how populations of neurons operate in concert to represent diverse stimuli. To meet this challenge, we have created "encoding manifolds" that reveal the overall responses of brain areas to diverse stimuli with the resolution of individual neurons and their response dynamics. Here we use encoding manifold to compare the population-level encoding of primary visual cortex (VISp) with five higher visual areas (VISam, VISal, VISpm, VISlm, and VISrl).

Combination Therapy of Endoscopic Gastric Remodeling with GLP-1RA for the Treatment of MASLD.

Purpose: The mainstay of treatment for metabolic dysfunction-associated steatotic liver disease (MASLD) is weight loss. Endoscopic gastric remodeling (EGR) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are effective weight loss therapies. This study aims to assess the effect of combining EGR with GLP-1RA on liver-related outcomes and weight profile.

Learning dynamic representations of the functional connectome in neurobiological networks.

The static synaptic connectivity of neuronal circuits stands in direct contrast to the dynamics of their function. As in changing community interactions, different neurons can participate actively in various combinations to effect behaviors at different times. We introduce an unsupervised approach to learn the dynamic affinities between neurons in live, behaving animals, and to reveal which communities form among neurons at different times.

Outcomes of High-Grade Immune Checkpoint Inhibitor Hepatitis in Hospitalized and Nonhospitalized Patients.

Background & Aims: Guidelines recommend hospitalization for severe immune checkpoint inhibitor (ICI) hepatitis. We compared patient outcomes in the inpatient versus outpatient settings.

Methods: We conducted a multicenter, retrospective cohort study of 294 ICI-treated patients who developed grade 3-4 ICI hepatitis.

Population encoding of stimulus features along the visual hierarchy.

The retina and primary visual cortex (V1) both exhibit diverse neural populations sensitive to diverse visual features. Yet it remains unclear how neural populations in each area partition stimulus space to span these features. One possibility is that neural populations are organized into discrete groups of neurons, with each group signaling a particular constellation of features.

The Development of Nonthermal Plasma and Tirapazamine as a Novel Combination Therapy to Treat Melanoma In Situ.

Although melanoma accounts for only 5.3% of skin cancer, it results in >75% of skin-cancer-related deaths. To avoid disfiguring surgeries on the head and neck associated with surgical excision, there is a clear unmet need for other strategies to selectively remove cutaneous melanoma lesions.

Liver Pathology Related to Onco-Therapeutic Agents.

Oncotherapeutic agents can cause a wide range of liver injuries from elevated liver functions tests to fulminant liver failure. In this review, we emphasize a newer generation of drugs including immune checkpoint inhibitors, protein kinase inhibitors, monoclonal antibodies, and hormonal therapy. A few conventional chemotherapy agents are also discussed.

The effect of endoscopic gastric plication on portosystemic pressure gradient in patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease.

Background:  The goals of therapy for patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease include weight loss and reduction of the portosystemic pressure gradient (PPG) to decrease the risk of hepatic decompensation. Endoscopic gastric plication (EGP) is an effective endoscopic weight loss procedure. This study aimed to assess the effect of EGP on PPG.

Teaching LGBTQ+ Health, a Web-Based Faculty Development Course: Program Evaluation Study Using the RE-AIM Framework.

Background: Many health professions faculty members lack training on fundamental lesbian, gay, bisexual, transgender, and queer (LGBTQ+) health topics. Faculty development is needed to address knowledge gaps, improve teaching, and prepare students to competently care for the growing LGBTQ+ population.

Objective: We conducted a program evaluation of the massive open online course Teaching LGBTQ+ Health: A Faculty Development Course for Health Professions Educators from the Stanford School of Medicine.

Population encoding of stimulus features along the visual hierarchy.

The retina and primary visual cortex (V1) both exhibit diverse neural populations sensitive to diverse visual features. Yet it remains unclear how neural populations in each area partition stimulus space to span these features. One possibility is that neural populations are organized into discrete groups of neurons, with each group signaling a particular constellation of features.

Early Liver Specialist Consultation is Associated With Faster Biochemical Resolution of Severe Immune Checkpoint Inhibitor-Induced Hepatitis.

Background: We evaluated the impact of gastroenterology/hepatology consultation, as recommended by guidelines, on the management of severe immune checkpoint inhibitor (ICI)-induced hepatitis.

Methods: We conducted a multicenter, retrospective cohort study of 294 patients who developed grade ≥3 (alanine aminotransferase [ALT] >200 U/L) ICI-induced hepatitis, with early gastroenterology/hepatology consultation defined as occurring within 7 days of diagnosis. The primary outcome was time to ALT normalization (≤40 U/L), and the secondary outcome was time to ALT improvement to ≤100 U/L.

IAN: Iterated Adaptive Neighborhoods for Manifold Learning and Dimensionality Estimation.

Invoking the manifold assumption in machine learning requires knowledge of the manifold's geometry and dimension, and theory dictates how many samples are required. However, in most applications, the data are limited, sampling may not be uniform, and the manifold's properties are unknown; this implies that neighborhoods must adapt to the local structure. We introduce an algorithm for inferring adaptive neighborhoods for data given by a similarity kernel.

GOOD CONTINUATION IN 3D: THE NEUROGEOMETRY OF STEREO VISION.

Classical good continuation for image curves is based on 2 position and orientation. It is supported by the columnar organization of cortex, by psychophysical experiments, and by rich models of (differential) geometry. Here we extend good continuation to stereo.

Regression of Hepatic Fibrosis After Endoscopic Gastric Plication in Nonalcoholic Fatty Liver Disease.

Introduction: Fibrosis stage is the strongest predictor of mortality in patients with nonalcoholic fatty liver disease (NAFLD). There is currently no approved therapy that specifically targets fibrosis. This study aims to assess the effect of endoscopic gastric plication on hepatic fibrosis in patients with underlying NAFLD.

Clinical Discordance in Monozygotic Twins With Autism Spectrum Disorder.

There is a significant concordance of autism spectrum disorder in monozygotic (MZ) twins, where behavioral manifestations are heavily influenced by genetic factors. We describe a case of male monozygotic twins with autism spectrum disorder (ASD), raised in the same household, that present with different clinical manifestations. One of the twins presents with intermittent frank syncopal episodes, sinus bradycardia, and elevated alkaline phosphatase (ALP), while the other has symptoms of attention-deficit/hyperactivity disorder (ADHD), normal cardiological findings, and normal ALP level.

Evaluating Medical Students' Views of the Complexity of Sexual Minority Patients and Implications for Care.

Sexual and gender minority (SGM) people experience many health care disparities. We aimed to determine if medical students viewed sexual minority patients (lesbian, gay, or bisexual [LGB] men/women) as more complex than heterosexual patients, even when presenting with the same symptoms, and whether this perceived complexity affected confidence caring for LGB patients. A fictional patient with an upper respiratory infection was presented with systematic variation of the patient's sexual orientation across six experimental conditions in an online, vignette-based experimental study.

From boundaries to bumps: When closed (extremal) contours are critical.

Invariants underlying shape inference are elusive: A variety of shapes can give rise to the same image, and a variety of images can be rendered from the same shape. The occluding contour is a rare exception: It has both image salience, in terms of isophotes, and surface meaning, in terms of surface normal. We relax the notion of occluding contour and, more accurately, the rim on the object that projects to it, to define closed extremal curves.

Effect of corticosteroid dosing on outcomes in high-grade immune checkpoint inhibitor hepatitis.

Background And Aims: Consensus guidelines recommend high-dose corticosteroids (1-2 mg/kg/day methylprednisolone equivalents) for treating grade ≥3 immune checkpoint inhibitor (ICI) hepatitis. We examined the effect of corticosteroid dosing on time to alanine aminotransferase (ALT) normalization, need for additional immunosuppression, and steroid-related complications.

Approach And Results: We conducted a retrospective cohort study of 215 ICI-treated patients from 2010 to 2020 who developed grade ≥3 (ALT > 200 U/L) ICI hepatitis.