Society for Immunotherapy of Cancer: updates and best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) image analysis and data sharing.

Objectives: Multiplex immunohistochemistry and immunofluorescence (mIHC/IF) are emerging technologies that can be used to help define complex immunophenotypes in tissue, quantify immune cell subsets, and assess the spatial arrangement of marker expression. mIHC/IF assays require concerted efforts to optimize and validate the multiplex staining protocols prior to their application on slides. The best practice guidelines for staining and validation of mIHC/IF assays across platforms were previously published by this task force.

Undergraduate Nursing Students' Perceptions of Geriatric Care and Nursing Curriculum.

Background: The geriatric population in the United States is growing rapidly with an expected increase of 22% by 2040. Nursing students, however, consistently report negative attitudes toward caring for geriatric patients.

Purpose: The purpose was to assess undergraduate nursing student perceptions of care for the geriatric population, how their nursing curriculum influenced these perceptions, and any perceived curricular changes, didactic or clinical, that could potentially improve students' preparedness and desire to seek a career in geriatric nursing.

A novel small molecule Enpp1 inhibitor improves tumor control following radiation therapy by targeting stromal Enpp1 expression.

The uniqueness in each person's cancer cells and variation in immune infiltrates means that each tumor represents a unique problem, but therapeutic targets can be found among their shared features. Radiation therapy alters the interaction between the cancer cells and the stroma through release of innate adjuvants. The extranuclear DNA that can result from radiation damage of cells can result in production of the second messenger cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) by cyclic GMP-AMP synthase (cGAS).

Multiple sclerosis disease-modifying therapy use in the department of veteran affairs and Medicare: A comparative analysis.

Background: High-cost disease-modifying therapies (DMT) for multiple sclerosis (MS) have created affordability challenges for people with MS (PwMS) and payers. The Department of Veterans Affairs (VA) is the largest integrated healthcare system in the US and uses a variety of approaches to manage utilization and cost of MS DMT. The objective of this paper is to compare national utilization trends in the VA to the US Medicare program, another large federal public healthcare program.

Safety and tolerability of tegoprubart in patients with amyotrophic lateral sclerosis: A Phase 2A clinical trial.

Background: The interaction of CD40L and its receptor CD40 on activated T cells and B cells respectively control pro-inflammatory activation in the pathophysiology of autoimmunity and transplant rejection. Previous studies have implicated signaling pathways involving CD40L (interchangeably referred to as CD154), as well as adaptive and innate immune cell activation, in the induction of neuroinflammation in neurodegenerative diseases. This study aimed to assess the safety, tolerability, and impact on pro-inflammatory biomarker profiles of an anti CD40L antibody, tegoprubart, in individuals with amyotrophic lateral sclerosis (ALS).

AGA Clinical Practice Update on Advances in Per-Oral Endoscopic Myotomy (POEM) and Remaining Questions-What We Have Learned in the Past Decade: Expert Review.

Description: This American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) aims to review the available evidence and provide expert advice regarding advances in per-oral endoscopic myotomy (POEM).

Methods: This CPU was commissioned and approved by the AGA Institute CPU Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Gastroenterology. This review is framed around best practice advice points agreed upon by the authors, based on the current available evidence and expert opinion in this field.

Systemic immunostimulation induces glucocorticoid-mediated thymic involution succeeded by rebound hyperplasia which is impaired in aged recipients.

The thymus is the central organ involved with T-cell development and the production of naïve T cells. During normal aging, the thymus undergoes marked involution, reducing naïve T-cell output and resulting in a predominance of long-lived memory T cells in the periphery. Outside of aging, systemic stress responses that induce corticosteroids (CS), or other insults such as radiation exposure, induce thymocyte apoptosis, resulting in a transient acute thymic involution with subsequent recovery occurring after cessation of the stimulus.

Intratumoral radiation dose heterogeneity augments antitumor immunity in mice and primes responses to checkpoint blockade.

Radiation therapy (RT) activates multiple immunologic effects in the tumor microenvironment (TME), with diverse dose-response relationships observed. We hypothesized that, in contrast with homogeneous RT, a heterogeneous RT dose would simultaneously optimize activation of multiple immunogenic effects in a single TME, resulting in a more effective antitumor immune response. Using high-dose-rate brachytherapy, we treated mice bearing syngeneic tumors with a single fraction of heterogeneous RT at a dose ranging from 2 to 30 gray.

SAGES guidelines for the surgical treatment of hiatal hernias.

Background: Hiatal hernia (HH) is a common condition. A multidisciplinary expert panel was convened to develop evidence-based recommendations to support clinicians, patients, and others in decisions regarding the treatment of HH.

Methods: Systematic reviews were conducted for four key questions regarding the treatment of HH in adults: surgical treatment of asymptomatic HH versus surveillance; use of mesh versus no mesh; performing a fundoplication versus no fundoplication; and Roux-en-Y gastric bypass (RYGB) versus redo fundoplication for recurrent HH.

Atypical cutaneous manifestations of methicillin resistant Staphylococcus aureus infections in two immunocompetent pediatric patients: Case reports and review of the literature.

Although many clinical variants of Staphylococcus aureus infection are well-recognized, atypical presentations may mimic other conditions. We describe two cases of atypical S. aureus infections in pediatric patients: a S.

Recommendations for Tumor Mutational Burden Assay Validation and Reporting: A Joint Consensus Recommendation of the Association for Molecular Pathology, College of American Pathologists, and Society for Immunotherapy of Cancer.

Tumor mutational burden (TMB) has been recognized as a predictive biomarker for immunotherapy response in several tumor types. Several laboratories offer TMB testing, but there is significant variation in how TMB is calculated, reported, and interpreted among laboratories. TMB standardization efforts are underway, but no published guidance for TMB validation and reporting is currently available.

Fluorescence tracking demonstrates T cell recirculation is transiently impaired by radiation therapy to the tumor.

T cells recirculate through tissues and lymphatic organs to scan for their cognate antigen. Radiation therapy provides site-specific cytotoxicity to kill cancer cells but also has the potential to eliminate the tumor-specific T cells in field. To dynamically study the effect of radiation on CD8 T cell recirculation, we used the Kaede mouse model to photoconvert tumor-infiltrating cells and monitor their movement out of the field of radiation.

Oncologic outcomes following transanal total mesorectal excision: the United States experience.

Aim: The benefits and short-term outcomes of transanal total mesorectal excision (taTME) for rectal cancer have been demonstrated previously, but questions remain regarding the oncologic outcomes following this challenging procedure. The purpose of this study was to analyze the oncologic outcomes following taTME at high-volume centers in the USA.

Methods: This was a multicenter, retrospective observational study of 8 tertiary care centers.

Differentiating Prodromal Dementia with Lewy Bodies from Prodromal Alzheimer's Disease: A Pragmatic Review for Clinicians.

This pragmatic review synthesises the current understanding of prodromal dementia with Lewy bodies (pDLB) and prodromal Alzheimer's disease (pAD), including clinical presentations, neuropsychological profiles, neuropsychiatric symptoms, biomarkers, and indications for disease management. The core clinical features of dementia with Lewy bodies (DLB)-parkinsonism, complex visual hallucinations, cognitive fluctuations, and REM sleep behaviour disorder are common prodromal symptoms. Supportive clinical features of pDLB include severe neuroleptic sensitivity, as well as autonomic and neuropsychiatric symptoms.

The potential role of chronic pain and the polytrauma clinical triad in predicting prodromal PD: A cross-sectional study of U.S. Veterans.

Introduction: The research criteria for prodromal Parkinson disease (pPD) depends on prospectively validated clinical inputs with large effect sizes and/or high prevalence. Neither traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), nor chronic pain are currently included in the calculator, despite recent evidence of association with pPD. These conditions are widely prevalent, co-occurring, and already known to confer risk of REM behavior disorder (RBD) and PD.

Five-Year Outcomes from a Prospective Study on Safety and Efficacy of Phasix ST Mesh Use at the Hiatus During Paraesophageal Hernia Repair.

Background: Laparoscopic paraesophageal hernia (PEH) repair has a high hernia recurrence rate. The aim of this study was to assess the 5-year hernia recurrence rate after PEH repair using a combination of bioresorbable mesh and advanced surgical techniques to address tension as needed in a prospective group of patients.

Study Design: In 2016, a prospective database was established for 50 patients undergoing primary, elective PEH repair with a new bioresorbable mesh (Phasix ST).

Management of symptomatic, asymptomatic, and recurrent hiatal hernia: a systematic review and meta-analysis.

Background: The surgical management of hiatal hernia remains controversial. We aimed to compare outcomes of mesh versus no mesh and fundoplication versus no fundoplication in symptomatic patients; surgery versus observation in asymptomatic patients; and redo hernia repair versus conversion to Roux-en-Y reconstruction in recurrent hiatal hernia.

Methods: We searched PubMed, Embase, CINAHL, Cochrane Library and the ClinicalTrials.