Safety and tolerability of the M2 muscarinic acetylcholine receptor modulator BAY 2413555 in heart failure with reduced ejection fraction in the REMOTE-HF study.

BAY 2413555 is a novel selective and reversible positive allosteric modulator of the type 2 muscarinic acetylcholine (M2) receptor, aimed at enhancing parasympathetic signaling and restoring cardiac autonomic balance for the treatment of heart failure (HF). This study tested the safety, tolerability and pharmacokinetics of this novel therapeutic option. REMOTE-HF was a multicenter, double-blind, randomized, placebo-controlled, phase Ib dose-titration study with two active arms.

Neoadjuvant anti-PD1 immunotherapy for surgically accessible recurrent glioblastoma: clinical and molecular outcomes of a stage 2 single-arm expansion cohort.

Glioblastoma is immunologically "cold" and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655).

Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer's disease, and primary age-related tauopathy hippocampi.

Introduction: Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition.

Methods: We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non-NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5).

Results: There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders.

Pediatric Acute Otitis Media Clinical Trials: An Analysis of Diversity.

Objective: This study aims to assess the diversity and equity of pediatric acute otitis media (AOM) trials using ClinicalTrials.gov, focusing on participant demographics and representation to identify gaps in inclusivity and inform strategies for promoting diversity in future pediatric AOM studies.

Study Design: Retrospective analysis.

Future Applications of Central Neuromodulation and Neurophysiological Testing in Cyclic Vomiting Syndrome.

Background: Cyclic vomiting syndrome (CVS) is defined by its episodic patterning. Furthermore, CVS is associated with other episodic disorders such as migraine and epilepsy. Indeed, many of the medications that are known to be useful for prophylaxis and abortive therapy in CVS are also effective in preventing and aborting migraines and seizures.

Expanding the phenotype and genotype spectrum of TAOK1 neurodevelopmental disorder and delineating TAOK2 neurodevelopmental disorder.

Purpose: The TAOK proteins are a group of serine/threonine-protein kinases involved in signalling pathways, cytoskeleton regulation, and neuronal development. TAOK1 variants are associated with a neurodevelopmental disorder (NDD) characterized by distinctive facial features, hypotonia and feeding difficulties. TAOK2 variants have been reported to be associated with autism and early-onset obesity.

A phase I study using bortezomib (Velcade), cladribine, and rituximab in treating patients over 50 years old with mantle cell lymphoma.

Unlabelled: Cladribine indirectly downregulates methylation of DNA, RNA, and histones by blocking the transfer of methyl groups from -adenosyl-methionine. The cladribine and rituximab combination showed a synergetic effect in treating B-cell lymphomas. Bortezomib (Velcade) is a Food and Drug Administration (FDA)-approved proteasome inhibitor for treating mantle cell lymphoma (MCL).

Sex differences in the relationships between 24-h rest-activity patterns and plasma markers of Alzheimer's disease pathology.

Background: Although separate lines of research indicated a moderating role of sex in both sleep-wake disruption and in the interindividual vulnerability to Alzheimer's disease (AD)-related processes, the quantification of sex differences in the interplay between sleep-wake dysregulation and AD pathology remains critically overlooked. Here, we examined sex-specific associations between circadian rest-activity patterns and AD-related pathophysiological processes across the adult lifespan.

Methods: Ninety-two cognitively unimpaired adults (mean age = 59.

Effect of postpartum clinical guideline on maternal outcomes in iranian women: a randomized controlled clinical trial.

Background: The postpartum period is a vital time for women, infants, spouses, parents, caregivers and families. Considering the importance of postpartum care and the necessity of using comprehensive and up-to-date clinical guidelines in Iran, this study was designed to implement a indigenized clinical guideline in Iran on maternal outcomes, including maternal functioning, postpartum depression and postpartum specific anxiety (primary outcomes) as well as infant care, maternal health problems, experiencing violence, feeding method and contraception use (secondary outcomes).

Methods: This randomized controlled trial was conducted with 272 postpartum women in Taleghani and Alzahra hospitals in Tabriz in 2023.

The Spatial Ventricular Gradient Is Associated with Pacing-Induced Cardiomyopathy.

Background: Pacing-induced cardiomyopathy (PICM) is a frequent complication of right ventricular pacing that often requires re-operation for biventricular or conduction system pacing. Better methods for predicting PICM may inform initial pacing strategy and follow-up monitoring.

Objective: To determine if the spatial ventricular gradient (SVG), a vectorcardiographic marker of ventricular electrical and mechanical heterogeneity, is associated with subsequent development of PICM.

Increasing Incidence of Serious Head and Neck Infections Among US Children, 2018-2023.

There has been a significant, post-pandemic increase in the incidence of serious head and neck infections (HNI) among children aged < 18 years since 2021, compared with the stable incidence of non-transmissible osteomyelitis and serious HNI in adults from 2018 to 2023. The etiology of this increase requires further study.

High water iodine levels are associated with the prevalence of subclinical hypothyroidism, thyroid nodules and goiter among pregnant women in Shandong, China.

Background: Both iodine deficiency and iodine excess can harm the thyroid glands during pregnancy. In areas without iodine fortification, the relationship between the water iodine concentration (WIC) and thyroid disease in pregnant women requires further investigation.

Objective: The aim of this study was to evaluate the relationship between water iodine levels and the prevalence of thyroid disease in pregnant women residing in areas with high water iodine levels without access to iodized salt.

Acute Decompensated Valvular Disease in the Intensive Care Unit.

Acute decompensated valvular disease encompasses a group of complex and challenging conditions, which are often the primary reason for admission to the cardiac intensive care unit and can also complicate the management of other primary cardiac disorders. Critically ill patients with valvular disease also present unique diagnostic and management challenges. Historically, medical and percutaneous interventional therapies have been limited and surgery was the only definitive treatment; however, surgical risk can at times be prohibitive.

Diversity-Related, Student-Led National Medical Organizations: Leadership Opportunities for Learners.

Introduction: In light of the lack of diversity in academic medicine leadership, diversity-related, student-led national medical organizations (NMOs) provide a space for solace and reprieve among common peers while providing an opportunity to develop leadership competencies in a supportive environment. Despite the impact NMOs have had on cultivating generations of leaders in medicine, trainees may not identify opportunities for leadership development that are transferable to future careers in academic medicine.

Methods: We designed and implemented a dynamic 60-minute workshop with an interactive PowerPoint presentation, author-owned video testimonials (from past student leaders of NMOs), two case presentations, and reflection exercises.

Virtual versus in-person didactic modalities: A national survey of emergency medicine residencies.

Background: Following the widespread shift from in-person to virtual delivery of didactics during the COVID-19 pandemic, some emergency medicine (EM) residency programs have retained virtual didactic time while others have returned exclusively to in-person didactics. In this national survey of EM residency programs, we explored the current national distribution of virtual versus in-person didactic time and the circumstances and motivators for use of each.

Methods: A cross-sectional survey with branched logic was designed via Qualtrics.

Revisiting Injectable Estrogen Dosing Recommendations for Gender-Affirming Hormone Therapy.

Injectable estrogens are options for gender-affirming hormone therapy per guidelines, which suggest intramuscular dosages of 5-30 mg every 2 weeks or 2-10 mg weekly with estradiol cypionate or valerate interchangeably. Data among transgender and gender-diverse patients are limited due to local unavailability and concerns around laboratory assay variability and estradiol (E2) level fluctuation. We note a concerning trend where patients are prescribed high-dose injections based on the guidelines leading to serum E2 levels well above the range recommended in the same guidelines.

Nephrotic Syndrome as a Complication of Systemic Calcitonin Amyloidosis From Long-Standing Metastatic Medullary Thyroid Cancer.

Background/objective: Medullary thyroid cancer often results in elevated calcitonin levels, which can cause localized formation of calcitonin amyloid, though rarely complications of systemic calcitonin amyloidosis have been reported. The objective of this report is to encourage awareness of calcitonin amyloid causing nephrotic syndrome in patients with metastatic medullary thyroid cancer.

Case Report: A 65-year-old woman with weakness, fatigue, anasarca, anemia, thrombocytopenia, venous and arterial thrombi, and a cavitary right lung lesion was transferred for care.

Racial Disparities in the Use of Minimally Invasive Surgery for Gastrointestinal Cancer.

Introduction: Racial disparities in minimally invasive surgery (MIS) utilization across gastrointestinal (GI) cancers are not well characterized. We evaluated racial/ethnic disparities in the use of MIS approaches and associated outcomes.

Methods: We analyzed a cohort of patients with GI cancer in the National Cancer Database (2010-2020).

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Approaches and outcomes of adalimumab discontinuation in patients with well-controlled inflammatory arthritis: a systematic search and review.

Objective: This systematic search and review aimed to evaluate the available literature on discontinuation of adalimumab and other tumor necrosis factor inhibitors (TNFi) for patients with well-controlled chronic inflammatory arthritides.

Methods: We conducted a publication search on adalimumab discontinuation from 2000-2023 using PubMed, CINAHL, EMBASE, and Cochrane Library. Included studies evaluated adalimumab discontinuation approaches, tapering schemes, and outcomes including successful discontinuation and recapture after flare, in patients with well-controlled disease.

Yes, We Can! Ensuring That our Graduating Resident's Procedural Skills Meet the Needs of Their Patients.

Objectives: There is a burgeoning discrepancy between the procedural competency of graduating diagnostic radiology residents and the needs of our patient population. The causes of this mismatch and opportunities for improvement are explored by the APDR Procedural Competency of Graduating DR Residents Task Force.

Materials And Methods: The APDR convened a task force consisting of diverse broad stakeholder viewpoints, drawing from organized radiology, academic and private practices.

Exploring a Novel Outcome Measure of Symptom Progression in Knee Osteoarthritis Utilizing a Large Randomized Trial.

Objectives: Explore a newly defined composite measure of symptom progression for knee osteoarthritis (KOA) in a large, randomized study of a potential disease-modifying osteoarthritis drug (DMOAD).

Design: Using longitudinal KOA studies, a potential composite endpoint of time to symptom progression was defined as the first occurrence of worsening of WOMAC Pain of ≥10 points with no improvement (≤9 point decrease) in WOMAC Function (0-100 scale). A post hoc analysis explored discrimination and association with structural outcomes in the sprifermin FORWARD trial through Years 3 and 5.