Exploration of heterogeneity of treatment effects across exercise-based interventions for knee osteoarthritis.

Objective: Variability exists in the degree of improvement patients experience following exercise-based interventions (EBIs) for knee osteoarthritis (KOA), but understanding of this heterogeneity is limited. Using a machine learning approach, this study leveraged data from two randomized controlled trials (RCTs) to identify patient characteristics contributing to differential treatment effects.

Design: The RCTs enrolled n ​= ​621 patients and evaluated three EBIs (group-based physical therapy (PT), individual PT, and a Stepped Exercise Program) and an education control group.

Preoperative botulinum toxin for complex abdominal wall reconstruction: a meta-analysis of propensity-score matched studies with trial sequential analysis.

Purpose: Large ventral hernias can be associated with significant loss of domain, and preoperative Botulinum Toxin A (BTA) has been suggested as an adjunct therapy to minimize the effects of ventral hernia repair and facilitate fascial closure. However, there is often bias in studies involving BTA and its use is associated with significant cost and its efficacy remains unclear.

Methods: We systematically searched Medline, Embase, Cochrane, and ClinicalTrial.

Elective Versus Corrective Cochlear Implant Revision Surgery of Legacy Internal Devices.

Objective: To assess the time course of speech recognition restoration for recipients of legacy devices who underwent cochlear implant revision (CIR) surgery in the presence or absence of device failure.

Study Design: Retrospective review.

Setting: Tertiary academic referral center.

Mitochondrial defects and metabolic vulnerabilities in Lynch syndrome-associated MSH2-deficient endometrial cancer.

Lynch syndrome (LS), caused by inherited mutations in DNA mismatch repair genes including MSH2, carries a 60% lifetime risk of developing endometrial cancer (EC). Beyond hypermutability, mechanisms driving LS-associated EC remain unclear. We investigated MSH2 loss in EC pathogenesis using a mouse model (PR-Cre Msh2LoxP/LoxP, abbreviated Msh2KO), primary cell lines, human tissues, and human EC cells with isogenic MSH2 knockdown.

Perioperative glucagon-like peptide-1 receptor agonist use and retained gastric contents: A retrospective analysis of patients undergoing elective upper endoscopy.

Introduction: Glucagon-like peptide-1 receptor (GLP-1R) agonists have been increasingly prescribed for weight loss and glycemic control. The potential side effect of slowed gastric emptying may increase risk of regurgitation and aspiration. Our primary aim was to investigate the incidence of retained gastric contents (RGCs) among appropriately fasted patients taking a GLP-1R agonist compared to those not taking a GLP-1R agonist presenting for upper gastrointestinal endoscopy (UE).

Dysfunctional mechanotransduction regulates the progression of PIK3CA-driven vascular malformations.

Somatic activating mutations in are common drivers of vascular and lymphatic malformations. Despite common biophysical signatures of tissues susceptible to lesion formation, including compliant extracellular matrix and low rates of perfusion, lesions vary in clinical presentation from localized cystic dilatation to diffuse and infiltrative vascular dysplasia. The mechanisms driving the differences in disease severity and variability in clinical presentation and the role of the biophysical microenvironment in potentiating progression are poorly understood.

Biomolecular condensation of human IDRs initiates endogenous transcription via intrachromosomal looping or high-density promoter localization.

Protein intrinsically disordered regions (IDRs) are critical gene-regulatory components and aberrant fusions between IDRs and DNA-binding/chromatin-associating domains cause diverse human cancers. Despite this importance, how IDRs influence gene expression, and how aberrant IDR fusion proteins provoke oncogenesis, remains incompletely understood. Here we develop a series of synthetic dCas9-IDR fusions to establish that locus-specific recruitment of IDRs can be sufficient to stimulate endogenous gene expression.

A Strategic Approach to Succeed on Clinical Case-Based Multiple-Choice Exams.

Despite the importance of case-based multiple-choice question (CBMCQ) exams, medical educators rarely discuss strategies to systematically approach these questions, and literature on the topic is limited. Through trial-and-error, many students develop more refined and efficient approaches to answering CBMCQs that help them maximize the application of their knowledge base. In this article we present a structured six-step approach to answering CBMCQs, grounded in dual process theory.

Fibroblast growth factor 23 and fibroblast growth factor receptor 4 promote cardiac metabolic remodeling in chronic kidney disease.

Chronic kidney disease (CKD) is a global health epidemic that greatly increases mortality due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiac injury in CKD. High serum levels of fibroblast growth factor (FGF) 23 in patients with CKD may contribute mechanistically to the pathogenesis of LVH by activating FGF receptor (FGFR) 4 signaling in cardiac myocytes.

Identification of Social Risk-Related Referrals in Discrete Primary Care Electronic Health Record Data: Lessons Learned From a Novel Methodology.

Objective: To assess the utility of using discrete primary care electronic health record (EHR) data to identify social risk referrals in a national network of community-based clinics.

Data Sources And Study Setting: Primary data were abstracted from the OCHIN network EHR (June 2016 to February 2022) of 1459 community-based clinics across the United States.

Study Design: Structured data elements included 913 commonly used smartphrases and 53 procedure codes that were considered potential indicators of social risk referrals.

Cerebrospinal fluid biomarkers of inflammation and immune activation associated with neurocognitive impairment among U.S. Latinos living with HIV.

Objective: Examine the association between markers of inflammation in the cerebrospinal fluid (CSF) and neurocognitive impairment (NCI) among diverse persons with HIV (PWH).

Background: Latino PWH are at higher risk for NCI than non-Latino White PWH (NLW). Evidence of inflammation in cerebrospinal fluid (CSF) can be higher among racial and ethnic minority PWH and has been linked to NCI.

Long-COVID incidence proportion in adults and children between 2020 and 2024.

Background: Incidence estimates of post-acute sequelae of SARS-CoV-2 infection, also known as long-COVID, have varied across studies and changed over time. We estimated long-COVID incidence among adult and pediatric populations in three nationwide research networks of electronic health records (EHR) participating in the RECOVER Initiative using different classification algorithms (computable phenotypes).

Methods: This EHR-based retrospective cohort study included adult and pediatric patients with documented acute SARS-CoV-2 infection and two control groups-- contemporary COVID-19 negative and historical patients (2019).

Hybrid versus vaccine immunity of mRNA-1273 among people living with HIV in East and Southern Africa: a prospective cohort analysis from the multicentre CoVPN 3008 (Ubuntu) study.

Background: With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak.

Methods: Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior SARS-CoV-2 infection. In a prospective cohort study design, we used covariate-adjusted Cox regression and counterfactual cumulative incidence methods to determine the hazard ratio and relative risk of COVID-19 and severe COVID-19 with hybrid versus vaccine immunity within six months.

Olfactory Function and Frailty in Older Adults.

This study investigated the relationship between olfactory impairment and frailty among 5,231 (mean age 75.3 (SD 5.0), 59% women, 22% Black) participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort located in the U.

Longitudinal Reliability of Milestones Learning Trajectories during Anesthesiology Residency.

Background: Longitudinal Milestones data reported to the Accreditation Council for Graduate Medical Education (ACGME) provide a structured framework for assessing the developmental progression of residents in key competencies and subcompetencies. This study aims to investigate the previously underexplored longitudinal reliability of Milestones data, with the goal of identifying patterns in learning trajectories that can inform targeted interventions for residents and programs.

Methods: We conducted a retrospective cohort study with national anesthesiology Milestones data collected from 2014 to 2020.

Understanding the Lymphatic System: Tissue-on-Chip Modeling.

The lymphatic vasculature plays critical roles in maintaining fluid homeostasis, transporting lipid, and facilitating immune surveillance. A growing body of work has identified lymphatic dysfunction as contributing to the severity of myriad diseases and to systemic inflammation, as well as modulating drug responses. Here, we review efforts to reconstruct lymphatic vessels in vitro toward establishing humanized, functional models to advance understanding of lymphatic biology and pathophysiology.

Estimating financial and health burden by initial Medicare plan choice and history of cancer.

Understanding the downstream consequences of initial Medicare plan selection is necessary to ensure access to and affordability of health care services, especially for older adults with serious illness. We used 2008-2020 data from the Health and Retirement Study to estimate financial and health burden by initial Medicare plan selection (traditional Medicare without supplemental coverage, traditional Medicare plus supplemental coverage, or Medicare Advantage) and self-reported history of cancer. Initially choosing benefits with greater financial protections (either traditional Medicare plus supplemental coverage or Medicare Advantage) relative to traditional Medicare without supplemental coverage was associated with lower levels of out-of-pocket spending and a lower likelihood of reporting cost-related medication nonadherence and fair or poor health.

Benefits of Cochlear Implantation and Hearing Preservation for Children With Preoperative Functional Hearing: A Prospective Clinical Trial.

Objectives: This study was designed to (1) compare preactivation and postactivation performance with a cochlear implant for children with functional preoperative low-frequency hearing, (2) compare outcomes of electric-acoustic stimulation (EAS) versus electric-only stimulation (ES) for children with versus without hearing preservation to understand the benefits of low-frequency acoustic cues, and (3) to investigate the relationship between postoperative acoustic hearing thresholds and performance.

Design: This was a prospective, 12-month between-subjects trial including 24 pediatric cochlear implant recipients with preoperative low-frequency functional hearing. Participant ages ranged from 5 to 17 years old.

First-in-human phase I trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, SL-172154 in patients with platinum-resistant ovarian cancer.

Background: SL-172154 is a hexameric fusion protein adjoining the extracellular domain of SIRPα to the extracellular domain of CD40L via an inert IgG-derived Fc domain. In preclinical studies, a murine equivalent SIRPα-Fc-CD40L fusion protein provided superior antitumor immunity in comparison to CD47- and CD40-targeted antibodies. A first-in-human phase I trial of SL-172154 was conducted in patients with platinum-resistant ovarian cancer.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

Qualitative assessment of proposed visual key information pages for informed consent.

Introduction: The 2018 Common Rule revision intended to improve informed consent by recommending a concise key information (KI) section, yet provided little guidance about how to describe KI. We developed innovative, visual KI templates with attention to health literacy and visual design principles. We explored end users' attitudes, beliefs, and institutional policies that could affect implementing visual KI pages.

Patient experience with eosinophilic esophagitis symptoms and impacts on daily life based on in-trial qualitative interviews.

Purpose: Eosinophilic esophagitis (EoE), a chronic immune-mediated progressive disease, causes dysphagia, food impaction, abdominal pain, vomiting, and heartburn. EoE requires long-term monitoring and can affect quality of life owing to its symptoms and associated emotional and social burden. This study aimed to understand patients' experiences with EoE.