Recent ucladom items

Milvexian with Antiplatelet Therapy after Acute Coronary Syndrome Event

Wed, 28 Oct 2026 00:00:00 +0000

Milvexian with Antiplatelet Therapy after Acute Coronary Syndrome Event

Xenium spatial transcriptomics identifies mesenchymal fibroblast expansion and conserved fibrotic ECM programs in keloid

Fri, 23 Oct 2026 00:00:00 +0000

Xenium spatial transcriptomics identifies mesenchymal fibroblast expansion and conserved fibrotic ECM programs in keloid

Management and Surveillance of Immune Checkpoint Inhibitor Myocarditis: Managing the Aftermath

Fri, 23 Oct 2026 00:00:00 +0000

Management and Surveillance of Immune Checkpoint Inhibitor Myocarditis: Managing the Aftermath

In search of social belonging: a qualitative study of drivers of alcohol use and barriers to alcohol reduction among pregnant women in South Africa

Thu, 22 Oct 2026 00:00:00 +0000

BackgroundAlcohol use during pregnancy remains a major public health concern in South Africa, particularly in communities with entrenched historical, social, and structural drivers of harmful drinking. Saldanha Bay, a peri-urban fishing community in the Western Cape, has among the highest reported rates of fetal alcohol spectrum disorder globally. Understanding the multilevel social and structural dynamics that sustain alcohol use in pregnancy is essential to inform contextually appropriate interventions.MethodsFormative qualitative research to inform the adaptation of a peer-led intervention to reduce alcohol use during pregnancy was conducted between January and June 2025. We held two focus group discussions, one with healthcare providers (n = 6) and one with community leaders (n = 7) and conducted in-depth interviews with male partners of women who drank during pregnancy (n = 15) and drinking peers (friends or family members; n = 16). We purposively recruited participants with...

Predicting Oral HIV Pre‐Exposure Prophylaxis Efficacy in Cisgender Women Across Pregnancy and Postpartum

Thu, 22 Oct 2026 00:00:00 +0000

Cisgender women face an increased risk of HIV acquisition during pregnancy and postpartum. Oral pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate (F/TDF) is recommended in pregnancy despite limited published pharmacokinetic (PK) and efficacy data during pregnancy. Altered PK during pregnancy may reduce prophylactic efficacy and necessitate higher adherence. Tenofovir alafenamide (TAF) is a newer tenofovir prodrug with higher tenofovir diphosphate (TFV-DP) exposure in peripheral blood mononuclear cells (PBMCs), but the prophylactic efficacy of F/TAF across different reproductive stages in women is understudied. We adapted a multiscale modeling framework to predict the prophylactic efficacy of F/TDF and F/TAF across varying adherence levels and during the second trimester, third trimester, and 6-12 weeks postpartum. Clinical trial simulations were conducted utilizing PBMC TFV-DP and emtricitabine triphosphate concentrations as surrogate markers...

Crystal Clear: Purity of consumer-level methamphetamine samples and methamphetamine-adulteration of other drugs in Los Angeles, 2023-2025

Wed, 21 Oct 2026 00:00:00 +0000

Introduction The United States has seen a rise in methamphetamine use disorders and methamphetamine-involved deaths. However, there is limited information on methamphetamine at the consumer level. We leverage data from a community-based drug checking program in Los Angeles to investigate the makeup of the retail illicit methamphetamine market and the extent methamphetamine plays a role as an adulterant in other drugs. Methods Participants accessing a community-based drug checking program provided samples of drug products and completed brief interviews in Los Angeles County, California, from 2023 to 2025. Samples underwent laboratory-based qualitative and quantitative mass spectrometry. We quantitated the presence and concentration of methamphetamine as well as all other identified substances among samples expected only to be methamphetamine and samples expected to be another substance (e.g., fentanyl, heroin) where methamphetamine was found as an adulterant/contaminant. Results...

Contemporary Management and Rechallenge Practices for 5-Fluorouracil-Associated Cardiotoxicity: Insights From an International Cardio-Oncology Society Survey.

Sat, 17 Oct 2026 00:00:00 +0000

Contemporary Management and Rechallenge Practices for 5-Fluorouracil-Associated Cardiotoxicity: Insights From an International Cardio-Oncology Society Survey.

Immunotherapy-Related Cardiac Arrythmias: Incidence, Pathobiology, Risk Factors and Management

Sun, 11 Oct 2026 00:00:00 +0000

Purpose of ReviewImmunotherapies have revolutionized treatment strategies for cancer patients, improving the prognosis in many populations with advanced malignancies. Immune check point inhibitors (ICI) and Chimeric antigen receptor (CAR) T cell therapy are being increasingly used. As the real-world use of immunotherapies increases and indications expand, an understanding of potential cardiovascular toxicities is required.Recent Findings Arrhythmias are among the top reasons for seeking cardiovascular care in immunotherapy treated patients. ICI and CART therapies have been associated with arrhythmias with wide range of estimates reported in randomized clinical trials and retrospective studies. The pathophysiology and risk factors behind ICI and CART therapies is unclear. Summary In this review, we summarize the incidence, mechanisms, risk factors, impact on patient outcomes and management of ICI and CAR-T cell therapy-associated arrhythmia complications.

Permissive Cardiotoxicity: An Evolving Paradigm

Sun, 11 Oct 2026 00:00:00 +0000

Permissive cardiotoxicity is an evolving clinical practice pattern that balances the management of cancer treatment‐associated cardiotoxicities with the risk of interrupting lifesaving or life‐extending cancer treatments. This paradigm shift has been catalyzed by advancements in the diagnostic and therapeutic tools available to treating clinicians, as well as a recognition of the consequences of withholding or delaying cancer therapy. Permissive cardiotoxicity has become a central tenet in the practice of cardio‐oncologists; however, recognition and confidence in managing cardiotoxicity is also crucial for the general cardiologist and oncologist due to the growing population of patients with cancer. This review aims to (1) highlight the philosophy of permissive cardiotoxicity, (2) provide a framework for risk stratification of cardiovascular toxicities, (3) describe systems of care considerations for successful implementation of permissive cardiotoxicity, and (4) review the existing...

Longitudinal Outcomes in Immune Checkpoint Inhibitor-Associated Uveitis

Sun, 11 Oct 2026 00:00:00 +0000

Longitudinal Outcomes in Immune Checkpoint Inhibitor-Associated Uveitis

The 3D framework for clinical image-based teaching

Wed, 7 Oct 2026 00:00:00 +0000

This AM Last Page provides educators with a framework they can use to engage learners with clinical images for diagnostic reasoning and examination teaching. An image-based teaching moment can deepen physical examination knowledge, augment visual intelligence, and promote self-directed learning.

Duration of effectiveness of tuberculosis preventive treatment across various tuberculosis burden settings: a systematic review and individual-participant meta-analysis

Wed, 7 Oct 2026 00:00:00 +0000

BACKGROUND: Millions of individuals at risk of tuberculosis are given tuberculosis preventive treatment (TPT) annually. However, questions remain regarding the duration of protection from TPT and potential variability across populations and settings with disparate tuberculosis risk. We aimed to assess the effect of TPT on time to tuberculosis among close contacts of individuals with tuberculosis and with evidence of Mycobacterium tuberculosis infection across high-burden, medium-burden, and low-burden settings. METHODS: In this systematic review and individual-participant meta-analysis, we searched MEDLINE, PubMed, Web of Science, BIOSIS, and Embase for cohort studies and randomised controlled trials published between Jan 1, 1998, and Aug 28, 2023. Studies were eligible if they included individuals (of any age) with household or close exposure to a person with microbiologically or clinically diagnosed tuberculosis (contacts); had at least 6 months of contact follow-up from baseline;...

Multiethnic and Multilingual Patients’ Perspectives on Hypertension Diagnosis, Education, Management, and Socioeconomic Factors Within the Safety Net

Wed, 7 Oct 2026 00:00:00 +0000

BackgroundUnderstanding the clinical, self-management, and resource needs of low-income, multilingual, racially and ethnically diverse safety-net patients with hypertension can guide interventions to improve outcomes in under-resourced communities.ObjectiveExplore barriers and contributors to equitable hypertension care.DesignWe conducted semi-structured virtual focus groups during April 2022 to April 2023.ParticipantsLos Angeles safety-net patients with hypertension (or their caregivers) self-identifying as Latino, Black/African American, Filipino, Korean, and Chinese were eligible; these groups had the lowest blood pressure control rates within a large public safety-net healthcare system.ApproachWe analyzed transcripts using reflexive thematic analysis.ResultsNine focus groups (43 hypertensive participants) across 5 racial/ethnic groups and 5 languages included three Latino (n = 13), two Black (n = 11), two Chinese (n = 12), one Filipino (n = 4), and one Korean (n = 3) groups....

Phylodynamic analysis reveals disparate transmission dynamics of Mycobacterium tuberculosis-complex lineages in Botswana

Wed, 7 Oct 2026 00:00:00 +0000

Tuberculosis epidemics have traditionally been conceptualized as arising from a single uniform pathogen. However, Mycobacterium tuberculosis-complex (Mtbc), the pathogen causing tuberculosis in humans, encompasses multiple lineages exhibiting genetic and phenotypic diversity that may be responsible for heterogeneity in TB transmission. We analysed a population-based dataset of 1,354 Mtbc whole-genome sequences collected over four years in Botswana, a country with high HIV and tuberculosis burden. We identified Lineage 4 (L4) as the most prevalent (87.4%), followed by L1 (6.4%), L2 (5.3%), and L3 (0.9%). Within L4, multiple sublineages were identified, with L4.3.4 being the predominant sublineage. Phylodynamic analysis revealed L4.3.4 expanded steadily from late 1800s to early 2000s. Conversely, L1, L4.4, and L4.3.2 showed population trajectories closely aligned with the HIV epidemic. Meanwhile, L2 saw rapid expansion throughout most of the 20^th century but declined...

Sildenafil Attenuates Inflammation and Oxidative Stress in Pelvic Ganglia Neurons after Bilateral Cavernosal Nerve Damage

Mon, 5 Oct 2026 00:00:00 +0000

Erectile dysfunction is a common complication for patients undergoing surgeries for prostate, bladder, and colorectal cancers, due to damage of the nerves associated with the major pelvic ganglia (MPG). Functional re-innervation of target organs depends on the capacity of the neurons to survive and switch towards a regenerative phenotype. PDE5 inhibitors (PDE5i) have been successfully used in promoting the recovery of erectile function after cavernosal nerve damage (BCNR) by up-regulating the expression of neurotrophic factors in MPG. However, little is known about the effects of PDE5i on markers of neuronal damage and oxidative stress after BCNR. This study aimed to investigate the changes in gene and protein expression profiles of inflammatory, anti-inflammatory cytokines and oxidative stress related-pathways in MPG neurons after BCNR and subsequent treatment with sildenafil. Our results showed that BCNR in Fisher-344 rats promoted up-regulation of cytokines (interleukin- 1...

Investigating the Kidney–Gut–Brain Axis in CKD: Uremic Toxins and Brain Microhemorrhages

Fri, 2 Oct 2026 00:00:00 +0000

Alterations of gut microbiota are common in chronic kidney disease (CKD) and contribute to increased uremic toxins including indoxyl sulfate (IS), p-cresyl sulfate (pCS) and trimethylamine N-oxide (TMAO), which are linked to cerebrovascular disease risk. This study examined the kidney-gut-brain axis in CKD mice and in dialysis patients. Male and female mice with adenine-induced CKD were fed a high-amino-acid (HAA) diet to increase precursors of gut-derived uremic toxins. A subgroup of mice received antibiotics in drinking water to suppress gut microbiota and evaluate its role in toxin generation. Behavior tests, gut microbiome composition and brain histology for cerebral microhemorrhages were analyzed. CKD mice had higher serum levels of creatinine, cystatin C and gut-derived toxins, a 2.5-fold increase in brain microhemorrhages, and decreased locomotor activity. The HAA diet significantly increased serum TMAO but not IS and pCS, and all three toxins were reduced by antibiotic...

Enhancing Evidence Generation by Linking Randomized Clinical Trials to Real‐World Data: The INVESTED‐Medicare Linkage Study

Tue, 29 Sep 2026 00:00:00 +0000

Real-world evidence (RWE) derived from real-world data (RWD) can complement randomized controlled trials (RCTs), yet the validity of RWD relative to RCT data remains insufficiently characterized. We obtained post hoc consent and linked individual participant data from the US-based INVESTED trial (2016-2019) with Medicare fee-for-service claims (2012-2020) to validate demographic factors, baseline characteristics (using 183-, 365-, and 730-day lookback periods) and outcomes, and to assess post-trial events. Among 5260 trial participants, 126 were enrolled and eligible for linkage. Among 115 participants with demographic information available from Medicare enrollment files, agreement between RCT- and RWD-based demographic factors was high: only one major age discrepancy, 100% agreement for sex, and an overall agreement of 0.89 for race. Participants with Medicare claims data (n = 65) were older and more likely to be White compared with the overall RCT population. For the 365-day...

The effectiveness of isoniazid preventive treatment among contacts of multidrug-resistant tuberculosis: a systematic review and individual-participant meta-analysis

Tue, 29 Sep 2026 00:00:00 +0000

RATIONALE: Recent empirical research suggests that isoniazid may lead to a risk reduction of incident tuberculosis (TB) among close TB contacts of someone with multidrug-resistant TB (MDR-TB). OBJECTIVES: To evaluate the association between isoniazid TB preventive treatment (TPT), compared to no treatment, upon incident TB in household contacts of MDR-TB cases using a large global consortium of TB contact tracing studies. METHODS: We conducted a systematic review and individual-participant meta-analysis among observational studies of household contact tracing studies. Participants were included if they were exposed to someone with MDR-TB and were given either 6 months of isoniazid TPT or no TPT. Our primary outcome was incident TB in contacts exposed to TB. We derived adjusted hazard ratios (aHRs) using mixed-effects, multivariable survival regression models with study-level random effects. The effectiveness of isoniazid TPT against incident TB was estimated through propensity...

National Mortality Databases to Assess Disease Burden in Systemic Autoimmune Diseases: A Valuable Resource But With Limitations

Thu, 24 Sep 2026 00:00:00 +0000

Trends in Dermatopolymyositis Mortality, 1999–2022: A Nationwide Population‐Based Study, United States

Thu, 24 Sep 2026 00:00:00 +0000

OBJECTIVE: We evaluated trends in dermatopolymyositis (DPM) mortality relative to all-cause mortality in the United States from 1999 to 2022. METHODS: We used the Centers for Disease Control and Prevention's databases (Multiple Causes of Death for 1999-2020 and Provisional Mortality Statistics for 2021 and 2022) to obtain death counts for DPM and non-DPM (all causes other than DPM). We calculated age-standardized mortality rates (ASMRs) for both groups and computed the ratio of DPM-ASMR to non-DPM-ASMR for each of the 24 years. We performed joinpoint regression analysis to estimate annual percent change (APC) in DPM-ASMRs and non-DPM-ASMRs and in the DPM-ASMR to non-DPM-ASMR ratios overall and by sex, age, and race and ethnicity. RESULTS: There were 12,882 DPM and 63,549,485 non-DPM deaths during 1999-2022. Mortality decreased at a higher APC (-3.8% [95% confidence interval (CI) -4.3% to -3.4%]) for DPM than for non-DPM (-1.2% [95% CI -1.5% to -0.9%]) until the start of the COVID-19...

Lupus, a Leading Cause of Years of Potential Life Lost in Young Women: Implications for Public Health Priorities and Research Funding

Thu, 24 Sep 2026 00:00:00 +0000

OBJECTIVE: Premature mortality burden is an important component of disease burden and can help guide health care and research priorities. However, relying solely on mortality rates may underestimate lupus mortality burden because a substantial proportion of deaths occur at younger ages. Years of potential life lost (YPLL) captures premature mortality by applying a predefined age threshold. We estimated the YPLL from lupus in US women relative to leading causes of death and other autoimmune diseases. METHODS: Using the US population-based national Multiple Cause-of-Death database, we obtained death counts for 28 diseases, including lupus, the Centers for Disease Control and Prevention's 15 leading causes of death, and 12 additional autoimmune diseases. We calculated YPLL before age 75 years by summing 75 minus age at death for deaths occurring before age 75. Official cause-of-death rankings were obtained from the Web-based Injury Statistics Query and Reporting System (WISQARS)....

SLE Among the Leading Causes of Years of Potential Life Lost in Young Women: Population-Based Study, 2000-2015

Thu, 24 Sep 2026 00:00:00 +0000

SLE Among the Leading Causes of Years of Potential Life Lost in Young Women: Population-Based Study, 2000-2015

Osteitis fibrosa cystica

Wed, 23 Sep 2026 00:00:00 +0000

Osteitis fibrosa cystica

Abstract 15287: Optimizing Guideline Directed Medical Therapy in Recently Hospitalized Patients With Heart Failure in a Large Urban Veterans Affairs Medical Center

Wed, 23 Sep 2026 00:00:00 +0000

Introduction: A quarter of patients hospitalized for heart failure either die or are re-hospitalized within 30 days. Optimization of guideline directed medical therapy (GDMT) has been shown to decrease both mortality and hospital readmissions. Methods: We used an existing heart failure clinical dashboard registry at our Veterans Affairs (VA) hospital to determine the rates of hospitalization from any medical cause and GDMT prescription rates from November to December 2022. We performed a retrospective chart review to validate dashboard results. Results: Twenty-nine patients in the registry were hospitalized within the last 30 days, with 5 patients excluded due to ongoing hospitalization; 19 were classified as heart failure with reduced ejection fraction (HFrEF, LVEF ≤ 40%), 4 as heart failure with preserved...

Identification of Chlamydia pneumoniae and NLRP3 inflammasome activation in Alzheimer’s disease retina

Wed, 23 Sep 2026 00:00:00 +0000

Chlamydia pneumoniae is an intracellular bacterium implicated in Alzheimer’s disease (AD), but its role in retinal pathology and disease progression is unclear. Here we identify Chlamydia pneumoniae inclusions in the retina, showing higher burden in AD retina and brain, increasing with APOEε4, disease stage, and cognitive deficit. Retinal and cortical proteomics reveal bacterial-infection and related NLRP3-inflammasome pathways. Retinal NLRP3 is elevated in mild cognitive impairment and activated in AD dementia, evidenced by increased caspase-1, cleaved interleukin-1β, and cleaved N-terminal gasdermin-D. Chlamydia pneumoniae associates with amyloid-β42, inflammation, apoptosis, pyroptosis, and AD status. In neuronal cultures and APPSWE/PS1ΔE9 model mice, infection induces amyloid-β, inflammasome activation, neuroinflammation, and neurotoxicity, and chronic infection worsens cognition. Fewer pathogen-colocalized microglia are found in AD retinas, implying impaired clearance. Machine...

S3753 Trust Your Gut: A Case of Methamphetamine-Induced Gastrointestinal Ischemia

Wed, 23 Sep 2026 00:00:00 +0000

S3753 Trust Your Gut: A Case of Methamphetamine-Induced Gastrointestinal Ischemia

Early Retinal UCHL1 Dysregulation Coupled With Synaptic Loss Reflects Alzheimer's Disease Severity

Wed, 23 Sep 2026 00:00:00 +0000

Synaptic dysfunction is a major driver of cognitive decline in Alzheimer's disease (AD), yet its extent and molecular basis in the retina remain poorly defined. We integrated postmortem retinal and matched brain histopathology with ultrastructural, proteomic, biochemical, and machine-learning analyses across cognitively normal, mild cognitive impairment, and AD cohorts. Retinal glutamatergic synapses exhibited early, progressive degeneration, marked by loss of presynaptic vesicular glutamate transporter 1 (VGLUT1) and synaptophysin and postsynaptic density protein 95 (PSD95) and N-methyl-D-aspartate receptor subunit 2A (NMDAR2A), along with ribbon synapse ultrastructural disruption. Synaptic deficits correlated with amyloid-β₄₂ (Aβ₄₂), pathogenic tau, oxidative stress, the Aβ-binding p75 neurotrophin receptor, and glial activation that paralleled disease progression. Proteomics revealed widespread synaptic remodeling accompanied by disease-associated...

Unexpected Right Ventricular Uptake: A Sign of Pulmonary Hypertension from a Large Pulmonary Embolism

Wed, 23 Sep 2026 00:00:00 +0000

Pulmonary embolism can be seen in patients with malignancy. Positron Emission Tomography/ Computerized Tomography (PET/CT) can show hypermetabolic activity in the right ventricle in patients with pulmonary embolism and right ventricular strain, representing a physiologic response to pressure overload rather than cardiac malignancy.

What Dose of Methamphetamine Do Regular Consumers Use Daily? Estimating Oral Amphetamine Milligram Equivalents

Fri, 11 Sep 2026 00:00:00 +0000

OBJECTIVES: The purity, accessibility, and affordability of illicit methamphetamine have increased in recent decades, which has been linked to rising rates of methamphetamine-involved overdoses, psychosis, cardiovascular events, and other health consequences. Nevertheless, information about the quantity of methamphetamine used by regular consumers has been limited, despite the potential clinical utility of exposure quantification. METHODS: From August 2024 to April 2026, self-reported daily methamphetamine consumption was assessed among n = 94 individuals in Los Angeles County. Methamphetamine samples (n = 256) were analyzed for purity using liquid chromatography-mass spectrometry. Bioavailability by route of administration and stimulant equivalency were obtained from the literature. A simulation model leveraging bootstrapping with 1,000,000 draws was used to estimate oral amphetamine milligram equivalents (AME). RESULTS: The average reported methamphetamine consumption was 1.09...

NCCN Guidelines® Insights: Survivorship, Version 3.2026.

Thu, 10 Sep 2026 00:00:00 +0000

The NCCN Guidelines for Survivorship offer guidance for health care providers who care for survivors of adult-onset cancer. These guidelines include screening, evaluation, and treatment recommendations for common physical and psychosocial problems resulting from cancer and its treatment and provide a framework for care coordination. They also present guidance for helping cancer survivors to enhance their wellness and maintain a healthy lifestyle. This article summarizes the panel's current recommendations and recent updates regarding anxiety, depression, distress, and trauma in cancer survivors.

Unpacking “High-Risk”: A Latent Class Analysis of Sexual Partnership Patterns and HIV Transmission Risk Among Gay, Bisexual, and Other Men Who Have Sex With Men in Perú

Thu, 10 Sep 2026 00:00:00 +0000

BACKGROUND: Gay, bisexual, and other men who have sex with men (GBMSM) are often considered a homogenous "high-risk" group. We aimed to differentiate subgroups based on participants' last sexual partner and explore associations with HIV transmission risk factors. SETTING: We utilized cross-sectional data (06/2022 to 03/2023) from "high-risk" GBMSM in Lima, Perú. METHODS: Participants included cisgender men and gender nonconforming adults assigned male at birth reporting condomless anal sex with ≥1 serodiscordant or unknown serostatus cisgender man or transgender woman in the past 6 months. Latent class analysis was performed using the last sexual partner characteristics, including partner type, sexual role, and condomless anal sex position. Multinomial logistic regression examined HIV risk factors associated with latent classes, including drug use, transactional sex, sexually transmitted infection diagnosis, sexual identity, hazardous alcohol use, and number of anonymous partners. RESULTS:...

Cabotegravir Maintains Protective Efficacy in the Setting of Bacterial Sexually Transmitted Infections: A Secondary Analysis of HPTN 083

Thu, 10 Sep 2026 00:00:00 +0000

BACKGROUND: Sexually transmitted infections (STIs) have been shown to facilitate human immunodeficiency virus (HIV) transmission and acquisition. HPTN 083, a global clinical trial, demonstrated superiority of long-acting cabotegravir (CAB-LA) versus daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV prevention among transgender women and cisgender men who have sex with men. This analysis assessed whether CAB-LA maintained protective efficacy when bacterial STIs (syphilis, rectal/urethral gonorrhea, and chlamydia) were present. METHODS: STI events per 100 person-years were calculated, including by subgroups (age, race/ethnicity, gender, education, treatment arm, drug use, alcohol use, region/country, condom usage, partner number, marital status, baseline STI). Association between baseline factors and STI incidence was modeled using Poisson regression. Cox proportional hazards modeling with STI status as a time-varying covariate was used to evaluate potential...

Leveraging Real-World Evidence to Inform Regulatory, Clinical, and Coverage Decisions Related to Glucagon-Like Peptide-1-Based Therapies: Synopsis of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

Thu, 10 Sep 2026 00:00:00 +0000

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed obesity and diabetes management, with rapidly expanding indications and use among U.S. adults. Despite their promise, key questions remain about optimal treatment pathways, long-term safety, effectiveness across diverse populations, adherence, and economic impact. Real-world evidence (RWE) derived from electronic health records, claims, and other data sources could address these gaps, but unique challenges complicate its use, such as inconsistent insurance coverage, high discontinuation rates, medication shortages, compounded formulations, and off-label prescribing. To explore these issues, the National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop in May 2025 with experts from regulatory agencies, guideline committees, payers, and academia. Discussions focused on identifying knowledge gaps in GLP-1RA use, evaluating how RWE informs practice, assessing limitations of real-world...

Dopamine signaling drives skin invasion by human-infective nematodes

Thu, 10 Sep 2026 00:00:00 +0000

Skin-penetrating nematodes are one of the most prevalent causes of disease worldwide. The World Health Organization has targeted these parasites for elimination by 2030, but the lack of preventative measures is a major obstacle to this goal. Infective larvae enter hosts through skin and blocking skin penetration could prevent infection. However, in order to prevent worm ingress via the skin, an understanding of the behavioral and neural mechanisms that drive skin penetration is required. Here, we describe the skin-penetration behavior of the human-infective threadworm Strongyloides stercoralis. We show that S. stercoralis engages in repeated cycles of pushing, puncturing, and crawling on the skin surface before penetrating. Pharmacological inhibition of dopamine signaling inhibits these behaviors in S. stercoralis and the human hookworm Ancylostoma ceylanicum, suggesting a critical role for dopamine signaling in driving skin penetration across distantly related nematodes. CRISPR-mediated...

Cardiovascular Toxicity of Antibody-Drug Conjugates in Breast Cancer Current Evidence and Evolving Considerations: JACC: CardioOncology Primer

Thu, 10 Sep 2026 00:00:00 +0000

Cardiovascular Toxicity of Antibody-Drug Conjugates in Breast Cancer Current Evidence and Evolving Considerations: JACC: CardioOncology Primer

Practice Pattern and Outcome Differences in the Emergency Department by Physician Sex

Wed, 9 Sep 2026 00:00:00 +0000

Practice Pattern and Outcome Differences in the Emergency Department by Physician Sex

Understanding the gastrointestinal microbiome in systemic sclerosis: methodological advancements and emerging research

Sun, 6 Sep 2026 00:00:00 +0000

PURPOSE OF REVIEW: This review highlights the role of the gastrointestinal (GI) microbiome in systemic sclerosis (SSc). We describe techniques for evaluating the GI microbiome in humans, and emerging research linking GI microbiome alterations (i.e., dysbiosis) and distinct SSc clinical manifestations. We also address the evolving treatment landscape targeting dysbiosis in SSc. RECENT FINDINGS: Recent literature brings into focus the complex relationship between the GI microbiome and SSc pathogenesis. Advanced techniques (e.g., shotgun metagenomics, meta-transcriptomics) provide deeper insights into microbial taxonomy and active gene expression, exposing dysbiosis as a potential driver of SSc. New studies demonstrate that SSc patients who possess specific SSc clinical features, (e.g., interstitial lung disease), have unique GI microbiome profiles. SUMMARY: Dysbiosis is associated with specific clinical features in patients with SSc. New tools for studying the GI microbiome have...

Real-world genetic testing data of ovarian cancer patients: Informing counseling and risk reduction in patients over age seventy

Thu, 27 Aug 2026 00:00:00 +0000

BACKGROUND: Older women are underrepresented in hereditary cancer guidelines, and the prevalence of pathogenic or likely pathogenic (P/LP) germline variants in ovarian cancer (OC) patients aged ≥70 remains poorly characterized. Current recommendations for risk-reducing interventions and surveillance rely heavily on variant and family history (FH), yet their applicability in older populations is uncertain. We evaluated age-stratified prevalence of P/LP variants at OC diagnosis to identify at-risk older patients and inform more inclusive genetic counseling strategies. METHODS: We conducted a retrospective analysis of 113,236 OC patients undergoing germline testing through the Myriad Collaborative Research Registry (1996-2024). Variant prevalence, ancestry, FH, and testing patterns were evaluated across age groups, with focus on patients ≥70. RESULTS: Overall, 14,513 patients (12.8%) harbored a P/LP variant, including 13,049 (11.5%) in established OC susceptibility genes. Among patients...

Ligandability at the Membrane Interface of GPx4 Revealed through a Reverse Micelle Fragment Screening Platform.

Thu, 27 Aug 2026 00:00:00 +0000

While they account for a large portion of drug targets, membrane proteins present a unique challenge for drug discovery. Peripheral membrane proteins (PMPs), a class of water-soluble proteins that bind to membranes, are also difficult targets, particularly those that function only when bound to membranes. The protein-membrane interface in PMPs is often where functional interactions and catalysis occur, making it a logical target for inhibition. However, protein-membrane interfaces are underexplored spaces in inhibitor design, and there is a need for enhanced methods for small-molecule ligand discovery. In an effort to better initiate drug discovery efforts for PMPs, this study presents a screening methodology using membrane-mimicking reverse micelles (mmRM) and NMR-based fragment screening to assess ligandability at the protein-membrane interface. The proof-of-principle target, glutathione peroxidase 4 (GPx4), is a lipid hydroperoxidase that is essential for the oxidative protection...

Time-restricted feeding enhances cross-tissue temporal coordination of mitochondrial-associated transcripts

Wed, 26 Aug 2026 00:00:00 +0000

Coordinating metabolism with the day-night cycle is essential for health. Circadian rhythms synchronize cellular and tissue functions with the external environment. Nutrient timing is a potent circadian cue that entrains peripheral clocks across organs. Mitochondria exhibit daily rhythms in energy metabolism and redox regulation; however, the temporal organization of mitochondrial-associated transcriptional programs across tissues remains unknown. We hypothesized that time-restricted feeding (TRF) enhances the cross-tissue coordination of mitochondrial-associated transcripts (MATs). Using a 22-tissue, 24-h transcriptomic dataset from mice under ad libitum or TRF conditions, we applied correlation- and phase-based analyses to quantify the intra- and inter-tissue alignment of MAT expression. TRF markedly increased cross-tissue coordination, nearly quadrupling the number of globally aligned MATs. Among these, Coq10b emerged as the most rhythmically aligned gene across...

On the Misuse of Virus-Transformed Human Corneal Epithelial Cells as Surrogates for Normal Cells

Wed, 26 Aug 2026 00:00:00 +0000

Research in corneal biology and pathology including disease modeling and drug testing largely depends on the availability of human ex vivo cultures. Because normal corneal epithelium can be cultured only for several passages, stable epithelial cell lines transformed by different agents or spontaneously have been developed. Telomerase immortalized diploid cell lines introduced more recently were shown to recapitulate traits of normal cells including the expression of some markers and stratification ability. At the same time, there are frequently used cell lines generated by transformation with viruses. The most popular lines were shown to be unstable, tetraploid, lacking important epithelial markers, having aberrant differentiation and deviating from normal cells by gene expression patterns. This perspective reviews properties of various corneal epithelial cell lines and cautions against the use of virally transformed, especially tumorigenic cell lines, as seriously deviating form...

Improving Medication Reconciliation at Discharge: A Cross-Sectional Survey.

Wed, 26 Aug 2026 00:00:00 +0000

Background

Medication discrepancies remain a persistent patient safety concern despite decades of quality improvement efforts. Research indicates that about half of hospitalized adults experience at least one such discrepancy after discharge, often stemming from unclear clinician roles and poor communication among nurses, physicians, and pharmacists. Understanding nurses' perspectives is critical to designing interventions that will improve medication reconciliation and enhance patient safety at discharge.

Purpose

This study aimed to explore RNs' perspectives of medication reconciliation during hospital discharge, focusing on barriers, communication patterns, and opportunities for system improvement.

Methods

A cross-sectional survey was administered to nursing staff across medical telemetry, cardiac observation, short-stay, and general observation units at a large quaternary academic teaching hospital between March 21 and April 30, 2022. The survey assessed...

Facile strategy enabling both high loading and high release amounts of the water-insoluble drug clofazimine using mesoporous silica nanoparticles

Fri, 21 Aug 2026 00:00:00 +0000

Facile strategy enabling both high loading and high release amounts of the water-insoluble drug clofazimine using mesoporous silica nanoparticles

Photothermal Nanoblades for Delivery of Large-Sized Cargo into Mammalian Cells at High Throughput

Fri, 21 Aug 2026 00:00:00 +0000

Technologies for transferring large-sized cargo into mammalian cells are needed to advance key applications in cell engineering. However, reliable methodologies for introducing large-sized cargo into mammalian cells are nearly completely lacking. This talk will present two new technologies, photothermal nanoblade and BLAST, that overcome the size limitation of cargo delivery into mammalian cells.

Discovery and cryoEM structure of FPM13, a periplasmic metalloprotein unique to Francisella

Thu, 20 Aug 2026 00:00:00 +0000

We report the identification and cryoEM structure of the Francisella protein FTN_1118, a previously uncharacterized 13 kDa periplasmic protein unique to the Francisella genus. The protein was serendipitously discovered during purification of Francisella type VI secretion system (T6SS) effector proteins and is hereby designated as FPM13 (Francisella Periplasmic Metalloprotein, 13 kDa) based on its cellular and biochemical properties. Identified by the cryoID approach based on our cryoEM density map, FPM13 exists naturally as a cylindrical 18-mer complex with 9-fold dihedral symmetry, formed by stacking two donut-shaped nonamers head-to-head. Measuring ~8 nm in height and outer diameter with a 3.5 nm central channel, the complex features a double-layered wall comprising an inner β-sheet core and an outer α-helical shell. Each FPM13 monomer adopts a compact fold comprising an N-terminus β-strand, an α-helix and two additional β strands at the C-terminus. Inter-ring loop interactions,...

Examining Undergraduates’ Intentions to Pursue a Science Career: A Longitudinal Study of a National Biomedical Training Initiative

Fri, 14 Aug 2026 00:00:00 +0000

Disparities in the participation of individuals from historically excluded groups in science careers persist, particularly at advanced career stages. In response to this challenge, the National Institutes of Health developed the BUilding Infrastructure Leading to Diversity (BUILD) initiative, aimed at undergraduate institutions to examine evidence-based strategies to engage and retain students across science-related fields. In this longitudinal study, we used propensity score matching and mixed-effects logistic regression models to examine the effects of BUILD on undergraduates' intentions to pursue science-related research careers. The results indicate that students who participated in BUILD are four times more likely to pursue a science-related research career in comparison to their non-BUILD counterparts. We also discuss and present the need to incorporate research training and mentorship to promote a diverse scientific workforce.

Institutionalizing grant-funded interventions: a multiple case study examining long-term investments in science, technology, engineering, mathematics, and medicine (STEMM)

Fri, 14 Aug 2026 00:00:00 +0000

Background, context, and purposeAlthough funding agencies make large investments and encourage program adoption, little is known about the process of institutionalizing grant-funded efforts in higher education. This multiple case study examined how grant-funded awardees of a biomedical training grant worked toward institutionalizing program activities. Cases included 10 diverse postsecondary institutions (368 study participants) across the United States charged with implementing a federal grant aimed at comprehensive and multi-level approaches to engage and retain students from diverse backgrounds in biomedical research.FindingsEmploying prior frameworks on institutionalization in higher education, we examined how embedded campus agents appealed to two determinants of institutionalization: compatibility and mutualism. We identified institutional resources as an additional determinant. Compatibility is most commonly sought after as early as the grant proposal stage, while agents...

Correlates of Risk for Disinhibited Behaviors in the Million Veteran Program Cohort

Fri, 14 Aug 2026 00:00:00 +0000

Importance: Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans' health, such as suicide-related behaviors and substance use disorders (SUDs). Objective: To explore correlates of risk for EXT disorders within the Veterans Health Administration (VA) Million Veteran Program (MVP). Design, Setting, and Participants: A series of phenome-wide association studies (PheWASs) of polygenic risk scores (PGSs) for EXT disorders was conducted using electronic health records. First, ancestry-specific PheWASs of EXT PGSs were conducted in the African, European, and Hispanic or Latin American ancestries. Next, a conditional PheWAS, covarying for PGSs of comorbid psychiatric problems (depression, schizophrenia, and suicide attempt; European ancestries only), was performed....

Community PrEP delivery preferences among pregnant and breastfeeding women using oral PrEP in south africa and kenya.

Thu, 13 Aug 2026 00:00:00 +0000

OBJECTIVE: We evaluated preferences for differentiated service delivery of oral pre-exposure prophylaxis (PrEP) versus clinic pick-up among oral PrEP-experienced pregnant and breastfeeding women (PBFW) in South Africa and Kenya. DESIGN AND METHODS: From September 2021 to February 2022, we surveyed PBFW in oral PrEP studies in South Africa and Kenya. We asked participants about their PrEP delivery preferences and used logistic regression models adjusted for age and country to identify predictors of preferring community over clinic-based PrEP delivery. RESULTS: We surveyed 394 South African and Kenyan PBFW (73% postpartum, median age 28 years). Overall, 59.5% of South African participants (n = 113) and 24.5% of Kenyan participants (n = 50, p < 0.01) were interested in community PrEP delivery, most frequently due to convenience (n = 80, 49.1%) and lower transportation costs (n = 78, 47.9%). Participants preferred clinic PrEP pick-up due to privacy (n = 174, 75.3%) and desire to...

Preferences and Acceptability for Long-Acting PrEP Agents Among Pregnant and Postpartum Women with Experience Using Daily Oral PrEP in South Africa and Kenya

Thu, 13 Aug 2026 00:00:00 +0000

Abstract Introduction Long-acting pre-exposure prophylaxis (PrEP) options could overcome some barriers to oral PrEP persistence during pregnancy and postpartum. We evaluated long-acting PrEP preferences among oral PrEP-experienced pregnant and postpartum women in South Africa and Kenya, two countries with high coverage of oral PrEP and with pending regulatory approvals for long-acting injectable cabotegravir and the dapivirine vaginal ring (approved in South Africa, under review in Kenya). Methods From September 2021 to February 2022, we surveyed pregnant and postpartum women enrolled in oral PrEP studies in South Africa and Kenya. We evaluated oral PrEP attitudes and preferences for existing and future long-acting PrEP methods. Results We surveyed 190 women in South Africa (67% postpartum; median age 27 years [IQR 22-32]) and 204 women in Kenya (79% postpartum; median age 29 years [IQR 25-33]). 75% of participants reported oral PrEP use within the last 30 days. Overall,...

Advancing the inclusion of pregnant and lactating populations in HIV PrEP research: ethical, regulatory, and surveillance recommendations from a multisectoral working group.

Thu, 13 Aug 2026 00:00:00 +0000

Despite a 60% decline in new HIV infections since 1995, significant challenges persist. In 2023, 1.3 million new HIV infections occurred, with 645,500 in sub-Saharan Africa, where cisgender adolescent girls and women represent over two-thirds of new cases. Approximately one-quarter of vertical HIV transmissions are linked to infections during pregnancy and lactation, yet data on PrEP use in these populations remains generally limited due to their exclusion from clinical trials, despite a recent movement toward inclusion, such as in the PURPOSE 1 trials evaluating the efficacy and safety of lenacapavir. This data gap is concerning given that women face an elevated risk of HIV acquisition during pregnancy. Despite this heightened risk, access to PrEP remains restricted among these groups. This article, based on insights from a multi-regional and multi-sectoral working group convened by the Forum for Collaborative Research between January 2024 and February 2025, addresses this critical...

Enabled self-care for HIV infection: an inflection point for sustainable epidemic control

Thu, 13 Aug 2026 00:00:00 +0000

Enabled self-care for HIV infection: an inflection point for sustainable epidemic control

Factors influencing implementation of point-of-care tests for maternal and newborn screening and diagnosis in low-resource settings: a systematic review

Thu, 13 Aug 2026 00:00:00 +0000

BackgroundDespite the potential of point-of-care (POC) tests to improve maternal and newborn health, implementation in low- and middle-income countries remains inconsistent. POC testing enables rapid, decentralized screening, but barriers across health system, facility, and individual levels may undermine uptake. This review synthesizes evidence on factors influencing the adoption, implementation, and sustainability of POC tests within maternal-child health programmes in low-resourced settings.MethodsA comprehensive search was performed across major bibliographic databases and grey literature sources using Boolean combinations of terms related to POC testing, maternal and newborn health, implementation, and low-resourced settings. Studies were eligible if they reported on adoption, implementation, or sustainability of POC tests for maternal or infant screening or diagnosis in low-resourced contexts. Data were extracted using a structured form capturing study characteristics, test...

Advancing ethical biomedical HIV prevention research for pregnant and lactating people

Thu, 13 Aug 2026 00:00:00 +0000

Advancing ethical biomedical HIV prevention research for pregnant and lactating people

Transforming HIV prevention: the promise of long-acting preexposure prophylaxis in high HIV burden settings

Thu, 13 Aug 2026 00:00:00 +0000

PURPOSE OF REVIEW: Recent research on efficacy and safety of long-acting preexposure prophylaxis (PrEP) holds the promise to transform HIV prevention in high HIV burden settings. We review emerging findings regarding early end-user acceptability of long-acting PrEP modalities, feasibility of integrating long-acting PrEP into health systems, and considerations regarding drug resistance and cost. RECENT FINDINGS: Long-acting PrEP, particularly injectables, was found to be highly acceptable among individuals across key populations in high HIV burden settings. Concerns around use of long-acting PrEP highlight the importance of choice and ability to switch methods. Existing provider-level barriers to oral PrEP implementation (e.g., overburdened staff, training gaps) may impact long-acting PrEP rollout - however, utilization of PrEP implementation strategies such as task-shifting, timely PrEP training for all providers, differentiated service delivery, and integration with sexual health...

Intersecting Vulnerabilities: Depression, Suicidality, and HIV Risk Among Young Mothers in South Africa

Thu, 13 Aug 2026 00:00:00 +0000

Many African women who are pregnant or parenting face intersecting challenges including intimate partner violence, unplanned pregnancies, and motherhood-related stresses that heighten vulnerability to poor mental health. Depression and suicidal ideation are associated with behaviors that increase HIV risk, yet limited research has explored these relationships in African contexts. This study examined associations between depressive symptoms, suicidal ideation, and sexual risk behaviors among unemployed young women aged 19–24 years in KwaZulu-Natal, South Africa. Baseline data were collected between June-October 2018 from participants who had been sexually active in the past year. Prolonged sadness (≥ 2 weeks) and suicidal ideation in the past year were measured using validated single-item indicators. The composite HIV risk outcome captured transactional sex, partners with unknown HIV/STI status, and substance-influenced sex. Poisson regression models adjusted for age, intimate...

Participatory Prototyping of a Tailored Undetectable Equals Untransmittable Message to Increase HIV Testing Among Men in Western Cape, South Africa

Thu, 13 Aug 2026 00:00:00 +0000

Daily antiretroviral therapy (ART) suppresses viral replication, rendering HIV undetectable through viral load (VL) testing. People living with HIV (PLWH) who have an undetectable VL cannot transmit HIV to sexual partners or through giving birth, a message commonly referred to as U = U (undetectable equals untransmittable). To increase knowledge and understanding of U = U among men, who have poorer HIV testing and treatment outcomes than women, we engaged men from high HIV burden communities in Cape Town in two interactive human-centered design cocreation workshops to develop local U = U messaging for men. Two trained workshop facilitators, explained the U = U message to 39 adult men (in two separate workshops), and asked them how to effectively communicate U = U to other men in the local language (isiXhosa). Participant-designed messages sought to inform men about U = U to help assuage fears of testing HIV positive (by removing the stigma of living with HIV and being a vector...

Long-term use of ART in African women of reproductive age

Thu, 13 Aug 2026 00:00:00 +0000

Long-term use of ART in African women of reproductive age

Exploration of Pregnant and Breastfeeding Women’s Acceptability of Rapid Point-of-Care Urine Testing Within Antenatal and Postnatal Care, and Its Perceived Impact on PrEP Adherence When Paired with PrEP Biofeedback Adherence Counselling in Cape Town, South Africa

Thu, 13 Aug 2026 00:00:00 +0000

Pregnant and breastfeeding women (PBFW) on oral pre-exposure prophylaxis (PrEP) face barriers to adherence and persistence which may be improved by point-of-care adherence monitoring using urine tenofovir testing. We explored the acceptability of urine tenofovir testing for PrEP adherence monitoring among PBFW on oral PrEP, and how this, together with PrEP biofeedback adherence counselling, may have shaped PBFW’s PrEP adherence and persistence. Between September 2022 and May 2024, we conducted a study among PBFW without HIV on oral PrEP in Cape Town, South Africa. Participants were randomized to intervention (urine tenofovir testing at each study visit with biofeedback adherence counselling) or standard-of-care arms (urine collected but not analyzed with participant, with standard PrEP adherence counselling). Participants, with consistent and inconsistent PrEP use, were purposively sampled from both study arms between October and December 2023 for qualitative interviews. Analysis...

Prevalence, symptomology, and correlates of curable sexually transmitted infections among pregnant women in Eastern Cape, South Africa

Thu, 13 Aug 2026 00:00:00 +0000

BackgroundCurable sexually transmitted infections (STIs) contribute to adverse maternal and neonatal outcomes. Syndromic management is standard care in South Africa. We evaluated prevalence, symptomology, and correlates of curable STIs, among pregnant women in Eastern Cape, South Africa.MethodsWe conducted a cross-sectional analysis using baseline data from a randomized controlled trial of pregnant women attending their first antenatal care visit at public clinics in Buffalo City Municipality (2021-2024). Participants were tested for Chlamydia (C.) trachomatis, Neisseria (N.) gonorrhoeae, Trichomonas (T.) vaginalis using GeneXpert point-of-care tests and for syphilis using Alere Determine TP rapid test. Symptoms were self-reported and clinically-observed. Adjusted prevalence ratios were estimated using Poisson regression models with robust standard errors.ResultsAmong 1491 participants (median age: 28 years (IQR: 24-33); gestational age: 13 weeks (IQR: 8-18);...

Community-Based Adaptation and Evaluation of a Peer-Led Intervention to Address Alcohol Use and HIV in Pregnant and Breastfeeding Women in South Africa: Protocol for the “Mentor Mothers Plus” Randomized Control Trial

Thu, 13 Aug 2026 00:00:00 +0000

BACKGROUND: In South Africa, pregnant and lactating women (PLW) face a dual burden of high alcohol use and HIV prevalence, both of which adversely affect maternal and infant health. However, few interventions address alcohol use and HIV risk concurrently in this population. OBJECTIVE: This study seeks to adapt and pilot-test in a randomized controlled trial (RCT) the peer-led multisession intervention Mentor Mothers Plus (MM+) to integrate alcohol reduction strategies with HIV prevention and care support (in a seroneutral intervention) among PLW in Saldanha Bay, Western Cape, South Africa. METHODS: Using the ADAPT-ITT (assessment, decision, adaptation, production, topical experts, integration, training, testing) framework, we adapted the evidence-based Mentor Mother (MM) model, originally aimed at reducing vertical HIV transmission among mothers with HIV. Our mixed methods design includes (1) qualitative research, including in-depth interviews (IDIs) and focus group discussions...

Dashboard-Directed Intervention to Improve Guideline-Directed Heart Failure Therapy for Veterans

Wed, 12 Aug 2026 00:00:00 +0000

BACKGROUND: Significant gaps in guideline-directed medical therapy (GDMT) persist in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Although population health dashboards can identify these gaps, sustainable workflows integrating them into routine practice remain largely underutilized. OBJECTIVES: This study aimed to evaluate the implementation and outcomes of a dashboard-based intervention in a novel clinical-educational hybrid model aimed to improve GDMT use. METHODS: From July 2024 to June 2025, a weekly, half-day HF Dashboard Population Health Clinic was implemented at a single Veterans Affairs center. A supervised team of cardiology fellows and nurse practitioners performed medical record reviews of patients with gaps in GDMT identified on the Veterans Affairs HF Dashboard, with a focus on underutilization of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in HFrEF patients. Clinicians executed targeted telehealth interventions, initiated therapies,...

Cefepime resistance with preserved ceftriaxone susceptibility in Proteus mirabilis osteomyelitis associated with bla OXA-1 gene amplification: Two case reports with genomic analysis

Wed, 12 Aug 2026 00:00:00 +0000

Objective Retrospective case series to describe an unusual cefepime-resistant, ceftriaxone-susceptible phenotype in Proteus mirabilis osteomyelitis associated with bla OXA-1 gene amplification. Patients Two adult patients with diabetes mellitus and chronic osteomyelitis, one with diabetic foot ulcer and one with infected hip prosthesis, both with prolonged antibiotic treatment. Methods Clinical data and antimicrobial susceptibility results were reviewed. Whole-genome sequencing was performed using short-read and long-read platforms with hybrid assembly. Resistance gene identification, phylogenetic analysis, and gene copy number estimation were conducted. Results Three isolates of P. mirabilis from two patients demonstrated an unusual phenotype of cefepime resistance (MIC 16–32 μg/mL) with susceptibility to ceftriaxone. Hybrid assembly and coverage analysis demonstrated amplification of the bla OXA-1-containing cassette, with approximately 16- and 24-fold duplication in patient...

Sisyphean Task of Cardiovascular Prevention: Real Gains, Unequal Progress

Wed, 12 Aug 2026 00:00:00 +0000

Sisyphean Task of Cardiovascular Prevention: Real Gains, Unequal Progress

Cost Offset With Quadruple Therapy for Heart Failure.

Wed, 12 Aug 2026 00:00:00 +0000

Importance: Contemporary guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF), which includes angiotensin receptor-neprilysin inhibitors (ARNI), β-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter 2 inhibitors (SGLT2i), reduces hospitalizations in randomized clinical trials (RCTs), but the combined economic impact of implementing full quadruple therapy after hospitalization is not well quantified. Objective: To estimate the 1-year health care cost offset and net cost associated with implementation of quadruple GDMT after hospitalization for HFrEF. Design, Setting, and Participants: This economic evaluation used Medicare-linked data from the American Heart Association's Get With The Guidelines-Heart Failure (GWTG-HF) registry to identify adults 65 years or older hospitalized with HFrEF from 2016 to 2020 with up to 1-year postdischarge follow-up. Data were analyzed from November 2025 to February...

Hydroxyurea-associated digital gangrene: a case report and narrative review of reported cases and emerging pathophysiology

Thu, 30 Jul 2026 00:00:00 +0000

BackgroundHydroxyurea (HU) is a first-line oral cytoreductive agent for selected patients with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), due to its efficacy and tolerability. Although cutaneous ulceration is a recognized complication of long-term HU exposure, HU-associated digital gangrene is rare, and upper-extremity involvement in PV has not previously been reported.Case presentationWe describe the first case of HU-associated digital gangrene in a patient with PV. A 72-year-old man with well-controlled Janus kinase 2 (JAK2)–positive PV, treated with HU for more than a decade, developed painless dry gangrene of the right index and middle fingers. Vascular imaging showed no significant arterial occlusion or embolic source. Hematologic parameters remained within target ranges, and the workup for autoimmune disease, infection, and hypercoagulability was unremarkable. HU was discontinued, and the ischemia stabilized without surgical intervention. With...

Addition of Ianalumab (VAY736) to Ibrutinib in Patients with Chronic Lymphocytic Leukemia on Ibrutinib Therapy: Results from a Phase Ib Study.

Thu, 30 Jul 2026 00:00:00 +0000

PURPOSE: This phase Ib dose-escalation/expansion trial (NCT03400176) enrolled patients with CLL who did not achieve a complete response (CR) with ibrutinib or had developed resistance mutations. Ianalumab (VAY736), an anti-B cell-activating factor receptor monoclonal antibody, combined with ibrutinib significantly improved survival and reduced tumor burden in preclinical chronic lymphocytic leukemia (CLL) models. PATIENTS AND METHODS: Patients received intravenous ianalumab (escalation: 0.3-9.0 mg/kg; expansion: 3.0 mg/kg) once every 2 weeks and continued ibrutinib (420 mg) once daily for up to eight cycles of 28 days. The study aimed to evaluate the safety, tolerability, recommended dose, and antitumor activity of this combination. RESULTS: Thirty-nine patients were treated (escalation: n = 15; expansion: n = 24). No dose-limiting toxicities were observed. Of the 39 patients, 38.5% were in CR or CR with incomplete marrow recovery at cycle 9 (C9). At C9 day 1, 17 patients...

Psychiatric Hospitalization Precipitants and Outcomes in a Comprehensive Dementia Care Program

Thu, 30 Jul 2026 00:00:00 +0000

OBJECTIVES: Characterize the precipitants and outcomes of psychiatric hospitalizations among patients enrolled in a comprehensive dementia care program and identify factors associated with discharge to higher-level residential setting. DESIGN: Retrospective cohort study. SETTING: UCLA Alzheimer's and Dementia Care Program. PARTICIPANTS: Patients hospitalized at the UCLA Resnick Neuropsychiatric Hospital (NPH). MEASUREMENTS: Precipitating reasons for hospitalization, patient demographic and clinical characteristics, hospitalization-level characteristics, and caregiver relationship. Discharge to higher-level residential settings (e.g., assisted living, nursing home). Change in scheduled Central Nervous System (CNS)-active medications (antipsychotics, antidepressants, and sedative/hypnotics). RESULTS: There were 180 psychiatric hospitalizations among 150 patients, with a median age of 79 years (IQR, 73-85) at admission and MMSE score of 17 (IQR, 12-24) at first hospitalization. Agitation...

The effectiveness of care coordination on medication adherence among high-need, high-cost commercially insured beneficiaries: A randomized controlled trial

Wed, 29 Jul 2026 00:00:00 +0000

Background

High-need, high-cost (HNHC) beneficiaries experience life stressors that complicate their medication self-management. Care coordination programs may improve medication-taking behavior, including for chronic conditions that require daily medication adherence.

Objective

To determine whether nurse-led care coordination is associated with improved adherence among an HNHC commercial population with a chronic condition.

Methods

We analyzed data from a pragmatic, national randomized controlled trial of a comprehensive care coordination program conducted by a large national insurer and assessed its impacts on medication adherence in diabetes, atrial fibrillation, and hypothyroidism. We performed intention-to-treat (ITT) analyses (primary) and instrumental variable (IV) analyses (secondary) for HNHC beneficiaries from 2019 through 2022. Analyses compared treatment of control arms for metformin in diabetes (n = 3,602), statins in diabetes (n = 3,938), direct...

Body composition changes during cardiac rehabilitation and long-term cardiovascular outcomes in patients with coronary artery disease

Wed, 29 Jul 2026 00:00:00 +0000

Aims: This study assesses whether changes in body composition - lean body mass (LBM) and body fat % (BF%) - and body mass index (BMI), in patients undergoing cardiac rehabilitation (CR), are associated with long-term outcomes. Methods: In this cohort study of 1234 adults with coronary artery disease (CAD) who participated in CR from April 2012 to June 2024, bioelectric impedance analysis was used at baseline and after CR to assess body composition. Outcomes assessed included net adverse cardiovascular events (NACE) and all-cause mortality. Results: Subjects were followed for a mean of 5.9 years (SD 3.2). We found that those who had an increase in BF% during CR had a higher risk of NACE (adjusted HR 1.44, 95% CI: 1.10, 1.90) compared to those who had a decrease in BF%. There was also a trend towards decreased mortality in patients with a moderate increase in LBM (adjusted HR 0.49, 95% CI 0.23, 1.02). There were no associations between changes in body mass index and any outcomes....

cfDNA derived gene signatures as surrogate for microvascular invasion in HCC.

Wed, 29 Jul 2026 00:00:00 +0000

Background & aim

Microvascular invasion (MVI) is a critical prognostic risk factor in hepatocellular carcinoma (HCC). This study evaluated the performance of 5-hydroxymethylcytosine (5hmC) modifications in circulating cell-free DNA (cfDNA) in preoperative assessment of MVI.

Methods

A total of 907 patients with HCC were enrolled from two centers, including 671 in the training cohort, 152 in the internal validation cohort, and 84 in the external validation cohort. Preoperative clinical data, laboratory parameters, and cfDNA-derived 5hmC profiles were collected. Feature selection was performed using XGBoost, and modeling was conducted using a multilayer perceptron (MLP) neural network. Survival analyses were performed to evaluate the prognostic significance of the MVI prediction model. RNA sequencing analysis was performed to explore the potential mechanism underlying the proposed model.

Results

The 181-5hmC-modification signature demonstrated strong discriminatory...

An Observational Study of Post-hip Fracture Outcomes in Older Adults with Type 2 Diabetes

Wed, 22 Jul 2026 00:00:00 +0000

BackgroundHip fracture is a global public health concern, with over 10 million cases worldwide in 2019. Post-hip fracture outcomes, including mortality, vary by type 2 diabetes (T2D) co-diagnosis and patient demographics.ObjectiveTo examine post-hip fracture outcomes and identify factors modifying mortality differences in a racially and ethnically diverse population of older United States (US) adults with T2D.DesignRetrospective cohort study using Medicare fee-for-service data from 2014 to 2020.ParticipantsMen and women aged > 65 years, with T2D diagnosis who had experienced a non-traumatic hip fracture.Main Measure(s)We evaluated associations between race and ethnicity and one-year mortality, dual energy x-ray absorptiometry (DXA) testing, osteoporosis treatment, and incident destitution post-hip fracture using multivariable Cox proportional hazards models.Key ResultsAmong 159,699 older adults with T2D, one-year post-hip fracture mortality was 30.4%. In age- and sex-adjusted...

Comparative Effectiveness of Tirzepatide Versus Dulaglutide or Semaglutide on Major Cardiovascular Events in Type 2 Diabetes and Cardiovascular Disease: Insights From Two Target-Trial Emulations.

Wed, 22 Jul 2026 00:00:00 +0000

OBJECTIVE: To evaluate the comparative effectiveness of dulaglutide or semaglutide versus tirzepatide on cardiovascular outcomes in adults with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). RESEARCH DESIGN AND METHODS: Two target trial emulations included commercially insured adults (June 2022-December 2024) with T2D and ASCVD who initiated subcutaneous tirzepatide, dulaglutide, or semaglutide. The primary outcome was modified major adverse cardiovascular events (MACE), defined as a composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. First, new users of tirzepatide and dulaglutide were propensity score (PS) matched one to one. Second, new users of tirzepatide and semaglutide were PS matched one to one. Incidence rates (IRs) per 1,000 person-years and hazard ratios (HRs) were estimated. RESULTS: After PS matching, 9,233 pairs of tirzepatide or dulaglutide initiators and 25,266 pairs of tirzepatide or semaglutide initiators...

Utilization Trends of Dual GIP/GLP-1 Receptor Agonist, Newer Glucose-Lowering Medications, and Anti-Obesity Medications Among Patients With Chronic Kidney Disease With and Without Type 2 Diabetes

Wed, 22 Jul 2026 00:00:00 +0000

Rationale & Objective: Tirzepatide, a dual GIP/GLP-1 receptor agonist, has been approved for type 2 diabetes (T2D) and obesity. However, the real-world utilization of tirzepatide remains unexplored, particularly in patients with chronic kidney disease (CKD), where the prevalence of T2D and obesity is high. This study aimed to describe the utilization trends of tirzepatide, glucose-lowering medications (GLMs), and anti-obesity medications (AOMs) in patients with CKD, with and without T2D. Study Design: A population-based, observational cohort study. Setting & Participants: Patients with CKD, with and without T2D, were identified from a large US health insurance claims database (from January 1, 2022 to September 30, 2023). Exposures: Tirzepatide, other GLMs, and AOMs. Outcomes: Medication utilization trends and patient characteristics. Any users were defined as those with prescription claims, and incident users as those with no previous dispensing within 365 days. Analytical...

The Risk of Acute Pancreatitis and Biliary Events After Initiation of Incretin-Based Medications In Patients with Type 2 Diabetes

Wed, 22 Jul 2026 00:00:00 +0000

OBJECTIVE: Patients with type 2 diabetes (T2D) are at increased risk of acute pancreatitis (AP) and biliary events. Evidence remains mixed regarding the association between incretin-based therapies, such as glucagon-like peptide 1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase 4 inhibitors (DPP-4is), and these outcomes. We examined the association between incretin medication use and risk of incident AP or biliary disease in patients with T2D. RESEARCH DESIGN AND METHODS: Using Medicare Fee-for-Service (FFS) and two U.S. commercial claims databases (2014-2021), we identified three pairwise cohorts of propensity score (PS)-based fine stratification-weighted patients aged ≥18 years (≥65 years in Medicare FFS) with T2D without prior AP or biliary disease who initiated treatment with GLP-1RAs versus sodium-glucose cotransporter 2 inhibitors (SGLT2is), DPP-4is versus SGLT2is, or GLP-1RAs versus DPP-4is. PS was estimated using 92 covariates. Weighted hazard ratios (HRs) with 95%...

Trends in Utilization of Glucose- and Weight-Lowering Medications after Tirzepatide Approval in the United States: A Population-Based Cohort Study

Wed, 22 Jul 2026 00:00:00 +0000

BACKGROUND: Recent trends in use of tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide receptor agonist (RA), versus other glucose-lowering medications (GLMs) and weight-lowering medications (WLMs) remain unexplored. OBJECTIVE: To describe trends in insurance claims for GLMs and WLMs after tirzepatide approval. DESIGN: Population-based cohort study. SETTING: Claims data from a large U.S. commercial database (January 2021 to December 2023). PARTICIPANTS: Adults (aged ≥18 years) with type 2 diabetes (T2D) and without diabetes with dispensations for GLMs and WLMs. Any use was defined as medication dispensation regardless of prior use. Incident use was defined as dispensation without use in the preceding year. MEASUREMENTS: Monthly trends in medication dispensations before and after tirzepatide market entry. Tirzepatide uptake was additionally compared with initial postapproval uptake of other GLMs and WLMs. RESULTS: Tirzepatide dispensations...

EKG Changes from Life-threatening Hyperkalemia