Recent ucladom_oapolicydeposits items

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...

81. Post-Treatment Imaging in Lung Cancer Patients: Adherence to Surveillance Guidelines Associated with Improved Survival in a Longitudinal Cohort

Sun, 19 Jul 2026 00:00:00 +0000

81. Post-Treatment Imaging in Lung Cancer Patients: Adherence to Surveillance Guidelines Associated with Improved Survival in a Longitudinal Cohort

Rule-based natural language processing to extract clinical trial and research study enrollment history from unstructured notes

Sun, 19 Jul 2026 00:00:00 +0000

Clinical trials are vital for advancing care. However, a systematic approach to tracking trial participation across different facilities and sponsors has been lacking. We developed natural language processing (NLP) methods to extract study enrollment history, including enrollment status, consent date, and study title from information on clinical trial participation recorded in clinical notes in the electronic health record based on national Veterans Affairs electronic health record data. The method exhibited high test-set precision for enrollment status (0.94), consent date (0.97), and study title (0.87) and acceptably high recall (0.76, 0.70, and 0.84, respectively). From a single center, the classifier correctly identified 111 of 125 trial participants (88.8%) across 12 distinct trials. Our study demonstrates the feasibility of using NLP to capture trial enrollment from a nationwide healthcare system. This algorithm creates a novel data resource for analyzing and tracking trial...

Air pollution and the risk of second primary lung cancer among lung cancer survivors: the prospective UK Biobank cohort study

Sun, 19 Jul 2026 00:00:00 +0000

BackgroundLung cancer survivors have a high risk of second primary lung cancer (SPLC). While air pollution is associated with the risk of initial primary lung cancer (IPLC), especially in never smokers, its effect on SPLC risk is unknown.MethodsWe identified 2439 IPLC patients from the UK Biobank, followed through 2017, linking baseline addresses to 2005–2007 annual average exposures of particulate matter (PM10) and nitrogen dioxide (NO2) from the EU-wide Land Use Regression model. Associations with SPLC risk were assessed using cause-specific Cox models adjusted for co-pollutants, socioeconomic factors, smoking, and tumour characteristics.ResultsOf 2439 IPLC patients, 92 (3.7%) developed SPLC over 6561 person-years. The 10-year cumulative incidence of SPLC was 3.98% (3.11–4.85%). A dose-response relationship was observed between PM10 and SPLC risk, with an adjusted hazard ratio (aHR) of 6.43 (2.38–17.32) in the highest vs. lowest (aHR = 1.69 [0.68–4.19]) quintile; a co-pollutant...

Evaluating Tumor Burden as a Predictive Biomarker for Epidermal Growth Factor Receptor Targeted Kinase Inhibitor Therapy in Advanced Non–Small Cell Lung Cancer

Sun, 19 Jul 2026 00:00:00 +0000

PURPOSE: As treatment options for advanced non-small cell lung cancer (NSCLC) evolve, biomarkers are needed to guide therapy selection while balancing efficacy and toxicity. Although tumor burden is a promising candidate, its prognostic role in guiding epidermal growth factor receptor (EGFR)-targeted kinase inhibitor (TKI) therapies remains understudied in real-world settings. METHODS: We identified patients with de novo stage IV EGFR-mutant NSCLC treated with first-line EGFR-TKI at Stanford Health Care (2000-2021). Tumor burden metrics were manually annotated from 592 baseline radiology reports, encompassing size, number, and location (1,807 lesions). Multivariable Cox regression evaluated associations between tumor burden metric and overall survival (OS), adjusting for confounders, in the overall cohort and an osimertinib subgroup. A weighted composite tumor burden score was constructed using statistically significant metrics to stratify risk. RESULTS: Of 312 patients,...

Adherence to Posttreatment Surveillance Guidelines in Non–Small Cell Lung Cancer: Retrospective Cohort Study

Sun, 19 Jul 2026 00:00:00 +0000

Background: Several guidelines recommend posttreatment surveillance for non-small cell lung cancer (NSCLC). However, studies evaluating surveillance patterns often cannot distinguish between imaging ordered for surveillance versus for symptoms suggestive of recurrence. Moreover, early recurrences and other competing events hamper efforts to determine true surveillance rates because of wide variability in reported guideline adherence in clinical practice. Leveraging comprehensive Veterans Health Administration data, we developed a novel competing risks framework to describe the patterns and predictors of NSCLC imaging surveillance. Objective: This study aims to examine posttreatment surveillance to estimate the true surveillance rates and predictors of guideline-concordant care in patients with early-stage NSCLC. Methods: The study cohort comprised veterans who were treated for stage 1 to 3 NSCLC between 2008 and 2016 and who survived for ≥6 months. Clinical documents and radiology...

Navigating the Complexity of Lung Cancer Surveillance Practices: Qualitative Pilot Study on Provider Perspectives

Sun, 19 Jul 2026 00:00:00 +0000

Background: Surveillance is noted to be an important part of survivorship to detect recurrence and/or second primary lung cancer (SPLC) at a curable stage. However, current surveillance guidelines remain controversial, and the factors providers consider in clinical decision-making are neither well-defined nor consistently applied. Objective: In order to inform the qualitative protocol for a larger national study, this pilot study aimed to understand the factors that influence lung cancer surveillance and how providers view risk stratification as a potential tool to inform surveillance practices. Methods: Semistructured interviews were conducted between October 2023 and July 2024 with purposively sampled providers involved in treating and surveilling patients with lung cancer from the US-based Palo Alto Veterans Affairs Medical Center and Stanford Medicine and its affiliate clinics. Providers were recruited through both email outreach and in-person invitations. Interviews were...

Provider Follow-Up and Adherence to Imaging Surveillance Recommendations for Lung Cancer Survivors in a Nationwide Health Care System.

Sun, 19 Jul 2026 00:00:00 +0000

PURPOSE: With the growing number of cancer survivors and projected shortages of oncology providers, understanding who delivers survivorship care has important implications for care quality. We examined follow-up provider patterns among lung cancer survivors in the Veterans Health Administration (VHA) system and assessed variation in receipt of guideline-concordant computed tomography (CT) imaging. METHODS: We conducted a retrospective cohort study of 20,532 Veterans with stage I to III non-small cell lung cancer who received definitive treatment between 2008 and 2016. The primary exposure was the lung cancer survivor's follow-up provider specialty, defined as the specialty with whom the patient received the most post-treatment follow-up visits. We evaluated associations between treatment type and follow-up provider specialty and compared receipt of guideline-concordant surveillance imaging, defined as chest CT performed 120-270 days after treatment, across specialties using multivariable...

Consumer Perceptions of Wearable Technology Devices: Retrospective Review and Analysis

Fri, 17 Jul 2026 00:00:00 +0000

BACKGROUND: Individuals of all ages are becoming more health conscious, and wearable technology devices (eg, Fitbit and Apple Watch) are becoming increasingly popular in encouraging healthy lifestyles. OBJECTIVE: The aim of this paper was to explore how consumers use wearable devices. METHODS: A retrospective review was done on the top-rated verified purchase reviews of the Fitbit One posted on Amazon.com between January 2014 and August 2018. Relevant themes were identified by qualitatively analyzing open-ended reviews. RESULTS: On retrieval, there were 9369 reviews with 7706 positive reviews and 1663 critical reviews. The top 100 positive and top 100 critical comments were subsequently analyzed. Four major themes were identified: sleep hygiene ("charts when you actually fall asleep, when you wake up during the night, when you're restless--and gives you a cumulative time of "actual sleep" as well as weekly averages."), motivation ("25 lbs lost after 8 months - best motivator ever!"),...

RhoGEF Ect2 supports RhoA activity at cell–cell junctions through desmoplakin

Thu, 16 Jul 2026 00:00:00 +0000

Desmoplakin (DP) is an essential component of the desmosomal adhesion complex, tethering intermediate filaments to sites of intercellular adhesion to confer mechanical integrity to tissues. As a frequent target for mutation in cardiocutaneous syndromes that vary widely in phenotype, DP's roles as a signaling hub are rapidly emerging. Here, we identify the RhoGEF Ect2 as a previously unappreciated component of intercellular junctions in close association with DP. DP promotes the localization of Ect2 to keratinocyte desmosomes and cardiac intercalated discs, where it maintains active RhoA (Rho-GTP) at the membrane. We demonstrate that Ect2 activity is regulated by PKC in a DP-dependent manner in cardiac myocytes. Finally, a truncated form of DP expressed in patients with Carvajal syndrome associated with severe cardiocutaneous defects is impaired in its ability to bind and localize Ect2 to cell junctions in cardiomyocytes and patient keratinocytes. Our findings delineate an important...

Skin capillary endothelial cells form a network of spatiotemporally conserved Ca2+ activity

Thu, 16 Jul 2026 00:00:00 +0000

Ca²⁺ signaling and its regulation are important for endothelial cell (EC) function and signaling. Yet, the spatiotemporal organization of Ca²⁺ activity and its regulation across a vascular plexus is poorly understood in an in vivo mammalian context. To overcome this gap in knowledge, we developed an intravital imaging approach to resolve Ca²⁺ activity with single-cell resolution in skin vasculature of adult mice via multiphoton microscopy. Here, we tracked thousands of Ca²⁺ events in the skin capillary plexus during homeostasis and observed signaling heterogeneity between ECs, with just over half displaying Ca²⁺ activity at any given time. Longitudinal tracking of the same mice revealed that the same capillary ECs maintain Ca²⁺ activity over days to weeks. Interestingly, activity dynamics, such as frequency and event duration, are not conserved at a single-cell level but are maintained at an EC population level....

Unmet social needs and colorectal cancer testing at 45-49 since the 2021 USPSTF recommendation

Wed, 15 Jul 2026 00:00:00 +0000

BACKGROUND: In 2021, the United States Preventive Services Task Force (USPSTF) lowered the recommended starting age for colorectal cancer (CRC) screening from 50 to 45 for average-risk individuals. However, screening uptake among younger adults has been slow, and little is known about how social factors influence screening behaviors in this early-midlife cohort. This study examined associations between unmet social needs and CRC testing and modality among adults aged 45-49 following the updated USPSTF recommendation. METHODS: This cross-sectional analysis of 2022 Behavioral Risk Factor Surveillance System data included adults aged 45-49 years. Outcomes included any CRC testing since the USPSTF recommendation update and initial modality (stool-based test vs colonoscopy) among tested individuals. Primary predictors included past-year housing, transportation, or food insecurity and total number of unmet social needs. Weighted binary logistic regression models were adjusted for sociodemographic...

Maternal residential proximity to oil and gas development in California and the risk of childhood cancer

Mon, 13 Jul 2026 00:00:00 +0000

This study investigates maternal residential proximity to oil and gas development (OGD) in pregnancy and the risk of multiple childhood cancers in California. Cases (N = 9487) were identified from California Cancer Registry and controls (N = 183834) were randomly selected from the California Birth Registry (20:1 frequency-matched by birth year: 1998-2016), restricting both to births within 10 km of OGD. Exposure was defined as residing within 1 km or 3 km of any well at birth; 'low' and 'high' exposures were defined by the median well count within each distance. Unconditional logistic regression models estimated cancer risks comparing each exposed group to the unexposed (residing 3-10 km from any well). The risks of several cancers among children of mothers exposed to any well increased: medulloblastoma (within 3 km: adjusted Odds Ratio (aOR): 1.40; 95% confidence interval (CI): 1.08, 1.82; low, aOR = 1.27; 95% CI = 0.93,...

Long COVID sequelae in heart transplant recipients

Thu, 2 Jul 2026 00:00:00 +0000

Post acute sequelae of SARS-CoV-2 infection (also known as Long COVID) have been defined as symptoms that persist after 3 months from initial acute episode of COVID-19. While the pathophysiology and mechanisms that cause Long COVID are hypothesized as secondary to persistent inflammation and immune dysregulation, the burden of this disease remains difficult to estimate due to varied symptomatology. Solid-organ transplant recipients in particular remain a vulnerable population that has been disproportionately affected by the COVID-19 pandemic, and the impact of Long COVID among orthotopic heart transplant recipients (OHTRs)-a patient population on chronic immunosuppressive therapy-remains incompletely characterized. We sought to evaluate patient-reported Long COVID symptoms between OHTRs compared to patients with baseline cardiomyopathy. We conducted a prospective survey-based study of adult OHTRs and cardiomyopathy control patients with documented SARS-CoV-2 infection. Participants...

A Hierarchical and Multiscale Framework for Characterizing Mouse Sleep-Wake Dynamics from 14-Day Continuous EEG: Validation of Age- and Sex-Dependent Remodeling.

Thu, 2 Jul 2026 00:00:00 +0000

Aging disrupts sleep, but how these changes are structured across circadian time, vigilance states, and sex remains poorly understood, because most prior studies used single-sex cohorts and few days of recordings. We continuously recorded 14 days of EEG/EMG in 24 C57BL/6J mice using a balanced 2 × 2 design (young vs. old; male vs. female; n = 6/group). A comprehensive multiscale analysis of the extended dataset enabled detailed reconstruction of 24 h sleep-wake architecture, better characterization of natural day-to-day variability including across multiple estrous cycles, and detection of rare bouts and transition events. Across seven levels of analysis, from circadian profiles to EEG spectral parameterization, the strongest aging effect was a dark-phase-specific 17-18% loss of theta-dominant active wake (TDW) in both sexes, with reciprocal increases in quiet wake (nTDW) and NREM sleep. We also identified a recurring N-shaped structural motif at the dark-to-light transition,...

Vision-language model-based semantic-guided imaging biomarker for lung nodule malignancy prediction

Wed, 1 Jul 2026 00:00:00 +0000

OBJECTIVE: Machine learning models have utilized semantic features, deep features, or both to assess lung nodule malignancy. However, their reliance on manual annotation during inference, limited interpretability, and sensitivity to imaging variations hinder their application in real-world clinical settings. Thus, this research aims to integrate semantic features derived from radiologists' assessments of nodules, guiding the model to learn clinically relevant, robust, and explainable imaging features for predicting lung cancer. METHODS: We obtained 938 low-dose CT scans from the National Lung Screening Trial (NLST) with 1,261 nodules and semantic features. Additionally, the Lung Image Database Consortium dataset contains 1,018 CT scans, with 2,625 lesions annotated for nodule characteristics. Three external datasets were obtained from UCLA Health, the LUNGx Challenge, and the Duke Lung Cancer Screening. For imaging input, we obtained 2D nodule slices in nine directions from 50×50×50mm...

Monoclonal Immunotactoid Glomerulopathy Associated With Chronic Lymphocytic Leukemia: A Case Report.

Mon, 29 Jun 2026 00:00:00 +0000

Immunotactoid glomerulopathy (ITG) is exceedingly rare in clinical practice. A majority of cases are associated with an underlying hematological disorder and specifically chronic lymphocytic leukemia (CLL). The treatment consists of managing the underlying disease and supportive therapy. We present the case of an 80-year-old patient with a history of CLL who presented with proteinuria and acute kidney injury and eventually developed hematuria. His renal biopsy revealed monoclonal ITG. He began a course of chemotherapy for CLL and achieved remission with improved renal function.

Campylobacter jejuni Enteritis Mimicking Mechanical Small Bowel Obstruction.

Mon, 29 Jun 2026 00:00:00 +0000

In this case, we present an 84-year-old patient admitted for small bowel obstruction (SBO) with radiographic evidence of a clear transition point in the proximal small bowel on a computed tomography (CT) scan. Given his prior history of hemicolectomy, surgical adhesions were suspected as the likely cause. After several days of poor response to supportive treatment, he developed significant secretory diarrhea with stool samples positive for Campylobacter jejuni. In rare cases, C. jejuni enteritis can mimic SBO. We suggest that his SBO initially resembled mechanical obstruction on imaging due to significant bacterial induced circumferential bowel thickening and edema as opposed to the usual pseudo-obstruction from bacterial activated pro-inflammatory mediators, which disrupt intestinal motility. His obstruction resolved with a course of azithromycin antibiotics and conservative measures.

The mental health and well-being effects of wildfire smoke: a scoping review.

Fri, 19 Jun 2026 00:00:00 +0000

Background

Smoke from wildfires is a growing public health risk due to the enormous amount of smoke-related pollution that is produced and can travel thousands of kilometers from its source. While many studies have documented the physical health harms of wildfire smoke, less is known about the effects on mental health and well-being. Understanding the effects of wildfire smoke on mental health and well-being is crucial as the world enters a time in which wildfire smoke events become more frequent and severe. We conducted a scoping review of the existing information on wildfire smokes impact on mental health and well-being and developed a model for understanding the pathways in which wildfire smoke may contribute to mental health distress.

Methods

We conducted searches using PubMed, Medline, Embase, Google, Scopus, and ProQuest for 1990-2022. These searches yielded 200 articles. Sixteen publications met inclusion criteria following screening and eligibility assessment....

Use of Evidence-Based Type 2 Diabetes Preventive Therapies and Rates of Progression to Diabetes Among Veterans with Prediabetes by Race and Ethnicity, 2010–2019

Thu, 18 Jun 2026 00:00:00 +0000

Use of Evidence-Based Type 2 Diabetes Preventive Therapies and Rates of Progression to Diabetes Among Veterans with Prediabetes by Race and Ethnicity, 2010–2019

End-of-Life Care Processes and Outcomes for Older Adults Treated by International Medical Graduates vs. US Medical Graduates

Thu, 18 Jun 2026 00:00:00 +0000

ImportanceInternational medical graduates (IMGs—physicians who graduated from a medical school outside the US) hold a significant role in the US healthcare system. Research suggests that clinicians’ attitudes towards end-of-life (EOL) care may vary across countries.ObjectiveTo compare EOL care processes and outcomes for older adults treated by IMGs vs. US medical graduates (USMGs).DesignCross-sectional study.ParticipantsA 20% random sample of Medicare fee-for-service beneficiaries aged 66 years or older who died in 2016–2019.Main MeasuresSeven EOL care-related measures: (i) palliative care counseling or hospice enrollment in the last 180 days of life; (ii) emergency department visits, (iii) hospital admissions, (iv) intensive care unit admissions, (v) use of mechanical ventilation or cardiopulmonary resuscitation, or (vi) feeding tube placement in the last 30 days of life; and (vii) death in an acute care hospital. We adjusted for beneficiary- and physician-level confounders;...

A diagnostically challenging case of pemphigus foliaceus without histologic evidence of acantholysis

Thu, 18 Jun 2026 00:00:00 +0000

A 77-year-old woman presented with pruritic, scaly, erythematous papules and plaques on the face which then spread to involve the trunk. Over nearly two years, five skin biopsies were performed which overall suggested a subacute to chronic eczematous process without acantholysis or intraepidermal bullae. After two years of failed treatment, antibody testing via enzyme-linked immunosorbent assay demonstrated elevated anti-Desmoglein-1 IgG and normal anti-Desmoglein-3 IgG, and a skin biopsy with direct immunofluorescence revealed IgG and C3 in the intercellular space. A diagnosis of pemphigus foliaceus was made, and the patient was treated with rituximab with significant improvement. Here, we present a diagnostically challenging case of pemphigus foliaceus in which multiple biopsies failed to detect acantholysis or intraepidermal bullae – classic histological findings of this condition, thus highlighting the importance of immunologic testing in the workup of suspected autoimmune...

Dietary Therapies for Gastrointestinal Disorders.

Thu, 18 Jun 2026 00:00:00 +0000

Alterations in gastrointestinal function (digestion, absorption, motility, secretion, and elimination) play important roles in the pathophysiology of many gastrointestinal disorders. Food also strongly influences gastrointestinal health and disease. Some foods act as antigens that trigger an enteric immune response, while others can serve as substrates with direct or indirect biological effects. Food can also be metabolized by gut microbes into bioactive molecules that alter physiology. This review discusses the current research evidence and the clinical use of food as medicine through dietary therapies for the management of various gastrointestinal conditions, including disorders of gut-brain interaction, eosinophilic esophagitis, celiac disease, inflammatory bowel disease, gastroparesis, and short bowel syndrome with intestinal failure.

Pharmacist-Led Discharge Care to Reduce Postdischarge Health Care Utilization

Wed, 17 Jun 2026 00:00:00 +0000

Importance: Pharmacist-led peridischarge transitions of care (TOC) interventions reduce adverse drug events after hospitalization. However, health care organizations do not usually see a financial incentive to fund these interventions. Objective: To test whether pharmacist-led TOC interventions could drive reductions in health care resource utilization after hospital discharge. Design, Setting, and Participants: This pragmatic randomized clinical trial was conducted in 2 urban teaching hospitals in the US. Participants were hospitalized adults aged 55 years or older taking 10 or more long-term prescribed medications or 3 or more high-risk medications (defined as anticoagulants, antiplatelet agents, or antihyperglycemics including insulin), enrolled between December 23, 2019, and December 30, 2022. Data were analyzed from January 2023 to June 2025. Intervention: Pharmacist-led peridischarge and postdischarge medication management with patients and their care partners, including...

A Rare Case of Methamphetamine-Induced Diffuse Gastrointestinal Ischemia

Wed, 17 Jun 2026 00:00:00 +0000

Methamphetamine is a widely used substance known for cardiovascular and neurological complications; however, its gastrointestinal effects remain poorly understood. While rare, methamphetamine-induced gastrointestinal ischemia has high morbidity and mortality rates, with limited case reports in the literature. We present a case of a 48-year-old man with a history of gastroesophageal reflux disease, alcohol use disorder in remission, and previously documented methamphetamine use who presented with two weeks of episodic abdominal pain, nausea, and hematemesis. Significant laboratory and imaging findings included acute anemia, urine toxicology confirming the presence of amphetamines, and computed tomography imaging showing wall thickening in the distal esophagus and stomach. On endoscopy, he was found to have diffuse ulcerations in the distal esophagus and post-pyloric region with pathology indicative of methamphetamine-induced gastrointestinal ischemia. This case highlights...

American Thyroid Association 2026 Guidelines for Thyroid Disease in Preconception, Pregnancy, and Postpartum.

Wed, 17 Jun 2026 00:00:00 +0000

Background

Thyroid disease in pregnancy, preconception, and postpartum is a common and clinically relevant problem. Since the publication of the American Thyroid Association (ATA) guidelines in 2017, substantial new clinical and scientific evidence has become available. The aim of these guidelines is to provide clinicians, patients, researchers, and policymakers with evidence-based recommendations on the care of women with thyroid disease before, during, and after pregnancy.

Methods

The clinical questions addressed were informed by prior ATA guidelines, stakeholder feedback, a global needs assessment, and input from the multidisciplinary task force. Systematic literature searches were conducted with the support from a medical librarian and evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Recommendations were formulated based on the quality of evidence, balance of benefits and harms, patient values, feasibility, and...

Evaluating the Acceptability of Using Virtual Reality to Promote Physical Activity Among Latino, Latina, and Latine Adults With Cardiometabolic Risk Factors and Obesity in Underresourced Settings: Protocol for a Qualitative Focus Group Study

Wed, 10 Jun 2026 00:00:00 +0000

Background: Obesity represents a significant public health challenge in the United States, particularly among Latino, Latina, and Latine communities and those in underresourced settings. Virtual reality (VR) is a new and innovative technology that can promote physical activity and has the potential to overcome some structural barriers. However, there are few studies that explore the acceptability of using this new technology among high-risk groups in underresourced settings. Objective: We outline a community-informed protocol for conducting focus groups with Latino, Latina, and Latine adults who have cardiometabolic risk factors and obesity residing in underresourced communities. The focus groups will assess the acceptability of a culturally aligned VR program to promote physical activity. Methods: Using a community-engaged approach informed by community health workers and a community advisory board, we delivered an immersive VR dance experience to Latino, Latina, and Latine adult...

Predictors of pathologic complete response in early-stage triple-negative breast cancer treated with neoadjuvant chemo-immunotherapy: a multi-institution study.

Fri, 5 Jun 2026 00:00:00 +0000

Introduction

The KEYNOTE-522 clinical trial demonstrated that the addition of pembrolizumab to 8 cycles of neoadjuvant chemotherapy (NAC) improves pathologic complete response (pCR) rates and overall survival in early-stage triple-negative breast cancer (TNBC). However, predictors of response and the benefit of alternative NAC backbones with immunotherapy are not known. This multi-institutional study evaluates clinical factors and treatment variables associated with pCR following NAC plus pembrolizumab in a diverse, real-world cohort.

Methods

This multi-institution retrospective study analyzed patients with early-stage TNBC diagnosed between July 1, 2021, and December 31, 2023, across three hospital systems. Eligible patients received at least one cycle of NAC and pembrolizumab. Predictors of pCR were assessed using logistic regression.

Results

Of the 374 patients included, the pCR rate was 61.2%. The cohort was racially and ethnically diverse, with 29.1%...

Translating a Preclinical Hydrogel Platform into a Human Therapeutic for Delivering Targeted Low-Dose Anti-CTLA-4

Thu, 4 Jun 2026 00:00:00 +0000

Systemic administration of antibodies that target immune checkpoint inhibitor pathways is a highly effective approach to cancer immunotherapy, but systemic toxicity can limit clinical utility. In preclinical testing, a peri-tumor injection of a low dose of hydrogel-encapsulated cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody was shown to selectively activate T cells in tumor-draining lymph nodes, induce tumor infiltration by cytotoxic T cells, and result in tumor regression, protective immunity, and long-term survival. In contrast to systemic therapy, there was limited systemic exposure or risk for autoimmune toxicity. The current study focuses on translating this platform into a biocompatible human therapeutic. The hydrogel matrix was reformulated using a low-molecular-weight hyaluronic acid. A recombinant human hyaluronidase (rHuPH20) was incorporated to promote lymph node targeting and self-resorbing features. Formulations were optimized to operate at neutral...

Elevated AD biomarkers do not explain cognitive performance in a community‐recruited clinical trial cohort

Thu, 4 Jun 2026 00:00:00 +0000

INTRODUCTION: To examine the generalizability of Alzheimer's disease (AD) biomarker models in real-world older adults, we examined AD biomarker relationships with cognition in two multicenter cohorts that differ with respect to recruitment approach and health risk factors but were matched on a variety of characteristics. METHODS: We compared harmonized health and demographic data, AD and cerebrovascular biomarkers, and cognitive performance in the community-recruited U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) Imaging substudy and a matched sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI) which recruited primarily from academic specialty clinics. RESULTS: Elevated β-amyloid (Aβ) and tau were associated with cognitive performance in ADNI but not U.S. POINTER. Findings were consistent across different cohort matching schemes, and were not explained by discrepancies in vascular risk. DISCUSSION: The role of Aβ...

Clinical Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors Among Older Patients Hospitalized for Heart Failure With Reduced Ejection Fraction.

Wed, 3 Jun 2026 00:00:00 +0000

BACKGROUND: SGLT2 (sodium-glucose cotransporter-2) inhibitors (SGLT2i) reduce cardiovascular events in randomized controlled trials of patients with heart failure with reduced ejection fraction (HFrEF), but these trials enrolled outpatient, relatively younger patients (median age 66-67). The effectiveness of SGLT2i in older patients hospitalized for HFrEF in routine US clinical practice is not well studied. METHODS: This study included Medicare beneficiaries aged ≥65 years hospitalized for HFrEF and eligible for SGLT2i in Get with the Guidelines-Heart Failure between July 1, 2021 and June 30, 2023. Primary outcomes were 30-day and 1-year all-cause mortality, all-cause readmission, and HF readmission. Association between SGLT2i and outcomes was assessed with Cox regression and overlap weighting using propensity score estimates. RESULTS: A total of 8847 patients were eligible for but not prescribed SGLT2i at hospital admission (Median age 77; 40% women; median left ventricular EF...

Disseminated multidrug-resistant Salmonella enterica serovar Dublin infection associated with plasmid-borne CMY-2 gene in a patient with travel to a farm in Mexico

Wed, 3 Jun 2026 00:00:00 +0000

Disseminated Salmonella enterica infections represent a severe form of non-typhoidal salmonellosis increasingly complicated by antimicrobial resistance. We describe a case of disseminated non-typhoidal Salmonella in a man presenting with septic shock concerning for a thoracoabdominal endovascular graft infection with involvement of the urinary and respiratory tracts and thoracic skeleton. Hybrid whole-genome sequencing identified Salmonella enterica serovar Dublin and two significant plasmids, an IncC multidrug resistance plasmid harboring blaCMY−2, blaTEM−206, tet(A), and sul2 and an IncFII(S)/IncX1 virulence plasmid containing a spvA-D/spvR operon associated with systemic infection. This case highlights a potential food-borne or zoonotic acquisition of invasive, plasmid-mediated AmpC-producing Salmonella Dublin.

Representation of People Experiencing Homelessness in U.S. Medical Licensing Exam Question Banks

Wed, 3 Jun 2026 00:00:00 +0000

Representation of People Experiencing Homelessness in U.S. Medical Licensing Exam Question Banks

A primer on quality improvement

Wed, 3 Jun 2026 00:00:00 +0000

This Last Page provides a guide that can help trainees and faculty navigate the quality improvement process, introduce them to available resources, and become valuable agents of change.

Medicaid Coverage Restrictions and On-Label Buprenorphine Prescribing for Chronic Pain

Wed, 3 Jun 2026 00:00:00 +0000

Medicaid Coverage Restrictions and On-Label Buprenorphine Prescribing for Chronic Pain

Postpartum Persistent Opioid Use After Opioid Exposure for Childbirth

Wed, 3 Jun 2026 00:00:00 +0000

Objective

To assess the association between opioid exposure in the childbirth period and persistent postpartum opioid use and to evaluate whether there are differential associations based on specific medication exposure.

Methods

Retrospective cohort study that used 2015-2021 Pennsylvania Medicaid claims of women aged 19-50 years with vaginal or cesarean delivery and Medicaid enrollment for at least 10 months during the postpartum year. Primary exposure was filled opioid prescription from 7 days before delivery to 8 weeks after delivery (childbirth period). The main outcome measure was persistent postpartum opioid use , defined as either a diagnosis of opioid use disorder or at least one filled opioid prescription in two or more calendar quarters from 8 weeks to 14 months postpartum. Multivariable logistic regression analyses included demographic information, mental health and behavioral comorbidities, obstetric trauma, and pre-existing pain conditions with subgroup...

Addressing Primary Care Needs in People Living With Sickle Cell Disease : A Narrative Review.

Wed, 3 Jun 2026 00:00:00 +0000

Adults with sickle cell disease (SCD) are living longer due to advances in care but face a growing burden of chronic comorbid conditions that fall within the scope of primary care. However, primary care providers often lack structured guidance because literature on managing these conditions in the context of SCD is limited. This article outlines clinical approaches to hypertension, diabetes, obesity, chronic constipation, reproductive health, cognitive impairments, depression, and anxiety in people living with SCD. The authors highlight relevant epidemiology, screening recommendations, and treatment considerations that differ from those in the general population. Primary care providers play a crucial role in delivering comprehensive and preventive care to people living with SCD. Specific management of common chronic conditions in this population is necessary to reduce morbidity and improve quality of life.

Oxysterol, Oxy210, Inhibits Hepatic Expression of Senescence-Associated and Pro-Fibrotic Genes in Humanized Hyperlipidemic Mice During Development of MASH and in Human Hepatocytes In Vitro

Wed, 3 Jun 2026 00:00:00 +0000

Background: Senescence, a state of permanent cell cycle arrest, is a complex cellular phenomenon closely affiliated with age-related diseases and pathological fibrosis. Cellular senescence is now recognized as a significant contributor to organ fibrosis, largely driven by transforming growth factor beta (TGF-β) signaling, such as in metabolic dysfunction-associated steatohepatitis (MASH), idiopathic pulmonary fibrosis (IPF), chronic kidney disease (CKD), myocardial fibrosis that can lead to heart failure, cystic fibrosis, and fibrosis in pancreatic tumors to name a few. MASH is a progressive inflammatory and fibrotic liver condition that has reached pandemic proportions, now considered the largest non-viral contributor to the need for liver transplantation. Methods: We previously studied Oxy210, an antifibrotic and anti-inflammatory, orally bioavailable, oxysterol-based drug candidate for MASH, using APOE*3-Leiden.CETP mice, a humanized hyperlipidemic mouse model that closely...

Cardiotoxicity prevention trials in the era of contemporary cancer therapies: a systematic review

Tue, 2 Jun 2026 00:00:00 +0000

BackgroundCardiovascular toxicity is an increasingly important limitation of effective contemporary cancer therapies. Yet, the extent to which trials focus on preventing cardiotoxic events in patients receiving contemporary therapies is unknown.MethodsLeveraging PubMed, CENTRAL, clinicaltrials.gov, and publicly available reviews to identify all randomized controlled trials (RCTs) testing interventions for prevention or management of cardiotoxicity in cancer patients through 2024, we assessed the proportion of cardiotoxicity prevention trials that studied contemporary cancer therapies (biologic, targeted, or immune-based therapies). We included RCTs of interventional therapies/strategies against cardiotoxicity during cancer treatment. Data on trial baseline characteristics, design, funding, and reporting were extracted. Regression models were used to define trial and population factors associated with drug selection, reporting bias, and subsequent translation into guidelines.ResultsOverall,...

Sex Differences in Cancer and Cardiotoxicity: Mechanisms, Outcomes, and Clinical Implications Across Solid and Hematological Malignancies

Tue, 2 Jun 2026 00:00:00 +0000

Sex differences influence cancer incidence, treatment response, and susceptibility to cardiovascular toxicity. Males exhibit higher rates and poorer outcomes in most non-sex-specific cancers, while females more frequently experience treatment-related adverse events, including cancer therapy-related cardiac dysfunction. Biological factors such as hormonal status, genetic polymorphisms, immune responses, and pharmacokinetics contribute to these disparities. In cardio-oncology, women—particularly premenopausal or with specific genotypes—may be at increased risk for cardiotoxicity after treatment with anthracyclines, immune checkpoint inhibitors or radiotherapy. Clonal hematopoiesis and certain germline genetic variants such as single nucleotide polymorphisms (e.g., RARG rs2229774, HAS3 rs2232228) are emerging as potential sex-informed biomarkers for predicting cardiotoxicity risk. Despite growing evidence, sex remains insufficiently integrated into clinical trials and guideline development...

Estimating Lung Cancer Screening Eligibility in the Veterans Health Administration Using Patient-Reported Smoking Histories

Fri, 22 May 2026 00:00:00 +0000

Background

The Veterans Health Administration (VHA) serves a population at increased risk for lung cancer, but lung cancer screening (LCS) rates historically have been low. Understanding the size and characteristics of the screening-eligible population can provide insights for improving screening rates. Many screening eligibility recommendations rely on smoking intensity quantified in "pack-years," which historically has been challenging to obtain at scale from the medical record. Recent introduction of structured smoking data as part of VHA LCS efforts now allows for more robust identification and estimation of the screening-eligible population using a large body of patient-reported smoking histories.

Objective

To estimate the magnitude and characteristics of the LCS-eligible population served by the VHA nationwide based on United States Preventive Services Task Force (USPSTF) and American Cancer Society (ACS) recommendations.

Design

We performed a retrospective,...

Assessing mpox knowledge and sexual behaviours within high-risk populations in the Democratic Republic of the Congo.

Fri, 22 May 2026 00:00:00 +0000

Background

Historically, the Democratic Republic of the Congo (DRC) has faced the greatest public health burden from mpox, including more than 70 000 probable cases from 1 January 2024 to 2 February 2025. However, there has been a relative paucity of investigation focused on mpox community engagement in DRC, including assessments of disease knowledge and risk perception.

Methods

Given the ongoing Clade I mpox public health emergency of international concern, and the linkage between sustained human-to-human transmission and dense sexual networks, we sought to investigate mpox knowledge and sexual behaviours among key populations. Between 20 March 2024 and 25 August 2024, we recruited 2794 participants distributed across Kinshasa, Kwango and North Kivu provinces, with a focus in urban centres where mpox risk was considered high.

Results

Most participants were considered other at-risk populations (948; 33.9%), followed by men who have sex with men (MSM, 828;...

Drp1 regulates mitochondrial health and controls skeletal muscle mass through the Erk1/2-Nur77 pathway

Fri, 22 May 2026 00:00:00 +0000

The maintenance of skeletal muscle mass relies on mitochondrial quality control, including balanced dynamics and mitophagy. Dynamin-related protein 1 (Drp1), a central mediator of mitochondrial fission, is essential for these processes, yet its role in muscle mass regulation remains incompletely defined. Here, we show that acute Drp1 deletion in the skeletal muscle increases Parkin-mediated mitochondrial degradation, reduces mitochondrial DNA (mtDNA) content, and leads to severe muscle atrophy. Although dual deletion of Drp1 and Parkin restores mtDNA content, muscle loss persists. Mechanistically, Drp1 loss impairs mitochondrial respiratory chain activity, suppressing extracellular signal-regulated kinase 1/2 (Erk1/2) signaling and down-regulating the nuclear receptor subfamily 4 group A member 1 (Nur77). Pharmacologic β2-adrenergic receptor activation with clenbuterol reactivated Erk1/2, restored Nur77 expression, and rescued muscle atrophy. These findings define a Drp1-Erk1/2-Nur77...

New age of Lupus Nephritis: Updates in guidelines, biomarkers, and therapies.

Thu, 21 May 2026 00:00:00 +0000

Lupus nephritis (LN) is the most common visceral organ manifestation of systemic lupus erythematosus (SLE). It affects approximately 50% of SLE patients, accounting for significant morbidity and mortality especially in ethnic minorities. Building on decades of landmark trials, the field has continued to evolve. The 2024 American College Rheumatology (ACR) Lupus Nephritis guideline represents an important shift toward earlier triple therapy. The guideline also recommends routine proteinuria screening and reaffirms kidney biopsy as the diagnostic gold standard. In parallel, urinary biomarkers are emerging as potential tools to better track infrarenal pathology. Furthermore, the therapeutic pipeline continues to expand with emerging strategies targeting B-cells, cytokine receptors, and co-stimulatory mechanisms. In this article, we review updates from the ACR guideline, the emerging data on urinary biomarkers, and highlight novel targeted therapies in LN.

Sleep Duration and Prostate Cancer Risk in the Southern Community Cohort Study

Thu, 21 May 2026 00:00:00 +0000

INTRODUCTION: The relationship between insufficient sleep and prostate cancer incidence is unclear. Our goal was to investigate the association of sleep duration, restless sleep, and prostate cancer incidence and aggressiveness, and whether race influences any sleep-prostate cancer association. METHODS: The Southern Community Cohort Study (SCCS) recruited study participants from 12 Southeastern states from 2002 to 2009. The cohort included nearly 35,000 males, predominantly African American (AA, 67%). Sleep exposures were measured via a baseline questionnaire at enrollment, which captured weekday and weekend sleep duration, weighted average sleep duration, and restless sleep. We used Cox proportional hazards models and multinomial logistic regression models to estimate associations between sleep and prostate cancer incidence and aggressiveness. RESULTS: During follow-up (median 10.9 years), 1345 men developed prostate cancer. Shorter sleep duration (< 6 h), in comparison to...

PFKM governs metabolic shifts throughout skeletal muscle differentiation

Mon, 18 May 2026 00:00:00 +0000

Metabolism is known to influence cell identity, but the underlying mechanisms remain unclear. Here we reveal spatiotemporal dynamics of phosphofructokinase 1 (PFK1), a key glycolytic enzyme, within the skeletal muscle lineage. The expression of PFKM (the muscle isoform of PFK1) is low in muscle stem cells and increases during differentiation. Mechanistically, Wnt signalling rapidly induces lysosomal degradation of PFKM through a methyl arginine degron motif, which gets selectively methylated by the protein arginine methyltransferase (PRMT1) and delivered to lysosomes through microautophagy. PFKM degradation shifts glucose metabolism from glycolysis to the pentose phosphate pathway. PFKM overexpression increases glycolysis and promotes differentiation into terminally differentiated myofibres. On the other hand, PFKM knockdown blunts differentiation, which can be rescued by supplementation with the downstream glycolytic intermediate 3-phosphoglycerate. In sum, our findings highlight...

Improving Primary Healthcare for Elderly Patients: How Chronic Disease Management Intensity Makes a Difference

Wed, 6 May 2026 00:00:00 +0000

Background: Since 2009, China has implemented a chronic disease management program within primary healthcare (PHC) institutions in response to challenges posed by an aging population. However, the effectiveness of the program has been reported as mixed, likely due to variations in PHC physicians’ efforts and the support they received from the health system and community. This multi-sector engagement was conceptualized as management intensity in this study, and its impact on the program’s effectiveness was evaluated. Methods: This study analyzed 60 885 patients under the chronic disease management program in Yuhuan, Zhejiang province, as of 2023. Management intensity, the primary predictor, was quantified by township-level residual measured based on patients’ length of follow-up after eliminating patient demographics. This approach removed the portion of follow-up length attributable to individual characteristics, leaving the residual serving as a purified exposure variable for...

Dissemination, adaptation, and uptake of patient-facing materials to improve care coordination in primary care

Wed, 6 May 2026 00:00:00 +0000

Objective: We sought to improve patients' experience of care coordination by promoting the uptake of patient-facing tools with evidence of sustained use in Veterans Affairs (VA) primary care clinics. We disseminated tools, adapted and improved tools in response to feedback, and tracked real-world uptake. Methods: We conducted outreach to leadership and frontline providers at local, regional, and national levels. We collaborated with frontline providers and veteran patients using human-centered design approaches to guide tool adaptation. We assessed dissemination and real-world uptake through website analytics and QR code tracking. Results: Tools included paper pamphlets that explained care processes, provided contact information, and answered frequently asked questions. Feedback resulted in use of larger fonts; pictures and colors; less dense text; and QR codes. Discussions led to development of new tools addressing current challenges coordinating care with VA-paid community providers....

p21+TREM2+ senescent macrophages fuel inflammaging and metabolic dysfunction-associated steatotic liver disease

Wed, 6 May 2026 00:00:00 +0000

Cellular senescence drives chronic sterile inflammation during aging via the senescence-associated secretory phenotype, yet the senescent cell types responsible are poorly defined. Macrophages share multiple features of senescence, including inflammatory secretion, yet whether macrophages can adopt a senescent state remains unclear. Here we identify p21⁺Trem2⁺ senescent macrophages as a major source of inflammaging, using primary mouse and human macrophage models of DNA damage and cholesterol-induced senescence characterized by multi-omic profiling. We found that senescent macrophages exhibit a distinctive p21-TREM2 expression profile and senescence-associated secretory phenotype, driven in part by type I interferon signaling via cytosolic mitochondrial DNA. We also found that senescent macrophage accumulation occurs in aging, metabolic dysfunction-associated steatotic liver disease mouse livers, and is enriched in human cirrhotic liver tissue. Finally, senolytic treatment targeting...

An Innovative Approach to Enhanced Care Management for High-Need Pediatric Medicaid Members: Retrospective Cohort Study.

Mon, 27 Apr 2026 00:00:00 +0000

Background

The California Advancing and Innovating Medi-Cal (CalAIM) initiative supports Enhanced Care Management (ECM) for high-need pediatric populations but published evidence of the impact of ECM in pediatric populations is lacking.

Objective

We evaluated a novel multidisciplinary care model (Pair Team) for delivering ECM services, focusing on implementation and early outcomes for children and adolescents enrolled in Californias Medicaid program (Medi-Cal).

Methods

We conducted a retrospective, observational cohort study of Medi-Cal-enrolled children and adolescents who enrolled in Pair Teams program between July 2022 and November 2024. Program engagement, health care engagement, and depressive symptoms were assessed using program data, electronic health records, and prescription data.

Results

The main cohort included 1294 enrollees with 12 months of follow-up data (mean age 8.9 years, 50.3% (651/1294) female, 81.8% (1058/1294) experiencing homelessness)....

Cost-Effectiveness of Medical Therapy for Heart Failure With Mildly Reduced and Preserved Ejection Fraction

Thu, 23 Apr 2026 00:00:00 +0000

BACKGROUND: Three medications are now guideline-recommended treatments for heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), however, the cost-effectiveness of these agents in combination has yet to be established. OBJECTIVES: The purpose of this study was to determine the cost-effectiveness of mineralocorticoid receptor antagonists (MRA), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium glucose co-transporter 2 inhibitors (SGLT2is) in individuals with HFmrEF/HFpEF. METHODS: Using a 3-state Markov model, we performed a cost-effectiveness study using simulated cohorts of 1,000 patients with HFmrEF and HFpEF. Treatment with 1-, 2-, and 3-drug combinations was modeled. Based on a United States health care sector perspective, outcome data was used to calculate incremental cost-effectiveness ratios (ICERs) in 2023 United States dollars based on a 30-year time horizon. RESULTS: Treatment with MRA, MRA+SGLT2i, and MRA+SGLT2i+ARNI therapy resulted...

2025 ACC/AHA Clinical Practice Guidelines Core Principles and Development Process A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Thu, 23 Apr 2026 00:00:00 +0000

2025 ACC/AHA Clinical Practice Guidelines Core Principles and Development Process A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

NATIONAL COSTS FOR CARDIOVASCULAR-RELATED HOSPITALIZATIONS AND INPATIENT PROCEDURES IN THE UNITED STATES, 2016-2021

Thu, 23 Apr 2026 00:00:00 +0000

NATIONAL COSTS FOR CARDIOVASCULAR-RELATED HOSPITALIZATIONS AND INPATIENT PROCEDURES IN THE UNITED STATES, 2016-2021

PREDICTORS FOR PATIENTS UNDERSTANDING REASON FOR HOSPITALIZATION

Thu, 23 Apr 2026 00:00:00 +0000

PREDICTORS FOR PATIENTS UNDERSTANDING REASON FOR HOSPITALIZATION

Perceived Inadequate Neighborhood Food Shopping and Cardiovascular Disease Risk: The Multi-Ethnic Study of Atherosclerosis.

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

BACKGROUND: Individuals with access to healthy food have healthier diets, improved cardiometabolic risk profiles, and decreased cardiovascular disease (CVD). However, previous studies have focused on the neighborhood food environment as distance to and density of food retailers. Our study examines the association between an individual's perceived adequacy of neighborhood food shopping and incident CVD. METHODS: We analyzed data from 6814 participants in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals aged 45 to 84 who were enrolled in the study between 2000 and 2002 and followed longitudinally. Cox proportional hazards models estimated hazard ratios (HRs) for incident CVD, adjusting for sociodemographic, behavioral, and cardiovascular risk factor covariates. RESULTS: Approximately 20% of participants reported inadequate neighborhood food shopping, with higher prevalence among Black and Hispanic participants, lower income, or educational...

Cardiogenic Shock from Chronic Immune Checkpoint Inhibitor Associated Myocarditis Causing Predominant Right Ventricular Failure

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

Cardiogenic Shock from Chronic Immune Checkpoint Inhibitor Associated Myocarditis Causing Predominant Right Ventricular Failure

Exploring Self-Employment and Cardiovascular Disease Risk among Hispanic Women.

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

Objective: Examine the association between self-employment, cardiovascular disease (CVD) risk factors, and health outcomes among Hispanic women. Methods: This observational study was conducted with data from the Behavioral Risk Factor Surveillance System (2003-2022) and a pooled cross-sectional study design to evaluate the association of self-employment with risk factors for CVD. The statistical models were weighted linear probability models that were adjusted for demographics, language, family structure, socioeconomic status, and health insurance. Results: Of the 165,609 working Hispanic women in the study, roughly 13% (20,946) were self-employed. Relative to working for wages or salary, self-employment was associated with a significant mean (95% confidence interval) decline in the predicted probability of reporting diabetes (-1.69% [-2.3%, -1.0%]), hypertension (-3.25% [-4.7%, -1.9%]), obesity (-5.92% [-7.5%, -4.7%]), binge drinking (-1.98% [-3.3%, -0.77%]), and poor health...

“It’s being uncomfortable for who you are, because I think HIV is part of me … ”: psychosocial adaptation and treatment engagement among GBMSM older and younger than 30 years engaged in a coping and disclosure skills intervention in the Eastern Cape, South Africa

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

Despite expanded antiretroviral therapy access since 2006 in South Africa, gay, bisexual and men who have sex with men (GBMSM) living with HIV face challenges navigating status-sharing risks with limited skills. Stigma, isolation and generational disparities further shape adherence and psychosocial needs across age groups. The Speaking Out and Allying Relationships (SOAR) intervention was designed to strengthen coping and disclosure skills with partners and family members, providing an opportunity to examine how younger and older GBMSM navigate HIV treatment, stigma and social networks. Between April and June 2024, participants completed in-depth interviews addressing intervention experiences, treatment motivators, social support and community perceptions. Guided by Social Cognitive Theory, Erikson's psychosocial development theory and the illness identity framework, systematic coding and comparative analysis explored living with HIV across two generations of GBMSM. Twenty-one...

‘I have a child i need to live for’: a qualitative study of parenthood and the TB experience in South Africa

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

Existing research highlights TB's economic and social stigma burdens and impacts behavior in households, but virtually unexplored is the dynamics of TB and parenthood. This qualitative study examines the interplay between TB diagnosis and treatment, and parenting experiences, focusing on the intersections of individual agency, societal expectations, and access to resources. From March 2021 to January 2022, we conducted in-depth interviews with 98 TB patients in Buffalo City, South Africa, including 44 mothers and 54 fathers. Guided by the Network-Individual-Resource (NIR) model, we applied layered coding, memoing, and causal mapping to analyze experiences through the lens of agency and societal expectations. Mothers reported primary caregiving responsibilities, drawing motivation from their children, and relying on multigenerational family support for childcare and treatment-adherence. Children frequently provided emotional and practical care, such as cooking and medication reminders....

Prevention and management of peptide receptor radionuclide therapy-induced hypertensive crisis in a patient with metastatic pheochromocytoma

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

Background/Objective: While peptide receptor radionuclide therapy (PRRT) with lutetium-177 DOTATATE has been increasingly used for metastatic pheochromocytoma management, PRRT-induced hypertensive crisis has been documented in prior reports. A case is reported here to demonstrate the prevention and management of PRRT-induced hypertensive crisis. Case Report A 75-year-old male developed PRRT-induced hypertensive crisis. He had known progressive metastatic pheochromocytoma. Despite scheduled daily alpha and beta blockade, he developed symptomatic hypertensive crisis shortly after completion of lutetium-177 DOTATATE infusion in the first two treatments, which was managed with as-needed oral alpha blockade. Additional alpha blocker was given right before the initiation of lutetium-177 DOTATATE infusion in the third and fourth treatments. Hypertensive crisis still occurred in the third but not in the fourth treatment. He required the 5th treatment due to tumor progression but he developed...

Which Adverse and Positive Childhood Experiences are most Strongly Associated with Young Peoples’ Arrests and Convictions?

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

Adverse childhood experiences (ACEs) are associated with young people’s criminal legal system involvement, but the extent to which distinct types of ACEs and positive childhood experiences (PCEs) differentially relate to arrests and convictions for youth is unknown. We identified childhood exposures that remain independently associated with arrests and convictions by age 26 among a broad set of ACEs and PCEs. We conducted a cross-sectional analysis of data from two components of the nationally representative Panel Study of Income Dynamics. We examined the occurrence and number of arrests and convictions by age 26 and constructed ACE- and PCE-type indicator variables and overall scores. Weighted, covariate-adjusted logistic and negative binomial regression models estimated associations between ACE types and arrests and conviction outcomes, controlling for PCE score. Similarly, we estimated PCE-type outcome associations controlling for ACE score. Finally, we examined sex differences...

Joint Biochemical and Genetic Prostate Cancer Risk Stratification

Fri, 17 Apr 2026 00:00:00 +0000

PURPOSE: Overdiagnosis of prostate cancer (PC) through PSA testing at short intervals remains common. While baseline serum PSA abundance < 1 ng/mL warrants infrequent screening, it is critical to foster advanced diagnostic practices for men with baseline serum PSA ≥ 1 ng/mL, who are at higher risk for clinically significant disease. We investigated whether common germline variants could enhance screening recommendations in men with PSA ≥ 1 ng/mL. MATERIALS AND METHODS: Polygenic hazard scores (PHS) for the risk of PC diagnosis (PHS290) were computed in a diverse, matched, prospective cohort of 310 men with baseline PSA ≥ 1 ng/mL with or without PC. Regression models were used to predict PC clinical risk groups with PHS290, while incorporating clinical covariates and an existing 5-year risk calculator score. RESULTS: PHS290 stratified individuals with PSA ≥ 1 ng/mL into risk groups and identified men with intermediate-risk and high-risk PC. Adding PHS290 to our model for predicting...

Advancing precision health discovery in a genetically diverse health system

Fri, 17 Apr 2026 00:00:00 +0000

Linking genetic data with electronic health records in hospital biobanks promises to advance precision medicine, but limited ancestral diversity constrains discovery and generalizability. We analyzed 93,936 participants from the UCLA ATLAS Community Health Initiative to inform disease prevalence and genetic risk across five continental and 36 fine-scale ancestry groups. We discovered numerous unreported gene-phenotype associations, including FN3K with intestinal disaccharidase deficiency in Europeans and admixed Americans. Polygenic scores (PGS) robustly predicted common diseases, with effects markedly diminished in non-Europeans. Furthermore, we reduced the pronounced European bias in curated clinical variants using computational predictors, uncovering unreported disease-gene associations, including ANKZF1 and peripheral vascular disease in African Americans. Longitudinal data revealed that semaglutide efficacy varies across ancestries, is associated with PGS for type 2 diabetes,...

Activating transcription factor-4 promotes mineralization in vascular smooth muscle cells

Wed, 15 Apr 2026 00:00:00 +0000

Emerging evidence indicates that upregulation of the ER stress-induced pro-osteogenic transcription factor ATF4 plays an important role in vascular calcification, a common complication in patients with aging, diabetes, and chronic kidney disease (CKD). In this study, we demonstrated the pathophysiological role of ATF4 in vascular calcification using global Atf4 KO, smooth muscle cell-specific (SMC-specific) Atf4 KO, and transgenic (TG) mouse models. Reduced expression of ATF4 in global ATF4-haplodeficient and SMC-specific Atf4 KO mice reduced medial and atherosclerotic calcification under normal kidney and CKD conditions. In contrast, increased expression of ATF4 in SMC-specific Atf4 TG mice caused severe medial and atherosclerotic calcification. We further demonstrated that ATF4 transcriptionally upregulates the expression of type III sodium-dependent phosphate cotransporters (PiT1 and PiT2) by interacting with C/EBPβ. These results demonstrate that...

A microbiome quantitative trait locus in SLC39A8 modulates disease severity in synucleinopathy-induced models of Parkinsons disease.

Wed, 15 Apr 2026 00:00:00 +0000

Parkinsons disease (PD) is a progressive neurodegenerative disorder characterized by motor deficits, dopaminergic neuron loss, and α-synuclein (α-syn) aggregation. While rare mutations underlie familial PD, around 85% of cases are idiopathic. Emerging evidence implicates common genetic variants and the gut microbiome in PD risk, but their interaction has not been studied. We previously demonstrated that the PD-protective SLC39A8 variant rs13107325 (human A391T, corresponding to A393T in mouse) is associated with microbial compositional shifts in humans and reshapes the microbiome in SLC39A8 A393T knock-in mice. Here, we test whether this SNP modifies PD phenotypes in two α-synucleinopathy mouse models. In the human α-synuclein overexpression model, A393T carrier mice show reduced motor deficits, consistent with a protective role. However, in the α-synuclein preformed fibril (PFF) injection model, A393T carriers exhibit worsened motor deficits, increased dopaminergic terminal loss,...

Multilineage Potential of Cells From the Artery Wall