Citations

Background: Stromal hyaluronic acid (HA) poses a physical barrier and protects tumor cells from immune surveillance. Stroma targeting with pegylated human recombinant PH20 hyaluronidase (PEGPH20) demonstrated improved infiltration of cytotoxic T-lymphocytes and delivery of chemotherapy and PD1/PD-L1 antibodies in tumor models. This multicenter phase II study of PEGPH20 plus pembrolizumab evaluated the efficacy, safety and immune and stromal biomarkers in patients with HA-high refractory metastatic pancreatic ductal adenocarcinoma (mPDA). Patients and Methods: Patients were treated with PEGPH20 3 µg/kg IV weekly and pembrolizumab 200 mg IV in 3-week cycles. Tumor and blood samples were collected at baseline and on-study for biomarker analyses. Results: Between May and November 2019, 38 patients were screened and 8 treated, with median age 68 years (range 60–73) and median two (range 1–4) prior therapies. The study was closed to accrual early by pharmaceutical sponsor. Treatment was well tolerated, with expected grade 1/2 musculoskeletal toxicities. Best response was stable disease in 2 of 7 evaluable patients (29%). Median overall and progression-free survival were 7.2 months (95% CI 1.2–11.8) and 1.5 months (95% CI 0.9–4.4), respectively. Prolonged survival (range 10.2–27.6 months) occurred in patients treated with subsequent chemotherapy. Higher baseline tumor T cell receptor (TCR) clonality correlated with longer survival. Conclusions: Pembrolizumab with PEGPH20 was safe but did not have significant efficacy in refractory HA-high metastatic PDA.

Abstract Background Emerging evidence suggests that premature ventricular contractions (PVCs) may influence atrial electrophysiology and remodeling, potentially leading to higher rates of atrial fibrillation (AF) recurrence. However, existing data is limited to small-scale studies. Therefore, we conducted a retrospective study to evaluate the potential association between PVCs and AF ablation outcomes, which may suggest the need for more aggressive management of ventricular ectopy in this population. Objective This study aims to assess the 5-year outcomes of catheter ablation for AF in patients with and without a diagnosis of PVCs. Methods Using the TriNetX Analytics Research Network, we included patients aged ≥ 18 years who underwent AF catheter between January 1, 2014, and January 1, 2020. Patients were further categorized into two groups based on the presence of a diagnosis of PVCs. Propensity score matching (PSM) was performed using patient demographics, left ventricular ejection fraction (LVEF), cardiac comorbidities, and medications. Study outcomes included all-cause mortality & hospitalization, acute heart failure (HF), and rhythm control interventions during a 5-year follow-up. Results A total of 15,987 patients with PVCs and 40,605 patients without PVCs were identified. After PSM, 15,152 patients from each group were included for further analysis. Compared to control group, patients with PVCs had significantly higher odds of all-cause mortality (odds ratio [OR], 1.138; 95% confidence interval [CI], 1.034–1.253), all-cause hospitalization (OR, 1.300; 95% CI, 1.243–1.360), acute heart failure (HF) (OR, 1.223; 95% CI, 1.162–1.287), and cardiogenic shock (OR, 2.059; 95% CI, 1.751–2.420) following catheter ablation for AF at 5-year follow-up. Additionally, higher odds of AF requiring cardioversion (OR, 1.135; 95% CI, 1.074–1.199) or repeated ablation (OR, 1.164; 95% CI, 1.085–1.249) were observed in the PVCs group. Conclusion Premature ventricular contractions were associated with poorer clinical outcomes and a higher odds of requiring additional rhythm control intervention following catheter ablation for AF. These findings suggest that PVCs may be a marker for worse outcomes after AF ablation.

Abstract Purpose This study synthesizes and characterizes pregnancy outcomes and complications among US female physician trainees. Method In this systematic review, the PubMed, Embase, Scopus, Web of Science, and Cochrane databases were searched in May 2024 and May 2025 for peer-reviewed, English-language articles published from January 2000 to May 2025 reporting pregnancy outcomes in US female residents or fellows. Medical Subject Headings and keywords for pregnancy complications, pregnancy outcomes, and women or female physicians were used. Cross-sectional, retrospective, prospective, and case-control studies were included. Opinion articles, editorials, systematic or scoping reviews, and other non–peer-reviewed articles were excluded. Abstracts and full-text articles were screened by 3 investigators. Extracted data were documented in standardized forms. Risk of bias was assessed regarding study population and outcome reporting and summarized using standardized quality assessment tools. Results Of 792 titles and abstracts screened, 10 articles involving 4,891 trainees were included. Eight of these 10 studies described pregnancy outcomes specifically in surgical trainees; all were cross-sectional surveys. The numbers of trainees experiencing pregnancy complications ranged from 38.9% to 56.0%. The most frequently described complication was preterm labor (9 of 10 studies), affecting 5.3% to 22.9% of surveyed trainees. The most cited fetal complication was miscarriage (5 of 10 studies), affecting 20.0% to 28.0% of trainee pregnancies. Other commonly reported complications included preeclampsia or eclampsia, hyperemesis gravidarum, and gestational hypertension. Conclusions Although pregnancy complications appear to be common among female physician trainees, current data on obstetric outcomes in this population remain limited. Most studies focus specifically on surgical trainees and rely on self-reported data, limiting generalizability. Residency programs may consider findings from this review to enhance support for childbearing trainees, although prospective studies are needed to better discern the impact of medical training on maternal and fetal outcomes.

Abstract Background Long-acting injectable buprenorphine (LAI-BUP) is safe and effective, however is dramatically underutilized in comparison to oral formulations. Little is known regarding how buprenorphine prescribers view LAI-BUP, and which medication attributes they prioritize when selecting treatment for opioid use disorder (OUD). Methods A secondary analysis of a national, cross-sectional online survey of U.S. physicians who prescribe buprenorphine for OUD was conducted. Respondents reported OUD caseload, LAI-BUP use, and the importance of medication attributes relevant to treatment selection (e.g., efficacy, safety, ease of administration, ease of prescribing, and administrative requirements). Providers were categorized as no LAI-BUP use or, among LAI-BUP prescribers, Low vs High use based on a median split. Group comparisons used chi-square (or Fisher’s exact) tests for categorical variables and Jonckheere–Terpstra tests for ordinal responses. Results Among 125 respondents, 39 (31.2%) reported no patients receiving LAI-BUP. The remaining 86 (68.8%) were LAI-BUP prescribers, split evenly into Low and High (n’s=43; 34.4%) groups using a median cut of 23.2%. LAI-BUP use did not differ meaningfully by specialty, region, or practice setting. Greater LAI-BUP use was reported by providers with larger OUD panels. Ratings of key medication attributes were uniformly high. Conclusions LAI-BUP remains underused, with uptake highest among clinicians managing larger OUD caseloads. Measured attitudes toward medication attributes did not explain these differences. Future work should assess clinic workflow, staffing, reimbursement, and REMS burden, testing targeted implementation strategies using mixed-methods trials. Identifying what shifts clinicians from no use to low and high use may guide scalable implementation interventions.

ABSTRACT Delayed onset muscle soreness (DOMS) is a musculoskeletal condition that typically follows unaccustomed exercise or muscle overload, most common after loaded eccentric contractions. This soreness manifests within 24–48 hours postexercise and can last several days, impacting muscle performance and recovery. Increased levels of anxiety may prolong the perception of soreness and discomfort. Evidence suggests that recovery times for DOMS vary because of multiple factors, which include psychological influences such as anxiety. This manuscript highlights the interplay between psychological states and the DOMS recovery sequelae. Although further studies are needed to fully understand the mechanisms by which anxiety influences DOMS and to confirm the efficacy of anxiety-reducing treatments, a deeper understanding of this relationship could offer strength and conditioning professionals new pathways for optimizing recovery strategies in individuals experiencing DOMS.

Abstract Metabolic disorders such as obesity, type 2 diabetes, and dyslipidaemia are major drivers of cardiovascular risk and have reached epidemic levels in Western populations. Recent advances in clinical research have uncovered unexpected and often beneficial effects of pharmacological classes of metabolic drugs on cardiovascular outcomes, revealing complex interactions between metabolism and cardiac pathology. Despite their clinical efficacy, the molecular and cellular mechanisms through which many of these agents act remain only partially understood. This gap in knowledge underscores the urgent need for fundamental research that not only dissects the biology of metabolic disorders and cardiovascular disease but also reveals the mechanistic basis of existing and emerging therapies, thereby enabling rational therapeutic development. This scientific statement, developed by researchers from the European Society of Cardiology (ESC) Council on Basic Cardiovascular Science and several ESC Working Groups, provides a state-of-the-art overview of the emerging molecular and cellular pathways linking metabolic abnormalities with vascular and cardiac disease. By illuminating these critical connections and unresolved questions, this article aims to catalyse innovation in the prevention and management of cardiovascular disease in the context of metabolic dysfunction and to suggest new directions for future research.