Citations

This Viewpoint reflects on a decay in surgical skill related to falling laparoscopic case volumes and describes strategies to preserve laparoscopic proficiency amid the rapid adoption of robotic platforms.

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

ABSTRACT Background Mycobacterium genavense is a rare opportunistic non-tuberculous mycobacterium primarily reported in advanced human immunodeficiency virus infection. Case Summary A 70-year-old woman with systemic lupus erythematosus developed progressive abdominal pain, weight loss, and mesenteric lymphadenitis repeatedly responsive to corticosteroids. Endoscopic biopsies revealed abundant acid-fast bacilli, and molecular testing confirmed the presence of M. genavense . Treatment with azithromycin, ethambutol, and rifabutin led to gradual recovery. Conclusion Steroid-responsive mesenteric inflammation in immunocompromised patients should prompt evaluation for infection, including mycobacteria and other culture-negative microorganisms using molecular diagnostics. This case report highlights the importance of plasma microbial cell-free DNA assays in the identification of fastidious organisms, like M. genavense , and, in some cases, serial testing may be useful to monitor treatment response.

ABSTRACT Surgery after response to first‐line chemoimmunotherapy may offer a potential curative option for patients with locally advanced biliary tract cancer (BTC) initially considered unresectable. However, robust real‐world evidence in this setting remains limited. We retrospectively analyzed patients with locally advanced BTC treated with first‐line cisplatin, gemcitabine, and durvalumab (CGD) across 55 centers in 12 countries. Endpoints included overall survival (OS), progression‐free survival (PFS), disease‐free survival (DFS) among resected patients, objective response rate (ORR), and the prognostic impact of surgery. A multivariable logistic regression model was developed to predict surgical conversion using baseline clinical and laboratory variables. Among 1358 screened patients, 219 had locally advanced disease and were included in the analysis. Median follow‐up was 14.5 months. ORR was 34.6%, with median PFS and OS of 10.0 and 20.7 months, respectively. Twenty‐four patients (10.9%) underwent surgical resection after systemic therapy. Median OS was 22.5 months in resected patients versus 19.9 months in those who did not undergo surgery. Median DFS after resection was 15.8 months. Pathological lymph node involvement was independently associated with shorter DFS. Larger baseline tumor size correlated with higher odds of radiological response but not with OS. An exploratory elastic‐net model retained four baseline variables and showed moderate discriminative ability for surgical conversion, with an apparent AUC of 0.72 and an optimism‐corrected AUC of 0.65. First‐line CGD enabled secondary resection in approximately 11% of patients with locally advanced BTC. A simple baseline model may support patient selection for conversion surgery, although prospective validation is needed.

Bachmann's bundle (BB) pacing is an emerging physiological atrial pacing strategy designed to preserve interatrial conduction and coordinated atrial activation. Conventional right atrial appendage pacing may produce non-physiological activation, contributing to atrial dyssynchrony, impaired left atrial function, and increased risk of atrial fibrillation. Because BB is the predominant pathway for right-to-left atrial conduction, targeted BB pacing can shorten the P-wave duration and improve atrial synchrony. Recent fluoroscopic, electrogram-guided, and P-wave morphology criteria have improved confirmation of BB capture. Available studies suggest that BB pacing is feasible and generally safe, with potential benefits in reducing the burden of atrial arrhythmias. However, the long-term clinical outcomes remain uncertain. Larger prospective studies are needed to standardize BB capture criteria, define optimal patient selection, and assess long-term outcomes.

ABSTRACT Background and Objectives Non‐rhabdomyosarcoma soft tissue sarcomas (NRSTS) account for less than 4% of pediatric cancers. Treatment and outcomes have been described in adults, but pediatric data are lacking. The purpose of this study is to review our institution's outcomes of extremity NRSTS in pediatric patients. Methods Ninety‐eight (56 male: 42 female) pediatric patients with NRSTS of the extremity at our institution were reviewed. Mean age at diagnosis was 11 ± 5 years, and mean follow‐up was 12 ± 10 years. The most common diagnosis was synovial sarcoma (27%), and 60% were high‐grade. Results Treatment included surgical resection in all patients, with 33% receiving radiation and 37% receiving systemic therapy. 20‐year local recurrence‐ (LRFS) and metastatic disease‐free survival (MDFS) were 91% and 91%, respectively, with 92% disease specific survival (DSS). High grade tumors were associated with lower LRFS ( p = 0.02) and DSS ( p = 0.03). Tumor size < 5 cm demonstrated improved MDFS ( p = 0.03), and stage 3 tumors showed worse MDFS ( p < 0.01). Conclusions Treatment of pediatric NRSTS was variable, with large, deep, high‐grade tumors more likely to receive neoadjuvant and adjuvant treatments. Multidisciplinary treatment was associated with high rates of local control and durable survival. This study provides an extended follow‐up of pediatric patients to identify late complications.

Stem cell-derived β (SC-β) cells are a promising therapy for type 1 diabetes (T1D), but their long-term efficacy is limited by immune-mediated graft rejection. Platelet-derived exosome product (PEP) has emerged as a novel immunomodulatory agent, although its effect on SC-β cell xenograft rejection remains unclear. Here, we evaluated PEP in stimulated human peripheral blood mononuclear cells (PBMCs) and in an immunocompetent mouse model of SC-β cell transplantation under the kidney capsule. Immune-related gene expression was assessed by quantitative PCR, immune cell infiltration by immunofluorescence, and graft function by circulating human insulin. In vitro, PEP reduced NK-cell-associated gene expression, including NK1.1, EOMES, and KLRK1, and increased IL-10 expression. In vivo, untreated SC-β cell xenografts showed progressive immune infiltration and loss of detectable human insulin by day 14, whereas PEP-treated grafts retained detectable insulin through day 14 across co-transplantation, pretreatment, and systemic administration strategies. PEP co-transplantation delayed, but did not prevent, xenograft rejection, with graft loss observed by day 21. This delay was associated with reduced NK1.1+ cell infiltration and lower expression of selected inflammatory and rejection-associated markers, including NK1.1, Nos2, and Nlrp3. These findings suggest that PEP modulates graft-associated immune responses and may serve as an adjunct immunomodulatory strategy for stem cell-based therapies for type 1 diabetes. Further studies are needed to evaluate sustained graft durability, safety, and translational efficacy.

Abstract Objectives Embedded pragmatic clinical trials (ePCTs) are conducted as part of routine clinical care and therefore use data collected from real-world data sources, such as electronic health record systems and administrative claims. A common approach for using these types of data across all phases of trial conduct is to create a computable phenotype (an explicitly defined data query data, including specified data types, data codes, and logical parameters) to capture patients with a clinical condition, exposure, symptom, characteristic, treatment, or outcome of interest. Materials and Methods The Electronic Health Record (EHR) Core Working Group of the NIH Pragmatic Trials Collaboratory captured the experiences of investigators in developing, adapting, and applying computable phenotype definitions in their studies. Results Four case studies describe different approaches to developing and using computable phenotypes in pragmatic trials. Discussion We recommend: (1) developing computable phenotypes as part of a team with multiple areas of expertise; (2) appropriate validation; (3) dissemination of salient details regarding phenotype creation; and (4) capturing and reporting any modifications made to phenotypes during the conduct of the trial. Conclusion A range of issues and decisions influence how computable phenotypes are developed and used in pragmatic clinical trials. Multidisciplinary teams that understand the context of the data, including the reason the data are collected and potential sources of bias, are best suited for the development and validation of phenotypes for ePCTs.

ABSTRACT Background Data on the global prevalence of alarm features in the general population and among individuals with disorders of gut–brain interaction (DGBI) are limited. Methods We analysed data from the Rome Foundation Global Epidemiology Study to estimate the prevalence of fourteen self‐reported alarm features in the global population and among individuals with Rome IV defined DGBI, including 54,127 participants from 26 countries. Differences between participants with and without DGBI were evaluated in a sample excluding those with self‐reported organic gastrointestinal disease, using univariable logistic regression. Analyses were stratified by age (< 50 vs. ≥ 50 years). Results Alarm features were reported by 63.1% of participants aged < 50 years and 51.8% of those aged ≥ 50 years. Individual self‐reported alarm features ranged from 0.9% to 18.3% in younger participants to 0.3%–13.3% in older participants. Haematemesis was the least frequently reported feature, while a major change in bowel movements was the most frequent in both age groups. Self‐reported alarm features were more frequent among participants with than without DGBI (< 50 years: 75.3% vs. 50.7%; OR 3.0 [2.8–3.1]; ≥ 50 years: 67.5% vs. 38.8%; OR 3.3 [3.1–3.5]). Participants with DGBI were also more likely to report multiple alarm features. Discussion Self‐reported alarm features are common in the general population and more prevalent among individuals with DGBI. These findings underscore the importance of interpreting alarm features within a broader clinical context rather than in isolation. Further studies are needed to clarify the diagnostic utility of alarm features in unselected populations, particularly among individuals with DGBI.