Citations

ABSTRACT Aging reshapes the architecture of human skeletal muscle, yet objective tissue‐level markers that capture this process remain limited. We combined large‐scale histology with deep learning to identify reproducible features of muscle aging and to test their biological relevance. We analyzed 974 hematoxylin–eosin whole‐slide images from a population resource using a dual‐attention convolutional neural network and an independent Mask R‐CNN model to quantify nuclear size and density, verified by manual review. The classifier distinguished young from aged muscle with high accuracy (AUC 0.91; accuracy 86.2%), and attention maps consistently highlighted nuclear enlargement and spatial disorganization as salient features. Nuclear diameter increased with age (Spearman's ρ = 0.71, p < 0.0001) across automated and manual measurements. Transcriptomes matched to the same donors showed that samples with larger nuclei were enriched for pathways related to chromatin remodeling, proteostasis, cellular senescence, mitochondrial activity, and telomere regulation, whereas smaller nuclei aligned with anti‐inflammatory and DNA repair programs. External pediatric inflammatory myopathies exhibited nuclear enlargement comparable to aged muscle, suggesting inflammation‐related premature histologic aging. These findings identify nuclear enlargement as a robust, quantifiable feature that integrates structural and molecular signatures of muscle aging. The proposed deep learning–based nuclear morphometry provides a scalable framework for tissue‐level aging biomarkers and suggests a potential “muscle aging clock” applicable to both physiological aging and disease states.

Introduction Individuals with inborn errors of immunity (IEI) are increasingly reaching reproductive age, yet guidance on fertility preservation, genetic counseling, medication adjustments in pregnancy and breastfeeding, monitoring for complications, and multidisciplinary coordination is lacking. This joint effort between two committees of the Clinical Immunology Society (CIS), the Women of the Clinical Immunology Society (WCIS) and the Adult Immune Deficiency Committee (AID) survey aimed to characterize current reproductive care practices for IEI patients. Methods A survey was disseminated to 809 CIS members. The response rate was 6.43% (52 respondents). The 24-item questionnaire addressed management of pregnancy in IEI, medications adjustment, participation in hematopoietic stem cell transplant (HSCT) care and fertility preservation, and maternal/neonatal outcomes. Results Because survey items were optional, the number of respondents varies by question. Forty-two participants completed core items: 64% (27/42) allergists/immunologists, 71% (30/42) practicing at academic centers, and 48% (20/42) with &gt;50% immunology-focused practices. Most respondents (78%, 41/52) currently or previously cared for pregnant/planning IEI patients. Preconception counseling was common (90%, 37/41), yet only 2% (1/41) have access to a formal reproductive multidisciplinary team. Among clinicians involved in HSCT care, 45% (13/29) referred patients for fertility preservation. More than half, 52% (22/42), observed reduced fertility in IEI patients, and 56% (20/36) observed adverse maternal outcomes. Medication management varied: 61% (24/39) discontinued known teratogenic medications, and 64% (25/39) adjusted dosing during pregnancy. Regarding immunoglobulin replacement therapy, 79% adjusted dosing based on IgG levels and 42% increased dosing by trimester. Conclusions This CIS survey reveals practice variability and notable gaps in reproductive health support for individuals with IEIs. Due to the relatively low response rate, generalizability across providers and practice settings is challenging. However, the results of this survey suggest that although most clinicians provide preconception counseling and manage IgG and immunomodulatory therapy during pregnancy, formal multidisciplinary structures are rare. High rates of reported fertility concerns and maternal complications underscore the need for enhanced collaboration with obstetrics/gynecology and the development of structured, evidence-based, multidisciplinary guidelines for reproductive care in IEI. Tabular data are included as downloadable supplement files.

Introduction Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) used to treat type 2 diabetes mellitus (T2D), has potential associations with higher rates of diabetic retinopathy (DR) complications including proliferative DR (PDR) and diabetic macular edema (DME). The purpose of this study was to determine whether an association exists between semaglutide and PDR and treatment-requiring DR/DME. Research design and methods This was a retrospective cohort study of 14 databases (six administrative claims and eight electronic health records) in the Observational Health Data Sciences and Informatics Evidence Network. Adults with T2D on semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from 1 December 2017 to 31 December 2023 were included. The association between semaglutide and PDR or treatment-requiring DR/DME was assessed using an active-comparator cohort design comparing new users of semaglutide as second-line T2D treatment to those on other GLP-1RAs and non-GLP-1RAs. Propensity score-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs). Network-wide HR estimates were generated using a random-effects meta-analysis. Results The study included 810 390 new semaglutide users for T2D. PDR risk for semaglutide was similar to dulaglutide (HR 0.81, 95% CI 0.42 to 1.54, p=0.51), empagliflozin (HR 0.83, 95% CI 0.53 to 1.30, p=0.41) and sitagliptin (HR 0.83, 95% CI 0.45 to 1.55, p=0.57) but was lower than glipizide (HR 0.59, 95% CI 0.39 to 0.88, p=0.01). The risk for treatment-requiring DR/DME for semaglutide was similar to empagliflozin (HR 0.66, 95% CI 0.43 to 1.02, p=0.06) but lower than dulaglutide (HR 0.53, 95% CI 0.31 to 0.91, p=0.02), sitagliptin (HR 0.46, 95% CI 0.26 to 0.81, p=0.008) and glipizide (HR 0.55, 95% CI 0.33 to 0.91, p=0.02). Conclusions and relevance We did not identify increased risk for either PDR or treatment-requiring DR/DME comparing semaglutide with other GLP-1RAs or non-GLP-1RAs. Patients with T2D should still undergo close eye care follow-up, particularly when initiating new antihyperglycemic medications.

ABSTRACT The deep inferior epigastric perforator (DIEP) flap remains the preferred flap option for autologous breast reconstruction following mastectomy. This case report presents the novel use of the cephalic vein (CV) as an interposition graft to alleviate venous congestion in a patient undergoing DIEP flap reconstruction. A 42‐year‐old woman experienced venous congestion following her initial autologous reconstruction, attributed to thrombus formation from kinking of the vascular pedicle. Despite initial attempts to resolve the congestion, the condition persisted. Since the flap was based on a single perforator, we decided to attempt a CV turndown. The CV was noted to be attenuated and not feasible for use in turndown; therefore, venous salvage was completed by using the CV as an interposition graft to bypass the affected flap vena comitans. The procedure successfully restored venous flow, allowing for flap salvage and subsequent healing. This case underscores the potential of CV as an interposition graft in autologous breast reconstruction, particularly when traditional CV turndown is not possible due to vessel attenuation.

Abstract Introduction The deep inferior epigastric artery perforator (DIEP) flap is widely used for breast reconstruction, with donor site complications influenced by various factors. This study assessed the impact of incisional negative pressure wound therapy (iNPWT) on donor site healing compared to standard dressings (SD). Methods A retrospective review of DIEP flap reconstructions performed between 2017 and 2022 was conducted. Donor sites were managed with either SD or iNPWT (PREVENA PLUS™, 3M). Outcomes assessed included donor-site complications, drain duration, length of stay, and readmissions. Predictors of complications were analyzed using univariable and multivariable logistic regression. Results A total of 320 patients were included; iNPWT was applied in 165 (51.6%) and SD in 155 (48.4%). Baseline demographics and comorbidities were comparable between groups. Complication rates within 30 days were 23.0% for iNPWT and 27.1% for SD (p = 0.401); iNPWT use was associated with significantly earlier drain removal (median 13 vs. 17 days, p = 0.004). Multivariable analysis identified smoking as an independent predictor of donor-site complications (aOR 1.74, 95% CI 1.05–2.86, p = 0.030); iNPWT was not significantly associated with reduced complication rates (OR 1.00, 95% CI 0.64–1.58, p = 0.977). Conclusions Smoking was confirmed as a significant predictor of donor-site morbidity. While iNPWT did not lower overall complication rates, it modestly reduced drain duration. Further prospective studies are warranted to define its role in DIEP flap reconstruction. Level of Evidence Level III, therapeutic study

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease provide strategies for the prevention, diagnosis, and treatment of venous thromboembolism (VTE) in adult patients with cancer. VTE is a common and life-threatening condition in patients with cancer, and its management often requires multidisciplinary efforts. The NCCN panel is comprised of specialists spanning various fields, including cardiology, hematology, medical oncology, internal medicine, interventional radiology, and pharmacology. The content featured in this issue specifically addresses the evaluation and recommended treatment options outlined in the NCCN Guidelines for the diverse subtypes of cancer-associated VTE.

AbstractBackgroundRecent CMS billing changes have raised concerns about insurance coverage for deep inferior epigastric perforator (DIEP) flap breast reconstruction. This study compared the costs and utilization of transverse rectus abdominis myocutaneous (TRAM), DIEP, and latissimus dorsi (LD) flaps in breast reconstruction.MethodThe study utilized the National Inpatient Sample database to identify female patients who underwent DIEP, TRAM, and LD flap procedures from 2016 to 2019. Key data such as patient demographics, length of stay, complications, and costs (adjusted to 2021 USD) were analyzed, focusing on differences across the flap types.ResultsA total of 17,770 weighted patient encounters were identified, with the median age being 51. The majority underwent DIEP flaps (73.5%), followed by TRAM (14.2%) and LD (12.1%) flaps. The findings revealed that DIEP and TRAM flaps had a similar length of stay (LOS), while LD flaps typically had a shorter LOS. The total hospital charges to costs using cost‐to‐charge ratio were also comparable between DIEP and TRAM flaps, whereas LD flaps were significantly less expensive. Factors such as income quartile, primary payer of hospitalization, and geographic region significantly influenced flap choice.ConclusionThe study's results appear to contradict the prevailing notion that TRAM flaps are more cost‐effective than DIEP flaps. The total hospital charges to costs using cost‐to‐charge ratio and hospital stays associated with TRAM and DIEP flaps were found to be similar. These findings suggest that changes in the insurance landscape, which may limit the use of DIEP flaps, could undermine patient autonomy while not necessarily reducing healthcare costs. Such policy shifts could favor less costly options like the LD flap, potentially altering the landscape of microvascular breast reconstruction.