Citations

BACKGROUND: Subtotal cholecystectomy is increasingly recommended as a bailout strategy for the difficult gallbladder, yet its long-term durability and the risk profile of subsequent completion cholecystectomy remain incompletely defined. STUDY DESIGN: We performed a population-based retrospective cohort study of adults undergoing laparoscopic or open subtotal cholecystectomy for acute cholecystitis from 2012 to 2021 using Healthcare Cost and Utilization Project state databases from New York and Florida. The primary endpoint was remnant cholecystitis, defined as a postoperative emergency, inpatient, or outpatient diagnosis of cholecystitis or need for subsequent cholecystectomy. Kaplan–Meier analysis estimated cumulative incidence. Secondary outcomes included completion cholecystectomy and bile duct injury requiring surgical repair. RESULTS: Among 2,682 patients (98.7% laparoscopic), the cumulative incidence of remnant cholecystitis was 13.3% during a median follow-up of 2 years (interquartile range [IQR] 0.7 to 4.1). The median time to developing remnant cholecystitis was 28 days (IQR 13 to 91), with 79.7% occurring within 6 months. Only 70 patients (2.6%) underwent completion cholecystectomy at a median of 103 days (IQR 43 to 202). Completion cholecystectomy was performed via open surgery in 47.1% of patients and was associated with a 7.1% bile duct injury rate and median length of stay of 3 days (IQR 1 to 7), compared with a 0.9% bile duct injury rate for subtotal cholecystectomy overall. CONCLUSIONS: Although remnant cholecystitis occurred in 13.3% of patients after subtotal cholecystectomy, few required completion cholecystectomy. When necessary, completion cholecystectomy was frequently open and associated with a substantially higher bile duct injury rate, supporting referral to experienced hepatobiliary centers for reoperation.

Biological heterogeneity among different breast cancer (BC) subtypes results in markedly varying clinical outcomes. Identification and analysis of key gene biomarkers that are differentially regulated during radiation therapy (RT) may pose multiple clinical challenges for BC treatment. The purpose of the study is to identify and analyze the expression of key gene biomarkers and their networks that are differentially regulated after hypofractionated RT. Patients with BC (cT0-T2, N0, M0) were treated with hypofractionated whole breast RT 25 Gy in five fractions, 4 to 8 weeks before breast conservation surgery (BCS). Biopsy (pre-RT; n = 5) and surgical (post-RT; n = 14 or 15) BC tumor samples were used for NanoString targeted sequencing. We identified 165 and 244 differentially expressed genes (DEGs; p < 0.05) in BC tumor samples from BC patients post-RT using the nCounter BC360 and IO360 panels, respectively. Gene networks and pathway analysis revealed that RT increases the gene signature of tumor inflammation (TIS), cytotoxicity, and apoptosis, while downregulating the gene signatures of tumor cell proliferation, differentiation, and cell adhesion, and increases the claudin-low gene score. RT-induced mammary stemness and enhanced infiltration of stroma, mast, and macrophage cells in the BC tumor microenvironment (TME). Further, the nCounter IO360 (immuno-oncology) panel analysis validated the findings of BC360 and demonstrated that RT increased the myeloid inflammation signature and chemokine expression, modulated B, T, NK, and DC cell activities, and enhanced residual cancer burden (RCB) in BC tumors, thus creating an immunosuppressive TME. Collectively, RT sensitized BC tumors by increasing the gene signature of TIS, cytotoxicity, apoptosis, and mammary stemness. RT facilitated an immunosuppressive environment and increased RCB, suggesting that the therapeutic potential of RT is highly individualized for each patient based on their unique tumor biology, genetic makeup, and TME.

The regulation of the cardiomyocyte cell cycle is central to understanding heart regeneration. In adult mammals, cardiomyocytes withdraw from the cell cycle, limiting their ability to proliferate and repair heart tissue after injury. This process is controlled by intrinsic genetic programs and extrinsic signals, which together restrict the regenerative response in mature hearts. Understanding the mechanisms that regulate cardiomyocyte cell cycle activity is therefore critical for advancing cardiac regenerative medicine. In this review, we provide a comparative and integrated overview of cardiomyocyte cell cycle regulation in lower vertebrates and mammals, and discuss the major intrinsic factors that govern this process, including cyclin/CDK pathways, transcription factors and co-activators, oxygen and metabolic regulation, and epigenetic mechanisms. We also review the influence of hormones and growth factors, as well as the supportive roles of nonmyocyte populations in heart regeneration. By integrating findings across species, developmental stages, and regulatory levels, these findings highlight the complex regulatory network controlling cardiomyocyte proliferation and provide insight into potential therapeutic strategies for stimulating cardiac repair in the adult mammalian heart.

Abstract Introduction Detecting and estimating blood volume loss are important for the diagnosis and management of life-threatening hemorrhage. There is a direct relationship between percent blood volume loss (BVL%) and falling in stroke volume (SV); furthermore, there is a direct relationship between diminishing SV and the corrected flow time of the carotid artery (ccFT). Therefore, we hypothesized that change in ccFT (ccFTΔ) would directly relate with BVL% in a phlebotomy paradigm. Materials and Methods A prospective, convenience sample of healthy volunteers was studied. Volunteers underwent blood donation protocol in a physiology lab. A wireless, wearable Doppler ultrasound system monitored ccFT during blood donation. Traditional vital signs were also measured throughout. The relationship between traditional vital signs as well as ccFTΔ were compared to BVL% using 2 mixed linear regression models. Results Data from 20 subjects and blood donations comprising 46,123 cardiac cycles are included. On average 413.5 ± 39 mL of blood were drawn representing 8.6 ± 1.6% BVL%. There was a significant and strong linear relationship between BVL% and ccFTΔ during blood draw with the regression slope demonstrating that for every 1 ms reduction in ccFT there was a 0.4% reduction in blood volume. Conclusions In healthy subjects and when blood loss is the sole mechanism for falling SV, we estimate that for every 1 ms reduction in ccFT, there is an approximate 0.4 BVL%. Validation of these results in patients with traumatic hemorrhage is underway.

Abstract Objective Evaluate how RAG architecture, including corpus structure, retrieval strategy, and pipeline complexity, affects LLM-based medical problem solving and knowledge retrieval in sleep medicine. Materials and Methods We benchmarked four open-source LLMs (Llama-3-8B, Llama -3 -70B, Qwen 2.5-14B, and Qwen 2.5-235B) using a knowledge base of five sleep medicine textbooks. We compared performance across three dimensions: corpus structure (raw text vs table-of-contents aligned.), retrieval strategy (dense embedding vs hybrid sparse-dense), and pipeline complexity (baseline vs augmented). Evaluation metrics included board-style multiple choice question (MCQ) accuracy and clinical case vignette diagnostic ranking. Results RAG improved MCQ accuracy for all models. Llama-8B saw the largest gain of 10.6% (61.8% to 72.4%), while Qwen-235B reached 87.3%. In clinical cases, Llama-8B accuracy dropped by 7.1% when using raw text and dense retrieval due to context noise. This was corrected by using structured hybrid configurations. Hybrid retrieval consistently outperformed dense-only methods. Overall, structured corpora improved primary diagnosis accuracy by 6.1% on average, with Qwen-235B reaching a peak 10.2% increase. Discussion RAG effectiveness depends on the balance between model size and data structure. Large models handle uncurated text well, but smaller models are easily distracted by irrelevant data. Hybrid retrieval is necessary to maintain precision with specialized medical terms. A structured corpus paired with a baseline hybrid pipeline offers the best stability and speed for clinical use. Conclusion Rigorous data curation and hybrid retrieval are as essential as model scale for deploying safe, guideline-compliant AI in sleep medicine.

Background/Objectives: Radiofrequency (RF) wire energy can be used for tissue ablation across many conditions. Adjusting RF generator parameters allows RF energy to puncture tissue with minimal adjacent damage. When RF energy is applied to tissue, however, microbubbles are produced, obstructing intravascular ultrasound (IVUS). Mitigation of RF-generated microbubbles has been studied for ablation but not for puncture. Methods: This paper describes an in vitro bench study using ex vivo bovine live tissue. A model was created with bovine liver tissue and an IVUS catheter submerged in a saline bath. Tissue was punctured with an RF guidewire to recreate microbubbles. Following the puncture, various methods were applied: altering the mechanical index of the IVUS, applying a VF10-5 Linear probe (Siemens), and applying a L12-3 Linear probe (Philips). Regions of interest (ROIs) were selected to track pixel brightness as a proxy for microbubbles. Results: The control increased ROI brightness by 1.5%. Altering the mechanical index of IVUS reduced ROI brightness by 1.2%. VF10-5 probe application increased ROI brightness by 1.2%. L12-3 probe application reduced ROI brightness by 33.0% (p = 0.046, n = 3, one-sample t-test). Brightness reduction was most pronounced at the site of initial RF wire puncture, where microbubbles accumulated. Tip visualization improved, allowing for more precise wire trajectory adjustments. Conclusions: External US with an L12-3 probe was able to dissipate microbubbles effectively to improve IVUS guidance following RF wire puncture in an in vitro exploratory bench model.

Background/Objectives: Non-typhoidal Salmonella (NTS) species are well-recognized causes of invasive infection in patients with sickle cell disease (SCD), with a particular predilection for the musculoskeletal system. Although Salmonella osteomyelitis is well described in this population, septic arthritis is uncommon, especially involving the shoulder joint. We describe a case of NTS bacteremia complicated by native shoulder septic arthritis in a patient with SCD and review its clinical implications. Methods: We report the clinical course, diagnostic evaluation, microbiologic findings, imaging studies, and management of a 22-year-old man with homozygous SCD who presented with a vaso-occlusive pain crisis and subsequently developed severe sepsis with persistent Salmonella enterica bacteremia following ingestion of undercooked poultry. Persistent bacteremia prompted further evaluation for metastatic infection using advanced imaging and diagnostic arthrocentesis. Results: Whole-body imaging identified septic arthritis of the native right shoulder, which was confirmed by synovial fluid cultures growing Salmonella species. The patient underwent arthroscopic irrigation and debridement for source control. Antimicrobial therapy was narrowed to intravenous ceftriaxone based on susceptibility data and continued for six weeks. The patient demonstrated clinical improvement with resolution of bacteremia and was discharged to rehabilitation to complete therapy. Conclusions: This case highlights the importance of a careful exposure history, including foodborne sources, in patients with SCD presenting with invasive Salmonella infection. Persistent bacteremia should prompt early investigation for metastatic foci, and timely surgical source control combined with targeted antimicrobial therapy is essential for optimal outcomes in this population.

ABSTRACT Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by antibody‐mediated platelet destruction, often driven by long‐lived plasma cells (LLPCs) resistant to conventional therapies. While most patients respond to corticosteroids and intravenous immunoglobulin (IVIG), a subset develops life‐threatening refractory disease. In this case series, we describe three patients aged 39, 85, and 58 with life‐threatening, multi‐agent refractory ITP and platelet nadirs < 2 × 10 9 /L who failed corticosteroids, IVIG, and thrombopoietin receptor agonists (TPO‐RAs). Following salvage therapy with daratumumab, a monoclonal antibody targeting CD38, all three patients achieved rapid hematologic recovery, with platelet count normalization within 1 week. This accelerated response allowed for urgent clinical stabilization, including safe anticoagulation and surgical intervention. The efficacy of daratumumab likely stems from a dual mechanism: the depletion of CD38+ LLPCs and the immediate modulation of Fc‐receptor‐mediated platelet clearance. These observations suggest that CD38‐targeted therapy can bypass traditional treatment resistance to achieve near‐immediate remission in high‐complexity, high‐risk clinical settings. While these results are compelling, prospective clinical trials are warranted to define the long‐term safety, durability, and optimal dosing of anti‐CD38 therapies in refractory ITP populations.

ABSTRACT Background Academic departments in medicine face increasing pressure to balance clinical productivity with their broader academic missions, including education, scholarship, mentorship, and service. While clinical work is routinely quantified through relative value units (RVUs), non‐clinical academic contributions are inconsistently measured and often undervalued. Academic Value Unit (AVU) systems have emerged as frameworks to quantify these activities, but adoption remains limited due to inconsistent funding models, lack of standardized frameworks, and minimal evidence demonstrating outcomes such as faculty satisfaction, retention, or return on investment (ROI). Methods This concept paper synthesizes current AVU implementation strategies in emergency medicine and proposes an evidence‐informed six‐step framework for AVU design, funding, and sustainability. The framework was informed by a literature review, analysis of institutional dashboards, and multi‐institutional input from the Society for Academic Emergency Medicine (SAEM) community, including feedback from a national didactic session at the 2025 SAEM Annual Meeting. Results The proposed framework outlines practical steps for AVU implementation: defining mission‐aligned domains, identifying measurable academic activities, establishing transparent weighting systems, integrating real‐time tracking dashboards, developing sustainable blended funding models, and engaging leadership and faculty through iterative review. The model incorporates customizable templates, adaptable activity menus, and suggested ROI metrics that departments can tailor to local institutional priorities and resources. Conclusions AVU systems offer a structured approach to recognizing and incentivizing non‐clinical academic contributions in emergency medicine. A transparent, mission‐aligned framework supported by sustainable funding and measurable ROI metrics may enhance faculty engagement, equity, and long‐term departmental sustainability. Future work should focus on establishing validated benchmarks for AVU weighting, integrating AVUs with faculty development and wellness initiatives, and evaluating longitudinal outcomes such as retention, satisfaction, and equity.