Citations

Abstract Skeletal muscle is a major determinant of functional status. The impact of advanced prostate cancer (aPC) systemic therapies on body composition is unknown. We identified aPC patients with serial PET-CTs receiving androgen deprivation therapy (ADT), androgen receptor pathway inhibitors (ARPI), chemotherapy, and/or Lutetium-177. An artificial intelligence algorithm quantified body composition changes from PET-CT images. Linear mixed effects models examined body composition changes over time by treatment type. The algorithm examined 2,342 PET-CTs from 468 patients. On multivariable analysis, ADT was associated with a 9% reduction in muscle density (-1.91 Hounsfield units), ARPIs an additional 6% (-1.4 Hounsfield units), and Lutetium-177 a subsequent 6% (-1.3 Hounsfield units), demonstrating progressive reduction in muscle density across later stages of systemic therapy. This large longitudinal analysis of body composition in aPC patients supports the use of an automated PET-CT algorithm to identify aPC patients on systemic therapy at risk for muscle wasting.

Hidradenitis suppurativa (HS) is a chronic, painful, immune-mediated inflammatory skin disease marked by recurrent nodules, abscesses, and draining sinus tracts in intertriginous regions. Although frequently under-recognized and subject to an average diagnostic delay exceeding a decade, HS does not affect all populations equally. United States epidemiologic data consistently demonstrate that Black and African American patients experience a higher incidence of HS, earlier age of onset, and greater disease severity, including nearly 3-fold higher odds of advanced (Hurley stage III) disease, than White patients, alongside a heavier burden of medical comorbidity. These disparities extend beyond biology, arising from an interplay of genetic, environmental, socioeconomic, and structural factors. Racial and ethnic minority patients face longer diagnostic delays, reduced access to dermatologic care, and persistent under-representation in the clinical trials that define the HS evidence base, while the substantial psychosocial burden of the disease, including elevated rates of depression, anxiety, and suicidality, further compounds these inequities. This article reviews the evidence for racial and ethnic disparities in HS across epidemiology, disease severity, social and structural determinants of care, psychosocial impact, and clinical trial representation. Because physician assistants frequently serve as the first point of clinical contact for patients with HS, they are uniquely positioned to shorten diagnostic delay and advance equitable care through earlier recognition, timely referral, and culturally responsive, patient-centered management.

ABSTRACT Neoplasia of the ileoanal pouch is uncommon, occurring in fewer than 1% of patients. Neuroendocrine carcinoma (NEC) is a rare neoplastic complication and can be difficult to diagnose due to symptoms overlapping with inflammatory pouch disorders. We describe a 36-year-old man with ileal pouch-anal anastomosis complicated by Crohn's-like disease of the pouch who underwent pouch excision for refractory disease. Histopathology revealed mixed poorly differentiated adenocarcinoma and NEC. Management may involve surgical resection for localized disease and systemic therapy for advanced stages. This case highlights the need to consider neoplastic processes, including NECs, in patients with persistent or atypical pouch symptoms.

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, yet therapeutic development is limited by experimental models that incompletely recapitulate human physiology, disease heterogeneity, and treatment responses. Emerging human-relevant models, including patient-derived induced pluripotent stem cells, cardiac organoids, engineered tissues, organ-on-chip systems, genome editing, multi-omics, and computational approaches, are improving the ability to investigate cardiovascular disease mechanisms and therapeutic responses. In this review, we critically compare these technologies with respect to physiological relevance, reproducibility, scalability, throughput, and translational potential. We highlight their applications in disease modeling, drug discovery, toxicity assessment, and precision medicine while examining persistent limitations, including cellular immaturity, incomplete vascularization and systemic integration, model variability, and limited clinical validation. We further discuss how integration of bioengineering, genome editing, multi-omics, and computational methods may improve predictive performance. Standardization, interlaboratory validation, regulatory qualification, and prospective benchmarking against human clinical outcomes will be essential for translating these platforms into reliable tools for cardiovascular research and therapeutic development. Collectively, the convergence of stem cell biology, bioengineering, genome editing, multi-omics, and computational approaches is establishing a new generation of human-centered cardiovascular models with the potential to strengthen mechanistic discovery and accelerate the development of more predictive and personalized therapies.

Objectives: To characterize the anatomic distribution, surgical management, perioperative outcomes, and early oncologic results of sinonasal glomangiopericytoma (SN-GPC) within a large single-institution cohort. Design: Multi-site, single-institution retrospective cohort study. Setting: Three tertiary care sites of a single academic medical center (Rochester, MN; Phoenix/Scottsdale, AZ; Jacksonville, FL). Participants: Twenty adults (≥18 years) with pathologically confirmed SN-GPC identified between September 2018 and August 2025. Main Outcome Measures: Tumor anatomic subsite, surgical approach, estimated blood loss, margin status, perioperative complications, and recurrence at follow-up. Results: Mean patient age was 66.4 ± 11 years (65% male). Tumors arose predominantly from the nasal cavity (95%), with 65% originating from the posterior-superior nasal septum near the olfactory cleft and 25% from the anterior-superior septum. Hypertension was the most common comorbidity (85%). All 18 definitively treated patients underwent endoscopic endonasal resection without preoperative embolization or conversion to open surgery. Mean estimated blood loss was 72.6 mL. Negative margins were achieved in 83% of cases. One intraoperative cerebrospinal fluid leak occurred and was repaired primarily. At mean follow-up of 18 months, no recurrences were observed regardless of margin status. No patient received adjuvant therapy. Conclusions: SN-GPC demonstrates a strong predilection for the septal olfactory cleft region. Endoscopic resection without preoperative embolization is safe and effective. The indolent behavior of this tumor supports observation as an acceptable strategy for select patients with positive margins at high-risk skull base locations. Keywords: glomangiopericytoma, sinonasal tumor, hemangiopericytoma, endoscopic resection, nasal cavity, skull base, olfactory cleft, mesenchymal tumor, nasal septum

Background: Robotic cholecystectomy use is increasing, but comparisons with laparoscopic cholecystectomy have largely excluded bailout procedures, limiting assessment of difficult acute cholecystitis. We compared bailout use, downstream outcomes, and 1-year costs between approaches. Study Design: This retrospective cohort study used Healthcare Cost and Utilization Project databases from New York and Florida (2012–2021) to identify adults undergoing inpatient, unscheduled robotic or laparoscopic cholecystectomy for acute cholecystitis. Bailout included conversion to open, subtotal cholecystectomy, or cholecystostomy tube placement. Multilevel regression evaluated bailout, and postoperative outcomes were assessed through 1 year. Results: Among 384,617 patients, 4% underwent robotic and 96% laparoscopic cholecystectomy. Robotic cholecystectomy had higher bailout rates (1.7% vs 1.4%; adjusted OR 1.38, 95% CI 1.21-1.58), including higher odds of conversion to open (OR 1.61, 95% CI 1.28-2.03) and subtotal cholecystectomy (OR 2.02, 95% CI 1.68-2.43), but lower odds of cholecystostomy tube placement (OR 0.42, 95% CI 0.28-0.62). Bile duct injury rates were similar (1.6% for both; p=0.998). Among 5,448 patients requiring bailout, robotic cholecystectomy was associated with fewer postoperative endoscopic biliary (3.1% vs 7.7%; p=0.007) and surgical interventions (2.3% vs 7.5%; p=0.002). Median 1-year cumulative costs remained higher with robotic cholecystectomy ($29,702 vs $24,483; p=0.002). Conclusions: Robotic cholecystectomy was associated with marginally higher bailout use and similar bile duct injury rates but fewer downstream interventions after bailout. These potential benefits did not offset higher 1-year costs.

ABSTRACT The HLA‐C*06:358 allele is characterised by a single nucleotide substitution in codon 95 in exon 3.

Introduction Pluripotent stem cell-derived alpha cells (SC-α cells) represent a promising component of next-generation cell therapies designed to more fully recapitulate human islet function; however, heterogeneity and the presence of undesired side populations limit their functional maturity and therapeutic potential. Here, we identify the cell surface protein CD98hc (SLC3A2), that when highly expressed in precursor cells, is associated with differentiation toward a more transcriptionally and functionally mature population of human SC-α cells. Methods Directed differentiation was used to generate SC-α cells from pluripotent stem cells, which were assessed via single cell RNA sequencing, flow cytometry, and immunofluorescence imaging. Following magnetic activated cell sorting (MACS) of CD98hc enriched precursors, SC-α cell function was assessed using glucose stimulated glucagon secretion (GSGS). Results We show that CD98hc is upregulated in SC-α cells expressing high levels of genes known to play important roles in α cell identity and function, and that CD98hc expression is elevated at the pre-α precursor stage relative to non–α cell populations. We demonstrate that magnetic enrichment of CD98hc⁺ pre-α cells derived from multiple pluripotent stem cell lines selectively increases the proportion of the highest CD98hc expressing glucagon-copositive precursors while depleting multiple undesired side populations, including somatostatin-positive and SOX9-positive cells. Although total α cell yield equalizes following complete differentiation, SC-α cells derived from high-CD98hc enriched precursors exhibit significantly enhanced glucose-responsive glucagon secretion compared to sham-sorted controls, indicating improved functional maturation of this precursor population. Discussion Together, these findings establish that high expression levels of CD98hc marks a functionally superior α cell precursor, that enrichment at the precursor stage can bias differentiation toward higher functional α cell output, that stem cell-derived α cell populations harbor intrinsic functional heterogeneity, and that selective targeting of precursor populations represents a generalizable strategy to improve the quality and performance of stem cell-derived endocrine cell products.