Citations

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.

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.

ABSTRACT Background and Objectives There is increasing use of neoadjuvant treatment (NAT) for patients with pancreatic adenocarcinoma (PDAC). The role of additional adjuvant chemotherapy (AT) is not well‐defined. This study aims to determine the impact of lymphovascular invasion (LVI) and lymph node (LN) involvement on overall survival (OS) in patients with resected PDAC and determine the impact of AT after NAT. Methods This is an observational cohort study of patients with PDAC who underwent NAT and surgical resection. A multivariable model was used to assess for differences in OS. An interaction term between LVI or LN involvement and AT use was utilized to test the benefit of additional AT. Results Seven thousand four hundred and fourteen patients were included; group A (LVI‐, LN‐) had 2787 patients, B (LVI + , LN‐) 652, C (LVI‐, LN + ) 1,712, and D (LVI + , LN + ) 2263. Median OS differed significantly between groups, A had the most favorable survival (34.1 months), followed by B (27.8 months), C (26.3 months), and D (21.2 months, p < 0.001). In patients with persistent LVI or LN involvement after NAT, additional AT was not associated with OS (group A, HR: 0.94, p = 0.4; B and C, HR: 1.0, p = 0.99; D, HR: 0.94, p = 0.32). Conclusions LVI and LN involvement were independently associated with worse OS. After NAT, the use of AT in patients with persistent LVI and LN involvement was not associated with improved OS.

ABSTRACT Background Prior studies in the pre‐MRI era suggest that patients with NCCN Intermediate and High Risk Grade Group 1 prostate cancer (GG1 PCa) on biopsy have increased risk for adverse oncologic outcomes. However, prostate MRI has altered patient selection for biopsy and improved prostate sampling. Herein, we examined factors associated with adverse pathologic features (APF) at radical prostatectomy (RP) and biochemical recurrence (BCR) among patients with GG1 in the MRI era. Methods A prospectively maintained institutional prostate cancer registry identified patients with GG1 PCa on biopsy who underwent RP from 2000 to 2023, stratified by MRI use. Multivariable logistic regression and Cox regression identified factors associated with APF at RP (GG3‐5, ≥ pT3a, or pN1) and BCR free survival (two consecutive PSA ≥ 0.2 ng/mL), respectively. Results Among patients without MRI ( n = 6732), NCCN risk group was associated with APF, BCR, and distant metastasis. Among 302 patients with GG1 and pre‐operative MRI, NCCN risk group was associated with neither APF nor BCR. Age (OR 1.07, 95% CI 1.01–1.14, p = 0.01), PIRADS ( p = 0.01), and % core positivity (OR 1.02, 95% CI 1.00–1.03, p = 0.04) were associated with APF. Age (HR 1.07, 95% CI 1.01–1.13, p = 0.03), APF (HR 4.36, 95% CI 2.14–8.86, p < 0.001), and positive margins (HR 4.88, 95% CI 2.39–9.98, p < 0.001) were associated with BCR. Conclusions Prior to prostate MRI, NCCN risk groups offered meaningful prognostication among patients with GG1 PCa. However, the utility of NCCN risk groups for GG1 in the MRI era appears limited. Contemporary risk stratification for GG1 should focus on biopsy and MRI characteristics rather than NCCN criteria.

Gut wall physiology in multiple sclerosis (MS) and autoimmune neurologic diseases remains underexplored. This review examines gut wall dysfunctions’ contribution to MS and autoimmune neurological disorder pathogenesis and progression. We discuss 3 inter‐related aspects of gut physiology: intestinal barrier, enteric nervous system (ENS), and mucosal immunity. We highlight the ENS as a putative target of immune injury in selected antibody‐mediated and T cell‐associated neurologic diseases. Finally, we propose a unifying framework in which the gut functions as a site of immune priming and target of autoimmune injury, bridging microbiome‐driven mechanisms in MS with ENS‐directed autoimmunity across neurologic diseases. ANN NEUROL 2026

Abstract Neuroanatomy remains a core competency in neurosurgical training, particularly in skull base education, where learners must integrate three‐dimensional spatial understanding, radiologic correlation, and stepwise procedural knowledge. Cadaveric dissection remains foundational, but adjunctive digital tools may strengthen repeated visualization and anatomical review. We describe the educational rationale and implementation of integrating stereoscopic teaching, a stepwise digital application, photogrammetry, and virtual reality within an established neurosurgical skull base curriculum. Within the Mayo Clinic cranial base course embedded in a broader longitudinal curriculum, four postgraduate year 4 neurosurgery residents participated in transcranial and endoscopic cadaveric dissections supported by stereoscopic lectures, workstation‐based tablet guidance, and immersive review using photogrammetry, virtual reality, and computed tomography/magnetic resonance imaging correlation. The integrated design aligned these modalities with course objectives in anatomical landmark recognition, operative corridor planning, radiologic‐anatomic translation, and stepwise procedural rehearsal. The educational contribution of this model lies in the intentional integration of digital adjuncts around cadaveric dissection rather than in a single technology alone. This multimodal sequence may support spatial understanding, procedural preparation, and competency‐oriented skull base training while extending review beyond the laboratory. Current evaluation is best interpreted as preliminary program evaluation rather than definitive learner‐outcome evidence. This model may offer a transferable approach for programs seeking to complement cadaveric education with emerging digital tools and provides a basis for future prospective evaluations using multiple low‐stakes assessment data points across the broader curriculum.