Citations

PURPOSE Deficient mismatch repair/microsatellite instability (dMMR, MSI-H) in biliary tract cancers (BTCs) is observed in 1%-5% of tumors. MSI-H across solid tumors has demonstrated durable response to immune checkpoint inhibitors (ICIs) regardless of the anatomic location. Here, we describe clinical outcomes and surgical conversion of MSI-H BTC treated with ICIs. Patients and Methods We conducted a multicenter, retrospective analysis of BTC patients with dMMR/MSI-H between 2017 and 2024 at Mayo Clinic, University of Michigan, and University Hospitals Seidman Cancer Center. Outcomes of interest were surgical resection rate, rate of pathologic response, 2-year overall survival (OS; time from initiation of treatment to death/last follow-up), and time to treatment discontinuation (TTD; time from initiation of treatment to cessation because of any cause). Analyses were descriptive. RESULTS Thirty patients with MSI-H BTC were identified: 19 with cholangiocarcinoma, three with gallbladder cancer, and 8 with BTC undefined. The median age at diagnosis was 61.5 years (range, 26-86). Twenty-six (86.7%) patients had advanced stage at diagnosis. Twenty-seven patients (90%) received first-line systemic therapy, and 13 (48.1%) continued onto second line. Six patients (23.1%) were restaged to resectable from advanced disease after ICI therapy and underwent resection; all remained recurrence-free at last follow-up. Of these six patients, 3 (50%) achieved a pathologic complete response. Among those receiving first-line therapy, the median TTD was 9.9 months (95% CI, 5.7 to 14.5 months) and the 2-year OS was 73% (95% CI, 56% to 94%). CONCLUSION ICI therapy in patients with MSI-H BTC demonstrated durable response and downstaged some BTC to a resectable stage. dMMR/MSI-H should be performed up-front to guide treatment decisions.

Pre-hospital use of whole blood is becoming increasingly prevalent in EMS and military medicine. Technologies to store, transport, warm up, and transfuse the blood are now available, and the outcome of whole blood transfusion seems to be superior to infusion of crystalloid solutions or plasma and at least equivalent to packed cells with plasma. The auto-transfusion tourniquet (A-TT®, Oneg HaKarmel Ltd., Tirat Carmel, Israel) is a non-invasive device that shifts the patient’s own blood from the legs to the core and blocks its reentry. The A-TT consists of an elastic ring made of a stainless-steel coil, wrapped by an elastic sleeve and pulling straps. When rolled up the leg(s), it squeezes the soft-tissues’ blood into the central circulation, and the ring stops the return of blood to the leg. The application time of the A-TT is less than 20 s per leg, and the A-TT transfers more than 500 mL of blood from each leg to the core. The auto-transfused blood is of the patient’s own type, has full oxygen carrying capacity, is normothermic, and is not anticoagulated. The device can be applied by a trained first responder, even during transport, and its use can be titrated to avoid overshooting the patient’s blood pressure. The device can be kept on the leg for up to 2 h, and as such, can serve as a bridge to blood or a bridge to definitive care. This paper is a hypothesis-generating review that defines the potential role of the A-TT in settings where blood is not available and is a call for others to help generate more data.

Autoimmune diseases arise from a breakdown of immune tolerance and complex interplay of genetic susceptibility, environmental triggers, tissue-specific immune responses, microbiota, and regulatory pathways. Mouse models remain essential for dissecting these mechanisms, but no single model fully reproduces the heterogeneity, chronicity, and immune complexity of autoimmune disease in humans. This review summarizes classical murine and humanized mouse models used to study inflammatory bowel disease (IBD), multiple sclerosis (MS), type-1 diabetes (T1D), and rheumatoid arthritis (RA). We also highlight disease-specific scoring systems, including clinical indices, histopathology, imaging, cytokine profiling, autoantibody assessment, and human immune-cell readouts, as essential tools for standardized interpretation. Conventional murine models provide experimental control and mechanistic clarity, whereas humanized models improve assessment of human immune responses, patient-specific biology, and therapeutic translation. However, humanized systems remain limited by incomplete immune reconstitution, graft-versus-host disease, donor variability, cost, and incomplete tissue architecture. By providing a comparative framework spanning both conventional and humanized models, this review aims to guide informed model selection tailored to specific research questions in autoimmune disease biology and translational therapeutic development.

ABSTRACT Objective To provide expert recommendations for the development of a specialty bipolar clinic that promotes best clinical practices for the delivery of safe and effective care. Methods Members of the National Network of Depression Centers (NNDC) Bipolar Clinics Work Group met in a series of 1‐h monthly video calls over 18 months to discuss all aspects of their respective institution's bipolar clinics, including services provided, administrative processes, staffing models, characteristics of patients treated, patient volumes, finances, and research. The group also invited psychiatrists from outside of the NNDC who ran large bipolar clinics to contribute their thoughts and experiences on the subject. In addition, the NNDC sent a 20‐question survey to all 27 sites asking clinic directors specific questions about their bipolar clinics, if applicable. Further meetings and discussions incorporating results from the survey took place to produce a comprehensive set of recommendations. Results Twenty‐one of 27 NNDC sites (81%) responded to the survey. Twelve of 21 (57%) sites had a specific bipolar clinic, and another 4 (19%) were looking to start one. Clinics were based in university settings. The meetings, clinic survey, and discussions resulted in 10 recommendations describing services and operations for bipolar specialty clinics. Conclusions Given the complexity of bipolar disorder, specialty clinics are important to enhance care. Clinics with a wide array of services that include consultation, medication management, bipolar‐specific psychotherapies, and patient/family psychoeducation provide the most comprehensive care. Challenges to these clinics include maintaining ongoing patient access as well as ensuring long‐term financial stability.

Abstract Background The Charlson comorbidity index (CCI) is a validated weighted measure of comorbidity burden, but has an unclear role in heart failure (HF). Objectives To characterize age-adjusted CCI (ACCI) in HF, its association with the use of guideline-directed medical therapy (GDMT) and with outcomes. Methods In the Swedish HF registry, patients were divided into 3 groups based on ACCI scores (low 1-3, intermediate 4-6, and high ≥7). We studied its association with clinical characteristics and GDMT use. Multivariable multinominal and Cox regressions were used to analyze ACCI and its association with ejection fraction (EF) category (reduced [HFrEF], mildly reduced [HFmrEF], preserved [HFpEF]), and with outcomes up to 3 years. Results Among 117,419 patients (age 75 [66-82], 36% women, 53% HFrEF, 24% HFmrEF, 23% HFpEF, median ACCI was 5, 6 and 6 respectively. ACCI ≥7 was present in 31% with HFrEF, 35% with HFmrEF and 42% with HFpEF. A higher ACCI score was associated with higher EF category, NYHA class, serum NT-proBNP, diuretic use, and lower quality of life and GDMT use (p<0.05 for all). The risk of composite CV mortality/first HF hospitalization was higher with intermediate (adjusted HR 1.34, 95% CI 1.29-1.39) and high vs low ACCI (1.76, 1.69-1.83). High ACCI category (vs low) was significantly associated with non-CV (adjusted HR 6.36, 95% CI 5.75-7.04), but also, CV mortality (4.35, 3.99-4.74), and total hospitalizations (adjusted IRR 2.16, 2.11-2.22) but also HF hospitalizations 1.23 (1.17-1.28) Conclusion The ACCI discriminates well in HF, with higher ACCI being associated with greater severity of HF, lesser GDMT use and worse quality of life. Higher ACCI was more strongly associated with death than hospitalization. Higher ACCI was more strongly associated with non-CV outcomes but also with CV and HF outcomes.

Abstract Background The expanding use of biologic and small-molecule therapies for ulcerative colitis (UC) has raised concerns regarding perioperative safety. We conducted a network meta-analysis to compare short-term postoperative complications associated with preoperative exposure to these agents in patients undergoing colorectal surgery. Methods We systematically searched PubMed, Web of Science, and the Cochrane Library through September 15, 2025, for cohort studies of adults with UC who were exposed to biologic or small-molecule therapy within 12 weeks prior to surgery. Interventions included biologic therapy, small-molecule therapy, and no biologic or small-molecule therapy (control). The primary outcome was overall postoperative complications at 30 and 90 days. Venous thromboembolism (VTE) was assessed as a key secondary outcome. Random-effects network meta-analysis was performed using risk ratios (RRs) with 95% confidence intervals (CIs). Results Sixteen retrospective cohort studies involving 3235 patients were included. At 30 days, ustekinumab and tofacitinib were associated with lower overall postoperative complication rates than control (RR: 0.29; 95% CI: 0.09-0.96; and RR: 0.66; 95% CI: 0.46-0.96, respectively). Anti-tumor necrosis factor (TNF) therapy was associated with higher complication rates compared with vedolizumab, ustekinumab, and tofacitinib at 30 days (RR: 1.27; 95% CI: 1.00-1.63; RR: 3.67; 95% CI: 1.12-12.03; and RR: 1.61; 95% CI: 1.14-2.27, respectively). At 90 days, anti-TNF therapy was associated with higher complication rates than control (RR 1.20, 95% CI 1.03-1.40), although the 90-day analysis was based on limited data. VTE rates were similar across treatments at both time points. Conclusion Preoperative ustekinumab and tofacitinib were associated with fewer 30-day postoperative complications than control or anti-TNF therapy, while vedolizumab was associated with fewer complications than anti-TNF therapy. At 90 days, anti-TNF therapy was associated with higher complication rates compared with control. These findings, particularly at 90 days based on limited data, should be interpreted with caution and require confirmation in well-designed prospective studies with rigorous adjustment for confounding factors.

Abstract Background Glioblastoma (GB) exhibits marked tumor microenvironmental heterogeneity, contributing to both therapy resistance and poor survival outcomes. Intercellular adhesion molecule 1 (ICAM1) is an inflammation-associated adhesion molecule implicated in immune-stromal interactions, but its clinical and biological significance in GB remains incompletely defined. Methods We performed ICAM1 immunohistochemistry, bulk RNA sequencing, DNA methylation analysis, single-nucleus RNA sequencing, and preoperative MRI-derived morphologic feature analysis across multi-institutional cohorts of treatment-naïve IDH-wildtype GB. Results High ICAM1 expression at both transcript and protein levels is associated with shorter overall survival, particularly within the mesenchymal transcriptional subtype. ICAM1 expression is inversely associated with promoter methylation. Single-nucleus RNA-sequencing analysis shows that ICAM1-high tumors are enriched for mesenchymal, hypoxia, stress-associated, and immunosuppressive myeloid programs, suggesting that ICAM1 reflects a multicompartment inflammatory tumor ecosystem. ICAM1 expression, tumor surface irregularity, and patient age are independently prognostic and minimally correlated, capturing complementary clinical, imaging, and molecular features of GB biology. When combined, our Clinical-Imaging-Molecular (CIM) framework refines outcome prediction across independent GB cohorts using routinely available clinical data, conventional imaging, and standard immunohistochemistry. Conclusions ICAM1 characterizes an immune-remodeled, stress-adapted GB ecosystem associated with poor clinical outcomes. Integrating patient age, surface irregularity, and ICAM1 expression yields a scalable and clinically accessible prognostic framework for GB, supporting tailored outcome prediction, particularly in low- and middle-resource settings without routine access to advanced molecular profiling.