Citations

Abstract Purpose: This multicenter, multi-surgeon retrospective study aimed to identify risk factors for postoperative cerebrospinal fluid (CSF) leak following endonasal resection of craniopharyngioma, while evaluating the "perception gap" through a surgeon survey. Methods: A retrospective review was conducted on 416 patients who underwent endoscopic transsphenoidal surgery (ETS) for craniopharyngioma from 20 institutions. Factors were compared between patients with and without postoperative CSF leak, and between Early (2007-2015) and Late (2016-2025) Epochs. Complementing the clinical data, a survey of 19 neurosurgeons captured expert perspectives on risk stratification and management strategies. Results: Overall postoperative CSF leak rate was 13.5% (56/416 patients). Univariate analysis identified predominantly cystic tumors (34% vs. 21%, p = 0.034)and intraoperative lumbar drain (LD) use ( p < 0.028) as associated with postoperative CSF leak. BMI ( p = 0.587), prior surgery ( p = 0.576), and tumor size ( p = 0.363) were not significant. In the multivariable analysis, LD use was associated with a higher postoperative CSF leak rate (OR 1.91, 95% CI 1.06–3.46; p = 0.030). Between Epochs, nasoseptal flap (NSF) utilization increased from 70.7% to 87.6% ( p <0.001). NSF was protective (OR 0.28, 95% CI 0.07–0.92; p = 0.037) in the Early Epoch; no factors were significant in the Late Epoch. The surgeons’ survey identified prior surgery and intraoperative high flow leaks as primary risks; however, their LD protocols diverged from clinical data. Conclusion: Despite increased use of NSF, CSF leak persists. The study highlights a significant divergence between expert perception and clinical data regarding lumbar drains.

Acute type A aortic dissection is a life-threatening condition requiring emergency surgery and complex postoperative management. Although survival rates have improved, many patients experience long-term functional impairments, reduced quality of life, and an elevated risk of complications. Despite strong evidence supporting cardiac rehabilitation in other cardiovascular populations, structured programs remain underutilized in patients with surgically resolved acute type A aortic dissection. Exercise-based cardiac rehabilitation appears feasible and can be delivered safely in carefully selected patients when appropriately adapted to individual needs and conducted under close supervision. Postoperative patients are often physically deconditioned, prone to hospital-acquired disability, and may misjudge exercise intensity. Therefore, individualized exercise prescription, guided by exercise testing when available, is important to support safe training thresholds. Early and gradual introduction of physical activity may help prevent complications associated with immobility, support blood pressure control, and contribute to improvements in functional capacity. However, training volume should be purposefully lower than in conventional program settings to reduce hemodynamic stress. Education on safe exercise parameters and self-monitoring plays a central role in enabling long-term adherence and promoting patient autonomy. Cardiac rehabilitation programs should incorporate dietary, nutritional, and psychological support. Although evidence specific to this patient population remains limited, available data suggest the feasibility and potential benefits of cardiac rehabilitation when delivered with appropriate precautions. Our review underscores the need for a tailored, multidisciplinary CR approach aimed at enhancing physical recovery, supporting cardiovascular stability, and improving overall quality of life in patients following surgery. Further research is required to define optimal program protocols.

Suppression of insulin-like growth factor-1 (IGF-1) signaling extends mammalian life span and protects against a range of age-related diseases. Unexpectedly, we found that reduced IGF-1 signaling fails to extend the life span of mitochondrial mutator mice. Most of the longevity pathways that are normally initiated by IGF-1 suppression were either blocked or blunted in the mutator mice. These observations suggest that the prolongevity effects of IGF-1 suppression critically depend on the integrity of the mitochondrial genome, revealing an unexpected hierarchy in the pathways that control mammalian aging. Together, these findings deepen our understanding of the interactions between the hallmarks of aging and underscore the need for interventions that preserve the integrity of the mitochondrial genome.

Abstract Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and remains difficult to treat due to the absence of targeted therapies. While recent advances in immunotherapy, particularly with immune checkpoint inhibitors (ICIs), have transformed the treatment landscape for many cancers, response rates to ICIs remain low for TNBC, largely due to tumor-intrinsic immune evasion mechanisms. Objective: We identify and characterize a novel immune evasion pathway in TNBC driven by deregulation of cancer cell-intrinsic protease-activated receptor 1 (PAR1), a thrombin receptor frequently upregulated in aggressive tumors. Methods and Results: Through integrative bioinformatic analyses, genetic perturbations, xenograft models (immunodeficient and immunocompetent), flow cytometry-based tumor immune profiling, and RNA-seq, we demonstrate that PAR1 activation enhances immune evasion in TNBC. Mechanistically, we show that the paracaspase MALT1 acts as a critical downstream effector of PAR1 signaling and promotes immune escape by driving PD-L1 expression in TNBC cells. Functional assays reveal that genetic depletion of MALT1 or PD-L1 increases TNBC cell susceptibility to T cell-mediated cytotoxicity in vitro and significantly suppresses tumor growth in vivo. Notably, through knock-in and rescue experiments using a catalytically inactive MALT1 mutant, we reveal that MALT1’s scaffolding - rather than protease - function is essential for PD-L1 regulation. Immune cell depletion assays further identify CD4+ T cells, CD8+ T cells, and natural killer (NK) cells as key mediators of the anti-tumor immune response suppressed by the PAR1-MALT1 axis. These findings are supported by human TNBC specimen analyses, where MALT1 expression inversely correlates with T cell activation and positively associates with PD-L1 in PAR1-high, but not PAR1-low, tumors. Conclusion: Our study reveals immune evasion as a novel mechanism of PAR1-driven breast cancer pathogenesis, mediated by a PAR1/MALT1/PD-L1 signaling cascade. These findings bridge a critical gap by positioning MALT1 at the interface between tumor-intrinsic signaling and the immune microenvironment - two areas of CARMA-BCL10-MALT1 (CBM) complex research that have largely evolved in parallel over the years. Importantly, targeting MALT1 may enhance immunotherapy efficacy in TNBC. Given the availability of MALT1 inhibitors in clinical development, our work supports combining MALT1 inhibition with ICIs or other immune-oncology agents as a promising strategy to overcome immune resistance in TNBC. Citation Format: Dong Hu, Prasanna Ekambaram, Zheqi Li, Linda Klei, Maria L. Beecher, Yi Liu, Zongyou Cai, John Little, Jeffrey A. Meridew, Jia-Ying Lee, E. Aubrey Thompson, Tullia C. Bruno, Lidija Covic, Seung-Oe Lim, Anushka Dongre, Heide L. Ford, Mien-Chie Hung, Adrian V. Lee, Steffi Oesterreich, Linda McAllister-Lucas, Peter C. Lucas. A cancer cell-intrinsic PAR1/MALT1/PD-L1 signaling pathway drives immune evasion in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7392.

Abstract Introduction Revascularization to prevent limb loss is not feasible or represents a very high risk in a significant proportion of patients with chronic limb-threatening ischaemia (CLTI). No standard definition currently exists to define this population of patients. The aim of this study was to develop a consensus-based, multidomain definition to improve clinical assessment and reporting of studies in people with ‘no option’ (NO) or ‘poor option’ (PO) CLTI. Methods A modified Delphi process was conducted with 164 specialists from 30 countries. Two iterative survey rounds were used to reach consensus, defined as ≥70% agreement with a score of ≥7 on a nine-point scale. Results Some 164 international vascular specialists participated in the study, averaging 19 years of experience. A multidomain framework including arterial disease anatomy, biology, risk, function, and context (ABRFC) achieved 83% consensus. A ‘desert foot’ was defined as the absence of distal arterial revascularization targets on advanced non-invasive imaging, invasive digital subtraction angiography, and at least one failed endovascular revascularization attempt (81.6% agreement). Inadequate autogenous bypass conduit was defined as the lack of usable autologous vein across all four limbs (85% agreement). Patients were classified as NO for revascularization if they present with ‘desert foot’, prohibitive medical risk, a non-functional limb, or in those patients who refused arterial revascularization. PO revascularization patients combined factors such as severe infection, lack of autologous vein, or treatment non-compliance (72.1% agreement). Conclusion This consensus study established a structured, expert-validated definition of no option or poor option for revascularisation of patients with CLTI. The multidomain ABRFC framework provides a foundation for standardized clinical assessment, trial design, and future guideline development.

Introduction/Objectives: House call programs provide care for homebound patients. We conducted a case-control study to compare hospitalization and/or emergency department (ED) use by patients enrolled in a primary care house call program versus ambulatory (community-dwelling) patients. Methods: Program enrollees (cases) were matched by age and self-reported gender to community-dwelling patients (controls). The primary exposure was the combination of hospitalization and/or ED visits for 1 year before the index date (October 1, 2024). We used unadjusted and adjusted conditional logistic regression to determine differences in health care use. Results: We identified 26 cases (median [range] age, 84 [66-98] years; 16 [62%] female) and 130 controls. All cases had 4 or more chronic diseases, as compared with 87 (67%) of controls ( P = .003). A higher proportion of cases than controls had previous hospitalization and/or ED visits (84.6% vs 27.7%; P < .001). After adjusting for the number of chronic illnesses, no differences in previous hospitalization and/or ED use were identified between groups. Conclusions: Cases had more chronic illnesses and more hospitalizations and/or ED visits than community-dwelling controls. The comorbid health burden of participants in the house call program drove greater health care use and justifies a higher level of care for this medically complex patient population.