Citations

Background: Given aspirin’s biologic plausibility for antifibrotic and antineoplastic effects, we conducted a systematic review and meta-analysis to examine the association between aspirin use and major liver-related outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD). To our knowledge, this is the first systematic review and meta-analysis restricted exclusively to patients with biopsy- or registry-confirmed MASLD. Methods: A comprehensive search of Ovid MEDLINE, Ovid EMBASE, Scopus, and Web of Science was performed in October 2025. Studies enrolling adults with a confirmed MASLD diagnosis were included; those with viral hepatitis or alcohol-related liver disease were excluded. Outcomes assessed included hepatocellular carcinoma (HCC), fibrosis progression, cirrhosis, all-cause and liver-related mortality, gastrointestinal (GI) bleeding, hemorrhagic stroke, and liver disease progression. Hazard ratios (HRs) with 95% CIs were pooled using random-effects models. Heterogeneity was assessed using I2 statistics. Results: Seven studies met the eligibility criteria, with approximately 720,000 individuals included. Pooled analysis showed that aspirin use was associated with a significantly lower HCC risk (HR 0.59; 95% CI 0.43–0.81; I2 = 83%). No statistically significant association was found between aspirin use and cirrhosis incidence (HR 0.55; 95% CI 0.13–2.37; I2 = 83.4%) or GI bleeding (HR 1.11; 95% CI 0.74–1.66; I2 = 98.9%). Among the two studies that explored all-cause mortality, aspirin was associated with a modest but statistically significant reduction in all-cause mortality (HR 0.86; 95% CI 0.78–0.95; I2 = 0%). Conclusions: Aspirin use is associated with a reduced risk of HCC and all-cause mortality in MASLD without significantly increasing GI bleeding or hemorrhagic strokes. These associations may reflect aspirin’s anti-inflammatory properties in liver disease. Further RCTs are needed to verify the causal role of aspirin in MASLD management.

ABSTRACT Background : Tirofiban is a GP IIb/IIIa inhibitor, an anti‐platelet drug that is used in ischemic stroke or acute coronary syndromes. The goal of this study is to assess the safety and efficacy of the drug in patients who have suffered an acute ischemic stroke. Methods : A comprehensive search of PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception to December 2025 yielded randomized controlled trials (RCTs) comparing Tirofiban and conventional management in patients with acute ischemic stroke. We assessed the risk of bias using the revised Cochrane “Risk of bias” tool for randomized trials (RoB 2.0). We analyzed the outcomes using RevMan 5.4, with risk ratio (RR) as the effect measure. Results : A total of 9 RCTs with 4210 patients were included in our meta‐analysis. According to our meta‐analysis, the tirofiban group was associated with a statistically significant increase in the patients showing functional independence at 90 days, measured by patients with Modified Rankin Score (mRS) of 0–2 (RR 1.13; CI = 1.06–1.20) and excellent outcome (mRS score 0–1) at 90 days (RR 1.17; CI = 1.05–1.29). We found no statistically significant difference between the two groups regarding mortality (RR 0.94; CI = 0.63–1.40). The tirofiban group had an increased incidence of intracranial hemorrhage (ICH) (RR 1.25; CI = 1.06–1.47) but had a similar incidence of symptomatic ICH as compared to the control group (RR 1.48; CI = 0.98–2.24). Conclusion : This meta‐analysis suggests that tirofiban may improve favorable functional outcomes (mRS 0–2) in acute ischemic stroke, although the certainty of evidence was moderate. While no significant increase in sICH was observed, some analyses showed a higher rate of overall intracranial hemorrhage. These findings should therefore be interpreted cautiously, and further high‐quality randomized trials are needed to confirm the efficacy and safety of tirofiban before routine guideline use.

Aging and neurodegenerative disorders like Alzheimer’s Disease (AD) are associated with progressive dysfunction of the blood-brain barrier (BBB) and neurovascular unit (NVU), contributing to impaired vascular integrity and neuronal vulnerability. Apolipoprotein E (APOE) is a key regulator of neurovascular function, and the rare APOE3-R136S “Christchurch” variant ( APOE3Ch ) confers protection against AD. Mesenchymal stromal cells (MSCs) represent a promising cell-based therapy for the treatment of neurodegenerative diseases due to their paracrine effect exerted on vascular and neural cells. To investigate how APOE3Ch influences MSC-mediated neurovascular support, we used isogenic iPSC-derived MSCs (iMSCs) with homozygous APOE3Ch or APOE3 . We found that APOE3Ch iMSCs have stronger immunosuppressive effect on LPS-induced NFκB activation of THP1 cells. APOE3Ch iMSCs also enhanced endothelial barrier resistance and angiogenic capacity compared to APOE3 iMSCs when directly co-cultured with endothelial cells. In addition, conditioned medium from APOE3Ch iMSCs promoted neurite outgrowth more efficiently than that from APOE3 iMSCs. Metabolic profiling revealed differences between APOE3Ch and APOE3 iMSCs, suggesting altered metabolic resilience. Together, these findings demonstrate that iMSCs support vascular and neuronal function through paracrine mechanisms and suggest that APOE3Ch variant improves specific aspects of MSC-mediated neurovascular support. This work highlights the potential of combining MSC-based therapies with protective APOE variants to target BBB and NVU dysfunction in aging and neurodegeneration.

Objective The United Nations defines sustainability as meeting needs of the present without compromising future generations. While often equated to “saving the planet”, sustainability is a diverse topic. Healthcare generates >5% of CO 2 emissions worldwide, yet sustainability efforts in urology are limited. The North Central Section of the American Urological Association (NCSAUA) recently convened a Sustainability Task Force to address this topic. This study queried members on sustainability in urologic practice. Methods Following literature review on sustainability in surgery/urology, a 19-item anonymous REDCap survey was developed and distributed via email to NCSAUA members (N = 1607). The survey assessed current best practice, institutional/personal sustainability, and demographics. Responses were compiled and summarized using descriptive statistics. Results Survey response rate was 4.9% (79/1607). Respondents were most commonly from metropolitan areas (82%), male (71%), and in practice for 5–14 years (29%). Sustainability topics were prioritized as: (1) financial, (2) future workforce, (3) environmental. Over half (56%) reported no institutional sustainability programs or were unaware of them. Instrument (67%), computer (68%), and paper (65%) recycling were supported by a majority of respondents. However, only 28% and 29% of respondents reported current institutional use of instrument and computer recycling, respectively. Telemedicine was infrequent, with most urologists (58%) conducting 0-5% of visits virtually. Conclusions Current institutional and urologic practice emphasis on sustainability is low. Respondents ranked highest sustainability priorities as financial and future workforce. Efforts to address environmental sustainability were also supported, namely reduction of disposables and waste. The findings support the development of targeted programs to advance sustainability priorities widely.

Abstract Purpose Modeling relative biological effectiveness (RBE) is central to carbon ion radiotherapy treatment planning. The modified Microdosimetric Kinetic Model (mMKM) is a clinically established RBE framework that has guided treatment protocols at many existing carbon centers, while the Mayo Clinic Florida Microdosimetric Kinetic Model (MCF MKM) is a recently developed alternative. This work aims to implement the MCF MKM in the open‐source treatment planning system matRad and to quantitatively compare its RBE‐weighted dose predictions with those of the clinically established mMKM using identical physical dose distributions across multiple disease sites. These findings will help assess their dosimetric equivalence and inform protocol development for carbon ion radiotherapy at MCF. Methods Monte Carlo simulations of the MCF carbon beamline were performed to generate physical (IDD, LET, lateral spread) and biological base data for integration of each RBE model into matRad . Treatment plans were generated for six patients, each corresponding to a different disease site, using clinical beam configurations with carbon‐reference dose prescriptions, and plans were optimized using the MCF MKM. To isolate differences attributable solely to the RBE model, the resulting physical dose distributions were held fixed and RBE‐weighted doses were recalculated using the mMKM. Dose volume histogram (DVH) metrics and spatial dose‐difference maps were used to compare target coverage and organ‐at‐risk doses between the two models. Results Across patient cases, RBE‐weighted dose distributions from MCF MKM and mMKM showed strong agreement. Differences in target coverage were small, with CTV D95% differing by less than 1.6% across all disease sites and maximum target dose differences not exceeding 0.88%. Organ‐at‐risk dose deviations were limited, with differences of 3.0% or less across evaluated DVH metrics. Spatial dose‐difference maps showed that the largest discrepancies occurred in regions of steep dose gradients near target to organ‐at‐risk interfaces, while overall dose conformity and plan quality remained comparable between the two models. Conclusions: This study served as the first systematic model comparison of the MCF MKM and mMKM within a treatment planning environment. These findings suggest that the MCF MKM and mMKM produce dosimetrically consistent RBE‐weighted dose predictions under realistic planning conditions using carbon‐reference parameters. Accordingly, the fractionation schemes developed from years of clinical experience with mMKM implementations may serve as a practical foundation for protocol development at MCF.

Abstract Germline variants in DDX41 are the most frequent genetic predisposition to adult hematologic malignancies. The most common variants are truncating, implicating loss of function in the pathogenesis. However, non-truncating variants account for 30-40% of cases, and their impact on essential DDX41 functions remains unknown. We utilized a genetic complementation assay to assess the functionality of 10 recurrent germline non-truncating variants of DDX41. All variants restored viability to Ddx41 -deficient hematopoietic progenitor cells at exogenous expression levels. In contrast, the hotspot mutant p.R525H, which is somatically acquired at disease onset in >50% of patients, failed to restore viability. CRISPR-based modeling in cell lines and mice revealed heterogeneity: some variants were non-functional at endogenous expression levels whereas others maintained complete functionality, supporting normal cell proliferation and even lifelong hematopoiesis in a homozygous setting. Notably, co-expression of p.R525H with some variants caused impaired hematopoietic progenitor cell viability, indicating a dominant-negative effect of p.R525H. In contrast, other variants, all classified as variants of unknown significance, were unaffected by the presence of p.R525H. A screen of 100 disease-associated variants confirmed that many non-truncating germline variants are susceptible to p.R525H-mediated dominant-negative effects, whereas wild-type DDX41 is not. These findings indicate that DDX41 variant curation is complicated by variable effects on functionality and variant-specific interactions with somatically-acquired DDX41 mutations. The dominant-negative effect of p.R525H provides a mechanistic basis for the conclusion of recent patient cohort analyses that co-occurrence with a somatic hotspot mutation is a reliable indicator of DDX41-driven disease in carriers of non-truncating variants.

ABSTRACT Incomplete aneurysm occlusion after flow disruption treatment strongly depends on the persistence of strong flow into the aneurysm, which in turn depends on the aneurysm and parent artery geometry as well as the device placement. However, at the time of treatment it remains challenging to predict future outcomes (complete or incomplete occlusion). This paper describes a strategy to evaluate the local hemodynamic environment created immediately after flow‐modifying device deployment to treat cerebral aneurysms and connect it to the subsequent long‐term outcomes. The approach is based on the concept of angiographic signatures that can be extracted from DSA sequences or computational models and represented as images that can be used to compare different aneurysmal environments. The methodology is demonstrated on two small series of four experimental rabbit aneurysms each, treated with either intrasaccular flow disruptors or endoluminal flow diverters. Noticeable differences in the angiographic signatures of completely and incompletely occluded aneurysms at follow‐up were observed. Specifically, larger values of mean transit times and longer time‐to‐peaks were observed deeper into the aneurysms that remained incompletely occluded in both series. The findings suggest that angiographic signatures can be used to assess the underlying hemodynamic environment immediately after device implantation and prognosticate the likelihood of future complete or incomplete occlusion.

Abstract The Africa Working Group, under the auspices of the Global Laboratory Quality Initiative of the Association for Diagnostics & Laboratory Medicine (ADLM), conducted several educational workshops in Africa to promote laboratory quality in the region. The challenges faced in maintaining quality in clinical laboratories in low-resource countries may differ from region to region and country to country. To better understand current gaps and inform our engagement with partners in Africa, a needs assessment survey was distributed to 1427 ADLM members in Africa and further disseminated through local partners, resulting in 121 responses from participants across 8 countries in the region. Additionally, interviews were conducted with laboratory professionals from the countries surveyed. The surveys primarily focused on quality management, continuing education, budgeting, infrastructure and funding, supplies, and staffing issues. The data collected from the surveys and interviews strongly indicate that respondents face major challenges in all areas assessed, including lack of funding, lack of equipment, lack of quality control (QC) and external quality assessment (EQA) materials, gaps in quality management, lack of appropriate budgeting, staffing issues, and lack of accessible training/continuing education. Consistent with the primary focus of ADLM;s Global Quality Initiative, improved access to continuing education was identified as the primary need by the participants (58%). The assessment highlights that while a strong role for educational workshops in mitigating some of the challenges continues to exist, there is also an opportunity to broaden the scope of the working groups beyond education.

Background: There is growing support for high-efficacy disease-modifying therapy (DMT) in multiple sclerosis (MS), but escalation (ESC) approaches remain common. Objective: To describe decision-making in a pragmatic trial of early high-efficacy treatment (EHT) versus ESC. Methods: DELIVER-MS is a multi-center, pragmatic, randomized controlled trial (RCT) with a parallel observational study (OBS), which enrolled treatment-naïve people with RRMS in 31 UK/US sites. Primary outcome was as follows: 36-month brain volume loss according to initial treatment approach (EHT vs. ESC). Stepwise multivariable logistic regression was used to predict participation in RCT versus OBS and choice of EHT versus ESC within the OBS cohort. Results: In total, 816 people with MS were enrolled. Participants declined randomization due to preference for a particular DMT (85%), efficacy concerns (20%), and safety concerns (9%). RCT versus OBS participation was associated with lower relapse rate ( p = 0.043) and greater brain parenchymal fraction ( p = 0.002). Among 374 in the OBS cohort, 125 (33%) chose ESC and 249 (67%) chose EHT. People commencing EHT had higher education attainment ( p < 0.001) and relapse rate ( p = 0.025). Conclusion: Baseline DELIVER-MS data demonstrate that participants with milder disease are more likely to participate in RCT. The choice of EHT versus ESC was associated with demographic factors and disease activity. Clinical trial registration: NCT03535298