Citations

Abstract Background: Clostridium ramosum ( C. ramosum ) is an anaerobic gram-positive bacillus of the human intestine and a rare cause of bacteremia. This retrospective cohort study evaluated clinical characteristics and outcomes of a multicenter cohort of adults with C. ramosum bacteremia. Methods: This multicenter retrospective cohort included adults (≥ 18 years) with true C. ramosum bacteremia at Mayo Clinic hospitals in Arizona, Florida, Minnesota, and Wisconsin from September 1, 2012, through December 31, 2025. Data were collected through search for C. ramosum in microbiological culture records. Clinical characteristics assessed included immune status, source of bacteremia, presence of sepsis, neutropenic fever, monomicrobial vs. polymicrobial bacteremia, antimicrobial resistance patterns, antimicrobial therapy, length of stay and 30-day all cause mortality. Exploratory odds ratios (ORs) with 95% confidence intervals (CIs) were reported. Results: Among 90 patients with a positive C. ramosum blood culture, 17 were classified as contaminants and 73 comprised the study cohort. Median age was 66.0 years (IQR, 56.0–75.0); 44 (60.3%) were male and 33 (45.2%) were immunocompromised (including 26 with active malignancy, while the remaining 7 were received biologic immunosuppression). The most common infection sources were gastrointestinal (32/73, 43.8%) and central line-related (8/73, 11%). At presentation, 50.7% of patients met criteria for sepsis and 15/73 (20.5%), were in septic shock. Of 73 isolates tested, 31/73 (44.3%) were clindamycin resistant and 9/73 (12.9%) tested intermediate. Anaerobic-active antimicrobial therapy was received by 53/73 (72.6%). Thirty-day mortality was 11/73 (15.1%). Mortality was 30.0% (6/20) with therapy without reliable anaerobic activity and 9.4% (5/53) with anaerobic-active antimicrobial therapy (OR, 4.02; 95% CI, 0.88–19.46; P = 0.060). The median hospital LOS was 8.0 days. Among 30-day survivors, anaerobic active antimicrobial therapy was associated with a shorter median LOS compared to therapy without reliable anaerobic activity (8.5 vs. 12.0 days). Immunocompromised patients had higher odds of monomicrobial C. ramosum bacteremia than immunocompetent patients (OR 3.16, 95% CI 1.19–8.39; p = 0.03). Patients with polymicrobial bacteremia had higher odds of sepsis (OR, 3.89; 95% CI, 1.43–10.55; P = 0.008) and septic shock (OR, 5.66; 95% CI, 1.17–27.36; P = 0.020). Patients with malignancy or neutropenia demonstrated significantly lower odds of presenting in septic shock (p = 0.018; p = 0.029 retrospectively). Microbiological clearance was achieved in 91.3% (42/46) of evaluable cases. Conclusions: This largest reported cohort defines the clinical and microbiological profile of C. ramosum bacteremia. Frequent clindamycin nonsusceptibility is clinically actionable. Several clinical associations found on univariable analysis should be further investigated in larger studies.

Background: Cocaine use and cardiovascular disease (CVD)-related mortality trends in the U.S. are underreported. Using the CDC’s Wide-Ranging Online Data for Epidemiologic Research database, we analyzed the relationship between cocaine use and CVD-related deaths. Methods: We analyzed death certificates from the Multiple Cause of Death dataset to identify CVD-related deaths involving cocaine use. Age-adjusted mortality rates (AAMRs) per 1 000 000 and annual percentage changes (APCs) were calculated using Joinpoint Regression. Results: From 1999 to 2022, 82 944 deaths were linked to cocaine use and CVDs. AAMRs rose from 9.6 in 1999 to 32 in 2022. Mortality trends varied by demographics and regions. Males and females showed early increases (1999–2006), declines (2006–2012), and sharp rises (2012–2022), with APCs of 11.8% and 12.8%, respectively. Non-Hispanic Black individuals exhibited consistently higher rates than non-Hispanic Whites, though both groups experienced sharp increases starting in 2014 (APCs: 12.5 and 12.7%). Geographic trends revealed early 2000s increases, mid-2000s declines, and rapid rises beginning in the 2010s. The Northeast and South had notable APCs of 13.5 and 12.6% (2013–2022). Rural areas initially showed steeper increases than urban areas but displayed steady upward trends since 2011 (APC: 9.5%). Age-wise, older adults experienced a particularly sharp rise from 2012 to 2022 (APC: 15.0%). Conclusion: Cocaine use and CVD-related mortality rose significantly from 1999 to 2022, with pronounced increases among men, non-Hispanic Black individuals, older adults, urban residents, and those in the South. These findings highlight a growing public health crisis.

Background Recurrent pericarditis may be mediated through inappropriate activation of the NACHT, leucine‐rich repeat, and pyrin domain‐containing protein 3 inflammasome. Pharmaceutically manufactured cannabidiol is an oral formulation that inhibits NACHT, leucine‐rich repeat, and pyrin domain‐containing protein 3 inflammasome activation and development of pericarditis in a preclinical model. Methods This Phase 2, open‐label, multicenter trial included adult patients with symptomatic recurrent pericarditis: pericarditis chest pain ≥4 on an 11‐point numerical rating scale with an elevated C‐reactive protein (≥1 mg/dL) or at least mild pericardial inflammation on cardiac magnetic resonance imaging. At enrollment, patients were on stable doses of non‐steroidal anti‐inflammatory drugs, colchicine, and/or corticosteroids. Cannabidiol was administered during an 8‐week treatment period and an optional 18‐week extension period when background therapy was tapered and discontinued. The primary efficacy end point was change in patient‐reported pericarditis pain. Secondary end points included normalization of C‐reactive protein and percentage of patients with recurrences. Results Among 27 patients (18 women, mean age 53 years), baseline maximal numerical rating scale pain score was 5.8±1.7, and 10 patients had elevated C‐reactive protein. At Week 8, maximal numerical rating scale pain score was 2.1±1.8, and median time to numerical rating scale score ≤2 was 5 days. Among the 10 patients with baseline C‐reactive protein elevation, C‐reactive protein was normal at Week 8 in 8 patients (80%). During the extension period, 17 (71%) of 24 patients remained free of pericarditis recurrence. A serious adverse event leading to cannabidiol discontinuation occurred in 1 patient. Conclusions In symptomatic patients with recurrent pericarditis, pharmaceutically manufactured cannabidiol appears safe and associated with reductions in pericarditis pain and systemic inflammation. Registration URL: clinicaltrials.gov ; Unique Identifier: NCT05494788.

Abstract Background: Immune checkpoint inhibitors (ICIs) have improved survival in non-small-cell lung cancer (NSCLC), yet only a subset of patients benefits, and biomarkers like PD-L1 remain limited. Here, we introduce a deep learning-based pathomics framework that utilizes routine H&E-stained slides to predict therapeutic response and survival outcomes in ICI-treated metastatic NSCLC. Methods: The study included 797 ICI-treated NSCLC patients from MD Anderson, with external validation in 280 patients from Mayo Clinic, Gustave Roussy, and the Phase III ICI-naïve LUSC Lung-MAP S1400I trial receiving nivolumab with or without ipilimumab. Path-IO (Pathology-Driven Immunotherapy Optimization) comprised of four major steps: (1) pathologist-verified tissue classifier segmented WSIs into eight compartments—Background, Bronchi, Immune, Lung, Necrosis, Stroma, Tumor, and Vessel—and was validated on TCGA and CPTAC dataset; (2) a survival prediction module generating patient-level risk scores in the MD Anderson cohort and validated across external datasets; (3) integration of Path-IO risk scores with radiomics and clinical features to improve prognostic accuracy; and (4) biological interpretability analyses correlating Path-IO risk immune contexture from multiplex immunofluorescence and transcriptomic signatures from NanoString profiling. Results: Path-IO effectively stratified patients into high and low-risk groups with significant survival differences. In the MD Anderson cohort, it achieved HR = 2.11 (p < 0.001) and HR = 2.51 (p < 0.001) for OS in the discovery and validation sets, and HR = 2.34 (p < 0.001) and HR = 1.87 (p < 0.001) for PFS, respectively. In the multicenter Phase III Lung-MAP S1400I trial, Path-IO achieved HR = 1.78 (p = 0.016) for OS and HR = 2.76 (p = 0.006) for PFS. In external validation, it predicted outcomes in the Gustave Roussy (OS = 1.97, p = 0.003; PFS = 1.51, p = 0.046) and Mayo Clinic (OS = 2.46, p = 0.007; PFS = 2.45, p = 0.027) cohorts. Path-IO outperformed PD-L1 and remained an independent predictor in multivariate analysis (p < 0.001). It enabled data-driven frontline selection between anti-PD-1 monotherapy and chemo-immunotherapy, offering guidance toward more personalized treatment decisions. Integration with radiomics and clinical features further improved predictive accuracy (OS 0.63→0.75; PFS C-index 0.58→0.70), while high Path-IO risk scores correlated with immune-cold phenotypes identified by multiplex immunofluorescence and NanoString transcriptomics. Conclusions: Path-IO demonstrates that deep learning models rooted in histopathologic architecture can generate interpretable and biologically informed survival predictions in NSCLC treated with ICIs. By integrating pathology, radiology, and clinical data, Path-IO provides complementary predictive value beyond established biomarkers such as PD-L1. Citation Format: Rukhmini Bandyopadhyay, Linghzi Hong, Mihaela Aldea, Shenduo Li, Lodovica Zullo, Frank R. Rojas, Maliazurina B. Saad, Maricel C. Marin, Muhammad Waqas, Jiexin Zhang, Eman Showkatian, Claudio A. Arrechedera, Xiaoyu Han, Yuliya Kitsel, Sherif Ismail, Muhammad Aminu, Bo Zhu, Carol C. Wu, Brett W. Carter, Joe Y Chang, Zhongxing Liao, Maria R. Ghigna, Davide Soldato, Hai T. Tran, Xiuning Le, Tina Cascone, Bingnan Zhang, Haniel A. Araujo, Mehmet Altan, Simon Heeke, David Jaffray, Don L. Gibbons, Ara Vaporciyan, J Jack Lee, Neda Kalhor, Cara Haymaker, Ignacio Wistuba, John V. Heymach, Yanyan Lou, Natalie Vokes, Luisa M. Solis Soto, Jianjun Zhang, Jia Wu. Path-IO: A deep learning pathomics framework for personalized immunotherapy selection and outcome prediction in metastatic non-small cell lung 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 4003.

Abstract Purpose Although the Woven EndoBridge (WEB) device is increasingly used for the treatment of wide-neck intracranial aneurysms, including in the acute rupture setting, comparative evidence assessing the impact of rupture status remains limited. This study compared angiographic, safety, and clinical outcomes between ruptured and unruptured intracranial aneurysms treated with WEB. Methods We conducted a retrospective analysis of prospectively collected data from the multicenter cohort registry WorldWideWEB, including consecutive adult patients with intracranial aneurysms treated with the WEB. Patients were stratified into groups of ruptured and unruptured aneurysms. Propensity score matching was used to balance baseline characteristics between both groups. Retreatment rate was the primary outcome. Secondary outcomes included mRS, safety events (thromboembolic complications) and angiographic outcomes (periprocedurally and last follow-up). Results Among 1,220 patients, 342 (28.0%) presented with ruptured aneurysms. There was no significant difference in the rate of thromboembolic complications between groups (11.8% vs 5.9%, p = 0.056). At follow-up, adequate occlusion was lower (82.2% vs 93.3%, p < 0.002) and functional outcomes were worse (mRS ≥2 in 34.1% vs 21.9%, p = 0.012) among patients with ruptured aneurysms. Periprocedural adequate occlusion (53.3% vs 53.8%, p>0.9) and retreatment rates (11.8% vs 7.1%, p = 0.14) did not differ between groups after matching. Conclusion Ruptured aneurysms demonstrated expected inferior follow-up functional and angiographic outcomes when compared with unruptured aneurysms, but no difference in retreatment rate and procedural safety. These findings support WEB as a safe and effective treatment option for appropriately selected ruptured intracranial aneurysms in routine clinical practice.

ABSTRACT Background Factor XI/XIa inhibitors are emerging anticoagulants with potential to reduce bleeding complications in atrial fibrillation (AF) patients. This meta‐analysis evaluated their efficacy and safety compared to direct oral anticoagulants (DOACs) and explored dose optimization. Methods A systematic search of PubMed, Cochrane, and Embase was conducted through March 2025 following PRISMA guidelines. Randomized controlled trials (RCTs) comparing Factor XI/XIa inhibitors with DOACs in AF patients were included. Outcomes assessed were major bleeding, stroke, systemic embolism, all‐cause and cardiovascular mortality and serious adverse events. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a Mantel‐Haenszel random‐effects model. Heterogeneity was evaluated with the I² statistic, and evidence certainty assessed by the GRADE approach. Trial Sequential Analysis (TSA) was performed. Results Three RCTs including 16,772 patients (mean age 73 years, CHA₂DS₂‐VASc 3.9–5) were analyzed. Factor XI/XIa inhibitors significantly reduced major bleeding (RR: 0.41, 95% CI: 0.36–0.46, I² = 0%) compared to DOACs. However, stroke risk was increased (RR: 3.42, 95% CI: 2.62–4.46), particularly with asundexian 50 mg (RR: 4.02). No significant differences were observed in all‐cause mortality (RR: 0.82) or cardiovascular death (RR: 1.05). Systemic embolism risk was higher (RR: 4.26), while serious adverse events were comparable (RR: 0.95). TSA indicated encouraging safety outcomes but highlighted the need for further large‐scale studies. Conclusion Factor XI/XIa inhibitors lower major bleeding risk in AF patients but increase stroke and systemic embolism rates without impacting mortality.

Background: Transradial artery access (TRA) is the favored approach for percutaneous coronary intervention (PCI) and coronary angiography (CAG). However, transulnar artery access (TUA) has emerged as an alternative, particularly when TRA is not feasible. This systematic review and meta-analysis aims to compare the efficacy and safety of TUA versus TRA in patients undergoing PCI and CAG. Methods: From inception to August 2025, a systematic search of electronic databases was conducted. Data were synthesized using a random-effects model, and heterogeneity was assessed using the I 2 statistic. Results: Nine RCTs involving 6089 patients were included. Meta-analysis revealed no significant difference in procedural success between TUA and TRA (RR: 0.93, 95% CI: 0.82–1.06, P = 0.28, I 2 = 99%). Similarly, puncture success rates were comparable (RR: 0.95, 95% CI: 0.91–1.00, P = 0.06, I 2 = 83%). Secondary outcomes showed no significant differences in puncture attempts or hematoma incidence, but TRA was associated with a shorter procedure time (MD: 0.89, 95% CI: 0.27–1.50, P = 0.005). Conclusion: TUA provides a viable alternative to TRA, with similar success rates and complication profiles. However, TRA remains superior in terms of procedure time. Further large-scale RCTs are warranted to confirm these findings and refine clinical guidelines.

Despite advances in percutaneous coronary procedures, in-stent restenosis remains a significant challenge. Although sirolimus- and paclitaxel-coated balloons are promising alternatives, their comparative safety and efficacy remain uncertain. PubMed, Embase, and Cochrane databases were searched using relevant keywords from inception until August 2025. A total of 11 studies (7 randomized controlled trials and 4 observational cohort studies) were included, comprising 3633 participants overall. The primary outcomes assessed were target lesion revascularization and target lesion failure. Meanwhile, the Secondary outcomes included stent thrombosis, all-cause mortality, myocardial infarction, major adverse cardiovascular events, survival, binary restenosis, and angiographic endpoints (acute gain, diameter stenosis, in-segment late lumen loss, in-lesion late lumen loss, and in-segment minimal lumen diameter). Interstudy heterogeneity was assessed using I ² and X ² statistics ( I ²>50% = significant heterogeneity). Interstudy heterogeneity was low for most outcomes, including all primary clinical endpoints, with moderate heterogeneity observed only for select angiographic measures (notably in-segment late lumen loss and diameter stenosis). Statistical analysis was conducted using R software and RStudio (version 4.4.2), with a P value of < 0.05 indicating statistical significance. This meta-analysis examined studies that compared paclitaxel-coated balloon (PCB) versus standard balloon [sirolimus-coated balloon (SCB)] angioplasty. Regarding primary outcomes, there were no notable variations in target lesion failure [risk ratio (RR), 1.08, 95% CI, 0.90–1.29, P = 0.36] or target lesion revascularization (RR, 1.16, 95% CI, 0.98–1.37, P = 0.08). With all aggregated estimates being nonsignificant, secondary outcomes such as stent thrombosis, all-cause mortality, myocardial infarction, major adverse cardiovascular events, and survival were similar between groups. Angiographic endpoints revealed no discernible variations in late lumen loss (in-lesion and in-segment), acute gain, or diameter stenosis. Nonetheless, the SCB group’s minimal lumen diameter was significantly smaller than that of the PCB group (MD, −0.08 mm, 95% CI, −0.14 to −0.01, P = 0.02). In treating coronary in-stent restenosis, SCB and PCBs show similar overall safety and effectiveness; lesion-specific angiographic variations indicate that customized selection may improve patient outcomes.

Background: Inflammatory bowel disease (IBD) is associated with systemic inflammation and potential cardiovascular complications. This meta-analysis evaluates long-term cardiovascular risks in IBD. Methods: Electronic databases were searched for studies examining cardiovascular, cerebrovascular, and thromboembolic risks in IBD. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Results: Fifty-three studies comprising 1,406,773 patients were analyzed. IBD was linked to increased risk of ischemic heart disease (aHR 1.25; p = 0.001) myocardial infarction (aHR 1.25; p = 0.01), acute coronary syndrome (aHR 1.43; p < 0.00001), heart failure (aHR 1.24; p < 0.00001), atrial fibrillation (aHR 1.20; p < 0.00001), and stroke (aHR 1.13; p < 0.00001). Elevated risks were also observed for peripheral arterial disease (aHR 1.41; p < 0.00001), diabetes mellitus (aHR 1.40; p < 0.00001), venous thromboembolism (aHR 1.98; p < 0.00001), deep vein thrombosis (aHR 2.85; p = 0.0004), and pulmonary embolism (aHR 1.98; p = 0.03). Importantly, IBD was associated with increased cardiovascular (aHR 1.14; p = 0.03) and all-cause mortality (aHR 1.53; p < 0.00001). Conclusions: IBD patients face higher risk for adverse cardiovascular outcomes, thromboembolic disease, and mortality, necessitating early cardiovascular risk assessment and targeted interventions in this population.

ABSTRACT Background Lung cancer (LC) and respiratory failure (RF) are leading causes of adult mortality worldwide. Analyzing long‐term mortality trends across demographic, racial, geographic, and socioeconomic groups is essential to address disparities and enhance outcomes. This study investigates US national mortality patterns for LC and RF from 1999 to 2023, focusing on changes in age‐adjusted mortality rates (AAMRs) and key disparities. Methods Mortality data from the CDC WONDER database (1999–2023) for adults aged 25+ with LC (ICD‐10: C34) or RF (ICD‐10: J96) were analyzed. AAMRs per 100,000 were calculated, stratified by gender, race/ethnicity, region, state, and urban–rural status. Temporal trends were assessed using Joinpoint regression to estimate annual percent changes (APCs) with 95% confidence intervals (CIs), with significance at p < 0.05. Results Over 1999–2023, 456,325 deaths from LC and RF were recorded. AAMRs declined from 1999 to 2010 (APC = −1.2, 95% CI: −1.6 to −0.9) but rose from 2010 to 2023 (APC = 1.4, 95% CI: 1.1–1.7). Men's AAMRs steadily decreased, whereas women's dropped initially, then increased from 2011 to 2023 (APC = 2.0, 95% CI: 1.7 to 2.5). Non‐Hispanic Whites saw a sharp AAMR rise from 2014 to 2017 (APC = 2.7, 95% CI: 0.9 to 3.3), with other racial/ethnic groups showing mixed trends. Regionally, the Northeast had the highest AAMRs (8.6, 95% CI: 8.5 to 8.7), and the Midwest the lowest (7.1, 95% CI: 7.0 to 7.1). Metropolitan areas saw increases post‐2006, whereas nonmetropolitan areas rose after 2009 (APC = 2.3, 95% CI: 1.8–3.1). Mississippi had the highest state AAMR (14.0, 95% CI: 13.7–14.4), Wisconsin the lowest (3.7, 95% CI: 3.5–3.8). Conclusion LC and RF mortality declined until 2010, then increased, revealing significant disparities. Targeted interventions are critical to address these trends and reduce inequities.