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Background The pathophysiology of CS is complex and is associated with increased inflammation and impaired vascular tone. Corticosteroids are recommended in septic shock and have been proposed as a potential treatment for other types of shock. Objectives We sought to evaluate the clinical outcomes associated with early corticosteroid use in patients with cardiogenic shock (CS). Methods Using a nationally representative database including over 1000 hospitals, we identified adults ≥18 years of age admitted from 2015–2023 with a diagnosis of CS. Patients with adrenal insufficiency, chronic rheumatologic conditions, COVID-19 infection and acute COPD exacerbation were excluded. Using inverse probability treatment weighting (IPTW), we assessed for the association of receiving early corticosteroids (within the first 2 days of admission) versus no early corticosteroids and in-hospital mortality. Results Of the 167,721 identified patients with CS, the mean (SD) age was 65.5 (±15.2) years and 35.0% were women. A total of 13.2% received any corticosteroid within the first 2 days of admission. The most common corticosteroid was hydrocortisone (73.9%). Mortality for those receiving and not receiving early corticosteroids was 48.8% and 29.6% ( p < 0.001), respectively. After IPTW, early corticosteroid use remained associated with a 3.1% (95% confidence interval [CI]: 2.4% to 3.8%, p < 0.001) higher mortality. Among patients with CS and concomitant sepsis, 27.6% received early corticosteroids, which was similarly associated with a higher mortality (weighted mean 5.8% [95% CI: 4.6% to 7.0%, p < 0.001]). Conclusions Approximately 1 in 7 patients with CS received corticosteroids early during their admission, which was associated with higher in-hospital mortality.

Introduction Women residing in rural areas or belonging to lower socioeconomic status (SES) strata experience disproportionately low rates of breast cancer screening, contributing to delayed diagnoses and poorer prognoses. In addition, their participation in clinical trials remains markedly limited, reducing opportunities to access preventive and screening interventions. Promoting research preparedness among women before disease onset may empower them to make informed decisions regarding their health and willingness to participate in clinical research with fewer emotional and logistical barriers. Methods and analysis This project applies a community-based participatory research approach to develop and refine the WeCARE (Women’s Engagement for Cancer Awareness, Resources and Education) intervention for women aged 50–74 years who have either never undergone breast cancer screening or have not received screening in the past 5 years and who reside in rural areas or belong to low SES groups. The intervention consists of two components. Component 1 is a single-day, in-person community forum that includes (a) an educational seminar led by an oncologist to address breast cancer risk and screening guidelines, (b) survivor storytelling to enhance emotional engagement and cultural resonance and (c) facilitated navigation to breast cancer screening and future research participation. Component 2 involves structured post-forum follow-up through multiple touchpoints (phone calls and mailed boosters) to reinforce knowledge, address barriers and support screening completion and research enrolment. Quantitative data (eg, screening completion, satisfaction and follow-up engagement) will be summarised using descriptive statistics to assess feasibility and reach on 50 participants. Qualitative feedback from participants will undergo thematic analysis to identify barriers, facilitators and perceived cultural relevance. Integrated mixed-method interpretation will inform iterative refinement of the WeCARE intervention and guide design of subsequent larger trials. Ethics and dissemination Approved by the Mayo Clinic Institutional Review Board (IRB #25–008934). All participants will provide informed consent. Procedures ensure confidentiality, cultural sensitivity and participant safety. Data will be stored in REDCap and disseminated through publications, conferences, local town halls and community reports.

PURPOSE Cholangiocarcinoma is a rare cancer associated with poor prognosis. Pemigatinib was the first FGFR1-3 inhibitor approved for second-line therapy and beyond, on the basis of the phase II FIGHT-202 trial. Here, we assess efficacy and safety of first-line pemigatinib. METHODS FIGHT-302 is a phase III, randomized, global trial evaluating pemigatinib as first-line therapy (ClinicalTrials.gov identifier: NCT03656536 ). Adults with advanced cholangiocarcinoma with FGFR2 rearrangement were randomized 1:1 to receive pemigatinib (13.5 mg once daily) or chemotherapy (1,000 mg/m 2 gemcitabine plus 25 mg/m 2 cisplatin once per day on days 1 and 8 of every 3-week cycle for ≤8 cycles) and were stratified by prior receipt of chemotherapy, geographic region, and tumor burden. Pemigatinib crossover was allowed for patients progressing on chemotherapy. The primary end point was progression-free survival (PFS). Secondary efficacy, safety, and exploratory end points were also analyzed. RESULTS Overall, 4,563 patients were prescreened, 196 were screened, and 167 randomly assigned to receive pemigatinib (n = 83) or chemotherapy (n = 84) before early closure of the study because of a change in standard of care. The median PFS was 8.3 months in the pemigatinib group versus 6.8 months in the chemotherapy group (hazard ratio, 0.58 [95% CI, 0.39 to 0.87]; nominal P = .0078); objective response rate was 47% versus 15%, and the median duration of response was 14.2 versus 6.3 months. Median overall survival was similar (24.4 v 25.0 months, respectively). In the crossover group (n = 42, second-line pemigatinib), the median PFS was 8.1 months. Safety was consistent with the known profile of pemigatinib. CONCLUSION To our knowledge, this was the largest, first-line, randomized, phase III trial of a targeted therapy for advanced FGFR2- rearranged cholangiocarcinoma. Pemigatinib demonstrated prolonged median PFS compared with chemotherapy, with no new safety findings.

Abstract Background and Aims A simple diagnostic method able to reliably exclude left main (LM) coronary artery disease (CAD) or LMCAD-equivalent would expand implementation of an initial non-invasive strategy in patients with chronic coronary syndrome (CCS). This study assessed the diagnostic utility of an approach using clinical and ECG stress testing (EST) variables in excluding LMCAD/LMCAD-equivalent in CCS patients. Methods In a multicentre case-control study, CCS patients undergoing invasive coronary angiography (CAG) after a maximal EST were evaluated. Cases were patients with angiographic ≥ 50% LM stenosis or ≥70% stenosis of both proximal left anterior descending and proximal circumflex arteries, matched with similar patients without them (controls) in a 1:3 ratio. A risk model developed through logistic regression was internally and externally validated. Results Three hundred and thirty-five cases were matched with 797 controls. The model area under the curve (AUC) was .78. Assuming LMCAD prevalence of 5% and a misclassification cost ratio of 1:100 (ratio of cost of performing CAG in a control to cost of not performing CAG in a case), negative predictive value was 98.2%. Thus, CAG could be safely avoided in 41% of patients, missing one LMCAD/LMCAD-equivalent diagnosis for every 58 CAGs safely spared in patients without them. Conclusions Among CCS patients, LMCAD/LMCAD-equivalent can be excluded with high negative predictive value through a model based on clinical and EST parameters, allowing initial non-invasive management of most patients able to exercise. This approach is potentially useful particularly in communities where access to computed tomography coronary angiography is limited.

PURPOSE In immunoglobulin light chain (AL) amyloidosis, amyloid fibrils cause organ dysfunction. Anselamimab, a monoclonal antibody, selectively binds to amyloid fibrils, accelerating their clearance. METHODS Newly diagnosed patients with European modification of Mayo 2004 stage IIIa or IIIb AL amyloidosis were randomly assigned to receive anselamimab or placebo with cyclophosphamide, bortezomib, and dexamethasone (with or without daratumumab). The primary end point was a hierarchical composite of time to all-cause mortality (ACM) and frequency of cardiovascular hospitalizations (CVHs), analyzed using the Finkelstein-Schoenfeld test and win ratio estimation. RESULTS Among 406 randomly assigned patients, the primary end point win ratio for anselamimab versus placebo was 1.11 (95% CI, 0.83, 1.50; P = .332) and the hazard ratio (HR) for ACM was 0.80 (95% CI, 0.57, 1.13; P = .290). CVH rates in the anselamimab and placebo groups were 0.59 (95% CI, 0.42, 0.83) and 0.89 (95% CI, 0.55, 1.43), respectively ( P = .145). Among patients with kappa isotype (n = 72), the win ratio was 2.06 (95% CI, 0.98, 4.31; P = .100) and anselamimab reduced ACM by 62% versus placebo (HR, 0.38; 95% CI, 0.17 to 0.86; nominal P = .012), and CVH by 71% (IRR, 0.29; 95% CI, 0.10 to 0.87; nominal P = .028) with improvements in Kansas City Cardiomyopathy Questionnaire-Overall Score. There was no clinical benefit observed in the lambda population. Anselamimab was generally well-tolerated; safety data were comparable between treatment arms overall. CONCLUSION Treatment with anselamimab, an antifibril antibody used alongside antiplasma cell dyscrasia therapy, while not meeting the primary end point in the overall population, significantly improved ACM and CVH in patients with kappa AL, potentially offering a new therapeutic option for this isotype.

Abstract Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45–74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45–74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen’s d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen’s d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P &lt; 0.00001) and an earlier age of first exposure to tackle football (P &lt; 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P &lt; 0.04) and rotational force (P &lt; 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.

TPS7101 Background: Patients with high-risk CLL/SLL not achieving a complete response (CR) after ≥ 12 months of BTK inhibitor (BTKi) monotherapy remain at risk for early progression due to residual disease and BTKi resistance. A BCL-2 inhibitor (BCL-2i) introduces a complementary, BCR-independent apoptotic mechanism that may deepen responses and prolong progression-free survival (PFS). Lisaftoclax, a selective oral BCL-2i with a short half-life (4-6 h), enables once-daily dosing and is approved in China as second-line CLL therapy. Lisaftoclax monotherapy has demonstrated overall response rates (ORRs) of 67% in relapsed/refractory CLL and 62.5% in BTKi-refractory disease, including del(17p)/ TP53 -mutated cases. Lisaftoclax combined with acalabrutinib achieved ORRs >97% with favorable tolerability. This study evaluates whether lisaftoclax plus BTKi (acalabrutinib, zanubrutinib, or ibrutinib) improves PFS and/or overall survival (OS) (vs continued BTKi monotherapy) in patients with CLL/SLL and residual disease after prolonged BTKi treatment. Methods: This study will enroll approximately 440 patients randomly allocated to receive lisaftoclax plus BTKi or BTKi alone. Eligible patients have CLL/SLL and, after ≥12 months of BTKi monotherapy (lines 1-3), have achieved neither CR nor progressive disease (PD). Randomization is stratified by del(17p)/ TP53 status. Key inclusion criteria include age ≥18 years, ECOG PS 0-2, and residual disease with either high-risk features (del(17p)/ TP53 mutation, unmutated IGHV , or complex karyotype [≥5 abnormalities]), or measurable residual disease with lymph nodes ≥2.5 cm in the absence of high-risk features. Exclusion criteria include prior BCL-2i therapy or Richter transformation. Patients in the investigational arm will undergo a 5-day oral lisaftoclax ramp-up to 400 mg once daily plus physician's choice of BTKi in 28-day cycles until progression or toxicity. Control patients continue their current BTKi monotherapy. Safety and disease assessments (CT/MRI) will occur regularly. The primary endpoint is PFS by independent review committee (iwCLL 2018); key secondary endpoint OS; and other secondary endpoints, PFS by investigator, ORR, duration of response, MRD negativity, and safety. Enrollment is ongoing across 126 sites in 18 countries (ClinicalTrials.gov ID: NCT06104566). Clinical trial information: NCT06104566 .

e20139 Background: Extensive-stage small cell lung cancer (ES-SCLC) frequently presents with brain metastases, affecting approximately 20% of the patients at diagnosis. The prognostic impact of baseline brain metastases on survival outcomes in patients treated with contemporary chemo-immunotherapy remains unclear, creating uncertainty in first-line treatment selection for this high-risk population. We conducted a systematic review and meta-analysis to evaluate the impact of baseline brain metastases on treatment outcomes in ES-SCLC. Methods: This PRISMA-compliant systematic review and meta-analysis was prospectively registered in PROSPERO. PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov were systematically searched from database inception through January 2026 to identify randomized controlled trials evaluating PD-1/PD-L1-based chemo-immunotherapy versus platinum-etoposide chemotherapy in adults with ES-SCLC. Two reviewers independently screened studies and extracted data, with discrepancies resolved by consensus. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled separately for patients with baseline brain metastases (BM+) and without brain metastases (BM−) using random-effects models with Hartung–Knapp adjustment. Analyses were performed using R. Prespecified subgroup analyses were conducted based on follow-up duration and immunotherapy regimen. Results: Twelve randomized controlled trials were included. Among patients with baseline brain metastases (BM+), pooled OS from seven studies did not show a significant survival benefit (HR 0.84, 95% CI 0.66–1.08, I² = 0.0%, P = 0.145), nor did pooled PFS from five studies (HR 1.03, 95% CI 0.60–1.79, I² = 0.0%). Subgroup analyses revealed no significant heterogeneity. In contrast, among patients without baseline brain metastases (BM−), pooled OS from nine studies demonstrated a significant survival benefit (HR 0.72, 95% CI 0.69–0.76, I² = 0.0%, P < 0.001), with corresponding improvement in PFS (HR 0.70, 95% CI 0.60–0.82, I² = 0.0%). These findings indicate a differential treatment effect according to baseline brain metastasis status. Conclusions: First-line chemo-immunotherapy does not apprear to confer a significant survival benefit in ES-SCLC patients with baseline brain metastases, reflecting a differential treatment effect by brain metastasis status. These findings suggest that baseline brain metastases should be considered in treatment selection and future clinical trial design and highlight the need for optimized systemic strategies for this high-risk population.

e16405 Background: Pancreatic cancer remains one of the most lethal malignancies, with a rising incidence and persistently poor survival outcomes. Gemcitabine plus nab-paclitaxel is an established standard regimen for advanced disease, however, the conventional triweekly schedule is frequently associated with significant toxicity. Biweekly dosing has been proposed to enhance tolerability while maintaining efficacy, although evidence remains limited and heterogeneous. The objective was to evaluate the efficacy and safety of biweekly versus standard gemcitabine/nab-paclitaxel in patients with advanced pancreatic cancer. Methods: A systematic search of PubMed, Embase, and the Cochrane Library was conducted to identify studies comparing Biweekly versus Standard Triweekly: gemcitabine / nab-paclitaxel in patients with advanced pancreatic cancer. The primary outcomes of interest included partial response, and treatment-related toxicities, specifically anemia, neutropenia, and use of growth factors. Statistical analyses were performed using Review Manager. Heterogeneity was assessed using the I 2 statistic, and risk of bias was evaluated using the ROBINS-I tool. Results: A total of 1357 patients from eight observational studies were included. Comparative analysis showed no significant difference in partial response between biweekly and standard triweekly gemcitabine/nab-paclitaxel in patients with advanced pancreatic cancer with a risk ratio (RR) of 0.77 (95% CI 0.57,1.04, p = 0.09). Similarly, no significant differences were observed between regimens in the incidence of anemia (RR = 1.09; 95% CI 0.74–1.59; p = 0.66) or neutropenia (RR = 1.09; 95% CI 0.86–1.37; p = 0.48). however, growth factor use was significantly lower with biweekly dosing (RR = 0.71; 95% CI 0.58–0.87; p = 0.0009). Overall survival was comparable between groups RR = 1.02 (95% CI 0.71, 1.45 p = 0.93). Conclusions: Administration of gemcitabine/nab-paclitaxel biweekly yielded clinical outcomes and safety profiles comparable to the conventional regimen, while significantly reducing the need for growth factors as supportive care. These data suggest that a biweekly regimen could be an effective alternative; however, further prospective randomized studies are necessary to verify these findings and better understand their clinical application.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are increasingly conceptualized as multisystem neurodevelopmental conditions involving behavioral, gastrointestinal, immune, and metabolic alterations. The microbiota–gut–brain axis (MGBA) has been proposed as a key framework linking these systems, although evidence from human studies remains heterogeneous and inconclusive. We conducted a structured narrative review of pediatric human studies investigating the microbiota-gut-brain axis (MGBA) in ASD and ADHD, excluding preclinical and animal studies. PRISMA 2020 principles were used as a transparency framework to support reporting of study identification, screening, and eligibility. Observational, cohort, and interventional studies were synthesized with particular attention to study design, methodology, associations with standardized clinical scales, dietary factors, and therapeutic implications. Across ASD ( n = 90), most studies were observational, predominantly cross-sectional or case-control in designs, reporting consistent associations between ASD symptom severity and gastrointestinal symptoms, intestinal permeability, immune activation, and dietary selectivity. Evidence in ADHD ( n = 21) was substantially more limited and largely observational. Diet emerged as a major modulating and confounding factor in microbiota–behavior associations. Interventional studies involving probiotics, microbiota transfer therapy, and other gut-directed approaches showed more consistent improved gastrointestinal outcomes but showed modest and heterogeneous effects on core ASD symptoms, often limited to subgroups with prominent gastrointestinal comorbidities. To strengthen interpretation of interventional findings, randomized trial reports and non-randomized interventional studies were appraised according to study design, whereas the predominantly heterogeneous observational literature was interpreted narratively. Overall, this review suggests that MGBA alterations may be better conceptualized as modifiers of symptom expression, particularly in ASD and with only emerging relevance in ADHD, rather than as disorder-specific causal mechanisms. This interpretation underscores the need for stratified, longitudinal, and clinically informed research frameworks, in line with the focus of the present research topic.