Citations

BACKGROUND: Left ventricular (LV) dysfunction is a potential cardioembolic source of ischemic stroke, but its role in recurrent stroke risk and treatment response remains unclear. We explore whether LV injury associates with the risk of recurrent stroke and modifies the association between anticoagulation and stroke recurrence using real-world data. METHODS: We performed a multicenter, retrospective study of Cardiac Abnormalities in Stroke Prevention and Recurrence cohort across 27 US sites. Patients with LV ejection fraction ≥20% were included. LV injury, defined as LV ejection fraction 20% to 40% and wall motion abnormality, was the primary exposure and treatment effect modifier. The treatment of interest was anticoagulant versus antiplatelet therapy. The composite outcome included recurrent stroke, major bleeding, or death. Outcomes were evaluated using unadjusted and inverse probability weighting adjusted Cox proportional hazards models, with treatment effect modification tested by LV injury status. RESULTS: Among 2685 patients enrolled, 2328 with complete data were analyzed (median age, 65 years; 49.8% female; median follow-up, 1.6 years). LV injury was present in 310 patients (13.3%). Overall, 535 events occurred: 258 recurrent ischemic strokes, 28 hemorrhagic strokes, 67 major hemorrhages, and 256 deaths. LV injury was associated with a higher unadjusted risk of the primary outcome (hazard ratio [HR], 1.51 [95% CI, 1.21–1.87]), though nonsignificant after inverse probability weighting adjustment (adjusted HR, 1.29 [95% CI, 0.97–1.70]). In the LV injury subgroup, anticoagulation versus antiplatelet therapy was associated with a lower risk of the primary outcome (adjusted HR, 0.24 [95% CI, 0.10–0.59]), relative to the non-LV injury subgroup (adjusted HR, 1.28 [95% CI, 0.83–1.95]; p[LV-interaction], 0.001). Similar interactions were seen for EF 20% to 40% (versus >40%; adjusted HR, 0.19 [95% CI, 0.04–0.86]; p[LV-interaction], 0.001) and wall motion abnormality (versus no wall motion abnormality; adjusted HR, 0.33 [95% CI, 0.15–0.73]). CONCLUSIONS: After cryptogenic stroke, anticoagulation in those with LV injury was associated with lower rates of recurrent stroke, major bleeding, and death. These findings warrant confirmation in a dedicated randomized controlled trial. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06398366.

Objectives: To determine the frequency with which emergency medical services (EMS) clinicians recognize patients enrolled in hospice and describe their prehospital management. Methods: Observational cohort study of patients enrolled in hospice who were transported by EMS within a health system between May 5, 2018, and June 4, 2023. Two physicians reviewed each encounter to determine whether interventions were comfort-focused (hospice philosophy) or life-sustaining care. Interrater reliability was 100% (k = 1.0). Descriptive statistics are provided. Results: EMS clinicians identified hospice enrollment in 51% ( n = 46) of 88 encounters. Most patients (90%, n = 79) received comfort-focused care. Life-sustaining care was provided to four patients identified as hospice-enrolled and included cardiopulmonary resuscitation, an advanced airway, and vasopressors ( n = 1, 25%); spinal immobilization ( n = 2, 50%), and naloxone ( n = 1, 25%). Conclusion: Most patients received care consistent with the philosophy of hospice. However, EMS clinicians may have only identified half of patients enrolled in hospice. This demonstrates an opportunity to improve recognition of patients’ care preferences, starting in the out-of-hospital setting.

Abstract Spatial transcriptomics analyses often require coordinating specialized Python and R methods. When analytical intent is translated through ad hoc scripts or unconstrained LLM generated code, workflows can be difficult to inspect, rerun, or compare. We present ChatSpatial, a schema enforced orchestration framework in which an LLM selects versioned tools and parameters rather than executable code. Built on the Model Context Protocol, ChatSpatial integrates 65 methods across 15 analytical categories into 20 typed tools with curated defaults. In two cancer case studies, ChatSpatial coordinated cross ecosystem workflows that recovered the analytical structure and central conclusions of published ovarian cancer and oral squamous cell carcinoma analyses. Across three LLMs, schema enforcement raised parameter validity from 20% to 98% and stabilized method selection. In end to end benchmarks against two code generation alternatives, it yielded higher execution success and output concordance.

IgA vasculitis (IgAV) and IgA nephropathy (IgAN) are closely related disorders that usually present in childhood. Pulmonary involvement is rare and histopathologic features thereof in adults are poorly understood. Institutional archives were searched for adults with IgAV or IgAN and diffuse parenchymal lung disease. Ten patients (6 men, median age 59 years) with lung tissue sampling were enrolled. Clinical history and pathology slides were reviewed. All patients were diagnosed with IgAV or IgAN before or concurrently with lung disease. Symptoms were nonspecific but hemoptysis was common. Radiologically, bilateral ground-glass opacities, consolidation, and reticulonodular densities were typical. Histologically, 6 cases (60%) featured acute or subacute diffuse alveolar hemorrhage (DAH) accompanied by definite (40%) or probable (20%) capillaritis. Two cases (20%) featured resolved DAH only, manifesting as alveolar hemosiderosis without other changes. And 2 cases featured organizing pneumonia without DAH. Five patients had a chronic interstitial pneumonia in the background, including 3 with nonspecific interstitial pneumonia (NSIP) and 2 with unclassifiable fibrosis. Findings were similar in IgAV versus IgAN. Of 4 patients with follow-up information, 2 died during hospitalization, one died 9 weeks later of secondary complications, and one was treated with rituximab and nintedanib and is alive 2 years later. To our knowledge, this is the largest series detailing pulmonary histopathologic findings in adults with IgAV or IgAN. Most cases show acute DAH with capillaritis; less commonly, old DAH, organizing pneumonia, NSIP, or unclassifiable fibrosis may be observed. Some patients do well with treatment but fatal cases also occur.

Abstract Background Clival metastases are a rare and clinically aggressive manifestation of advanced prostate cancer, associated with cranial nerve palsy and poor survival. The molecular features of prostate cancers giving rise to clivus metastases remain unknown. Patients and methods We performed a multi-center retrospective study across six institutions, identifying prostate cancer patients with radiographically confirmed clival metastases and available next-generation sequencing (NGS) data. Baseline characteristics and clinical outcomes were collected. Genomic alterations from tissue- and/or blood-based assays were aggregated at the patient level and compared with a publicly available metastatic castration-resistant prostate cancer (mCRPC) cohort (SU2C/PCF). Results Fifty-nine patients with clival metastases contributed 87 molecular assays. More than half of patients had Gleason grade group 5 cancer and presented with de novo metastatic (M1) disease. The median interval from initial prostate cancer diagnosis to clival metastasis was 71.4 months (95% CI, 42.0-101.7), while median overall survival following clival involvement was only 15.3 months (95% CI, 6.9-22.8). Compared with the SU2C/PCF mCRPC cohort, clival metastases showed significant enrichment of BRAF and CHEK2 alterations as well as homologous recombination repair (HRR) with relative depletion of AR-related, PI3K pathway, and G2–M pathway alterations. Conclusion Prostate cancers giving rise to clival metastases exhibit a distinct molecular profile enriched for DNA damage–repair and RAF kinase alterations, suggesting unique metastatic biology and potential therapeutic vulnerabilities.

Abstract Dysphagia is defined as a subjective sensation of difficulty swallowing and can result from oropharyngeal or esophageal etiologies based upon patient symptoms. Dysphagia affects approximately 16% of adults in the general population, with prevalence increasing with age. Esophagogastroduodenuoscopy (EGD) is initially performed to assess for structural abnormalities resulting in esophageal dysphagia. However, if EGD reveals no pathologic abnormalities, high-resolution manometry (HRM) and barium esophagography are performed in order to assess for underlying causes of dysmotility. Esophageal motility disorders (EMDs) are an underrecognized cause of dysphagia and can be characterized by impaired esophageal peristalsis or lower esophageal sphincter dysfunction. High-resolution manometry (HRM) measures key metrics such as integrated relaxation pressure (IRP), which is the deglutitive relaxation across the LES, and metrics of esophageal body peristalsis based on distal contractile integral (DCI) and distal latency (DL). The Chicago Classification version 4 (CCv4.0), published in 2021, provides a standardized classification scheme for differentiating EMDs using metrics from HRM. Additionally, barium esophagography has remained an important adjunctive diagnostic modality, as this may identify strictures, neoplasms, or hiatal hernias, but can also identify major motility disorders such as achalasia and distal esophageal spasm. The combined use of HRM with timed barium esophagram can enhance the diagnostic accuracy of EMDs, particularly when HRM demonstrates inconclusive findings. Therefore, radiologists should be familiar with how imaging findings from barium esophagram integrate with findings noted on HRM. The aim of this review is to highlight the findings of EMDs noted on HRM in conjunction with barium esophagography, thereby illustrating characteristic patterns of primary and secondary EMDs.

PURPOSE BRCA carriers face high risks of developing both breast and ovarian/fallopian tube cancers (hereafter referred to as ovarian ). Among BRCA carriers with ovarian cancer, it is not clear whether the risk of breast cancer is sufficiently high that risk-reducing mastectomy should be offered. This study aimed to assess the risk of breast cancer BRCA carriers after a diagnosis of ovarian cancer. METHODS We included women with a pathogenic/likely pathogenic variant in BRCA1 or BRCA2 , a diagnosis of ovarian cancer, and no other cancer history and no risk-reducing bilateral mastectomy. Women were followed for incident breast cancer from the date of ovarian cancer diagnosis or the date of baseline questionnaire, whichever came last. The 5-, 10-, and 15-year cumulative risks of breast cancer were compared for women with ovarian cancer and an age-matched set of control women without ovarian cancer. RESULTS A total of 960 participants with ovarian cancer were identified (814 BRCA1 and 146 BRCA2 carriers). After a mean follow-up of 4.9 years, 41 women (4.3%) developed breast cancer, at a mean age at diagnosis of 57.5 years (range, 39-74). Actuarial cumulative breast cancer risks after ovarian cancer were 4.4%, 8.9%, and 11.5% at 5, 10, and 15 years, respectively. Only three breast cancer–related deaths occurred. Among 741 age-matched BRCA carriers without ovarian cancer, actuarial cumulative risks of breast cancer were 20.9%, 38.6%, and 47.2% at 5, 10, and 15 years, respectively. The hazard ratio for breast cancer, after an ovarian cancer diagnosis, compared with no ovarian cancer, was 0.18 ([95% CI, 0.12 to 0.27]; P < .0001). CONCLUSION After ovarian cancer, BRCA carriers have a relatively low risk of breast cancer. Risk-reducing mastectomy should not be recommended routinely, but might be considered for long-term survivors. Magnetic resonance imaging surveillance and/or mammography is a realistic alternative.