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The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. The mean scores for the teams were calculated. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. The Dice score for the winning team was 0.65 ± 0.25. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space. The Dice scores and lesion detection rates of all algorithms diminished with decreasing tumor size, particularly for tumors smaller than 100 mm3. In conclusion, algorithms for BM segmentation require further refinement to balance high sensitivity in lesion detection with the minimization of false positives and negatives. The BraTS-METS 2023 challenge successfully curated well- annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied environments and providing the tools for future development of personalized volumetric reports to patients undergoing BM treatment.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45–1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28–2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35–5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53–20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18–0.88]; P interaction =0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

ABSTRACT Background Kidney disease significantly increases the risk of dementia, including among kidney transplant (KTx) recipients. To date, the cost implications of dementia after KTx are not well described. Methods We performed a retrospective cohort study of US Renal Data System (USRDS) data (2006–2020) to estimate cost of care for ≥65‐year‐old Medicare insured KTx recipients (2006–2020) with newly diagnosed dementia ( n = 3285), compared to propensity‐matched controls without dementia ( n = 6570). KTx recipients age 65+ years with post‐KTx dementia were identified by diagnosis codes, and costs were computed based on payments on Medicare claims. Average costs per month, marginal costs per month, and cumulative costs were compared after dementia diagnosis versus after the equivalent time post‐KTx in controls. Results Dementia was diagnosed at a mean of 5.1 ± 3.4 years post‐KTx. Patients' characteristics were well matched in cases versus controls, including age (mean: 70.1 vs. 69.9 years), sex (38.4% vs. 37.9% women), race (23.7% vs. 22.2% African American), and cause of ESKD (45.4% vs. 43.7% diabetes). Over 4 years post‐KTx, dementia was associated with reduced survival (27% vs. 68%) along with $66 145 (95% CI $51 560‐$78 489) higher Medicare spending. Average monthly costs in dementia patients reached a maximum of $12 713 and exceeded the cost of unaffected patients by up to $9789 per month. Conclusions Post‐KTx dementia dramatically increased resource utilization and reduced post‐KTx surivival. These findings highlight the need for care pathways that better integrate cognitive health assessment and management into the care of KTx candidates and recipients.

PURPOSE To compare overall survival (OS) in patients with baseline metastatic gastric adenocarcinoma (GA) with and without ovarian metastasis (OM). Furthermore, within the group that had ovarian metastases, we aimed to assess whether there was a survival benefit (SB) with palliative oophorectomy (PO). PATIENTS AND METHODS This is a single-institution retrospective analysis of the clinicopathological features of women diagnosed with metastatic GA with a comparison of outcomes based on PO status. We identified 240 women with baseline metastatic GAs who were treated at MD Anderson Cancer Center between February 2003 and September 2022. Among these women, we categorized a subgroup of 102 women who had OM from their primary GA. Patients were analyzed whether they underwent PO. RESULTS Patients who developed OM were most often non-Caucasian, had peritoneal involvement, and had tumors that were both human epidermal growth factor receptor 2–negative and PD-L1–negative, with signet ring cell features and diffuse histological type. Among patients with ovarian metastases, those who had PO had an Eastern Cooperative Oncology Group = 0, more comprehensive molecular and immunohistochemical profiling, lower percentage of family history of gastroesophageal malignancies, and lower interval between diagnosis of the GA primary and the OM. PO was associated with significantly improved OS in this subgroup (hazard ratio, 0.5 [95% CI, 0.31 to 0.81]; P = .005). CONCLUSION To our knowledge, this is the largest multiethnic population study assessing SB of PO in patients with GA with OM. Additionally, it is the largest study analyzing survival in this population according to the patient's multiethnic characteristics and metastasis timing and growth patterns. PO presents as a therapeutic option for women with GAs with OM if the patient is clinically suitable for surgical resection.

BACKGROUND: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection. METHODS: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks. RESULTS: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P =0.02; I 2 =0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P =0.03, I 2 =0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants. CONCLUSIONS: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.

e17035 Background: 177 Lu-PSMA-617 was approved in March 2022 for patients with mCRPC pretreated with an androgen receptor pathway inhibitor (ARPI) and a taxane. There are limited data on the effectiveness of treatments post- 177 Lu-PSMA-617. The aim of this study was to describe prostate-specific antigen (PSA) responses among patients with mCRPC receiving a guideline-recommended therapy as the next therapy after 177 Lu-PSMA-617 treatment. Methods: This retrospective, observational study used real-world data from the PRECISION data platform, a proprietary dataset developed by Novartis, comprised of patient-level electronic health record and claims data that represent the US advanced prostate cancer population in the community, academic, urology, and medical oncology settings. Patients with mCRPC who received any guideline-recommended therapy at least 14 days after treatment with 177 Lu-PSMA-617 between March 23, 2022 and July 31, 2024 were included. Guideline-recommended therapies included abiraterone, enzalutamide, darolutamide, apalutamide, cabazitaxel, docetaxel, pembrolizumab, sipuleucel-T, niraparib, olaparib, talazoparib, rucaparib, and radium-223. Patients’ PSA values while on 177 Lu-PSMA-617 treatment were compared with their PSA values during the subsequent therapy course. Proportions of patients achieving reductions in PSA levels ≥50% (PSA50) and ≥80% (PSA80) were estimated. All analyses were descriptive. Results: A total of 152 patients receiving any subsequent guideline-recommended therapy after 177 Lu-PSMA-617 were identified. Mean age was 72.1 years. Most patients received an ARPI (n=93, 61.2%) – abiraterone (n=38), enzalutamide (n=37), darolutamide (n=10), or apalutamide (n=8) – as their subsequent therapy. Of patients who received a taxane (n=42, 27.6%), 24 received cabazitaxel and 18 received docetaxel. Median time to initiation of subsequent therapy was 206 days (interquartile range [IQR] 101–301 days) from 177 Lu-PSMA-617 initiation and 44 days (IQR 17–119 days) from 177 Lu-PSMA-617 discontinuation. Overall, among patients with sufficient information for PSA evaluation (n=30), 46.7% achieved PSA50 and 40.0% PSA80 post- 177 Lu-PSMA-617. Among patients receiving an ARPI, PSA50 was observed in 11/18 (61.1%) and PSA80 in 10/18 (55.6%). Among patients receiving a taxane, PSA50 and PSA80 were seen in 3/12 (25.0%) and 2/12 (16.7%), respectively. Conclusions: In this real-world analysis, the majority of patients who received guideline-recommended therapies after 177 Lu-PSMA-617 achieved at least a PSA50 response, suggesting that 177 Lu-PSMA-617 treatment does not preclude response to other subsequent therapies.

e17030 Background: The broad therapeutic arsenal for mCRPC, with overlapping indications, makes selecting the optimal treatment sequence challenging in clinical practice. The aim of this study was to evaluate the prostate-specific antigen (PSA) responses and overall survival (OS) among patients with mCRPC receiving 177 Lu-PSMA-617 based on prior ARPI and taxane treatment exposure. Methods: This retrospective, observational study used real-world data from the PRECISION data platform, a harmonized dataset of advanced prostate cancer patients in the US from diverse clinical settings. Patients with mCRPC who had received ≥1 dose of 177 Lu-PSMA-617 between March 23, 2022 and July 31, 2024, after prior treatment with ≥1 ARPI and ≥1 taxane, were included. To assess PSA response, the baseline PSA value obtained within 90 days before starting 177 Lu-PSMA-617 was compared with the on-treatment PSA value obtained ≥28 days after 177 Lu-PSMA-617 initiation. The number of patients achieving PSA reductions ≥50% (PSA50) and ≥80% (PSA80) were estimated, with patients classified into two cohorts based on prior ARPI and taxane exposure: (1) prompt cohort: after only 1 ARPI and 1 taxane, and (2) deferred cohort: >1 ARPI and/or >1 taxane. Patient characteristics and treatment patterns were evaluated descriptively. OS from 177 Lu-PSMA-617 initiation was estimated using Kaplan–Meier methodology. Results: A total of 431 patients were included: 177 patients in the prompt cohort and 254 patients in the deferred cohort. Of patients in the deferred cohort, 185 (72.8%) received ≥1 ARPI and 1 taxane, 32 (12.6%) received 1 ARPI and ≥1 taxane, and 37 (14.6%) received ≥1 ARPI and ≥1 taxane. Median (interquartile range) age was 73 (67–78) years and most demographic characteristics were balanced between groups. Patients in the deferred cohort had higher median PSA levels at baseline (63.1 ng/mL vs 25.2 ng/mL). PSA50 was observed in 18/33 (55%) patients in the prompt cohort vs 28/66 (42%) in the deferred cohort. PSA80 was observed in 13/33 (39%) patients in the prompt cohort vs 21/66 (31%) in the deferred cohort. Across both cohorts, median OS was 18.0 months (95% confidence interval [CI]: 15.1 months–not reached [NR]). Median OS was NR in patients in the prompt cohort vs 15.1 months in patients in the deferred cohort (95% CI: 11.6 months–NR). Conclusions: In this large real-world study, prompt initiation of 177 Lu-PSMA-617 (after only 1 ARPI and 1 taxane) showed superior clinical outcomes versus deferred initiation of 177 Lu-PSMA-617. Patients were more likely to achieve a PSA reduction ≥50% and ≥80% and had longer OS with prompt initiation of 177 Lu-PSMA-617. These results may help to guide treatment sequencing in clinical practice.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

Background Right ventricular (RV) maladaptation to elevated pulmonary afterload is the primary determinant of outcomes in pulmonary artery (PA) hypertension; however, the pathobiological mechanisms underlying RV decompensation remain poorly understood. Methods We performed global untargeted metabolomics on plasma from 55 patients who underwent gold‐standard RV‐PA coupling measurements using multibeat pressure volume loop assessment in a single‐center cohort and from 1027 patients with coupling surrogate measurements in a larger multicenter cohort, the PVDOMICS (Pulmonary Vascular Disease Phenomics) study. Age and sex‐adjusted linear regression was performed to identify associations between metabolites and coupling metrics. Additionally, we performed a metabolic flux analysis using gene expression data from RV tissue in an independent cohort of 32 patients. Partial least squares–discriminant analysis was used to identify metabolites and reactions characteristic of the decompensated RV. Results RV‐PA coupling was negatively associated with tricarboxylic acid (TCA) cycle intermediate levels. Specifically, plasma α‐ketoglutarate and fumarate were significantly associated with all coupling metrics in both cohorts. Metabolic flux analysis indicated that decompensated RVs exhibited aberrant TCA cycle activity, including reduced acetyl coenzyme A entry and increased lactate elimination, suggesting a shift from the TCA cycle toward glycolysis at the RV tissue level. Conclusions We identify an association between circulating TCA cycle intermediate levels and RV‐PA uncoupling in 2 independent cohorts, and dysregulated TCA cycle metabolism in decompensated PA hypertension RVs, suggesting that aberrant TCA cycle metabolism could represent a hallmark of RV maladaptation in PA hypertension. Further study of this pathway is warranted to develop novel biomarkers of RV function or RV‐targeted therapies.

ABSTRACTBackground/AimsMany patients with digestive symptoms describe underlying urinary or gynecologic symptoms, which may increase visceral sensitivity in the abdominopelvic region and amplify distress around digestive symptoms. The aim of this study was to describe the prevalence of urinary and gynecologic symptoms in patients with disorders of gut–brain interaction (DGBI).MethodsConsecutive adult patients with a female reproductive tract who were referred for GI behavioral medicine evaluation for DGBI at a tertiary care center between 2022 and 2023 were prospectively evaluated for symptoms associated with urinary and gynecologic dysfunction. Descriptive statistics were conducted to assess the prevalence of these symptoms within this population by anatomic region affected (esophagus, stomach, and bowel).ResultsA total of 432 patients were included in our cohort with a mean (SD) age of 40.0 years [Q1;Q3 29.0–52.0], with a predominantly White population (86.1%). Dysmenorrhea (61.0%) and menorrhagia (58.6%) were commonly reported among women with digestive symptoms. Urinary symptoms were less common, with 18.7% reporting pain with urination, 33.0% reporting difficulty voiding urine, and 26.1% reporting a history of frequent UTIs. 23% of women experienced ≥ 4 urinary/gynecologic symptoms. There were no significant differences in the type of urogynecologic symptoms reported based on the affected area of the GI tract.ConclusionUrogynecologic symptoms are common among patients with DGBIs affecting the entirety of the GI tract. We presume the presence of these comorbid symptoms is likely to impact symptom severity, quality of life, and could affect treatment response. Future studies are necessary to understand the mechanisms behind these shared conditions as well as develop effective treatments that address their overlap.