Citations

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.

Abstract Introduction Combat casualty care requires standardized proficiency criteria to ensure readiness in austere environments, yet gaps persist in defining performance thresholds for critical trauma skills. The Combat Medical Skills Sustainment Consortium (CMSSC), a novel military-civilian collaboration, aimed to validate competency thresholds for 21 Department of Defense-identified trauma skills. Materials and Methods A prospective cohort study (2022-2025) enrolled 1,495 military and civilian personnel across five academic centers, stratified by experience (novice, intermediate, expert). Skills, including cricothyroidotomy, whole blood transfusion, and ultrasound-guided vascular access, were assessed using validated checklists in Role 2-congruent simulations. Statistical analysis compared checklist performance against participant experience with a priori checklist scores estimated at 40% (novices) and 90% (experts). Results Competency thresholds were established, ranging from 77% (mechanical ventilation) to 100% (handoff). Experts achieved 85%-98% proficiency across most skills, with novices at 34%-97%. A ceiling effect was observed for less complex skills consistent with the power law of practice. Conclusion The Combat Medical Skills Sustainment Consortium validated standardized assessment tools, with potential to address readiness gaps through military-civilian synergy. Findings support consortium-guided curriculum development and highlight the need for longitudinal skill decay studies. Impact This study sets a benchmark for trauma care skills assessment, facilitating rapid adoption across military and civilian settings.

ABSTRACT Background Acute kidney injury (AKI) in hospitalised children is a major complication associated with significant morbidity and mortality. The integration of artificial intelligence (AI)/machine learning (ML) models may enable early detection and risk stratification. This systematic review evaluates the performance of AI/ML models for predicting paediatric AKI across clinical settings. Methods We systematically searched PubMed, Embase, and Web of Science for studies applying AI/ML models to predict AKI in paediatric populations. Studies reporting performance metrics such as the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and F1 score were included. Results Among 470 records identified, 11 studies met the inclusion criteria, with 14 AI/ML models used. The overall sample size included 33 949 paediatric patients with an AKI proportion of 12.5%. Meta-analyses of the AUC were conducted on neural network, gradient boosting, and logistic regression. Gradient boosting had the highest pooled AUC of 0.873 (95% confidence interval 0.836–0.909). Random forest demonstrated the highest median sensitivity (0.821), specificity (0.942), PPV (0.860), NPV (0.935), and accuracy (0.821); however, these metrics could not be pooled due to inconsistent reporting and limited validation. Conclusion Gradient boosting, random forest, and logistic regression demonstrated reasonable predictive performance for paediatric AKI prediction within specific clinical contexts. However, small sample size, heterogeneity, lack of testing/validation cohorts, insufficient data, and inconsistent patient populations and AKI diagnostic criteria restrict generalisability.