Citations

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

Background: Ischemic stroke remains a leading cause of morbidity and mortality worldwide. Cardioembolic sources account for a significant proportion of these events, necessitating accurate identification of underlying structural heart abnormalities. Traditionally, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have been utilized for this purpose, although both have limitations. Cardiac computed tomography (CCTA) has emerged as a potential alternative, offering non-invasive imaging with high sensitivity and specificity for detecting intracardiac thrombi. Objective: This study aimed to evaluate the diagnostic yield of CCTA compared to TTE and TEE in detecting high-risk cardioaortic sources of embolism, including left ventricular (LV) thrombus, left atrial (LA) thrombus, valvular thrombus, and ulcerated aortic plaques, in patients with ischemic stroke. Methods: We conducted a retrospective, single-center cohort study at Mayo Clinic, Rochester, MN, including 426 ischemic stroke patients who underwent CCTA within 30 days of stroke onset between March 2019 and June 2023. We compared the diagnostic yields of CCTA, TTE, and TEE in detecting structural cardiac sources of embolism. Results: The overall diagnostic yield of CCTA for detecting high-risk cardioaortic sources was 15.5%. Specifically, CCTA identified LV thrombus in 2.3% of patients, LA thrombus in 4.0%, valvular thrombus in 2.8%, and ulcerated aortic plaques in 7.0%. In comparative analysis, CCTA demonstrated a higher yield than TTE (16.0% vs 3.5%, p < 0.001) and a comparable yield to TEE (25.3% vs 20.7%, p = 0.47) in detecting these sources. Conclusions: CCTA proved to be a viable option for identifying high-risk structural sources of cardioembolism in ischemic stroke patients. Its non-invasive nature, coupled with the ability to perform imaging soon after stroke onset, underscores its clinical utility. However, further prospective and blinded studies are required to validate these findings and fully establish the efficacy of CCTA in this context.

Post-transplant lymphoproliferative disorder is a rare and serious complication of organ and stem cell transplant secondary to immunosuppressive therapies, most commonly of monomorphic B-cell subtype. Here we describe the first reported case of a pediatric heart transplant patient who developed both monomorphic B-cell and nondestructive PTLD with plasmacytic hyperplasia followed by an unrelated case of monomorphic T-cell and nondestructive PTLD with plasmacytic hyperplasia, which later relapsed. We detail the patient’s risk factors for development of PTLD and her successful treatment regimens. This case highlights the potential relationship between Epstein-Barr virus and/or cytomegalovirus and PTLD.

Background and Purpose Informed consent (IC) practices for endovascular thrombectomy (EVT) in acute stroke are not well elucidated. We investigated the roles and specialties of those obtaining EVT IC, aiming to provide insights for enhancing the process. Methods We conducted a survey from July- December 2023 among acute stroke care clinicians. Utilizing Qualtrics, we disseminated a questionnaire through various national and international online platforms. This analysis summarizes the characteristics of individuals who obtain IC at respondents’ institution. Results Among 168 respondents, 71% were staff physicians, 70% practiced in the US and 70% worked at academic centers. Neurology (77%) was the most common specialty obtaining EVT IC, followed by neurosurgery (41%), radiology (30%) and emergency medicine (EM) (10%). Staff physicians were the most frequently involved (61%), followed by fellows (43%), residents (48%) and advanced practice providers (APPs) (36%). Comparatvely, non-US institutions were more likely to utilize neurologists alone (50% vs 31%, P = 0.016) and staff physicians (76% vs 54%, P = 0.008), while US institutions more often utilized neurosurgeons (51% vs 18%, P < 0.001), APPs (43% vs 18%, P = 0.002) and residents (56% vs 28%, P = 0.001). Non-academic institutions used EM (25% vs 5%, P < 0.001) and APPs (50% vs 31%, P = 0.031), while academic institutions commonly utilized neurosurgeons (48% vs 18%, P = 0.001), residents (59% vs 13%, P < 0.001) and fellows (52% vs 18%, P < 0.001). Conclusion Neurologists and staff physicians are the primary providers obtaining EVT IC, with variations based on region and institution type. Future efforts to optimize the IC process should integrate various specialties and be widely adaptable.

Sudden death in children and young adults, while uncommon, carries profound clinical and societal implications. Cardiac causes, particularly inherited arrhythmias and cardiomyopathies, account for most cases, though neurologic, toxicologic, traumatic, and infectious etiologies also contribute significantly. This review explores the epidemiology, classification, and pathophysiologic mechanisms of sudden death in this population, emphasizing early clinical warning signs and identifiable risk factors. We also outline diagnostic and preventive strategies, including electrocardiography, genetic testing, and postmortem evaluation. Despite guidelines advocating preparticipation screening, real-world implementation remains inconsistent. Advances in genomics and artificial intelligence offer new opportunities for early risk detection. Finally, we discuss public health interventions such as defibrillator access, cardiopulmonary resuscitation education, and school-based protocols as essential components of a broader prevention strategy.

A 3-month-old infant presented with a painless, gradually enlarging swelling in their right orbital and temporal region. What is your diagnosis?

Abstract Erdheim-Chester disease (ECD) is a rare systemic histiocytic neoplasm, with cardiac morbidities, including cardiovascular (CV) risk factors and cardiac conditions, playing a significant yet poorly understood role in the disease burden. This study evaluated the prevalence, characteristics, and prognosis of ECD in patients with (ECD-C) and without cardiac involvement (ECD-noC) and compared the burden of cardiac morbidities with matched controls. Patients diagnosed with ECD between 1990 and 2021 at a tertiary center were included, with cardiac involvement centrally assessed using radiographic studies. Cardiac morbidities were compared with a control group without ECD, matched for age, sex, body mass index, and smoking history. Among 104 patients with ECD, 39 (37%) had cardiac involvement. Patients with ECD-C had higher rates of hypertension (67% vs 46%), hyperlipidemia (67% vs 40%), heart failure (36% vs 8%), and pericardial effusion (28% vs 2%) than those with ECD-noC. Compared with the matched non-ECD cohort, patients with ECD had higher prevalence of coronary artery disease (20% vs 7%), heart failure (18% vs 4%), and antihypertensive drug use (55% vs 40%). Notably, patients with ECD-C had inferior progression-free survival (PFS) from frontline therapy compared with patients with ECD-noC (5-year PFS, 28.3% vs 70.5%). These findings highlight the burden of CV risk factors and cardiac conditions in ECD, even without a clinical diagnosis of ECD-C. Importantly, this cardiac morbidity burden is substantial for patients with ECD-C compared with ECD-noC. Our findings highlight the need for comprehensive cardiac risk assessment and management strategies to improve patient outcomes.

This cross-sectional study analyzes patient-reported outcome findings from the Enhanced, Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) trial to investigate level of symptom burden in adolescents and young adults with cancer.