Citations

Background: Critical congenital heart disease (CCHD) screening algorithms based on pulse oximetry have up to 27% false positive rate at high altitudes (>2500 m) despite altitude-specific cutoff changes. We examined the added value of an adult-based AI model applied to phonocardiography (AI-PCG) in the digital stethoscope EKO Core 500 in these settings. Research Question: What is the diagnostic performance of AI-PCG model compared to pulse oximetry in detecting neonatal CCHD across different altitudes in Latin America? Methods: This observational, prospective, case-control study included newborns born at different altitudes from 0 to 4380 meters in Peru, Mexico, Colombia and Bolivia. All underwent preductal and postductal oximetry at least 18 hours after birth, electrocardiography and PCG with the digital stethoscope. All CCHD cases were confirmed by echocardiography. Non-CCHD cases were defined by echocardiography or clinically if they were alive for 1 month and had 1) negative pulse oximetry, 2) no hospitalization due to cardiac or pulmonary causes and 3) no cyanosis or pneumonia. Those with abnormal pulse oximetry, genetic syndromes or murmur detection underwent echocardiography. Diagnostic performance metrics [area under the receiving operating characteristic curve (AUROC), sensitivity, specificity and false positive rate] were evaluated per modality. Results: A total of 1152 newborns were enrolled, 725 at <2500 m [13 (1.8%) with CCHD] and 427 at >2500 m [6 (1.4%) with CCHD]. Out of 19 CCHD cases, 17 had positive pulse oximetry and 9 had a positive AI-PCG model. One newborn with severe coarctation of the aorta and atrial septal defect had negative pulse oximetry and AI-PCG model. Pulse oximetry showed superior AUROC (0.932 vs 0.664), sensitivity (89.5% vs 47.4%), specificity (97% vs 85.5%) and lower false positive rate (3% vs 14.5%) compared to the AI-PCG model across altitudes. Diagnostic accuracy varied with altitude (Figure): at <2500 m, pulse oximetry showed higher AUROC (0.999 vs 0.612) and lower false positive rate (0.1% vs 16%) than AI-PCG model, but at >2500 m, pulse oximetry had similar AUROC (0.794 vs 0.774) and lower false positive rate (7.8% vs 11.9%) than the AI-PCG model. Conclusion: Pulse oximetry has superior diagnostic performance than an adult-based AI-PCG model when screening for neonatal CCHD at <2500 m, but similar performance is found >2500 m.

Objective To evaluate outcomes in patients with type 2 endoleak (T2E) and the impact of treatment outside the device instructions for use (IFU). Methods This retrospective single-center study included abdominal aortic aneurysms (AAA) patients who underwent EVAR (2011- 2024). Primary outcomes were 30-day and mid-term complications, reintervention, and mortality by T2E status. Propensity score matching was applied and secondary analysis stratified outcomes by IFU compliance, comparing within ( in IFU) or outside( out IFU) IFU in each T2E group. Results Among 154 EVAR patients (137 men (89.1%) and 17 women (11.0%); mean age 77.5 ± 7.6 years), 77 were T2E(−), and 77 were T2E(+). Baseline characteristics were similar. Thirty-day complications were comparable (T2E(−): 5, 6.4% vs T2E(+): 2, 2.56%, P = 0.72). The mean follow-up duration was 2.7 ± 2.4 years. Sac diameter change (Δ) decreased in the T2E(−) (7.7 ± 8.4 mm) and enlarged in the T2E(+) (1.79 ± 12.5 mm; P < 0.01). Mid-term graft-related complications (T2E(−): 3, 3.8% vs T2E(+): 49, 62.8%, P < 0.01) and reinterventions (T2E(−): 3, 3.8%, vs T2E(+): 20, 25.6% P < 0.01) were higher in the T2E(+) with no difference in mortality ( P = 1.00). These findings remained after excluding type 1 endoleaks. Among the T2E(+), those treated out IFU had longer hospital stays ( out IFU: 3.0 ± 2.8 days vs in IFU: 1.8 ± 2.0 days, P = 0.03), higher T1E ( out IFU: 3, 33.3% vs in IFU: 1, 4.34%, P < 0.01), higher rates of reintervention ( out IFU: 9, 100.0% vs in IFU:17; 24.6%, P < 0.01) and higher all-cause mortality than those within IFU criteria ( out IFU: 5, 55.0% vs in IFU: 13, 18.8%, P < 0.01). IFU status did not significantly affect outcomes in T2E(−) patients. Conclusions T2E is associated with sac growth and increased reinterventions, but not higher mortality. On subgroup analysis, those T2E(+) treated out IFU had longer hospitalizations, higher T1E rates, more reinterventions, and higher all-cause; but not aneurysmal-related mortality.

Importance Adjuvant radiotherapy can improve locoregional control and survival in patients with olfactory neuroblastoma (ONB), particularly with advanced-stage and histologic-grade disease. Standard radiotherapy treatment is with intensity-modulated radiotherapy (IMRT). Proton beam radiotherapy (PBRT) provides theoretical advantages in greater sparing of dose to uninvolved organs at risk. Objective To investigate if there are differences in the effectiveness and radiation treatment–related adverse events (RTAEs) between adjuvant IMRT and PBRT for patients with ONB. Design, Setting, and Participants This propensity score–matched cohort study included patients with ONB treated between February 2005 and April 2021 with either IMRT or PBRT at 9 academic tertiary care centers in North America. Patients were matched 1:2 based on age, modified Kadish stage, and Hyams grade. Data were analyzed from July 2024 to January 2025. Exposure Adjuvant IMRT or adjuvant PBRT. Main Outcomes and Measures Local recurrence-free survival (RFS), any RFS, and overall survival (OS). RTAEs, ie, grade 2 events or higher based on Common Terminology Criteria for Adverse Events, were recorded for both modalities. Results Of 54 included patients, 27 (50%) were female, and the mean (SD) age was 46.2 (15.4) years. A total of 18 were treated with PBRT and 36 were treated with IMRT. Most patients had modified Kadish stage C disease (33 of 54 [61%]), and 24 patients (44%) had Hyams grade III or IV disease. The RTAE rate was 20% (8 of 40); IMRT had a rate of 21% (6 of 29), and PBRT had a rate of 18% (2 of 11). The difference in the point estimates for 10-year RFS showed a potential clinical benefit favoring IMRT, although the wide confidence interval indicates uncertainty (10-year RFS: IMRT, 63.3%; 95% CI, 44.6-89.8; PBRT, 37.8%; 95% CI, 14.2-100; difference, 25.5 percentage points; 95% CI, −17.6 to 68.6). There were no clinically meaningful differences in 10-year local RFS (IMRT, 75.6%; 95% CI, 59.8-95.4; PBRT, 72.7%; 95% CI, 45.2-100; difference, 2.9 percentage points; 95% CI, −35.9 to 41.7) or 10-year OS (IMRT, 61.8%; 95% CI, 42.8-89.1; PBRT, 57.1%; 95% CI, 24.3-100; difference, 4.7 percentage points; 95% CI, −49.2 to 58.6), although wide confidence intervals indicate considerable uncertainty. Conclusions and Relevance Due to the imprecision of estimates, no definitive conclusions can be made regarding the comparative effectiveness of IMRT vs PBRT for patients with ONB. These preliminary data may inform the design of appropriately powered prospective studies evaluating the efficacy of PBRT vs IMRT in this population.

Abstract Clinical flow cytometry laboratories are facing rising test volumes, greater assay complexity, and increasing requirements for quality control and assay validation. In response, the International Clinical Cytometry Society (ICCS) conducted a workload survey in early 2023 to gather updated information on assay volumes, complexity, staffing, and technology. Data analysis focused on identifying correlations between length of time to introduce new assays and other factors as a means to gain insight about laboratories that seem to be either adapting or struggling. Flow cytometry assays were categorized into 3 levels of technical/interpretative complexity: high (e.g., measurable/minimal residual disease (MRD assays)), moderate (e.g., leukemia/lymphoma assays (Assays L&L ), excluding MRD assays), and low (e.g., CD4 count). Annual assays per staff member were calculated according to staff involved in case sign‐out (Staff Signout ) or other laboratory operations (Staff LabOps ). Respondents were from 101 laboratories in the United States (69.3%), Canada (4.0%), and other countries (26.7%). Low, moderate, and high technical/interpretative complexity assays were performed in 85.1%, 97.0%, and 47.5% of all laboratories, respectively. Median annual total assays (Assays Total ) per laboratory were 3515 and, based on complexity, were 1518.5 (low), 1808.8 (moderate), and 350 (high). Among all laboratories, the median time (interquartile range) to introduce new Assays L&L was 6 mos. (4–12 mos.), to introduce MRD assays was 11 mos. (5–12 mos.), and to validate/go‐live with new cytometers was 8 mos. (4–12 mos.); these times positively correlated with each other. This study confirmed significantly increased workload since the prior ICCS 2013 workload survey with a concurrent decrease in Staff LabOps . Faster introduction of new assays correlated with other successes, including quicker validation of and going live with new cytometers. Among all laboratories, those that performed myeloid MRD assays versus those that did not were also found to be faster to introduce new assays. The need for sufficient staffing has been emphasized because laboratories with both higher annual volumes of myeloma MRD assays and higher ratios of Assays Total per Staff LabOps were slower to introduce new assays. “Lack of staff and/or time dedicated or protected for assay development” and, more generally, “staff number” were the most commonly identified major barriers for new assay development, with the former specifically linked to slower introduction of new assays among all laboratories.

ABSTRACT Objectives This portion of the Geriatric Emergency Department (GED) Guidelines 2.0 focuses on delirium in the emergency department (ED). Methods A multidisciplinary group applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and develop recommendations related to older ED patients with possible delirium. Results The GED Guidelines 2.0 Delirium Work Group derived six evidence‐based recommendations for risk stratification, diagnosis, and brain imaging. To reduce universal screening, the Delirium Risk Score may be used to identify older adults at low risk for delirium, though the evidence certainty is very low. In adults over 65 admitted to ED observation units, Zucchelli's risk assessment tool (threshold ≥ 4) may stratify delirium risk, also with very low certainty. For adults over 75, the REDEEM Score may be used to identify low‐ or high‐risk individuals, again with very low certainty. For diagnosis, 4AT, bCAM, CAM‐ICU, mCAM, AMT‐4, or RASS may be used to rule delirium in or out, based on very low certainty. The Delirium Triage Screen (DTS) may be used to rule out, but not to rule in, delirium, also with very low certainty. For diagnostic imaging, there is very low certainty of evidence to recommend for or against obtaining a head CT as part of the evaluation for older ED patients with delirium. All recommendations are conditional, reflecting very low certainty of evidence due to the lack of high‐quality ED‐based studies and comparative effectiveness research. Conclusion Rigorous ED‐based research is needed to strengthen evidence and guide delirium care for older adults in geriatric emergency medicine.

OBJECTIVES The Pediatric Emergency Care Applied Research Network (PECARN) cervical spine injury (CSI) clinical prediction rule (CPR) was developed to reduce unnecessary imaging in pediatric trauma patients and ensure accurate diagnosis. This study aimed to identify barriers and facilitators to future implementation of this rule in diverse emergency department (ED) settings. METHODS We conducted 40 interviews with 48 clinicians, including ED physicians, surgeons, nurses, and advanced practice providers at 21 health care facilities across the United States. Semistructured interviews explored determinants impacting implementation, guided by the Tailored Implementation for Chronic Diseases (TICD) framework. We conducted a deductive thematic analysis using the TICD domains as a priori codes. Three researchers independently coded the transcripts and identified key themes aligned with the TICD framework. RESULTS Barriers included limited guideline accessibility, workflow disruptions, and inconsistent integration with electronic health records. Clinicians’ concerns regarding the applicability and adherence to guidelines were also significant. Facilitators identified included institutional support, stakeholder engagement, and targeted education that addressed knowledge gaps. Implementation strategies varied by context, with suggestions for electronic health record-based decision tools in resource-equipped facilities and external aids, such as pocket cards, in lower-resource settings. Addressing legal concerns, clinician resistance, and workflow alignment emerged as critical priorities. CONCLUSION Implementing the PECARN CSI CPRs requires addressing contextual barriers such as workflow challenges, clinician adherence, and technology integration. Context-sensitive strategies are essential for successful adoption and improved decision-making in pediatric trauma care. Future research should evaluate the impact of these strategies on clinician behavior and patient outcomes.

Abstract Background Upper gastrointestinal Crohn’s disease (UGICD) is an uncommon phenotype with limited management guidelines. We reviewed evidence on the safety and efficacy of pharmacological interventions for UGICD. Methods We searched MEDLINE, Embase, and Cochrane CENTRAL (1990-2025) for randomized controlled trials (RCTs) and comparative observational studies evaluating pharmacological or dietary interventions for UGICD, including esophagus to jejunum. Two reviewers screened studies, extracted data, and assessed bias (Newcastle–Ottawa Scale). Primary outcomes were clinical remission and response. Due to limited, heterogeneous evidence, data are summarized descriptively. Results Of 1207 citations, 11 observational studies (nine retrospective, two prospective) and post-hoc analyses from two RCTs met the criteria, involving 387 patients. Most had ileocolonic involvement (280/387; 72.3%); only 8.5% (33/387) had isolated UGICD. Five studies (137 patients) reported esophageal CD. Follow-up ranged from 6 weeks to 28 years. Interventions and outcomes varied. Anti-tumor necrosis factor (anti-TNF) drugs and corticosteroids, alone or combined with other treatments, were associated with improvements in clinical outcomes, endoscopic healing, and histology, but controlled data are lacking. Other therapies, including proton pump inhibitors, H2-receptor antagonists, enteric nutrition, immunomodulators, anti-integrins, and anti-interleukin12/23, showed moderate to minimal improvement. Conclusions Our systematic review highlights a paucity of evidence to inform therapeutic strategies in UGICD. Positive outcomes were reported for corticosteroids and anti-TNF, but from small observational and uncontrolled studies. Data for most advanced therapies remain limited, highlighting a large unmet need to inform clinical practice.

Abstract INTRODUCTION Preclinical Alzheimer's disease (AD) can be described relative to biomarker positivity onset time. METHODS We estimated time from amyloid positivity (A+) using sampled iterative local approximation (SILA) in a longitudinal autosomal dominant AD (ADAD) sample ( N = 379) with amyloid positron emission tomography. We compared (1) predicted age at A+ to imputed age, (2) estimated age at A+ to estimated age at symptom onset, and (3) variance in cognitive performance explained. RESULTS Mean error between imputed and SILA‐estimated age at A+ ( N = 26) was 1.15 years. Age at A+ explained 39% of estimated years to symptom onset (EYO) variance. Time from A+ explained 19% of cognitive composite variance and 14% of Clinical Dementia Rating Sum of Boxes CDR‐SB variance; EYO explained 43% and 57%, respectively. DISCUSSION SILA estimates A+ age in ADAD with reasonably good accuracy. SILA‐estimated time from A+ describes the start of pathology, but the time from A+ onset to symptoms is variable in ADAD and better described by EYO. Highlights Amyloid chronicity predicts a 14‐year preclinical AD phase in ADAD. SILA accurately estimates age at A+ (MAE < 2 years). EYO outperforms chronicity in predicting symptom onset. APP mutation carriers show atypical amyloid accumulation. Chronicity models help reveal AD heterogeneity in preclinical stages.

Purpose: To compare stone clearance, stone-free status, and complications between patients undergoing ureteroscopy for renal stones using either Flexible and Navigable Ureteral Access Sheath (FANS) or the CVAC 2.0 system. Materials and Methods: A prospective study was completed on patients undergoing flexible ureteroscopy for renal stones at a single institution from March 2024 to December 2024. Subject demographics, intra-op data, volumetric and single-dimension stone clearance on non-contrast CT, and complications were compared. Stone-free rates (SFRs) using standardized cutoffs were compared. Pearson correlation analysis was performed to assess the relationship between preoperative stone volume and postoperative stone burden. Subanalysis was performed for patients with preoperative stone burden >1.5 cm. Results: A total of 123 cases (CVAC 2.0-36, FANS-87) were included, with 64 eligible for volumetric analysis. Preoperative stone volume was larger in the CVAC group vs FANS (1075 mm 3 vs 397 mm 3 ; p < 0.001). Absolute stone clearance was greater in the CVAC group (1016 mm 3 vs 392 mm 3 ; p < 0.001), whereas residual stone volume (4.1 mm 3 vs 15.0 mm 3 ; p = 0.55) and SFRs (90% vs 81%; p = 0.48) were similar. In individuals with >1.5 cm preoperative stone burden, relative stone clearance was greater with CVAC 2.0 (98.9% vs 95.1%; p = 0.026). Pearson correlation analysis revealed positive linear relationship between preoperative stone volume and residual stone volume for FANS, but not for CVAC 2.0. Conclusions: In this comparative study of FANS and CVAC 2.0, over 95% stone clearance was observed in both groups despite large initial stone burdens. In contrast to FANS, residual stone volumes with CVAC 2.0 did not increase significantly with increasing preoperative stone volumes.

Introduction: Family medicine contributes less scholarship and receives much less grant money than other specialties. Understanding when and how this disparity begins is a key step in addressing the gap in family medicine scholarship. Methods: We analyzed data from the National Resident Matching Program’s (NRMP’s) Charting Outcomes in the Match (2016–2024) to compare family medicine applicants with applicants to other specialties (ie, internal medicine, pediatrics, and all specialties combined). We examined the mean number of research experiences and the number of presentations and publications applicants had completed prior to starting residency. Additionally, we analyzed NRMP surveys to evaluate the weight applicants placed on institutional research support when choosing a residency program and the weight program directors placed on applicants’ research experience. Results: Family medicine applicants consistently reported fewer research experiences and presentations/publications than applicants to internal medicine, pediatrics, and all specialties combined. Osteopathic applicants showed the lowest research participation across all specialties we compared. Among other specialties, family medicine applicants placed less importance on programs’ research support, and family medicine residency program directors were less likely to consider research involvement when selecting applicants. Conclusions: Our results suggest that family medicine’s underrepresentation in research begins during the residency application process or sooner. Increased involvement in family medicine research among medical students should be a key component of strategies for bridging the research gap.