Citations

ImportanceStudies suggest that everolimus may reduce the risk of rejection, cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), and cytomegalovirus (CMV) after heart transplant. Everolimus use is controversial because of data demonstrating higher infection deaths when everolimus is introduced de novo after transplant. It is unclear whether everolimus is safe and effective when initiated at 6 months posttransplant in children, a population in which median graft survival is limited to 15 years and randomized clinical trials are lacking.ObjectiveTo evaluate the safety and efficacy of everolimus combined with low-dose tacrolimus to prevent major adverse transplant events (MATEs) in children after heart transplant.Design, Setting, and ParticipantsMulticenter, randomized, open-label, clinical trial enrolling 211 patients who were alive 6 months after pediatric heart transplant at 25 US sites from February 2018 to August 2020. The last date of follow-up was April 17, 2023.InterventionsParticipants were randomized to receive everolimus and low-dose tacrolimus (n = 107) or standard-dose tacrolimus and mycophenolate mofetil (n = 104) for 30 months.Main Outcomes and MeasuresThe primary efficacy end point was the MATE-3 score at 30 months, a validated composite ordinal end point including acute cellular rejection, CAV, and CKD. The primary safety end point was the MATE-6 score, encompassing the MATE-3 score plus antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder.ResultsAmong 211 children randomized, the mean age was 8.2 (SD, 6.3) years, 97 (46%) underwent transplant for congenital heart disease, and 49 (23%) were treated for rejection before 6 months. At 30 months, the mean MATE-3 score did not differ between the 2 treatment groups (mean difference, −0.32; 95% CI, −0.90 to 0.20; P = .16). The mean MATE-6 score was no higher in the everolimus group than in the mycophenolate group (baseline-adjusted mean difference, −0.40; 95% CI, −1.81 to 0.93), meeting the success criterion for safety (noninferiority margin <3). There were no differences in graft survival, MATE-free survival, or freedom from any individual MATE. Everolimus was associated with greater improvement in estimated glomerular filtration rate at 12 months (mean difference, 10.5 mL/min/1.73 m2; 95% CI, 1.09-19.91 mL/min/1.73 m2) and a lower incidence of CMV infection (hazard ratio, 0.50; 95% CI, 0.26-0.93).Conclusions and RelevanceAmong 6-month pediatric heart transplant survivors, everolimus and low-dose tacrolimus did not differ from tacrolimus and mycophenolate in preventing the composite of cellular rejection, CAV, and CKD at 30 months. However, everolimus and low-dose tacrolimus appear to be safe based on the total burden of 6 MATEs and may be associated with improved kidney function and less CMV infection.Trial RegistrationClinicalTrials.gov Identifier: NCT03386539

Abstract Error analysis is a critical step in evaluating and improving clinical concept extraction models, the most common clinical natural language processing (NLP) task. Unlike corpus annotation, which follows standardized protocols for creating gold-standard datasets, error analysis requires nuanced judgment grounded in both clinical expertise and NLP knowledge. This is especially important given the heterogeneity of clinical text, where variations in documentation style, note structure, and terminology can substantially influence model behavior. Despite its importance, there is currently no standardized, user-level framework to support systematic error analysis in clinical concept extraction task. In this study, we developed and validated MedError, a machine-assisted, human-in-the-loop framework designed to standardize and enhance error analysis for clinical concept extraction tasks. We collected and manually curated a corpus of 1,187 unique errors from a total of 4,237 notes across three different distinct hospitals. The error categories were defined using our previously validated error taxonomy and included 480 false negatives and 707 false positives across 25 error types and 48 clinical concept categories. We evaluated the performance of three proprietary and three open-source large language models (LLMs) in automatically classifying these errors into 26 and 15 predefined categories. We further developed a machine-assisted framework, MedError, which integrates best practices in error analysis, LLM-assisted classification and reasoning, and a user-friendly interface to enable more efficient, reproducible, and context-aware error analysis. The framework supports both single-site and federated multisite error analysis, facilitating the effective translation of clinical NLP systems into real-world settings.

Précis: Glaucoma patients with significant visual field defects show poorer driving performance, higher collision risks, and a greater likelihood of driving cessation. They face difficulties with lane maintenance, slower hazard responses, and self-regulation while driving. Purpose: Glaucoma is a chronic, progressive optic neuropathy associated with visual field (VF) defects, which in advanced disease has been shown to affect patients’ activities of daily living. This systematic review qualitatively analyzes existing literature that explores the impact of glaucomatous VF loss on the driving performance of glaucoma patients, the extent of driving limitation and cessation, as well as the risk of motor vehicle collisions (MVCs). Methods: A literature search of MEDLINE and Embase (via Ovid), PubMed, Cochrane Library, and Web of Science databases was performed for studies published from 2003 to 2023, with the terms “glaucoma,” “visual field defect/disorder,” and “driving,” followed by selective vetting based on inclusion criteria. Within studies, data pertaining to study design, subject demographics, VF defect characteristics, driving performance and related outcomes were extracted. Results: Initial search yielded 835 studies, with 20 studies selected. Three more studies were included through hand-searching, with a total of 23 studies included for final review. Moderate to severe VF defects resulted in poorer driving performance, with slower response times to road hazards, decreased ability for lane maintenance, and increased difficulty driving at night. Patients with more severe VF defects and with bilateral glaucoma were more likely to limit or cease driving compared with those with milder and unilateral glaucoma. A greater severity of VF loss was associated with a higher risk of MVCs. Conclusion: More severe glaucomatous VF and bilateral glaucoma is associated with worse driving performances and a higher risk of MVCs, in both simulator and real-world settings.

Background: There is a lack of data regarding the current state of lactation accommodations at continuing medical education (CME) events to guide best practice recommendations. Objective: To evaluate CME attendee attitudes, experiences, and preferences as it pertains to lactation support accommodations at CME events. Design: A cross-sectional study utilizing an electronic-based survey. Methods: Surveys were administered electronically to attendees of seven CME courses from August 2022 to October 2023, and de-identified data were collected to a secure database. Attitudes regarding lactation accommodations, personal preferences for lactation accommodations, and experiences with lactation at CME events were analyzed. Results: Of the 337 survey respondents, 169 had personal experience with lactation and 47 had experience with lactation at a CME course within the past 10 years. The majority of respondents agreed that lactation accommodations should be a priority ( n = 264, 83%) and are a medical need ( n = 285, 89%). Of those with recent experience lactating at a CME course, only 19% ( n = 9) indicated adequate lactation accommodations were provided. Due to inadequate accommodations, 77% ( n = 36) of respondents experienced decreased participation in the CME course content, 70% ( n = 33) claimed fewer hours of CME credit, and 74% ( n = 35) experienced decreased satisfaction in the CME course. Preferences for lactation accommodations included proximity to the meeting, audio–visual streaming of content, privacy, security, and signage supporting lactation in addition to an adequate designated space with access to an electrical plug and water supply. Conclusions: The current state of lactation accommodations at CME courses is inadequate and contributes to inequitable experiences for lactating participants. Course participants are supportive of lactating healthcare professionals at CME courses and recognize lactation accommodations as a priority. Further work is needed to inform and institute changes to lactation accommodations for healthcare professionals.

ABSTRACT Antimicrobial resistance mediated by carbapenemases significantly complicates treatment options. A case report by Morelan et al. (ASM Case Reports 1:e00094-25, 2025, https://doi.org/10.1128/asmcr.00094-25 ) illustrates how delayed recognition of Klebsiella pneumoniae carbapenemase (KPC) production in an Escherichia coli urinary tract infection resulted in suboptimal cefepime therapy, despite in vitro susceptibility. This case underscores the urgent need for clinical laboratories to implement on-site carbapenemase testing, as recommended by the Infectious Diseases Society of America and the Clinical and Laboratory Standards Institute (CLSI). Timely detection of KPC, coupled with reporting strategies for cefepime susceptibility results (suppression or editing results as resistant) in carbapenemase producers, may have facilitated earlier administration of a more appropriate antimicrobial and prevented recurrent infections and readmissions. In this commentary, we highlight recent updates to CLSI guidance for carbapenemase testing and antimicrobial susceptibility reporting strategies. Using this case report as an example, we outline the potential impact of these strategies on patient management and outcomes, further emphasizing the role of the clinical microbiology laboratory in antimicrobial stewardship.

Objectives To develop an internationally validated, structured robot‐assisted radical nephroureterectomy (RARNU) training programme through expert consensus. Materials and Methods A RARNU‐specific questionnaire was developed/adapted from previously published, validated questionnaires for robot‐assisted urological procedures. This included five key domains and 11 surgical steps. In all, 30 upper tract urothelial carcinoma experts were invited to participate. A two‐stage modified Delphi approach was employed. Consensus was defined as ≥80% agreement. Modifications and additional statements were proposed during the second round following qualitative/quantitative feedback from the initial round. Results Response rates for the first and second Delphi rounds were 80% (24/30) and 92% (22/24), respectively. All agreed that adoption of a standardised training curriculum can improve clinical outcomes during the RARNU learning curve. There was ≥92% agreement on all proposed RARNU steps. Five RARNU clinical modules of increasing complexity were defined using individual step difficulty and number of prior RARNU cases required, with ≥96% agreement among respondents. Respondents unanimously agreed that the final assessment should be based on a procedure‐specific scale focusing on the hilar dissection, ureteric dissection, and bladder cuff excision steps. No consensus was reached for the annual minimum RARNU volume required for eligibility as a RARNU curriculum host centre. Conclusion This is the first structured training curriculum for RARNU using international expert consensus. This will help guide surgical educators and trainees toward independent completion of a full RARNU.

Abstract Background: Cardiac arrest, characterized by the sudden loss of heart function, accounts for over 400,000 deaths annually in the United States, often resulting from unwitnessed ventricular arrhythmias. Stiff Person Syndrome (SPS), a rare neurological disorder, is marked by progressive muscle rigidity, painful spasms, which can occasionally lead to autonomic dysfunction and fulminant myocarditis. Case Presentation: We present a rare case of a male patient in his 30s with SPS who developed whole-body spasms, syncope, and respiratory distress. During extubation, he experienced cardiac arrest, requiring advanced cardiac life support (ACLS) and reintubation. Comprehensive evaluations including ECG, cardiac MRI, and laboratory testing suggested autonomic dysfunction and myocarditis as potential contributors to ventricular arrhythmias. Management involved sedation, diazepam, gabapentin, corticosteroids, and implantation of an implantable cardioverter-defibrillator (ICD) for non-sustained ventricular tachycardia. Conclusion: This case highlights the critical need for recognizing cardiac involvement in SPS and emphasizes early diagnosis and intervention to prevent fatal arrhythmias and improve patient outcomes.