Faculty Bibliography

Age is the greatest risk factor for mortality and morbidity. We previously reported premature ageing in PKP2 arrhythmogenic cardiomyopathy (PKP2-ACM). However, depiction of cardiomyocyte molecular anatomy in premature ageing remains incomplete. Furthermore, the relationship between myocyte premature ageing and the molecular components of electrical homeostasis in PKP2-deficient hearts remains understudied. Therefore, we aimed to identify molecular anatomical changes of premature ageing in PKP2-deficient adult cardiomyocytes, the corresponding gene cohort and its imprint in the human electrocardiogram (ECG). We used a murine model of cardiomyocyte-specific PKP2 knockout. Molecular anatomy was resolved by expansion and structured illumination microscopy, allowing 3D-nanometric visualization, and by serial block-face scanning electron microscopy. We used omics databases to distill a subset of genes related to ageing and PKP2 deficiency containing single nucleotide polymorphisms (SNPs) with an ECG-relevant genomic signature. We found increased DNA damage and reduced abundance of transcriptionally repressed heterochromatin at the lamin-associated domain (LAD), and disrupted mitochondria ultrastructure at the intercalated disc. Genes dysregulated in ageing hearts and PKP2-deficient cells were distilled to identify those in the PKP2 human left ventricular gene network (by GTEx) that contain SNPs with an imprint in the human ECG (based on ECG GWAS). These findings indicate that in PKP2 deficiency, transcriptionally repressed heterochromatin in the LAD is vulnerable to damage, and erasing of otherwise transcriptionally inaccessible genomic regions, consistent with premature cellular ageing and transcriptional reprogramming. Multi-omics analysis indicates that reduced PKP2 expression accelerates cardiomyocyte ageing, and the age-related gene network contributes to dysfunction of cell metabolism and arrhythmia risk in PKP2-ACM. KEY POINTS: We used advanced imaging technology to unveil DNA damage and loss of heterochromatin architecture in the lamin-associated domain (LAD), and mitochondrial remodelling at the intercalated disc, as features of premature myocyte ageing in adult PKP2-deficient murine cardiomyocytes. Multi-omics analysis identified a network of genes dysregulated by ageing and by PKP2 deficiency. Cross-correlation with the ECG GWAS database found a subset of single nucleotide polymorphisms with an imprint in the human electrocardiogram. These results provide novel insight into the mechanisms of transcriptional remodelling and take an initial step toward a better understanding of the oligogenic bases of arrhythmia risk in PKP2-deficient hearts.

Clinical histories are essential for accurate radiologic interpretation but are often lengthy and time-consuming to review amid increasing radiologist workloads. Large language models (LLMs) offer a potential solution by generating concise, clinically focused summaries from existing documentation; however, the optimal presentation format for radiologists remains unclear. This retrospective reader study evaluated the readability, efficiency, and radiologist preference for a two-stage LLM-based summarization pipeline designed to identify the optimal summary format for radiologic use. Ninety imaging studies across multiple modalities and care settings were processed to generate structured timeline summaries (stage 1) and brief narrative summaries (stage 2). Text length was reduced by approximately 86.8% and 95.2% for stage 1 and stage 2, respectively. Four radiologists independently rated representative subsets of cases for clarity, relevance, usefulness, and comprehensiveness and indicated their order of preference. Stage 2 summaries were preferred in 89% of ratings and were rated significantly higher than stage 1 for perceived clarity, relevance, and usefulness (p < 0.0001), with equivalent comprehensiveness. Longer source documents and longer stage 1 summaries were associated with lower ratings for the detailed timeline format, whereas no such associations were observed for the brief narrative summaries. Manual review identified 25 total hallucinations across 90 cases, of which one was considered capable of altering image interpretation in a case with borderline radiographic features. These findings demonstrate that summary format, and particularly brevity, is critical for optimizing readability and radiologist preference. Automated summarization holds promise to reduce cognitive load and improve information accessibility in radiology practice.

IMPORTANCE:Although fluoride exposure at high levels during the perinatal period has been associated with socioemotional problems among children, there is limited evidence regarding potential associations at lower levels of fluoride exposure, particularly in the US. OBJECTIVE:To examine the association between prenatal exposure to public drinking water fluoride levels and children's socioemotional problems in a pooled US pediatric consortium. DESIGN, SETTING, AND PARTICIPANTS:This cohort study used observational pregnancy cohort data from January 1, 2005, to December 31, 2019, on children aged 1.5 to 17 years from the Environmental Influences on Child Health Outcomes (ECHO) Cohort, which took place at 20 prenatal pediatric cohort sites across 34 US states. Statistical analysis was conducted from December 2024 to December 2025. EXPOSURE:Area-level, time-weighted, mean fluoride concentrations in public water were estimated based on residential addresses during pregnancy. MAIN OUTCOMES AND MEASURES:Children's socioemotional problems were assessed using caregiver reports of internalizing and externalizing problems via the Child Behavior Checklist. Generalized estimating equation models evaluated the adjusted mean difference in T scores (1) across the range of exposure values in cubic spline models, (2) per 500.0-µg/L higher fluoride level in linear models, (3) across quartiles of exposure, and (4) at the US Public Health Services recommended cutoff (≤700.0 µg/L; 3998 less than the cutoff). RESULTS:The cohort comprised 5520 children (mean [SD] age, 5.8 [3.0] years; 2849 boys [51.6%]). The mean (SD) prenatal time-weighted water fluoride level was 407.9 (361.0) µg/L (range, <1.4-3272.5 µg/L). The adjusted mean difference in emotional and behavioral problem T scores per 500.0-μg/L higher exposure to prenatal public water fluoride was -0.15 (95% CI, -0.85 to 0.56) for internalizing problems and 0.06 (95% CI, -0.44 to 0.55) for externalizing problems, consistently showing no associations at the continuous level. However, some positive associations were observed only when using change point models for externalizing problems (adjusted mean difference, 1.59 [95% CI, 0.72-2.47] per 500.0-µg/L increase above the inflection point), and for some subgroups. CONCLUSIONS AND RELEVANCE:In this cohort study, prenatal exposure to fluoride levels in regulated public water was not associated with internalizing and externalizing problems among offspring. In change point models, positive associations were found for externalizing problems. The results contribute to growing evidence that could inform future policy decisions regarding fluoride in the US public water systems. Additional studies are needed to further investigate this association, especially examining other sources of fluoride that may have an association with children's emotional and behavioral problems.

Prostate MRI has become integral to prostate cancer diagnosis and management, extending beyond prebiopsy triage to biopsy guidance, local staging, active surveillance, focal therapy planning, posttreatment surveillance, and evaluation of biochemical recurrence. As MRI use expands, image quality has emerged as a critical determinant of diagnostic reliability. Suboptimal prostate MRI quality can reduce cancer detection, increase equivocal PI-RADS assessments, compromise staging and longitudinal assessment, and undermine referring clinician confidence in MRI-directed care. The Prostate Imaging Quality System, or PI-QUAL, provides a standardized framework for assessing the diagnostic adequacy of prostate MRI examinations. Initially developed as a research quality-control tool using data from the multicenter PRECISION trial, PI-QUAL has been refined by the European Society of Urogenital Radiology into a more practical version applicable to both multiparametric and biparametric MRI examinations. In this Special Series Review, we describe the rationale for PI-QUAL, summarize evidence linking image quality with prostate MRI performance and patient management, and propose a stepwise approach for clinical implementation, including multidisciplinary training, retrospective audits, protocol optimization, structured reporting, quality dashboards, benchmark development, and artificial intelligence tools. Incorporating PI-QUAL into routine practice can make prostate MRI quality easier to measure, communicate, and improve.

Gluteal tendon tears are typically degenerative and often only partial. For patients who fail nonoperative management, endoscopic repair is a reasonable option. Traditionally, a knotted side-to-side suture repair technique has been used, though this can be technically demanding and leave knot stacks adjacent to the trochanteric bursa. Using a suture staple technique may increase the tendon-footprint contact area and avoids the knot stacks. Although the biomechanics seem theoretically in favor of the staple technique, this has yet to be proven. Clinically, the techniques are likely comparable, though more research is needed on several fronts before a determination can be made.

A strong working relationship between nurse practitioners and registered nurses is essential for strengthening staff morale and a collaborative learning environment. Within our academic health system, leaders are expected to support collaboration while striving for exceptional quality care and sustained staff engagement in a transplant unit. In recent years, through strong nursing leadership, clear goals, and shared ownership, we have improved quality metrics and strengthened nurse practitioner-registered nurse collaboration. Upholding these principles has enabled the team to consistently deliver safe, high-quality care while enhancing outcomes for both patients and staff. This article highlights the evolution of effective team building on an acute solid organ transplant unit, emphasizing shared professional goals, engagement, accountability, and the application of high-reliability organization principles. Leadership-driven interventions centered on communication, collaboration, transparency, respect, and role clarity have positively influenced patient experience, job satisfaction, and staff wellness.

INTRODUCTION/BACKGROUND:Critical acyanotic congenital heart lesions are uncommon but potentially life-threatening causes of neonatal shock and cardiovascular collapse. OBJECTIVE:This review highlights key aspects of acyanotic CHD, including presentation, diagnosis, and management in the emergency department (ED), based on current evidence. DISCUSSION/CONCLUSIONS:Acyanotic CHD encompasses a number of conditions, including critical coarctation of the aorta (CoA), interrupted aortic arch (IAA), critical aortic stenosis (AS), and anomalous left coronary artery from the pulmonary artery (ALCAPA). These conditions should be considered in critically ill neonates presenting with shock and cardiovascular collapse, often without prominent cyanosis. Evaluation involves a thorough assessment of the patient's cardiovascular and respiratory status. Diagnostic tools include pulse oximetry, laboratory testing, electrocardiogram, chest radiograph, and ultrasonography. Management requires prompt recognition and hemodynamic stabilization, which may involve the administration of prostaglandin, vasoactive/inotropic agents, and airway management. Expert consultation and coordination of transfer to a tertiary or quaternary care center are crucial. Surgical repair serves as the definitive treatment. CONCLUSION/CONCLUSIONS:A thorough understanding of acyanotic congenital heart disease is essential for emergency clinicians to effectively diagnose and manage these potentially life-threatening conditions.