Faculty Bibliography

BACKGROUND:Poor sleep after acute cardiovascular events is associated with increased mortality. Women are more likely than men to report sleep disturbances after cardiovascular events, but other sleep metrics linked to cardiometabolic health remain underexplored. OBJECTIVES/OBJECTIVE:We characterize multiple dimensions of sleep and examine factors associated with poor sleep among women with prior myocardial infarction (MI). METHODS:Participants completed 7 nights of wrist actigraphy, which measured sleep duration, sleep efficiency, and wake after sleep onset (WASO), and sleep diary, which measured self-reported sleep quality using a Likert scale. Multivariable regression modeled associations between sociodemographic, clinical, and psychosocial characteristics and sleep measures. RESULTS:Among 94 post-MI women (median days since MI 93; IQR: 69-709), mean age was 60 years, and 67.0% identified as non-Hispanic White. The mean sleep duration was 405.1 minutes (approximately 6.8 hours), sleep efficiency 86.3%, WASO 61.6 minutes, and self-reported sleep quality 3.3, indicating fair-to-good sleep quality. Overall, 64.9% of women had short (<7 hours) or long (>9 hours) sleep duration, 33% low sleep efficiency (<85%), and 88.3% long WASO (>30 minutes). In exploratory analyses, associations with poor sleep included identifying as other than non-Hispanic White (shorter sleep duration, lower efficiency, and longer WASO), being nonpartnered (shorter sleep duration), hypertension (lower sleep efficiency), and higher depressive symptoms (lower sleep quality). CONCLUSIONS:Many women with prior MI had suboptimal sleep (short or long sleep duration, low sleep efficiency, and/or long WASO). Our results highlight the importance of discussing multiple dimensions of sleep with women post-MI to optimize cardiovascular health.

Dysembryoplastic neuroepithelial tumors (DNTs) are low-grade glioneuronal tumors with FGFR1 alterations. They show significant histologic and molecular overlap with other glioneuronal tumors, complicating diagnosis. We analyzed 44 tumors that were either classified as DNT by DNA methylation (n = 37), or were diagnosed histologically as DNT but did not classify as DNT by DNA methylation (n = 7). 13/37 (35%) DNT-classifying tumors were histologically diagnosed as DNTs. High-confidence DNTs (score >0.9, 23 cases, 62%) demonstrated variable histology, most frequently DNT (39%), oligodendroglioma, and ganglioglioma and most frequently harbored FGFR1 alterations. Lower-confidence DNTs (score < 0.9, 14 cases, 38%) showed greater heterogeneity; their histologic diagnoses included papillary glioneuronal tumor, extraventricular neurocytoma, and pilocytic astrocytoma. Tumors with low confidence score exhibited diverse molecular alterations including BRAF V600E mutations, PDGFRA amplification, or multiple gene fusions. Among 7 histologically diagnosed DNTs that did not classify as DNT by methylation, most grouped with the myxoid glioneuronal PDGFRA-mutant class despite lacking canonical PDGFRA mutations. Thus, DNTs with high confidence scores are relatively homogenous but DNTs with low methylation confidence scores are heterogenous, highlighting the importance of integrated molecular profiling. Our findings also suggest that the myxoid glioneuronal tumor methylation class may require further classification of underlying drivers.

Despite major advances in lipid-lowering therapies, a significant unmet need remains, particularly for patients with homozygous familial hypercholesterolemia (HoFH), severe heterozygous familial hypercholesterolemia (HeFH), and those who fail to achieve guideline-recommended LDL-C targets. Nucleic acid-based therapeutics have emerged as a transformative approach for treating hypercholesterolemia. Antisense oligonucleotides and small interfering RNAs (siRNAs) have demonstrated durable hepatic gene silencing and have led to approved therapies, while gene replacement and in vivo genome-editing strategies offer the potential for long-lasting, and possibly one-time, interventions. In parallel, microRNAs (miRNAs) have attracted increasing interest because of their ability to coordinately regulate multiple genes involved in lipoprotein metabolism, cholesterol transport, and lipid homeostasis. Human genetic studies further support the importance of miRNA-mediated regulation, exemplified by a rare ~2.5 kb deletion in the distal LDLR 3'UTR ("del2.5") that disrupts miRNA-binding sites and is associated with lifelong low LDL-C levels. This review summarizes recent advances, mechanisms of action, clinical progress, and remaining challenges across antisense oligonucleotides, siRNAs, gene therapy, genome editing, and emerging miRNA-based therapeutics for hypercholesterolemia. As an example of the latter approach, the liver-directed miR-30c analog C2 has demonstrated preclinical activity by coordinately reducing hepatic lipoprotein secretion and lipogenesis while enhancing cholesterol elimination, resulting in reduced LDL-C and atherosclerosis. However, it must be noted that these findings remain preclinical, and further optimization of delivery, pharmacokinetics, safety, and long-term efficacy will be required before clinical evaluation. Continued advances in RNA chemistry, targeted delivery, and genome engineering are expected to further expand the therapeutic landscape for dyslipidemia and cardiovascular disease.

BACKGROUND:Genotype-phenotype correlations in pediatric hypertrophic cardiomyopathy (HCM) are not well established. Determining whether specific genes or variants correlate with disease severity may impact clinical care. OBJECTIVES/OBJECTIVE:This study aims to identify associations between pathogenic genetic variants in pediatric HCM and echocardiographic maximal left ventricular wall thickness. METHODS:Children with primary HCM from pediatric cardiomyopathy centers were recruited for research-based exome sequencing. Associations between genetic findings, imaging, and clinical outcomes were assessed. Genetic variants in established HCM genes were classified according to established guidelines. Left ventricular hypertrophy (LVH) at enrollment was classified as mild (z-score <12), moderate (z-score ≥12), or severe (z-score ≥17) based on LV septal or posterior wall thickness z-scores measured by a core echocardiography laboratory. RESULTS:Severity of LVH was determined in 143 children with adequate echocardiograms. The median age at enrollment was 11.5 years (range: 3.8-14.4 years). Overall, 51% had a pathogenic variant, of which 93% were in sarcomeric genes. Children with severe LVH (n = 40, 28%) were diagnosed at younger ages than those with mild LVH (n = 78, 55%) at a median of 6.4 vs 12.9 years, P = 0.005. Those with severe LVH were more likely to have pathogenic variants; this association was driven by variants in MYBPC3 (OR: 4.1; 95% CI: 1.7-9.9). Missense variants in MYBPC3 predominated over stop, insertion-deletion, or splicing variants in severe cases. CONCLUSIONS:In this population of children with primary HCM, severe LVH was associated with a younger age at enrollment and a higher likelihood of harboring a pathogenic variant in MYBPC3. (Genotype-Phenotype Associations in Pediatric Cardiomyopathy [PCM GENES]; NCT01873963).

OBJECTIVE/UNASSIGNED:The objective of this study is to determine the optimal first trimester reticulocyte hemoglobin cutoff to predict iron deficiency anemia at 24 to 28 weeks' gestation and to compare its performance to first trimester ferritin. STUDY DESIGN/UNASSIGNED:weeks. Patients with first trimester anemia or blood transfusion 3 months prior to pregnancy were excluded. Iron deficiency anemia was defined as hemoglobin < 10.5 g/dL and ferritin < 30 µg/L. Optimal cutoffs were calculated using the receiver operating characteristic curve and the sensitivity/specificity pairs with the largest Youden index. RESULTS/UNASSIGNED:Of 600 nonanemic, pregnant participants enrolled, 499 participants were eligible for analysis at 24 to 28 weeks' gestation; 40 (8%) had iron deficiency anemia. The area under the curve of reticulocyte hemoglobin was 0.69 (95% confidence interval [CI]: 0.61-0.78) compared with 0.73 (95% CI: 0.65-0.81) for ferritin. The optimal first trimester cutoff was 32.6 pg for reticulocyte hemoglobin (sensitivity 42.5%, specificity 86.9%) and 29 µg/L for ferritin (sensitivity 47.5, specificity 87.6%). CONCLUSION/UNASSIGNED:First trimester reticulocyte hemoglobin did not outperform ferritin in predicting iron deficiency anemia at 24 to 28 weeks' gestation. Both reticulocyte hemoglobin and ferritin were weak predictors of iron deficiency anemia at 24 to 28 weeks and were more effective in identifying patients at low risk of iron deficiency anemia at 24 to 28 weeks.

OBJECTIVE/UNASSIGNED:To test whether AI-generated, clinician-edited after-visit summaries (AVS) are more patient-friendly than clinician-generated AVS, without compromising safety, when implemented in a live inpatient setting. PATIENTS AND METHODS/UNASSIGNED:grade reading levels, and presence of a "simplified" description of both the diagnosis and treatment/interventions. Our composite outcome was positive if all 3 of these outcomes were positive. We also surveyed patients, nurses, and clinicians on perceptions of safety, empathy, and understandability. RESULTS/UNASSIGNED:grade than the control group (8.5 vs 10.6, P <.001). The AI-generated, clinician-edited AVS were also more likely to contain simplified explanations of diagnoses (96.7% vs 12.9%, P <.001) and hospital interventions (86.7% vs 12.9%, P <.001). Our composite outcome favored AI-generated, clinician-edited summaries (13.3% vs 6.5%, p = 0.637). CONCLUSION/UNASSIGNED:In this small, randomized trial, exploratory and component measures suggest improved patient-friendliness in AI-generated, clinician-edited AVS, although no significant difference was observed in the primary outcome. CLINICALTRIALSGOV NUMBER/UNASSIGNED:NCT06711458.

Patients with chronic or end stage kidney disease often require multiple medications as part of their treatment regimen. The role of nephrology nurses in medication administration is to follow the five rights of medication administration, ensure all medication-related education is completed, and provide patient safety that enhances the delivery of quality care. By adding a medication and barcode scanning process in our outpatient dialysis units, we are demonstrating a solid commitment to accuracy and engagement in patient safety processes. Just as there is a need in the hospital for safety parameters for medication administration, medication safety strategies need to be implemented in outpatient settings. This approach helps minimize the risk of medication errors and adverse medication errors caused by polypharmacy and drug interactions.

BACKGROUND:Starting a pediatric subspecialty fellowship presents numerous challenges to trainees. Virtual Symposium of Pediatric Hematology/Oncology of New York (v-SYMPHONY), an educational collaborative organized by 18 pediatric hematology-oncology (PHO) programs, initiated an annual bootcamp in 2022 aimed at easing the transition from pediatric residency to PHO fellowship. METHODS:The bootcamp consisted of virtual clinical lectures and fellow-led panels, which were created with input from diverse program leadership, educators, and past fellows using Kern's six-step module of curriculum development. It was offered to incoming fellows, first in the NY/NJ/CT region, and subsequently expanded nationally. RESULTS:Over 4 years (2022-2025), 147 pediatric residents completed this virtual bootcamp. The number of residents attending the live sessions increased from 19 in 2022 to 62 in 2025. Forty-four participants completed pre- and post-bootcamp surveys over this period, which showed significant improvement in both self-reported medical knowledge and preparedness and reported a decrease in transition to fellowship anxiety scores. CONCLUSION/CONCLUSIONS:These results highlight the need and benefits of a standardized orientation program that can be delivered virtually to ease the transition of PHO trainees from residency to fellowship. Such a standardized curriculum is feasible, adaptable, and potentially scalable to a national level.