Faculty Bibliography

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: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.

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.

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.

INTRODUCTION/UNASSIGNED:Recent federal funding cuts have created pauses in admissions, hiring, and execution of research studies at academic medical centers internationally. These monetary reductions have also impacted allowances for non-essential faculty travel. As a result, faculty may now be faced with challenges in how they obtain professional development. METHODS/UNASSIGNED:A cross-sectional, exploratory study was implemented to discover the impact of funding cuts on faculty travel for professional development opportunities, as well as strategies medical educators are using to mitigate the current landscape. RESULTS/UNASSIGNED:Findings indicate that faculty now must use alternative methods to obtain professional development and that institutional guidance is lacking in how to do so. DISCUSSION/UNASSIGNED:Authors provide concrete action steps for faculty to take amidst this challenge to remain engaged in professional development.

OBJECTIVES/OBJECTIVE:Chronic hepatitis C can complicate the treatment of coronary artery disease (CAD), especially among racial and ethnic minority patients. This study explores racial and ethnic differences in the prevalence of hepatitis C and inpatient mortality among patients admitted to the hospital primarily for a CAD event in the USA. METHODS:An observational analysis was conducted using data from the 2016 to 2021 National Inpatient Sample, including 1,946,182 CAD patients, of whom 7426 (0.38%) had chronic hepatitis C. We performed weighted logistic regressions to analyze the relationship between race and ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, and other races) regarding the prevalence of hepatitis C and inpatient mortality, adjusting for patient sociodemographic characteristics and comorbidities. RESULTS:Non-Hispanic Black patients had the highest prevalence of hepatitis C (adjusted odds ratio [aOR] = 1.57, 95% confidence interval [CI] 1.48-1.67) and Hispanic patients with underlying hepatitis C had the highest in-hospital mortality (aOR = 1.56, 95% CI 1.11-2.20) compared to non-Hispanic White patients and other racial groups. CONCLUSIONS:We found significant racial and ethnic differences in the prevalence of hepatitis C and mortality among patients with underlying chronic hepatitis C admitted primarily for CAD events in the USA. This disparity may exist due to lower rates of hepatitis C virus (HCV) treatment, higher severity and prevalence of underlying health conditions, poorer healthcare access and insurance coverage, and a higher rate of alcohol use and cirrhosis progression in minority populations.

Kaplan-Meier analysis of time to first all-cause readmission over 12 months among older adults with ischemic heart disease randomized to 3 months of mobile health cardiac rehabilitation (mHealth-CR) or usual care. There was no significant difference in time to first readmission between groups (log-rank P = 0.26).