Citations

Abstract Witte, BC, Schouten, TC, Westphal, JA, VanZile, AW, Jones, DD, Widenhoefer, TL, Dobbs, WC, Jagim, AR, Luedke, JA, and Almonroeder, TG. The modified reactive strength index is a valid measure of lower-body explosiveness in male and female high school athletes. J Strength Cond Res 38(8): 1428–1432, 2024—The modified reactive strength index (mRSI) is a commonly used metric to quantify lower-body explosiveness during countermovement jump (CMJ) performance. However, few studies have attempted to examine its validity as a measure of explosiveness, particularly among high school athletes. The purpose of this study was to examine the validity of the mRSI as a measure of lower-body explosiveness among a relatively large sample of male and female high school athletes from various sports. As part of this study, male ( n = 132) and female ( n = 43) high school athletes performed CMJs, while ground reaction forces were recorded using a force platform. The vertical ground reaction force data collected during the CMJs were used to derive the following variables: peak force (PF), peak power, time to PF, time to take-off, peak rate of force development, and the mRSI. Principal component analysis was applied and reduced these variables into 2 components related to “force” and “speed.” The mRSI loaded on both the force (loading = 0.82) and speed (loading = −0.46) components, indicating that it incorporates elements of both force and speed, although it loaded more strongly on the force component than the speed component. The observed pattern of cross-loading suggests that the mRSI is generally a valid measure of lower-body explosiveness for male and female high school athletes.

Background: There is sparse comparative data on short-term readmissions following Transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). Methods: The study cohort was derived from the National Readmission Data (NRD) 2013, a subset of the Healthcare Cost and Utilization Project (HCUP) sponsored by AHRQ. TAVR and SAVR were identified using appropriate ICD-9-CM codes (TAVR - 35.05, 35.06 & SAVR - 35.21, 35.22) as either primary or secondary procedural codes. Variables which could affect treatment assignment, were adjusted with propensity score match analysis and Match (1:1) cohort was generated. Readmission causes were identified by ICD 9 code in primary diagnosis. Results: Our analysis included 3,886 TAVR and SAVR procedures each in the propensity matched cohorts. There was no significant difference in terms of readmission rates amongst patients who underwent TAVR vs. SAVR [21.41% vs. 21.07% (OR: 1.02, 95% CI: 0.92 - 1.14) p = 0.702]. Cardiac etiologies were more likely to be responsible for readmissions following SAVR (42.66% vs. 35.91%, p = 0.006). Atrial fibrillation (AF) was a much more common cause of readmission following SAVR (7.81% vs. 3.37%, p <0.001). Overall vascular (3.24% vs. 1.32%, p = 0.006) and bleeding complications (9% vs. 6.2%, p = 0.025) were more likely to result in readmission in patients undergoing TAVR. Cost of care of index admission and readmission was similar in both groups. Readmission mortality was higher amongst patient with TAVR vs. SAVR (6.49 vs. 3.91, p = 0.02). 50% of TAVR and SAVR readmission occur within 11 days post discharge. Conclusion: In our study from a large nationwide database, there was no significant difference in readmission rate, median readmission rate and resource utilization between TAVR and SAVR. Arrhythmias especially AF accounted for more SAVR readmission and Bleeding/vascular complications were more commonly responsible for readmissions following TAVR.

BACKGROUND COVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined. METHODS This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization–equivalent anti–Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis. RESULTS SARS-CoV-2 anti–S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01). CONCLUSION In unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors’ antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use. TRIAL REGISTRATION ClinicalTrials.gov NCT04373460. FUNDING Department of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

Background: Disease progression in heart failure (HF) reflects multiple neurohormonal derangements resulting in adverse prognosis in the absence of overt clinical events. ST2 is up-regulated in response to cardiac injury/hemodynamic stress while modulating cardiac remodeling via inflammatory and apoptotic pathways. Accordingly, we evaluated changes in ST2 over time in conjunction with troponin T (cTnT) and BNP in ambulatory patients with chronic HF. Methods: A cohort of 191 NYHA class III-IV HF patients was prospectively evaluated with serial specimens collected every 3 months over a 2-year period. Primary end points were death or cardiac transplantation; secondary end points were combined death/transplantation and HF-related hospitalization. Plasma ST2 (Critical Diagnostics) was evaluated against contemporary cTnT (Roche 4th generation) and BNP (Shinogi) assays. Gender specific cut-points (>49.3 and >33.5 ng/mL for males and females, respectively) and a clinically defined optimal cut-point for ST2 (>35 ng/mL) were evaluated. Results: Time-dependent analyses (dichotomous and continuous variable) demonstrated ST2 gender specific cut-points were superior to a single ST2 cut-point and associated with an increased risk of death or transplantation (HR 4.8, 95% CI 2.8 to 8.3, p<0.0001) and combined death/transplantation/HF-hospitalization (HR 2.1, 95% CI 1.7 to 2.5, p<0.0001). Although cTnT remained the strongest predictor of death/transplantation (HR 3.2, 95% CI 1.6 to 5.4, p<0.0001) in multivariate analyses adjusted for cTnT and BNP, ST2 (HR 3.0, 95% CI 1.6 to 5.4, p=0.0003) added significantly to predictive accuracy. Furthermore, elevated ST2 was the only independent predictor of HF-hospitalization (HR 1.7, 95% CI 1.4 to 2.1, p<0.0001). In these models BNP was no longer significantly predictive (HR 1.2, 95% CI 0.7 to 2.2, p=0.58). Conclusions: Serial monitoring of changes in ST2 using gender specific cut-points adds to the diagnostic ability of cTnT in predicting mortality and/or transplantation in outpatients with chronic HF. ST2 uniquely predicts HF-hospitalization/death/transplantation, suggesting a serial monitoring strategy with cTnT and ST2 will optimize identification of HF patients at increased risk for events.

Implantable cardioverter-defibrillator (ICD) therapy in children and congenital heart disease (CHD) patients is hampered by poor long-term lead survival. Lead extraction is technically difficult and carries substantial morbidity. Manufacturers developed distinct strategies for this issue: thinner lead bodies or a Gore ePTFE coil coating. Both design changes were thought to improve ease of lead removal, but have not been directly compared in children or adults. The purpose of this study was to assess thin and ePTFE-coated ICD lead survival in pediatric and CHD pts. Methods: The Pediatric Lead Extractability and Survival Evaluation (PLEASE) Study began as a Phase IV multicenter open-label prospective study [ NCT00335036 ], facilitated by the Pediatric & Congenital EP Society. Initially designed as a randomized study, it changed to a parallel assignment registry when 1 lead had an advisory due to high incidence of failure, prompting concern about continued clinical equipoise. Pediatric and CHD pts who underwent ICD lead implant from 2005-2010 were eligible. The end date was NCDR ICD Registry v2.0 release (includes pediatric & lead data). 23 centers participated; each site obtained IRB approval. De-identified data was sent to the PI center for verification and statistical analyses. Results: A total of 982 ICD pts (357 VVI, 558 DDD, 67 CRT-D) entered the PLEASE study, incl. 423 pts (43%) with CHD. Mean age at implant = 18.3 ± 9.9 yrs. Thin (< 7Fr) ICD leads accounted for 51%, 23% were ePTFE-coated, 26% neither thin nor coated. There were 113 ICD lead failures (11.5%) at a mean lead-age of 2.2 ± 1.7 yrs, causing shocks in 55 pts. Failure occurred in 21% of thin leads vs 3.5% of ePTFE leads (p<0.01). Extraction was performed on 142 (14.5%) leads overall; 21% of thin leads (incl. extraction of 29 functioning leads due to recall) vs. 4.4% of ePTFE leads (p<0.01). There were 7 major extraction complications (4.9%), but no procedural mortality. Among thin leads, 90/270 (33.3%) of recalled leads failed vs 15/229 (6.6%) non-recalled thin leads. Conclusions: This Phase IV study demonstrates that ICD leads in children and CHD pts have suboptimal performance overall. Thinner leads were much more likely to fail and/or be extracted compared with ePTFE leads, chiefly driven by one lead type.

Abstract Introduction High sodium intake can increase blood pressure (BP) and future cardiovascular risk. Individuals with narcolepsy have an elevated cardiovascular comorbidity burden before considering medication-specific risks. Low-sodium oxybate (LXB; Xywav®) is approved by the US Food and Drug Administration (FDA) to treat excessive daytime sleepiness or cataplexy in patients ≥7 years of age with narcolepsy and idiopathic hypersomnia in adults. LXB has the same active moiety as high-sodium oxybates (sodium oxybate [SXB, Xyrem®] and fixed-dose SXB [Lumryz™]) but contains 92% less sodium. The objective of XYLO is to measure ambulatory and in-clinic systolic BP (SBP) changes after switching to LXB from a high-sodium oxybate in participants with narcolepsy (NCT05869773). Methods This 6-week, open-label, multicenter, switch study is enrolling participants 18–70 years of age with narcolepsy (type 1 or 2) taking 6–9 g/night of high-sodium oxybate for ≥6 weeks. Hybrid enrollment supports both on-site and decentralized (monitored at the participant’s home by mobile health professionals) participation, and may broaden the pool of eligible participants. After ≥2 weeks on stable high-sodium oxybate dose/regimens (screening period), participants switch to the same dose/regimen of LXB for 6 weeks (intervention period). The primary endpoint is the change in 24-hour SBP from baseline (the most recent screening measurement prior to switching) to the end-of-treatment visit (approximately 6 weeks after switching) measured via 24-hour ambulatory BP monitoring (ABPM). Secondary endpoints evaluate change from baseline to end-of-treatment visit in-clinic SBP, as well as daytime average SBP and nighttime average SBP measured via 24-hour ABPM. Results Recruitment began in June 2023. This study uses a group sequential design with an adaptive sample size target of 57–77 participants completing the 6-week intervention period. This design provides 90% power to detect a mean difference of 3.5 mmHg (a clinically relevant change) in 24-hour SBP (assuming a standard deviation of the differences in 24-hour SBP of 8 mmHg). Conclusion XYLO will enable the assessment of 24-hour BP changes following transition from a high-sodium oxybate to LXB. Planned hybrid enrollment with a decentralized option may increase study access leading to a more diverse clinical trial population. Support (if any) Jazz Pharmaceuticals

Abstract Purpose: Aromatase inhibitor (AI)–associated musculoskeletal symptoms (AIMSS) are common and frequently lead to AI discontinuation. SNPs in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate the association between 10 SNPs and AI discontinuation due to AIMSS. Patients and Methods: Postmenopausal women with stage I to III hormone receptor–positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcome measures to assess AIMSS (Stanford Health Assessment Questionnaire) at baseline, 3, 6, 9, and 12 months. We estimated that 40% of participants would develop AIMSS and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial stratum provided 80% power to detect an effect size of 1.5 to 4. SNPs were found in ESR1 (rs2234693, rs2347868, and rs9340835), CYP19A1 (rs1062033 and rs4646), TCL1A (rs11849538, rs2369049, rs7158782, and rs7159713), and HTR2A (rs2296972). Results: Of the 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. Although more Black and Asian women developed AIMSS than White women (49% vs. 39%, P = 0.017; 50% vs. 39%, P = 0.004, respectively), the AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population or in distinct cohorts. The OR for rs2296972 (HTR2A) approached significance for developing AIMSS. Conclusions: We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, patient-reported outcome predictors of AIMSS, and differences by race.

Abstract Febrile infection‐related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non‐FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non‐FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non‐FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non‐infection‐related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein‐1 alpha (MIP‐1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non‐FIRES NORSE are very similar conditions.

Objective: Our goal was to assess the fertility knowledge and educational experiences of graduating U.S. medical students to evaluate areas of improvement for future educational interventions. Design: Web-based cross-sectional survey. Subjects: Medical students graduating in 2023 from the University of Miami Miller School of Medicine (SOM), New York University (NYU) Grossman SOM, Wayne State University SOM, Perelman SOM at the University of Pennsylvania, and Mayo Clinic Alix SOM. Main Outcome Measures: Fertility-related knowledge and educational experiences of U.S. medical students in their final year of school. Results: In total, 117 students (14.4%) completed the survey. The average knowledge score was 78%. Twenty-three (22%) overestimated the age of most precipitous fertility decline, and 50 (52%) overestimated the chance of getting pregnant for a 40-year-old person with ovaries. One-third of students (30, 32%) incorrectly believe that physicians have equivalent infertility rates to the general population. Students were less cognizant of male fertility issues, incorrectly believing there was no negative impact on male fertility by age (43, 42%) among other factors. Seventy-five (81%) reported less than 5 hours of fertility-related education in medical school. Only one-third (32%) were satisfied or very satisfied with the fertility education they received. In an open-response question, students expressed interest in additional education on transgender and cancer patient care, fertility preservation, assisted reproductive technologies, and reproductive life planning in medicine. Conclusions: There is a need and an opportunity for medical education programs to enhance fertility education. Giving students and trainees the knowledge required to make informed decisions for their family-building purposes and improving their ability to counsel patients adequately should be a goal of future educational endeavors. The data collected in this study will serve as a guide for the development of fertility-related learning modules for medical students and trainees.