High-throughput label-free opioid receptor binding assays using an automated desorption electrospray ionization mass spectrometry platform.

The current opioid epidemic has incentivized the discovery of new non-addictive analgesics, a process that requires the screening of opioid receptor binding, traditionally performed using radiometric assays. Here we describe a label-free alternative based on high-throughput (1 Hz) ambient mass spectrometry for screening the receptor binding of new opioid analogues.

Immediate versus staged complete revascularisation in patients presenting with STEMI and multivessel disease.

BACKGROUND: Complete revascularisation is supported by recent trials in patients with ST-elevation myocardial infarction (STEMI) and multivessel disease (MVD) without cardiogenic shock. However, the optimal timing of non-culprit lesion revascularisation is currently debated. AIMS: This prespecified analysis of the BioVasc trial aims to determine the effect of immediate complete revascularisation (ICR) compared to staged complete revascularisation (SCR) on clinical outcomes in patients with STEMI. METHODS: Patients presenting with STEMI and MVD were randomly assigned to ICR or SCR. The primary endpoint was the composite of all-cause mortality, myocardial infarction, any unplanned ischaemia-driven revascularisation, or cerebrovascular events at 1-year post-index procedure. RESULTS: Between June 2018 and October 2021, 608 (ICR: 305, SCR: 303) STEMI patients were enrolled. No significant differences between ICR and SCR were observed at 1-year follow-up in terms of the primary endpoint (7.0% vs 8.3%, hazard ratio [HR] 0.84, 95% confidence interval [CI]: 0.47-1.50; p=0.55): all-cause mortality (2.3% vs 1.3%, HR 1.77, 95% CI: 0.52-6.04; p=0.36), myocardial infarction (1.7% vs 3.3%, HR 0.50, 95% CI: 0.17-1.47; p=0.21), unplanned ischaemia-driven revascularisation (4.1% vs 5.0%, HR 0.80, 95% CI: 0.38-1.71; p=0.57) and cerebrovascular events (1.4% vs 1.3%, HR 1.01, 95% CI: 0.25-4.03; p=0.99). At 30-day follow-up, a trend towards a reduction of the primary endpoint in the ICR group was observed (ICR: 3.0% vs SCR: 6.0%, HR 0.50, 95% CI: 0.22-1.11; p=0.09). ICR was associated with a reduction in overall hospital stay (ICR: median 3 [interquartile range {IQR} 2-5] days vs SCR: median 4 [IQR 3-6] days; p<0.001). CONCLUSIONS: Clinical outcomes at 1 year were similar for STEMI patients who had undergone ICR and those who had undergone SCR.

Dose Reduction of Edoxaban in Patients 80 Years and Older With Atrial Fibrillation: Post Hoc Analysis of the ENGAGE AF-TIMI 48 Randomized Clinical Trial.

Importance: In older patients with atrial fibrillation who take anticoagulants for stroke prevention, bleeding is increased compared with younger patients, thus, clinicians frequently prescribe lower than recommended doses in older patients despite limited randomized data. Objective: To evaluate ischemic and bleeding outcomes in patients 80 years and older with atrial fibrillation receiving edoxaban, 60 mg vs 30 mg, and edoxaban, 30 mg vs warfarin. Design, Setting, and Participants: The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a parallel-design, double-blind, global clinical trial that randomized patients with atrial fibrillation to either one of 2 edoxaban dosing regimens or warfarin. This secondary analysis focused on patients 80 years or older without dose-reduction criteria receiving edoxaban, 60 mg vs 30 mg, as well as patients with or without dose-reduction criteria receiving edoxaban, 30 mg, vs warfarin. Study data were analyzed between October 2022 and December 2023. Interventions: Oral edoxaban, 30 mg once daily; edoxaban, 60 mg once daily; or warfarin. Main Outcomes and Measures: Primary net clinical outcome of death, stroke or systemic embolism, and major bleeding and each individual component. Results: The current analysis included 2966 patients 80 years and older (mean [SD] age, 83 [2.7] years; 1671 male [56%]). Among 1138 patients 80 years and older without dose-reduction criteria, those receiving edoxaban, 60 mg vs 30 mg, had more major bleeding events (hazard ratio [HR], 1.57; 95% CI, 1.04-2.38; P = .03), particularly gastrointestinal hemorrhage (HR, 2.24; 95% CI, 1.29-3.90; P = .004), with no significant difference in efficacy end points. Findings were supported by analyses of endogenous factor Xa inhibition, a marker of anticoagulant effect, which was comparable between younger patients receiving edoxaban, 60 mg, and older patients receiving edoxaban, 30 mg. In 2406 patients 80 years and older with or without dose-reduction criteria, patients receiving edoxaban, 30 mg, vs warfarin had lower rates of the primary net clinical outcome (HR, 0.78; 95% CI, 0.68-0.91; P = .001), major bleeding (HR, 0.59; 95% CI, 0.45-0.77; P < .001), and death (HR, 0.83; 95% CI, 0.70-1.00; P = .046), whereas rates of stroke or systemic embolism were comparable. Conclusions and Relevance: In this post hoc analysis of the ENGAGE AF-TIMI 48 randomized clinical trial, in patients 80 years and older with atrial fibrillation, major bleeding events were lower in patients randomized to receive edoxaban, 30 mg per day, compared with either edoxaban, 60 mg per day (in patients without dose-reduction criteria), or warfarin (irrespective of dose-reduction status), without an offsetting increase in ischemic events. These data support the concept that lower-dose anticoagulants, such as edoxaban, 30 mg, may be considered in older patients with atrial fibrillation even in the absence of dose-reduction criteria. Trial Registration: ClinicalTrials.gov Identifier: NCT00781391.

Echocardiography Core Laboratory Methodology for TAVR: A Transatlantic Consensus.

Inter-echocardiography core laboratory (ECL) harmonization is pivotal to consider data from different ECLs interchangeable. On the basis of the experience of the first trans-Atlantic harmonization of 2 established ECLs in the field of transcatheter aortic valve replacement (TAVR) trials, this review describes the harmonized ECL methodology in analyzing and adjudicating the post-TAVR echocardiographic endpoints according to Valve Academic Research Consortium 3 definitions. This review presents the feasibility and intra- and inter-ECL reproducibility, explains the root cause of potential important inter-ECL variability, and formulates ECL recommendations for optimal post-TAVR echocardiographic image acquisition. The implementation of inter-ECL harmonization may further define the best practice of ECLs and have logistic and regulatory implications for the realization of future TAVR trials.

Structural Heart Imaging Using 3-Dimensional Intracardiac Echocardiography: JACC Cardiovascular Imaging Position Statement.

3-dimensional (3D) intracardiac echocardiography (ICE) is emerging as a promising complement and potential alternative to transesophageal echocardiography for imaging guidance in structural heart interventions. To establish standardized practices, our multidisciplinary expert position statement serves as a comprehensive guide for the appropriate indications and utilization of 3D-ICE in various structural heart procedures. The paper covers essential aspects such as the fundamentals of 3D-ICE imaging, basic views, and workflow recommendations specifically tailored for ICE-guided structural heart procedures, such as transeptal puncture, device closure of intracardiac structures, and transcatheter mitral and tricuspid valve interventions. Current challenges, future directions, and training requirements to ensure operator proficiency are also discussed, thereby promoting the safety and efficacy of this innovative imaging modality to support expanding its future clinical applications.

Performance of Purpose-Built vs Off-Label Transcatheter Devices for Aortic Regurgitation: The PURPOSE Study.

BACKGROUND: Severe pure aortic regurgitation (AR) carries a high mortality and morbidity risk, and it is often undertreated because of the inherent surgical risk. Transcatheter heart valves (THVs) have been used off-label in this setting with overall suboptimal results. The dedicated "purpose-built" Jena Valve Trilogy (JVT, JenaValve Technology) showed an encouraging performance, although it has never been compared to other THVs. OBJECTIVES: The aim of our study was to assess the performance of the latest iteration of THVs used off-label in comparison to the purpose-built JVT in inoperable patients with severe AR. METHODS: We performed a multicenter, retrospective registry with 18 participating centers worldwide collecting data on inoperable patients with severe AR of the native valve. A bicuspid aortic valve was the main exclusion criterion. The primary endpoints were technical and device success, 1-year all-cause mortality, and the composite of 1-year mortality and the heart failure rehospitalization rate. RESULTS: Overall, 256 patients were enrolled. THVs used off-label were used in 168 cases (66%), whereas JVT was used in 88 (34%). JVT had higher technical (81% vs 98%; P < 0.001) and device success rates (73% vs 95%; P < 0.001), primarily driven by significantly lower incidences of THV embolization (15% vs 1.1%; P < 0.001), the need for a second valve (11% vs 1.1%; P = 0.004), and moderate residual AR (10% vs 1.1%; P = 0.007). The permanent pacemaker implantation rate was comparable and elevated for both groups (22% vs 24%; P = 0.70). Finally, no significant difference was observed at the 1-year follow-up in terms of mortality (HR: 0.99; P = 0.980) and the composite endpoint (HR: 1.5; P = 0.355). CONCLUSIONS: The JVT platform has a better acute performance than other THVs when used off-label for inoperable patients with severe AR. A longer follow-up is conceivably needed to detect a possible impact on prognosis.

Changes in Countermovement Vertical Jump Force-Time Metrics During a Game in Professional Male Basketball Players.

ABSTRACT: Cabarkapa, D, Johnson, QR, Cabarkapa, DV, Philipp, NM, Eserhaut, DA, and Fry, AC. Changes in countermovement vertical jump force-time metrics during a game in professional male basketball players. J Strength Cond Res 38(7): 1326-1329, 2024-As technology within elite basketball advances and is more available to sporting organizations, novel approaches for assessing and addressing athletic performance during practice or competition are being continuously explored. The aim of this investigation was to examine changes in neuromuscular performance during live basketball play. Eight professional male basketball players volunteered to participate in this study. The testing procedures were conducted during a pre-tournament camp over a span of 2 days. During the first day, the athletes were familiarized with the testing procedures, and baseline measurements were obtained. Using a uni-axial force plate system sampling at 1,000 Hz, each athlete performed 3 countermovement vertical jumps (CVJ) without an arm swing before proceeding with their regular training activities. During the second day of the pre-tournament camp, the athletes repeated identical CVJ testing procedures before the start of the first quarter and post-first, second, third, and fourth quarter of a simulated 5-on-5 basketball game. Repeated-measures testing design was used to examine statistically significant differences in various force-time metrics of interest in comparison to the baseline levels (p < 0.05). Besides a trivial decrease in eccentric mean force, the findings of this study revealed no statistically significant changes in any force-time metrics of interest within both eccentric and concentric phases of the CVJ (i.e., mean and peak force and power, jump height, impulse, velocity, and contraction time). Thus, we can conclude that these variables were not sensitive to acute fatigue, suggesting that the neuromuscular performances of professional male basketball players tend to remain unchanged throughout a 5-on-5 simulated game.

Mixed Reality in the Operating Room: An Initial Use in Frontal Sinus Setback in Gender-affirming Facial Surgery.

Demand for gender-affirming facial surgery is growing rapidly. Frontal sinus setback, one of the key procedures used in gender-affirming facial surgery, has a particularly high impact on gender perception. Mixed reality (MR) allows a user to view and virtually overlay three-dimensional imaging on the patient and interact with it in real time. We used the Medivis's SurgicalAR system in conjunction with the Microsoft HoloLens Lucille2 (Microsoft). Computed tomography imaging was uploaded to SurgicalAR, and a three-dimensional (3D) hologram was projected onto the display of the HoloLens. The hologram was registered and matched to the patient, allowing the surgeon to view bony anatomy and underlying structures in real time on the patient. The surgeon was able to outline the patient's frontal sinuses using the hologram as guidance. A 3D printed cutting guide was used for comparison. Negligible difference between the mixed reality-based outline and 3D-printed outline was seen. The process of loading the hologram and marking the frontal sinus outline lasted less than 10 minutes. The workflow and usage described here demonstrate significant promise for the use of mixed reality as imaging and surgical guidance technology in gender-affirming facial surgery.

Role of Lipid-Lowering and Anti-Inflammatory Therapies on Plaque Stabilization.

Atherosclerosis is the predominant underlying etiopathology of coronary artery disease. Changes in plaque phenotype from stable to high risk may spur future major adverse cardiac events (MACE). Different pharmacological therapies have been implemented to mitigate this risk. Over the last two decades, intravascular imaging modalities have emerged in clinical studies to clarify how these therapies may affect the composition and burden of coronary plaques. Lipid-lowering agents, such as statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors, were shown not only to reduce low-density lipoprotein levels and MACE but also to directly affect features of coronary plaque vulnerability. Studies have demonstrated that lipid-lowering therapy reduces the percentage of atheroma volume and number of macrophages and increases fibrous cap thickness. Future studies should answer the question of whether pharmacological plaque stabilization may be sufficient to mitigate the risk of MACE for selected groups of patients with atherosclerotic coronary disease.

Case report of increased left ventricular end-diastolic pressure with pulsatile left ventricular assist device.

Background: Left ventricular assist devices (LVADs) are increasingly utilized in cardiogenic shock and high-risk percutaneous coronary interventions (PCIs). These devices aspirate and expel blood from the left ventricle (LV) into the aorta, consequently reducing left ventricular end-diastolic pressure (LVEDP). We report a case of unexpected LVEDP rise under LV-to-aorta LVAD in the context of transcatheter aortic valve implantation (TAVI) and concomitant multi-vessel PCI. Case summary: A patient with acute heart failure, severely depressed systolic LV function, severe aortic stenosis, and multi-vessel coronary artery disease underwent TAVI and concomitant PCI under pulsatile LVAD. Notably, the patient experienced unexpected shortness of breath and elevated LVEDP while under LVAD, which normalized immediately upon LVAD removal. Discussion: Pulsatile LVAD enhances cardiac output by providing pulsatile support through a percutaneous bi-directional flow catheter. Despite expectations of reduced LVEDP and improved myocardial oxygen supply under LVAD support, we observed high LVEDP and clinical complaints of shortness of breath following TAVI and multi-vessel PCI. This case illustrates that an LVAD across the aortic valve may immobilize aortic leaflets and generate acute aortic regurgitation.

Tailored vs. General COVID-19 prevention for adults with mental disabilities residing in group homes: a randomized controlled effectiveness-implementation trial.

BACKGROUND: People with serious mental illness (SMI) and people with intellectual disabilities/developmental disabilities (ID/DD) are at higher risk for COVID-19 and more severe outcomes. We compare a tailored versus general best practice COVID-19 prevention program in group homes (GHs) for people with SMI or ID/DD in Massachusetts (MA). METHODS: A hybrid effectiveness-implementation cluster randomized control trial compared a four-component implementation strategy (Tailored Best Practices: TBP) to dissemination of standard prevention guidelines (General Best-Practices: GBP) in GHs across six MA behavioral health agencies. GBP consisted of standard best practices for preventing COVID-19. TBP included GBP plus four components including: (1) trusted-messenger peer testimonials on benefits of vaccination; (2) motivational interviewing; (3) interactive education on preventive practices; and (4) fidelity feedback dashboards for GHs. Primary implementation outcomes were full COVID-19 vaccination rates (baseline: 1/1/2021-3/31/2021) and fidelity scores (baseline: 5/1/21-7/30/21), at 3-month intervals to 15-month follow-up until October 2022. The primary effectiveness outcome was COVID-19 infection (baseline: 1/1/2021-3/31/2021), measured every 3 months to 15-month follow-up. Cumulative incidence of vaccinations were estimated using Kaplan-Meier curves. Cox frailty models evaluate differences in vaccination uptake and secondary outcomes. Linear mixed models (LMMs) and Poisson generalized linear mixed models (GLMMs) were used to evaluate differences in fidelity scores and incidence of COVID-19 infections. RESULTS: GHs (n=415) were randomized to TBP (n=208) and GBP (n=207) including 3,836 residents (1,041 ID/DD; 2,795 SMI) and 5,538 staff. No differences were found in fidelity scores or COVID-19 incidence rates between TBP and GBP, however TBP had greater acceptability, appropriateness, and feasibility. No overall differences in vaccination rates were found between TBP and GBP. However, among unvaccinated group home residents with mental disabilities, non-White residents achieved full vaccination status at double the rate for TBP (28.6%) compared to GBP (14.4%) at 15 months. Additionally, the impact of TBP on vaccine uptake was over two-times greater for non-White residents compared to non-Hispanic White residents (ratio of HR for TBP between non-White and non-Hispanic White: 2.28, p = 0.03). CONCLUSION: Tailored COVID-19 prevention strategies are beneficial as a feasible and acceptable implementation strategy with the potential to reduce disparities in vaccine acceptance among the subgroup of non-White individuals with mental disabilities. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04726371, 27/01/2021. https://clinicaltrials.gov/study/NCT04726371 .

Predictors of COVID-19 infection and hospitalization in group homes for individuals with intellectual and/or developmental disabilities.

BACKGROUND: More than seven million people with intellectual and/or developmental disabilities (ID/DD) live in the US and may face an elevated risk for COVID-19. OBJECTIVE: To identify correlates of COVID-19 and related hospitalizations among people with ID/DD in group homes in Massachusetts. METHODS: We collected data during March 1, 2020-June 30, 2020 (wave 1) and July 1, 2020-March 31, 2021 (wave 2) from the Massachusetts Department of Public Health and six organizations administering 206 group homes for 1035 residents with ID/DD. The main outcomes were COVID-19 infections and related hospitalizations. We fit multilevel Cox proportional hazards models to estimate associations with observed predictors and assess contextual home- and organizational-level effects. RESULTS: Compared with Massachusetts residents, group home residents had a higher age-adjusted rate of COVID-19 in wave 1 (incidence rate ratio [IRR], 12.06; 95 % confidence interval [CI], 10.51-13.84) and wave 2 (IRR, 2.47; 95 % CI, 2.12-2.88) and a higher age-adjusted rate of COVID-19 hospitalizations in wave 1 (IRR, 17.64; 95 % CI, 12.59-24.70) and wave 2 (IRR, 4.95; 95 % CI, 3.23-7.60). COVID-19 infections and hospitalizations were more likely among residents aged 65+ and in group homes with 6+ resident beds and recent infection among staff and residents. CONCLUSIONS: Aggressive efforts to decrease resident density, staff-to-resident ratios, and staff infections through efforts such as vaccination, in addition to ongoing access to personal protective equipment and COVID-19 testing, may reduce COVID-19 and related hospitalizations in people with ID/DD living in group homes.

Current knowledge and practice of Candida auris screening in France: A nationwide survey from the French Society of Medical Mycology (SFMM).

Due to large outbreaks observed worldwide, Candida auris has emerged as a major threat to healthcare facilities. To prevent these phenomena, a systematic screening should be performed in patients transferred from regions where the pathogen is highly endemic. In this study, we recorded and analyzed French mycologists' current knowledge and practice regarding C. auris screening and diagnosis. Thirty-six centers answered an online questionnaire. Only 11 (30.6 %) participants were aware of any systematic screening for C. auris for patients admitted to their hospital. In the case of post-admission screening, axillae/groins (n = 21), nares (n = 7), rectum (n = 9), and mouth (n = 6) alone or various combinations were the body sites the most frequently sampled. Only six centers (8.3 %) reported using a commercially available plate allowing the differentiation of C. auris colonies from that of other Candida species, while five laboratories (13.8 %) had implemented a C. auris-specific qPCR. Considering the potential impact on infected patients and the risk of disorganization in the care of patients, it is crucial to remember to biologists and clinicians the utmost importance of systematic screening on admission.

Drivers and Pathways for the Recovery of Critical Metals from Waste-Printed Circuit Boards.

The ever-increasing importance of critical metals (CMs) in modern society underscores their resource security and circularity. Waste-printed circuit boards (WPCBs) are particularly attractive reservoirs of CMs due to their gamut CM embedding and ubiquitous presence. However, the recovery of most CMs is out of reach from current metal-centric recycling industries, resulting in a flood loss of refined CMs. Here, 41 types of such spent CMs are identified. To deliver a higher level of CM sustainability, this work provides an insightful overview of paradigm-shifting pathways for CM recovery from WPCBs that have been developed in recent years. As a crucial starting entropy-decreasing step, various strategies of metal enrichment are compared, and the deployment of artificial intelligence (AI) and hyperspectral sensing is highlighted. Then, tailored metal recycling schemes are presented for the platinum group, rare earth, and refractory metals, with emphasis on greener metallurgical methods contributing to transforming CMs into marketable products. In addition, due to the vital nexus of CMs between the environment and energy sectors, the upcycling of CMs into electro-/photo-chemical catalysts for green fuel synthesis is proposed to extend the recycling chain. Finally, the challenges and outlook on this all-round upgrading of WPCB recycling are outlined.

Serial cardiac biomarkers, pulmonary artery pressures and traditional parameters of fluid status in relation to prognosis in patients with chronic heart failure: Design and rationale of the BioMEMS study.

AIMS: Heart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF-related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early-stage intervention, since haemodynamic congestion precedes clinical symptoms. METHODS: The BioMEMS study, a substudy of the MONITOR-HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR-HF trial were collected at baseline, 3-, 6-, and 12-month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS-HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death. CONCLUSION: Since the prognostic value of single baseline measurements of biomarkers like N-terminal pro-B-type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively.

Loss of protein tyrosine phosphatase receptor delta PTPRD increases the number of cortical neurons, impairs synaptic function and induces autistic-like behaviors in adult mice.

BACKGROUND: The brain cortex is responsible for many higher-level cognitive functions. Disruptions during cortical development have long-lasting consequences on brain function and are associated with the etiology of brain disorders. We previously found that the protein tyrosine phosphatase receptor delta Ptprd, which is genetically associated with several human neurodevelopmental disorders, is essential to cortical brain development. Loss of Ptprd expression induced an aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRß in neural precursor cells. However, whether these alterations have long-lasting consequences in adulthood remains unknown. RESULTS: Here, we found that in Ptprd+/- or Ptprd-/- mice, the developmental increase of excitatory neurons persists through adulthood, affecting excitatory synaptic function in the medial prefrontal cortex. Likewise, heterozygosity or homozygosity for Ptprd also induced an increase of inhibitory cortical GABAergic neurons and impaired inhibitory synaptic transmission. Lastly, Ptprd+/- or Ptprd-/- mice displayed autistic-like behaviors and no learning and memory impairments or anxiety. CONCLUSIONS: These results indicate that loss of Ptprd has long-lasting effects on cortical neuron number and synaptic function that may aberrantly impact ASD-like behaviors.

Investigating the stretch-shortening cycle fatigue response to a high-intensity stressful phase of training in collegiate men's basketball.

Introduction: While using force-plate derived measures of vertical jump performance, reflective of stretch-shortening-cycle (SSC) efficiency is common practice in sport science, there is limited evidence as to which tests and measures may be most sensitive toward neuromuscular fatigue. The aim of this study was to explore the SSC fatigue response to a one-week high-intensity fatiguing phase of training in National Collegiate Athletic Association (NCAA) Division-I basketball players. Methods: The study timeline consisted of three weeks of baseline measures, one week of high-intensity training, and two weeks of follow-up testing. Countermovement jumps (CMJ) and 10-5 hop tests were performed at baseline, as well as at two time-points during, and three time-points following the fatiguing training period, allowing for performance-comparisons with baseline. Results: Compared to the weekly training sum at baseline, during the high intensity training phase, athletes were exposed to very large increases in selected external load metrics (ES = 1.44-3.16), suggesting that athletes experienced fatigue acutely, as well as potential longer lasting reductions in performance. Vertical jump data suggested that in the CMJ, traditional metrics such as jump height, as well as metrics reflecting kinetic outputs and movement strategies, were sensitive to the stark increase in high-intensity training exposure. The 10-5 hop test suggested a fatigue-induced loss of tolerance to ground impact reflected by performance reductions in metrics related to jump height and reactive strength qualities. Discussion: These findings emphasize that when monitoring neuromuscular fatigue, variables and assessments may not be looked at individually, but rather as part of a more global monitoring approach.

Pediatric Facial Fractures: Demographics, Injury Patterns, and Associated Injuries in 3334 Patients.

Pediatric craniofacial fractures are fundamentally distinct from their adult counterparts because of unique injury patterns and effects on future growth. Understanding patterns and injury context informs management and risk mitigation. Previous studies include only inpatients, operative patients, or are specialty-specific. In contrast, our study presents a comprehensive assessment of all pediatric facial fracture patients seen at a single institution. Patients under 18 years old who were evaluated for facial fractures at a level I pediatric trauma center between 2006 and 2021 were reviewed. Subanalysis was performed for groups defined by age. Variables studied included demographics, etiology, fracture pattern, associated injuries, management, and outcomes. Three thousand thirty-four patients were included. Mean age at presentation was 11.5 to 4.9 years. The majority were Caucasian (82.6%) and male (68.4%). Sports were the leading cause of injury in older patients (42.2% of patients over 12 y), compared with activities of daily living in patients under 6 years (45.5%). Thirty-two percent of patients were hospitalized, 6.0% required ICU care, and 48.4% required surgery. Frequency of ICU admission decreased with age (P<0.001), whereas operative intervention increased with age (P<0.001). Zygomaticomaxillary complex (P=0.002) and nasal fractures (P<0.001) were common in older patients, whereas younger patients experienced more skull (P<0.001) and orbital fractures (P<0.001). The most associated injuries were soft tissue (55.7%) and neurologic (23.6%). This large-scale study provides updated characterization of craniofacial fractures in the pediatric population, providing a necessary framework for future studies on outcomes assessments and preventative care.

Defining high bleeding risk in patients undergoing transcatheter aortic valve implantation: a VARC-HBR consensus document.

The identification and management of patients at high bleeding risk (HBR) undergoing transcatheter aortic valve implantation (TAVI) are of major importance, but the lack of standardised definitions is challenging for trial design, data interpretation, and clinical decision-making. The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) is a collaboration among leading research organisations, regulatory authorities, and physician-scientists from Europe, the USA, and Asia, with a major focus on TAVI-related bleeding. VARC-HBR is an initiative of the CERC (Cardiovascular European Research Center), aiming to develop a consensus definition of TAVI patients at HBR, based on a systematic review of the available evidence, to provide consistency for future clinical trials, clinical decision-making, and regulatory review. This document represents the first pragmatic approach to a consistent definition of HBR evaluating the safety and effectiveness of procedures, devices and drug regimens for patients undergoing TAVI..

Timing of Complete Revascularization Stratified by Index Presentation During On- and Off-Hours.

Recent trials suggested immediate complete revascularization (ICR) as a safe alternative to staged complete revascularization (SCR), but the impact of the respective percutaneous coronary intervention strategies between on- versus off-hours is unclear. On-hours was defined as an index revascularization performed between 8:00 a.m. and 6:00 p.m., Monday to Friday, or else the procedure was defined as performed during off-hours. The primary end point consisted of a composite of all-cause mortality, myocardial infarction, unplanned ischemia-driven revascularization, and cerebrovascular events at 1-year follow-up. We used Cox regression models to relate randomized treatment with study end points. We evaluated multiplicative and additive interactions between on- versus off-hours and randomized treatment. The BIOVASC (Percutaneous Complete Revascularization Strategies Using Sirolimus Eluting Biodegradable Polymer Coated Stents in Patients Presenting With Acute Coronary Syndromes and Multivessel Disease) trial enrolled 1,097 and 428 patients during on- and off-hours, respectively. Patients randomized during off-hours were more likely to present with ST-segment elevation myocardial infarction (66.4% vs 29.5%, p <0.001). The composite primary outcome occurred in 8.4% and 10.1% of patients randomized to ICR and SCR, respectively, during on-hours (hazard ratio 0.80, 95% confidence interval 0.54 to 1.19). During off-hours, the primary composite outcome occurred in 5.4% and 7.7% in ICR and SCR (0.69, 95% confidence interval 0.32 to 1.46) with no evidence of a differential effect (interaction pmultiplicative = 0.70, padditive = 0.56). No differential effect was found between treatment allocation and on- versus off-hours in any of the secondary outcomes. In conclusion, no differential treatment effect was found when comparing ICR versus SCR in patients presenting with acute coronary syndrome and multivessel disease during on- or off-hours.