ObjectiveTo investigate the aetiology and incidence of sudden cardiac arrest and death (SCA/D) in US competitive athletes.MethodsProspective surveillance was conducted from 1 July 2014 to 30 June 2018 through the National Center for Catastrophic Sports Injury Research in collaboration with national sports organisations. Autopsy reports, death certificates, and medical records were reviewed by an expert panel to determine aetiology. Athlete participation statistics from the National Federation of State High School Associations and the National Collegiate Athletic Association (NCAA) were used to calculate incidence rates per athlete-years (AY). Comparisons of incidence rates were calculated using incidence rate ratios (IRR) with 95% CIs.Results331 cases of confirmed SCA/D (158 survivors; 173 fatalities) were identified; 15.4% in middle school, 61.6% in high school and 16.6% in college and professional athletes. Average age was 16.7 (11–29) years, and the majority were in male (83.7%), basketball (28.7%) or American football (25.4%) athletes. Common causes included hypertrophic cardiomyopathy (20.6%), idiopathic left ventricular hypertrophy (13.4%), coronary artery anomalies (12.0%) and autopsy-negative sudden unexplained death (9.6%). Coronary anomalies were more common in middle school athletes (28%), while cardiomyopathies (hypertrophic, arrhythmogenic, dilated, non-compaction or restricted) accounted for 47% of cases in college and professional athletes. Incidence was higher in male versus female athletes at the high school (1:43 932 AY (95% CI 1:38 101 to 1:50 907) vs 1:203 786 AY (95% CI 1:145 251 to 1:293 794); IRR 4.6 (95% CI 3.1 to 7.2)) and NCAA (1:34 906 AY (95% CI 1:25 385 to 1:49 173) vs 1:123 278 AY (95% CI 1:66 078 to 1:249 853); IRR 3.5 (95% CI 1.5 to 9.5)) levels. African American male NCAA Division I basketball players had the highest annual incidence rate of SCA/D (1:2087 AY (95% CI 1:1073 to 1:4 450)).ConclusionsCardiomyopathies account for nearly half of SCA/D cases in college and professional athletes, while coronary artery anomalies play a more prominent role than expected in middle school athletes. Over half of SCA cases in athletes result in sudden death, calling for improved prevention strategies.

Objective Elevated serum phosphate has emerged as a major risk factor for vascular calcification. The sodium-dependent phosphate cotransporter, PiT-1, was previously shown to be required for phosphate-induced osteogenic differentiation and calcification of cultured human VSMCs, but its importance in vascular calcification in vivo, as well as the potential role of its homologue, PiT-2, have not been determined. We investigated the in vivo requirement for PiT-1 in vascular calcification using a mouse model of chronic kidney disease, and the potential compensatory role of PiT-2 using in vitro knockdown and over-expression strategies. Approach and Results Mice with targeted deletion of PiT-1 in VSMCs were generated (PiT-1Δsm). PiT-1 mRNA levels were undetectable whereas PiT-2 mRNA levels were increased 2 fold in the vascular aortic media of PiT-1Δsm compared to PiT-1flox/flox control. When arterial medial calcification was induced in PiT-1Δsm and PiT-1flox/flox by chronic kidney disease followed by dietary phosphate loading, the degree of aortic calcification was not different between genotypes, suggesting compensation by PiT-2. Consistent with this possibility, VSMCs isolated from PiT-1Δsm mice had no PiT-1 mRNA expression, increased PiT-2 mRNA levels, and no difference in sodium-dependent phosphate uptake or phosphate-induced matrix calcification compared to PiT-1flox/flox VSMCs. Knockdown of PiT-2 decreased phosphate uptake and phosphate-induced calcification of PiT-1Δsm VSMCs. Furthermore, over-expression of PiT-2 restored these parameters in human PiT-1-deficient VSMCs. Conclusions PiT-2 can mediate phosphate uptake and calcification of VSMCs in the absence of PiT-1. Mechanistically, PiT-1 and PiT-2 appear to serve redundant roles in phosphate-induced calcification of vascular smooth muscle cells.

Public access defibrillator programs should be universal in schools and youth sporting venues and have the potential to increase survival after SCA in young athletes.

The etiology of SCA/D in competitive athletes involves a wide range of clinical disorders. More robust reporting mechanisms, standardized autopsy protocols, and accurate etiology data are needed to better inform prevention strategies.

ObjectiveMinority student-athletes have a lower survival rate from sudden cardiac arrest (SCA) than non-minority student-athletes. This study examined the relationship between high school indicators of socioeconomic status (SES) and survival in student-athletes with exercise-related SCA.MethodsHigh school student-athletes in the USA with exercise-related SCA on school campuses were prospectively identified from 1 July 2014 to 30 June 2018 by the National Center for Catastrophic Sports Injury Research. High school indicators of SES included the following: median household and family income, proportion of students on free/reduced lunch and percent minority students. Resuscitation details included witnessed arrest, presence of an athletic trainer, bystander cardiopulmonary resuscitation and use of an on-site automated external defibrillator (AED). The primary outcome was survival to hospital discharge. Differences in survival were analysed using risk ratios (RR) and univariate general log-binomial regression models.ResultsOf 111 cases identified (mean age 15.8 years, 88% male, 49% white non-Hispanic), 75 (68%) survived. Minority student-athletes had a lower survival rate compared with white non-Hispanic student-athletes (51.1% vs 75.9%; RR 0.67, 95% CI 0.49 to 0.92). A non-significant monotonic increase in survival was observed with increasing median household or family income and with decreasing percent minority students or proportion on free/reduced lunch. The survival rate was 83% if an athletic trainer was on-site at the time of SCA and 85% if an on-site AED was used.ConclusionsMinority student-athletes with exercise-related SCA on high school campuses have lower survival rates than white non-Hispanic athletes, but this difference is not fully explained by SES markers of the school.

Background Iron deficiency anemia (IDA) and heavy menstrual bleeding are prevalent, interrelated issues impacting over 300 million premenopausal women worldwide. IDA is generally associated with increased platelet counts; however, the effects of IDA and its correction on platelet function in premenopausal women remain unknown. Objectives We sought to determine how IDA and intravenous iron affect platelet count and platelet function in premenopausal women. Methods Hematologic indices were assessed in a multicenter, retrospective cohort of 231 women repleted with intravenous iron. Pre‐ and postinfusion blood samples were then obtained from a prospective cohort of 13 women to analyze the effect of intravenous iron on hematologic parameters as well as platelet function with flow cytometry and platelet aggregation assays under physiologic shear. Results Following iron replacement, anemia improved, and mean platelet counts decreased by 26.5 and 16.0 K/mm3 in the retrospective and prospective cohorts, respectively. Replacement reduced baseline platelet surface P‐selectin levels while enhancing platelet secretory responses to agonists, including collagen‐related peptide and ADP. Platelet adhesion and aggregation on collagen under physiologic shear also significantly increased following repletion. Conclusion We find that intravenous iron improves anemia while restoring platelet counts and platelet secretory responses in premenopausal women with iron deficiency. Our results suggest that iron deficiency as well as iron replacement can have a range of effects on platelet production and function. Consequently, platelet reactivity profiles should be further examined in women and other groups with IDA where replacement offers a promising means to improve anemia as well as quality of life.

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IntroductionOrthopaedic trauma and fracture care commonly cause perioperative anaemia and associated functional iron deficiency due to a systemic inflammatory state. Modern, strict transfusion thresholds leave many patients anaemic; managing this perioperative anaemia is an opportunity to impact outcomes in orthopaedic trauma surgery. The primary outcome of this pilot study is feasibility for a large randomised controlled trial (RCT) to evaluate intravenous iron therapy (IVIT) to improve patient well-being following orthopaedic injury. Measurements will include rate of participant enrolment, screening failure, follow-up, missing data, adverse events and protocol deviation.Methods and analysisThis single-centre, pilot, double-blind RCT investigates the use of IVIT for acute blood loss anaemia in traumatically injured orthopaedic patients. Patients are randomised to receive either a single dose infusion of low-molecular weight iron dextran (1000 mg) or placebo (normal saline) postoperatively during their hospital stay for trauma management. Eligible subjects include adult patients admitted for lower extremity or pelvis operative fracture care with a haemoglobin of 7–11 g/dL within 7 days postoperatively during inpatient care. Exclusion criteria include history of intolerance to intravenous iron supplementation, active haemorrhage requiring ongoing blood product resuscitation, multiple planned procedures, pre-existing haematologic disorders or chronic inflammatory states, iron overload on screening or vulnerable populations. We follow patients for 3 months to measure the effect of iron supplementation on clinical outcomes (resolution of anaemia and functional iron deficiency), patient-reported outcomes (fatigue, physical function, depression and quality of life) and translational measures of immune cell function.Ethics and disseminationThis study has ethics approval (Oregon Health & Science University Institutional Review Board, STUDY00022441). We will disseminate the findings through peer-reviewed publications and conference presentations.Trial registration numberNCT05292001; ClinicalTrials.gov.