Changes in the incidence of stress reactions and fractures among intercollegiate athletes after the COVID-19 pandemic

PurposeThe purpose of this study was to characterize the impact of detraining due to the COVID-19 pandemic on incidence of bony injuries and stress fractures in collegiate athletes.MethodsA comprehensive collegiate athletic conference injury database was queried for all in-season, sport-related bony injuries (defined as all stress reactions and fractures) that occurred across all sports from January 2016 to June 2021. The bony injury rate per 1000 athlete exposure hours (AEH) was calculated and compared between the immediate post-hiatus season and historic rates from pre-hiatus seasons (2016-2019). Injury characteristics were also compared between the pre- and post-hiatus time periods.ResultsA total of 868 bony injuries across 23 sports were identified. The sports with highest overall baseline bony injury rates in historic seasons were women's cross country (0.57 injuries per 1000 AEH) and men's cross country (0.32). Compared to historic pre-hiatus rates, female cross-country runners demonstrated a significantly lower bony injury incidence rate in the post-hiatus season (0.24 vs. 0.57, p = 0.016) while male swimming athletes demonstrated a statistically significant increase in bony injury rate (0.09 vs. 0.01, p = 0.015). The proportion of bony injuries attributed to repetitive trauma increased; while, the proportion of injuries attributed to running decreased between the pre- and post-hiatus seasons.ConclusionAcross all sports, there was no consistent trend toward increased rates of bony injury in the immediate post-hiatus season. However, female cross-country runners demonstrated lower rates of bony injury in the post-hiatus season while male swimmers demonstrated higher rates. Furthermore, bony injuries in the post-hiatus season were more likely to be the result of repetitive trauma and less likely to be from running.Level of evidenceLevel III, retrospective, cross sectional study

Impact of the COVID-19 Pandemic Hiatus From Sports Activities on Injuries Observed Among Division I NCAA Athletes

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic significantly disrupted athletic activities, including those in the Pacific 12 (Pac-12) Conference of the National Collegiate Athletic Association. It is currently unknown how the disruption in training and competition impacted athletes' risk of injury upon resumption of activities.PurposeTo describe and compare the rate, timing, mechanism, and severity of injuries among collegiate athletes across multiple sports in the Pac-12 Conference before and after the COVID-19 pandemic-associated hiatus of intercollegiate athletic activities.Study designDescriptive epidemiology study.MethodsDescriptive and injury data among intercollegiate athletes from both the season before the hiatus and the season after the hiatus were acquired from the Pac-12 Health Analytics Program database. Injury elements (timing of injury onset, injury severity, mechanism, recurrence, outcome, need for procedural intervention, and event segment during which the injury took place) were compared by time using the chi-square test and a multivariate logistic regression model. Subgroup analyses were performed on knee and shoulder injuries among athletes participating in sports with traditionally high rates of knee and shoulder injuries.ResultsA total of 12,319 sports-related injuries across 23 sports were identified, with 7869 pre-hiatus injuries and 4450 post-hiatus injuries. There was no difference in the overall incidence of injury between the pre-hiatus and post-hiatus seasons. However, the proportion of noncontact injuries was higher in the post-hiatus season for football, baseball, and softball players, and the proportion of nonacute injuries in the post-hiatus season was higher among football, basketball, and rowing athletes. Finally, the overall proportion of injuries sustained by football players in the final 25% of competition or practice was higher in the post-hiatus season.ConclusionAthletes competing in the post-hiatus season were observed to have higher rates of noncontact injuries and injuries sustained in the final 25% of competition. This study demonstrates that the COVID-19 pandemic has had varied effects on athletes from different sports, suggesting that many factors must be considered when designing return-to-sports programs for athletes after an extended absence from organized training

Short-Term Outcomes and Long-Term Implant Survival After Inpatient Surgical Management of Geriatric Proximal Humerus Fractures

IntroductionThe most common surgical options for geriatric proximal humerus fractures are open reduction and internal fixation (ORIF), hemiarthroplasty (HA), and reverse total shoulder arthroplasty. We used a longitudinal inpatient discharge database to determine the cumulative incidence of conversion to arthroplasty after ORIF of geriatric proximal humerus fractures. The rates of short-term complications and all-cause reoperation were also compared.Patients and methodsAll patients 65 or older who sustained a proximal humerus fracture and underwent either ORIF, HA, or shoulder arthroplasty (SA) as an inpatient from 2000 through 2017 were identified. Survival analysis was performed with ORIF conversion to arthroplasty and all-cause reoperation as the endpoints of interest. Rates of 30-day readmission and short-term complications were compared. Trends in procedure choice and outcomes over the study period were analyzed.ResultsA total of 27 102 geriatric patients that underwent inpatient surgical management of proximal humerus fractures were identified. Among geriatric patients undergoing ORIF, the cumulative incidence of conversion to arthroplasty within 10 years was 8.2%. The 10-year cumulative incidence of all-cause reoperation was 12.1% for ORIF patients and less than 4% for both HA and SA patients. Female sex was associated with increased risk of ORIF conversion and younger age was associated with higher all-cause reoperation. ORIF was associated with higher 30-day readmission and short-term complication rates. Over the study period, the proportion of patients treated with ORIF or SA increased while the proportion of patients treated with HA decreased. Short-term complication rates were similar between arthroplasty and ORIF patients in the later cohort (2015-2017).ConclusionThe 10-year cumulative incidence of conversion to arthroplasty for geriatric patients undergoing proximal humerus ORIF as an inpatient was found to be 8.2%. All-cause reoperations, short-term complications, and 30-day readmissions were all significantly lower among patients undergoing arthroplasty, but the difference in complication rate between arthroplasty and ORIF was attenuated in more recent years. Younger age was a risk factor for reoperation and female sex was associated with increased risk of requiring conversion to arthroplasty after ORIF

MELD score predicts short-term outcomes after surgical management of proximal humerus fractures: a matched analysis

ObjectiveWe aimed to evaluate the difference in 30-day outcomes after surgical management of proximal humerus fractures (PHFs) between patients with and without chronic liver disease as defined by a MELD score greater than 10.DesignThis was a retrospective database review.SettingAll centers participating in the American College of Surgeons National Surgical Quality Improvement Program database were included.Patients/participantsPatients with proximal humerus fractures who (1) underwent ORIF, HA, or SA and (2) had calculable MELD scores were included.InterventionOpen reduction and internal fixation, hemiarthroplasty, or shoulder arthroplasty was used for treatment.Main outcome measurementsThirty-day complications, mortality, readmission, and reoperation rates were measured.ResultsOf the total 1732 PHF patients identified, 300 had a MELD score higher than 10. After propensity matching by significant covariates, MELD score higher than 10 was found to be significantly associated with higher rates of 30-day mortality, 30-day readmission, transfusion within 72 hours, and systemic complications. Among patients with a MELD score higher than 10, treatment with SA or HA instead of ORIF was associated with a higher rate of transfusion and longer operative time. There were no significant differences between treatment cohorts regarding mortality, reoperation, readmission, or complications.ConclusionsA MELD score higher than 10 is associated with higher risk of surgical complications, transfusion, and death in patients undergoing surgery for proximal humerus fractures. Among patients with a MELD score higher than 10, ORIF was associated with a lower transfusion rate and shorter operative time than arthroplasty or hemiarthroplasty.Level of evidencePrognostic Level III

Novel bisphosphonate-based cathepsin K-triggered compound targets the enthesis without impairing soft tissue-to-bone healing

Background: Osteoadsorptive fluorogenic sentinel 3 (OFS-3) is a recently described compound that contains a bone-targeting bisphosphonate (BP) and cathepsin K (Ctsk)-triggered fluorescence signal. A prior study in a murine Achilles repair model demonstrated its effectiveness at targeting the site of tendon-to-bone repair, but the intrinsic effect of this novel bisphosphonate chaperone on tendon-to-bone healing has not been previously explored. We hypothesized that application of this bisphosphonate-fluorophore cargo conjugate would not affect the biomechanical properties or histologic appearance of tendon-bone repairs.Materials and Methods: Right hindlimb Achilles tendon-to-bone repair was performed on 12-week old male mice. Animals were divided into 2 groups of 18 each: 1) Achilles repair with OFS-3 applied directly to the repair site prior to closure, and 2) Achilles repair with saline applied prior to closure. Repaired hindlimbs from 12 animals per group were harvested at 6 weeks for biomechanical analysis with a custom 3D-printed jig. At 4 and 6 weeks, repaired hindlimbs from the remaining animals were assessed histologically using H&E, immunohistochemistry (IHC) staining for the presence of Ctsk, and second harmonic generation (SHG) imaging to evaluate collagen fibers.Results: At 6 weeks, there was no significant difference in failure load, stiffness, toughness, or displacement to failure between repaired hindlimbs that received OFS-3 versus saline. There was no difference in tissue healing on H&E or Ctsk staining on immunohistochemistry between animals that received OFS-3 versus saline. Finally, second harmonic generation imaging demonstrated no difference in collagen fiber parameters between the two groups.Conclusion: OFS-3 did not significantly affect the biomechanical properties or histologic appearance of murine Achilles tendon-to-bone repairs. This study demonstrates that OFS-3 can target the site of tendon-to-bone repair without causing intrinsic negative effects on healing. Further development of this drug delivery platform to target growth factors to the site of tendon-bone repair is warranted

Activation of Hif1α by the Prolylhydroxylase Inhibitor Dimethyoxalyglycine Decreases Radiosensitivity

Hypoxia inducible factor 1α (Hif1α) is a stress responsive transcription factor, which regulates the expression of genes required for adaption to hypoxia. Hif1α is normally hydroxylated by an oxygen-dependent prolylhydroxylase, leading to degradation and clearance of Hif1α from the cell. Under hypoxic conditions, the activity of the prolylhydroxylase is reduced and Hif1α accumulates. Hif1α is also constitutively expressed in tumor cells, where it is associated with resistance to ionizing radiation. Activation of the Hif1α transcriptional regulatory pathway may therefore function to protect normal cells from DNA damage caused by ionizing radiation. Here, we utilized the prolylhydroxylase inhibitor dimethyloxalylglycine (DMOG) to elevate Hif1α levels in mouse embryonic fibroblasts (MEFs) to determine if DMOG could function as a radioprotector. The results demonstrate that DMOG increased Hif1α protein levels and decreased the sensitivity of MEFs to ionizing radiation. Further, the ability of DMOG to function as a radioprotector required Hif1α, indicating a key role for Hif1α's transcriptional activity. DMOG also induced the Hif1α -dependent accumulation of several DNA damage response proteins, including CHD4 and MTA3 (sub-units of the NuRD deacetylase complex) and the Suv39h1 histone H3 methyltransferase. Depletion of Suv39h1, but not CHD4 or MTA3, reduced the ability of DMOG to protect cells from radiation damage, implicating increased histone H3 methylation in the radioprotection of cells. Finally, treatment of mice with DMOG prior to total body irradiation resulted in significant radioprotection of the mice, demonstrating the utility of DMOG and related prolylhydroxylase inhibitors to protect whole organisms from ionizing radiation. Activation of Hif1α through prolylhydroxylase inhibition therefore identifies a new pathway for the development of novel radiation protectors

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexit

Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression