Pharmacokinetics of Envarsus in pediatric kidney transplant recipients - phase 1 pilot conversion study.

INTRODUCTION: Tacrolimus is the standard immunosuppressant for pediatric kidney transplants and is routinely administered twice daily (BD-tac). Envarsus (LCP-tac), an extended-release formulation, is approved for adults but not for pediatric patients. METHODS: We conducted a pilot open-label phase 1 study in stable pediatric kidney transplant recipients (age < 18 at the time of study). Our primary objective was to compare the pharmacokinetics (Pk) of LCP-tac versus BD-tac. We conducted two 24-h Pk studies: pre-conversion (BD-tac) and 4 weeks post-conversion to LCP-tac. Patients were followed for 6 months, with the option to continue LCP-tac. RESULTS: Five patients completed the study, with no returns to BD-tac. Median age was 15 years (range 11-17). LCP-tac exhibited an extended-release profile versus the bimodal profile of BD-tac. Time to maximum concentration was delayed (5 h vs. 1 h), and maximum concentration was lower (9.9 ng/mL vs. 14.4 ng/mL). Tacrolimus area under the curve (24 h) was comparable (141 ± 46.5 ng/mL vs. 164 ± 27.8 ng/mL). No new safety concerns arose. There were no rejection and no difference in eGFR at the study's end (1.5 mL/min/1.73 m2 , range - 1.7 to 2.3 mL/min/1.73 m2 ). Concentration/dose ratio was higher in LCP-tac (1.8 ± 0.64 vs. 0.8 ± 0.39). The final conversion ratio was 0.6 (BD-tac: LCP-tac). CONCLUSION: Our pilot study confirms the extended-release Pk profile and improved absorption of LCP-tac compared to BD-tac. A larger study is needed to further evaluate the population Pk characteristics in children.

The International Olympic Committee framework on fairness, inclusion and nondiscrimination on the basis of gender identity and sex variations does not protect fairness for female athletes.

The International Olympic Committee (IOC) recently published a framework on fairness, inclusion, and nondiscrimination on the basis of gender identity and sex variations. Although we appreciate the IOC's recognition of the role of sports science and medicine in policy development, we disagree with the assertion that the IOC framework is consistent with existing scientific and medical evidence and question its recommendations for implementation. Testosterone exposure during male development results in physical differences between male and female bodies; this process underpins male athletic advantage in muscle mass, strength and power, and endurance and aerobic capacity. The IOC's "no presumption of advantage" principle disregards this reality. Studies show that transgender women (male-born individuals who identify as women) with suppressed testosterone retain muscle mass, strength, and other physical advantages compared to females; male performance advantage cannot be eliminated with testosterone suppression. The IOC's concept of "meaningful competition" is flawed because fairness of category does not hinge on closely matched performances. The female category ensures fair competition for female athletes by excluding male advantages. Case-by-case testing for transgender women may lead to stigmatization and cannot be robustly managed in practice. We argue that eligibility criteria for female competition must consider male development rather than relying on current testosterone levels. Female athletes should be recognized as the key stakeholders in the consultation and decision-making processes. We urge the IOC to reevaluate the recommendations of their Framework to include a comprehensive understanding of the biological advantages of male development to ensure fairness and safety in female sports.

A consensus process to identify research priorities in paediatric urology in the United Kingdom.

INTRODUCTION: Paediatric urologists manage a spectrum of conditions, much of the evidence for relevant treatment pathways is of low quality. For many conditions treatment varies according to location and surgeon; children with the same condition might have surgery in one unit but watchful waiting in another. Underlying this variation are differences in opinion, and insufficient high-level evidence with few prospective randomized studies. Such studies may be challenging to design, fund and recruit into, and are more likely to succeed if there is a collaborative approach. Research prioritization is a tool to identify the research of most value. Delphi methodology is an interpretive technique aiming to gain the consensus view of interested parties. The British Association of Paediatric Urologists (BAPU) set out to ascertain consensus on what paediatric urologists, working in the UK, consider to be areas of priority for research. This paper describes the process used, and the resulting list of research questions. METHODS: A scoping survey of paediatric urologists in the UK was undertaken to identify an initial set of research questions. These were refined by the BAPU research committee (BAPU RC), then prioritized using a modified Delphi process. During Stage 1a multiple new research questions were submitted leading to Stage 1b, an interim process. All UK paediatric urologists were invited to take part in Stage 2 of the prioritization process. RESULTS: Sixty-five questions were submitted to the scoping survey by 24 paediatric urologists. The BAPU RC refined these to 60 questions, which were submitted to Stage 1a of the modified Delphi process. Sixty-seven people completed Stage 1a, at the same time submitting 224 additional research questions. The BAPU RC revised the entire question set, ensuring the key subject of the original question was not altered and novel questions were retained. The BAPU RC undertook interim scoring of the resultant 79 questions, the top scoring 25 questions plus 5 lower scoring 'wild card' questions (to ensure the breadth of the specialty was represented) were put forward to Stage 2. A total of 65 people completed Stage 2, including a lay representative. A list of 30 priority research questions was generated; the top 10 includes management of neuropathic bladder, posterior urethral valves, antibiotic prophylaxis, DSD & CAH, continence, male external genitalia, VUR and transition care (Table). CONCLUSION: This process has provided BAPU, paediatric urologists in the UK, and funders with areas of research considered a priority in the specialty.

Impact of changes to invite methodology on equality of access to the National Breast Screening Programme in the South of England.

In response to the COVID-19 pandemic, a temporary change in policy was implemented in 2020. Breast screening services in England were advised to change from timed appointments to an open invitation for invitees to contact the service and arrange an appointment. This change to invitation methodology had potential benefits and risks including impacting inequalities in uptake. Qualitative data were collected by online questionnaire from 23 service providers and routinely collected quantitative uptake data were analysed to investigate the impact of open invitations on the National Programme in the South of England. Office for National Statistics and general practitioner (GP) practice profile data enabled the modelling of sociodemographic characteristics of breast screening invitees at each GP practice. Most services changed to open invitations (17/23), 82% of which altered administrative capacity and/or procedures to accommodate this change. Logistic benefits were reported including a more consistent flow of participants, fewer long gaps and fewer wasted slots. The change to open invitations was associated with a 7.2% reduction in the percentage of participants screened, accounting for participant sociodemographics and historical screening provider uptake. The inequality in screening uptake experienced by participants of minority ethnic background was exacerbated by the change to open invitations. Open invitations, whilst affording logistic benefits in an unprecedented pandemic era, were associated with reduced overall uptake and exacerbation of existing health inequality experienced by women of minority ethnic background. The broader impact on services highlighted the need for sustainability of measures taken to accommodate such operational changes.

The UK kidney donor risk index poorly predicts long-term transplant survival in paediatric kidney transplant recipients.

Background: The UK kidney offering scheme introduced a kidney donor risk index (UK-KDRI) to improve the utility of deceased-donor kidney allocations. The UK-KDRI was derived using adult donor and recipient data. We assessed this in a paediatric cohort from the UK transplant registry. Methods: We performed Cox survival analysis on first kidney-only deceased brain-dead transplants in paediatric (<18 years) recipients from 2000-2014. The primary outcome was death-censored allograft survival >30 days post-transplant. The main study variable was UK-KDRI derived from seven donor risk-factors, categorised into four groups (D1-low risk, D2, D3 and D4-highest risk). Follow-up ended on 31-December-2021. Results: 319/908 patients experienced transplant loss with rejection as the main cause (55%). The majority of paediatric patients received donors from D1 donors (64%). There was an increase in D2-4 donors during the study period, whilst the level of HLA mismatching improved. The KDRI was not associated with allograft failure. In multi-variate analysis, increasing recipient age [adjusted HR and 95%CI: 1.05(1.03-1.08) per-year, p<0.001], recipient minority ethnic group [1.28(1.01-1.63), p<0.05), dialysis before transplant [1.38(1.04-1.81), p<0.005], donor height [0.99 (0.98-1.00) per centimetre, p<0.05] and level of HLA mismatch [Level 3: 1.92(1.19-3.11); Level 4: 2.40(1.26-4.58) versus Level 1, p<0.01] were associated with worse outcomes. Patients with Level 1 and 2 HLA mismatches (0 DR +0/1 B mismatch) had median graft survival >17 years regardless of UK-KDRI groups. Increasing donor age was marginally associated with worse allograft survival [1.01 (1.00-1.01) per year, p=0.05]. Summary: Adult donor risk scores were not associated with long-term allograft survival in paediatric patients. The level of HLA mismatch had the most profound effect on survival. Risk models based on adult data alone may not have the same validity for paediatric patients and therefore all age-groups should be included in future risk prediction models.

The Genetic Association with Athlete Status, Physical Performance, and Injury Risk in Soccer.

The aim of this review was to critically appraise the literature concerning the genetic association with athlete status, physical performance, and injury risk in soccer. The objectives were to provide guidance on which genetic markers could potentially be used as part of future practice in soccer and to provide direction for future research in this area. The most compelling evidence identified six genetic polymorphisms to be associated with soccer athlete status (ACE I/D; ACTN3 rs1815739; AGT rs699; MCT1 rs1049434; NOS3 rs2070744; PPARA rs4253778), six with physical performance (ACTN3 rs1815739; AMPD1 rs17602729; BDNF rs6265; COL2A1 rs2070739; COL5A1 rs12722; NOS3 rs2070744), and seven with injury risk (ACTN3 rs1815739; CCL2 rs2857656; COL1A1 rs1800012; COL5A1 rs12722; EMILIN1 rs2289360; IL6 rs1800795; MMP3 rs679620). As well as replication by independent groups, large-scale genome-wide association studies are required to identify new genetic markers. Future research should also investigate the physiological mechanisms associating these polymorphisms with specific phenotypes. Further, researchers should investigate the above associations in female and non-Caucasian soccer players, as almost all published studies have recruited male participants of European ancestry. Only after robust, independently replicated genetic data have been generated, can genetic testing be considered an additional tool to potentially inform future practice in soccer.

The PPARGC1A Gly482Ser polymorphism is associated with elite long-distance running performance.

Success in long-distance running relies on multiple factors including oxygen utilisation and lactate metabolism, and genetic associations with athlete status suggest elite competitors are heritably predisposed to superior performance. The Gly allele of the PPARGC1A Gly482Ser rs8192678 polymorphism has been associated with endurance athlete status and favourable aerobic training adaptations. However, the association of this polymorphism with performance amongst long-distance runners remains unclear. Accordingly, this study investigated whether rs8192678 was associated with elite status and competitive performance of long-distance runners. Genomic DNA from 656 Caucasian participants including 288 long-distance runners (201 men, 87 women) and 368 non-athletes (285 men, 83 women) was analysed. Medians of the 10 best UK times (Top10) for 10 km, half-marathon and marathon races were calculated, with all included athletes having personal best (PB) performances within 20% of Top10 (this study's definition of "elite"). Genotype and allele frequencies were compared between athletes and non-athletes, and athlete PB compared between genotypes. There were no differences in genotype frequency between athletes and non-athletes, but athlete Ser allele carriers were 2.5% faster than Gly/Gly homozygotes (p = 0.030). This study demonstrates that performance differences between elite long-distance runners are associated with rs8192678 genotype, with the Ser allele appearing to enhance performance.

Collagen Gene Polymorphisms Previously Associated with Resistance to Soft-Tissue Injury Are More Common in Competitive Runners Than Nonathletes.

ABSTRACT: Dines, HR, Nixon, J, Lockey, SJ, Herbert, AJ, Kipps, C, Pedlar, CR, Day, SH, Heffernan, SM, Antrobus, MR, Brazier, J, Erskine, RM, Stebbings, GK, Hall, ECR, and Williams, AG. Collagen gene polymorphisms previously associated with resistance to soft-tissue injury are more common in competitive runners than nonathletes. J Strength Cond Res 37(4): 799-805, 2023-Single-nucleotide polymorphisms (SNPs) of collagen genes have been associated with soft-tissue injury and running performance. However, their combined contribution to running performance is unknown. We investigated the association of 2 collagen gene SNPs with athlete status and performance in 1,429 Caucasian subjects, including 597 competitive runners (354 men and 243 women) and 832 nonathletes (490 men and 342 women). Genotyping for COL1A1 rs1800012 (C > A) and COL5A1 rs12722 (C > T) SNPs was performed by a real-time polymerase chain reaction. The numbers of "injury-resistant" alleles from each SNP, based on previous literature (rs1800012 A allele and rs12722 C allele), were combined as an injury-resistance score (RScore, 0-4; higher scores indicate injury resistance). Genotype frequencies, individually and combined as an RScore, were compared between cohorts and investigated for associations with performance using official race times. Runners had 1.34 times greater odds of being rs12722 CC homozygotes than nonathletes (19.7% vs. 15.5%, p = 0.020) with no difference in the rs1800012 genotype distribution ( p = 0.659). Fewer runners had an RScore 0 of (18.5% vs. 24.7%) and more had an RScore of 4 (0.6% vs. 0.3%) than nonathletes ( p < 0.001). Competitive performance was not associated with the COL1A1 genotype ( p = 0.933), COL5A1 genotype ( p = 0.613), or RScore ( p = 0.477). Although not associated directly with running performance among competitive runners, a higher combined frequency of injury-resistant COL1A1 rs1800012 A and COL5A1 rs12722 C alleles in competitive runners than nonathletes suggests these SNPs may be advantageous through a mechanism that supports, but does not directly enhance, running performance.

Gene variants previously associated with reduced soft tissue injury risk: Part 1 - independent associations with elite status in rugby.

There is growing evidence of genetic contributions to tendon and ligament pathologies. Given the high incidence and severity of tendon and ligament injuries in elite rugby, we studied whether 13 gene polymorphisms previously associated with tendon/ligament injury were associated with elite athlete status. Participants from the RugbyGene project were 663 elite Caucasian male rugby athletes (RA) (mean (standard deviation) height 1.85 (0.07) m, mass 101 (12) kg, age 29 (7) yr), including 558 rugby union athletes (RU) and 105 rugby league athletes. Non-athletes (NA) were 909 Caucasian men and women (56% female; height 1.70 (0.10) m, mass 72 (13) kg, age 41 (23) yr). Genotypes were determined using TaqMan probes and groups compared using Χ2 and odds ratio (OR). COLGALT1 rs8090 AA genotype was more frequent in RA (27%) than NA (23%; P = 0.006). COL3A1 rs1800255 A allele was more frequent in RA (26%) than NA (23%) due to a greater frequency of GA genotype (39% vs 33%). For MIR608 rs4919510, RA had 1.7 times the odds of carrying the CC genotype compared to NA. MMP3 rs591058 TT genotype was less common in RA (25.1%) than NA (31.2%; P < 0.04). For NID1 rs4660148, RA had 1.6 times the odds of carrying the TT genotype compared to NA. It appears that elite rugby athletes have an inherited advantage that contributes to their elite status, possibly via resistance to soft tissue injury. These data may, in future, assist personalised management of injury risk amongst athletes.Highlights The elite rugby athletes we studied had differing genetic characteristics to non-athletes regarding genetic variants previously associated with soft-tissue injury risk.COLGALT1 rs8090, COL3A1 rs1800255, MIR608 rs4919510, MMP3 rs591058 and NID1 rs4660148 were all associated with elite status in rugby.We propose that elite rugby athletes might possess an inherited resistance to soft tissue injury, which has enabled them to achieve elite status despite exposure to the high-risk environment of elite rugby.

Concussion-Associated Gene Variant COMT rs4680 Is Associated With Elite Rugby Athlete Status.

OBJECTIVE: Concussions are common match injuries in elite rugby, and reports exist of reduced cognitive function and long-term health consequences that can interrupt or end a playing career and produce continued ill health. The aim of this study was to investigate the association between elite rugby status and 8 concussion-associated risk polymorphisms. We hypothesized that concussion-associated risk genotypes and alleles would be underrepresented in elite rugby athletes compared with nonathletes. DESIGN: A case-control genetic association study. SETTING: Institutional (university). PARTICIPANTS: Elite White male rugby athletes [n = 668, mean (SD) height 1.85 (0.07) m, mass 102 (12) kg, and age 29 (7) years] and 1015 nonathlete White men and women (48% men). INTERVENTIONS: Genotype was the independent variable, obtained by PCR of genomic DNA using TaqMan probes. MAIN OUTCOME MEASURE: Elite athlete status with groups compared using χ 2 and odds ratio (OR). RESULTS: The COMT rs4680 Met/Met (AA) genotype, Met allele possession, and Met allele frequency were lower in rugby athletes (24.8%, 74.6%, and 49.7%, respectively) than nonathletes (30.2%, 77.6%, and 54.0%; P < 0.05). The Val/Val (GG) genotype was more common in elite rugby athletes than nonathletes (OR 1.39, 95% confidence interval 1.04-1.86). No other polymorphism was associated with elite athlete status. CONCLUSIONS: Elite rugby athlete status is associated with COMT rs4680 genotype that, acting pleiotropically, could affect stress resilience and behavioral traits during competition, concussion risk, and/or recovery from concussion. Consequently, assessing COMT rs4680 genotype might aid future individualized management of concussion risk among athletes.

Gene variants previously associated with reduced soft-tissue injury risk: Part 2 - Polygenic associations with elite status in Rugby.

Part 1 of this genetic association series highlighted several genetic variants independently associated with elite status in rugby. However, it is highly likely that the genetic influence on elite status is polygenic due to the interaction of multiple genes. Therefore, the aim of the present study was to investigate whether polygenic profiles of elite rugby athletes differed from non-athletes utilising 13 genetic polymorphisms previously associated with tendon/ligament injury. Total genotype score (TGS) was calculated and multifactor dimensionality reduction (MDR) was used to calculate SNP-SNP epistasis interactions. Based on our elite rugby data from Part 1, mean TGS was significantly higher in elite rugby athletes (52.1 ± 10.7) than non-athletes (48.7 ± 10.8). There were more elite rugby athletes (54%) within the upper TGS quartile, and fewer (46%) within the lower quartile, compared to non-athletes (31% and 69%, respectively; P = 5·10-5), and the TGS was able to distinguish between elite rugby athletes and non-athletes (area under the curve = 0.59; 95% confidence interval 0.55-0.63; P = 9·10-7). Furthermore, MDR identified a three-SNP model of COL5A1 rs12722, COL5A1 rs3196378 and MIR608 rs4919510 that was best able to predict elite athlete status, with a greater frequency of the CC-CC-CC genotype combination in elite rugby athletes (9.8%) than non-athletes (5.3%). We propose that elite rugby athletes possess "preferable" musculoskeletal soft-tissue injury-associated polygenic profiles that have helped them achieve success in the high injury risk environment of rugby. These data may, in future, have implications for the individual management of musculoskeletal soft-tissue injury.HighlightsElite rugby athletes have preferable polygenic profiles to non-athletes in terms of genetic variants previously associated with musculoskeletal soft-tissue injury.The total genotype score was able to distinguish between elite rugby athletes and non-athletes.COL5A1 rs12722, COL5A1 rs3196378 and MIR608 rs4919510 produced the best model for predicting elite athlete status.We propose that elite rugby athletes may have an inherited advantage to achieving elite status due to an increased resistance to soft-tissue injury.

A BURST-BAUS consensus document for best practice in the conduct of scrotal exploration for suspected testicular torsion: the Finding consensus for orchIdopeXy In Torsion (FIX-IT) study.

OBJECTIVES: To produce a best practice consensus guideline for the conduct of scrotal exploration for suspected testicular torsion using formal consensus methodology. MATERIALS AND METHODS: A panel of 16 expert urologists, representing adult, paediatric, general, and andrological urology used the RAND/UCLA Appropriateness Consensus Methodology to score a 184 statement pre-meeting questionnaire on the conduct of scrotal exploration for suspected testicular torsion. The collated responses were presented at a face-to-face online meeting and each item was rescored anonymously after a group discussion, facilitated by an independent chair with expertise in consensus methodology. Items were scored for agreement and consensus and the items scored with consensus were used to derive a set of best practice guidelines. RESULTS: Statements scored as with consensus increased from Round 1 (122/184, 66.3%) to Round 2 (149/200, 74.5%). Recommendations were generated in ten categories: consent, assessment under anaesthetic, initial incision, intraoperative decision making, fixation, medical photography, closure, operation note, logistics and follow-up after scrotal exploration. Our statements assume that the decision to operate has already been made. Key recommendations in the consent process included the discussion of the possibility of orchidectomy and the possibility of subsequent infection of the affected testis or wound requiring antibiotic therapy. If after the examination under anaesthesia, the index of suspicion of testicular torsion is lower than previously thought, then the surgeon should still proceed to scrotal exploration as planned. A flow chart guiding decision making dependent on intraoperative findings has been designed. If no torsion is present on exploration and the bell clapper deformity is absent, the testis should not be fixed. When fixing a testis using sutures, 3 or 4-point is acceptable and non-absorbable sutures are preferred. CONCLUSIONS: We have produced consensus recommendations to inform best practice in the conduct of scrotal exploration for suspected testicular torsion.

Polygenic Models Partially Predict Muscle Size and Strength but Not Low Muscle Mass in Older Women.

Background: Heritability explains 45-82% of muscle mass and strength variation, yet polygenic models for muscle phenotypes in older women are scarce. Therefore, the objective of the present study was to (1) assess if total genotype predisposition score (GPSTOTAL) for a set of polymorphisms differed between older women with low and high muscle mass, and (2) utilise a data-driven GPS (GPSDD) to predict the variance in muscle size and strength-related phenotypes. Methods: In three-hundred 60- to 91-year-old Caucasian women (70.7 ± 5.7 years), skeletal muscle mass, biceps brachii thickness, vastus lateralis anatomical cross-sectional area (VLACSA), hand grip strength (HGS), and elbow flexion (MVCEF) and knee extension (MVCKE) maximum voluntary contraction were measured. Participants were classified as having low muscle mass if the skeletal muscle index (SMI) < 6.76 kg/m2 or relative skeletal muscle mass (%SMMr) < 22.1%. Genotyping was completed for 24 single-nucleotide polymorphisms (SNPs). GPSTOTAL was calculated from 23 SNPs and compared between the low and high muscle mass groups. A GPSDD was performed to identify the association of SNPs with other skeletal muscle phenotypes. Results: There was no significant difference in GPSTOTAL between low and high muscle mass groups, irrespective of classification based on SMI or %SMMr. The GPSDD model, using 23 selected SNPs, revealed that 13 SNPs were associated with at least one skeletal muscle phenotype: HIF1A rs11549465 was associated with four phenotypes and, in descending number of phenotype associations, ACE rs4341 with three; PTK2 rs7460 and CNTFR rs2070802 with two; and MTHFR rs17421511, ACVR1B rs10783485, CNTF rs1800169, MTHFR rs1801131, MTHFR rs1537516, TRHR rs7832552, MSTN rs1805086, COL1A1 rs1800012, and FTO rs9939609 with one phenotype. The GPSDD with age included as a predictor variable explained 1.7% variance of biceps brachii thickness, 12.5% of VLACSA, 19.0% of HGS, 8.2% of MVCEF, and 9.6% of MVCKE. Conclusions: In older women, GPSTOTAL did not differ between low and high muscle mass groups. However, GPSDD was associated with muscle size and strength phenotypes. Further advancement of polygenic models to understand skeletal muscle function during ageing might become useful in targeting interventions towards older adults most likely to lose physical independence.

Concussion-Associated Polygenic Profiles of Elite Male Rugby Athletes.

Due to the high-velocity collision-based nature of elite rugby league and union, the risk of sustaining a concussion is high. Occurrence of and outcomes following a concussion are probably affected by the interaction of multiple genes in a polygenic manner. This study investigated whether suspected concussion-associated polygenic profiles of elite rugby athletes differed from non-athletes and between rugby union forwards and backs. We hypothesised that a total genotype score (TGS) using eight concussion-associated polymorphisms would be higher in elite rugby athletes than non-athletes, indicating selection for protection against incurring or suffering prolonged effects of, concussion in the relatively high-risk environment of competitive rugby. In addition, multifactor dimensionality reduction was used to identify genetic interactions. Contrary to our hypothesis, TGS did not differ between elite rugby athletes and non-athletes (p ≥ 0.065), nor between rugby union forwards and backs (p = 0.668). Accordingly, the TGS could not discriminate between elite rugby athletes and non-athletes (AUC ~0.5), suggesting that, for the eight polymorphisms investigated, elite rugby athletes do not have a more 'preferable' concussion-associated polygenic profile than non-athletes. However, the COMT (rs4680) and MAPT (rs10445337) GC allele combination was more common in rugby athletes (31.7%; p < 0.001) and rugby union athletes (31.8%; p < 0.001) than non-athletes (24.5%). Our results thus suggest a genetic interaction between COMT (rs4680) and MAPT (rs10445337) assists rugby athletes in achieving elite status. These findings need exploration vis-à-vis sport-related concussion injury data and could have implications for the management of inter-individual differences in concussion risk.

Injury risk is greater in physically mature versus biologically younger male soccer players from academies in different countries.

OBJECTIVES: To investigate if maturity status was associated with injury risk in male academy soccer players. DESIGN: Prospective cohort surveillance study. SETTING: Professional soccer academies. PARTICIPANTS: 501 players (aged 9-23 years) from eight academies in England, Spain, Uruguay and Brazil. MAIN OUTCOME MEASURES: Players were grouped by maturity offset as pre-peak height velocity (PHV), circa-PHV, post-PHV or adult. Injury prevalence proportion (IPP) and days missed were recorded for one season per player, with training/match exposure recorded in a sub-sample (n = 166). RESULTS: IPP for all injuries combined increased with advancing maturity, with circa-PHV (p = 0.032), post-PHV (p < 0.001) and adult (p < 0.001) higher than pre-PHV. IPP was higher in post-PHV and adult than pre-PHV for non-contact (p = 0.001 and p = 0.012), soft-tissue (both p < 0.001), non-contact soft-tissue (p < 0.001 and p = 0.005), muscle (both p < 0.001), thigh (both p < 0.001), ankle (p = 0.035 and p = 0.007) and hamstring injuries (p = 0.041 and p = 0.017). Ligament/tendon IPP was greater in adult versus pre-PHV (p = 0.002). IPP for growth-related injuries was lower in post-PHV than pre-PHV (p = 0.039). Injury incidence rates (n = 166) exhibited similar patterns to IPP in the full cohort. CONCLUSIONS: Injury patterns were similar between post-PHV and adult academy players but, crucially, relatively more of these groups suffered injuries compared to pre- and circa-PHV (except growth-related injuries).

Playing Position and the Injury Incidence Rate in Male Academy Soccer Players.

CONTEXT: Whether playing position influences injury in male academy soccer players (ASPs) is unclear. OBJECTIVE: To determine if playing position was associated with injury in ASPs. DESIGN: Descriptive epidemiology study. SETTING: English, Spanish, Uruguayan, and Brazilian soccer academies. PATIENTS OR OTHER PARTICIPANTS: A total of 369 ASPs from the under-14 to under-23 age groups, classified as post-peak height velocity using maturity offset, and grouped as goalkeepers, lateral defenders, central defenders, lateral midfielders, central midfielders, or forwards. MAIN OUTCOME MEASURE(S): Injuries were recorded prospectively over 1 season. Injury prevalence proportion (IPP), days missed, and injury incidence rate (IIR, injuries/1000 training or match hours, n = 116) were analyzed according to playing position. RESULTS: No association with playing position was observed for any injury type or location regarding IPP (P ≥ .089) or days missed (P ≥ .235). The IIR was higher in central defenders than in lateral defenders for general (9.30 versus 4.18 injuries/1000 h, P = .009), soft tissue (5.14 versus 1.95 injuries/1000 h, P = .026), and ligament or tendon injuries (2.69 versus 0.56 injuries/1000 h, P = .040). The central versus lateral or forward positions were not associated with IPP (P ≥ .051) or days missed (P ≥ .083), but general IIR was greater in the central position than the lateral or forward positions (8.67 versus 6.12 injuries/1000 h, P = .047). CONCLUSIONS: Academy soccer players' playing positions were not associated with IPP or days missed, but the higher general, soft tissue, and ligament or tendon IIRs in central defenders suggest that this position warrants specific attention regarding injury-prevention strategies. These novel findings highlight the importance of considering training or match exposure when investigating the influence of playing position on injury in ASPs.

Polygenic Profile of Elite Strength Athletes.

ABSTRACT: Moreland, E, Borisov, OV, Semenova, EA, Larin, AK, Andryushchenko, ON, Andryushchenko, LB, Generozov, EV, Williams, AG, and Ahmetov, II. Polygenic profile of elite strength athletes. J Strength Cond Res 36(9): 2509-2514, 2022-Strength is a heritable trait with unknown polygenic nature. So far, more than 200 DNA polymorphisms associated with strength/power phenotypes have been identified majorly involving nonathletic populations. The aim of the present study was to investigate individually and in combination the association of 217 DNA polymorphisms previously identified as markers for strength/power phenotypes with elite strength athlete status. A case-control study involved 83 Russian professional strength athletes (53 weightlifters, 30 powerlifters), 209 Russian and 503 European controls. Genotyping was conducted using micro-array analysis. Twenty-eight DNA polymorphisms (located near or in ABHD17C , ACTG1 , ADCY3 , ADPGK , ANGPT2 , ARPP21 , BCDIN3D , CRTAC1 , DHODH , GBE1 , IGF1 , IL6 , ITPR1 , KIF1B , LRPPRC , MMS22L , MTHFR , NPIPB6 , PHACTR1 , PLEKHB1 , PPARG , PPARGC1A , R3HDM1 , RASGRF1 , RMC1 , SLC39A8 , TFAP2D , ZKSCAN5 genes) were identified to have an association with strength athlete status. Next, to assess the combined impact of all 28 DNA polymorphisms, all athletes were classified according to the number of "strength" alleles they possessed. All highly elite strength athletes were carriers of at least 22 (up to 34) "strength" alleles, whereas 27.8% of Russian controls had less than 22 "strength" alleles ( p < 0.0001). The proportion of subjects with a high (≥26) number of "strength" alleles was significantly greater in highly elite strength athletes (84.8%) compared with less successful strength athletes (64.9%; odd ratio [OR] = 3.0, p = 0.042), Russian (26.3%; OR = 15.6, p < 0.0001) or European (37.8%; OR = 6.4, p < 0.0001) controls. This is the first study to demonstrate that the likelihood of becoming an elite strength athlete depends on the carriage of a high number of strength-related alleles.

The genetic association with injury risk in male academy soccer players depends on maturity status.

It is currently unknown if injury risk is associated with genetic variation in academy soccer players (ASP). We investigated whether nine candidate single nucleotide polymorphisms were associated (individually and in combination) with injury in ASP at different stages of maturation. Saliva samples and one season's injury records were collected from 402 Caucasian male ASP from England, Spain, Uruguay, and Brazil, whose maturity status was defined as pre- or post-peak height velocity (PHV). Pre-PHV COL5A1 rs12722 CC homozygotes had relatively higher prevalence of any musculoskeletal soft tissue (22.4% vs. 3.0%, p = 0.018) and ligament (18.8% vs. 11.8%, p = 0.029) injury than T-allele carriers, while VEGFA rs2010963 CC homozygotes had greater risk of ligament/tendon injury than G-allele carriers. Post-PHV IL6 rs1800795 CC homozygotes had a relatively higher prevalence of any (67.6% vs. 40.6%, p = 0.003) and muscle (38.2% vs. 19.2%, p = 0.013) injuries than G-allele carriers. Relatively more post-PHV EMILIN1 rs2289360 CC homozygotes suffered any injury than CT and TT genotypes (56.4% vs. 40.3% and 32.8%, p = 0.007), while the "protective" EMILIN1 TT genotype was more frequent in post- than pre-PHV ASP (22.3 vs. 10.0%, p = 0.008). Regardless of maturity status, T-alleles of ACTN3 rs1815739 and EMILIN1 rs2289360 were associated with greater absence following ankle injury, while the MMP3 rs679620 T-allele and MYLK rs28497577 GT genotype were associated with greater absence following knee injury. The combination of injury-associated genotypes was greater in injured vs. non-injured ASP. This study is the first to demonstrate that a genetic association exists with injury prevalence in ASP, which differs according to maturity status.

Bladder urothelial cell carcinoma as a rare cause of haematuria in children: Our experience and review of current literature.

OBJECTIVES: To report our experience of bladder urothelial cell carcinoma (UCC) in children and review contemporary management and follow-up of paediatric UCC. PATIENTS AND METHODS: Between 2004 and 2020, five patients (4 boys and 1 girl) were managed at our centre for urothelial cell carcinoma of the bladder. Data was collected by note review for age at presentation, symptoms, clinical findings, investigations, treatment and follow-up. RESULTS: All five patients presented with visible haematuria, two had dysuria and one had suprapubic pain. Bladder ultrasound scan (USS) showed exophytic bladder lesions in only 4 patients. Definitive diagnosis and treatment were achieved by cystoscopic excision. Four patients had PUNLMP while one had Grade 3 pTa UCC of the bladder which required further cystoscopic excision and intravesical Mitomycin C (MMC) instillation. All patients were followed up clinically, with renal USS and cystoscopy. We have observed recurrence of the carcinoma in two patients requiring further cystoscopic excision and intravesical MMC. CONCLUSION: Bladder urothelial cell carcinoma in children should be suspected in children presenting with haematuria. If renal USS is normal, cystoscopy should be considered for diagnosis and treatment. Compared to adults, children with bladder UCC often have favourable histopathology and prognosis. Close follow-up is necessary with renal USS and cystoscopy to detect recurrence even in PUNLMP.