The Comparative Effect of Different Timings of Whole Body Cryotherapy Treatment With Cold Water Immersion for Post-Exercise Recovery.

Despite several established benefits of Whole Body Cryotherapy (WBC) for post-exercise recovery, there is a scarcity of research which has identified the optimum WBC protocol for this purpose. This study investigated the influence of WBC treatment timing on physiological and functional responses following a downhill running bout. An additional purpose was to compare such responses with those following cold water immersion (CWI), since there is no clear consensus as to which cold modality is more effective for supporting athletic recovery. Thirty-three male participants (mean ± SD age 37.0 ± 13.3 years, height 1.76 ± 0.07 m, body mass 79.5 ± 13.7 kg) completed a 30 min downhill run (15% gradient) at 60% VO2 max and were then allocated into one of four recovery groups: WBC1 (n = 9) and WBC4 (n = 8) underwent cryotherapy (3 min, -120°C) 1 and 4 h post-run, respectively; CWI (n = 8) participants were immersed in cold water (10 min, 15°C) up to the waist 1 h post-run and control (CON, n = 8) participants passively recovered in a controlled environment (20°C). Maximal isometric leg muscle torque was assessed pre and 24 h post-run. Blood creatine kinase (CK), muscle soreness, femoral artery blood flow, plasma IL-6 and sleep were also assessed pre and post-treatment. There were significant decreases in muscle torque for WBC4 (10.9%, p = 0.04) and CON (11.3% p = 0.00) and no significant decreases for WBC1 (5.6%, p = 0.06) and CWI (5.1%, p = 0.15). There were no significant differences between groups in muscle soreness, CK, IL-6 or sleep. Femoral artery blood flow significantly decreased in CWI (p = 0.02), but did not differ in other groups. WBC treatments within an hour may be preferable for muscle strength recovery compared to delayed treatments; however WBC appears to be no more effective than CWI. Neither cold intervention had an impact on inflammation or sleep.

Tendon and Ligament Genetics: How Do They Contribute to Disease and Injury? A Narrative Review.

A significant proportion of patients requiring musculoskeletal management present with tendon and ligament pathology. Our understanding of the intrinsic and extrinsic mechanisms that lead to such disabilities is increasing. However, the complexity underpinning these interactive multifactorial elements is still not fully characterised. Evidence highlighting the genetic components, either reducing or increasing susceptibility to injury, is increasing. This review examines the present understanding of the role genetic variations contribute to tendon and ligament injury risk. It examines the different elements of tendon and ligament structure and considers our knowledge of genetic influence on form, function, ability to withstand load, and undertake repair or regeneration. The role of epigenetic factors in modifying gene expression in these structures is also explored. It considers the challenges to interpreting present knowledge, the requirements, and likely pathways for future research, and whether such information has reached the point of clinical utility.

The role of vancomycin-soaking of the graft in anterior cruciate ligament reconstruction.

Approximately 1% of anterior cruciate ligament reconstruction (ACLR) procedures develop septic arthritis despite intravenous antibiotic prophylaxis and other preventive measures. Infection is most commonly due to contamination during autograft harvest and preparation by introducing bacteria into the knee during graft insertion. Pre-soaking ACL grafts in 5 mg/mL vancomycin ("vancomycin wrap") has been utilised to eradicate such bacterial contamination. Many level III studies have reported a marked decrease in infection rates with no increase in graft failure rates. However, the lack of prospective randomised control trials and these studies' heterogeneity do not allow a universal recommendation for vancomycin pre-soaking of all grafts during ACLR. Randomised controlled trials are needed to confirm efficacy in reducing sepsis rates.

The Effect of Repetitive Whole Body Cryotherapy Treatment on Adaptations to a Strength and Endurance Training Programme in Physically Active Males.

Despite its potential merit in sport and exercise recovery, the implications of repetitive Whole Body Cryotherapy (WBC) during training programmes require further review due to the possibility of repetitive cold interfering with long term adaptations. This study investigated the impact of two weekly 3 min WBC sessions (30 s at -60°C, 150 s at -120°C) on adaptations to a 6 week strength and endurance training programme. Sixteen male participants (mean ± SD age 33.4 ± 9.8 years, body mass 82.3 ± 9.8 kg) randomly allocated into WBC (n = 7) and non-cryotherapy control (CON, n=9) groups completed the programme consisting of two weekly strength and plyometric training sessions and two weekly 30 min runs (70% VO2 max). Participants were assessed for body fat, VO2 max, muscle torque, three repetition maximum barbell squat and countermovement jump height before and after the programme. Resistance and running intensities were progressed after 3 weeks. Participants in both groups significantly improved muscle torque (WBC: 277.1 ± 63.2 Nm vs. 318.1 ± 83.4 Nm, p < 0.01, d = 0.56; CON: 244.6 ± 50.6 Nm vs. 268.0 ± 71.8 Nm, p = 0.05, d = 0.38) and barbell squat (WBC: 86.4 ± 19.5 kg vs. 98.9 ± 15.2 kg, p = 0.03, d = 0.69; CON: 91.1 ± 28.7 kg vs. 106.1 ± 30.0 kg, p < 0.01, d=0.51) following the 6 week programme. For the CON group, there was also a significant reduction in body fat percentage (p = 0.01) and significant increase in jump height (p = 0.01). There was no significant increase in VO2 max for either group (both p > 0.2). There was no difference between WBC and CON for responses in muscle torque, 3RM barbell squat and body fat, however WBC participants did not increase their jump height (p = 0.23). Repetitive WBC does not appear to blunt adaptations to a concurrent training programme, although there may be an interference effect in the development of explosive power. Sports practitioners can cautiously apply repetitive WBC to support recovery post-exercise without undue concern on athletes' fitness gains or long term performance, particularly throughout training phases focused more on general strength development than explosive power.

Vitamin D and the athlete-patient: state of the art.

Vitamin D deficiency is common in athletes. The conventional measurement of vitamin D levels provides a general indicator of body stores. However, there are nuances in its interpretation as values of 25(OH)D do not correlate absolutely with the amount of 'bioavailable' vitamin to the cells. Vitamin D should be regarded as a hormone and influences between 5% and 10% of our total genome. Determining the precise effect of the vitamin, isolated from the actions of other cofactors, is not straightforward and restricts our complete understanding of all of its actions. Deficiency has harmful effects on not only bone and muscle but also wider areas, including immunity and respiratory and neurological activities. More caution should be applied regarding the ability of supranormal vitamin D levels to elevate athletic performance. Hopefully, future research will shed more light on optimal levels of vitamin D and supplementation regimes, and improved understanding of its intracellular control of our genetic mechanisms and how extrinsic influences modify its activity.

Functional COL1A1 variants are associated with the risk of acute musculoskeletal soft tissue injuries.

Studies have reported the association of the COL1A1 Sp1 binding site variant (rs1800012) with the risk of acute musculoskeletal soft tissue injuries. Interaction with the COL1A1 promoter variant (rs1107946) has also been proposed to modulate acute injury risk. Conversely, neither of these loci have been associated with chronic musculoskeletal soft tissue phenotypes. Therefore, the primary aim of this study involved characterizing these variants in a cohort of participants with chronic Achilles tendinopathy. Second, this study aimed to support the contribution of the rs1107946 and rs1800012 variants to the profile predisposing for acute musculoskeletal soft tissue injuries including Achilles tendon and anterior cruciate ligament (ACL) ruptures. A hypothesis-driven association study was conducted. In total, 295 control participants, 210 participants with clinically diagnosed Achilles tendinopathy, and 72 participants with Achilles tendon ruptures recruited independently from South Africa and the United Kingdom were genotyped for the prioritized variants. In addition, a cohort including 232 control participants and 234 participants with surgically diagnosed ACL ruptures was also analyzed. Although no associations were observed in the recruited cohorts, the rare rs1800012 TT genotype was associated with decreased ACL injury risk when the results from the current study were combined with that from previously published studies (P = .040, OR: 2.8, 95% CI: 1.0-11.0). In addition, the G-T (rs1107946-rs1800012) inferred haplotype was associated with decreased risk for Achilles tendon ruptures. These results support previous observations and reiterate the heterogeneity of musculoskeletal phenlotypes whereby certain markers may be common to the predisposing profiles while others may be unique.

Variability within the human iNOS gene and Achilles tendon injuries: Evidence for a heterozygous advantage effect.

OBJECTIVES: The aim of this case control genetic association study was to explore whether two variants within the inducible nitric oxide synthase (iNOS) gene, rs2779249 (C/A) and rs2248814 (A/G), influenced the risk of Achilles tendinopathy in a British population. DESIGN: Candidate gene, case control association study. METHOD: We recruited 145 individuals diagnosed with Achilles tendon pathology and 132 asymptomatic controls. All participants were genotyped for the iNOS variants using qPCR and significant associations were discovered using a combination of Chi squared and ANOVA type analysis. RESULTS: The CA genotype of the iNOS rs2779249 variant was protective and conformed to a heterozygous advantage model of inheritance as it was overrepresented in the control participants (p=0.009). In sex specific analysis the protective association persisted in male participants (p=0.016) but not in females. Unlike the rs2779249 variant, the rs2248814 variant was not associated with Achilles tendinopathy or Achilles tendon rupture. CONCLUSION: The rs2779249 CA genotype within the human iNOS gene appears to protect individuals from Achilles tendinopathy. This study further supports a genetic contribution to modifying the risk of Achilles tendon problems. The study also infers an important role for nitric oxide in tendon healing and/or degradation.

Vitamin D and foot and ankle trauma: An individual or societal problem.

BACKGROUND: Vitamin D deficiency is a worldwide health concern. Hypovitaminosis D may adversely affect recovery from bone injury. The authors aimed to perform an audit of the Vitamin D status of patients in three centres in the United Kingdom presenting with foot and ankle osseous damage. METHODS: Serum 25-hydroxyvitamin-D (vitamin D) levels were obtained in patients presenting with imaging confirmed foot and ankle osseous trauma. Variables including age, gender, ethnicity, location, season, month, anatomical location and type of bone injury were recorded. RESULTS: 308 patients were included from three different centres. 66.6% were female. The average age was 47.7 (range; 10-85). The mean hydroxyvitamin-D levels were 52.0 nmol/L (SD 28.5). 18.8% were grossly deficient, 23.7% deficient, 34.7% insufficient and 22.7% within normal range. 351 separate bone injuries were identified of which 104 were categorised as stress reactions, 134 as stress fractures, 105 as fractures and 8 non-unions. Age, gender, anatomical location and fracture type did not statistically affect vitamin D levels. Ethnicity did affect Vitamin D levels: non-Caucasians mean levels were 32.4 nmols/L compared to Caucasian levels of 53.2 nmol/L (p=0.0026). CONCLUSION: Only 18.8% of our trauma patients had a normal Vitamin D level and 22.7% were grossly deficient. Patient age, gender, anatomical location and injury type did not statistically affect vitamin D levels. No difference between trauma and elective patients were found. Hypovitaminosis D is a problem of society in general rather than specific to certain foot and ankle injury patterns or particular patient groups sustaining trauma. LEVEL OF EVIDENCE: 2b.

Vitamin D levels in 577 consecutive elective foot & ankle surgery patients.

BACKGROUND: Vitamin D deficiency is a global concern impacting upon large communities and certain disease populations. It can adversely affect the outcome of orthopaedic operations. We aimed to perform an audit of the Vitamin D status of patients in two centres in the United Kingdom undergoing elective foot and ankle surgery. METHODS: Serum 25-hydroxyvitamin-D (vitamin D) levels were obtained prospectively in 577 consecutive elective patients undergoing elective foot and ankle surgery between October 2014 and March 2017 (29 months). Variables including age, gender, ethnicity, location, season, month and procedure type were recorded. RESULTS: 577 patients were included over the study period. 62.0% were female. Mean age was 53.2 (median 54.5, range 16.7-86.6). 300 patients were treated in Northampton and 277 in Leicester. The serum 25-hydroxyvitamin-D levels for the patient group were normally distributed. The mean was 52.3nmol/L (SD 28.0; range 7.5-175) and the median 47.5nmol/L. 21.7% were grossly deficient, 31.9% deficient, 28.9% insufficient and 17.5% within normal range. Age, gender and procedure type did not statistically affect vitamin D levels (p=0.5, t-test). Ethnicity, location and Winter season did affect Vitamin D levels (p<0.05). August was the most significant month with levels significantly higher than January, February, March, April, June, November and December (p<0.05, one-way ANOVA). CONCLUSIONS: Only 1 in 5.7 patients had a normal Vitamin D level and 1 in 4.6 were grossly deficient. Ethnicity and patient location significantly affected Vitamin D results. Summer months were noted to demonstrate significantly the highest levels and August the highest. We did not find that age or gender affected Vitamin D levels in our cohort.

Polymorphisms within the COL5A1 gene and regulators of the extracellular matrix modify the risk of Achilles tendon pathology in a British case-control study.

Several genetic loci have been associated with risk of Achilles tendon pathology (ATP) within South African and Australian populations. The aim of this study was, therefore, to evaluate eight previously implicated genetic variants in an independent British population. A total of 130 asymptomatic controls (CON) and 112 participants clinically diagnosed with ATP comprising 87 individuals with chronic Achilles tendinopathy (TEN) and 25 with Achilles tendon ruptures (RUP) were included. All participants were genotyped for variants within the COL5A1, MIR608, IL-1ß, IL-6 and CASP8 genes. Primary findings implicated COL5A1 and CASP8. Three inferred allele combinations constructed from COL5A1 rs12722, rs3196378 and rs71746744 were identified as risk modifiers. The T-C-D combination was associated with increased risk of ATP (P = 0.023) and RUP (P < 0.001), the C-A-I combination was associated with increased risk of ATP (P = 0.011), TEN (P = 0.011) and RUP (P = 0.011) and the C-C-D combination was associated with decreased risk of ATP (P = 0.011) and RUP (P = 0.004). The CASP8 rs3834129 DD genotype was associated with decreased risk of TEN (P = 0.020, odds ratio: 0.45, 95% confidence interval: 0.22-0.90) and the CASP8 I-G (rs3834129-rs1045485) inferred allele combination was associated with increased risk of TEN (P = 0.031). This study further highlights the importance of polymorphisms within COL5A1 and CASP8 in the aetiology of ATP.

Human Genetic Variation, Sport and Exercise Medicine, and Achilles Tendinopathy: Role for Angiogenesis-Associated Genes.

Sport and Exercise Medicine is one of the important subspecialties of 21st century healthcare contributing to improving the physical function, health, and vitality of populations while reducing the prevalence of lifestyle-related diseases. Moreover, sport and exercise are associated with injuries such as Achilles tendinopathy, which is a common tendon injury. The angiogenesis-associated signaling pathway plays a key role in extracellular matrix remodeling, with increased levels of angiogenic cytokines reported after cyclic stretching of tendon fibroblasts. We investigated the variants in angiogenesis genes in relation to the risk of Achilles tendinopathy in two population samples drawn independently from South Africa (SA) and the United Kingdom (UK). The study sample comprised 120 SA and 130 UK healthy controls, and 108 SA and 87 UK participants with Achilles tendinopathy. All participants were genotyped for five functional polymorphisms in the vascular endothelial growth factor, A isoform (VEGFA) (rs699947, rs1570360, rs2010963) and kinase insert-domain receptor (KDR) genes (rs1870377, rs2071559). The VEGFA A-G-G inferred haplotype was associated with an increased risk of Achilles tendinopathy in the SA group (15% in controls vs. 20% in cases, p = 0.048) and the combined SA+UK group (14% in controls vs. 20% in cases, p = 0.009). These new findings implicate the VEGFA gene with Achilles tendinopathy risk, while highlighting the potential biological significance of the angiogenesis signaling pathway in the etiology of Achilles tendinopathy. The evidence suggesting a genetic contribution to the susceptibility of sustaining a tendon injury is growing. We anticipate that high-throughput and multi-omics approaches, building on genomics, proteomics, and metabolomics, may soon uncover the pathophysiology of many diseases in the field of Sports and Exercise Medicine, as a new frontier of global precision medicine.

MMP3 and TIMP2 gene variants as predisposing factors for Achilles tendon pathologies: Attempted replication study in a British case-control cohort.

Variants within the MMP3 (rs679620) and TIMP2 (rs4789932) genes have been associated with the risk of Achilles tendon pathology (ATP) in populations from South Africa and Australia. This study aimed to determine whether these variants were associated with the risk of ATP in British Caucasians. We recruited 118 cases with ATP, including a subset of 25 individuals with Achilles tendon rupture (RUP) and 131 controls. DNA samples were isolated from saliva and genotyped using qPCR. For the TIMP2 rs4789932 variant we found a significant (p = 0.038) difference in the genotype distribution frequency between males with ATP (CC, 39.4%; CT, 43.7%; TT, 16.9%) compared to male controls (CC, 20.7%; CT, 59.8%; TT, 19.5%). We also observed a difference in the TIMP2 rs4789932 genotype distribution between males with rupture compared to male controls (p = 0.038). The MMP3 rs679620 GG genotype was found to be overrepresented in the Achilles tendon rupture (RUP) group (AA, 24.0%; AG, 32.0%; GG, 44.0%) compared to controls (AA, 26.7%; AG, 54.2%; GG, 19.1%). In conclusion, the CT genotype of the TIMP2 rs4789932 variant was associated with lower risk of ATP in males. Furthermore, while we revealed differences for both variants in genotype distribution between the RUP and control groups, the sample size of the RUP group was small and confirmation would be required in additional cohorts. Finally, although both the TIMP2 rs4789932 and MMP3 rs679620 variants tentatively associated with ATP, there were differences in the direction of association compared to earlier work.

A review of ligament augmentation with the InternalBrace™: the surgical principle is described for the lateral ankle ligament and ACL repair in particular, and a comprehensive review of other surgical applications and techniques is presented.

This article reviews the surgical decision-making considerations when preparing to undertake an anatomic ligament repair with augmentation using the InternalBrace™. Lateral ankle ligament stabilization of the Broström variety and ACL repair in particular are used to illustrate its application. The InternalBrace™ supports early mobilization of the repaired ligament and allows the natural tissues to progressively strengthen. The principle established by this experience has resulted in its successful application to other distal extremity ligaments including the deltoid, spring, and syndesmosis complex. Knee ligament augmentation with the InternalBrace™ has been successfully applied to all knee ligaments including anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL), lateral collateral ligament (LCL), anterolateral ligament (ALL), and patellofemoral ligament (PFL). The surgical technique and early results will be reviewed including multi-ligament presentations. Upper limb experience with acromioclavicular (AC) joint augmentation and ulnar collateral ligament (UCL) repair of the elbow with the InternalBrace™ will also be discussed. This article points to a change in orthopaedic practice positioning reconstruction as a salvage procedure that has additional surgical morbidity and should be indicated only if the tissues fail to heal adequately after augmentation and repair.

Variation within three apoptosis associated genes as potential risk factors for Achilles tendinopathy in a British based case-control cohort.

Achilles tendon pathology (ATP) is a degenerative condition which exhibits excessive tenocyte apoptosis. Tumour necrosis factor receptor 1 (TNFR1), caspase-3 (CASP3) and caspase-8 (CASP8) are important regulators of apoptosis. To date, the effects of variation within the genes for TNFR1 and CASP3 as risk factors for ATP have not been described. There is evidence that two single nucleotide polymorphisms (SNPs) within the CASP8 gene are associated with ATP, but only in populations from the Southern Hemisphere. The primary aim of this study was to determine whether SNPs within the TNFRSF1A and CASP3 genes were associated with ATP in British Caucasians. We additionally sought to determine whether copy number variation (CNV) within the CASP8 gene was associated with ATP. We recruited 262 (131 ATP cases and 131 asymptomatic controls) Caucasian participants for this genetic association study and used quantitative PCR with chi-squared (χ(2)) tests and ANOVA to detect significant associations. For our entire cohort, we found no association between the TNFRSF1A rs4149577 (p=0.561), CASP3 rs1049253 (p=0.643) and CASP8 variants (p=0.219) and ATP. Likewise, when we tested potential interactions between gender, genotype and the risk of ATP, we found no association with the variants investigated. In conclusion, the TNFRSF1A, CASP3 and CASP8 gene variants were not associated with ATP in British Caucasians.

The management of posterior ankle impingement syndrome in sport: a review.

A literature review has been undertaken to assess the efficacy of management of Posterior Ankle Impingement Syndrome with an emphasis on sport. The evidence is confined to Level IV and V studies. There is a lack of prospective studies on the natural history of this condition and the outcomes of conservative treatment. Dance dominates the literature accounting for 62% of reported sports. Forty-seven papers have reported on the surgical outcomes of 905 procedures involving both open and artho-endoscopic techniques. 81% of patients required excision of osseous pathology and 42% soft-tissue problems resolving. There is a lack of standardisation of outcome reporting particularly in the open surgery group. However, the complication rates are relatively low: 3.9% for open medial, 12.7% for open lateral and 4.8% for arthro-endocopic surgery. Return to sport appears quicker for all activities in the arthro-endoscopic group but comparison of long term outcomes is more difficult with no evidence supporting superior long term results of one technique over another. Soccer players appear to return more quickly to activity than dancers.

A functional variant within the MMP3 gene does not associate with human range of motion.

A recent heritability study has demonstrated that human range of motion (ROM) has a substantial genetic component. Furthermore, the COL5A1BstUI RFLP has now been identified as the first gene variant to be associated with human ROM. Interestingly, this variant is known to interact with a functional variant within the MMP3 gene (rs679620) to increase risk of Achilles tendinopathy. We sought to determine whether the MMP3 rs679620 variant was associated with ROM both as a single marker and as an interacting marker with the COL5A1 BstUI RFLP. One hundred and twenty one participants were included in this study. All participants were genotyped for the MMP3 rs679620 variant, and performed passive straight leg raise (SLR) and sit and reach (SR) measurements. There were no significant differences in left leg SLR (L-SLR), right leg SLR (R-SLR), or SR measurements between the genotype groups (L-SLR, P=0.494; R-SLR, P=0.435; SR, P=0.266). Furthermore, there was no evidence of an interaction between the COL5A1 BstUI RFLP and the MMP3 rs679620 variant. Our study suggests that the MMP3 rs679620 variant does not associate with passive ROM.

Components of the transforming growth factor-beta family and the pathogenesis of human Achilles tendon pathology--a genetic association study.

OBJECTIVES: Achilles tendon pathology is a multifactorial condition for which various risk factors, including genetic factors, have been identified. Gene transfection of two members of the TGF-ß family, TGF-ß1 and growth/differentiation factor-5 (GDF-5), have been shown to enhance tendon repair and mechanical strength within animal Achilles tendon injury models. The objective of this study was to investigate whether two functional 5' untranslated region (UTR) single nucleotide polymorphisms (SNPs), the TGFB1 rs1800469 variant and the GDF5 rs143383 variant, were associated with ATP within an Australian ('AUS') and a South African ('SA') case-control cohort. METHODS: One hundred and seventy-one subjects (58 AUS and 112 SA) with Achilles tendon pathology (ATP group) and 235 (142 AUS and 96 SA) asymptomatic control (CON group) subjects were genotyped for the selected SNPs using custom-designed Taqman assays. A χ(2)-analysis or Fisher's exact test was used to analyse any differences in the genotype and allele frequencies. Significance was accepted when P < 0.05. RESULTS: There were no significant TGFB1 rs1800469 genotype (P = 0.491) or allele (P = 0.400) frequency differences between the ATP and CON groups. The TT genotype of the GDF5 rs143383 variant was significantly over-represented in the ATP group of the AUS cohort [P = 0.011; odds ratio (OR) = 2.24; 95% CI 1.21, 4.16], and when the AUS and SA cohorts were combined (P = 0.004; OR = 1.82; 95% CI 1.23, 2.74). CONCLUSIONS: In conclusion, this study suggests that individuals with a TT genotype of the functional GDF5 rs143383 variant have twice the risk of developing ATP. This finding highlights a role of GDF-5 in the pathogenesis of Achilles tendon pathology.

No association between coding polymorphism within Exon 4 of the human surfactant protein B gene and pulmonary function in healthy men.

The coding polymorphism (rs1130866) within the surfactant protein B gene is known to associate with certain respiratory abnormalities. We investigated, using spirometry and fluorescence-based PCR, whether this variant influenced pulmonary function in healthy, nonsmoking men. We found no association of pulmonary function with genotype at the rs1130866 locus.