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Introduction: In recent years, biotherapy in orthopedics has become widespread, and platelet-rich plasma (PRP) has been readily used to treat sports injuries and osteoarthritis. Production of freeze-dried PRP (PRP-FD) results in PRP that is in powder form, allowing it to be stored for long periods at room temperature. Using this technology, we have developed Valuable Platelet-Derived Factor Concentrate Freeze Dry (VFD). However, whether VFD contains sufficient levels of bioactive substances (BS) remains unknown and retains the same levels of BS during long-term storage. In this study, we examined whether VFD contains sufficient amounts of BS and whether they retain these BS levels during long-term storage. Methods: Peripheral blood was collected from 10 healthy men (mean ± SD: 46.5 ± 15 years old) and various BS, including transforming growth factor β (TGF-β), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), tissue inhibitors of metalloproteinases-1 (TIMP-1), interleukin-1 receptor antagonist (IL-1ra), matrix metallopeptidase-9 (MMP-9), and interleukin-6 (IL-6), were compared between VFD and normal PRP samples, including both leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP). VFD was prepared using two rounds of centrifugation. LP-PRP and LR-PRP were activated by freezing and thawing before measurement. To evaluate the effects of long-term storage, the BS of VFD purified from five professional football players was compared between baseline and 1 year after storage. Results: In terms of the growth factors, the TGF-β and EGF levels were higher in LR-PRP than in VFD and LP-PRP (p

Introduction: Although numerous studies have reported outcomes with various conservative approaches for the iliopsoas impingement after total hip arthroplasty (THA), reports on the use of locoregional autologous platelet rich plasma (PRP) injections for the iliopsoas impingement after THA are lacking. This phase 1 study therefore aimed to investigate the safety and feasibility of locoregional PRP injection for iliopsoas impingement after THA. Materials and methods: Patients diagnosed with iliopsoas impingement after THA who met the criteria for participation (symptoms persisting for more than 3 months, aged 20 years or older, and unable to receive non-steroidal analgesic or anti-inflammatory drugs) were eligible to participate in this clinical study. The primary endpoint was observed adverse events including procedure-related pain, and the secondary endpoints included pain and functionality of the hip joint, that were assessed using the Western Ontario and McMaster Universities Arthritis Index, Japanese Hip Disease Evaluation Questionnaire, and Forgotten Joint Score-12. Results: Three patients were screened for eligibility, and 3 patients were finally included in this study. Two participants (patients 1 and 2; aged 66 and 65 years, respectively) were female. The third participant (patient 3; age 73 years) was male. All patients experienced adverse events; however, none were found to be serious. None of the patients experienced any infections, or intra- or post-operative symptoms of nerve damage, or subcutaneous haemorrhage owing to the administration of locoregional PRP. Although patient 2 showed almost complete resolution of the symptom, patient 1 and 3 demonstrated persistent groin pain after the injection. Conclusion: We demonstrated the results of preliminary phase 1 prospective observational clinical study that administration of locoregional PRP injections for iliopsoas impingement following THA is both, safe and feasible.

Introduction: Platelet-rich plasma (PRP) therapy is used to treat pathological conditions such as degenerative inflammatory diseases including osteoarthritis (OA) by enhancing tissue repair and promoting anti-inflammatory effects. Although PRP therapy for patients with knee OA improved pain and functional scores, the association of clinical outcomes and quality of PRP including cell composition and concentration is unclear. Methods: Therefore, this study analyzed blood cell counts, including the immature platelet fraction (IPF), in peripheral blood and PRP of 144 patients with knee OA who underwent PRP therapy. The mean leukocyte and platelet concentrations in whole blood and PRP were analyzed using an XN-1000 automated hematology analyzer. Visual analogue scale (VAS) scores and knee injury and osteoarthritis outcome scores (KOOS) before and 1 month after a single PRP injection were also determined. Results: Higher platelet and lower leukocyte concentration rates were observed in PRP compared with whole blood. The platelet concentration in whole blood was negatively correlated with VAS improvement. The percentage of IPF (IPF%) in whole blood was positively correlated with VAS improvement and KOOS (pain) improvement, whereas the IPF% in PRP tended to correlate with VAS improvement. Furthermore, multivariate logistic regression demonstrated the high IPF% in whole blood was significantly associated with VAS improvement. The low percentage of neutrophil (neutrophil%) in PRP was significantly associated with the VAS improvement and KOOS (ADL) improvement. Conclusions: Therefore, PRP efficacy for OA might depend on the patient's biological status.

Introduction The elevated cytokine levels in patients suffering from anterior cruciate ligament (ACL) rupture may lead to acute post-traumatic arthritis (APTA) and post-traumatic osteoarthritis (PTOA). Due to its chondrogenerative and anti-inflammatory effect, platelet-rich plasma (PRP) therapy is expected to show a positive outcome in APTA and PTOA. The proposed trial aims to quantitatively measure the efficacy of PRP injection in arresting post-traumatic cartilage degeneration among patients after ACL reconstruction.Methods and analysis This will be a single-blind, randomised, prospective, controlled clinical trial designed following the Consolidated Standards of Reporting Trials guidelines. After ACL reconstruction, 80 patients will be randomised to receive either leucocyte-poor PRP injection after joint aspiration or a placebo control group receiving only joint aspiration. Participants (age 20–49 years) will be those who have undergone ACL reconstruction within the past 2 weeks with a body mass index

Abstract It is difficult to investigate clinical features in a single-center study because atypical periprosthetic femoral fracture (APFF) is rare. This study aims to perform a nationwide survey of APFF to investigate the characteristics of this fracture and compare the clinical outcome with that of typical periprosthetic femoral fracture (typical PFF). A nationwide survey was performed asking for cooperation from 183 councilors of the Japanese Society for Fracture Repair. The subjects were patients with APFF injured between 2008 and 2017. The control group was comprised of patients with typical PFF of our facility injured in the same period. A total of 43 patients met the APFF definition. The control group was comprised of 75 patients with typical PFF. The rate of bisphosphonate use was significantly higher in the APFFs group than in the typical PFF group (62.8% and 32%, p

ObjectiveDisrupted sleep and training behaviors in athletes have been reported during the COVID-19 pandemic. We aimed at investigating the combined effects of Ramadan observance and COVID-19 related lockdown in Muslim athletes.MethodsFrom an international sample of athletes (n = 3,911), 1,681 Muslim athletes (from 44 countries; 25.1 ± 8.7 years, 38% females, 41% elite, 51% team sport athletes) answered a retrospective, cross-sectional questionnaire relating to their behavioral habits pre- and during- COVID-19 lockdown, including: (i) Pittsburgh sleep quality index (PSQI); (ii) insomnia severity index (ISI); (iii) bespoke questions about training, napping, and eating behaviors, and (iv) questions related to training and sleep behaviors during-lockdown and Ramadan compared to lockdown outside of Ramadan. The survey was disseminated predominately through social media, opening 8 July and closing 30 September 2020.ResultsThe lockdown reduced sleep quality and increased insomnia severity (both p < 0.001). Compared to non-Muslim (n = 2,230), Muslim athletes reported higher PSQI and ISI scores during-lockdown (both p < 0.001), but not pre-lockdown (p > 0.05). Muslim athletes reported longer (p < 0.001; d = 0.29) and later (p < 0.001; d = 0.14) daytime naps, and an increase in late-night meals (p < 0.001; d = 0.49) during- compared to pre-lockdown, associated with lower sleep quality (all p < 0.001). Both sleep quality (χ2 = 222.6; p < 0.001) and training volume (χ2 = 342.4; p < 0.001) were lower during-lockdown and Ramadan compared to lockdown outside of Ramadan in the Muslims athletes.ConclusionMuslim athletes reported lower sleep quality and higher insomnia severity during- compared to pre-lockdown, and this was exacerbated by Ramadan observance. Therefore, further attention to Muslim athletes is warranted when a circadian disrupter (e.g., lockdown) occurs during Ramadan.

Objective: To investigate the effect of 1) lockdown duration and 2) training intensity on sleep quality and insomnia symptoms in elite athletes.Methods: 1,454 elite athletes (24.1 ± 6.7 years; 42% female; 41% individual sports) from 40 countries answered a retrospective, cross-sectional, web-based questionnaire relating to their behavioral habits pre- and during- COVID-19 lockdown, including: 1) Pittsburgh sleep quality index (PSQI); 2) Insomnia severity index (ISI); bespoke questions about 3) napping; and 4) training behaviors. The association between dependent (PSQI and ISI) and independent variables (sleep, napping and training behaviors) was determined with multiple regression and is reported as semi-partial correlation coefficient squared (in percentage).Results: 15% of the sample spent < 1 month, 27% spent 1–2 months and 58% spent > 2 months in lockdown. 29% self-reported maintaining the same training intensity during-lockdown whilst 71% reduced training intensity. PSQI (4.1 ± 2.4 to 5.8 ± 3.1; mean difference (MD): 1.7; 95% confidence interval of the difference (95% CI): 1.6–1.9) and ISI (5.1 ± 4.7 to 7.7 ± 6.4; MD: 2.6; 95% CI: 2.3–2.9) scores were higher during-compared to pre-lockdown, associated (all p < 0.001) with longer sleep onset latency (PSQI: 28%; ISI: 23%), later bedtime (PSQI: 13%; ISI: 14%) and later preferred time of day to train (PSQI: 9%; ISI: 5%) during-lockdown. Those who reduced training intensity during-lockdown showed higher PSQI (p < 0.001; MD: 1.25; 95% CI: 0.87–1.63) and ISI (p < 0.001; MD: 2.5; 95% CI: 1.72–3.27) scores compared to those who maintained training intensity. Although PSQI score was not affected by the lockdown duration, ISI score was higher in athletes who spent > 2 months confined compared to those who spent < 1 month (p < 0.001; MD: 1.28; 95% CI: 0.26–2.3).Conclusion: Reducing training intensity during the COVID-19-induced lockdown was associated with lower sleep quality and higher insomnia severity in elite athletes. Lockdown duration had further disrupting effects on elite athletes’ sleep behavior. These findings could be of relevance in future lockdown or lockdown-like situations (e.g., prolonged illness, injury, and quarantine after international travel).

Abstract Purpose Although platelet-rich plasma (PRP) therapy has become an increasingly popular treatment for sports-related injuries, the molecular mechanisms of PRP on tissue healing process remain poorly understood. The aim of the present study was to develop an experimental method quantifying the efficacy of PRP with murine patellar tendon injury model, leading to future elucidation of the mechanisms of PRP on healing processes. Methods Full-thickness defects were created in the central third of the murine patellar tendon. The prepared allogenic PRP gel was applied on the defect of the patellar tendon (PRP group), while the remaining mice served as the untreated control group. Mice were sacrificed at 2, 4, 6, 8, and 10 weeks after the operation, with histological sections obtained in each time point (n = 4 / time point / group). Semi-quantitative histological evaluation was performed in accordance with the Bonar score. The variables included in this scoring system were cell morphology, ground substance, collagen arrangement, and vascularity, with higher grades indicating worse tendon structures. In addition, the ratio of the collagen fibers to the entire tendon tissue (FT ratio) was measured using KS400 software as a quantitative histological evaluation. Results The total Bonar score in the PRP group was significantly lower than in control group. With regard to the variables in the Bonar score, the vascularity score was significantly higher in the PRP group at 2 and 4 weeks, while the collagen arrangement score was significantly lower in the PRP group at 8 weeks. Based on a quantitative evaluation, the recovery speed of the patellar tendon determined by FT ratio was significantly faster in the PRP group than in the control group at 6 and 8 weeks. Conclusions We have developed an experimental method for histological and quantitative evaluation of the effects of PRP on tissue healing using murine patellar tendon injury model. The results of this study suggest that the local application of PRP could enhance the tissue-healing process both directly through action on localized cells and indirectly through the recruitment of reparative cells through the blood flow. Further investigations will be needed to confirm the mechanisms of PRP in tissue-healing processes with the development of this experimental model.

Introduction: Researchers have investigated the use of platelet-rich plasma (PRP) therapy. However, the mechanisms through which PRP affects tissue repair remain unclear. We hypothesize that PRP promotes tissue repair through not only via direct manner on the local cells but also via indirect manner that encourage the recruitment of reparative cells such as macrophages (MPs), and it depends on the quality of PRP including the concentration of leukocytes. The aim of this study is to elucidate the actions of the MPs in the mechanisms of PRP on tissue repair processes. Methods: Leukocyte-rich (LR) PRP and leukocyte-poor (LP) PRP were prepared from 12-week-old C57BL6 mice. Full-thickness defects were created in central third of patellar tendons of 12-week-old C57BL/6 mice for histologic analysis (n = 36) and 12-week-old B6.129P-Cx3cr1tm1Litt/J mice for flow cytometry analysis (n = 108). B6.129P-Cx3cr1tm1Litt/J mouse is GFP-positive only in the MP-linage cells thus MPs recruited to the repair tissue can be distinguished whether it had originated from administrated PRP or recruited from host mouse. Mice were treated either with LR-PRP, LP-PRP, or without PRP (control group). Histological analyses were performed to evaluate the tendon healing using Bonar score as semi-quantitative histological scoring system. Flow cytometric analyses were performed to count the number of GFP-positive cells around repaired patellar tendon. In addition, the ratio of pro-inflammatory MPs (M1)/anti-inflammatory MPs (M2) were analyzed in those GFP-positive cells. The statistical analysis was performed using GraphPad Prism ver6. P values

Abstract Background and purpose Psychological factors including fear of pain, re-injury during movement (kinesiophbia) affect return-to-sport rates after anterior cruciate ligament (ACL) reconstructive surgery. Clinicians often encounter in the daily practice that athletes explain lack of self-confidence or psychological readiness during the sports activity. The Tampa Scale for Kinesiophobia (TSK) has been used to evaluate psychological outcomes in patients with ACL injuries in many countries and translated into Japanese version in 2013. However, no researchers validated its reliability, validity, and responsiveness of TSK for patients with ACL injury up to now. The purpose of this study was to evaluate the measurement properties of the Japanese version of the TSK (TSK-J) in patients with ACL injuries. Study design Cohort study (Diagnostic); Level of evidence, 2. Methods This prospective study was performed in the department of orthopaedic surgery at the university hospital of Juntendo from Sep 2016 and Apr 2017. Patients who diagnosed with ACL injury with or without reconstruction surgery completed several patient-reported outcome measures (PROMs) were included in this study. The COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) guidelines were used to evaluate reliability, validity, responsiveness, and interpretability of the TSK-J. Results 222 patients were included in this study. The TSK-J for ACL injured patients showed good internal consistency (Cronbach’s alpha = 0.79) and excellent test-retest reliability (intra-class correlation coefficient, ICC2,1 = 0.90, 95% CI = 0.81 to 0.95). In addtion, the TSK-J was significantly but moderately correlated with the IKDC-SKF (r = − 0.49, P

Background/aims This study aimed to assess the efficacy and sterility of stored platelet-rich plasma (PRP) eye-drops for corneal epithelial wound healing compared with those of autologous serum (AS) eye-drops. Methods At our single institution, PRP and AS eye-drops were prepared using peripheral blood obtained from six healthy volunteers and stored at 4°C. Platelet and leucocyte counts and transforming growth factor (TGF)-β1, epidermal growth factor (EGF), and fibronectin levels were assessed during storage for up to 4 weeks. Sterility was assessed by culturing 4-week poststorage samples. PRP, AS, and phosphate-buffered saline (PBS) eye-drop efficacies were compared using corneal epithelial wound healing assays in vitro and in vivo and monitoring wound areas under a microscope every 3 hours. Results Higher platelet and lower leucocyte counts were seen in PRP than in whole blood on the day of preparation. After storage, TGF-β1, EGF, and fibronectin levels were significantly higher in PRP than in AS eye-drops. In vitro and in vivo, PRP eye-drops used on the day of preparation significantly promoted corneal epithelial wound healing compared with PBS. Moreover, PRP eye-drops stored for 4 weeks significantly promoted corneal wound healing compared with PBS and AS eye-drops. Conclusion PRP eye-drops stored at 4°C for 4 weeks promoted corneal epithelial wound healing with higher levels of growth factors than those observed in AS eye-drops, while maintaining sterility, suggesting that this preparation satisfies the unmet medical needs in the treatment of refractory keratoconjunctival epithelial disorders. [ABSTRACT FROM AUTHOR]

Objective The fifth metatarsal stress fracture is a common injury among football players. Although several risk factors have been proposed, the association between the playing surface and development of fifth metatarsal stress fractures (MT-5) has not been evaluated. We conducted an epidemiological study using a computerbased survey to investigate the association between the playing surface and development of MT-5. Methods This study included 1854 football players, of which 41 experienced MT-5 within the past 24 months. Baseline demographic data and the percentage of time spent playing on artificial turf and clay fields were compared between the non-MT-5 and MT-5 player groups, and the risks for development of MT-5 associated with the playing surfaces were estimated by univariate and multivariate analyses. Results There were significant differences in body mass index, years of play, playing categories and playing time on artificial turf between non-MT-5 and MT-5 groups (p<0.05). Generalised estimating equations analyses adjusted for multiple confounders demonstrated that relative to the risk of playing <20% of the time on each surface, the OR (OR: 95% CI) for MT-5 for playing on artificial turf >80% of the time increased (3.44: 1.65 to 7.18), and for playing on a clay field 61%-80% of the time, the OR decreased (0.25: 0.11 to 0.59). Conclusions A higher percentage of playing time on an artificial turf was a risk factor for developing MT-5 in football players. This finding could be beneficial for creating strategies to prevent MT-5. [ABSTRACT FROM AUTHOR]

Objective: To assess the longitudinal outcomes of osteochondritis dissecans (OCD) fixation and to detect the influencing factor for the results of OCD. Methods: 22 OCD fixation using bioabsorbable pins were assessed Lysholm score, Tegner activity scale and KOOS4 at preoperative, postoperative short (3.0 years) and mid-long (11.9 years) term. Results: Postoperative Lysholm score was significantly better than the preoperative time. There was no factor influencing KOOS4 at mid-long term. Conclusion: OCD fixation contributes good results for a long time regardless of skeletal maturity, the size and the severity of OCD. [ABSTRACT FROM AUTHOR]

Background: The fifth metatarsal bone is a common site of stress fractures in soccer athletes. Although several endocrine risk factors for stress fractures have been proposed, the endocrine risks for fifth metatarsal (5-MT) stress fractures have not been evaluated. Methods: To evaluate the endocrine risks of fifth metatarsal stress fractures, we conducted a cumulative case-control study. The present study included 37 athletes, of which 18 had a history of a zone 2 or zone 3 fifth metatarsal stress fracture and 19 controls. We analyzed serum 25-hydroxyvitamin D (25-OHD), serum parathyroid hormone (PTH), as well as biochemical markers of bone turnover by univariate or multivariate analyses. Results: Logistic regression analyses adjusted for multiple confounders revealed that insufficient serum 25-OHD levels less than 30 ng/mL (odds ratio [OR], 23.3), higher serum PTH levels (OR, 1.01), or higher serum bone-specific isoform of alkaline phosphatase levels (OR, 1.10) rather than serum tartrate-resistant acid phosphatase 5b were associated with statistically significantly increased odds of 5-MT stress fractures. A postestimation calculation demonstrated that 25-OHD levels of 10 and 20 ng/mL were associated with 5.1 and 2.9 times greater odds for 5-MT stress fractures, respectively. Conclusion: 25-OHD insufficiency was associated with an increased incidence of 5-MT stress fractures. This insight may be useful for intervening to prevent 5-MT stress fractures. Level of Evidence: Level III, case-control study. [ABSTRACT FROM AUTHOR]

Background: Acute patellar tendon ruptures with poor tissue quality. Ruptures that have been neglected are difficult to repair. Several surgical techniques for the repair of the patellar tendon have been reported, however, these techniques remain difficult because of contractures, adhesions, and atrophy of the quadriceps muscle after surgery. Case presentation: We report the cases of 2 Japanese patients (Case 1: a 16-year-old male and Case 2: a 43-year-old male) with patellar tendon ruptures who were treated by reconstruction using semitendinosus-gracilis (STG) tendons with preserved distal insertions. Retaining the original insertion of the STG appears to preserve its viability and provide the revascularization necessary to accelerate healing. Both tendons were placed in front of the patella, in a figure-of-eight fashion, providing stability to the patella. Conclusion: Both patients recovered near normal strength and stability of the patellar tendon as well as restoration of function after the operation. [ABSTRACT FROM AUTHOR]

Osteoclasts regulate homeostasis of bone development. A defect in osteoclast development results in osteopetrosis. Recently, the involvement of several molecules in osteoclast development has been found. Osteoclast‐associated receptor (OSCAR) is one of such molecules critical for osteoclast differentiation. However, it remains unclear how OSCAR transduces signals for osteoclast differentiation. Here, we found that the FcRγ chain, a signal transducing adaptor molecule for Fc receptors, is associated with OSCAR and is involved in the cell surface expression of OSCAR. Furthermore, FcRγ is required for signal transduction by OSCAR. These findings suggest that the FcRγ‐mediated signal transduction by OSCAR is involved in osteoclast differentiation. [ABSTRACT FROM AUTHOR]