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Background This study used a novel protocol to test the hypothesis that a plateau in oxygen consumption (VO(2max)) during incremental exercise testing to exhaustion represents the maximal capacity of the cardiovascular system to transport oxygen. Methods Twenty-six subjects were randomly divided into two groups matched by their initial VO(2max). On separate days, the reverse group performed (i) an incremental uphill running test on a treadmill (INC(1)) plus verification test (VER) at a constant workload 1 km h(-1) higher than the last completed stage in INC(1); (ii) a decremental test (DEC) in which speed started as same as the VER but was reduced progressively and (iii) a final incremental test (INC(F)). The control group performed only INC on the same days that the reverse group was tested. Results VO(2max) remained within 0.6 ml kg(-1) min(-1) across the three trials for the control group (p=0.93) but was 4.4% higher during DEC compared with INC(1) (63.9±3.8 vs 61.2±4.8 ml kg(-1) min(-1), respectively, p=0.004) in the reverse group, even though speed at VO(2max) was lower (14.3±1.1 vs 16.2±0.7 km h(-1) for DEC and INC(1), respectively, p=0.0001). VO(2max) remained significantly higher during INC(F) (63.6±3.68 ml kg(-1) min(-1), p=0.01), despite an unchanged exercise time between INC(1) and INC(F). Conclusion These findings go against the concept that a plateau in oxygen consumption measured during the classically described INC and VER represents a systemic limitation to oxygen use. The reasons for a higher VO(2) during INC(F) following the DEC test are unclear. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide (NAD + ) coenzymes are the central electron carriers in biological energy metabolism. Low NAD + levels are proposed as a hallmark of ageing and several diseases, which has given rise to therapeutic strategies that aim to tackle these conditions by boosting NAD + levels. As a lifestyle factor with preventive and therapeutic effects, exercise increases NAD + levels across various tissues, but so far human trials are mostly focused on skeletal muscle. Given that immune cells are mobilized and redistributed in response to acute exercise, we conducted two complementary trials to test the hypothesis that a single exercise session alters NAD + metabolism of peripheral blood mononuclear cells (PBMCs). In a randomized crossover trial (DRKS00017686) with 24 young adults (12 female) we show that acute exercise increases gene expression and protein abundance of several key NAD + metabolism enzymes with high conformity between high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). In a longitudinal exercise trial (DRKS00029105) with 12 young adults (6 female) we confirm these results and reveal that - similar to skeletal muscle - NAD + salvage is pivotal for PBMCs in response to exercise. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD + salvage pathway, displayed a pronounced increase in gene expression during exercise, which was accompanied by elevated intracellular NAD + levels and reduced serum levels of the NAD + precursor nicotinamide. These results demonstrate that acute exercise triggers NAD + biosynthesis of human PBMCs with potential implications for immunometabolism, immune effector function, and immunological exercise adaptions., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C.B. serves as a scientific advisor and holds equity interests in ChromaDex, Alphina Therapeutics and Juvenis., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: The Oxford knee score (OKS) and OKS Activity and Participation Questionnaire (OKS-APQ) are patient-reported outcome measures used to assess people undergoing knee replacement surgery. They have not explicitly been tested for unidimensionality (whether they measure one underlying trait such as 'knee health'). This study applied item response theory (IRT) to improve the validity of the instruments to optimize for ongoing use., Study Design and Setting: Participants undergoing primary total knee replacement (TKR) provided preoperative and postoperative responses for OKS and OKS-APQ. Confirmatory factor analysis (CFA) were performed on the OKS and OKS-APQ separately and then on both when pooled into one. An IRT model was fitted to the data., Results: 2972 individual response patterns were analyzed. CFA demonstrated that when combining OKS and OKS-APQ as one instrument, they measure one latent health trait. A user-friendly, free-to-use, web app has been developed to allow clinicians to upload raw data and instantly receive IRT scores., Conclusions: The OKS and OKS-APQ can be combined to use effectively as a single instrument (producing a single score). For the separate OKS and OKS-APQ the original items and response options can continue to be posed to patients, and this study has confirmed the suitability of IRT-weighted scoring. Applying IRT to existing responses converts traditional sum scores into continuous measurements with greater granularity, including individual measurement error., Competing Interests: Declaration of competing interest Chetan Khatri received a salary as a clinical research fellow as a part of the RACER Knee trial (Award ID: NIHR128768). As a part of the RACER Knee trial, Stryker, a medical device company, fund some treatment costs and imaging costs. This manuscript received no funding from Stryker. The independence of the research is protected by legal agreements and have no bearing on the presented study. Nick Clement reports that he is an Editorial board member of the (i) Bone and Joint Journal and (ii) Bone and Joint Research. Chloe Scott reports consulting fees from Smith and Nephew. In addition, she reports payment for delivering educational courses for Stryker and DePuy. She is a part of an advisory board for Pfizer. Andrew Metcalfe reports no conflicts of interest relevant to the current study. He is Chief Investigator for the RACER trial. He is an investigator on three National Institute for Health and Care Research (NIHR)-funded trials (Chief Investigator for START:REACTS and RACER-Knee and co-investigator for RACER-Hip), for which Stryker, a medical device company, fund some treatment costs and some imaging costs. For all these studies, the full independence of the study team is protected by legal agreements, and they have no bearing on the presented study. Conrad Harrison, Deborah MacDonald and Jeremy Rodrigues report no declarations or conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The kynurenine pathway (KP) of tryptophan degradation generates several metabolites such as kynurenine (KYN) or kynurenic acid (KA) that serve as endogenous ligands of the aryl hydrocarbon receptor (AHR). Due to its distinct biological roles particularly modulating the immune system, the AHR is a current therapeutic target across different inflammation-related diseases. Here, we show an acute exercise-induced increase in AHR ligand availability on a systemic level and a kynurenine pathway activation in peripheral blood mononuclear cells (PBMCs). Concurrently, the AHR is activated in PBMCs following acute exercise. Exercise effects on both, kynurenic acid and AHR activation in PBMCs were greater in response to high-intensity interval exercise (HIIE) (50 min, six 3-min intervals at 90% V̇o 2peak , and 3-min intervals at 50% V̇o 2peak in between) compared with workload-matched moderate-intensity continuous exercise (MICE) (50 min). In conclusion, these data indicate a novel mechanistic link in how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases. NEW & NOTEWORTHY The findings of this study show that acute endurance exercise activates a receptor that has been described to integrate metabolic signals into the immune system. We uncover a potential mechanistic link on how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases and of relevance for other cell types.

Background: The Forgotten Joint Score (FJS), a commonly used patient-reported outcome measure, was developed without fully confirming assumptions such as unidimensionality (all items reflect 1 underlying factor), appropriate weighting of each item in scoring, absence of differential item functioning (in which different groups, e.g., men and women, respond differently), local dependence (pairs of items are measuring only 1 underlying factor), and monotonicity (persons with higher function have a higher score). We applied item response theory (IRT) to perform validation of the FJS according to contemporary standards, and thus support its ongoing use. We aimed to confirm that the FJS reflects a single latent trait. In addition, we aimed to determine whether an IRT model could be fitted to the FJS., Methods: Participants undergoing primary total knee replacement provided responses to the FJS items preoperatively and at 6 and 12 months postoperatively. An exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and Mokken analysis were conducted. A graded response model (GRM) was fitted to the data., Results: A total of 1,774 patient responses were analyzed. EFA indicated a 1-factor model (all 12 items reflecting 1 underlying trait). CFA demonstrated an excellent model fit. Items did not have equal weighting. The FJS demonstrated good monotonicity and no differential item functioning by sex, age, or body mass index. GRM parameters are reported in this paper., Conclusions: The FJS meets key validity assumptions, supporting its use in clinical practice and research. The IRT-adapted FJS has potential advantages over the traditional FJS: it provides continuous measurements with finer granularity between health states, includes individual measurement error, and can compute scores despite more missing data (with only 1 response required to estimate a score). It can be applied retrospectively to existing data sets or used to deliver individualized computerized adaptive tests., Level of Evidence: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: No external funding was received for this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H930 )., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Objective: To assess the impact of an open fracture intervention bundle on clinical management and patient outcomes of adults in Malawi with open tibia fractures., Methods: We conducted a before-and-after implementation study in Malawi in 2021 and 2022 to assess the impact of an open fracture intervention bundle, including a national education course for clinical officers and management guidelines for open fractures. We recruited 287 patients with open tibia fractures. The primary outcome was a before-and-after comparison of the self-reported short musculoskeletal function assessment score, a measure of patient function. Secondary outcomes included clinical management; and clinician knowledge and implementation evaluation outcomes of 57 health-care providers attending the course. We also constructed multilevel regression models to investigate associations between clinical knowledge, patient function, and implementation evaluation before and after the intervention., Findings: The median patient function score at 1 year was 6.8 (interquartile range, IQR: 1.5 to 14.5) before intervention and 8.4 (IQR: 3.8 to 23.2) after intervention. Compared with baseline scores, we found clinicians' open fracture knowledge scores improved 1 year after the intervention was implemented (mean posterior difference: 1.6, 95% highest density interval: 0.9 to 2.4). However, we found no difference in most aspects of clinicians' open fracture management practice., Conclusion: Despite possible improvement in clinician knowledge and positive evaluation of the intervention implementation, our study showed that there was no overall improvement in clinical management, and weak evidence of worsening patient function 1 year after injury, after implementation of the open fracture intervention bundle., ((c) 2024 The authors; licensee World Health Organization.)

Acute exercise induces changes within the T-cell compartment, especially in cytotoxic CD8 +  memory subsets, depending on exercise intensity and duration. It is unclear whether exercise-induced changes in major T-cell subsets differ in response to acute high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) and whether sex-specific effects exist. Twenty-four recreationally active runners (females: n=12, 27.8±4.1years, 54.4±4.6 ml*kg -1 *min -1 ; males: n=12, 31.6±3.8years, 58.9±7.7 ml*kg -1 *min -1 ) participated in this randomized controlled crossover study, and conducted an energy- and duration-matched HIIT and MICT session. Blood was sampled before (T 1 ), immediately (T 2 ) and 1 h after exercise (T 3 ). Flow cytometry was used to identify T-cell populations. HIIT decreased the proportion of CD8 +  T-cells more pronounced at T 3 compared to MICT (p=0.007), induced a significantly stronger increase in the CD8 +  effector memory (T EM ) cell proportion at T 2 (p=0.032), and decreased CD4 +  central memory proportion more pronounced at T 2 (p=0.029). A decrease below baseline CD8 +  T EM proportion at T 3 was observed only after HIIT (p<0.001). No interaction effects between sexes were revealed. Taken together, HIIT represents a more potent stimulus to induce shifts mainly within the cytotoxic CD8 +  T-cell compartment, thereby giving implications to investigate the role of HIIT on the cell´s effector phenotype and function in more detail., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: The haphazard adoption of new surgical technologies into practice has the potential to cause patient harm and there are many misconceptions in the decision-making behind the adoption of new innovations. The aim of this study was to synthesize factors affecting a surgeon's decision to adopt a novel surgical innovation into clinical practice., Methods: A systematic literature search was performed to obtain all studies where surgeon views on the adoption of a novel surgical innovation into clinical practice have been collected. The databases screened were MEDLINE, Embase, Science Direct, Scopus, the Web of Science, and the Cochrane Library of Systematic Reviews (last accessed October 2022). Innovations covered multiple specialties, including cardiac, general, urology, and orthopaedics. The quality of the papers was assessed using a 10-question Critical Appraisal Skills Programme (CASP) tool for qualitative research., Results: A total of 26 studies (including 1112 participants, of which 694 were surgeons) from nine countries satisfied the inclusion and exclusion criteria. Types of study included semi-structured interviews and focus groups, for example. Themes and sub-themes that emerged after a thematic synthesis were categorized using five causal factors (structural, organizational, patient-level, provider-level, and innovation-based). These themes were further split into facilitators and barriers. Key facilitators to adoption of an innovation include improved clinical outcomes, cost-effectiveness, and support from internal and external stakeholders. Barriers to adoption include lack of organizational support and views of senior surgeons., Conclusion: There are multiple complex factors that dynamically interact, affecting the adoption of a novel surgical innovation into clinical practice. There is a need to further investigate surgeon and other stakeholder views regarding the strength of clinical evidence required to support the widespread adoption of a surgical innovation into clinical practice., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Purpose: Acute exercise elicits a transient anti-inflammatory state during the early recovery period. Since recent studies reported on regimen-specific effects on immune-related humoral factors and cellular subsets, this study compared the effects of intensity- and time-matched acute interval and continuous exercise on peripheral anti-inflammatory cellular and humoral immune parameters with a particular focus on the PD-1 expression in CD4 + regulatory T cells (T regs )., Methods: Twenty-four recreationally active runners (age: 29.7 ± 4.3 years, BMI: 22.2 ± 2.4, VO 2peak : 56.6 ± 6.4 ml × kg -1  × min -1 ) participated in this crossover RCT. Each subject conducted a moderate continuous (MCE) and a high-intensity interval exercise (HIIE) session in a counterbalanced design. Blood was drawn before, immediately after, and 1 h after exercise. T reg subsets and levels of PD-1 and Foxp3 were assessed by flow cytometry. Serum levels of IL-10 and IL-6 were quantified by ELISA., Results: PD-1 levels on T regs increased within the recovery period after HIIE (p < .001) and MCE (p <  0.001). Total counts of T regs (HIIE: p = 0.044; MCE: p = .021), naïve T regs (HIIE: p  < 0.001; MCE: p  < 0.001), and PD-1 + effector T regs (eT regs ) (HIIE: p = .002) decreased 1 h after exercise. IL-10 increased 1 h after HIIE (p < 0.001) and MCE (p = 0.018), while IL-6 increased immediately after both HIIE (p = 0.031) and MCE (p = 0.021). Correlations between changes in IL-6 and IL-10 (p = 0.017, r = 0.379) and baseline VO 2peak and T reg frequency (p = 0.002, r = 0.660) were identified., Conclusion: This is the first study that investigates PD-1 expression in circulating T regs after acute exercise, revealing an increase in PD-1 levels on eT regs during the early recovery period after intensity- and time-matched HIIE and MCE. Future studies are needed to investigate the PD-1 signalosome in eT regs , together with the expression of key effector molecules (i.e., IL-10, TGF-β, IL-35, CTLA-4) to elucidate PD-1-dependent changes in cellular function. Based on changes in serum cytokines, this study further reveals a regimen-independent establishment of an anti-inflammatory milieu and underpins the role of the IL-6/IL-10 axis., (© 2023. The Author(s).)

Background: Injuries are a major cause of disability globally and injury incidence is rapidly increasing, largely due to road traffic injuries in low-income and middle-income countries. Current estimates of the scale and consequences of disability from injury are largely based on modelling studies, with a scarcity of empirical evidence from severe injuries in low-income countries. We aimed to better understand the outcomes for individuals with open tibia fractures in Malawi., Methods: In this multicentre, prospective cohort study, adults (aged ≥18 years) with open tibia fractures were systematically recruited at six hospitals in Malawi (two tertiary hospitals and four district hospitals). Follow-up lasted at least 1 year, during which in-person follow-up reviews were done at 6 weeks, 3 months, 6 months, and 1 year post-injury. The primary outcome was function at 1 year post-injury, measured by the Short Musculoskeletal Functional Assessment (SMFA) score. Secondary outcomes included quality-adjusted life-years (QALYs; as determined via the European Quality of Life 5-Dimensions 3-Levels [EQ-5D-3L] survey) and fracture-related infection at 1 year post-injury. Multilevel regression models investigated associations between SMFA score, EQ-5D-3L, baseline factors, and orthopaedic management., Findings: Between Feb 12, 2021, and March 14, 2022, 287 participants were enrolled (median age 34 years [IQR 25-44]; 84% male). The most common mode of injury was road traffic injuries (194 [68%] of 287). Overall, 268 (93%) participants had debridement; of the 63 participants who were debrided in district hospitals, 47 (75%) had the procedure under local or no anaesthesia. Following substantial declines by 6 weeks after injury, function and quality of life had not recovered by 1 year post-injury for participants with Gustilo grade I-II fractures (posterior mean SMFA at 1 year: 10·5, 95% highest density interval [HDI]: 9·5-11·6; QALYs: 0·73, 95% HDI: 0·66-0·80) nor Gustilo grade III fractures (posterior mean SMFA at 1 year: 14·9, 95% HDI: 13·4-16·6; QALYs: 0·67, 95% HDI: 0·59-0·75). For all fracture grades, intramedullary nailing substantially improved function and quality of life at 1 year post-injury. Delayed definitive fixation after 5 days had 5-times greater odds of infection compared with early management within 2 days (adjusted odds ratio: 5·1, 95% CI 1·8-16·1; p=0·02)., Interpretation: Adults with open tibia fractures in Malawi have poor function and quality of life in the 1 year following injury. Centralised orthopaedic surgical management, including early definitive fixation and intramedullary nailing for more severe injuries, might improve outcomes., Funding: Wellcome Trust., Translation: For the Chichewa translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests. AJM is an investigator on three National Institute for Health and Care Research-funded trials (Chief Investigator for START:REACTS and RACER-Knee and co-investigator for RACER-Hip), for which Stryker, a medical device company, fund some treatment costs and some imaging costs. For all these studies, the full independence of the study team is protected by legal agreements and they have no bearing on the presented study., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Although largely successful, patellofemoral joint arthroplasty (PFA) has a less than satisfactory outcome in some patients. It was hypothesized that certain factors can be identified on radiological review that correlate with poor patient reported outcomes following PFA., Methods: A retrospective cohort review of 369 patients undergoing PFA at our institution between 2005 and 2018 identified 43 "poor outcome" patients with an Oxford Knee Score (OKS) of less than 20 at 2 years follow up. These cases were matched by sex and age with 43 "good outcome" patients who had an OKS above 40 at 2 years post-op. Multiple radiological measurements were performed including anterior trochlea offset ratio (ATOR), component flexion/extension, component varus/valgus, component to bone width ratio and retinacular index. The OKS PROM was the primary outcome of the study. Stepwise logistic regression was performed to analyze the differences in radiological indices between the two groups., Results: Intraclass correlation coefficients for inter-observer and intra-observer reliability were 0.90-0.98 for all indices measured. The only index demonstrating statistical significance between the groups was the ATOR (p = 0.003). The good outcome group had a mean ATOR of 0.19 whereas the poor outcome group had a mean ATOR of 0.24., Conclusions: Lower ATOR on radiological review was strongly associated with improved outcomes following PFA. The surgeon should therefore take particular care to prevent increasing the anterior offset of the trochlea component when performing PFA., Level of Evidence: Retrospective cohort study, Level III., (© 2022. The Author(s).)

Objectives: Despite major advances in prevention, sudden infant death syndrome (SIDS) remains an important cause of infant mortality. The aim of our study was to determine actual knowledge and intentions to implement SIDS prevention measures among new mothers and to identify potential knowledge gaps for improved postpartum counselling strategies., Methods: Data was collected in a standardized interview from participants of the KUNO-Kids birth cohort study before discharge from maternity ward. The mothers did not receive any specific teaching prior to the interview., Results: The majority of 2,526 interviewed mothers were able to actively report important recommendations for safe infant sleep, including the exclusive face-up position. However, 154 mothers (9%) intended to position the newborn face-down sometimes or often. The most frequently envisaged sleeping furniture was a bedside sleeper (n=1,144, 47%), but 2.2% of mothers indicated that the intended default sleeping place for the newborn would be the parents' bed (which is discouraged by the recommendations). For 43% of the infants (n=1,079), mothers planned to have loose objects in the bed and 189 mothers (7%) intended to use a loose blanket. 22% of infants (n=554) will live in a household with a smoker. Multivariate regression showed a significant association of "good knowledge" with maternal age and with not being a single parent, whereas the household size was negatively associated., Conclusion: Although the majority of mothers in our birth cohort were aware of many recommendations for safe infant sleep, our data also uncovered weaknesses in SIDS prevention knowledge and point to specific areas with potential for improved counselling., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Recognized anatomic variations that lead to patella instability include patella alta and trochlea dysplasia. Lateralization of the extensor mechanism relative to the trochlea is often considered to be a contributing factor; however, controversy remains as to the degree this contributes to instability and how this should be measured. As the tibial tuberosity-trochlear groove (TT-TG) is one of most common imaging measurements to assess lateralization of the extensor mechanism, it is important to understand its strengths and weaknesses. Care needs to be taken while interpreting the TT-TG value as it is affected by many factors. Medializing tibial tubercle osteotomy is sometimes used to correct the TT-TG, but may not truly address the underlying anatomical problem. This review set out to determine whether the TT-TG distance sufficiently summarizes the pathoanatomy, and if this assists with planning of surgery in patellar instability. Cite this article: Bone Jt Open  2022;3(3):268-274.

Objective: To investigate whether a cycling test based on decremental loads (DEC) could elicit higher maximal oxygen uptake (V˙O2max) values compared with an incremental test (INC)., Design: Nineteen well-trained individuals performed an INC and a DEC test on a single day, in randomized order., Methods: During INC, the load was increased by 20 W·min-1 until task failure. During DEC, the load started at 20 W higher than the peak load achieved during INC (familiarization trial) and was progressively decreased. Gas exchange and electromyography (EMG) activity (n = 11) from 4 lower-limb muscles were monitored throughout the tests. Physiological and EMG data measured at V˙O2max were compared between the 2 protocols using paired t tests., Results: V˙O2max during the DEC was 3.0% (5.9%) higher than during INC (range 94%-116%; P = .01), in spite of a lower power output (-21 [20] W, P < .001) at V˙O2max. Pulmonary ventilation (P = .036) and breathing rate (P = .023) were also higher during DEC. EMG activity measured at V˙O2max was not different between tests, despite the lower output during DEC., Conclusions: A DEC exercise test produces higher V˙O2max in cycling compared with an INC test, which was accompanied by higher pulmonary ventilation and similar EMG activity. The additional O2 uptake during DEC might be related to extra work performed either by the respiratory muscles and/or the less oxidatively efficient leg muscles.

Background : Road traffic injury (RTI) is the largest cause of death amongst 15-39-year-old people worldwide, and the burden of injuries such as open tibia fractures are rapidly increasing in Malawi. This study aims to investigate disability and economic outcomes of people with open tibia fractures in Malawi and improve these with locally delivered implementation of open fracture guidelines. Methods : This is a prospective cohort study describing function, quality of life and economic burden of open tibia fractures in Malawi. In total, 160 participants will be recruited across six centres and will be followed-up with face-to-face interviews at six weeks, three months, six months and one year following injury. The primary outcome will be function at one year measured by the short musculoskeletal functional assessment (SMFA) score. Secondary outcomes will include quality of life measured by EuroQol EQ-5D-3L, catastrophic loss of income and implementation outcomes (acceptability, adoption, appropriateness, costs, feasibility, fidelity, penetration, and sustainability) at one year. A nested pilot pre-post implementation study of an interventional bundle for all open fractures will be developed based on other implementation studies from low- and middle-income countries (LMICs). Regression analysis will be used to model and investigate associations between SMFA score and fracture severity, infection and the pre- and post-training course period. Outcome: This prospective cohort study will report patient reported outcomes from open tibia fractures in low-resource settings. Subsequent detailed evaluation of both the clinical and implementation components of the study will promote sustainability of improved open fractures management in the study sites and further scale-up of open fracture management guidelines. Ethics: Ethics approval has been obtained from the Liverpool School of Tropical Medicine and College of Medicine Research and Ethics committee., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Schade AT et al.)

Background: Open tibia fractures are a common injury following road traffic collisions and place a large economic burden on patients and healthcare systems. Summarising their economic burden is key to inform policy and help prioritise treatment., Methods: All studies were identified from a systematic search of Medline, Embase and the Cochrane Central Register of Controlled Trials. We included any human with a diagnosed open tibia fracture, following any intervention. The primary outcome was any costs reported or patient return to work status. Secondary outcomes included average length of stay, wage loss, absenteeism and complications such as infection, amputation and nonunion. Data was extracted and we performed a descriptive narrative summary., Results: We reviewed 1,204 studies from our searches. A total of 34 studies were included from 14 different countries. The average age was 37.7 years old and 76% of the patients were male. 6.5% were Gustilo I, 12% Gustilo II and 82% Gustilo III. Initial direct hospitalisation costs were reported to be between £356 to £126,479 with an average length of stay of 56 days (3.1-244). 89% of participants were working pre-injury, 60% fully returned to work, 17% returned to work part time or changed profession and 22% did not return to work at one-year. The most common complications reported were 22% infection, 11% nonunion and 16% amputation. Mean follow-up duration for the studies was 25 months., Conclusion: The economic burden of open tibia fractures varies greatly, but it is costly for both hospitals and patients. The current evidence is predominantly from high-income countries (HICs), especially the USA. Further research is required to investigate the costs of open tibia fractures using validated costing tools, especially in low-income countries (LICs), to help inform and direct policy., Competing Interests: Declaration of Competing Interest All authors report no conflict of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: This cross-sectional questionnaire-based study aims to compare physical activity and nature exposure levels between people living in France and Germany during the lockdown. Furthermore, the secondary aim is to observe the relationship between perceived stress, psychological health, physical activity, and nature exposure in Germany and France during the coronavirus disease 2019 (COVID-19)-related lockdown of April/May 2020. Methods: The study includes 419 participants who have completed the Perceived Stress Scale 10, the World Health Organization Quality of Life - BREF, the Godin-Shephard Leisure-Time Physical Activity Questionnaire, the modified Nature Exposure Scale, and complementary questions related to the lockdown period from April 19 to May 11, 2020. Multiple regression models were constructed to evaluate the relationship of nature exposure and physical exercise with overall stress perception and psychological health in France and Germany when considering a broad range of covariates. Results: Exposure to nature during the lockdown (η p 2 = 0.034, p < 0.001), amount of physical activity η p 2 = 0.014, p < 0.001), and psychological health (η p 2 = 0.041, p < 0.001) were greater in German compared with French participants. Godin Index and Nature Exposure Scale total score were both inversely correlated to stress perception and positively correlated to psychological health. The stress and psychological health regression models explained 10% of the results' variance. Physical activity (Godin Index) was a significant for both models. Nature Exposure Scale total score was a significant predictor only for psychological health. When including all significant covariates, the regression models explained 30.7% for the perceived stress and 42.1% for the psychological health total overall variance. Conclusion: Physical activity and nature exposure are significant predictors of psychological health. Even though both variables are associated with stress perception, only physical activity is a significant predictor of stress perception. Our results suggest that physical activity and nature exposure were key factors to go through the lockdown period in France and Germany., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with one of the author SL., (Copyright © 2021 Javelle, Laborde, Hosang, Metcalfe and Zimmer.)

Emerging evidence highlights the substantial role of the kynurenine pathway in various physiological systems and pathological conditions. Physical exercise has been shown to impact the kynurenine pathway in response to both single (acute) and multiple (chronic) exercise training stimuli. In this perspective article, we briefly outline the current knowledge concerning exercise-induced modulations of the kynurenine pathway and discuss underlying mechanisms. Furthermore, we expose the potential involvement of exercise-induced kynurenine pathway modulations on energy homeostasis (eg, through de novo synthesis of NAD + ) and finally suggest how these modulations may contribute to exercise-induced benefits in the prevention and treatment of chronic diseases., Competing Interests: Declaration of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Objectives: Exercise-induced cellular mobilization might play a role in treatment and prevention of several diseases. However, little is known about the impact of different exercise modalities on immune cell mobilization and clinical cellular inflammation markers. Therefore, the present study aimed to investigate differences between acute endurance exercise (EE) and resistance exercise (RE) on cellular immune alterations., Methods: Twenty-four healthy men conducted an acute EE (cycling at 60% of peak power output) and RE (five exercise machines at 70% of the one-repetition maximum) session lasting 50 minutes in randomized order. Blood samples were collected before, after and one hour after exercise cessation. Outcomes included counts and proportions of leukocytes, neutrophils (NEUT), lymphocytes (LYM), LYM subsets, CD4/CD8 ratio, and the clinical cellular inflammation markers NEUT/LYM ratio (NLR), platelets/LYM ratio (PLR), and systemic immune inflammation index (SII)., Results: Alterations in all outcomes were revealed except for CD8 + T cells, CD4/CD8 ratio, NLR, and PLR. EE induced a stronger cellular immune response and provoked alterations in more immune cell populations than RE. SII was altered only after EE., Conclusion: An acute EE session causes a stronger mobilization of immune cells than RE. Additionally, SII represents an integrative marker to depict immunological alterations., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Open tibia fractures are a common cause of admission following road traffic accidents in low and middle income countries (LMICs), resulting in substantial mortality and disability. It is important to summarise the clinical course of this injury using patient reported scores in order to assess best treatment in LMICs., Objectives: To summarise the disability after sustaining an open tibia fracture in LMICs METHODS: All studies were identified from a systematic search of Medline, Embase and the Cochrane Central Register of Controlled Trials. We included any human with a diagnosed open tibia fracture, following any intervention. Studies were performed in a low or middle income country. The primary outcome was any validated patient reported outcome score reported after three months. Secondary outcomes included economic impact and complications such as infection, non-union and amputation. Data was extracted and summarised., Results: We reviewed 3,593 articles from our search. A total of 18 studies were included from 10 countries with 8 different outcome scores. The average age was 35 years old and 86% of the patients were male. Thirty-one percent were Gustilo I, 28% Gustilo II, 19% Gustilo IIIA, 17% Gustilo IIIB and 5% Gustilo IIIC. The most common complications reported were 18% infection, 15% non-union and 15% amputation. Economic impact was reported in only one study with 100% patients working pre-injury and 20% post-injury at 12 months. Mean follow-up duration for outcome scores was 19.8 months. There was heterogeneity between the studies in terms of subject of the studies, outcome criteria, fracture type, surgical technique and length of follow-up. Therefore, no meta-analysis could be performed., Conclusion: The clinical history of open tibia fractures in low or middle income countries remains largely unknown in terms of patient reported outcomes. Further studies are required to define these outcomes in open tibia fractures before best treatments can be assessed., Competing Interests: Declaration of Competing Interest None, (Copyright © 2019. Published by Elsevier Ltd.)

Introduction: The essential amino acid tryptophan (TRP) is primarily degraded through the kynurenine (KYN) pathway, which is dysregulated in several chronic diseases. KYN pathway metabolites have immune- and neuro-modulatory properties and are involved in th de novo synthesis of nicotinamide adenine dinucleotide (NAD+). Currently, little evidence exists demonstrating that physical exercise may influence this pathway. However, differences between acute and chronic stimuli as well as the influence of exercise modalities remain to be investigated. Here, we provide an overview of existing studies and present results of a randomized cross-over trial on acute effects of a single-bout of resistance and endurance exercise., Methods: 24 healthy male adults conducted both an acute endurance exercise (EE) and resistance exercise (RE) session. Blood samples were collected before, immediately after and one hour after cessation of each exercise session. Outcomes comprised serum levels of TRP, KYN, kynurenic acid (KA), quinolinic acid (QA) and calculated ratios. Gene expression of the enzymes indoleamine 2,3 dioxygenase (IDO) 1 and kynurenine aminotransferase (KAT) 4 was measured in peripheral blood mononuclear cells (PBMCs). Moreover, serum concentrations of the potential KYN pathway mediators interleukin (IL)-6 and cortisol were determined. Finally, we investigated baseline correlations between immune cell subsets, potential mediators and initial KYN pathway activation outcomes., Results: The KYN/TRP ratio correlated positively with IL-6 and CD56bright NK-cells and negatively with CD56dim NKcells. Expression of IDO1 in PBMCs correlated positively with IL-6, regulatory T-cells and CD56bright NK-cells, whereas negative correlations to cytotoxic T-cells and CD56dim NKcells were revealed. A significant time effect on KYN/TRP ratio was detected for RE. Regarding KA and KA/KYN ratio, an increase after exercise followed by a decrease at the follow- up measurement was revealed in EE. KAT4 expression also increased after exercise in EE. Moreover, elevated QA levels were observed after the EE session., Conclusions: In contrast to chronic exercise interventions, single-bouts of endurance exercise provoke acute alterations on KYN pathway outcomes in humans. Our results indicate that EE induces stronger alterations than RE. Enhanced conversion of KYN to both, KA and QA suggest a peripheral KYN clearance, thereby preventing pathological accumulation within the CNS. Future acute and chronic exercise studies are needed to examine the role of NAD+ synthesis starting with TRP and the interplay between KYN pathway activation and mid- to long-term immunological modulations., (Copyright © 2020 International Society of Exercise and Immunology. All rights reserved.)

Background: The relevance of regular moderate to intense exercise for ameliorating psychomotor symptoms in persons with multiple sclerosis (pwMS) is becoming increasingly evident. Over the last two decades, emerging evidence from clinical studies and animal models indicate immune regulatory mechanisms in both periphery and the central nervous system that may underlie these beneficial effects. The integrity of the blood-brain barrier as the main structural interface between periphery and brain seems to play an important role in MS. Reducing the secretion of proteolytic matrix metalloproteinases (MMP), i.e. MMP-2, as disruptors of blood-brain barrier integrity could have profound implications for MS., Methods: In this two-armed randomized controlled trial 64 participants with relapsing-remitting MS (RRMS) (EDSS 0-4.0) will be allocated to either an intervention group or a passive wait list control group. The intervention group will perform 60 min of combined functional resistance and endurance exercises 3x per week over a period of 12 weeks in a community-based and publicly available setting. Changes in serum concentration of MMP-2 will be the primary outcome. Secondary outcomes are numbers of immune cell subsets, soluble (anti-) inflammatory factors, physical capacity, cognitive performance, physical activity behavior, gait performance, and patient-reported outcomes. All outcome measures will be assessed at baseline and after week 12 with an additional blood sampling before, during and immediately after a single training session in week 6., Discussion: To our knowledge, this will be the first RCT to investigate both the acute and chronic effects of a community-based intense functional resistance and endurance exercise regimen in persons with RRMS. Combining analysis of biological and cognitive or psychological outcomes may provide a better understanding of the MS-specific symptomology., Trial Registration: DRKS00017091; 05th of April, 2019; International Clinical Trials Registry Platform.

Background: Patellar instability is a common condition, and recurrent instability can be highly disabling. It is important to understand the patho-anatomy of patellar instability in order to treat it effectively, with the trochlear shape, patellar height and the integrity of the medial retinaculum being the most important factors in determining the risk of ongoing instability., Clinical Assessment and Radiographic Assessment: Clinical assessment is based around correct diagnosis of instability, identification of at risk features and an assessment of neuromuscular control and factors that may affect the potential for rehabilitation before or after surgery. Radiology is important to assess features predisposing to instability and to determine the best treatment plan for each individual., Treatment: There are a range of surgical options for the treatment of patellar instability and these should be chosen based on an each patients individual patho-anatomy. Lateral release is not recommended as a treatment for patellar instability. Medial patello-femoral ligament reconstruction, tibial tubercle distalisation, trochleoplasty or occasionally tibial or femoral osteotomies for correction of rotational or coronal plane mal-alignment may all be used either individually or in combination. High quality physiotherapy is an essential part of post-operative management and should address the whole of the kinetic chain, working on strength and control of the lower limbs to optimise balance and movement patterns in order to achieve the best results., (Copyright © 2019. Published by Elsevier B.V.)

Background: Rotator cuff tears are the most common tendon injury in the adult population, resulting in substantial morbidity. The optimum management for these patients is not known., Purpose: To assess the overall treatment response to all interventions in full-thickness rotator cuff tears among patients enrolled in randomized clinical trials., Study Design: Systematic review and meta-analysis., Methods: Randomized controlled trials (RCTs) were identified from a systematic search of Medline, Embase, CINHAL, and the Cochrane Central Register of Controlled Trials. Patients were aged ≥18 years with a full-thickness rotator cuff tear. The primary outcome measure was change in Constant shoulder score from baseline to 52 weeks. A meta-analysis to assess treatment response was calculated via the standardized mean change in scores., Results: A total of 57 RCTs were included. The pooled standardized mean change as compared with baseline was 1.42 (95% CI, 0.80-2.04) at 3 months, 2.73 (95% CI, 1.06-4.40) at 6 months, and 3.18 (95% CI, 1.64-4.71) at 12 months. Graphic plots of treatment response demonstrated a sustained improvement in outcomes in nonoperative trial arms and all operative subgroup arms., Conclusion: Patients with full-thickness rotator cuff tears demonstrated a consistent pattern of improvement in Constant score with nonoperative and operative care. The natural history of patients with rotator cuff tears included in RCTs is to improve over time, whether treated operatively or nonoperatively.

Background: Bayesian adaptive designs can improve the efficiency of trials, and lead to trials that can produce high quality evidence more quickly, with fewer patients and lower costs than traditional methods. The aim of this work was to determine how Bayesian adaptive designs can be constructed for phase III clinical trials in critical care, and to assess the influence that Bayesian designs would have on trial efficiency and study results., Methods: We re-designed the High Frequency OSCillation in Acute Respiratory distress syndrome (OSCAR) trial using Bayesian adaptive design methods, to allow for the possibility of early stopping for success or futility. We constructed several alternative designs and studied their operating characteristics via simulation. We then performed virtual re-executions by applying the Bayesian adaptive designs using the OSCAR data to demonstrate the practical applicability of the designs., Results: We constructed five alternative Bayesian adaptive designs and identified a preferred design based on the simulated operating characteristics, which had similar power to the original design but recruited fewer patients on average. The virtual re-executions showed the Bayesian sequential approach and original OSCAR trial yielded similar trial conclusions. However, using a Bayesian sequential design could have led to a reduced sample size and earlier completion of the trial., Conclusions: Using the OSCAR trial as an example, this case study found that Bayesian adaptive designs can be constructed for phase III critical care trials. If the OSCAR trial had been run using one of the proposed Bayesian adaptive designs, it would have terminated at a smaller sample size with fewer deaths in the trial, whilst reaching the same conclusions. We recommend the wider use of Bayesian adaptive approaches in phase III clinical trials., Trial Registration: OSCAR Trial registration ISRCTN, ISRCTN10416500 . Retrospectively registered 13 June 2007.

Background: Gait analysis can be used to measure variations in joint function in patients with knee osteoarthritis (OA), and is useful when observing longitudinal biomechanical changes following Total Knee Replacement (TKR) surgery. The Cardiff Classifier is an objective classification tool applied previously to examine the extent of biomechanical recovery following TKR. In this study, it is further developed to reveal the salient features that contribute to recovery towards healthy function., Methods: Gait analysis was performed on 30 patients before and after TKR surgery, and 30 healthy controls. Median TKR follow-up time was 13 months. The combined application of principal component analysis (PCA) and the Cardiff Classifier defined 18 biomechanical features that discriminated OA from healthy gait. Statistical analysis tested whether these features were affected by TKR surgery and, if so, whether they recovered to values found for the controls., Results: The Cardiff Classifier successfully discriminated between OA and healthy gait in all 60 cases. Of the 18 discriminatory features, only six (33%) were significantly affected by surgery, including features in all three planes of the ground reaction force (p<0.001), ankle dorsiflexion moment (p<0.001), hip adduction moment (p = 0.003), and transverse hip angle (p = 0.007). All but two (89%) of these features remained significantly different to those of the control group after surgery., Conclusions: This approach was able to discriminate gait biomechanics associated with knee OA. The ground reaction force provided the strongest discriminatory features. Despite increased gait velocity and improvements in self-reported pain and function, which would normally be clinical indicators of recovery, the majority of features were not affected by TKR surgery. This TKR cohort retained pre-operative gait patterns; reduced sagittal hip and knee moments, decreased knee flexion, increased hip flexion, and reduced hip adduction. The changes that were associated with surgery were predominantly found at the ankle and hip, rather than at the knee., Competing Interests: The authors have declared that no competing interests exist.

Background: There is ongoing debate in the literature as to whether or not patellofemoral joint overstuffing has a clinically significant effect on postoperative outcomes following total knee arthroplasty (TKA). This study investigates the effect of patellofemoral joint overstuffing on patient-reported outcomes using novel methods of radiographic measurement., Methods: The study population consisted of a prospective cohort of 266 patients receiving a Triathlon® (Stryker, Kalamazoo, MI, USA) TKA between 2006 and 2009. Participants completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire preoperatively and at 12 months postoperatively. Pre- and postoperative radiographic measurements were taken according to a defined protocol to assess for patellofemoral overstuffing. Measurement reproducibility was assessed using inter-observer intraclass correlation coefficients. Associations between radiographic measurements and patient-reported outcomes were analysed using linear regression analysis., Results: A total of 107 patients had adequate images and were included in the analysis for this study. Three different radiographic measurements were used to identify patellofemoral overstuffing all with good intra- and inter-observer reliability. There was no association identified between combined (patella and trochlea) patellofemoral overstuffing measurements and WOMAC scores. However, a statistically significant association was identified between an increase in anterior trochlear offset and worse knee pain and function scores (P < 0.05)., Conclusions: There is no identifiable association between true patellofemoral overstuffing and clinical outcome; however, there is a small association with the anterior trochlear offset though further studies are warranted to confirm the clinical significance of this finding., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Tryptophan (TRP) is an essential amino acid. Metabolites of TRP have been identified as important mediators in immune regulation and function of the central nervous system. Inflammation strongly stimulates to the breakdown of TRP into Kynurenine (KYN), representing the initial step of the KYN pathway. Recently, exercise interventions have been able to demonstrate a modification of the KYN pathway plausibly by altering inflammation. However, modifications differ between acute and chronic exercise interventions. As such, this review examines the current studies that have investigated the effect of an acute (single bout) or chronic (training) exercise intervention on levels of TRP and KYN in both healthy and diseased populations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims: This study reports on the medium- to long-term implant survivorship and patient-reported outcomes for the Avon patellofemoral joint (PFJ) arthroplasty., Patients and Methods: A total of 558 Avon PFJ arthroplasties in 431 patients, with minimum two-year follow-up, were identified from a prospective database. Patient-reported outcomes and implant survivorship were analyzed, with follow-up of up to 18 years., Results: Outcomes were recorded for 483 implants (368 patients), representing an 86% follow-up rate. The median postoperative Oxford Knee Score (0 to 48 scale) was 35 (interquartile range (IQR) 25.5 to 43) and the median Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, 0 to 100 scale) was 35 (IQR 25 to 53) at two years. There were 105 revisions, 61 (58%) for progression of osteoarthritis. All documented revisions were to primary knee systems without augmentation. The implant survival rate was 77.3% (95% confidence interval (CI) 72.4 to 81.7, number at risk 204) at ten years and 67.4% (95% CI 72.4 to 81.7 number at risk 45) at 15 years. Regression analysis of explanatory data variable showed that cases performed in the last nine years had improved survival compared with the first nine years of the cohort, but the individual operating surgeon had the strongest effect on survivorship., Conclusion: Satisfactory long-term results can be obtained with the Avon PFJ arthroplasty, with maintenance of patient-reported outcome measures (PROMs), satisfactory survival, and low rates of loosening and wear. Cite this article: Bone Joint J 2018;100-B:1162-7.

Introduction: Efficient adoption of clinically effective novel surgical innovations has great potential benefits for patients. Factors affecting the adoption of surgical innovation are not well understood and proposed models of adoption do not accurately correlate with historical evidence. This protocol is for a systematic review that aims to identify the qualitative evidence relating to surgeon views regarding the adoption of novel surgical innovation into clinical practice., Methods and Analysis: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance will be performed. Two independent reviewers will search the following databases: MEDLINE, Embase, Science Direct, Scopus, Web of Science and the Cochrane Library of Systematic Reviews. Inclusion criteria are studies which report on the views of surgeons who adopt a novel surgical innovation into clinical practice. Each article will be screened for inclusion and assessed according to a Critical Appraisal Skills Programme tool. Data will be synthesised and analysed according to thematic analysis. Given the anticipated yield of a small heterogeneous body of evidence meeting the eligibility criteria for the review, a narrative-based summary is planned., Ethics and Dissemination: This review does not require formal ethical approval as it does not involve direct patient contact or patient-identifiable data. The results of this review will be published in a peer-reviewed journal and presented at relevant conferences. The results will also inform an empirical qualitative study exploring surgeon and other stakeholder views regarding the introduction of novel surgical technology and procedures into clinical practice., Prospero Registration Number: CRD42017076715., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The ingredients of Actovegin ® were analyzed and its effects on the muscle cell proliferation were investigated. C2C12 myoblasts were cultured in medium. Actovegin ® was added in five different concentrations (1, 5, 25, 125, and 250 µg) to the differentiation medium. The formations of proliferation factor Ki67 and myosin heavy chains were measured by immunofluorescence. The first primary antibody was anti-Ki67 and anti-Mf20. Cells were washed and treated with the second fluorochrome. Thirty-one Actovegin ® ingredients were found to contain significantly higher concentrations and twenty-nine ingredients were found to contain significantly lower concentrations, compared to the mean ranges as described in the literature for the normal physiological concentrations in human adult serum/plasma. A significant increase in the formation of Ki67 was observed in Actovegin ® groups, compared to controls. The mean area of myotubes was significantly increased in Actovegin ® groups. A significant decrease in the number of myotubes was observed. An increased myotube size (fusion) was observed. The intensity of Mf20 was significantly increased in Actovegin ® groups. It could be demonstrated that Actovegin ® contains many physiological substances in significantly higher and some in lower concentrations compared to human adult serum. Furthermore, it could be shown that Actovegin ® improves muscle cell proliferation., Competing Interests: Conflict of interest: The authors have no conflict of interest to declare., (© Georg Thieme Verlag KG Stuttgart · New York.)

The leukocyte heat shock response (HSR) is used to determine individual's thermotolerance. The HSR and thermotolerance are enhanced following interventions such as preconditioning and/or acclimation/acclimatization. However, it is unclear whether the leukocyte HSR is an appropriate surrogate for the HSR in other tissues implicated within the pathophysiology of exertional heat illnesses (e.g., skeletal muscle), and whether an acute preconditioning strategy (e.g., downhill running) can improve subsequent thermotolerance. Physically active, non-heat acclimated participants were split into two groups to investigate the benefits of hot downhill running as preconditioning strategy. A hot preconditioning group (HPC; n = 6) completed two trials (HPC1 HOTDOWN and HPC2 HOTDOWN ) of 30 min running at lactate threshold (LT) on -10% gradient in 30°C and 50% relative humidity (RH) separated by 7 d. A temperate preconditioning group (TPC; n = 5) completed 30 min running at LT on a -1% gradient in 20°C and 50% (TPC1 TEMPFLAT ) and 7 d later completed 30 min running at LT on -10% gradient in 30°C and 50% RH (TPC2 HOTDOWN ). Venous blood samples and muscle biopsies (vastus lateralis; VL) were obtained before, immediately after, 3, 24, and 48 h after each trial. Leukocyte and VL Hsp72, Hsp90α, and Grp78 mRNA relative expression was determined via RT-QPCR. Attenuated leukocyte and VL Hsp72 (2.8 to 1.8 fold and 5.9 to 2.4 fold; p < 0.05) and Hsp90α mRNA (2.9 to 2.4 fold and 5.2 to 2.4 fold; p < 0.05) responses accompanied reductions ( p < 0.05) in physiological strain [exercising rectal temperature (-0.3°C) and perceived muscle soreness (~ -14%)] during HPC2 HOTDOWN compared to HPC1 HOTDOWN (i.e., a preconditioning effect). Both VL and leukocyte Hsp72 and Hsp90α mRNA increased ( p < 0.05) simultaneously following downhill runs and demonstrated a strong relationship ( p < 0.01) of similar magnitudes with one another. Hot downhill running is an effective preconditioning strategy which ameliorates physiological strain, soreness and Hsp72 and Hsp90α mRNA responses to a subsequent bout. Leukocyte and VL analyses are appropriate tissues to infer the extent to which the HSR has been augmented.

Unilateral knee replacement is often followed by a contralateral replacement in time and the biomechanics of the other knee before and after knee replacement remains poorly understood. The aim of this paper is to distinguish the features of arthritic gait in the affected and unaffected legs relative to a normal population and to assess the objective recovery of gait function post-operatively, with the aim of defining patients at risk of poor post-operative function. Twenty patients with severe knee OA but no pain or deformity in any other lower limb joint were compared to twenty healthy subjects of the same age. Gait analysis was performed and quadriceps and hamstrings co-contraction was measured. Fifteen subjects returned 1year following knee arthroplasty. Moments and impulses were calculated, principal component analysis was used to analyse the waveforms and a classification technique (the Cardiff Classifier) was used to select the most discriminant data and define functional performance. Comparing pre-operative function to healthy function, classification accuracies for the affected and unaffected knees were 95% and 92.5% respectively. Post-operatively, the affected limb returned to the normal half of the classifier in 8 patients, and 7 of those patients returned to normal function in the unaffected limb. Recovery of normal gait could be correctly predicted 13 out of 15 times at the affected knee, and 12 out of 15 times at the unaffected knee based on pre-operative gait function. Focused rehabilitation prior to surgery may be beneficial to optimise outcomes and protect the other joints following knee arthroplasty., (Copyright © 2017. Published by Elsevier B.V.)

Purpose: To describe the within-season external workloads of professional male road cyclists for optimal training prescription., Methods: Training and racing of 4 international competitive professional male cyclists (age 24 ± 2 y, body mass 77.6 ± 1.5 kg) were monitored for 12 mo before the world team-time-trial championships. Three within-season phases leading up to the team-time-trial world championships on September 20, 2015, were defined as phase 1 (Oct-Jan), phase 2 (Feb-May), and phase 3 (June-Sept). Distance and time were compared between training and racing days and over each of the various phases. Times spent in absolute (<100, 100-300, 400-500, >500 W) and relative (0-1.9, 2.0-4.9, 5.0-7.9, >8 W/kg) power zones were also compared for the whole season and between phases 1-3., Results: Total distance (3859 ± 959 vs 10911 ± 620 km) and time (240.5 ± 37.5 vs 337.5 ± 26 h) were lower (P < .01) in phase 1 than phase 2. Total distance decreased (P < .01) from phase 2 to phase 3 (10911 ± 620 vs 8411 ± 1399 km, respectively). Mean absolute (236 ± 12.1 vs 197 ± 3 W) and relative (3.1 ± 0 vs 2.5 ± 0 W/kg) power output were higher (P < .05) during racing than training, respectively., Conclusion: Volume and intensity differed between training and racing over each of 3 distinct within-season phases.

Aims: The Bereiter trochleoplasty has been used in our unit for 12 years to manage recurrent patellar instability in patients with severe trochlea dysplasia. The aim of this study was to document the outcome of a large consecutive cohort of patients who have undergone this operation., Patients and Methods: Between June 2002 and August 2013, 214 consecutive trochleoplasties were carried out in 185 patients. There were 133 women and 52 men with a mean age of 21.3 years (14 to 38). All patients were offered yearly clinical and radiological follow-up. They completed the following patient reported outcome scores (PROMs): International Knee Documentation Committee subjective scale, the Kujala score, the Western Ontario and McMaster Universities Arthritis Index score and the short-form (SF)-12., Results: Outcomes were available for 199 trochleoplasties in 173 patients giving a 93% follow-up rate at a mean of 4.43 years (1 to 12). There were no infections or deep vein thromboses. In total, 16 patients reported further patella dislocation, giving an 8.3% rate of recurrence. There were 27 re-operations, giving a rate of re-operation of 14%. Overall, 88% were satisfied with the operation and 90% felt that their symptoms had been improved., Conclusion: All PROMs improved significantly post-operatively except for the mental component score of the SF-12. Trochleoplasty performed using a flexible osteochondral flap is an effective treatment for recurrent patellar instability in patients with severe trochlea dysplasia and gives good results in the medium term. Cite this article: Bone Joint J 2017;99-B:344-50., (©2017 The British Editorial Society of Bone & Joint Surgery.)

Background: The anatomy of the anterior cruciate ligament (ACL) has become the subject of much debate. There has been extensive study into attachment points of the native ligament, especially regarding the femoral attachment. Some of these studies have suggested that fibers in the ACL are of differing functional importance. Fibers with higher functional importance would be expected to exert larger mechanical stress on the bone. According to Wolff's law, cortical thickening would be expected in these areas., Purpose: To examine cortical thickening in the region of the ACL footprint (ie, the functional footprint of the ACL)., Study Design: Descriptive laboratory study., Methods: Using micro-computed tomography with resolutions ranging from 71 to 91 μm, the cortical thickness of the lateral wall of the intercondylar notch in 17 cadaveric knees was examined, along with surface topography. After image processing, the relationship between the cortical thickening and surface topology was visually compared., Results: A pattern of cortical thickening consistent with the functional footprint of the ACL was found. On average, this area was 3 times thicker than the surrounding bone and significantly thicker than the remaining lateral wall ( P < .0001). This thickening was roughly elliptical in shape (with a mean centroid at 23.5 h:31 t on a Bernard and Hertel grid) and had areas higher on the wall where greater thickness was present. The relationship to previously reported osseous landmarks was variable, although the patterns were broadly consistent with those reported in previous studies describing direct and indirect fibers of the ACL., Conclusion: The findings of this study are consistent with those of recent studies describing fibers in the ACL of differing functional importance. The area in which the thickening was found has been defined and is likely to represent the functional footprint of the ACL., Clinical Relevance: This information is of value to surgeons when determining the optimal place to position the femoral attachment site of the reconstructed ACL.

Background: The Journey patellofemoral joint arthroplasty (PFA) was designed to improve patient outcomes following surgical management of patellofemoral joint osteoarthritis. It is based on the asymmetric trochlear geometry of the Genesis II total knee arthroplasty, with Oxinium components, to provide a reliable treatment option in an often young, high demand group of patients., Methods: We report the minimum five year functional outcome and survivorship of the Journey PFA performed at our institution between October 2005 and September 2009., Results: A total of 101 Journey PFAs were implanted in 83 patients, and we have complete outcomes for 90 implants (89%). There were 80 implants in female patients, and the mean age at time of surgery was 60years (26 to 86). The median Oxford Knee Score (0 to 48) improved from 18 to 30, and median Western Ontario and McMaster University Osteoarthritis Short Form Index (0 to 60) improved from 22 to 35. There were a total of 12 revisions, with mean time to revision 50months (10 to 99)., Conclusions: The Journey PFA gives a good medium-term functional outcome with 88% survivorship at a mean of seven years. This is the largest study of Journey PFA in the literature, and it provides a reliable option for patients with isolated patellofemoral joint osteoarthritis when arthroplasty is considered., (Copyright © 2016. Published by Elsevier B.V.)

Stressors within humans and other species activate Hsp72 and Hsp90α mRNA transcription, although it is unclear which environmental temperature or treadmill gradient induces the largest increase. To determine the optimal stressor for priming the Hsp system, physically active but not heat-acclimated participants (19.8 ± 1.9 and 20.9 ± 3.6 yr) exercised at lactate threshold in either temperate (20°C, 50% relative humidity; RH) or hot (30°C, 50% RH) environmental conditions. Within each condition, participants completed a flat running (temperate flat or hot flat) and a downhill running (temperate downhill or hot downhill) experimental trial in a randomized counterbalanced order separated by at least 7 days. Venous blood samples were taken immediately before (basal), immediately after exercise, and 3 and 24 h postexercise. RNA was extracted from leukocytes and RT-quantitative PCR conducted to determine Hsp72 and Hsp90α mRNA relative expression. Leukocyte Hsp72 mRNA was increased immediately after exercise following downhill running (1.9 ± 0.9-fold) compared with flat running (1.3 ± 0.4-fold; P = 0.001) and in hot (1.9 ± 0.6-fold) compared with temperate conditions (1.1 ± 0.5-fold; P = 0.003). Leukocyte Hsp90α mRNA increased immediately after exercise following downhill running (1.4 ± 0.8-fold) compared with flat running (0.9 ± 0.6-fold; P = 0.002) and in hot (1.6 ± 1.0-fold) compared with temperate conditions (0.9 ± 0.6-fold; P = 0.003). Downhill running and exercise in hot conditions induced the largest stimuli for leukocyte Hsp72 and Hsp90α mRNA increases., (Copyright © 2015 the American Physiological Society.)

The novel self-paced, cycle-based maximal oxygen uptake (V̇O2max) test (SPV) has been shown to produce higher V̇O2max values than standard graded exercise test (GXT) protocols. This study sought to ascertain whether these observations would also be apparent in a self-paced, treadmill-based test design. Fourteen trained male runners performed a standard GXT on a motorised treadmill and a self-paced V̇O2max test on a nonmotorised treadmill in a counter-balanced design. The GXT included a plateau verification and was designed to last between 8 and 12 min. The self-paced test included 5 × 2 min stages and allowed participants to set their own running speed based on fixed increments in rating of perceived exertion. Significantly higher V̇O2max values (t[13] = 3.71, p = 0.003) were achieved in the self-paced test (64.4 ± 7.3 mL · kg(-1) · min(-1)) compared with the GXT (61.3 ± 7.3 mL · kg(-1) · min(-1)), and 13 of the 14 participants achieved the same or higher V̇O2max values in the self-paced test. Higher (p = 0.01) maximum heart rates were observed in the GXT (191 ± 10 beats · min(-1) vs. 187 ± 7 beats · min(-1)), but no differences were observed in any other recorded variables. The self-paced V̇O2max test may provide a more valid means of measuring V̇O2max than the GXT and suggests that a V̇O2 plateau during a GXT does not always signify achievement of a definitive V̇O2max. These results provide further support that self-paced V̇O2max testing produces higher values for maximal oxygen uptake.

Our aim was to develop a patient reported outcome measure of satisfaction following total knee arthroplasty (TKA) and assess its correlation with Oxford knee score (OKS), Quality of life (EQ5D) and Visual analogue scale for pain (VAS). 172 patients with minimum 5year follow up post primary total knee arthroplasty completed CASI, OKS, EQ5D and VAS for pain. Receiver-operator curve analysis was performed to identify an OKS threshold of poor satisfaction defined by CASI rarely/never. The CASI showed positive correlation with the OKS, VAS for pain, and EQ5D, (Spearman's rho); 0.779; 0.711; 0.629. A threshold of 20 for the Oxford Knee score had 85% specificity and 85% sensitivity for poor satisfaction on CASI. The CASI is a useful measure of patient satisfaction following TKA., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The aim of this study was to examine the loading of the other joints of the lower limb in patients with unilateral osteoarthritis (OA) of the knee. We recruited 20 patients with no other symptoms or deformity in the lower limbs from a consecutive cohort of patients awaiting knee replacement. Gait analysis and electromyographic recordings were performed to determine moments at both knees and hips, and contraction patterns in the medial and lateral quadriceps and hamstrings bilaterally. The speed of gait was reduced in the group with OA compared with the controls, but there were only minor differences in stance times between the limbs. Patients with OA of the knee had significant increases in adduction moment impulse at both knees and the contralateral hip (adjusted p-values: affected knee: p < 0.01, unaffected knee p = 0.048, contralateral hip p = 0.03), and significantly increased muscular co-contraction bilaterally compared with controls (all comparisons for co-contraction, p < 0.01). The other major weight-bearing joints are at risk from abnormal biomechanics in patients with unilateral OA of the knee.

Background: The aim of this study was to document the development of bilateral knee osteoarthritis over a 12 year period using a middle-aged population-based cohort with knee pain at inclusion., Methods: One hundred and forty three patients aged 35 to 54 were recruited from a population based cohort of 279 subjects who had knee pain at baseline and assessed with clinical and radiographic data, with 5 and 12 year follow up. The data was analysed with regard to the development and progression of uni- and bilateral knee osteoarthritis over 12 years. A definition of KL = 1 was used to define radiographic disease., Results: 24 of the 30 (80%) patients with unilateral disease at baseline developed bilateral disease after 12 years. At baseline 37 patients (26%) had bilateral disease, whereas that number increased to 65 (52%) at 5 years and 100 (70%) at the 12 year follow up. The most common pattern was medial compartment involvement in both knees. Six patients had lateral compartment disease in one knee and medial in the other whereas only two had lateral compartment disease bilaterally., Conclusions: Bilateral knee osteoarthritis is very common with time, as the majority of sufferers will eventually develop radiographic disease in both knees. Clinicians need to be aware of the 'joint at risk' and researchers need to remember to account for both knees when assessing the relationship between physical function, pain and structural disease. The other knee should not be used for comparison, even if it appears to be normal at baseline.