The maintenance of skeletal muscle mass contributes substantially to health and to issues associated with the quality of life. It has been well recognized that skeletal muscle mass is regulated by mechanically induced changes in protein synthesis, and that signaling by mTOR is necessary for an increase in protein synthesis and the hypertrophy that occurs in response to increased mechanical loading. However, the role of mTOR signaling in the regulation of protein synthesis and muscle mass during decreased mechanical loading remains largely undefined. In order to define the role of mTOR signaling, we employed a mouse model of hindlimb immobilization along with pharmacological, mechanical and genetic means to modulate mTOR signaling. The results first showed that immobilization induced a decrease in the global rates of protein synthesis and muscle mass. Interestingly, immobilization also induced an increase in mTOR signaling, eIF4F complex formation and cap-dependent translation. Blocking mTOR signaling during immobilization with rapamycin not only impaired the increase in eIF4F complex formation, but also augmented the decreases in global protein synthesis and muscle mass. On the other hand, stimulating immobilized muscles with isometric contractions enhanced mTOR signaling and rescued the immobilization-induced decrease in global protein synthesis through a rapamycin-sensitive mechanism that was independent of ribosome biogenesis. Unexpectedly, the effects of isometric contractions were also independent of eIF4F complex formation. Similar to isometric contractions, overexpression of Rheb in immobilized muscles enhanced mTOR signaling, cap-dependent translation and global protein synthesis, and prevented the reduction in fiber size. Therefore, we conclude that the activation of mTOR signaling is both necessary and sufficient to alleviate the decreases in protein synthesis and muscle mass that occur during immobilization. Furthermore, these results indicate that the activation of mTOR signaling is a viable target for therapies that are aimed at preventing muscle atrophy during periods of mechanical unloading.

Skeletal muscle rapidly remodels in response to various stresses, and the resulting changes in muscle mass profoundly influence our health and quality of life. We identified a diacylglycerol kinase ζ (DGKζ)–mediated pathway that regulated muscle mass during remodeling. During mechanical overload, DGKζ abundance was increased and required for effective hypertrophy. DGKζ not only augmented anabolic responses but also suppressed ubiquitin-proteasome system (UPS)–dependent proteolysis. We found that DGKζ inhibited the transcription factor FoxO that promotes the induction of the UPS. This function was mediated through a mechanism that was independent of kinase activity but dependent on the nuclear localization of DGKζ. During denervation, DGKζ abundance was also increased and was required for mitigating the activation of FoxO-UPS and the induction of atrophy. Conversely, overexpression of DGKζ prevented fasting-induced atrophy. Therefore, DGKζ is an inhibitor of the FoxO-UPS pathway, and interventions that increase its abundance could prevent muscle wasting.

Purpose (I) To determine the incidence of periprosthetic tibial fractures in cemented and cementless unicompartmental knee arthroplasty (UKA) and (II) to summarize the existing evidence on characteristics and risk factors of periprosthetic fractures in UKA. Methods Pubmed, Cochrane and Embase databases were comprehensively searched. Any clinical, laboratory or case report study describing information on proportion, characteristics or risk factors of periprosthetic tibial fractures in UKA was included. Proportion meta-analysis was performed to estimate the incidence of fractures only using data from clinical studies. Information on characteristics and risk factors was evaluated and summarized. Results A total of 81 studies were considered to be eligible for inclusion. Based on 41 clinical studies, incidences of fractures were 1.24% (95%CI 0.64–2.41) for cementless and 1.58% (95%CI 1.06–2.36) for cemented UKAs (9451 UKAs). The majority of fractures in the current literature occurred during surgery or presented within 3 months postoperatively (91 of 127; 72%) and were non-traumatic (95 of 113; 84%). Six different fracture types were observed in 21 available radiographs. Laboratory studies revealed that an excessive interference fit (press fit), excessive tibial bone resection, a sagittal cut too deep posteriorly and low bone mineral density (BMD) reduce the force required for a periprosthetic tibial fracture to occur. Clinical studies showed that periprosthetic tibial fractures were associated with increased body mass index and postoperative alignment angles, advanced age, decreased BMD, female gender, and a very overhanging medial tibial condyle. Conclusion Comparable low incidences of periprosthetic tibial fractures in cementless and cemented UKA can be achieved. However, surgeons should be aware that an excessive interference fit in cementless UKAs in combination with an impaction technique may introduce an additional risk, and could therefore be less forgiving to surgical errors and patients who are at higher risk of periprosthetic tibial fractures. Level of evidence V.

Background: There has been a considerable increase in total joint arthroplasty (TJA) research using machine learning (ML). Therefore, the purposes of this study were to synthesize the applications and efficacies of ML reported in the TJA literature, and to assess the methodological quality of these studies.Methods: PubMed, OVID/MEDLINE, and Cochrane libraries were queried in January 2021 for articles regarding the use of ML in TJA. Study demographics, topic, primary and secondary outcomes, ML model development and testing, and model presentation and validation were recorded. The TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guidelines were used to assess the methodological quality.Results: Fifty-five studies were identified: 31 investigated clinical outcomes and resource utilization; 11, activity and motion surveillance; 10, imaging detection; and 3, natural language processing. For studies reporting the area under the receiver operating characteristic curve (AUC), the median AUC (and range) was 0.80 (0.60 to 0.97) among 26 clinical outcome studies, 0.99 (0.83 to 1.00) among 6 imaging-based studies, and 0.88 (0.76 to 0.98) among 3 activity and motion surveillance studies. Twelve studies compared ML to logistic regression, with 9 (75%) reporting that ML was superior. The average number of TRIPOD guidelines met was 11.5 (range: 5 to 18), with 38 (69%) meeting greater than half of the criteria. Presentation and explanation of the full model for individual predictions and assessments of model calibration were poorly reported (<30%). Conclusions:The performance of ML models was good to excellent when applied to a wide variety of clinically relevant outcomes in TJA. However, reporting of certain key methodological and model presentation criteria was inadequate. Despite the recent surge in TJA literature utilizing ML, the lack of consistent adherence to reporting guidelines needs to be addressed to bridge the gap between model development and clinical implementation.T he application of artificial intelligence (AI) within orthopaedic surgery research has undergone a substantial increase in recent years [1][2][3][4][5][6][7][8][9][10][11][12] . Machine learning (ML) represents a subset within AI that includes algorithms that autonomously learn from data and make predictions without explicit programmed instructions. The adoption of ML in orthopaedic research has been a function of increasing data availability and several purported benefits including (1) optimization of model performance through "learning," (2) avoidance of limitations inherent to traditional regression analyses, and (3) ability to integrate individualized patient elements to provide individu-alized explanations of anticipated outcomes 6,[13][14][15] . Despite the proliferation of ML literature and the theoretical benefits of ML, it is important to assess whether these analyses have resulted in meaningful results that may influence clinical practice.Current investigations using ML within the total j...

Background: Radiographic features of femoroacetabular impingement (FAI) are prevalent in kicking athletes, especially soccer players. However, there remains a paucity of data on the characteristics of symptomatic soccer players with an established diagnosis of FAI. Purpose: To report on patient demographics, injury, and clinical and radiographic characteristics in a large cohort of soccer players who underwent primary hip arthroscopy for FAI and to perform a sex- and competition level–specific analysis of these data. Study Design: Cross-sectional study; Level of evidence, 3. Methods: An institutional hip preservation registry containing 3318 consecutive primary hip arthroscopies for FAI performed between March 2010 and January 2016 was retrospectively reviewed for patients identified as soccer players. Patient demographics, injury characteristics, and clinical and radiographic findings were recorded, and sex- and competition level–specific differences were analyzed. Results: A total of 421 hips (336 soccer players) were identified, including 257 (61.0%) men and 164 (39.0%) women. Of these, 105 (24.9%) were reported as highly competitive, 194 (46.1%) as competitive, 75 (17.8%) as recreational, and 47 (11.2%) did not report a level. The majority of the 336 soccer players (231 hips; 55%) reported chronic hip pain lasting >6 months with no acute injury at the initial visit. Alpha angle, coronal center-edge angle, and femoral version on computed tomography scan measured 64.5°± 12°, 32.3°± 9°, and 13.7°± 10° (mean ± SD), respectively. There were 230 (55%) hips with a type 2 anterior inferior iliac spine (AIIS), 78 (18.5%) with a type 1 AIIS, and 19 (4.5%) with a type 3 AIIS. When compared with male athletes, female athletes had more hip internal rotation on physical examination (14.9° vs 8°; P < .001), lower alpha angles (57.5° vs 68.5°; P < .001), and lower-grade AIIS morphology ( P = .003). Acute injury as the reason for hip symptoms was most likely in the highly competitive group ( P < .001). Conclusion: Female soccer players were more likely to have less severe clinical and radiographic findings than were male soccer players. Acute injury as the cause of hip symptoms was more common in highly competitive players. Clinical Relevance: Focusing on soccer players with an established FAI diagnosis, the findings of this study suggest that there are sex- and competition level–based differences in the presentation, physical examination, and imaging characteristics among the players. These findings can better guide clinicians in the diagnostic evaluation of symptomatic soccer players with FAI and in tailoring treatment recommendations to specific cohorts.

Aims It remains controversial whether patellofemoral joint pathology is a contraindication to lateral unicompartmental knee arthroplasty (UKA). This study aimed to evaluate the effect of preoperative radiological degenerative changes and alignment on patient-reported outcome scores (PROMs) after lateral UKA. Secondarily, the influence of lateral UKA on the alignment of the patellofemoral joint was studied. Methods A consecutive series of patients who underwent robotic arm-assisted fixed-bearing lateral UKA with at least two-year follow-up were retrospectively reviewed. Radiological evaluation was conducted to obtain a Kellgren Lawrence (KL) grade, an Altman score, and alignment measurements for each knee. Postoperative PROMs were assessed using the Kujala (Anterior Knee Pain Scale) score, Knee Injury and Osteoarthritis Outcome Score Joint Replacement (KOOS JR), and satisfaction levels. Results A total of 140 knees (130 patients) were identified for analysis. At mean 4.1 years (2.0 to 8.5) follow-up, good to excellent Kujala scores were reported. The presence of mild to moderate preoperative patellofemoral joint osteoarthritis had no impact on these scores (KL grade 0 vs 1 to 3, p = 0.203; grade 0 to 1 vs 2 to 3, p = 0.674). Comparable scores were reported by patients with osteoarthritis (Altman score of ≥ 2) evident on either the medial or lateral patellofemoral joint facet (medial, p = 0.600 and lateral, p = 0.950). Patients with abnormal patellar congruence and tilt angles (≥ 17° and ≥ 14°, respectively) reported good to excellent Kujala scores. Furthermore, lateral UKA resulted in improvements to patellofemoral alignment. Conclusion This is the first study demonstrating that mild to moderate preoperative radiological degenerative changes and malalignment of the patellofemoral joint are not associated with poor patient-reported outcomes at mid-term follow-up after lateral fixed-bearing UKA. Our data suggest that this may be explained by realignment of the patella and thereby redistribution of loads across the patellofemoral joint. Cite this article: Bone Joint J 2020;102-B(6):727–735.

Objectives: Return to sport is a common co ncern in those undergoing arthroscopic surgery for the treatment of femoroacetabular impingement. These are commonly young active individuals with high-level athletic aspirations. Setting expectations in terms of appropriate time frame and success rates are an integral piece of pre-operative education and planning. The goals of this study were to examine return to play (RTP) rates and time frames in professional and collegiate athletes following hip arthroscopy, evaluate sex differences in return to play (morphology and rates), and evaluate differences in return to play for the most common sports. Methods: A retrospective review of a continuous cohort of patients undergoing hip arthroscopy for the treatment of femoroacetabular impingement and labral injury was conducted between January 2014 and December 2018. Athletes whom were participating in collegiate or professional sports prior to surgery were included. Chart review was conducted to gather sport specific information, morphologic data, clearance dates, successful return, and subsequent surgery. Successful return to sport was determined by being able to return to participation following clearance in at least one season. Descriptive statistics were utilized to summarize the data set and chi-square and t-tests were utilized to examine differences between groups. Results: 265 patients undergoing 332 hip arthroscopies participating in collegiate or professional sports prior to surgery were identified (75.4% male and 24.6% female), with 237 collegiate athletes and 95 professional athletes. There was a significant difference in mean alpha angles between males and females, 70.2 ± 10.5 males and 60.7± 10.0 in females, (p<0.001), but no significant differences in coronal center edge angles or femoral version. 87% of the athletes participated in hockey, football, lacrosse, soccer, baseball, soccer, or basketball. Given that a significant portion of the athletes were in college, there was a portion that graduated and thus no longer participated in collegiate athletics (27 hips), and 3 athletes (all with bilateral hip arthroscopies) were unable to return to sport due to other conditions. 91.9% of athletes were able to return to sport. 19 athletes (22 hips) were unable to return to sport. The group that was unable to return was predominantly female (73%), and this difference was significant (p<0.001). There was a significant difference between the returning group and the group that failed to return to sport in alpha angle (RTP 68.6 ± 10.8 vs No RTP 60.7± 10.6), but there were no differences in coronal center edge angle or femoral version. The difference in alpha angle is due to the predominance of females (whom had significantly lower alphas) in the unable to return group. 10 athletes (11 hips, 3.3%) required subsequent surgery (revision arthroscopy, conversion to periacetabular osteotomy, or hip resurfacing). Times for return to play were available to 205 of the athletes, averaging 6.8 months± 2.8. There was no significant difference between the males and females for return to play. There was trend towards shorter length of return for hockey athletes. There was a significant difference in the return to sport rates between the sport groups, but there were some groups with smaller sample sizes that should be taken into account. The groups with more athletes unable to return were soccer and lacrosse; these sports also had a high number of female athletes. There were no hockey athletes that were unable to return, and only 1 football athlete was unable to return. Conclusions: Hip arthroscopy for the treatment of femoroacetabular impingement and labral injury allows patients to return to sport at a high level within an average of 6.8 months. However, female athletes are less likely to have a successful return and should potentially be counseled as such. This may also inform pre-operative rehabilitation programs and intra-operative planning for female athletes. Further research should examine causes for decreased rate of return for females, and potential ways to maximize recovery and return to sport following hip arthroscopy. [Table: see text]

The Patient-Reported Outcomes Measurement Information System (PROMIS) Global-10 assesses generic-related quality of life, but has not been well studied in the orthopaedic literature. The purpose was to compare PROMIS Global-10 and legacy hip-specific patient-reported outcome measures (PROMs) in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS). This study included patients who underwent primary hip arthroscopy with complete preoperative and 6-month post-operative follow-up. PROMIS Global-10 Physical (PROMIS-P) and Mental (PROMIS-M) components, as well as the modified Harris hip score (mHHS) and International Hip Outcome Tool-33 (iHOT-33) were assessed. PROM analysis included: post-operative changes, correlations, floor and ceiling effects and responsiveness. Final analysis included 112 patients. Average age and body mass index were 36.1±11.7 years and 24.8±3.9 kg/m2, respectively. All 6-month PROMs, except PROMIS-M, were significantly improved compared to preoperative level (P&lt;0.02). Preoperatively, PROMIS-P was poorly correlated with mHHS and iHOT-33 (rs &lt;0.4) whereas PROMIS-M was only poorly correlated with iHOT-33 (rs &lt;0.4, 95% CI of 0.02–0.37). Post-operatively, the iHOT-33 was poorly correlated with both PROMIS measures (rs &lt;0.4). The mHHS was fairly correlated with both PROMIS measures (rs &lt;0.6) post-operatively. The effect sizes for mHHS and iHOT-33 were high (d=1.2 and 1.40, respectively), whereas the effect sizes for PROMIS Global-10 were small (d&lt;0.3). PROMIS Global-10 demonstrated lower effect sizes and poor to fair correlation with legacy hip-specific PROMs, and appears to have a limited role in the assessment of patients undergoing hip arthroscopy for FAIS. Therefore, the PROMIS Global-10 may have a limited role in assessing patients with FAIS.