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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, by infecting cells via the interaction of its spike protein (S) with the primary cell receptor angiotensin-converting enzyme (ACE2). To search for inhibitors of this key step in viral infection, we screened an in-house library of multivalent tryptophan derivatives. Using VSV-S pseudoparticles, we identified compound 2 as a potent entry inhibitor lacking cellular toxicity. Chemical optimization of 2 rendered compounds 63 and 65 , which also potently inhibited genuine SARS-CoV-2 cell entry. Thermofluor and microscale thermophoresis studies revealed their binding to S and to its isolated receptor binding domain (RBD), interfering with the interaction with ACE2. High-resolution cryoelectron microscopy structure of S, free or bound to 2 , shed light on cell entry inhibition mechanisms by these compounds. Overall, this work identifies and characterizes a new class of SARS-CoV-2 entry inhibitors with clear potential for preventing and/or fighting COVID-19.

The Caton-Deschamps Index (CDI) is a measurement used to evaluate patella alta based on true lateral radiographs; however, no prior study has investigated how altering the degree of radiograph aberrancy affects CDI measurement. The primary and secondary purpose of this study was to evaluate effects of rotational radiographic changes on patella height measurements and compare these findings to MRI measurements, respectively. Five cadaver knees ( n  = 5) were utilized in this study. True lateral radiographs were obtained for each specimen by using a fluoroscopic C-arm machine. The C-arm was then altered in two planes (axial and coronal) in both the clockwise and counterclockwise direction and radiographs were taken at 5, 10, and 15 degrees of error from the true lateral position. A CDI measurement of each specimen was performed based on sagittal magnetic resonance imaging (MRI) slices and compared with radiographic CDI measurements. Three orthopedic surgeons measured the CDI for each radiograph and MRI performed. Interrater reliability and changes in CDI were analyzed. Clinically significant difference in CDI was set to 0.1. Mean intraclass correlation coefficient was high (≥0.7) at true lateral and at all varying degrees of error. When performing a pairwise comparison of mean CDI from the true lateral position to increasing degrees of error, statistically significant differences were observed in the axial plane. The largest change in CDI measurements was seen with rotational malposition in the axial plane and counterclockwise direction. No statistically significant differences in mean CDI were observed in the coronal plane. The change in CDI from the true lateral position reached an absolute maximum of at least 0.1 in all four scenarios at each tested degree of error. This study found that aberrant radiographic rotation in the axial plane resulted in a significantly different mean CDI measurement when compared with true lateral radiographs. All degrees of error in both directions and in both planes could have a clinically significant effect on CDI (≥0.1). Our findings confirm the importance of a perfect true lateral radiograph when measuring patella height., Competing Interests: None declared., (Thieme. All rights reserved.)

The S:A222V point mutation, within the G clade, was characteristic of the 20E (EU1) SARS-CoV-2 variant identified in Spain in early summer 2020. This mutation has since reappeared in the Delta subvariant AY.4.2, raising questions about its specific effect on viral infection. We report combined serological, functional, structural and computational studies characterizing the impact of this mutation. Our results reveal that S:A222V promotes an increased RBD opening and slightly increases ACE2 binding as compared to the parent S:D614G clade. Finally, S:A222V does not reduce sera neutralization capacity, suggesting it does not affect vaccine effectiveness., Competing Interests: NO authors have competing interests.

Purpose: Patients with isolated medial compartment osteoarthritis and varus deformity may undergo high tibial osteotomy (HTO) to reduce the contact pressure in the medial compartment. The purpose of this investigation is (1) examine the timeline of return to work (RTW) following HTO and (2) evaluate RTW stratified by occupational intensity., Methods: Consecutive patients undergoing HTO were reviewed retrospectively at a minimum of 2-years postoperatively. Patients completed a subjective work questionnaire, a visual analogue scale for pain, Single Assessment Numerical Evaluation, and a satisfaction questionnaire., Results: Thirty-eight patients were included at an average of 9.0 ± 3.3 years postoperatively. Thirty-seven patients (average age 43.4 ± 7.8 years, 91.9% with a Kellgren-Lawrence grade of III/IV) were employed within 3 years prior to surgery. Eighteen patients (48.6%) underwent subsequent surgery with 14 patients (37.8%) receiving a salvage knee arthroplasty at an average of 6.1 ± 3.5 years following HTO. Thirty-five patients (94.5%) returned to work at an average of 2.9 ± 2.0 months. The rate of RTW for sedentary, light, moderate, and heavy duties were 87.5%, 100%, 100%, and 93.3%, respectively, while the duration until RTW was 1.0 months, 1.1 months, 2.4 months, and 3.3 months, respectively., Conclusion: In a young and active population with osteoarthritis or varus deformity, an HTO allows patients to return to work; however, patients with high-intensity occupations may be absent from work longer than those with lesser physically demanding occupations. HTO is not a definitive treatment option as nearly 40% of patients underwent knee arthroplasty by 6.1 years postoperatively., Level of Evidence: IV, case series.

Case: Throughout the COVID-19 pandemic, prone positioning has decreased mortality in patients with severe acute respiratory distress syndrome. We present the unique case of a patient who developed left median nerve mononeuropathy and bilateral meralgia paresthetica after prone positioning while afflicted with COVID-19. These nerve injuries have been rarely reported in the literature and never before in the same patient., Conclusion: Our case highlights the importance of increased care when positioning patients prone by padding bony prominences, evenly distributing pressure across known sites of peripheral nerve entrapment, and giving consideration to prone-positioning time intervals when caring for intubated patients., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B674)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Objective: The purpose of this article is to review the orthopedic literature regarding patient understanding of articular cartilage disease, interpret literature reporting patient expectations for surgical management of articular cartilage injuries of the knee, and review patient-reported outcomes and patient satisfaction with management of these injuries., Design: A retrospective review of the current literature using the PubMed database (1980-current) was performed on July 15, 2017. The search terms used were "patient understanding knee cartilage," "patient satisfaction knee cartilage," "patient expectation knee cartilage," and "patient reported outcomes knee cartilage." All searches were filtered to human studies and English language only and were reviewed by 2 independent reviewers. Studies not relevant to articular cartilage injury and/or surgical management in the knee were excluded. Additional references were found by backtracing references from obtained articles., Results: The published study search results for the terms: "patient understanding knee cartilage," "patient satisfaction knee cartilage," "patient expectation knee cartilage," and "patient reported outcomes knee cartilage" displayed a total of 873 studies. Two independent reviewers screen all studies A total of 50 published studies were relevant and included., Conclusion: The subjective and objective clinical outcomes reported are inconsistently obtained resulting in difficulty drawing comparisons between studies. While the relationship between preoperative patient expectations and patient-reported outcomes and patient satisfaction has yet to be well developed, authors have reported patient and injury specific variables associated with superior and inferior outcomes. In conclusion, more work is needed to correlate patient-reported outcomes and satisfaction for cartilage treatments with preoperative expectations and health literacy.

Background: The management of complex cartilage pathology in young, otherwise healthy patients can be difficult., Purpose: To determine the nature of the design, endpoints chosen, and rate at which the endpoints were met in published studies and ongoing clinical trials that investigate cartilage repair and restoration procedures., Study Design: Systematic review., Methods: A systematic review of the publicly available level I/II literature and of the publicly listed clinical trials regarding cartilage repair and restoration procedures for the knee was conducted adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: Seventeen published studies and 52 clinical trials were included. Within the 17 published studies, the most common procedure studied was microfracture (MFX) + augmentation ( N = 5; 29.4%) and the most common comparison/control group was MFX ( N = 10; 58.8%). In total, 13 different cartilage procedure groups were evaluated. For published studies, the most common patient-reported outcome (PRO) measures assessed is the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Visual Analog Scale-Pain (VAS) ( N = 10 studies, 58.8% each, respectively). Overall, there are 10 different PROs used among the included studies. Ten studies demonstrate superiority, 5 demonstrate noninferiority, and 2 demonstrate inferiority to the comparison or control groups. For the clinical trials included, the most common procedure studied is MFX + augmentation ( N = 16; 30.8%). The most common PRO assessed is KOOS ( N = 36 trials; 69.2%), and overall there are 24 different PROs used among the included studies., Conclusions: Recently published studies and clinical trials evaluate a variety of cartilage repair and restoration strategies for the knee, most commonly MFX + augmentation, at various time points of outcome evaluation, with KOOS and VAS scores being used most commonly. MFX remains the most common comparison group for these therapeutic investigations. Most studies demonstrate superiority versus comparison or control groups. Understanding the nature of published and ongoing clinical trials will be helpful in the investigation of emerging technologies required to navigate the regulatory process while studying a relatively narrow population of patients.

Background: Distal femoral varus osteotomy (DFVO) is a well-described procedure to address valgus deformity of the knee. There is a paucity of information available regarding patients' ability to return to work (RTW) after DFVO., Purpose: To report the objective findings for RTW rates and times for patients receiving a DFVO for lateral compartment osteoarthritis secondary to valgus deformity of the knee., Study Design: Cohort study; Level of evidence, 3., Methods: This was a retrospective study of patients who received a lateral-wedge opening DFVO. Patients must have worked within 3 years before their operation to be included for analysis. Patients were contacted at a minimum of 2 years postoperatively for interview and questionnaire evaluation, including a subjective work questionnaire, visual analog scale (VAS) for pain, Single Assessment Numerical Evaluation (SANE), and a satisfaction questionnaire., Results: Overall, 32 patients were contacted at a mean follow-up of 7.1 ± 4.1 years (range, 2.2-13.3 years). The mean ± SD age at the time of surgery was 30.8 ± 8.8 years (range, 17.2-46.5 years), and 65.6% of patients were female. Eleven patients (34.4%) received a concomitant meniscal allograft transplant, and 12 (37.5%) received a cartilage grafting procedure. The average VAS pain score decreased significantly from 6.1 preoperatively to 3.2 postoperatively ( P = .03). All patients were able to RTW, at a mean time of 6.0 ± 13.2 months postoperatively (range, 0-72 months). When stratified by work intensity, the average time to return was 13.8, 3.1, 2.7, and 2.9 months for high, moderate, light, and sedentary occupations, respectively. There was no significant difference between these RTW times ( P = .16), although this analysis may have been limited by the small sample size. Four patients whose work was classified as heavy work (50%) and 3 whose work was classified as moderate work (18.8%) either switched jobs or kept the same job with lighter physical duties as a result of their procedures., Conclusion: In a young and active population, DFVO for valgus deformity reliably afforded the ability to RTW within a relatively short time for patients with sedentary, light, and moderate occupational demands. However, patients with moderate- to high-intensity occupational demands may be unable to RTW at their preoperative level., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: J.N.L. has received educational support from Arthrex and Smith & Nephew and hospitality payments from Exactech and Wright Medical. G.H.G. has received educational support from Arthrex and Smith & Nephew and hospitality payments from Wright Medical. A.B.Y. has received research support from Arthrex, Organogenesis, and Vericel; educational support from Smith & Nephew and Arthrex; and consulting fees from Aastrom Biosciences, JRF Ortho, Olympus, Patient IQ, Smith & Nephew, and Sparta Biomedical. B.J.C. has received research support from Aesculap/B.Braun, Arthrex, and Regentis; educational support from Medwest; consulting fees from Acumed, Anika Therapeutics, Arthrex, Bioventus, Flexion Therapeutics, Geistlich Pharma, Regentis, Smith & Nephew, Vericel, and Zimmer Biomet; speaking fees from Arthrex and Lifenet Health; hospitality payments from GE Healthcare; honoraria from Vericel; other financial or material support from Athletico and JRF Ortho; and royalties from Arthrex, DJO, Elsevier, and Operative Techniques in Sports Medicine; and has stock/stock options in Bandgrip, Ossio, and Regentis. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2020.)

Purpose: To analyze the topographic matching of oblong osteochondral allografts to treat large oval medial femoral condyle (MFC) lesions using computer simulation models. The secondary objective was to determine whether lateral femoral condyle (LFC) grafts would have a similar surface matching when compared with MFC grafts in this setting., Methods: Human femoral hemicondyles (10 MFCs, 7 LFCs) underwent 3-dimensional computed tomography. Models were created from computed tomography images and exported into point-cloud models. Donor-recipient matches with large condylar width mismatch were excluded. The remaining specimen were divided into 3 donor-recipient groups with 2 defect sizes (17 × 30 mm and 20 × 30 mm): 20 MFC donor (MFCd)-MFC recipient (MFCr), 27 ipsilateral LFC donor (LFCd)-MFCr, and 26 contralateral LFCd-MFCr. Grafts were optimally virtually aligned with the MFCr defect. Mismatch of the articular cartilage and subchondral bone surfaces between the graft and the defect and articular step-off were calculated., Results: MFCd grafts resulted in articular cartilage surface mismatch and peripheral step of less than 0.5 mm for both defect sizes. The subchondral bone surface mismatch was significantly greater than the articular cartilage surface mismatch (P < .01) in both defect sizes). Conversely, the ipsilateral and contralateral LFCd grafts resulted in significantly greater articular cartilage surface mismatch and step-off for both defect sizes when compared to MFCd grafts (P < .01)., Conclusions: Oblong MFC allografts provide acceptable topographic matching for large oval MFC lesions when condylar width differences are minimized. However, concern exists in using oblong LFC allografts for MFC defects, as this can result in increased peripheral step-off and surface mismatch., Clinical Relevance: These data reinforce the ability to use oblong MFC osteochondral allograft for treating oval cartilage lesions of the MFC when condylar width is considered. Although other studies have demonstrated LFCs can be used to treat circular defects on the MFC, this may not be true for oblong grafts., (Copyright © 2020 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose : Osteoarthritis (OA) of the knee is a debilitating, expensive, and prevalent disease, and interest in the non-surgical management of knee OA has grown recently. Our objective was to systematically assess the level of heterogeneity among all clinical trials and published studies regarding injections for knee osteoarthritis, in terms of treatment of interest, outcomes evaluated, and time points of outcome assessment. Methods : The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized to review all published studies and publically available clinical trials from 1 January 2013 to 3 May 2019evaluating intra-articular injections to treat knee OA. Their treatment group and specifics of methodology were scrutinized and compared. Results : 84 published studies and 114 clinical trials were included. Within the 84 published studies, the most common injection treatment studied was hyaluronic acid [N = 22; 26.2%]. In total, 29 different injection treatment groups were utilized. The most common time point for patient evaluation post-injection was 6 months (N = 33 studies; 50.0%), and ranged from 1 week (N = 9 studies; 13.6%) to 7 years (N = 1 study; 1.5%). The most common patient-reported outcome (PRO) measure assessed in the included studies was Western Ontario and McMaster's University Osteoarthritis Index (WOMAC) [N = 44 studies; 66.7%]. For the 114 clinical trials identified, the most common injection treatment studied is platelet-rich plasma in isolation (N = 19; 16.7%). Forty-two different injection treatment types/groups are utilized. The most common PRO measure assessed was WOMAC (N = 77 trials; 67.5%). Overall there were 34 different patient-reported outcome measures used. Conclusions : Research efforts to find the most effective injection therapy for knee OA continue with a tremendous number of injection therapies still being evaluated. Substantial heterogeneity exists in these completed and ongoing trials in terms of patient demographics, OA grades, outcome scores and relatively short-term timing of assessments, with no clear standardization of testing protocol despite proposing to answer the same clinical question. We recommend that studies of this genre going forward be standardized in terms of outcome measures and longer-term follow-up time points, and should incorporate functional assessment evaluations and imaging studies.

Purpose: To investigate patient return to sport and satisfaction after meniscal allograft transplantation (MAT)., Methods: Patients undergoing MAT using a bone bridge technique between 2013 and 2015 with minimum 2-year follow-up were retrospectively reviewed. They completed a survey regarding return to sport, satisfaction, and subsequent surgery in addition to patient-reported outcome measures., Results: Of 117 patients, 87 (74.4%) were available at an average follow-up of 3.64 years (range, 2.01-5.13 years). The mean age at the time of surgery was 28.99 ± 8.26 years. Lateral MAT was performed in 44 cases (50.6%); medial MAT, 42 (48.3%); and combined medial and lateral MAT, 1 (1.1%). Concomitant procedures were performed in 72 patients (82.7%) including cartilage restoration (n = 65, 74.7%), realignment (n = 9, 10.3%), and anterior cruciate ligament reconstruction (n = 9, 10.3%). Patients experienced significant improvement in the Lysholm score (P < .001), International Knee Documentation Committee score (P < .001), Knee Injury and Osteoarthritis Outcome Score (KOOS)-Quality of Life (P < .001), KOOS-Activities of Daily Living (ADL) (P < .001), KOOS-Pain (P < .001), KOOS-Sports (P = .001), KOOS-Symptoms (P = .003), Short Form 12 physical score (P < .001), and Veterans Rand-12 physical score (P < .001). Reoperation was performed in 26 patients (29.9%); failure occurred in 12 patients (13.8%; total knee arthroplasty in 1, unicompartmental arthroplasty in 2, and total meniscectomy in 9). Overall, 77.0% of patients were satisfied with their outcome. Prior to MAT, 82 patients (94.3%) participated in sporting activities; 62 patients (75.6%) returned to at least one sport at 12.58 ± 6.20 months postoperatively, with 30 (48.4%) reaching their preoperative level of intensity and 72 (87.8%) discontinuing at least one of their preoperative sports. The most common reasons for sports discontinuation postoperatively were prevention of further damage (73.6%), pain with activity (51.4%), fear of further injury (48.6%), surgeon recommendation (33.3%), and swelling with activity (30.6%). Patients were satisfied with their sports participation at a rate of 62.1%., Conclusions: In a complex patient population undergoing arthroscopic MAT, 75.6% of patients were able to return to at least one sport at an average of 12.58 ± 6.20 months postoperatively. The level of sport declined, with 93.5% of patients restricting involvement to recreational sports after MAT and 48.4% returning to their preoperative level of activity intensity. In addition, 87.8% of patients reported discontinuing a sport in which they had participated preoperatively. The most common reasons for decreasing level of sport were prevention of further damage, pain or swelling with sports, and fear of further injury. The reoperation rate after MAT was 29.9%. Most patients were satisfied with the outcome of surgery, with 77.0% satisfied in general and 62.1% satisfied with their ability to play sports., Level of Evidence: Level IV, retrospective case series., (Copyright © 2020 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: Young patients with symptomatic chondral defects in the medial compartment with varus malalignment may undergo opening wedge high tibial osteotomy (HTO) with concomitant osteochondral allograft transplantation (OCA) (HTO + OCA). Although patients have demonstrated favorable outcomes after HTO + OCA, limited information is available regarding return to sporting activities after this procedure., Purpose: To evaluate (1) the timeline to return to sports (RTS), (2) patient satisfaction, and (3) reasons for discontinuing sporting activity after HTO + OCA, and to identify predictive factors of RTS., Study Design: Case series; level of evidence, 4., Methods: Consecutive patients who underwent HTO + OCA for varus deformity and medial femoral condyle focal chondral defects with a minimum 2-year follow-up were retrospectively reviewed. Patients completed a subjective sports questionnaire, satisfaction questionnaire, visual analog scale for pain, and Single Assessment Numerical Evaluation., Results: Twenty-eight patients with a mean age of 36.97 ± 7.52 years were included at mean follow-up of 6.63 ± 4.06 years. Fourteen patients (50.0%) required reoperation during the follow-up period, with 3 (10.7%) undergoing knee arthroplasty. Twenty-four patients participated in sports within 3 years before surgery, with 19 patients (79.2%) able to return to at least 1 sport at a mean 11.41 ± 6.42 months postoperatively. However, only 41.7% (n = 10) were able to return to their preoperative level. The most common reasons for sports discontinuation (n = 20; 83.3%) were a desire to prevent further damage to the knee (70.0%), persistent pain (55.0%), persistent swelling (30.0%), and fear (25.0%)., Conclusion: In young, active patients with varus deformity and focal medial femoral condyle chondral defects, HTO + OCA enabled 79.2% of patients to RTS by 11.41 ± 6.42 months postoperatively. However, only 41.7% of patients were able to return to their preinjury level or better. It is imperative that patients be appropriately educated to manage postoperative expectations regarding sports participation after HTO + OCA.

Purpose: To define the contributions of the of the medial patellofemoral ligament (MPFL) and medial quadriceps tendon femoral ligament (MQTFL) to lateral patellar translation as the knee moves through a 90° arc of motion., Methods: Six pairs of bilateral cadaveric knee specimens (12 knees) were dissected and potted in perfect lateral position using fluoroscopy. An eye screw was placed in the midpoint on the lateral aspect of the patella. Each knee underwent testing in 4 conditions after sequential sectioning: intact, lateral retinacular release, randomized MQTFL or MPFL sectioning, and complete proximal medial patellar restraint (PMPR) sectioning. With a custom machined jig, all knees were tested at 0, 10, 20, 30, 45, 60, and 90° of flexion on an MTS machine with 20N of lateral patellar force applied and displacement recorded., Results: PMPR extensor mechanism insertion on all specimens was identified 50% on the quadriceps tendon and 50% on the proximal aspect of the medial patella. Isolated MPFL sectioning resulted in significantly increased lateral displacement compared to the lateral release state at all flexion angles tested except 0°. There was significantly increased lateral patellar displacement with complete sectioning compared with isolated proximal sectioning at all degrees of knee flexion except 0°. However, complete sectioning following isolated MPFL sectioning did not demonstrate significance at any angle., Conclusions: Compared with the MQTFL, the MPFL is primarily responsible for resistance to lateral patellar translation throughout a 0° to 90° arc of motion. The MPFL provides a similar resistance to lateral patellar displacement as the fully intact PMPR; however, the MQTFL may contribute to resistance in full extension., Clinical Significance: Proximal medial patellar restraint reconstruction techniques involving both the patellar and quadriceps insertion have been described; however, the unique contributions of the native anatomy to lateral patellar restraint have not been investigated., (Copyright © 2020 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: Patella alta has been identified as an important risk factor for lateral patellar instability and medial patellofemoral complex (MPFC) reconstruction failure., Purpose: To evaluate the length changes of the MPFC at multiple possible reconstruction locations along the extensor mechanism in varying degrees of patella alta throughout knee motion., Study Design: Controlled laboratory study., Methods: Eight fresh-frozen cadaveric knees were used in this study. The MPFC was identified and dissected with the patellar tendon and quadriceps tendon. A custom-made jig was utilized to evaluate lengths from 0° to 90° of flexion with physiological quadriceps loading. Length was measured with a 3-dimensional robotic arm at 4 possible reconstruction locations along the extensor mechanism: the midpoint patella (MP), the MPFC osseous center (FC), the superior medial pole of the patella (SM) at the level of the quadriceps insertion, and 1 cm proximal to the SM point along the quadriceps tendon (QT). These measurements were repeated at 0°, 20°, 40°, 60° and 90° of flexion. Degrees of increasing severity of patella alta at Caton-Deschamps index (CDI) ratios of 1.0, 1.2, 1.4, and 1.6 were then investigated., Results: Patella alta and MPFC attachment site location significantly affected changes in MPFC length from 0° to 90° of flexion ( P < .0005). Length changes at attachment MP showed no difference when CDI 1.0 was compared with all patella alta values (CDI 1.2, 1.4, 1.6; P > .05). Similarly, FC showed no difference in length change from 0° to 90° until CDI 1.6, in contrast to proximal attachments (SM, QT), which demonstrated significant changes at CDI 1.4 and 1.6. When length changes were analyzed at each degree of flexion (0°, 20°, 40°, 60°, 90°), Spearman correlation analysis showed a moderate negative linear correlation for QT at CDI 1.0 ( r = -0.484; P = .002) and 1.6 ( r = -0.692; P < .0005), demonstrating constant loosening at the QT point at normal and elevated patellar height. In contrast, no differences in length were observed for MP at CDI 1.0 throughout flexion, and at CDI 1.6, there was a difference only at 0° ( P < .05). Points FC and MP at CDI 1.6 had similar length change properties to points SM and QT at CDI 1.0 ( P > .05), suggesting that distal attachments in the setting of patella alta may provide similar length changes to proximal attachmentswith normal height., Conclusion: Anisometry of the MPFC varies not only with attachment location on the extensor mechanism but also with patellar height. Increased patellar height leads to more significant changes in anisometry in the proximal MPFC attachment point as compared with the distal component. In the setting of patella alta, including a CD ratio of 1.6, the osseous attachments of the MPFC remain nearly isometric wheras the proximal half length changes increase significantly., Clinical Significance: The results of this study support the idea that the MPFC should be considered as 2 separate entities (proximal medial quadriceps tendon femoral ligament and distal medial patellofemoral ligament) owing to their unique length change properties.

Purpose: To assess the timeline of return to work (RTW) following opening-wedge high tibial osteotomy (HTO) with concomitant osteochondral allograft transplantation (OCA) of the medial femoral condyle., Methods: Consecutive patients undergoing HTO + OCA due to focal chondral deficiency and varus deformity were retrospectively identified and reviewed at a minimum of 2 years following surgery. Patients completed a subjective work questionnaire, a visual analog scale for pain, Single Assessment Numerical Evaluation, and a satisfaction questionnaire., Results: Twenty-eight patients (average age: 36.0 ± 7.9 years) were included at 6.7 ± 4.1 years postoperatively. Twenty-six patients were employed before surgery and 25 patients (96.2%) returned to work following HTO + OCA. However, only 88.5% of patients were able to return to the same level of occupational intensity by 3.5 ± 2.9 months postoperatively. The rate of RTW to the same occupational intensity for sedentary, light, medium, and heavy intensity occupations was 100%, 100%, 88.9%, and 80% (P = .8), whereas the duration of RTW was 9.0 ± 7.1 months, 1.7 ± 1.4 months, 2.7 ± 0.9 months, and 4.2 ± 1.9 months (P = .006), respectively. Two patients (7.7%) underwent knee replacement by 5.3 ± 3.1 years postoperatively due to progression of osteoarthritis in the medial compartment., Conclusions: In patients with focal chondral deficiency and varus deformity, HTO + OCA provides a high rate of RTW (96.2%) by 3.5 ± 2.9 months postoperatively. However, patients with greater-intensity occupations may take longer to return to work than those with less physically demanding occupations., Level of Evidence: IV, Retrospective Case Series., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: To prospectively evaluate the transferability of skills acquired on a low-cost, at-home, nonanatomic triangulation simulation system to cadaveric models., Methods: We randomized 28 medical students into either a simulator-training group (n = 14) or group with no training (control, n = 14). All subjects were pretested using a standardized checklist of arthroscopic skills on cadaveric knees and shoulders. Training-group subjects practiced on the triangulation simulator for 90 minutes per week for 4 consecutive weeks. Control subjects received no training. All subjects completed a post-test checklist of arthroscopic skills on cadaveric knees and shoulders, as well as 4 training tasks on the simulator. A blinded orthopaedic surgeon evaluated the arthroscopic videos using the Arthroscopic Surgical Skill Evaluation Tool (ASSET) score., Results: Training-group knee and shoulder ASSET scores increased from 12.2 ± 1.85 to 14.6 ± 2.76 ( P  = .02) and from 14.6 ± 3.5 to 17.9 ± 4.5 ( P  = .29), respectively. In the control group, knee and shoulder ASSET scores increased from 14.3 ± 3.12 to 14.25 ± 4.67 ( P  = .99) and from 14.2 ± 2.7 to 17.07 ± 6.7 ( P  = .58), respectively. There were no significant differences in the mean post-test ASSET scores between the training group and control group for either knee or shoulder arthroscopy. The post-test ASSET safety subscore during knee arthroscopy was significantly higher in the training group ( P  = .03). The training group was able to complete significantly more simulator tasks compared with controls ( P  = .003) at post-testing. A significant positive correlation was found between knee arthroscopy performance and the number of tasks completed during simulation post-testing ( P  = .043). There was no significant correlation between shoulder arthroscopy performance and simulation performance ( P  = .532)., Conclusions: Basic triangulation skills may be acquired by training on a low-cost, at-home, nonanatomic triangulation simulation system, although the degree of transferability and universal joint applicability, as well as the existence of an early ceiling effect in skill development, could not be shown., Level of Evidence: Level II, randomized controlled trial., (© 2019 by the Arthroscopy Association of North America. Published by Elsevier Inc.)

Purpose: To evaluate the time and rate of return to sport (RTS), as well as outcomes, in young and active patients receiving concomitant lateral meniscal allograft transplantation (MAT) and distal femoral varus osteotomy (DFVO) for lateral meniscal deficiency and valgus malalignment., Methods: This was a retrospective study of consecutive patients who underwent concomitant MAT and DFVO by a single surgeon. The exclusion criteria were any concomitant procedures other than cartilage restoration procedures for focal full-thickness cartilage defects of the lateral femoral condyle and less than 2 years of follow-up. At final follow-up, patients were asked to complete a subjective sports questionnaire, the Marx Activity Rating Scale, a visual analog scale (VAS), the Single Assessment Numeric Evaluation, and a satisfaction questionnaire. Changes in patient-reported outcome measures were assessed using nonparametric statistical testing., Results: A total of 21 patients met the inclusion criteria, of whom 17 were included for analysis at an average follow-up of 7.5 years (range, 2.2-13.3 years). The average age at the time of surgery was 23.3 years (range, 16.9-36.2 years), and 76.5% of patients were female patients. The average VAS score decreased from 5.7 preoperatively to 2.6 postoperatively (P = .02). Of the 15 patients who participated in sports within 3 years prior to their surgical procedure, 14 (82.4%) returned to 1 or more sports at an average of 16.9 months (range, 6-36 months); however, only 46.7% were able to return to their preinjury level of participation or higher. Furthermore, 88.2% of patients reported being satisfied with their sport-related outcomes. Direct rates of sport-specific return were as follows: weightlifting, 100%; skiing, 100%; running, 66.7%; and basketball, 50%., Conclusions: In our study population, concomitant MAT and DFVO afforded a high rate of RTS at an average of 16.9 months postoperatively, as well as a significant decrease in VAS pain scores. These findings are essential to note when counseling patients receiving these procedures who wish to resume sports and physical activities so that they may expect an extensive recovery process before they can RTS., Level of Evidence: Level IV, case series., (Copyright © 2019 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

The use of allografts has become a vital option for orthopaedic surgeons in the treatment of a variety of musculoskeletal lesions, ranging from osteochondral defects in the glenohumeral joint to meniscal deficiency in the young athlete. Nevertheless, barriers to treating a patient with an allograft-based procedure may arise from concerns over disease transmission, the navigation of tissue banks that supply allografts, the process of obtaining insurance approval, or optimal storage methods. This review serves to support orthopaedic surgeons in the incorporation of allografts into their practice by quelling these potential concerns. Fresh osteochondral allografts, fresh-frozen meniscal allografts, soft tissue allografts, and off-the-shelf cartilage products are the focus of this review amid broad overviews of allograft safety and tissue bank practices in the United States., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: B.J.C. has received research support from Aesculap/B. Braun, Arthrex, National Institutes of Health (NIAMS & NICHD), and Regentis; consulting fees from Anica Therapeutics, Arthrex, Bioventus, Geistlich Pharma, Genzyme, Pacira, Regentis, Smith & Nephew, Vericel, and Zimmer; royalties from Arthrex, DJO, Elsevier, and Operative Techniques in Sports Medicine; educational support from Arthrex and Pacira; financial/material support from Athletico and JRF Ortho; nonconsulting fees from Carticept Medical and LifeNet Health; stock/stock options in Ossio and Regentis; and hospitality payments from Aesculap/B.Braun, DePuy, and GE Healthcare. R.M.F. has received institutional support from Arthrex and Smith & Nephew; research support from Arthrex; and royalties from Elsevier; and is a consultant for Arthrex, JRF, and AlloSource. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2019.)

Purpose: To determine the biomechanical effect of limited lateral retinacular and capsular release on lateral patellar translation as a function of constant force at various knee flexion angles., Methods: Six pairs of bilateral cadaveric knee specimens (12 knees) were obtained from a tissue bank, dissected, and potted in a perfect lateral position based on fluoroscopy. A direct lateral force was applied to the patella through an eye screw in the midpoint of the lateral patella, and each knee underwent testing in the intact state and after lateral retinacular and capsular release. All knees were tested at 0°, 10°, 20°, 30°, 45°, 60°, and 90° of flexion using a custom-machined jig on a materials testing system with a 20-N lateral force applied to the patella. Patellar displacement was recorded and compared for each specimen., Results: Lateral displacement was significantly greater at all degrees of flexion for the lateral-release specimens than for an intact lateral retinaculum ( P < .05). Compared with intact specimens, lateral-release specimens experienced 30% more translation at 0° of flexion and between 6% and 9% more lateral translation at 10° to 90° of flexion., Conclusions: Lateral retinacular and capsular release results in significantly increased lateral patellar translation at all flexion angles compared with intact specimens. This finding suggests that the lateral retinaculum may function as a significant restraint to lateral translation even with intact medial soft-tissue restraints., Clinical Relevance: Arthroscopic and open limited lateral retinacular releases should be performed with extreme caution when treating lateral patellar instability given the lateral retinaculum's apparent role as a secondary restraint., (© 2019 Published by Elsevier on behalf of the Arthroscopy Association of North America.)

Background: The purposes of the study are as follows: (1) examine the timeline of return to sport (RTS) following isolated high tibial osteotomy (HTO), (2) evaluate the degree of participation and function upon RTS and (3) identify reasons that patients do not return or discontinue participation in sport activity., Methods: Patients undergoing isolated HTO were reviewed retrospectively at a minimum of two years post-operatively. Patients completed a subjective sports questionnaire, a visual analog scale for pain, Single Assessment Numerical Evaluation, and a satisfaction questionnaire., Results: Thirty-eight patients (70.4%) were included at an average of 9.0 ± 3.3 years. Thirty-four patients (average age 42.7 ± 7.2 years, 90.0% with a Kellgren-Lawrence grade of III/IV) participated in sports within three years prior to surgery. Eighteen patients (52.9%) returned to the operating room by the time of final follow-up, including 13 patients (38.2%) who underwent salvage arthroplasty by 6.1 ± 3.6 years following HTO. Thirty patients (88.2%) returned to ≥1 sport at an average of 7.5 ± 5.0 months; however only 41.2% were able to return to preinjury level of participation., Conclusions: In patients with medial osteoarthritis and varus deformity, isolated high tibial osteotomy provides a high rate (88.2%) of return to sport by 7.5 months postoperatively, yet only a fraction of patients returned to their preinjury level. HTO is not a definitive treatment option as nearly 40% of patients underwent knee arthroplasty by 6.1 years post-operatively. Patient expectations regarding return to sport can be appropriately managed with adequate preoperative patient education., Level of Evidence: IV., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Dietary guidelines for egg consumption for general population differ among public health agencies. Our aim was to investigate the association between egg intake and both all-cause and specific-cause of mortality in a Mediterranean population., Methods: The European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort included 40,621 men and women aged 29-69 years old in the nineties from 5 Spanish regions. After a mean of 18 years of follow-up, 3,561 deaths were recorded, of which 1,694 were from cancer, 761 from CVD, and 870 from other causes. Data on egg consumption was collected using a validated diet history at recruitment. Cox proportional hazards models, adjusted for confounders, were used in the analyses., Results: The mean (standard deviation) egg consumption was 22.0 g/day (15.8) and 30.9 g/day (23.1) in women and men, respectively. No association was observed between egg consumption and all-cause mortality for the highest vs the lowest quartile (HR 1.01; 95% CI 0.91-1.11; P trend = 0.96). Likewise, no association was observed with cancer and cardiovascular diseases mortality. However, an inverse association was found between egg consumption and deaths for other causes (HR 0.76; 95% CI 0.63-0.93; P trend = 0.003), particularly for deaths from the nervous system (HR 0.59; 95% CI 0.35-1.00; P trend = 0.036). No interaction was detected with the adherence to Mediterranean diet., Conclusions: This study shows no association between moderate egg consumption, up to 1 egg per day, and main causes of mortality in a large free-living Mediterranean population.

The epidemiological evidence regarding the association of coffee and tea consumption with prostate cancer risk is inconclusive, and few cohort studies have assessed these associations by disease stage and grade. We examined the associations of coffee (total, caffeinated and decaffeinated) and tea intake with prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 142,196 men, 7,036 incident prostate cancer cases were diagnosed over 14 years of follow-up. Data on coffee and tea consumption were collected through validated country-specific food questionnaires at baseline. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CI). Models were stratified by center and age, and adjusted for anthropometric, lifestyle and dietary factors. Median coffee and tea intake were 375 and 106 mL/day, respectively, but large variations existed by country. Comparing the highest (median of 855 mL/day) versus lowest (median of 103 mL/day) consumers of coffee and tea (450 vs. 12 mL/day) the HRs were 1.02 (95% CI, 0.94-1.09) and 0.98 (95% CI, 0.90-1.07) for risk of total prostate cancer and 0.97 (95% CI, 0.79-1.21) and 0.89 (95% CI, 0.70-1.13) for risk of fatal disease, respectively. No evidence of association was seen for consumption of total, caffeinated or decaffeinated coffee or tea and risk of total prostate cancer or cancer by stage, grade or fatality in this large cohort. Further investigations are needed to clarify whether an association exists by different preparations or by concentrations and constituents of these beverages., (© 2018 UICC.)

Background: Traditionally, the primary outcome in meniscal allograft transplantation (MAT) has been long-term survivorship; however, short-term clinically significant outcomes are necessary to fully evaluate patient improvement after surgery., Purpose: To (1) establish the minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) with respect to patient-reported outcome measures (PROMs) and (2) evaluate preoperative and intraoperative variables correlated with achieving these threshold values., Study Design: Cohort study (diagnosis); Level of evidence, 2., Methods: A prospectively maintained institutional registry was queried for all MATs performed between 1999 and 2017. The following PROM scores were collected: International Knee Documentation Committee (IKDC) score, Lysholm score, and Knee injury and Osteoarthritis Outcome Score (KOOS). Patients who completed preoperative and postoperative PROMs within a 1-month window were included to calculate the distribution-based MCID at this interval. An anchor question regarding satisfaction with surgery was asked at the same time point and was employed to determine the PASS using nonparametric receiver operating characteristic curve/area under the curve analysis. Multivariate regression analysis was performed to correlate patient demographics, medical history, and concomitant procedures to propensity in achieving the MCID and PASS., Results: A total of 98 patients who underwent MAT met the inclusion/exclusion criteria, of whom 10 underwent concomitant ligamentous procedures, 65 underwent concomitant cartilage procedures, and 7 underwent concomitant realignment procedures. The mean patient age was 29.4 ± 9.0 years, and the mean body mass index (BMI) was 26.8 ± 5.2 kg/m 2 . The distribution-based MCID and PASS were determined for the Lysholm score (12.3 and 66.5) and IKDC (9.9 and 36.0) as well as the KOOS Pain (9.9 and N/A ), Symptoms (9.7 and 73.0), Activities of Daily Living (9.5 and N/A), Sport (13.3 and N/A), and Quality of Life (14.6 and 53.0) subscales, respectively. A preoperative Short Form Physical Component Summary (SF PCS) score greater than 32.0 was predictive of postoperative satisfaction. Patients with work-related claims had a reduced likelihood of achieving the MCID for the IKDC and the PASS for the KOOS Symptoms. An increased BMI was also associated with failing to achieve the PASS for the KOOS Quality of Life (QOL)., Conclusion: This study established the MCID and PASS for the Lysholm score, IKDC, and KOOS in patients undergoing MAT. Workers' compensation and higher BMI were associated with failing to achieve clinically significant values. Lower preoperative Lysholm, IKDC, and KOOS scores were predictive of achieving the MCID, while higher preoperative SF PCS scores were associated with achieving satisfaction after MAT., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: A.B.Y. has received hospitality payments from Stryker, Organogenesis, Arthrex, Ceterix Orthopaedics, Aastrom Biosciences, and Smith & Nephew; receives research support from Arthrex and MedWest; is a consultant for Aastrom Biosciences; and has received educational support from Arthrex and Smith & Nephew. B.J.C. is a consultant for Arthrex, Geistlich Pharma, Smith & Nephew, Bioventus, Vericel, Zimmer Biomet, Anika Therapeutics, Pacira Pharmaceuticals, and Isto Technologies; receives royalties from Arthrex, DJO, and Encore Medical; is a paid speaker/presenter for Arthrex, LifeNet Health, Carticept Medical, and Pacira Pharmaceuticals; has received educational support from Arthrex and Pacira Pharmaceuticals; and has received hospitality payments from Arthrex, Geistlich Pharma, LifeNet Health, GE Healthcare, Vericel, Aesculap Biologics, DePuy Synthes, Genzyme, and Pacira Pharmaceuticals. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Purpose: To provide updated surgical trends of cartilage procedures differentiated by the classic groups of palliative, repair, and restorative modalities., Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried from 2010-2016 for the following cartilage procedures: chondroplasty, microfracture, arthroscopic osteochondral autograft or allograft transplantation, open osteochondral autograft or allograft transplantation, and autologous chondrocyte implantation. Demographic variables and short-term (30-day) complications were analyzed with 1-way analysis of variance and post hoc analysis. Linear regression analysis was performed to analyze trends over time., Results: A total of 15,609 procedures performed between 2010 and 2016 were analyzed. On average, 342.2 ± 27.9 cartilage procedures were performed per 100,000 operations. There was a linear increase in the management of overall cartilage procedures per 100,000 operations (P = .002). There were also linear increases in arthroscopic osteochondral autograft transplantation, arthroscopic osteochondral allograft transplantation, open osteochondral autograft transplantation, open osteochondral allograft transplantation, and autologous chondrocyte implantation (P < .001, P = .037, P = .001, P = .006, and P = .002, respectively). Meniscectomy was the most frequently performed concomitant procedure (9.7%-64.2% of cases). Chondroplasty and microfracture showed no change in frequency over time (P = .140 and P = .720, respectively). The overall complication rate was 2.1% for chondroplasty, 1.4% for microfracture, 1.8% for arthroscopic osteochondral autograft transplantation, 1.0% for arthroscopic osteochondral allograft transplantation, 1.4% for open osteochondral autograft transplantation, 1.1% for open osteochondral allograft transplantation, and 0.75% for autologous chondrocyte implantation. Deep vein thrombosis was the most common complication, occurring in 0.4% to 1.0% of cases. No statistically significant difference was found in complication rates between procedures (P = .105)., Conclusions: Cartilage restoration is becoming an increasingly popular modality to address chondral defects. Minimal complication rates suggest that these procedures may be safely performed concomitantly with other interventions., Level of Evidence: Level IV, retrospective database analysis., (Copyright © 2019 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: Midlevel providers (i.e. physician assistants [PAs] and nurse practitioners [NPs]) are being integrated into systems of care due to the exponentially increasing demand for orthopaedic care. There is a lack of studies which investigate orthopaedic patients' perspectives regarding midlevel providers., Methods: An anonymous questionnaire was administered to 538 first-time patients of four orthopaedic surgeons before their new patient visit. Content included patient perspectives regarding: optimal scope of practice, midlevel provider importance in physician selection, and reimbursement equity with physicians., Results: Of 538 consecutive patients, 415 (77%) responded. 57% were female with an average age of 63.9 ± 11.4 years. Most patients (68%) considered the training background of the surgeon's midlevel provider when initially choosing an orthopaedic surgeon. 34% of all patients perceived PAs to be more highly trained than NPs while 17% perceived the opposite. Patients had specific preferences regarding which services should be surgeon-provided: follow-up for abnormal tests (82%), initial postoperative appointment (81%), new patient visits (81%), and determining the need for advanced diagnostic studies (e.g. MRI) (76%). Patients had specific preferences regarding which services could be midlevel-provided: preoperative teaching (73%), minor in-office procedures (65%), long term postoperative appointments (61%), and prescriptions (61%). Patients lacked a consensus on reimbursement equity for midlevel providers and orthopaedic surgeons, despite most patients (78%) reporting the surgeon provides a higher-quality consultation., Conclusions: As health care becomes increasingly consumer-centric and value-driven, a databased utilization of midlevel staff will allow orthopaedic physicians to optimize efficiency and patient satisfaction. Surgeons may consider our results in division of clinical duties among midlevel staff since patients had specific preferences regarding which services should be physician-provided or midlevel-provided. Orthopaedic surgeons may also consider including the midlevel provider in marketing efforts, as most patients considered the midlevel provider's training background when initially choosing a surgeon and perceived PAs to be more highly trained than NPs. Patients lacked a consensus towards reimbursement equity for orthopaedic surgeons and midlevels, despite reporting that the surgeon provides a higher quality consultation. These findings are important as the midlevel workforce grows in response to the rising demand for orthopaedic care. Level of Evidence: IV., Competing Interests: Disclosures: The authors report no potential conflicts of interest related to this study.

Hyaline articular cartilage is critical for the normal functioning of the knee joint. Untreated focal cartilage defects have the potential to rapidly progress to diffuse osteoarthritis. Over the last several decades, a variety of interventions aiming at preserving articular cartilage and preventing osteoarthritis have been investigated. Reparative cartilage procedures, such as microfracture, penetrate the subchondral bone plate in effort to fill focal cartilage defects with marrow elements and stimulate fibrocartilaginous repair. In contrast, restorative cartilage procedures aim to replace the defective articular surface with autologous or allogeneic hyaline cartilage. This review focuses on the preservation of articular cartilage, and discusses the current reparative and restorative surgical techniques available for treating focal cartilage defects.

Background: Midlevel providers (eg, nurse practitioners and physician assistants) have been integrated into orthopaedic systems of care in response to the increasing demand for musculoskeletal care. Few studies have examined patient perspectives toward midlevel providers in orthopaedic sports medicine., Purpose: To identify perspectives of orthopaedic sports medicine patients regarding midlevel providers, including optimal scope of practice, reimbursement equity with physicians, and importance of the physician's midlevel provider to patients when initially selecting a physician., Study Design: Cross-sectional study; Level of evidence, 3., Methods: A total of 690 consecutive new patients of 3 orthopaedic sports medicine physicians were prospectively administered an anonymous questionnaire prior to their first visit. Content included patient perspectives regarding midlevel provider importance in physician selection, optimal scope of practice, and reimbursement equity with physicians., Results: Of the 690 consecutive patients who were administered the survey, 605 (87.7%) responded. Of these, 51.9% were men and 48.1% were women, with a mean age of 40.5 ± 15.7 years. More than half (51.2%) perceived no differences in training levels between physician assistants and nurse practitioners. A majority of patients (62.9%) reported that the physician's midlevel provider is an important consideration when choosing a new orthopaedic sports medicine physician. Patients had specific preferences regarding which services should be physician provided. Patients also reported specific preferences regarding those services that could be midlevel provided. There lacked a consensus on reimbursement equity for midlevel practitioners and physicians, despite 71.7% of patients responding that the physician provides a higher-quality consultation., Conclusion: As health care becomes value driven and consumer-centric, understanding patient perspectives on midlevel providers will allow orthopaedic sports medicine physicians to optimize efficiency and patient satisfaction. Physicians may consider these data in clinical workforce planning, as patients preferred specific services to be physician or midlevel provided. It may be worthwhile to consider midlevel providers in marketing efforts, given that patients considered the credentials of the physician's midlevel provider when initially selecting a new physician. Patients lacked consensus regarding reimbursement equity between physicians and midlevel providers, despite responding that the physician provides a higher-quality consultation. Our findings are important for understanding the midlevel workforce as it continues to grow in response to the increasing demand for orthopaedic sports care., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: C.P.H. receives research support from the Orthopaedic Research and Education Foundation. B.F. receives research support from Arthrex, Smith & Nephew, and Stryker; is a paid presenter/speaker for Arthrosurface and Sonoma; has stock/stock options in Jace Medical; and is a paid consultant for Sonoma and Stryker. S.J.N. receives research support from Allosource, Arthrex, Athletico, DJ Orthopaedics, Linvatec, Miomed, Smith & Nephew, and Stryker; receives royalties from Ossur and Springer; and is a paid consultant for Ossur, Pivot Medical, and Stryker. B.R.B. receives research support from Arthrex, ConMed Linvatec, DJ Orthopaedics, Ossur, Smith & Nephew, and Tornier and receives publishing royalties from SLACK Inc.

YiiP is a dimeric antiporter from the cation diffusion facilitator family that uses the proton motive force to transport Zn 2+ across bacterial membranes. Previous work defined the atomic structure of an outward-facing conformation, the location of several Zn 2+ binding sites, and hydrophobic residues that appear to control access to the transport sites from the cytoplasm. A low-resolution cryo-EM structure revealed changes within the membrane domain that were associated with the alternating access mechanism for transport. In the current work, the resolution of this cryo-EM structure has been extended to 4.1 Å. Comparison with the X-ray structure defines the differences between inward-facing and outward-facing conformations at an atomic level. These differences include rocking and twisting of a four-helix bundle that harbors the Zn 2+ transport site and controls its accessibility within each monomer. As previously noted, membrane domains are closely associated in the dimeric structure from cryo-EM but dramatically splayed apart in the X-ray structure. Cysteine crosslinking was used to constrain these membrane domains and to show that this large-scale splaying was not necessary for transport activity. Furthermore, dimer stability was not compromised by mutagenesis of elements in the cytoplasmic domain, suggesting that the extensive interface between membrane domains is a strong determinant of dimerization. As with other secondary transporters, this interface could provide a stable scaffold for movements of the four-helix bundle that confers alternating access of these ions to opposite sides of the membrane., Competing Interests: The authors declare no conflict of interest.

The treatment of patellofemoral cartilage defects presents several distinct challenges when compared with cartilage restoration techniques used for other compartments of the knee due to the unique anatomy and distribution of forces. The etiologies of patellofemoral articular cartilage lesions include acute traumatic instability injuries, such as dislocation and subluxation, osteochondritis dissecans, and chronic degenerative changes. Regardless of the etiology, untreated patellofemoral cartilage lesions can contribute to activity-limiting anterior knee pain. The goal of patellofemoral cartilage restoration procedures is to impart symptomatic relief and improve quality of life by repairing the articular cartilage surface and any comorbid malalignment or maltracking.Microfracture and osteochondral autograft transplantation (OAT) are two cartilage restoration procedures to consider when treating full-thickness patellofemoral chondral defects. Considered by some experts to be the gold standard therapy, microfracture is one of the most common procedures used for cartilage restoration. The technique involves the perforation of the subchondral bone plate for the release of marrow elements, filling the defect with a fibrocartilage clot repair. Though less commonly used, OAT allows defect replacement with native hyaline cartilage via autologous transplantation from a non-weight bearing area. The purpose of this article is to discuss the indication, technical considerations, and outcomes of microfracture and OAT when used for treating chondral lesions of the patellofemoral joint., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Surgical strategies for knee joint preservation are numerous, with the procedure(s) of choice for a given patient dependent on the status of the articular cartilage, meniscus, overall alignment, and ligamentous stability. For patients with large, isolated, osteochondral defects of the articular cartilage of the femoral condyle, osteochondral allograft transplantation (OCA) is often performed in an effort to reduce pain and improve function. Similarly, for appropriately indicated patients with symptomatic meniscus deficiency, meniscus allograft transplantation (MAT) is an excellent surgical solution. Often patients require concomitant MAT and OCA as part of a joint preservation strategy. In this Technical Note, we describe the surgical technique for performing arthroscopic-assisted concomitant lateral MAT and lateral femoral condyle OCA as part of a knee joint preservation strategy.

The function of protein products generated from intramembraneous cleavage by the γ-secretase complex is not well defined. The γ-secretase complex is responsible for the cleavage of several transmembrane proteins, most notably the amyloid precursor protein that results in Aβ, a transmembrane (TM) peptide. Another protein that undergoes very similar γ-secretase cleavage is the p75 neurotrophin receptor. However, the fate of the cleaved p75 TM domain is unknown. p75 neurotrophin receptor is highly expressed during early neuronal development and regulates survival and process formation of neurons. Here, we report that the p75 TM can stimulate the phosphorylation of TrkB (tyrosine kinase receptor B). In vitro phosphorylation experiments indicated that a peptide representing p75 TM increases TrkB phosphorylation in a dose- and time-dependent manner. Moreover, mutagenesis analyses revealed that a valine residue at position 264 in the rat p75 neurotrophin receptor is necessary for the ability of p75 TM to induce TrkB phosphorylation. Because this residue is just before the γ-secretase cleavage site, we then investigated whether the p75(αγ) peptide, which is a product of both α- and γ-cleavage events, could also induce TrkB phosphorylation. Experiments using TM domains from other receptors, EGFR and FGFR1, failed to stimulate TrkB phosphorylation. Co-immunoprecipitation and biochemical fractionation data suggested that p75 TM stimulates TrkB phosphorylation at the cell membrane. Altogether, our results suggest that TrkB activation by p75(αγ) peptide may be enhanced in situations where the levels of the p75 receptor are increased, such as during brain injury, Alzheimer's disease, and epilepsy., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

Adult height and sitting height may reflect genetic and environmental factors, including early life nutrition, physical and social environments. Previous studies have reported divergent associations for height and chronic disease mortality, with positive associations observed for cancer mortality but inverse associations for circulatory disease mortality. Sitting height might be more strongly associated with insulin resistance; however, data on sitting height and mortality is sparse. Using the European Prospective Investigation into Cancer and Nutrition study, a prospective cohort of 409,748 individuals, we examined adult height and sitting height in relation to all-cause and cause-specific mortality. Height was measured in the majority of participants; sitting height was measured in ~253,000 participants. During an average of 12.5 years of follow-up, 29,810 deaths (11,931 from cancer and 7,346 from circulatory disease) were identified. Hazard ratios (HR) with 95% confidence intervals (CI) for death were calculated using multivariable Cox regression within quintiles of height. Height was positively associated with cancer mortality (men: HRQ5 vs. Q1 = 1.11, 95%CI = 1.00-1.24; women: HRQ5 vs. Q1 = 1.17, 95%CI = 1.07-1.28). In contrast, height was inversely associated with circulatory disease mortality (men: HRQ5 vs. Q1 = 0.63, 95%CI = 0.56-0.71; women: HRQ5 vs. Q1 = 0.81, 95%CI = 0.70-0.93). Although sitting height was not associated with cancer mortality, it was inversely associated with circulatory disease (men: HRQ5 vs. Q1 = 0.64, 95%CI = 0.55-0.75; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.49-0.74) and respiratory disease mortality (men: HRQ5 vs. Q1 = 0.45, 95%CI = 0.28-0.71; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.40-0.89). We observed opposing effects of height on cancer and circulatory disease mortality. Sitting height was inversely associated with circulatory disease and respiratory disease mortality.