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BACKGROUND: Complications of immobilization after quadriceps and patellar tendon repairs include decreased patellar mobility, limited flexion, persistent pain, muscle weakness, and patella baja. In contrast, early motion limits muscle atrophy, accelerates tendon healing, and prevents joint stiffness. HYPOTHESIS: Quadriceps and patellar tendon repairs protected with a 'relaxing suture' are strong enough to safely permit early motion, full weightbearing, and brace-free ambulation. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twenty quadriceps and 30 patellar tendon ruptures were treated with a primary repair augmented with a single No. 5 Ethibond suture, a postoperative regimen of controlled motion and full weightbearing at 7 to 10 days, and brace-free ambulation at 6 weeks after surgery. At a minimum follow-up of 12 months, results of surgery were assessed with the Lysholm knee rating system. RESULTS: Six weeks after surgery, 120 degrees of flexion and brace-free ambulation were the goals and were achieved at a mean of 7.2 and 7.7 weeks, respectively. By 6 months, all patients reached their preinjury levels of activity (eg, basketball, softball, Rocky Mountain tour guide), 40 had full active extension, and 10 lacked 3 degrees to 10 degrees of active extension. There were no postoperative complications. At a mean follow-up of 4 years (range, 1-12 years), the Lysholm scores averaged 92 points (range, 84-100 points), and there were 35 excellent, 15 good, and no fair or poor results. CONCLUSION: Quadriceps and patellar tendon repairs protected by a relaxing suture were strong enough to safely permit early motion, weightbearing, and brace-free ambulation while producing good and excellent results. [ABSTRACT FROM AUTHOR]

BACKGROUND: Radiofrequency and laser thermal chondroplasty procedures are performed to debride and smooth fibrillated, articular cartilage. HYPOTHESIS: Temperature requirements necessary to achieve morphological change will be lower in fibrillated arthritic cartilage as compared with nonarthritic articular cartilage. STUDY DESIGN: Controlled laboratory study. METHODS: A thermal cell-culture chamber was mounted on a stereoscopic microscope and coordinated with a custom temperature-control program. Nonarthritic and osteoarthritic articular cartilage specimens were sectioned into full-thickness slices. The articular sections were exposed to temperatures incrementally from 37 masculine C to 75 masculine C. Real-time, digital capture microscopy was used to visualize and analyze the morphological changes undergone by the articular cartilage specimens. RESULTS: Arthritic articular cartilage displayed morphological change at 56.5 +/- 1.7 masculine C. Loss of fibrillation was the initial morphological change visualized. Continued thermal exposure caused a shrinkage effect of the entire tissue section that was similar to the change seen in nonarthritic sections. Nonarthritic cartilage displayed morphological change at 60.9 +/- 1.9 masculine C. CONCLUSIONS: Consistent characteristic morphological changes were found at distinct temperatures in osteoarthritic and nonarthritic articular cartilage. CLINICAL RELEVANCE: This information begins to establish the thermal parameters required for morphological change of osteoarthritic articular cartilage. [ABSTRACT FROM AUTHOR]

As people with AIDS live longer, neoplasms have more time to develop -- much as latent cancer does in renal transplant recipients. Screen new HIV-positive patients for likely malignancies, including lymphomas. [ABSTRACT FROM AUTHOR]

Background: Health insurance status and access to care are recurring topics of discussion and concern. The purpose of this investigation was to examine access to care on the basis of insurance status for patients with anterior cruciate ligament (ACL) injuries in South Florida.Methods: From March 2010 to March 2011, eighty patients with ACL injuries were identified at a county hospital sports medicine clinic and a university-based sports medicine practice. Demographic and injury-specific data were obtained with attention to the date of injury, the date of diagnosis, and the number of medical visits. Hazard ratios and 95% confidence intervals were calculated from multivariable Cox proportional-hazards regression models to determine the effect of insurance type on the time to diagnosis of an ACL tear.Results: Patients with private insurance were diagnosed at a median fourteen days after the injury, whereas those receiving Medicaid and those without insurance were diagnosed a median of fifty-six and 121 days after the injury, respectively (p < 0.001). Patients without insurance and those receiving Medicaid had more medical visits prior to diagnosis (median, four; range two to six) than those with private insurance (median, three; range, one to five) (p = 0.006). Differences for patient delays due to not seeking care were not significant among the three groups (p = 0.484).Conclusions: When grouped according to insurance status, subjects receiving Medicaid in South Florida faced greater system-related delays in obtaining care than did subjects with private insurance. System-related factors such as lack of access to specialized care result in an increased number of medical encounters. These regional findings are consistent with those of other regional studies on access to orthopaedic care. [ABSTRACT FROM AUTHOR]

The purpose of this work was to provide a simple method to determine reactive strength during the 6-meter timed hop test (6mTH) and evaluate its association with isokinetic peak torque in patients following anterior cruciate ligament reconstruction (ACLR). Twenty-nine ACLR patients who were at least four months from surgery were included in this analysis. Participants were brought into the laboratory on one occasion to complete functional testing. Quadriceps and hamstring isokinetic testing was completed bilaterally at 60, 180, and 300 deg∙s-1, using extension peak torque from each speed as the outcome measure. The 6mTH was completed bilaterally using a marker-based motion capture system, and reactive strength ratio (RSR) was calculated from the vertical velocity of the pelvis during the test. An adjustment in RSR was made using the velocity of the 6mTH test to account for different strategies employed across participants. Repeated measures correlations were used to determine associations among isokinetic and hop testing variables. A two-way mixed analysis of variance was used to determine differences in isokinetic and hop testing variables between operated and non-operated legs and across male and female participants. Moderate positive associations were found between RSR (and adjusted RSR) and isokinetic peak torque at all speeds (r = .527 to .577). Mean comparisons showed significant main effects for leg and sex. Patients showed significant deficits in their operated versus non-operated legs in all isokinetic and hop testing variables, yet only isokinetic peak torque and timed hop time showed significant differences across male and female groups. Preliminary results are promising but further development is needed to validate other accessible technologies available to calculate reactive strength during functional testing after ACLR. Pending these developments, the effects of movement strategies, demographics, and levels of participation on RSR can then be explored to translate this simple method to clinical environments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ripic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Anterior cruciate ligament (ACL) tears are devastating for elite athletes, including those in the National Basketball Association (NBA). The purpose of this study was to describe common in-game mechanisms of injury, playing situations, and anatomic positioning of players who sustained an ACL injury in the NBA., Methods: ACL tears which occurred in NBA games during the previous 16 seasons (2007-2022) and had accessible video clips were identified through publicly available reports., Results: Thirty-one ACL tears were identified with quality videos available. Nearly all players were on offense (93.5%, 29/31). Most ACL tears (29/31, 93.5%) did not involve direct contact to the injured extremity. The most common physical activity at the time of injury was landing from any type of jump (45.2%, 14/31). Anatomically, the knee was frequently in early flexion (58.8%, 10/17) and abducted (77.4%, 24/31); the foot was commonly abducted (87.1%, 27/31); and the hip was usually abducted (64.5%, 20/31) and flexed (80.6%, 25/31). Almost all players had another individual near them at the time of injury, with 90.3% (28/31) and 96.8% (30/31) having someone within 2ft and 5ft., Conclusions: Most ACL tears occurred inside the lane, regardless of mechanism of injury (26/31, 83.9%). ACL tears in the NBA were primarily not due to direct contact of the injured extremity but did have common anatomic patterns. The findings of this study can be used in the future to help reduce the risk of injury through the adaptation of current training activities.

The importance of mechanical loading and its relationship to orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA) is beginning to receive attention. This review explores the current efficacy of orthobiologic interventions, notably platelet-rich plasma (PRP), bone marrow aspirate (BMA), and mesenchymal stem/stromal cells (MSCs), in combating PTOA drawing from a comprehensive review of both preclinical animal models and human clinical studies. This review suggests why mechanical joint loading, such as running, might improve outcomes in PTOA management in conjunction with orthiobiologic administration. Accumulating evidence underscores the influence of mechanical loading on chondrocyte behavior and its pivotal role in PTOA pathogenesis. Dynamic loading has been identified as a key factor for optimal articular cartilage (AC) health and function, offering the potential to slow down or even reverse PTOA progression. We hypothesize that integrating the activation of mechanotransduction pathways with orthobiologic treatment strategies may hold a key to mitigating or even preventing PTOA development. Specific loading patterns incorporating exercise and physical activity for optimal joint health remain to be defined, particularly in the clinical setting following joint trauma., 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., (Copyright © 2024 Gardashli, Baron, Huang, Kaplan, Meng, Kouroupis and Best.)

Knee pathology, including anterior cruciate ligament (ACL) tears, meniscal tears, articular cartilage lesions, and intra-articular masses or cysts are common clinical entities treated by orthopedic surgeons with arthroscopic surgery. Preoperatively, magnetic resonance imaging (MRI) is now standard in confirming knee pathology, particularly detecting pathology less evident with history and physical examination alone. The radiologist's MRI interpretation becomes essential in evaluating intra-articular knee structures. Typically, the radiologist that interprets the MRI does not have the opportunity to view the same pathology arthroscopically. Thus, the purpose of this article is to illustratively reconcile what the orthopedic surgeon sees arthroscopically with what the radiologist sees on magnetic resonance imaging when viewing the same pathology. Correlating virtual and actual images can help better understand pathology, resulting in more accurate MRI interpretations. In this article, we present and review a series of MR and correlating arthroscopic images of ACL tears, meniscal tears, chondral lesions, and intra-articular masses and cysts. Short teaching points are included to highlight the importance of radiological signs and pathological MRI appearance with significant clinical and arthroscopic findings., Competing Interests: There are no conflicts of interest., (© 2024 Published by Scientific Scholar on behalf of Journal of Clinical Imaging Science.)

Abstract: Cohen, JL, Cade, WH, Harrah, TC, Costello II, JP, and Kaplan, LD. The surgical management of NCAA Division 1 college football injuries post COVID-19: A single institution retrospective review. J Strength Cond Res 38(5): 906-911, 2024-The unprecedented COVID-19 pandemic had a significant impact on college football operations, including athletes' training regimens. As a result of these changes, concern for increased injury susceptibility post COVID-19 regulations has become a point of discussion. The current study sought to evaluate the incidence of surgical injury among NCAA Division 1 college football players at the authors' institution during the first full season after start of the COVID-19 pandemic compared with previous years. Retrospective chart review was performed for all players who sustained injuries requiring surgery while a member of the NCAA Division 1 football program during the 2009-2021 seasons. A p -value of ≤0.05 was used to determine significance. A total of 23 surgical injuries occurred in 22 players during the 2021 season compared with 121 in 118 players in the 12 previous seasons combined ( p = 0.0178; RR = 1.47). There was a significant increase in shoulder injuries ( n = 13 vs. n = 31; p = <0.0001; RR = 3.05) and specifically a significant increase in labral tears ( n = 10 vs. n = 30; p = 0.0003; RR = 2.74). No difference was seen in knee injuries ( n = 10 vs. n = 77; p = 0.27; RR = 1.35) and specifically no difference in anterior cruciate ligament injuries ( n = 3 vs. n = 31; p = 0.77; RR = 1.17). This phenomenon is multifactorial in nature, but alterations to players' training and preparations because of the COVID-19 pandemic likely resulted in suboptimal conditioning, leading to the increased incidence of surgical injuries emphasizing the importance of adequate strength training and conditioning., (Copyright © 2023 National Strength and Conditioning Association.)

Abstract: Costello II, JP, Wagner, JD, Dahl, VA, Cohen, JL, Reuter, AM, and Kaplan, LD. Effects of COVID-19 on rate of injury and position-specific injury during the 2020 National Football League season. J Strength Cond Res 38(1): 97-104, 2024-Because of the COVID-19 pandemic, the National Football League (NFL) made changes to its operations for the 2020 season. We hypothesize an increase in the rate of injuries during the 2020 season. Publicly available data were reviewed to identify NFL injuries from the 2015-2020 seasons. Player position, description of injury, date of injury, and injury setting were recorded. p ≤ 0.05 was considered statistically significant. For the 2020 season, compared with the 2015-2019 seasons, there was an increased risk of injury during the regular season overall relative risk (RR) = 1.308 ( p < 0.05), week (W)1 RR = 7.33 ( p < 0.05), W1-6 RR = 1.964 ( p < 0.05), W7-12 RR = 1.8909 ( p < 0.05), and during the postseason overall RR = 1.1444 ( p < 0.05), calculated using analysis of variance. There was an overall increased risk of abdominal or core injuries RR = 1.248 ( p < 0.05), groin or hip injuries RR = 2.534 ( p < 0.05), and hamstring injuries RR = 3.644 ( p < 0.05). There was an increased risk of hamstring injuries in cornerbacks RR = 3.219 ( p < 0.05) and running backs RR = 1.1394 ( p < 0.05), hip or groin injuries in guards RR = 1.105 ( p < 0.05), Achilles tendon injuries in safeties RR = 1.6976 ( p < 0.05), quadriceps injuries in running backs RR = 1.6191 ( p < 0.05), and arm injuries in defensive tackles RR = 1.221 ( p < 0.05). There was an increase in the overall rate of injuries in the 2020 NFL season, both in the regular season and postseason, compared with the 2015-2019 seasons. The overall rate of abdominal or core, groin or hip, and hamstring injuries increased. Specific player positions saw unique increases in rates of injuries. These findings may be due to numerous operational changes implemented, such as reduced in-person training and the elimination of the preseason, leading to suboptimal, sports-specific conditioning and increased risk of musculoskeletal injury., (Copyright © 2023 National Strength and Conditioning Association.)

An 18-year-old collegiate baseball player sustained an acute batter's shoulder injury causing a posterior shoulder dislocation with type IX 360° superior labrum from anterior to posterior tear. To the authors' knowledge, this description of batter's shoulder is not within the literature. The patient ultimately underwent arthroscopic labral repair and has fully returned to sport. In understanding the complexity of the shoulder during the batter's swing, this case demonstrates an expansion to the previously described pathophysiology of batter's shoulder., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background: Both partial- and full-thickness quadriceps tendon (QT) graft harvests are used for anterior cruciate ligament reconstruction (ACLR)., Purpose: To evaluate the impact of QT graft harvest depth (full or partial thickness) on electromechanical delay (EMD), peak torque (PT), and rate of torque development (RTD) after ACLR., Study Design: Controlled laboratory study., Methods: A total of 26 patients who underwent either partial-thickness (n = 14) or full-thickness (n = 12) autograft QT ACLR were recruited between June and November 2021 (>1 year before participation). Patients performed isokinetic knee extension testing with surface electromyography of the quadriceps muscles. Mixed repeated-measures analysis of variance with least significant difference post hoc testing was used to determine significant differences (mean difference [MD] ± SE) or interactions for all variables., Results: A significant speed×depth interaction was seen for the vastus medialis ( P = .005). Pairwise analyses showed significantly longer EMD for the partial-thickness graft than the full-thickness graft (MD ± SE, 19.92 ± 6.33 ms; P = .006). In the partial-thickness graft, the EMD was significantly longer at 90 deg/s versus 180 deg/s (MD ± SE, 19.11 ± 3.95 ms; P < .001) and 300 deg/s (MD ± SE, 16.43 ± 5.30 ms; P = .006). For PT, the full-thickness graft had a significantly lower PT on the operated versus nonoperated side at all speeds (MD ± SE: 90 deg/s, -57.0 ± 10.5 N·m, P < .001; 180 deg/s, -26.0 ± 10.2 N·m, P = .020; 300 deg/s, -20.3 ± 8.9 N·m, P = .034). For RTD, the full-thickness graft showed significantly Slower RTD for the operated versus nonoperated side at all time points (MD ± SD: RTD 0-25 (0-25% of the range of motion), -131.3 ± 50.9 N·m/s, P = .018; RTD 25-50 , -197.0 ± 72.5 N·m/s, P = .014; RTD 50-75 , -113.3 ± 39.8 N·m/s, P = .013; RTD 75-100 , -149.4 ± 35.9 N·m/s, P < .001)., Conclusion: Compared with partial-thickness QT, full-thickness QT showed a shorter vastus medialis EMD at higher loading, and therefore greater stiffness, as well as slower RTD and lower PT across all testing speeds., Clinical Relevance: The impact of full-thickness QT autograft on EMD and neuromuscular performance should be considered for ACLR., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: M.G.B. has received education payments from Southern Edge Orthopaedics, consulting fees from Arthrex and LifeNet Health, nonconsulting fees from Arthrex, and hospitality payments from Smith & Nephew. L.D.K. has received education payments from Southern Edge Orthopaedics, nonconsulting fees from Arthrex, and royalties from Arthrex and Smith & Nephew. T.M.B. has received consulting fees from Bioventus and hospitality payments from GE Healthcare. 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) 2023.)

Background Due to the COVID-19 pandemic, many professional sports leagues such as the National Hockey League (NHL) made significant changes to their schedules and operating procedures. Changes included a modified 2019-2020 playoff format, the removal of the 2020-2021 preseason, and condensed game schedules. Though these modifications were made in an effort to protect players from COVID-19, they resulted in decreased training time and preparation. The purpose of this study was to assess the impact of these changes on the rate of player injuries in the NHL both after the resumption of the midseason stoppage and during the subsequent seasons. Hypothesis/purpose Changes to the NHL schedule amid the COVID-19 pandemic resulted in a significant increase in player injury rates. Methods NHL injuries were obtained from an NHL injury database for the 2018-2019 through the 2021-2022 seasons. The date of injury, date of return, injury description, player age, and player position were recorded. Injury rates were calculated as the number of total athlete injuries per 1000 game exposures (GEs). The primary outcome was the injury proportion ratio (IPR) when comparing the injury rates of the post-COVID-19 season with baseline seasons. Secondary measures analyzed injuries based on age, anatomic location, month in the season, position, length of injury, season-ending injuries, and recurring injuries. Results A total of 4604 injuries were recorded between 2018 and 2022. The modified 2019-2020 playoffs had significantly higher rates of injury (IPR = 1.84, 95% confidence interval {CI} = 1.36-2.49) with more game exposures per week. The 2020-2021 season had significantly higher rates of overall player injury compared to baseline seasons (IPR = 1.19, 95% CI = 1.09-1.30) and also had a higher rate of season-ending injuries (IPR = 1.71, 95% CI = 1.38-2.11). Most injuries occurred in the first few months of the 2020-2021 season. There was no significant difference in injury rate based on age group and no significant difference in the average length of injury between seasons. Conclusion Increases in injury rates could be due to decreased offseason training between seasons, the elimination of preseason games, and increased game density. Decreasing typical training timelines and eliminating the preseason to rapidly return to normal competition after unexpected events (pandemics, lockdowns, etc.) may pose a risk to player safety in the NHL. These findings should be considered before future schedule changes in professional hockey., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ehlen et al.)

Importance: Both augmented reality (AR) and virtual reality (VR) have had increasing applications in medicine, including medical training, psychology, physical medicine, rehabilitation, and surgical specialties, such as neurosurgery and orthopedic surgery. There are little data on AR's effect on patients' anxiety and experiences., Objective: To determine whether the use of an AR walkthrough effects patient perioperative anxiety., Design, Setting, and Participants: This randomized clinical trial was conducted at an outpatient surgery center in 2021 to 2022. All patients undergoing elective orthopedic surgery with the senior author were randomized to the treatment or control group. Analyses were conducted per protocol. Data analysis was performed in November 2022., Intervention: AR experience explaining to patients what to expect on their day of surgery and walking them through the surgery space. The control group received the standard educational packet., Main Outcomes and Measures: The main outcome was change in State-Trait Anxiety Inventory (STAI) from the screening survey to the preoperative survey., Results: A total of 140 patients were eligible, and 45 patients either declined or were excluded. Therefore, 95 patients (63 [66.3%] male; mean [SD] age, 38 [16] years) were recruited for the study and included in the final analysis; 46 patients received the AR intervention, and 49 patients received standard instructions. The AR group experienced a decrease in anxiety from the screening to preoperative survey (mean score change, -2.4 [95% CI, -4.6 to -0.3]), while the standard care group experienced an increase (mean score change, 2.6 [95% CI, 0.2 to 4.9]; P = .01). All patients postoperatively experienced a mean decrease in anxiety score compared with both the screening survey (mean change: AR, -5.4 [95% CI, -7.9 to -2.9]; standard care, -6.9 [95% CI, -11.5 to -2.2]; P = .32) and preoperative survey (mean change: AR, -8.0 [95% CI, -10.3 to -5.7]; standard care, -4.2 [95% CI, -8.6 to 0.2]; P = .19). Of 42 patients in the AR group who completed the postoperative follow-up survey, 30 (71.4%) agreed or strongly agreed that they enjoyed the experience, 29 (69.0%) agreed or strongly agreed that they would recommend the experience, and 28 (66.7%) agreed or strongly agreed that they would use the experience again. No differences were observed in postoperative pain levels or narcotic use., Conclusions and Relevance: In this randomized clinical trial, the use of AR decreased preoperative anxiety compared with traditional perioperative education and handouts, but there was no significant effect on postoperative anxiety, pain levels, or narcotic use. These findings suggest that AR may serve as an effective means of decreasing preoperative patient anxiety., Trial Registration: ClinicalTrials.gov Identifier: NCT04727697.

The onset and progression of human inflammatory joint diseases are strongly associated with the activation of resident synovium/infrapatellar fat pad (IFP) pro-inflammatory and pain-transmitting signaling. We recently reported that intra-articularly injected IFP-derived mesenchymal stem/stromal cells (IFP-MSC) acquire a potent immunomodulatory phenotype and actively degrade substance P (SP) via neutral endopeptidase CD10 (neprilysin). Our hypothesis is that IFP-MSC robust immunomodulatory therapeutic effects are largely exerted via their CD10-bound small extracellular vesicles (IFP-MSC sEVs) by attenuating synoviocyte pro-inflammatory activation and articular cartilage degradation. Herein, IFP-MSC sEVs were isolated from CD10High- and CD10Low-expressing IFP-MSC cultures and their sEV miRNA cargo was assessed using multiplex methods. Functionally, we interrogated the effect of CD10High and CD10Low sEVs on stimulated by inflammatory/fibrotic cues synoviocyte monocultures and cocultures with IFP-MSC-derived chondropellets. Finally, CD10High sEVs were tested in vivo for their therapeutic capacity in an animal model of acute synovitis/fat pad fibrosis. Our results showed that CD10High and CD10Low sEVs possess distinct miRNA profiles. Reactome analysis of miRNAs highly present in sEVs showed their involvement in the regulation of six gene groups, particularly those involving the immune system. Stimulated synoviocytes exposed to IFP-MSC sEVs demonstrated significantly reduced proliferation and altered inflammation-related molecular profiles compared to control stimulated synoviocytes. Importantly, CD10High sEV treatment of stimulated chondropellets/synoviocyte cocultures indicated significant chondroprotective effects. Therapeutically, CD10High sEV treatment resulted in robust chondroprotective effects by retaining articular cartilage structure/composition and PRG4 (lubricin)-expressing cartilage cells in the animal model of acute synovitis/IFP fibrosis. Our study suggests that CD10High sEVs possess immunomodulatory miRNA attributes with strong chondroprotective/anabolic effects for articular cartilage in vivo. The results could serve as a foundation for sEV-based therapeutics for the resolution of detrimental aspects of immune-mediated inflammatory joint changes associated with conditions such as osteoarthritis (OA).

The prognostic relevance of diagnosis to treatment interval (DTI) in patients with newly diagnosed mantle cell lymphoma (MCL) is unknown. Hence, we sought to evaluate the impact of DTI on outcomes in MCL using 3 large datasets (1) the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource, (2) patients enrolled in the ALL Age Asthma Cohort/CALGB 50403, and (3) a multisitecohort of patients with MCL. Patients were a priori divided into 2 groups, 0 to 14 days (short DTI) and 15 to 60 days (long DTI). The patients in whom observation was deemed appropriate were excluded. One thousand ninety-seven patients newly diagnosed with MCL and available DTI were included in the study. The majority (73%) had long DTI (n=797). Patients with short DTI had worse eastern cooperative oncology group performance status (ECOG PS ≥2), higher lactate dehydrogenase, bone marrow involvement, more frequent B symptoms, higher MCL International Prognostic Index (MIPI ≥6.2), and were less likely to receive intensive induction therapy than long DTI group. The median progression-free survival (2.5 years vs 4.8 years, p<0.0001) and overall survival (7.8 years vs. 11.8 years, p<0.0001) were significantly inferior in the short DTI group than the long DTI cohort and remained significant for progression-free survival and overall survival in multivariable analysis. We show that the DTI is an important prognostic factor in patients newly diagnosed with MCL and is strongly associated with adverse clinical factors and poor outcomes. DTI should be reported in all the patients newly diagnosed with MCL who are enrolling in clinical trials and steps must be taken to ensure selection bias is avoided., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Osteoarthritis (OA) is the most common cause of disability worldwide among the elderly. Alarmingly, the incidence of OA in individuals less than 40 years of age is rising, likely due to the increase in obesity and post-traumatic osteoarthritis (PTOA). In recent years, due to a better understanding of the underlying pathophysiology of OA, several potential therapeutic approaches targeting specific molecular pathways have been identified. In particular, the role of inflammation and the immune system has been increasingly recognized as important in a variety of musculoskeletal diseases, including OA. Similarly, higher levels of host cellular senescence, characterized by cessation of cell division and the secretion of a senescence-associated secretory phenotype (SASP) within the local tissue microenvironments, have also been linked to OA and its progression. New advances in the field, including stem cell therapies and senolytics, are emerging with the goal of slowing disease progression. Mesenchymal stem/stromal cells (MSCs) are a subset of multipotent adult stem cells that have demonstrated the potential to modulate unchecked inflammation, reverse fibrosis, attenuate pain, and potentially treat patients with OA. Numerous studies have demonstrated the potential of MSC extracellular vesicles (EVs) as cell-free treatments that comply with FDA regulations. EVs, including exosomes and microvesicles, are released by numerous cell types and are increasingly recognized as playing a critical role in cell-cell communication in age-related diseases, including OA. Treatment strategies for OA are being developed that target senescent cells and the paracrine and autocrine secretions of SASP. This article highlights the encouraging potential for MSC or MSC-derived products alone or in combination with senolytics to control patient symptoms and potentially mitigate the progression of OA. We will also explore the application of genomic principles to the study of OA and the potential for the discovery of OA phenotypes that can motivate more precise patient-driven treatments.

Background: Anterior cruciate ligament reconstruction (ACLR) using the quadriceps tendon is an increasingly popular technique. Both partial-thickness quadriceps tendon (PT-Q) and full-thickness quadriceps tendon (FT-Q) graft depths are employed., Hypothesis/purpose: This study was designed to assess isokinetic peak torque, average power, and total work during knee extension in patients with FT-Q or PT-Q grafts for ACLR. We hypothesized that both groups would show lower isokinetic values for the operated side, with greater deficits in the FT-Q group than in the PT-Q group., Study Design: Cohort study; Level of evidence, 3., Methods: A total of 26 patients who underwent ACLR with either an FT-Q or PT-Q graft were recruited between June 2021 and November 2021. Patients underwent isokinetic knee extension testing at > 1 year after surgery. Mixed repeated-measures analysis of covariance with least square difference post hoc testing was used to determine significant differences or interactions for all variables., Results: Peak torque was significantly lower for the operated limb than the nonoperated limb in the FT-Q group (mean difference [MD] ± standard error [SE], -38.6 ± 8.3 Nċm [95% CI, -55.7 to -21.5 Nċm]; P < .001; d = 0.90) but not in the PT-Q group (MD ± SE, -7.3 ± 7.7 Nċm [95% CI, -23.2 to 8.5 Nċm]; P = .348; d = 0.20). Similarly, average power for the operated limb was lower than that for the nonoperated limb in the FT-Q group (MD ± SE, -53.6 ± 13.4 W [95% CI, -81.3 to -26.9 W]; P < .001; d = 0.88) but not in the PT-Q group (MD ± SE, -4.1 ± 12.4 W [95% CI, -29.8 to 21.5 W]; P = .742; d = 0.07), and total work was lower for the operated limb compared with the nonoperated limb in the FT-Q group (MD ± SE, -118.2 ± 27.1 J [95% CI, -174.3 to -62.2 J]; P < .001; d = 0.96) but not in the PT-Q group (MD ± SE, -18.3 ± 25.1 J [95% CI, -70.2 to 33.6 J]; P = .472; d = 0.15)., Conclusion: The FT-Q group showed significant deficits in the operated limb compared with the nonoperated limb for all isokinetic variables. In contrast, no significant differences were found between the nonoperated and operated limbs for the PT-Q group.

Tendinopathies encompass a highly prevalent, multi-faceted spectrum of disorders, characterized by activity-related pain, compromised function, and propensity for an extended absence from sport and the workplace. The pathophysiology of tendinopathy continues to evolve. For decades, it has been related primarily to repetitive overload trauma but more recently, the onset of tendinopathy has been attributed to the tissue's failed attempt to heal after subclinical inflammatory and immune challenges (failed healing model). Conventional tendinopathy management produces only short-term symptomatic relief and often results in incomplete repair or healing leading to compromised tendon function. For this reason, there has been increased effort to develop therapeutics to overcome the tissue's failed healing response by targeting the cellular metaplasia and pro-inflammatory extra-cellular environment. On this basis, stem cell-based therapies have been proposed as an alternative therapeutic approach designed to modify the course of the various tendon pathologies. Mesenchymal stem/stromal cells (MSCs) are multipotent stem cells often referred to as "medicinal signaling cells" due to their immunomodulatory and anti-inflammatory properties that can produce a pro-regenerative microenvironment in pathological tendons. However, the adoption of MSCs into clinical practice has been limited by FDA regulations and perceived risk of adverse events upon infusion in vivo . The introduction of cell-free approaches, such as the extracellular vesicles of MSCs, has encouraged new perspectives for the treatment of tendinopathies, showing promising short-term results. In this article, we review the most recent advances in MSC-based and MSC-derived therapies for tendinopathies. Preclinical and clinical studies are included with comment on future directions of this rapidly developing therapeutic modality, including the importance of understanding tissue loading and its relationship to any treatment regimen., 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., (Copyright © 2023 Quintero, Perucca Orfei, Kaplan, de Girolamo, Best and Kouroupis.)

The perivascular localization of endometrial mesenchymal stem/stromal cells (eMSC) allows them to sense local and distant tissue damage, promoting tissue repair and healing. Our hypothesis is that eMSC therapeutic effects are largely exerted via their exosomal secretome (eMSC EXOs) by targeting the immune system and angiogenic modulation. For this purpose, EXOs isolated from Crude and CD146+ eMSC populations were compared for their miRNA therapeutic signatures and immunomodulatory functionality under inflammatory conditions. eMSC EXOs profiling revealed 121 in Crude and 88 in CD146+ miRNAs, with 82 commonly present in both populations. Reactome and KEGG analysis of miRNAs highly present in eMSC EXOs indicated their involvement among others in immune system regulation. From the commonly present miRNAs, four miRNAs (hsa-miR-320e, hsa-miR-182-3p, hsa-miR-378g, hsa-let-7e-5p) were more enriched in CD146+ eMSC EXOs. These miRNAs are involved in macrophage polarization, T cell activation, and regulation of inflammatory cytokine transcription (i.e., TNF-α, IL-1β, and IL-6). Functionally, stimulated macrophages exposed to eMSC EXOs demonstrated a switch towards an alternate M2 status and reduced phagocytic capacity compared to stimulated alone. However, eMSC EXOs did not suppress stimulated human peripheral blood mononuclear cell proliferation, but significantly reduced secretion of 13 pro-inflammatory molecules compared to stimulated alone. In parallel, two anti-inflammatory proteins, IL-10 and IL-13, showed higher secretion, especially upon CD146+ eMSC EXO exposure. Our study suggests that eMSC, and even more, the CD146+ subpopulation, possess exosomal secretomes with strong immunomodulatory miRNA attributes. The resulting evidence could serve as a foundation for eMSC EXO-based therapeutics for the resolution of detrimental aspects of tissue inflammation.

Background: While numerous studies have evaluated National Football League injuries, there is limited literature evaluating hamstring injuries sustained in games. Our primary aim is to analyze the effect of player position on the relative incidence of hamstring injuries in the National Football League. Our secondary aims are to analyze the effects of field surface, week of the season, and short rest weeks., Methods: Official National Football League game books containing injury data from the 2013-2016 regular seasons were used. Data were analyzed to determine the incidence of hamstring injuries by field surface, rest, and week of the season. Field surface was considered either turf or grass. Short rest was considered four days. Relative incidence of hamstring injuries by position was performed with standardized incidence ratios. P values < 0.05 were considered statistically significant., Results: Seventy-eight qualifying hamstring injuries were identified and included in our analysis. Linebackers had the highest relative incidence per play with a standardized incidence ratio of 2.02 (CI: 1.14-2.91), followed by Defensive Backs (1.62; 95% CI: 1.14-1.62). Offensive linemen and defensive linemen had standardized incidence ratios significantly less than 1. Fifty-seven percent of hamstring injuries occurred on turf fields (p = 0.082). There was no significant difference between the proportion of hamstring injuries that occurred on short rest and the proportion of games played on short rest (p = 0.959). Hamstring injuries were not more likely to occur than the pooled group of all other types of injuries on short rest (p = 0.861). With a 17-week season, the mean week of hamstring injury was 8.05 (95% CI: 7.06-9.04), while the median week was 7.5., Conclusions: Linebackers and Defensive Backs have the highest relative incidence of hamstring injuries compared to other position groups, while offensive and defensive linemen have the lowest. Field surface and a short rest period did not show significance., Competing Interests: None., (© 2022 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Background: Medial collateral ligament (MCL) injury is a common orthopaedic knee injury with a plethora of published articles regarding evaluation, treatment, and outcome., Purpose: To perform a comprehensive bibliometric analysis of the 50 most cited articles in MCL research., Study Design: Cross-sectional study., Methods: We performed a keyword search of the Institute for Scientific Information's Web of Knowledge database for the identification of articles published before September 2021 encompassing the MCL. The conducted search yielded 9534 articles. The results were then filtered using predetermined guidelines and criteria, and the 50 most cited articles were selected for analysis. Extracted data included title, authors, citation count, year of publication, topic, journal, article type, country of origin, and level of evidence., Results: The selected 50 articles ranged from 1976 to 2013. The largest proportion was classified as having level 4 evidence (n = 12; 24%). The majority of the articles were published in the decade from 2000 to 2009 (n = 17; 34%), followed by 1990 to 1999 (n = 16; 32%). The mean raw citation score per article was 133 (range, 74-422). The most popular topic discussed was surgical technique and outcome (n = 14; 28%), followed by anatomy and biomechanics (n = 13; 26%)., Conclusion: This study provides a comprehensive and objective measure of the most cited articles on MCL research. Knowledge of the characteristics of these most influential articles improves the understanding of MCL injury and can guide discussion for future research., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: L.D.K. has received education payments from Southern Edge Othopaedics and speaking fees and royalties from Arthrex. M.G.B. has received education payments, consulting fees, and speaking fees from Arthrex and hospitality payments from Smith & Nephew. 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) 2022.)

The treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved in recent years. Targeted therapy with Bruton's tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors has emerged as an effective chemotherapy-free option for patients with previously untreated or relapsed/refractory CLL/SLL. Undetectable minimal residual disease after the end of treatment is emerging as an important predictor of progression-free and overall survival for patients treated with fixed-duration BCL-2 inhibitor-based treatment. These NCCN Guidelines Insights discuss the updates to the NCCN Guidelines for CLL/SLL specific to the use of chemotherapy-free treatment options for patients with treatment-naïve and relapsed/refractory disease.

Purpose: To (1) identify the percentage of patients seen in an orthopaedic sports medicine practice who use social media and (2) identify the role that social media has in physician selection as compared with other factors., Methods: After institutional review board approval was received, new patients aged 18 years or older who attended a single orthopaedic sports medicine office from February 2020 to May 2021 were identified for inclusion. Sociodemographic information was recorded, and each patient was asked to fill out a questionnaire that assessed social media usage and online resources used to choose and formulate opinions regarding the patient's provider., Results: Two hundred patients met the inclusion criteria and completed the questionnaire. Of these, 96.5% reported social media use. The most common online method of searching for and identifying a physician was Google (50.5%). Social media outlets such as Facebook, Instagram, or LinkedIn were only used 15.5% of the time to search for and select a physician. Older patients were more likely to use recommendations from friends and family in their consideration when selecting a physician., Conclusions: Despite almost all participants stating that they use social media, only 15.5% of patients reported that they used social media to search for and potentially select their physician. Our study suggests that although social media can be a helpful tool for patient education, other factors such as physician education and physician reputation through word-of-mouth referrals, online reviews, and online ratings seem to play a larger role in the patient's selection of his or her physician., Clinical Relevance: This information may be of value to orthopaedic surgeons looking for ways to build their patient base, online reputation, or other aspects of their practice on the Internet., (© 2022 The Authors.)

Within the human knee infrapatellar fat pad (IFP) and synovium, resident synoviocytes and macrophages contribute to the onset and progression of inflammatory joint diseases. Our hypothesis is that IFP-derived mesenchymal stem cells (IFP-MSC) robust immunomodulatory therapeutic effects are largely exerted via their exosomal (IFP-MSC EXOs) secretome by attenuating synoviocytes and macrophages pro-inflammatory activation. IFP-MSC EXOs showed distinct miRNA and protein immunomodulatory profiles. Reactome analysis of 24 miRNAs highly present in exosomes showed their involvement in the regulation of six gene groups, including immune system. Exosomes were enriched for immunomodulatory and reparative proteins that are involved in positive regulation of cell proliferation, response to stimulus, signal transduction, signal receptor activity, and protein phosphorylation. Stimulated synoviocytes or macrophages exposed to IFP-MSC EXOs demonstrated significantly reduced proliferation, altered inflammation-related molecular profiles, and reduced secretion of pro-inflammatory molecules compared to stimulated alone. In an acute synovial/IFP inflammation rat model, IFP-MSC EXOs therapeutic treatment resulted in robust macrophage polarization towards an anti-inflammatory therapeutic M2 phenotype within the synovium/IFP tissues. Based on these findings, we propose a viable cell-free alternative to MSC-based therapeutics as an alternative approach to treating synovitis and IFP fibrosis., (© 2022. The Author(s).)

Purpose: To contribute to future quadriceps tendon harvest and fixation guidelines in the setting of anterior cruciate ligament reconstruction by comparing 2-year patient-reported subjective knee outcome scores and incidence of graft-related complications between the shorter harvest all-inside tibial-femoral suspensory fixation (TFSF) approach versus the longer harvest standard tibial interference screw fixation technique., Methods: Patients who underwent primary anterior cruciate ligament reconstruction with all soft tissue quadriceps tendon autograft from January 2017 to May 2019 were identified for inclusion. Patients were matched into 2 cohorts of 62 based on reconstruction technique. All patients completed baseline and minimum 2-year International Knee Documentation Committee, Tegner Activity Level, and Lysholm questionnaires and were queried regarding subsequent procedures and complications to the operative knee., Results: Average graft length for the all-inside TFSF was 69.55 (95% confidence interval 68.99-70.19) mm versus 79.27 (95% confidence interval 77.21-81.34) mm in the tibial screw fixation cohort (P = .00001). Two-year Lysholm scores were greater in the TFSF cohort (P = .04) but were not clinically significant. There was no difference in 2-year International Knee Documentation Committee (P = .09) or Tegner (P = .69) scores between cohorts, but more patients in the TFSF cohort returned to or exceeded their baseline activity level compared with the tibial screw fixation cohort (73% vs 61%, P = .25). Seven patients in the TFSF cohort versus 13 in the tibial screw fixation cohort reported anterior knee pain or kneeling difficulty (P = .22). There were no differences in reported complications., Conclusions: All-inside soft-tissue quadriceps tendon autograft with TFSF resulted in clinically comparable subjective outcome scores at 2 years to tibial screw fixation. There were also no differences in complications or reports of anterior knee pain or kneeling difficulty. All-inside TFSF can be a viable alternative to tibial screw fixation for all-soft tissue quadriceps autograft., Level of Evidence: III, comparative therapeutic trial., (Copyright © 2021 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Abstract: Burke, J, Geller, JS, Perez, JR, Naik, K, Vidal, AF, Baraga, MG, and Kaplan, LD. The effect of passing plays on injury rates in the national football league. J Strength Cond Res 35(12S): S1-S4, 2021-The National Football League (NFL) has one of the highest all-cause injury rates in sports, yet our understanding of extrinsic injury risk factors is limited. The objective of this study was to assess the effect of play type on injury incidence in the NFL. We obtained data for every regular season game played during the 2013-2016 seasons from the official NFL game books. There were 2,721 in-game injuries during the 4 seasons examined, with an overall rate of 1.33 injuries per team per game. For statistical analysis, p < 0.05 was considered significant. Passing plays conferred significantly higher odds of injury than running plays (odds ratio [OR] 1.4, 95% confidence interval [CI]: 1.3-1.5, p < 0.0001). This primarily stems from increased risks in quarterbacks (OR 6.9, 95% CI: 3.6-13.3, p < 0.0001), receivers (OR 5.0, 95% CI: 3.7-6.6, p < 0.0001), and defensive backs (OR 2.3, 95% CI: 1.9-2.7, p < 0.0001). Our study suggests that passing plays confer a greater risk of overall injuries in the NFL when compared with running plays, specifically regarding concussions and core or trunk injuries., (Copyright © 2021 National Strength and Conditioning Association.)

Background: Orthopedic specialties have begun to embrace telehealth as an alternative to in-person visits. We have not found studies assessing telehealth in sports medicine. Our goal is to evaluate patient perception of telehealth in an orthopedic sports medicine practice. Methods: Institutional review board (IRB) approval was obtained. The first 100 patients 18 years and older who had their initial videoconference telehealth appointment with our sports medicine providers from March to April 2020 were contacted at the conclusion of their visit. Surveys assessed satisfaction with telehealth, the provider, and whether attire played a role in their perception of the quality of the telehealth visit. Results: Patients on average stated excellent satisfaction with their visit (4.76 out of 5) and their provider (4.98 out of 5). Patients slightly disagreed with the notion that telehealth is equivalent to in-person provider visits (2.95 out of 5). This did not affect their perception to telehealth itself. It did not discourage patients from recommending telehealth or their provider to future patients. Patients overall felt that attire of the provider does not influence their opinion as to the standard of care they received. Returning patients versus new patient visits were more likely to recommend telehealth to others (4.83 vs. 4.56, p  = 0.04). The responses from both groups were overwhelmingly positive. Conclusion: Telehealth is a viable clinic option in an orthopedic sports medicine clinic. Patients who have seen providers in-person previously are more likely to recommend telehealth versus new patients. New patients were satisfied with their telehealth experience. Level of Evidence: IV.

Abstract: The past two decades have built on the successes of the Human Genome Project identifying the impact of genetics and genomics on human traits. Given the importance of exercise in the physical and psychological health of individuals across the lifespan, using genomics to understand the impact of genes in the sports medicine field is an emerging field. Given the complexity of the systems involved, high-throughput genomics is required to understand genetic variants, their functions, and ultimately their effect on the body. Consequently, genomic studies have been performed across several domains of sports medicine with varying degrees of success. While the breadth of these is great, they focus largely on the following three areas: 1) performance; 2) injury susceptibility; and 3) sports associated chronic conditions, such as osteoarthritis. Herein, we review literature on genetics and genomics in sports medicine, offer suggestions to bolster existing studies, and suggest ways to ideally impact clinical care., (Copyright © 2021 by the American College of Sports Medicine.)

The pathogenesis and progression of knee inflammatory pathologies is modulated partly by residing macrophages in the infrapatellar fat pad (IFP), thus, macrophage polarization towards pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes is important in joint disease pathologies. Alteration of M1/M2 balance contributes to the initiation and progression of joint inflammation and can be potentially altered with mesenchymal stem cell (MSC) therapy. In an acute synovial/IFP inflammation rat model a single intra-articular injection of IFP-MSC was performed, having as controls (1) diseased rats not receiving IFP-MSC and (2) non-diseased rats. After 4 days, cell specific transcriptional profiling via single-cell RNA-sequencing was performed on isolated IFP tissue from each group. Eight transcriptomically distinct cell populations were identified within the IFP across all three treatment groups with a noted difference in the proportion of myeloid cells across the groups. Largely myeloid cells consisted of macrophages (>90%); one M1 sub-cluster highly expressing pro-inflammatory markers and two M2 sub-clusters with one of them expressing higher levels of canonical M2 markers. Notably, the diseased samples (11.9%) had the lowest proportion of cells expressing M2 markers relative to healthy (14.8%) and MSC treated (19.4%) samples. These results suggest a phenotypic polarization of IFP macrophages towards the pro-inflammatory M1 phenotype in an acute model of inflammation, which are alleviated by IFP-MSC therapy inducing a switch towards an alternate M2 status. Understanding the IFP cellular heterogeneity and associated transcriptional programs may offer insights into novel therapeutic strategies for disabling joint disease pathologies.

Background: Quadriceps tendon (QT) autografts are increasingly popular for anterior cruciate ligament reconstruction (ACLR). However, no study has compared QT autografts with bone-patellar tendon-bone (BTB) autografts regarding the electromechanical delay (EMD), the peak torque (PT), and the rate of force development (RFD) in the superficial quadriceps muscles (rectus femoris [RF], vastus medialis [VM], and vastus lateralis [VL])., Hypotheses: We hypothesized (1) there would be a significantly lower PT, lower RFD, and longer quadriceps EMD of the operative limb for the QT versus the BTB autograft; (2) the PT, the RFD, and the quadriceps EMD of the operative limb would be significantly depressed compared with those of the nonoperative limb, regardless of the surgical technique; and (3) there would be greater increases in the RF EMD than in the VM or the VL EMD., Study Design: Cohort study; Level of evidence, 3., Methods: A total of 34 patients (age, 18-40 years), who had undergone ACLR (QT, n = 17; BTB, n = 17) at least 1 year before testing and performed 3 perceived maximal effort isometric tests, which were time synchronized with surface electromyography (EMG) on their operative and nonoperative limbs, were included in this study. EMD, PT, and RFD data were analyzed using a 2 (limb) × 2 (graft) × 3 (repetition) mixed repeated-measures analysis of variance., Results: The EMD, the PT, and the RFD were not significantly affected by graft choice. For the VL, a significant repetition × graft × limb interaction was detected for the VL EMD ( P = .027; ηp = 0.075), with repetition 3 having longer EMD than repetition 2 (mean difference [MD], 16 milliseconds; P = .039). For the RF EMD, there was a significant repetition × limb interaction ( P = .027; ηp = 0.074), with repetition 3 being significantly longer on the operative versus the nonoperative limb (MD, 24 milliseconds; P = .004). Further, the operative limb EMD was significantly longer for repetition 3 versus repetition 2 (MD, 17 milliseconds; P = .042). For the PT, there was a significant effect for repetition ( P = .003; ηp = 0.114), with repetition 1 being significantly higher than both repetitions 2 (MD, 8.52 N·m; P = .001) and 3 (MD, 7.79 N·m; P = .031). For the RFD, significant limb ( P = .034; ηp = 0.092) and repetition ( P = .010; ηp = 0.093) effects were seen, with the nonoperative limb being significantly faster than the operative limb (MD, 23.7 N·m/s; P = .034) and repetition 1 being significantly slower than repetitions 2 (MD, -20.46 N·m/s; P = .039) or 3 (MD, -29.85 N·m/s; P = .002)., Conclusion: The EMD, the PT, and the RFD were not significantly affected by graft type when comparing QT and BTB autografts for ACLR; however, all neuromuscular variables were affected regardless of the QT or the BTB harvest., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: M.G.B. has received education payments and consulting fees from Arthrex and hospitality payments from Smith & Nephew. T.M.B. has received hospitality payments from GE Healthcare. L.D.K. has received education payments and speaking fees from Arthrex and royalties from Smith & Nephew. 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) 2021.)

Our understanding of tendon biology continues to evolve, thus leading to opportunities for developing novel, evidence-based effective therapies for the treatment of tendon disorders. Implementing the knowledge of tendon stem/progenitor cells (TSPCs) and assessing their potential in enhancing tendon repair could fill an important gap in this regard. We described different molecular and phenotypic profiles of TSPCs modulated by culture density, as well as their multipotency and secretory activities. Moreover, in the same experimental setting, we evaluated for different responses to inflammatory stimuli mediated by TNFα and IFNγ. We also preliminarily investigated their immunomodulatory activity and their role in regulating degradation of substance P. Our findings indicated that TSPCs cultured at low density (LD) exhibited cobblestone morphology and a reduced propensity to differentiate. A distinctive immunophenotypic profile was also observed with high secretory and promising immunomodulatory responses when primed with TNFα and IFNγ. In contrast, TSPCs cultured at high density (HD) showed a more elongated fibroblast-like morphology, a greater adipogenic differentiation potential, and a higher expression of tendon-related genes with respect to LD. Finally, HD TSPCs showed immunomodulatory potential when primed with TNFα and IFNγ, which was slightly lower than that shown by LD. A shift from low to high culture density during TSPC expansion demonstrated intermediate features confirming the cellular adaptability of TSPCs. Taken together, these experiments allowed us to identify relevant differences in TSPCs based on culture conditions. This ability of TSPCs to acquire distinguished morphology, phenotype, gene expression profile, and functional response advances our current understanding of tendons at a cellular level and suggests responsivity to cues in their in situ microenvironment., 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., (Copyright © 2021 Perucca Orfei, Bowles, Kouroupis, Willman, Ragni, Kaplan, Best, Correa and de Girolamo.)

We report a first in-depth comparison of immune reconstitution in patients with HIV-related lymphoma following autologous hematopoietic cell transplant (AHCT) recipients (n=37, lymphoma, BEAM conditioning), HIV(-) AHCT recipients (n=30, myeloma, melphalan conditioning) at 56, 180, and 365 days post-AHCT, and 71 healthy control subjects. Principal component analysis showed that immune cell composition in HIV(+) and HIV(-) AHCT recipients clustered away from healthy controls and from each other at each time point, but approached healthy controls over time. Unsupervised feature importance score analysis identified activated T cells, cytotoxic memory and effector T cells [higher in HIV(+)], and naïve and memory T helper cells [lower HIV(+)] as a having a significant impact on differences between HIV(+) AHCT recipient and healthy control lymphocyte composition (p<0.0033). HIV(+) AHCT recipients also demonstrated lower median absolute numbers of activated B cells and lower NK cell sub-populations, compared to healthy controls (p<0.0033) and HIV(-) AHCT recipients (p<0.006). HIV(+) patient T cells showed robust IFNγ production in response to HIV and EBV recall antigens. Overall, HIV(+) AHCT recipients, but not HIV(-) AHCT recipients, exhibited reconstitution of pro-inflammatory immune profiling that was consistent with that seen in patients with chronic HIV infection treated with antiretroviral regimens. Our results further support the use of AHCT in HIV(+) individuals with relapsed/refractory lymphoma., Competing Interests: PS, Seattle Genetics, Research funding. AK, Celgene, Consultancy, Speakers Bureau, Millennium/Takeda, Consultancy, Speakers Bureau, Onyx, Consultancy, Speakers Bureau, Janssen, Consultancy, Speakers Bureau. Hofmeister, Signal Genetics, Inc., Membership on an entity’s Board of Directors or advisory committees, Celgene, Research Funding; Arno Therapeutics, Inc., Research Funding, Incyte, Corp, Membership on an entity’s Board of Directors or advisory committees, Janssen, Pharmaceutical Companies of Johnson & Johnson, Research Funding, Karyopharm Therapeutics, Research Funding, Takeda Pharmaceutical Company, Research Funding, Teva, Membership on an entity’s Board of Directors or advisory committees. SF, Mustang Therapeutics, Other, Construct licensed by City of Hope. WN, Atara Biotherapeutics, employment, stock ownership. GL, Boehringer Ingelheim, Research Funding, Beckman Coulter, Research Funding, Stemline Therapeutics Inc., Research Funding, Genentech. RB, Prelude Therapeutics, Research Funding and Scientific Advisory Board, Viracta, Scientific Advisory Board. AN, Janssen, Membership on a Board or Advisory Committee; Medscape, Honoraria; Morphosys, Membership on a Board or Advisory Committee; Pharmacyclics, Research Funding, Honoraria; Rafael Pharma, Research Funding; Epizyme, Membership on a Board or Advisory Committee; Physician Education Resource, Consulting. MM and AMM are employed by EMMES Company. The remaining 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., (Copyright © 2021 Shindiapina, Pietrzak, Seweryn, McLaughlin, Zhang, Makowski, Ahmed, Schlotter, Pearson, Kitzler, Mozhenkova, Le-Rademacher, Little, Akpek, Ayala, Devine, Kaplan, Noy, Popat, Hsu, Morris, Mendizabal, Krishnan, Wachsman, Williams, Sharma, Hofmeister, Forman, Navarro, Alvarnas, Ambinder, Lozanski and Baiocchi.)

Purpose: Patients with non-Hodgkin lymphoma (NHL) have a median age of 67, with 70% surviving over 5 years. Chemotherapy for aggressive NHL includes cyclophosphamide, anthracycline, and high doses of corticosteroids, which can impair bone health. By reviewing clinical characteristics and standard-of-care CT scans, we evaluate the prevalence and incidence of fractures and the clinical correlates of fractures in patients treated for aggressive B-cell NHL., Methods: We retrospectively reviewed patients seen at the University of California San Francisco lymphoma clinic from January 1, 2016, to March 31, 2017 who had (1) aggressive B-cell NHL, (2) received first-line therapy with R-CHOP-like regimens, and had (3) CT scans pre- and post-treatment available for review. Associations between clinical variables and vertebral, rib, and pelvic fracture outcomes were assessed, and multivariate logistic regression models were used to identify predictors of prevalent and incident fractures., Results: We identified 162 patients who met the inclusion criteria. Median age at diagnosis was 60 years. Of the 162 patients, 38 patients (28%) had prevalent fractures prior to receiving chemotherapy. Within 1 year after treatment, 16 patients (10%) developed new fractures. Having a prevalent fracture strongly predicted developing a new fracture after treatment, with incident fractures occurring in 12 of 38 patients with prevalent fractures versus 4 of 124 without prevalent fractures (odds ratio 10.45, p<0.0005)., Conclusion: Our results suggest that patients with aggressive B-cell NHL who receive R-CHOP-like therapy should be screened for fractures prior to treatment and those with existing fractures should be considered for therapy to decrease risk of new fractures., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Context: Management of isolated grade III medial collateral ligament injuries is controversial, as both nonoperative and operative management can result in return to play. However, operative management is recommended in elite athletes who have a grade III injury with distal avulsion., Objective: We present a standardized rehabilitation protocol in a case series of 7 National Collegiate Athletic Association Division I American football athletes who sustained grade III distal medial collateral ligament tears that were repaired operatively, with emphasis on return to play., Results: Median time to surgery was 4 days (range = 2-67 days). Median time from surgery to noncontact drills was 120.5 days (range = 104-168 days), and median time from surgery to full-contact sport was 181 days (range = 139-204 days). All athletes returned to play at their preinjury level of competition., Conclusions: Our study highlighted how operative management with a standardized rehabilitation protocol can be applied to Division I football players and result in safe return to play., (© by the National Athletic Trainers' Association, Inc.)

Objectives: We sought to examine the natural history of geriatric assessment (GA) and quality of life (QOL) domains among adults age ≥ 50 years undergoing autologous hematopoietic cell transplantation (autoHCT)., Materials and Methods: A QOL tool and cancer-specific GA were completed before autoHCT in patients ≥50 years, and at 100 days, six months, and one year post-transplant., Results: One hundred eighty-four patients completed the pre-transplant QOL/GA assessment, 169 (92%) completed the 100-day assessment, 162 (88%) completed the six-month assessment, and 145 (79%) completed the twelve-month assessment. Functional status, as measured by instrumental activities of daily living (IADL), decreased from baseline to day 101 (mean change -0.42 points, 95% CI, -0.75 to -0.09, p = 0.01) but returned to baseline by one year. Physical function as measured by Medical Outcomes Study-Physical Health (MOS-PH) increased by mean of 3.27 points (95% CI, -0.02 to 6.56, p = 0.05) by one year. Physician-rated KPS improved by one year, but patient-rated KPS did not. No QOL metric deteriorated from baseline. Baseline factors predictive of IADL and MOS-PH as measured over time included comorbidities and disease status at transplant. IADL and MOS-PH as measured over time were not significantly associated with age., Conclusions: AutoHCT for adults age ≥ 50 years resulted in an initial decrease in functional status, with subsequent improvement back to baseline by one year. Physical health and QOL measures were improved or unchanged over time. AutoHCT is well tolerated in well selected older patients, using patient reported geriatric metrics as outcomes., Competing Interests: Declaration of Competing Interest Rebecca Olin was supported in this work by a Hellman Family Award for Early-Career Faculty, 2013–2014. Dr. Andreadis reports personal fees from Genentech, grants from Novartis, grants from Celgene/Juno, grants from Amgen, grants from Merck, personal fees from Gilead/Kite, personal fees from Jazz Pharmaceuticals, personal fees from Astellas, personal fees from Seattle Genetics, outside the submitted work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Meniscal injuries are among the most common orthopaedic injuries, with a significant volume of published literature., Purpose: To perform a comprehensive bibliometric analysis that appropriately evaluates the 50 most cited articles in meniscal research., Study Design: Cross-sectional study., Methods: We performed a keyword search of the ISI Web of Knowledge database and then pared the results down to the 50 most cited articles using specific inclusion and exclusion criteria. Data extracted included title, first author, citation count, year of publication, topic, journal, article type, country of origin, and level of evidence. Correlation coefficients were calculated between publication date and citation density and between publication date and raw citation count., Results: The 50 most cited articles were published from 1975 to 2013. The mean number of citations was 258.24 (range, 163-926; median, 225). The majority of articles were published in The American Journal of Sports Medicine (19%), the Journal of Bone and Joint Surgery (12%), and Arthritis & Rheumatology (14%). Most articles focused on either the anatomy and biomechanics of meniscal injury or on prevention and physical rehabilitation (12 papers each)., Conclusion: The most popular fields of meniscal research involved anatomy/biomechanics and prevention/rehabilitation, and both are areas that will likely increase the probability of an article's being highly cited in the future. This study provided a quality selection of the most cited articles on meniscal injury and may provide a foundation for both beginner and senior clinician readers for further discussion and research., Competing Interests: One or more of the authors has declared the following potential conflicts of interest or source of funding: D.D. has received education payments from Southern Edge Orthopaedics. M.G.B. has received education payments from Arthrex and Southern Edge Orthopaedics; consulting fees and nonconsulting fees from Arthrex; and hospitality payments from Smith & Nephew. L.D.K. has received education payments from Arthrex and Southern Edge Orthopaedics; nonconsulting fees from Arthrex; and royalties from Arthrex and Smith & Nephew. 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) 2021.)

Four cycles of rituximab plus CHOP chemotherapy is as effective as 6 cycles in low-risk diffuse large B-cell lymphoma (DLBCL). Here we report a post-hoc analysis of a prospective clinical trial in patients with HIV-associated DLBCL and high-grade lymphoma treated with 4-6 cycles of EPOCH plus rituximab based a response-adapted treatment strategy. 106 evaluable patients with HIV-associated DLBCL or high-grade CD20-positive non-Hodgkin's lymphoma were randomized to receive rituximab (375 mg/m2) given either concurrently prior to each infusional EPOCH cycle, or sequentially (weekly for 6 weeks) following completion of EPOCH. EPOCH consisted of a 96-hour IV infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by IV bolus cyclophosphamide every 21 days for 4 to 6 cycles. Patients received 2 additional cycles of therapy after documentation of a complete response (CR) by computerized tomography after cycles 2 and 4. 64 of 106 evaluable patients (60%, 95% CI 50%, 70%) had a CR in both treatment arms. The 2-year event-free survival (EFS) rates were similar in the 24 patients with CR who received 4 or fewer EPOCH cycles (78%, 95% confidence intervals [55%, 90%]) due to achieving a CR after 2 cycles, compared with those who received 5-6 cycles of EPOCH (85%, 95% CI 70%, 93%) because a CR was first documented after cycle 4. A response-adapted strategy may permit a shorter treatment duration without compromising therapeutic efficacy in patients with HIV-associated lymphoma treated with EPOCH plus rituximab, which merits further evaluation in additional prospective trials. Clinical Trials.gov identifier NCT00049036.

Introduction: We designed a multicenter, phase Ib dose-escalation trial of carfilzomib with bendamustine and rituximab in patients with relapsed/refractory non-Hodgkin lymphoma (NCT02187133) in order to improve the response rates of this difficult-to-treat population. Chemoimmunotherapy with bendamustine and rituximab has shown activity in a variety of lymphomas, and proteasome inhibitors have demonstrated pre-clinical synergy and early clinical activity in this population. The objectives were to determine the maximum tolerated dose of carfilzomib and the preliminary efficacy of this combination., Patients and Methods: The protocol followed a 3+3 design of carfilzomib dose escalation combined with standard doses of bendamustine and rituximab. Patients were treated for up to 6 cycles with an interim positron emission tomography/computed tomography after cycle 3., Results: Ten patients were treated on the dose-escalation phase. The study was terminated at a carfilzomib dose of 56 mg/m 2 , and the maximum tolerated dose was not reached. The most common grade 3/4 adverse event was thrombocytopenia. There was 1 dose-limiting toxicity observed, grade 3 febrile neutropenia, and there were no treatment-related deaths. The overall response rate was 40% (complete response rate, 30%), with a median duration of response of 12 months and a median progression-free survival of 2.1 months., Conclusion: Carfilzomib in combination with bendamustine and rituximab is a safe and well-tolerated treatment for patients with relapsed/refractory non-Hodgkin lymphoma. Preliminary data indicate that this combination may have efficacy with an acceptable side effect profile in this heavily pre-treated patient population with limited treatment options., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To identify and evaluate the top 50 most-cited articles pertaining to SLAP tears., Methods: The ISI Web of Knowledge database was used to conduct a query for articles pertaining to SLAP tears. Our query was conducted in April 2020 with multiple Boolean operative combinations performed by 2 independent reviewers. Articles on the final list were further reviewed to extract the following data: manuscript title, first author, total citation count, year of publication, citation density since publication, current citation rate since 2013, journal, country of origin, and level of evidence., Results: Our initial search yielded 2,597 articles. Within this cohort, the top 50 publications pertaining to SLAP tears were identified that met our search criteria. The top article was cited 802 times while the 50th ranked article was cited 46 times. The average number of citations per publication was 131, whereas the average citation density since year of publication was 7.3. No strong correlations were found between citation density and year published. Twelve journals published articles pertaining to SLAP tears, with Arthroscopy accounting for the greatest number (15 articles, 30%). Most articles were graded with a level of evidence (LOE) of IV (n = 24, 48%), followed by review articles without LOE (n = 8, 16%). Only 2 articles achieved an LOE of I (4%). Articles typically addressed the arthroscopic management (n = 11, 22%), whereas anatomy/classification (n =10, 20%), and outcomes (n = 9, 18%) also were reported., Conclusions: This review provides a quantitative analysis of the most-referenced literature pertaining to SLAP tears. This body of knowledge helps surgeons search for literature regarding these injuries and identify trends regarding SLAP tear research., Clinical Relevance: This research provides practitioners with an easily accessible and comprehensive collection of the major contributions regarding SLAP tears and offers insight into future areas for research., (© 2020 by the Arthroscopy Association of North America. Published by Elsevier Inc.)

Background: To investigate the in vitro and in vivo anti-inflammatory/anti-fibrotic capacity of IFP-MSC manufactured as 3D spheroids. Our hypothesis is that IFP-MSC do not require prior cell priming to acquire a robust immunomodulatory phenotype in vitro in order to efficiently reverse synovitis and IFP fibrosis, and secondarily delay articular cartilage damage in vivo., Methods: Human IFP-MSC immunophenotype, tripotentiality, and transcriptional profiles were assessed in 3D settings. Multiplex secretomes were assessed in IFP-MSC spheroids [Crude (non-immunoselected), CD146 + or CD146 - immunoselected cells] and compared with 2D cultures with and without prior inflammatory/fibrotic cell priming. Functionally, IFP-MSC spheroids were assessed for their immunopotency on human PBMC proliferation and their effect on stimulated synoviocytes with inflammation and fibrotic cues. The anti-inflammatory and anti-fibrotic spheroid properties were further evaluated in vivo in a rat model of acute synovitis/fat pad fibrosis., Results: Spheroids enhanced IFP-MSC phenotypic, transcriptional, and secretory immunomodulatory profiles compared to 2D cultures. Further, CD146 + IFP-MSC spheroids showed enhanced secretory and transcriptional profiles; however, these attributes were not reflected in a superior capacity to suppress activated PBMC. This suggests that 3D culturing settings are sufficient to induce an enhanced immunomodulatory phenotype in both Crude and CD146-immunoselected IFP-MSC. Crude IFP-MSC spheroids modulated the molecular response of synoviocytes previously exposed to inflammatory cues. Therapeutically, IFP-MSC spheroids retained substance P degradation potential in vivo, while effectively inducing resolution of inflammation/fibrosis of the synovium and fat pad. Furthermore, their presence resulted in arrest of articular cartilage degradation in a rat model of progressive synovitis and fat pad fibrosis., Conclusions: 3D spheroids confer IFP-MSC a reproducible and enhanced immunomodulatory effect in vitro and in vivo, circumventing the requirement of non-compliant cell priming or selection before administration and thereby streamlining cell products manufacturing protocols.