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Rotator cuff tears represent a large burden of muscle-tendon injuries in our aging population. While small tears can be repaired surgically with good outcomes, critical size tears are marked by muscle atrophy, fibrosis, and fatty infiltration, which can lead to failed repair, frequent re-injury, and chronic disability. Previous animal studies have indicated that Transforming Growth Factor-β (TGF-β) signaling may play an important role in the development of these muscle pathologies after injury. Here, we demonstrated that inhibition of TGF-β1 signaling with the small molecule inhibitor SB431542 in a mouse model of massive rotator cuff tear results in decreased fibrosis, fatty infiltration, and muscle weight loss. These observed phenotypic changes were accompanied by decreased fibrotic, adipogenic, and atrophy-related gene expression in the injured muscle of mice treated with SB431542. We further demonstrated that treatment with SB431542 reduces the number of fibro/adipogenic progenitor (FAP) cells-an important cellular origin of rotator cuff muscle fibrosis and fatty infiltration, in injured muscle by promoting apoptosis of FAPs. Together, these data indicate that the TGF-β pathway is a critical regulator of the degenerative muscle changes seen after massive rotator cuff tears. TGF-β promotes rotator cuff muscle fibrosis and fatty infiltration by preventing FAP apoptosis. TGF-β regulated FAP apoptosis may serve as an important target pathway in the future development of novel therapeutics to improve muscle outcomes following rotator cuff tear.

Background: Early sport specialization is not a requirement for success at the highest levels of competition and is believed to be unhealthy physically and mentally for young athletes. It also discourages unstructured free play, which has many benefits. Purpose: To review the available evidence on early sports specialization and identify areas where scientific data are lacking. Study Design: Think tank, roundtable discussion. Results: The primary outcome of this think tank was that there is no evidence that young children will benefit from early sport specialization in the majority of sports. They are subject to overuse injury and burnout from concentrated activity. Early multisport participation will not deter young athletes from long-term competitive athletic success. Conclusion: Youth advocates, parents, clinicians, and coaches need to work together with the sport governing bodies to ensure healthy environments for play and competition that do not create long-term health issues yet support athletic competition at the highest level desired.

Tears within the stabilizing muscles of the shoulder, known as the rotator cuff (RC), are the most common cause of shoulder pain—often presenting in older patients and requiring expensive advanced imaging for diagnosis. Despite the high prevalence of RC tears within the elderly population, there is no previously published work examining shoulder kinematics using markerless motion capture in the context of shoulder injury. Here we show that a simple string pulling behavior task, where subjects pull a string using hand-over-hand motions, provides a reliable readout of shoulder mobility across animals and humans. We find that both mice and humans with RC tears exhibit decreased movement amplitude, prolonged movement time, and quantitative changes in waveform shape during string pulling task performance. In rodents, we further note the degradation of low dimensional, temporally coordinated movements after injury. Furthermore, a logistic regression model built on our biomarker ensemble succeeds in classifying human patients as having a RC tear with > 90% accuracy. Our results demonstrate how a combined framework bridging animal models, motion capture, convolutional neural networks, and algorithmic assessment of movement quality enables future research into the development of smartphone-based, at-home diagnostic tests for shoulder injury.

Background Macrophage polarization has been observed in the process of muscle injuries including rotator cuff (RC) muscle atrophy and fatty infiltration after large tendon tears. In our previous study, we showed that fibrogenesis and white adipogenesis of muscle residential fibro/adipogenic progenitors (FAPs) cause fibrosis and fatty infiltration and that brown/beige adipogenesis of FAPs promotes rotator cuff muscle regeneration. However, how polarized macrophages and their exosomes regulate FAP differentiation remains unknown. Methods We cultured FAPs with M0, M1, and M2 macrophages or 2 × 10 9 exosomes derived from M0, M1 and M2 with and without GW4869, an exosome inhibitor. In vivo, M0, M1, and M2 macrophages were transplanted or purified macrophage exosomes (M0, M1, M2) were injected into supraspinatus muscle (SS) after massive tendon tears in mice ( n  = 6). SS were harvested at six weeks after surgery to evaluate the level of muscle atrophy and fatty infiltration. Results Our results showed that M2 rather than M0 or M1 macrophages stimulates brown/beige fat differentiation of FAPs. However, the effect of GW4869, the exosome inhibitor, diminished this effect. M2 exosomes also promoted FAP Beige differentiation in vitro. The transplantation of M2 macrophages reduced supraspinatus muscle atrophy and fatty infiltration. In vivo injections of M2 exosomes significantly reduced muscle atrophy and fatty infiltration in supraspinatus muscle. Conclusion Results from our study demonstrated that polarized macrophages directly regulated FAP differentiation through their exosomes and M2 macrophage-derived exosomes may serve as a novel treatment option for RC muscle atrophy and fatty infiltration.

Mechanical stimuli, such as stretch, shear stress, or compression, activate a range of biomolecular responses through cellular mechanotransduction. In the nervous system, studies on mechanical stress have highlighted key pathophysiological mechanisms underlying traumatic injury and neurodegenerative diseases. However, the biomolecular pathways triggered by mechanical stimuli in the nervous system has not been fully explored, especially compared to other body systems. This gap in knowledge may be due to the wide variety of methods and definitions used in research. Additionally, as mechanical stimulation techniques such as ultrasound and electromagnetic stimulation are increasingly utilized in psychological and neurorehabilitation treatments, it is vital to understand the underlying biological mechanisms in order to develop accurate pathophysiological models and enhance therapeutic interventions. This review aims to summarize the cellular signaling pathways activated by various mechanical and electromagnetic stimuli with a particular focus on the mammalian nervous system. Furthermore, we briefly discuss potential cellular mechanosensors involved in these processes.

Background: Mild to moderate glenohumeral joint osteoarthritis is a common finding among patients who are evaluated for rotator cuff tears. However, the impact of preoperative shoulder joint degeneration on patient-reported outcomes after rotator cuff repair (RCR) is not well-established. Purpose: To apply the magnetic resonance imaging (MRI)–based Shoulder Osteoarthritis Severity (SOAS) score to the evaluation of patients undergoing RCR and determine the relationship between preoperative shoulder pathology present on MRI and postoperative Patient-Reported Outcomes Measurement Information System–Upper Extremity (PROMIS-UE) scores. Study Design: Case-control study; Level of evidence, 3. Methods: Seventy-one MRI scans corresponding to 71 patients were analyzed by 2 independent reviewers and scored using the SOAS criteria. Intraclass correlation coefficients were calculated for total SOAS score as well as for each subscore. Spearman correlations were calculated between averaged SOAS scores, patient characteristics, and PROMIS-UE scores. Linear regression analysis was performed between the independent variables of patient age, sex, body mass index, and significant SOAS score components determined by univariate analysis with the dependent variable of PROMIS-UE score. Significance was defined as P < .05 for univariate analyses and < .0125 for multivariate analyses using the Bonferroni correction. Results: The mean PROMIS-UE score of this cohort was 51.5 ± 7.4, while the mean total SOAS score was 21.5 ± 8.4. There was a negative correlation between total SOAS score and postoperative PROMIS-UE score (r = –0.24; P = .040). Both cartilage wear (r = –0.33; P = .0045) and acromioclavicular joint degeneration (r = –0.24; P = .048) individually demonstrated negative correlations with PROMIS-UE score. When a multivariate linear regression with Bonferroni correction was applied to the significant variables identified in univariate analysis along with patient characteristics, none were independently correlated with PROMIS-UE score. Conclusion: In this cohort of patients undergoing RCR, increasing preoperative total SOAS score was predictive of lower postoperative PROMIS-UE scores. SOAS subscores with the strongest negative correlations with PROMIS-UE scores included cartilage wear and acromioclavicular joint degeneration. The cartilage subscore was negatively correlated with PROMIS-UE scores independent of patient factors in multivariate analysis.

To compare preoperative femoral (FNB) with combined femoral and sciatic nerve block (CFSNB) in patients undergoing arthroscopic anterior cruciate ligament (ACL) reconstruction. Prospective, randomized clinical trial. Ambulatory surgery center affiliated with an academic medical center. Sixty-eight American Society of Anesthesiology physical status I and II patients undergoing arthroscopic ACL reconstruction. Subjects randomized to the CFSNB group received combined femoral and sciatic nerve blocks preoperatively, whereas patients randomized to the FNB group only received femoral nerve block preoperatively. Both groups then received a standardized general anesthetic with a propofol induction followed by sevoflurane or desflurane maintenance. Intraoperative pain was treated with fentanyl. Pain in the postanesthesia care unit (PACU) was treated with ketorolac and opiates. Patients with significant pain despite ketorolac and opiates could receive a rescue nerve block. Our primary outcome variable was highest Numeric Rating Scale (NRS) pain score in PACU. NRS pain scores, opioid consumption, opioid adverse effects, and patient satisfaction were assessed perioperatively until postoperative day 3. The highest PACU NRS pain score was significantly higher in the FNB group compared with the CFSNB group (7 [3-10] vs 5 [0-10], P=.002). The FNB group required significantly larger doses of opioids perioperatively (31.8 vs 19.8mg intravenous morphine equivalents, P<.001). PACU length of stay was significantly longer in the FNB group (128.2 vs 103.1minutes, P=.006). There was no significant difference in opioid consumption, pain scores, or patient satisfaction on postoperative days 1-3 between groups. Preoperative CFSNB for arthroscopic ACL reconstruction improves analgesia, decreases opioid consumption perioperatively, and decreases PACU length of stay when compared with FNB alone. •Femoral block alone before ACL surgery leads to more PACU analgesic interventions.•We compared preoperative femoral block with femoral-sciatic block for ACL surgery.•Preoperative femoral-sciatic block for ACL reconstruction improves analgesia.•It also decreases opioid consumption and decreases PACU length of stay.•These differences are limited to the day of surgery.

Background: Current evaluation of muscle fatty infiltration has been limited by subjective classifications. Quantitative fat evaluation through magnetic resonance imaging (MRI) may allow for an improved longitudinal evaluation of the effect of surgical repair on the progression of fatty infiltration. Hypotheses: We hypothesized that (1) patients with isolated full-thickness supraspinatus tendon tears would have less progression in fatty infiltration compared with patients with full-thickness tears of multiple tendons and (2) patients with eventual failed repair would have higher baseline levels of fatty infiltration. Study Design: Cohort study; Level of evidence, 2. Methods: Thirty-five patients with full-thickness rotator cuff tears were followed longitudinally. All patients received a shoulder MRI, including the iterative decomposition of echoes of asymmetric length (IDEAL) sequence for fat measurement, prior to surgical treatment and at 6 months after surgical repair. Fat fractions were recorded for all 4 rotator cuff muscles from measurements on 4 sagittal slices centered at the scapular-Y. Demographics and tear characteristics were recorded. Baseline and follow-up fat fractions were compared for patients with isolated supraspinatus tears versus multitendon tears and for patients with intact repairs versus failed repairs. Statistical significance was set at P < .05. Results: The mean fat fractions were significantly higher at follow-up than at baseline for the supraspinatus (9.8% ± 7.0% vs 8.3% ± 5.7%; P = .025) and infraspinatus (7.4% ± 6.1% vs 5.7% ± 4.4%; P = .027) muscles. Patients with multitendon tears showed no significant change for any rotator cuff muscle after repair. Patients with isolated supraspinatus tears showed a significant progression in the supraspinatus fat fraction from baseline to follow-up (from 6.8% ± 4.9% to 8.6% ± 6.8%; P = .0083). Baseline supraspinatus fat fractions were significantly higher in patients with eventual failed repairs compared with those with intact repairs (11.7% ± 6.8% vs 7.1% ± 4.8%; P = .037). Conclusion: Contrary to our initial hypothesis, patients with isolated supraspinatus tears showed a significant progression of fatty infiltration. Patients with eventual repair failure had higher baseline fat fractions in the supraspinatus.

Absract Background Paraspinal muscles are crucial for vertebral stabilization and movement. These muscles are prone to develop fatty infiltration (FI), fibrosis, and atrophy in many spine conditions. Fibro‐adipogenic progenitors (FAPs), a resident muscle stem cell population, are the main contributors of muscle fibrosis and FI. FAPs are involved in a complex interplay with satellite cells (SCs), the primary myogenic progenitor cells within muscle. Little is known about the stem cell composition of the multifidus. The aim of this study is to examine FAPs and SCs in the multifidus in disc herniation patients. Multifidus muscle samples were collected from 10 patients undergoing decompressive spine surgery for lumbar disc herniation. Hamstring muscle was collected from four patients undergoing hamstring autograft ACL reconstruction as an appendicular control. Multifidus tissue was analyzed for FI and fibrosis using Oil‐Red‐O and Masson's trichrome staining. FAPs and SCs were visualized using immunostaining and quantified with fluorescence‐activated cell sorting (FACS) sorting. Gene expression of these cells from the multifidus were analyzed with reverse transcription‐polymerase chain reaction and compared to those from hamstring muscle. FI and fibrosis accounted for 14.2%± 7.4% and 14.8%±4.2% of multifidus muscle, respectively. The multifidus contained more FAPs (11.7%±1.9% vs 1.4%±0.2%; P<.001) and more SCs (3.4%±1.6% vs 0.08%±0.02%; P=.002) than the hamstring. FAPs had greater α Smooth Muscle Actin (αSMA) and adipogenic gene expression than FAPs from the hamstring. SCs from the multifidus displayed upregulated expression of stem, proliferation, and differentiation genes. Conclusion The multifidus in patients with disc herniation contains large percentages of FAPs and SCs with different gene expression profiles compared to those in the hamstring. These results may help explain the tendency for the multifidus to atrophy and form FI and fibrosis as well as elucidate potential approaches for mitigating these degenerative changes by leveraging these muscle stem cell populations. Paraspinal muscles are known to develop muscle fatty infiltration (FI), fibrosis, and atrophy in a number of spine conditions, including intervertebral disc herniation. In this study, we histologically examined multifidus muscle specimens harvested from patients undergoing spine surgery for the degree of degenerative muscle pathology and characterized fibro‐adipogenic progenitors (FAPs) and Satellite cells (SCs) within the muscle in terms of quantity and gene expression profiles. We discovered a high degree of FI and fibrosis in the multifidus as well as large quantities of FAPs and SCs that displayed different gene expression profiles than those taken from healthy hamstring muscle controls.

Purpose Little is known about the early changes in cartilage composition and tibiofemoral kinematics following partial meniscectomy. The purpose of this study was to determine the effects of partial meniscectomy on cartilage compositional properties using T1 ρ and T 2 relaxation time mapping and to assess changes in tibiofemoral kinematics. It is hypothesize that abnormal tibiofemoral kinematics and relaxation time elevation (a reflection of changes in cartilage biochemical composition) in the weight-bearing regions of the knees following meniscectomy will be observed. Methods Nine patients (7 males and 2 females; mean age, 48.6 ± 10.8 years; BMI = 27.3 ± 3.8 kg/m 2 ) with tears of the posterior horn of the medial meniscus underwent arthroscopic partial meniscectomy. Pre-surgical and 6 months post-surgical MRIs were obtained in all subjects to evaluate cartilage relaxation times and tibiofemoral kinematics. Paired t tests were performed to determine significant changes in cartilage relaxation times from baseline. Results T 1ρ relaxation time in the region of the medial femoral condyle directly adjacent to the resection showed an increase of 7.4 % at 6 months ( p  = 0.02). T 2 relaxation times in both the medial and lateral tibial plateaus showed significant elevation at 6 months. Consistent kinematic trends were not found in post-meniscectomized knees. Conclusions These results suggest that arthroscopic partial meniscectomy affects the biochemical composition of articular cartilage in the knee in as early as 6 months. The largest responses were observed in the weight-bearing regions and the cartilage immediately adjacent to the resection. This suggests that the loading environment has been altered enough to result in cartilage compositional changes in a very brief period of time following meniscectomy. Level of evidence IV.