Andrew R. Jensen

Skeletal and cardiac muscle pericytes: Functions and therapeutic potential

Pericytes are periendothelial mesenchymal cells residing within the microvasculature. Skeletal muscle and cardiac pericytes are now recognized to fulfill an increasing number of functions in normal tissue homeostasis, including contributing to microvascular function by maintaining vessel stability and regulating capillary flow. In the setting of muscle injury, pericytes contribute to a regenerative microenvironment through release of trophic factors and by modulating local immune responses. In skeletal muscle, pericytes also directly enhance tissue healing by differentiating into myofibers. Conversely, pericytes have also been implicated in the development of disease states, including fibrosis, heterotopic ossication and calcification, atherosclerosis, and tumor angiogenesis. Despite increased recognition of pericyte heterogeneity, it is not yet clear whether specific subsets of pericytes are responsible for individual functions in skeletal and cardiac muscle homeostasis and disease.

Perivascular stem cells diminish muscle atrophy following massive rotator cuff tears in a small animal model

Background: Rotator cuff tears are a common cause of shoulder pain and often necessitate operative repair. Muscle atrophy, fibrosis, and fatty infiltration can develop after rotator cuff tears, which may compromise surgical outcomes. This study investigated the regenerative potential of 2 human adipose-derived progenitor cell lineages in a murine model of massive rotator cuff tears. Methods: Ninety immunodeficient mice were used (15 groups of 6 mice). Mice were assigned to 1 of 3 surgical procedures: sham, supraspinatus and infraspinatus tendon transection (TT), or TT and denervation via suprascapular nerve transection (TT + DN). Perivascular stem cells (PSCs) were harvested from human lipoaspirate and sorted using fluorescence-activated cell sorting into pericytes (CD146+ CD34− CD45− CD31−) and adventitial cells (CD146− CD34+ CD45− CD31−). Mice received no injection, injection with saline solution, or injection with pericytes or adventitial cells either at the time of the index procedure (“prophylactic”) or at 2 weeks following the index surgery (“therapeutic”). Muscles were harvested 6 weeks following the index procedure. Wet muscle weight, muscle fiber cross-sectional area, fibrosis, and fatty infiltration were analyzed. Results: PSC treatment after TT (prophylactic or therapeutic injections) and after TT + DN (therapeutic injections) resulted in less muscle weight loss and greater muscle fiber cross-sectional area than was demonstrated for controls (p < 0.05). The TT + DN groups treated with pericytes at either time point or with adventitial cells at 2 weeks postoperatively had less fibrosis than the TT + DN controls. There was less fatty infiltration in the TT groups treated with pericytes at either time point or with adventitial cells at the time of surgery compared with controls. Conclusions: Our findings demonstrated significantly less muscle atrophy in the groups treated with PSCs compared with controls. This suggests that the use of PSCs may have a role in the prevention of muscle atrophy without leading to increased fibrosis or fatty infiltration. Clinical Relevance: Improved muscle quality in the setting of rotator cuff tears may increase the success rates of surgical repair and lead to superior clinical outcomes.

Injuries Sustained by the Mixed Martial Arts Athlete

Context: Mixed martial arts (MMA) is rapidly growing in popularity in the United States and abroad. This combat sport joins athletes from a wide variety of martial art disciplines, each with characteristic and distinguishing injury profiles, together in competition. Because of increasing participation by professionals and amateurs alike, injuries sustained by MMA athletes have been on the rise. Evidence Acquisition: A review of relevant publications using the search term mixed martial arts and each of its component combat sports (eg, Muay Thai, Brazilian jiu-jitsu) from 1980 through 2015 was completed using PubMed and Google Scholar. Study Design: Clinical review. Level of Evidence: Level 5. Results: The majority of studies on MMA injuries evaluate those sustained during competition, which range in incidence from 22.9 to 28.6 per 100 fight-participations. Striking-predominant disciplines such as boxing, karate, and Muay Thai have high rates of head and facial injuries, whereas submission-predominant disciplines such as Brazilian jiu-jitsu, judo, and wrestling have high rates of joint injuries. Conclusion: Numerous studies have evaluated injuries in athletes who participate in MMA and its component disciplines during competition but much remains to be discovered about injuries sustained during training and in specific patient populations such as adolescents and women.

Evaluation of the Trends, Concomitant Procedures, and Complications With Open and Arthroscopic Rotator Cuff Repairs in the Medicare Population:

Background: Medicare insures the largest population of patients at risk for rotator cuff tears in the United States. Purpose: To evaluate the trends in incidence, concomitant procedures, and complications with open and arthroscopic rotator cuff repairs in Medicare patients. Study Design: Cohort study; Level of evidence, 3. Methods: All Medicare patients who had undergone open or arthroscopic rotator cuff repair from 2005 through 2011 were identified with a claims database. Annual incidence, concomitant procedures, and postoperative complications were compared between these 2 groups. Results: In total, 372,109 rotator cuff repairs were analyzed. The incidence of open repairs decreased (from 6.0 to 4.3 per 10,000 patients, P < .001) while the incidence of arthroscopic repairs increased (from 4.5 to 7.8 per 10,000 patients, P < .001) during the study period. Patients in the arthroscopic group were more likely to have undergone concomitant subacromial decompression than those in the open group (87% vs 35%, P < .001), and the annual incidence of concomitant biceps tenodesis increased for both groups (from 3.8% to 11% for open and 2.2% to 16% for arthroscopic, P < .001). While postoperative complications were infrequent, patients in the open group were more likely to be diagnosed with infection within 6 months (0.86% vs 0.37%, P < .001) but no more likely to undergo operative debridement (0.43% vs 0.26%, P = .08). Additionally, patients in the open group were more likely to undergo intervention for shoulder stiffness within 1 year (1.4% vs 1.1%, P = .01). Conclusion: In the Medicare population, arthroscopic rotator cuff repairs have increased in incidence and now represent the majority of rotator cuff repair surgery. Among concomitant procedures, subacromial decompression was most commonly performed despite evidence suggesting a lack of efficacy. Infections and stiffness were rare complications that were slightly but significantly more frequent in open rotator cuff repairs.

Neer Award 2018: Platelet-derived growth factor receptor α co-expression typifies a subset of platelet-derived growth factor receptor β–positive progenitor cells that contribute to fatty degeneration and fibrosis of the murine rotator cuff

BACKGROUND AND HYPOTHESIS After massive tears, rotator cuff muscle often undergoes atrophy, fibrosis, and fatty degeneration. These changes can lead to high surgical failure rates and poor patient outcomes. The identity of the progenitor cells involved in these processes has not been fully elucidated. Platelet-derived growth factor receptor β (PDGFRβ) and platelet-derived growth factor receptor α (PDGFRα) have previously been recognized as markers of cells involved in muscle fibroadipogenesis. We hypothesized that PDGFRα expression identifies a fibroadipogenic subset of PDGFRβ+ progenitor cells that contribute to fibroadipogenesis of the rotator cuff. METHODS We created massive rotator cuff tears in a transgenic strain of mice that allows PDGFRβ+ cells to be tracked via green fluorescent protein (GFP) fluorescence. We then harvested rotator cuff muscle tissues at multiple time points postoperatively and analyzed them for the presence and localization of GFP+ PDGFRβ+ PDGFRα+ cells. We cultured, induced, and treated these cells with the molecular inhibitor CWHM-12 to assess fibrosis inhibition. RESULTS GFP+ PDGFRβ+ PDGFRα+ cells were present in rotator cuff muscle tissue and, after massive tears, localized to fibrotic and adipogenic tissues. The frequency of PDGFRβ+ PDGFRα+ cells increased at 5 days after massive cuff tears and decreased to basal levels within 2 weeks. PDGFRβ+ PDGFRα+ cells were highly adipogenic and significantly more fibrogenic than PDGFRβ+ PDGFRα- cells in vitro and localized to adipogenic and fibrotic tissues in vivo. Treatment with CWHM-12 significantly decreased fibrogenesis from PDGFRβ+ PDGFRα+ cells. CONCLUSION PDGFRβ+ PDGFRα+ cells directly contribute to fibrosis and fatty degeneration after massive rotator cuff tears in the mouse model. In addition, CWHM-12 treatment inhibits fibrogenesis from PDGFRβ+ PDGFRα+ cells in vitro. Clinically, perioperative PDGFRβ+ PDGFRα+ cell inhibition may limit rotator cuff tissue degeneration and, ultimately, improve surgical outcomes for massive rotator cuff tears.

Arthroscopic Removal of Proximal Femoral Locking Screws: A Novel Application of Hip Arthroscopy

The authors describe a novel application of hip arthroscopy. Symptomatic proximal locking screws can readily be removed via an arthroscope. Not only can the proximal screw be removed with much less morbidity than in previously described procedures, but the abductor mechanisms can also be evaluated for injury sustained during the index procedure. Furthermore, scarred or inflamed trochanteric bursal tissue may be resected during this arthroscopic approach.

Preoperative Vitamin D Deficiency Is Associated With Higher Postoperative Complication Rates in Total Knee Arthroplasty

The purpose of this study was to determine the relative incidence of postoperative complications in 25-hydroxyvitamin D (25D)-deficient and -sufficient patients undergoing total knee arthroplasty (TKA). Patients who were either serum 25D deficient (25D <20 ng/mL) or 25D sufficient (25D ≥20 ng/mL) 90 days prior to primary TKA from 2007 to 2016 were identified using the Humana administrative claims registry. The incidence of postoperative medical and surgical complications was determined by querying for relevant International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. Risk-adjusted odds ratios (ORs) were calculated using multivariate logistic regression with age, sex, and Charlson Comorbidity Index as covariates. In total, 868 of 6593 patients who underwent TKA from 2007 to 2016 were 25D deficient, corresponding to a 13.2% prevalence rate. On adjustment for age, sex, and Charlson Comorbidity Index, 25D-deficient patients had a higher incidence of postoperative stiffness requiring manipulation under anesthesia (OR, 1.69; 95% confidence interval [CI], 1.39-2.04; P<.001), surgical site infection requiring irrigation and debridement (OR, 1.76; 95% CI, 1.25-2.48; P=.001), and prosthesis explantation (OR, 2.97; 95% CI, 2.04-4.31; P<.001) at 1 year. Patients who were 25D deficient also had higher rates of postoperative deep venous thrombosis (OR, 1.80; 95% CI, 1.36-2.38; P<.001), myocardial infarction (OR, 2.11; 95% CI, 1.41-3.15; P<.001), and cerebrovascular accident (OR, 1.73; 95% CI, 1.17-2.57; P=.006). Thus, serum 25D levels below 20 ng/mL are associated with a higher incidence of postoperative complications and may be a perioperative modifiable risk factor in TKA. [Orthopedics. 2018; 41(4):e489-e495.].

Trends and Complications in Open Versus Endoscopic Carpal Tunnel Release in Private Payer and Medicare Patient Populations

Purpose: The purpose of this study was to report trends, complications, and costs associated with endoscopic carpal tunnel release (ECTR) and open carpal tunnel release (OCTR). Methods: Using Current Procedural Terminology (CPT) and International Classification of Diseases, Ninth Revision (ICD-9) codes, patients who had open versus endoscopic carpal tunnel release (CTR) were identified retrospectively in the PearlDiver database from both the Medicare and Humana (a private payer health insurance) populations from 2005 to 2014. These groups were then evaluated for postoperative complications, including wound infection within 90 days, wound dehiscence within 90 days, and intraoperative median nerve injury. We also used the data output for each group to compare the cost of the 2 procedure types. Data were analyzed via the Student t test. Statistical significance was set at P < .05. Results: A significantly lower percentage of patients in the endoscopic CTR group had a postoperative infection (5.21 vs 7.97 per 1000 patients per year, P < .001; 7.36 vs 11.23 per 1000 patients per year, P < .001) and wound dehiscence (1.58 vs 2.87 per 1000 patients per year, P < .001; 2.14 vs 3.73 per 1000 patients per year, P < .05) than open CTR group in the Medicare and Humana populations, respectively. Median nerve injury occurred 0.59/1000 ECTRs versus 1.69/1000 OCTRs (Medicare) and 1.96/1000 ECTRs versus 3.72/1000 OCTRs (Humana). Endoscopic CTR cost was more than open CTR for both the Medicare population (

PDGFRα+ Progenitor Cells Contribute to Muscle Fibroadipogensis Following Massive Rotator Cuff Tears in a Mouse Model

1643 vs

Perivascular Stem Cells Diminish Muscle Atrophy and Retain Viability in a Rotator Cuff Tear Model

1015 per procedure, P < .001) and Humana population (