Background The combination of autologous mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) synergistically reduces scar size and improves cardiac function in ischemic cardiomyopathy. Whereas allogeneic (allo-)MSCs are immunoevasive, the capacity of CSCs to similarly elude the immune system remains controversial, potentially limiting the success of allogeneic cell combination therapy (ACCT). Objective We tested the hypothesis that ACCT synergistically promotes cardiac regeneration without provoking immunologic reactions. Methods Gottingen swine with experimental ischemic cardiomyopathy were randomized to receive transendocardial injections of either allo-MSC + allo-CSC (ACCT: 200 million MSCs/1 million CSCs, n=7), 200 million allo-MSC (n=8), 1 million allo-CSC (n=4), or placebo (Plasma-Lyte A, n=6)]. Swine were assessed by cardiac magnetic resonance imaging (cMR) and pressure volume catheterization. Immune response was tested by histological analyses. Results Both ACCT and allo-MSCs reduced scar size by −11.1±4.8%, (p=0.012) and −9.5±4.8 (p=0.047), respectively. Only ACCT, but not MSC or CSC, prevented ongoing negative remodeling by offsetting increases in chamber volumes. Importantly, ACCT exerted the greatest effect on systolic function, improving the end-systolic pressure volume relation (+0.98±0.41 mmHg/mL, p=0.016) The ACCT group had more phospho-histone H3 (pHH3)+ (a marker of mitosis) cardiomyocytes (p=0.04), and non-cardiomyocytes (p=0.0002) compared to the placebo group in some regions of the heart. Inflammatory sites in ACCT and MSC swine contained immunotolerant CD3+/CD25+/FoxP3 regulatory T cells (p<0.0001). Histologic analysis showed absent to low grade inflammatory infiltrates without cardiomyocyte necrosis. Conclusion ACCT demonstrates synergistic effects to enhance cardiac regeneration and left ventricular functional recovery in a swine model of chronic ischemic cardiomyopathy without adverse immunological reaction. Clinical translation to humans is warranted.

Background Epilepsy is a common neurological disorder that affects approximately 50 million people worldwide. Both risk of epilepsy and response to treatment partly depend on genetic factors, and gene identification is a promising approach to target new prediction, treatment, and prevention strategies. However, despite significant progress in the identification of genes causing epilepsy in families with a Mendelian inheritance pattern, there is relatively little known about the genetic factors responsible for common forms of epilepsy and so-called epileptic encephalopathies. Study design The Epilepsy Phenome/Genome Project (EPGP) is a multi-institutional, retrospective phenotype–genotype study designed to gather and analyze detailed phenotypic information and DNA samples on 5250 participants, including probands with specific forms of epilepsy and, in a subset, parents of probands who do not have epilepsy. Results EPGP is being executed in four phases: study initiation, pilot, study expansion/establishment, and close-out. This article discusses a number of key challenges and solutions encountered during the first three phases of the project, including those related to (1) study initiation and management, (2) recruitment and phenotyping, and (3) data validation. The study has now enrolled 4223 participants. Conclusions EPGP has demonstrated the value of organizing a large network into cores with specific roles, managed by a strong Administrative Core that utilizes frequent communication and a collaborative model with tools such as study timelines and performance-payment models. The study also highlights the critical importance of an effective informatics system, highly structured recruitment methods, and expert data review.

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Purpose: (1) To compare the pre- and postoperative driving performance in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS); (2) to examine the differences in driving performance between patients with versus without capsular repair. Methods: Patients who underwent arthroscopic hip surgery for FAIS were included. Driving performance of participating patients was collected using a driving simulator preoperatively and at 2 weeks, 4–6 weeks and 8–12 weeks postoperatively. Data collected included demographics, surgery laterality, intraoperative procedures, left and right turn reaction time, total turn reaction time, gas off time (GOF), and break reaction time (BRT). Repeated measures analysis of variance (ANOVA) was used for statistical analysis. Results: 21 subjects (9 males, 12 females) with a mean age of 30 ± 9 years were included and 57.1% of the subjects had right-sided surgery. There was no difference between the mean preoperative and the 2-week postoperative left (0.72 seconds and 0.75 seconds, respectively) right (0.77 seconds and 0.75 seconds, respectively), and total (0.74 seconds and 0.75 seconds, respectively) turn reaction times as well as GOF (0.62 seconds and 0.60 seconds, respectively) and BRT (0.92 seconds and 0.93 seconds, respectively), indicating that the patients’ driving performance returned to the preoperative level as early as 2 weeks following hip arthroscopy for FAIS. There was no significant difference amongst any of the driving variables between patients who underwent capsular repair (50%) and those who did not. There was no significant difference amongst any of the driving variable s between patients who underwent left versus right hip arthroscopy. Conclusions: Patients’ driving performance returns to the preoperative level as early as 2 weeks after hip arthroscopy for FAIS. Surgery laterality nor capsular repair make any significant difference in the time for driving abilities to return to baseline. The impact of intraoperative procedures performed, and the analgesic medications used postoperatively on the driving ability of patients undergoing hip arthroscopy warrants further investigation in larger patient populations.

Athletes participating in overhead sports are at particularly high risk of shoulder impingement syndrome. Subcoracoid impingement is defined as impingement of the anterior soft tissues of the shoulder between the coracoid process and the lesser tuberosity. Subacromial impingement syndrome (SIS) occurs due to extrinsic compression of the rotator cuff between the humeral head and coracoacromial structures or intrinsic degeneration of the supraspinatus tendon and subsequent superior migration of the humerus. Internal impingement is a major cause of shoulder pain in overhead athletes, and it occurs due to repetitive impingement of the articular surface of the rotator cuff with the glenoid during maximum abduction and external rotation of the arm. When examining athletes with suspected impingement of the shoulder, it is important to discuss the sport-specific motion that regenerates the symptoms and perform a combination of physical examination tests to improve the diagnostic accuracy. Radiographic evaluation is recommended, and the extent of soft tissue abnormalities can be assessed on ultrasound or magnetic resonance imaging of the shoulder. Management of shoulder impingement syndrome can be conservative or operative, based on the severity and chronicity of symptoms and the associated structural abnormalities. This review provides an update on the management of SIS, subcoracoid impingement, and internal impingement in the athletic population.