Divergent effects of canonical and non-canonical TGF-ß signalling on mixed contractile-synthetic smooth muscle cell phenotype in human Marfan syndrome aortic root aneurysms.

Aortic root aneurysm formation is a cardinal feature of Marfan syndrome (MFS) and likely TGF-ß driven via Smad (canonical) and ERK (non-canonical) signalling. The current study assesses human MFS vascular smooth muscle cell (SMC) phenotype, focusing on individual contributions by Smad and ERK, with Notch3 signalling identified as a novel compensatory mechanism against TGF-ß-driven pathology. Although significant ERK activation and mixed contractile gene expression patterns were observed by traditional analysis, this did not directly correlate with the anatomic site of the aneurysm. Smooth muscle cell phenotypic changes were TGF-ß-dependent and opposed by ERK in vitro, implicating the canonical Smad pathway. Bulk SMC RNA sequencing after ERK inhibition showed that ERK modulates cell proliferation, apoptosis, inflammation, and Notch signalling via Notch3 in MFS. Reversing Notch3 overexpression with siRNA demonstrated that Notch3 promotes several protective remodelling pathways, including increased SMC proliferation, decreased apoptosis and reduced matrix metalloproteinase activity, in vitro. In conclusion, in human MFS aortic SMCs: (a) ERK activation is enhanced but not specific to the site of aneurysm formation; (b) ERK opposes TGF-ß-dependent negative effects on SMC phenotype; (c) multiple distinct SMC subtypes contribute to a 'mixed' contractile-synthetic phenotype in MFS aortic aneurysm; and (d) ERK drives Notch3 overexpression, a potential pathway for tissue remodelling in response to aneurysm formation.

Epidemiology of Shoulder Instability Injuries in Collision Collegiate Sports From 2009 to 2014.

PURPOSE: To describe the types, mechanisms, and severity of shoulder instability injuries in collegiate collision athletes during the 2009-2010 through 2013-2014 academic years using the National Collegiate Athletic Association Injury Surveillance Program; to compare the injury incidence between men's collision sports and their women's non-collision counterparts, when possible; and to compare injury outcomes between Divisions I, II, and III. METHODS: Data regarding men's football, wrestling, ice hockey, and lacrosse, as well as women's ice hockey and lacrosse, were obtained. Injuries requiring attention from a health care provider were reported. Incidence rates per 100,000 athlete-exposures (AEs) were calculated with 95% confidence intervals (CIs). Analysis of variance was used to compare time loss (TL), and χ2 analysis was used to compare surgery rates between divisions. RESULTS: A total of 445 shoulder instability injuries occurred in 1,421,561 AEs from 2009-2010 to 2013-2014 (incidence rate, 31.30 injuries/100,000 AEs; 95% CI, 28.4-34.21 injuries/100,000 AEs). Subluxation accounted for 59.1% of injuries, with anterior subluxation (35.3%) being the most common injury. Dislocation resulted in the most TL per injury (17.58 days). Mean TL for all injuries was 8.17 days (standard deviation, 7.21 days). When non-time-loss injuries were excluded from analysis, players experienced a mean TL of 18.34 days (standard deviation, 8.44 days). Divisions I (4.77 days), II (20.52 days), and III (11.23 days) differed significantly in mean TL (P = .01). Of the injuries, 29.3% required surgery. The surgery rates for Divisions I (32.9%), II (38.1%), and III (19.4%) also differed significantly (P = .04). Men's ice hockey and lacrosse players sustained a 2.17-fold (95% CI, 1.04-4.50) higher incidence of shoulder instability than their female counterparts. CONCLUSIONS: Anterior subluxation and dislocation accounted for 52.1% of all shoulder instability injuries. Injured athletes missed 8 days on average, and nearly 30% of injuries required surgery. Surgery rates and TL were significantly different between Divisions I, II, and III. Female athletes playing non-collision ice hockey and lacrosse experienced significantly lower shoulder instability rates than their male counterparts. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

A Sport-specific Analysis of the Epidemiology of Hip Injuries in National Collegiate Athletic Association Athletes From 2009 to 2014.

PURPOSE: To describe the injury rates, mechanisms, time loss, and rates of surgery for hip/groin injuries in National Collegiate Athletic Association (NCAA) athletes across 25 collegiate sports during the 2009/10 to 2013/14 academic years. METHODS: Data from the 2009/10 to 2013/14 academic years were obtained from the NCAA Injury Surveillance Program (ISP). Rates of hip/groin injuries, mechanism of injury, time lost from competition, and surgical treatment were calculated. Differences between sex-comparable sports were quantified using rate ratios and injury proportion ratios. A sport-specific biomechanical classification system, which included cutting, impingement, overhead/asymmetric, endurance, and flexibility sports, was applied for subgroup analysis. RESULTS: In total, 1,984 hip injuries were reported in 25 NCAA sports, including 9 male and female sports, 3 male-only sports, and 4 female-only sports between the years 2009/10 and 2013/14, resulting in an overall hip injury rate of 53.1/100,000 athletic exposures (AEs). In sex-comparable sports, (basketball, cross-country, lacrosse, ice hockey, indoor track, outdoor track, soccer, swimming, and tennis), men were more commonly affected than women (59.53 vs 42.27 per 100,000 AEs respectively; rate ratio, 1.41; 95% confidence interval, 1.28-1.55). Subgroup analysis demonstrated that the highest rate of hip injuries per 100,000 AEs occurred in impingement sports (96.9). Endurance sports had the highest proportion of injured athletes with time lost >14 days (9.5%). For impingement-type sports, the most common mechanism of injury was no apparent contact (48.2%). The rate of athletes undergoing surgery per 100,000 AEs was highest in impingement-type sports (2.0). CONCLUSIONS: We have identified that impingement-type sports are most frequently associated with hip injuries. Additionally, this study demonstrates that hip injuries sustained in athletes who played impingement-type sports had a significantly higher rate of surgical intervention than other sport classifications. LEVEL OF EVIDENCE: Level III, prognostic study.

Softball pitching mechanics and shoulder injuries: a narrative review.

Softball is the third most popular women's collegiate sport in the United States, with 19,680 total athletes as of the 2015-2016 season. Despite its popularity and growth in recent years, research focusing on the biomechanics of the windmill pitch and its associated shoulder injuries is relatively scarce. The incidence of shoulder injury is highest during the preseason and the beginning of the regular season. The windmill pitch can be divided into distinct phases, with the shoulder experiencing the greatest force during the delivery phase. Significant demands placed on the shoulder during the windmill pitch put pitchers at a higher risk of developing shoulder injuries than position players. Maximum shoulder compression/distraction forces during the windmill pitch have been shown to be comparable to those experienced during the baseball overhand throw, dispelling the myth that the windmill pitch is not taxing on the shoulder. Injuries associated with the high compression/distraction forces include lesions to the rotator cuff, glenoid labrum, and biceps brachii. Pitcher-specific training, cross-training, and whole-body conditioning should be incorporated into current training regimens to decrease the risk of shoulder injuries.

Enhanced Recovery After Surgery Protocols for Head and Neck Cancer: Systematic Review and Meta-analysis.

OBJECTIVE: Enhanced recovery after surgery (ERAS) protocols aim to optimize the pre-, intra-, and postoperative care of patients to improve surgery outcomes, reduce complications, decrease length of stay, and more. We aim to perform a systematic review and meta-analysis of ERAS protocols for head and neck cancer surgery with or without microvascular reconstruction. DATA SOURCES: PubMed, Embase, and Web of Science databases were queried, and abstracts were screened independently by 2 investigators. REVIEW METHODS: This review was conducted in accordance with the PRISMA guidelines. We included comparative observational studies but excluded animal studies, case reports, and case series. RESULTS: Of 557 articles initially reviewed by title and/or abstract, we identified 30 for full-text screening, and 9 met the criteria for qualitative synthesis. Meta-analysis of length of stay revealed a mean decrease of 1.37 days (95% CI, 0.77-1.96; I2 = 0%; P < .00001) with the ERAS group as compared with non-ERAS controls. The standardized mean difference of the morphine milligram equivalent was 0.72 lower (95% CI, 0.26-1.18; I2 = 82%; P = .002) in the ERAS group vs controls. The quality of studies was moderate with a median MINORS score of 18.5 (range, 13.5-21.5). CONCLUSION: Implementation of ERAS protocols can lead to decreases in length of stay and opioid drug utilization. However, further high-quality prospective studies of ERAS protocols are needed, especially with stratified analysis of outcomes based on the type of head and neck cancer surgery.

Research Productivity of Orthopaedic Sports Medicine Fellowship Programs in the United States.

PURPOSE: To survey orthopaedic sports medicine fellowship program directors to determine the current research productivity of both fellows and faculty in Accreditation Council for Graduate Medical Education-accredited orthopaedic sports medicine fellowship programs in the United States. METHODS: An anonymous 18-question survey was distributed via e-mail to all 95 Accreditation Council for Graduate Medical Education-accredited orthopaedic sports medicine fellowship program directors in the United States. Descriptive statistics were used for data analysis. Questions included whether fellows are required to complete a certain number of projects during their fellowship year and whether fellows have protected research time. RESULTS: Of the programs, 31 (33%) responded to the survey. Twenty-four programs (80%) require fellows to complete 1 to 4 projects. Twenty-one programs (71%) provide 4 to 8 hours of weekly protected research time. Twenty-four programs (77%) publish 1 to 2 manuscripts per fellow during the fellowship. Twenty-two programs (71%) have fellows work on 1 to 2 projects at a time. Annually, 26 programs (84%) give 0 to 5 podium presentations, 24 (80%) present 0 to 5 posters, and 15 (48%) report 0 to 5 publications. Twenty-four programs (77%) have research fellows and/or assistants to help with research. The presence of dedicated research assistants and more than 25 annual fellowship program publications were found to be useful screening data for more than 2 and more than 4 average publications per fellow, respectively. CONCLUSIONS: The research productivity of orthopaedic sports medicine fellowship programs may be an important consideration for applicants. Applicants who desire to be productive in research during their fellowship year should consider programs with dedicated research assistants and/or programs that publish more than 25 times annually. CLINICAL RELEVANCE: This is a descriptive epidemiologic study that helps define the research productivity landscape in orthopaedic sports medicine fellowships. A more accurate understanding of sports medicine fellowship research experience may facilitate a better match between a program's research expectations and an applicant's research interests.

Horizontal Instability of the Acromioclavicular Joint: A Systematic Review.

BACKGROUND: Injuries to the acromioclavicular (AC) joint are common and should be suspected in patients who have shoulder pain in the region of the acromion and clavicle. Injuries to the AC ligament can cause horizontal instability and are often neglected or underdiagnosed, which can lead to poor patient outcomes. PURPOSE: To perform a systematic review of the literature on the diagnosis and treatment of horizontal instability of the AC joint. STUDY DESIGN: Systematic review. METHODS: The authors performed a systematic review using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed and EMBASE were searched for studies that investigated diagnosis, treatment, and failure of operative management of acute and chronic AC separations. Studies that did not specifically evaluate AC joint injuries, were not written in English, or were specific only to vertical instability of the AC joint were excluded. RESULTS: Overall, 23 articles met the inclusion criteria and were therefore included in this systematic review. Diagnosing horizontal AC instability is difficult using plain radiographs; dynamic views were shown in some cases to better detect horizontal instability than with static views. More than 60 procedures for treating AC joint injuries have been published, but many focus on vertical rather than horizontal instability. Modifications to current surgical procedures to incorporate reconstruction of the horizontal component showed improved patient outcomes. Such modifications included additional AC joint suture cord cerclage, combined AC and coracoclavicular ligament reconstruction, and the Twin Tail TightRope triple button technique. Failure after surgical stabilization of AC joint separation has been reported to occur in 15% to 80% of cases. CONCLUSION: No consensus is available regarding the best practices for diagnosis, evaluation, and treatment of acute or chronic horizontal instability of the AC joint. Moreover, horizontal instability injuries are often neglected or poorly understood, making diagnosis difficult, which may lead to high complication rates and failure after surgical stabilization.

Recovery after volleyball: a narrative review.

Volleyball is a popular sport, but there has been little research to date investigating the recovery process. Volleyball involves short bouts of high intensity exertion, often with limited time to rest between matches. This literature review highlights the specific methods used to recover after playing volleyball and evaluates their effectiveness. Recovery strategies have been shown to increase performance and prevent injury. Specific techniques identified include nutritional strategies, proper sleep, mental and psychological techniques, cold water immersion, and laser therapy. Some, such as nutrition and sleep, have been definitively shown to benefit volleyball players, while others, such as cold water immersion and laser therapy, have shown promise but require further research to determine their overall effect. Other areas of future research include evaluating the effectiveness of combined recovery techniques as well as determining which are best for rapid recovery.

Surgical Skills Course for Fourth Year Medical Students Entering an Orthopaedic Surgery Residency.

This article was migrated. The article was marked as recommended. Surgical skills training outside of the operating room is a critical component of surgical education. There has been little incorporation of these programs for medical students entering orthopaedic surgery residencies. As such, there is concern that incoming orthopaedic residents matriculate with skills below residency programs' expectations. This study aimed to assess the need for an orthopaedic surgical skills course during the 4 th year of medical school.An anonymous electronic survey was emailed to 1457orthopaedic surgery residents and 732 current orthopaedic residency applicants using application data from a single orthopaedic residency program during the 2015-2016 through 2017-2018 cycles. 200 resident and 31 applicant emails were returned undeliverable, resulting in distribution to 1257 residents and 701 applicants. 135 junior residents (11% response rate) and 181 applicants (26% response rate) completed portions of the survey. 76 of 117 (65%) residents and 170 of 181 (94%) applicants did not participate in a formal orthopaedic surgical skills course. 110 of 118 (93%) residents and 160 of 171 (94%) applicants indicated that implementing such a course before entering residency would be beneficial. Applicants rated basic fracture reduction (95%; 171/180), casting/splinting (94%; 170/180), and reading basic x-rays (90%; 162/180) as the most important potential course components.Most respondents were not exposed to an orthopaedic skills course prior to residency. Participants indicated that such a course would be beneficial to incoming orthopaedic residents. Pilot programs should be developed to optimize an orthopaedic preparatory skills course for 4 th year medical students pursuing careers in orthopaedic surgery.

Patient understanding, expectations, outcomes, and satisfaction regarding surgical management of shoulder instability.

Shoulder instability is a common condition encountered by sports medicine and shoulder surgeons. Management can be challenging, both with regards to the underlying pathology and the high expectations associated with the very active patient population that this condition typically affects. High-performance athletes who are used to performing at activity levels which typically challenge the normal physiologic limits of the glenohumeral joint may be particularly difficult to treat. As physicians increasingly evaluate patient reported outcomes (PROs), a growing body of literature has emerged related to patient expectations for a variety of orthopaedic conditions, including shoulder instability. Physicians may face difficulty when using the literature to counsel patients due to the difference between a successful PRO and true patient satisfaction. Having a better understanding of patient expectations may improve preoperative evaluation, patient counseling, postoperative PROs, and patient satisfaction with shoulder instability surgery. The purpose of this paper was to review the literature regarding patient understanding of shoulder instability injuries, expectations following surgical repair of shoulder instability pathology, and satisfaction with operative intervention. Additionally, we sought to determine the effect of patient expectations on outcomes.

Formal leadership training for orthopedic surgeons: Limited opportunities amongst growing demand.

Leadership skills are important to all orthopedic surgeons, regardless of practice or location, as interactions with patients, staff, and other physicians necessitate professionalism and leadership. Leadership skills are best developed through formal training and experiential opportunities. Several programs emphasizing leadership skills for orthopedic surgeons exist; however, the number of programs is not adequate to meet the demand. It is difficult for orthopedic surgeons to take advantage of these opportunities, given clinical and professional responsibilities. To appropriately adapt to the changing healthcare environment and ensure advancement of the orthopedic field, formal leadership skills development should be widely integrated into orthopedic training.

The Perception of Pregnancy and Parenthood Among Female Orthopaedic Surgery Residents.

INTRODUCTION: Orthopaedic surgery has the lowest percentage of female residents of all surgical specialties. Female medical students may believe that the demands of the specialty, both during training and in clinical practice, may be less conducive to becoming a parent. The purpose of this study was to determine the perceptions of and experiences with pregnancy and parenthood among female orthopaedic surgery trainees. METHODS: An anonymous 24-question online survey was distributed to all current female orthopaedic surgery trainees in the United States via the American Academy of Orthopaedic Surgeons Diversity Advisory Board. Survey questions included the demographics of the residents' programs, the parental status of the respondents, and their experiences with pregnancy and parenthood during training. RESULTS: Of the respondents, 83.7% did not have children during residency and were not currently pregnant. Furthermore, 48.4% responded that they had deferred having children because they were in residency. One hundred and thirteen respondents (59.5%) reported that they experienced bias from co-residents about women having children during residency, whereas 94 (49.5%) reported such bias from attendings. CONCLUSION: This study demonstrates that most female orthopaedic trainees do not have children during residency. Most respondents experienced bias from co-residents about women having children during residency, and nearly half experienced such bias from orthopaedic attendings. Combating bias about pregnancy during residency may help encourage more women to pursue a career in orthopaedics.

Epidemiological Patterns of Patellofemoral Injuries in Collegiate Athletes in the United States From 2009 to 2014.

BACKGROUND: As many as 30% of patients with knee pain seen in sports medicine clinics have complaints related to the patellofemoral joint. There is a paucity of research available regarding patellofemoral injuries, mechanism of injury, and playing time lost in collegiate athletes. PURPOSE: To describe the rates, mechanisms, severity, and potential sex-based differences of patellofemoral injuries in collegiate athletes across 25 National Collegiate Athletic Association (NCAA) sports. STUDY DESIGN: Descriptive epidemiology study. METHODS: Data from the 2009-2010 through the 2013-2014 academic years were obtained from the NCAA Injury Surveillance Program and were analyzed to calculate patellofemoral injury rates, mechanisms of injury, time lost, and need for surgery. Rate ratios and injury proportion ratios were used to quantify discernible differences between sex-comparable sports and timing of injury (ie, practice vs competition), respectively. RESULTS: The overall patellofemoral injury incidence rate was 16.10 per 100,000 athlete-exposures (AEs). Women's volleyball had the highest incidence of all sports (39.57 per 100,000 AEs). Injuries were 66% more likely to occur in competition than during practice. Female athletes experienced significantly more patellofemoral injuries than males in similar sports. Patellar tendinitis accounted for 49.2% of all patellofemoral injuries and was the most common injury in 20 of 25 studied sports. Patellar subluxation accounted for the most total days missed, and patellar dislocation had the highest mean days missed per injury (11.42 days). Patella fracture was the most likely injury to require surgery (80%). CONCLUSION: Patellofemoral injuries were most common in sports that require jumping and quick changes of direction, specifically women's volleyball, men's and women's basketball, and women's soccer. The majority of patellofemoral injuries in this cohort were classified as patellar tendinitis caused by overuse. Most injuries resulted in no competition or practice time lost. This information may contribute to the development of prevention programs aimed at addressing the most prevalent types and mechanisms of injury in each sport to reduce the incidence of patellofemoral injury in these athletes.

Variability in training Experience during orthopaedic surgery post-graduate year-1.

This article was migrated. The article was marked as recommended. Background: Recently, the orthopaedic surgery PGY-1 curriculum was redesigned to maximize time spent on orthopaedic surgery rotations. Additionally, surgical skills modules were introduced to standardize curricula for orthopaedic interns in the United States. Objective: The purpose of this study is to determine the implementation of the curriculum guidelines were implemented on a national level. Methods: An anonymous survey with 14 multiple choice questions was electronically distributed to program directors (PDs) for all ACGME-accredited orthopaedic surgery residency programs in the US (n=163) in January 2017. Seventy-nine of the 162 PDs (49%) completed the survey in its entirety. Results: The most common non-orthopaedic rotations included: general surgery trauma (67/79=85%), surgical/medical intensive care unit (60/79=76%), plastic and burn surgery (56/79=71%), musculoskeletal radiology (44/79=56%), and vascular surgery (40/79=51%). Seventy-two of 162 residency programs (91%) have a formal surgical skills curriculum for first-year residents, separate from intern boot camp. A variety of training modalities were utilized to teach the interns, most commonly saw bones for fracture fixation (68/79=86%) and cadaveric specimens for surgical approaches (63.79=80%). Conclusions: While all PGY-1 orthopaedic residents are now required to spend six months on orthopaedic rotations, the remaining six months are variable. These non-orthopaedic rotations are likely determined by the PD and available services at the trainee's institution. This variability has granted PDs the opportunity to individualize the intern experience by maximizing each institution's assets and designing their own surgical skill curriculum to train their interns using the resources available.

Strength and conditioning in adolescent female athletes.

Despite evidence that strength and conditioning (S&C) programs decrease injury risk and increase sport performance, young females are rarely offered S&C programs comparable to those of their male counterparts. The purpose of this study was to evaluate the current body of available literature regarding S&C in adolescent female athletes, describe potential benefits, and generate recommendations for S&C programs for female adolescent athletes. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Systematic searches of the PubMed and Google Scholar databases were conducted using the following keywords: 'female athletes,' 'injury prevention,' 'adolescent,' 'physical fitness,' 'strength,' 'female adolescent,' and 'conditioning.' Studies included in this review evaluated the effectiveness of S&C protocols and/or the habits and attitudes of coaches and athletic trainers working with female adolescent athletes. Seven articles evaluating S&C programs for the adolescent female athlete were used as the basis for this systematic review. These articles described current protocols and/or factors that should be taken into account when designing S&C programs. The identified articles focused on improving the strength of adolescent female athletes, decreasing the risk of injury, and exposing female athletes to the benefits of S&C that are routinely afforded to their male counterparts. Despite the critical potential benefits of S&C training, such as improved landing mechanics, coaches and athletic trainers do not routinely implement S&C programs for female adolescent athletes. The lack of such programs is largely due to misconceptions surrounding female athletes, such as the perception that females fear bulking up. S&C programs for adolescent female athletes should incorporate stretching of the hip adductors, targeted hamstring, gluteal and quadriceps strengthening, and a synergistic adaptation model, which tailors training protocols to an athlete's pubertal stage.

Limited root repair in acute type A aortic dissection is safe but results in increased risk of reoperation.

OBJECTIVE: Management of the aortic root is a challenge for surgeons treating acute type A aortic dissection. METHODS: We performed a retrospective review of the acute type A aortic dissection experience at Stanford Hospital between 2005 and 2015 and identified patients who underwent either limited root repair or aortic root replacement. Differences in baseline characteristics were balanced with inverse probability weighting to estimate the average treatment effect on the controls. Weighted logistic regression was used to evaluate in-hospital mortality. Weighted Cox proportional hazards regression was used to evaluate differences in the hazard for mid-term death. Reoperation was evaluated with death as a competing risk with the Fine-Gray subdistribution hazard. RESULTS: After we excluded patients managed either nonoperatively or with definitive endovascular repair, there were 293 patients without connective tissue disease who underwent either limited root repair or aortic root replacement. There was no difference in weighted perioperative mortality, odds ratio 0.89 (95% confidence interval [CI], 0.44-1.76, P = .7), and there was no difference in weighted survival, hazard ratio 1.12 (95% CI, 0.54-2.31, P = .8). Risk of reoperation was greater in limited root repair (11.8%, 95% CI, 0.0%-23.8%) than for root replacement (0%), P < .001. CONCLUSIONS: Limited root repair was associated with increased risk of late reoperation after repair of acute type A aortic dissection. Surgeons with adequate experience may consider aortic root replacement in well-selected patients. However, given good outcomes after limited root repair, surgeons should not feel compelled to perform this more-complex operation.

Outcomes in the Orthopaedic Sports Medicine Fellowship Match, 2010-2017.

BACKGROUND: Sports medicine is one of the most competitive fellowships in orthopaedic surgery. Despite its popularity, fellowship applicants have limited understanding of the orthopaedic sports medicine fellowship match process. PURPOSE: To define key outcomes in the orthopaedic sports medicine fellowship match, including the overall match rate, number of programs filled, and number of applicants ranked by programs that filled between 2010 and 2017. STUDY DESIGN: Cross-sectional study. METHODS: This study utilized data regarding the orthopaedic sports medicine fellowship match collected by the American Orthopaedic Society for Sports Medicine (AOSSM) from 2010 through 2017. Applicant data included number of applicants, number of matched and unmatched applicants, and percentage of applicants matching into their top choices. Fellowship program data included number of programs participating in the match and number of applicants ranked by filled and unfilled programs. RESULTS: Between 2010 and 2017, the mean number of orthopaedic sports medicine fellowship applicants was 244.8. On average, 92.0% of applicants matched into a fellowship program. The mean number of programs participating in the fellowship match was 92.9, with a mean of 219.9 accredited positions and 5.4 nonaccredited positions. Over the time period studied, a mean of 75.8% of programs matched all available positions. Programs that matched fully ranked 9.0 applicants per position, on average, compared with a mean of 6.5 applicants ranked per position among programs that did not fully match (P = .0016). CONCLUSION: From 2010 to 2017, the number of applicants, positions available, overall match rate, and number of programs participating in the orthopaedic sports medicine fellowship match have remained consistent. The mean number of applicants per position ranked by fully matched fellowship programs was 9.0 compared with a mean of 6.5 applicants per position ranked by programs that did not fully match. These data may be helpful as we look to the future of orthopaedic sports medicine fellowship positions and the match process. In addition, this study reveals characteristics that divide sports medicine fellowship programs that fully match from those that do not. Applicants and/or fellowship program directors may utilize this information to modify their approach to the match process going forward.

Statins Reduce Thoracic Aortic Aneurysm Growth in Marfan Syndrome Mice via Inhibition of the Ras-Induced ERK (Extracellular Signal-Regulated Kinase) Signaling Pathway.

Background Statins reduce aneurysm growth in mouse models of Marfan syndrome, although the mechanism is unknown. In addition to reducing cholesterol, statins block farnesylation and geranylgeranylation, which participate in membrane-bound G-protein signaling, including Ras. We dissected the prenylation pathway to define the effect of statins on aneurysm reduction. Methods and Results Fbn1C1039G/+ mice were treated with (1) pravastatin (HMG-CoA [3-hydroxy-3-methylglutaryl coenzyme A] reductase inhibitor), (2) manumycin A ( MA ; FPT inhibitor), (3) perillyl alcohol ( GGPT 1 and -2 inhibitor), or (4) vehicle control from age 4 to 8 weeks and euthanized at 12 weeks. Histological characterization was performed. Protein analysis was completed on aortic specimens to measure ERK (extracellular signal-regulated kinase) signaling. In vitro Fbn1C1039G/+ aortic smooth muscle cells were utilized to measure Ras-dependent ERK signaling and MMP (matrix metalloproteinase) activity. Pravastatin and MA significantly reduced aneurysm growth compared with vehicle control (n=8 per group). In contrast, PA did not significantly decrease aneurysm size. Histology illustrated reduced elastin breakdown in MA -treated mice compared with vehicle control (n=5 per group). Although elevated in control Marfan mice, both phosphorylated c-Raf and phosphorylated ERK 1/2 were significantly reduced in MA -treated mice (4-5 per group). In vitro smooth muscle cell studies confirmed phosphorylated cR af and phosphorylated ERK 1/2 signaling was elevated in Fbn1C1039G/+ smooth muscle cells (n=5 per group). Fbn1C1039G/+ smooth muscle cell Ras-dependent ERK signaling and MMP activity were reduced following MA treatment (n=5 per group). Corroborating in vitro findings, MMP activity was also decreased in pravastatin-treated mice. Conclusions Aneurysm reduction in Fbn1C1039G/+ mice following pravastatin and MA treatment was associated with a decrease in Ras-dependent ERK signaling. MMP activity can be reduced by diminishing Ras signaling.

Long-term miR-29b suppression reduces aneurysm formation in a Marfan mouse model.

Aortic root aneurysm formation and subsequent dissection and/or rupture remain the leading cause of death in patients with Marfan syndrome. Our laboratory has reported that miR-29b participates in aortic root/ascending aorta extracellular matrix remodeling during early aneurysm formation in Fbn1C1039G/+ Marfan mice. Herein, we sought to determine whether miR-29b suppression can reduce aneurysm formation long-term. Fbn1C1039G/+ Marfan mice were treated with retro-orbital LNA-anti-miR-29b inhibitor or scrambled-control-miR before aneurysms develop either (1) a single dose prenatally (pregnant Fbn1C1039G/+ mice at 14.5 days post-coitum) (n = 8-10, each group) or (2) postnatally every other week, from 2 to 22 weeks of age, and sacrificed at 24 weeks (n = 8-10, each group). To determine if miR-29b blockade was beneficial even after aneurysms develop, a third group of animals were treated every other week, starting at 8 weeks of age, until sacrificed (n = 4-6, each group). miR-29b inhibition resulted in aneurysm reduction, increased elastogenesis, decreased matrix metalloproteinase activity and decreased elastin breakdown. Prenatal LNA-anti-miR-29b inhibitor treatment decreased aneurysm formation up to age 32 weeks, whereas postnatal treatment was effective up to 16 weeks. miR-29b blockade did not slow aortic growth once aneurysms already developed. Systemic miR-29b inhibition significantly reduces aneurysm development long-term in a Marfan mouse model. Drug administration during aortic wall embryologic development appears fundamental. miR-29b suppression could be a potential therapeutic target for reducing aneurysm formation in Marfan syndrome patients.