Gregory L. Cvetanovich

Human regulatory T cells in autoimmune diseases

Human regulatory T cells (Tregs) play a critical role in preventing autoimmunity, and their failure contributes to autoimmune diseases. In recent years, our understanding of human Tregs has been greatly enhanced by improvements in the definition and isolation of pure human Tregs, as well as by the discovery of phenotypically and functionally distinct human Treg subsets. This progress has also yielded a better understanding of the mechanisms of human Treg suppression and the role of human Tregs in autoimmune diseases. An unexpected discovery is that human Tregs have considerable plasticity that allows them to produce the pro-inflammatory cytokine IL-17 under certain conditions. These recent advances highlight the importance of studying the roles of both mouse and human Tregs in autoimmunity.

Does Double-Bundle Anterior Cruciate Ligament Reconstruction Improve Postoperative Knee Stability Compared With Single-Bundle Techniques? A Systematic Review of Overlapping Meta-analyses

PURPOSE Multiple meta-analyses of randomized controlled trials, the highest available level of evidence, have been conducted to determine whether double-bundle (DB) or single-bundle (SB) anterior cruciate ligament reconstruction (ACL-R) provides superior clinical outcomes and knee stability; however, results are discordant. The purpose of this study was to conduct a systematic review of meta-analyses comparing SB and DB ACL-R to discern the cause of the discordance and to determine which of these meta-analyses provides the current best available evidence. METHODS We evaluated available scientific support for SB as compared with DB ACL-R by systematically reviewing the literature for published meta-analyses. Data on patient clinical outcomes and knee stability (as measured by KT arthrometry and pivot-shift testing) were extracted. Meta-analysis quality was judged using the Oxman-Guyatt and Quality of Reporting of Meta-analyses systems. The Jadad algorithm was then applied to determine which meta-analyses provided the highest level of evidence. RESULTS Nine meta-analyses were included, of which 3 included Level I Evidence and 6 included both Level I and Level II Evidence. Most studies found significant differences favoring DB reconstruction on pivot-shift testing, KT arthrometry measurement of anterior tibial translation, and International Knee Documentation Committee objective grading. Most studies detected no significant differences between the 2 techniques in subjective outcome scores (Tegner, Lysholm, and International Knee Documentation Committee subjective), graft failure, or complications. Oxman-Guyatt and Quality of Reporting of Meta-analyses scores varied, with 2 studies exhibiting major flaws (Oxman-Guyatt score <3). After application of the Jadad decision algorithm, 3 concordant high-quality meta-analyses were selected, with each concluding that DB ACL-R provided significantly better knee stability (by KT arthrometry and pivot-shift testing) than SB ACL-R but no advantages in clinical outcomes or risk of graft failure. CONCLUSIONS The current best available evidence suggests that DB ACL-R provides better postoperative knee stability than SB ACL-R, whereas clinical outcomes and risk of graft failure are similar between techniques. LEVEL OF EVIDENCE Level II, systematic review of Level I and II studies.

Tibial Tuberosity Osteotomy Indications, Techniques, and Outcomes

Tibial tuberosity osteotomy (TTO) is a well-described treatment option for a broad range of patellofemoral joint disorders, including patellofemoral instability, patellar and trochlear focal chondral lesions, and patellofemoral arthritis. The purpose of this article is to review the evolution of the TTO procedure, from the original Hauser procedure to the current anteromedialization procedure, as well as discuss the pertinent anatomy and radiographs that accompany this procedure. The article highlights the surgical techniques for some of the more commonly performed TTO procedures and discusses the outcomes of the various TTO techniques. Complications, as well as clinical pearls to avoid these complications, are also included.

Return-to-Sport and Performance After Anterior Cruciate Ligament Reconstruction in National Basketball Association Players.

Background: Anterior cruciate ligament (ACL) rupture is a significant injury in National Basketball Association (NBA) players. Hypotheses: NBA players undergoing ACL reconstruction (ACLR) have high rates of return to sport (RTS), with RTS the season following surgery, no difference in performance between pre- and postsurgery, and no difference in RTS rate or performance between cases (ACLR) and controls (no ACL tear). Study Design: Case-control. Methods: NBA players undergoing ACLR were evaluated. Matched controls for age, body mass index (BMI), position, and NBA experience were selected during the same years as those undergoing ACLR. RTS and performance were compared between cases and controls. Paired-sample Student t tests, chi-square, and linear regression analyses were performed for comparison of within- and between-group variables. Results: Fifty-eight NBA players underwent ACLR while in the NBA. Mean player age was 25.7 ± 3.5 years. Forty percent of ACL tears occurred in the fourth quarter. Fifty players (86%) RTS in the NBA, and 7 players (12%) RTS in the International Basketball Federation (FIBA) or D-league. Ninety-eight percent of players RTS in the NBA the season following ACLR (11.6 ± 4.1 months from injury). Two players (3.1%) required revision ACLR. Career length following ACLR was 4.3 ± 3.4 years. Performance upon RTS following surgery declined significantly (P < 0.05) regarding games per season; minutes, points, and rebounds per game; and field goal percentage. However, following the index year, controls’ performances declined significantly in games per season; points, rebounds, assists, blocks, and steals per game; and field goal and free throw percentage. Other than games per season, there was no significant difference between cases and controls. Conclusion: There is a high RTS rate in the NBA following ACLR. Nearly all players RTS the season following surgery. Performance significantly declined from preinjury level; however, this was not significantly different from controls. ACL re-tear rate was low. Clinical Relevance: There is a high RTS rate in the NBA after ACLR, with no difference in performance upon RTS compared with controls.

Performance and Return to Sport After Anterior Cruciate Ligament Reconstruction in Male Major League Soccer Players

Background: Anterior cruciate ligament (ACL) rupture is a significant injury in male Major League Soccer (MLS) players in the United States. Purpose: To determine (1) return-to-sport (RTS) rate in MLS following ACL reconstruction (ACLR), (2) timing of RTS, (3) performance upon RTS, and (4) the difference in RTS and performance between players who underwent ACL reconstruction (ACLR) and controls. Study Design: Case-control study; Level of evidence, 3. Methods: MLS players undergoing ACLR between 1996 and 2012 were evaluated. Player data were extracted from publically available sources. All demographic data were analyzed. A control group of players matched by age, body mass index (BMI), sex, position, performance, and MLS experience (occurred at 2.6 years into career, designated “index year”) was selected from the MLS during the same years as those undergoing ACLR. The RTS and performance in the MLS were analyzed and compared between cases and controls. Student ttests were performed for analysis of within- and between-group variables. Results: A total of 52 players (57 knees) that met inclusion criteria underwent ACLR while in the MLS. Mean player age was 25.6 ± 3.98 years. Forty players were able to resume play (77%). Of the 40 players (45 knees), 38 (43 knees; 95%) resumed play the season following ACLR (mean, 10 ± 2.8 months after surgery). Mean career length in the MLS after ACLR was 4.0 ± 2.8 years. The revision rate was 10%. There was a significant increase in the incidence of ACL tears in the MLS by year (P < .001), and there was a significantly (P= .002) greater number of ACL tears on the left knee as opposed to the right. Performance in the MLS upon RTS after ACLR was not significantly different versus preinjury. There was no significant difference in survival in the MLS between cases and controls after ACLR or index year. The only significant performance differences between cases and controls were that cases had significantly greater shots taken per season (P= .005) and assists (P= .005) than did controls after the index year. Conclusion: There is a high RTS rate in the MLS following ACLR. Nearly all players resumed play the season after surgery. Performance was not significantly different from preinjury. Only 2 performance measures (shots taken and assists) were significantly different between cases and controls. A significantly greater number of ACL tears occur in the left versus the right knee.

Industry Financial Relationships in Orthopaedic Surgery: Analysis of the Sunshine Act Open Payments Database and Comparison with Other Surgical Subspecialties

BACKGROUND Industry financial relationships for orthopaedic surgeons in the United States are now publicly reported in the Sunshine Act Open Payments database. We sought to present these data in a more easily understandable format and to describe how industry relationships in orthopaedic surgery compare with other surgical subspecialties. METHODS The Open Payments database was searched for all records of industry financial relationships for orthopaedic surgeons. Data analyzed included the value of reported financial relationships per surgeon, the type of financial relationship, and geographic region. Similar analytics were collected for neurological surgery, urology, plastic surgery, and otolaryngology. Data were normalized to the overall number of providers in each subspecialty in the United States from the American Medical Association 2012 data. RESULTS For 12,320 orthopaedic surgeons, 58,127 industry financial relationships were reported, with a total value of

Osteochondral Allograft Transplantation of the Knee: Analysis of Failures at 5 Years:

80.2 million. Royalties or licensing fees, which were received by 1.7% of U.S. orthopaedic surgeons, accounted for 69.5% of the total monetary value of payments to orthopaedic surgeons. Between August and December 2013, 50.1% of U.S. orthopaedic surgeons had a reported financial relationship. Orthopaedics had the second lowest percentage of physicians with industry financial relationships among the five surgical subspecialties studied. The overall value of payments per orthopaedic surgeon was higher than in the other subspecialties, driven by the large value of royalties and licensing. CONCLUSIONS One-half of U.S. orthopaedic surgeons have industry financial relationships reported in the Open Payments database. Orthopaedic surgeons are less likely than most surgical subspecialists to receive industry payments, and the majority of the overall value of orthopaedic financial relationships is driven by a small number of orthopaedic surgeons receiving royalties and licensing for reimbursable innovation within the field.

Economic Analyses in Anterior Cruciate Ligament Reconstruction: A Qualitative and Systematic Review.

Background: Osteochondral allograft transplantation (OAT) is being performed with increasing frequency, and the need for reoperations is not uncommon. Purpose: To quantify survival for OAT and report findings at reoperations. Study Design: Case series; Level of evidence, 4. Methods: A review of prospectively collected data of 224 consecutive patients who underwent OAT by a single surgeon with a minimum follow-up of 2 years was conducted. The reoperation rate, timing of reoperation, procedure performed, and findings at surgery were reviewed. Failure was defined by revision OAT, conversion to knee arthroplasty, or gross appearance of graft failure at second-look arthroscopic surgery. Results: A total of 180 patients (mean [±SD] age, 32.7 ± 10.4 years; 52% male) who underwent OAT with a mean follow-up of 5.0 ± 2.7 years met the inclusion criteria (80% follow-up). Of these, 172 patients (96%) underwent a mean of 2.5 ± 1.7 prior surgical procedures on the ipsilateral knee before OAT. Forty-eight percent of OAT procedures were isolated, while 52% were performed with concomitant procedures including meniscus allograft transplantation (MAT) in 65 (36%). Sixty-six patients (37%) underwent a reoperation at a mean of 2.5 ± 2.5 years, with 32% (21/66) undergoing additional reoperations (range, 1-3). Arthroscopic debridement was performed in 91% of patients with initial reoperations, with 83% showing evidence of an intact graft; of these, 9 ultimately progressed to failure at a mean of 4.1 ± 1.9 years. A total of 24 patients (13%) were considered failures at a mean of 3.6 ± 2.6 years after the index OAT procedure because of revision OAT (n = 7), conversion to arthroplasty (n= 12), or appearance of a poorly incorporated allograft at arthroscopic surgery (n = 5). The number of previous surgical procedures was independently predictive of reoperations and failure; body mass index was independently predictive of failure. Excluding the failed patients, statistically and clinically significant improvements were found in the Lysholm score, International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, and Short Form–12 physical component summary at final follow-up (P < .001 for all), with inferior outcomes (albeit overall improved) in patients who underwent a reoperation. Conclusion: In this series, there was a 37% reoperation rate and an 87% allograft survival rate at a mean of 5 years after OAT. The number of previous ipsilateral knee surgical procedures was predictive of reoperations and failure. Of the patients who underwent arthroscopic debridement with an intact graft at the time of arthroscopic surgery, 82% experienced significantly improved outcomes, while 18% ultimately progressed to failure. This information can be used to counsel patients on the implications of a reoperation after OAT.

Publication and Level of Evidence Trends in The American Journal of Sports Medicine From 1996 to 2011

Background: As the health care system in the United States (US) transitions toward value-based care, there is an increased emphasis on understanding the cost drivers and high-value procedures within orthopaedics. To date, there has been no systematic review of the economic literature on anterior cruciate ligament reconstruction (ACLR). Purpose: To evaluate the overall evidence base for economic studies published on ACLR in the orthopaedic literature. Data available on the economics of ACLR are summarized and cost drivers associated with the procedure are identified. Study Design: Systematic review. Methods: All economic studies (including US-based and non–US-based) published between inception of the MEDLINE database and October 3, 2014, were identified. Given the heterogeneity of the existing evidence base, a qualitative, descriptive approach was used to assess the collective results from the economic studies on ACLR. When applicable, comparisons were made for the following cost-related variables associated with the procedure for economic implications: outpatient versus inpatient surgery (or outpatient vs overnight hospital stay vs >1-night stay); bone–patellar tendon–bone (BPTB) graft versus hamstring (HS) graft source; autograft versus allograft source; staged unilateral ACLR versus bilateral ACLR in a single setting; single- versus double-bundle technique; ACLR versus nonoperative treatment; and other unique comparisons reported in single studies, including computer-assisted navigation surgery (CANS) versus traditional surgery, early versus delayed ACLR, single- versus double-incision technique, and finally the costs of ACLR without comparison of variables. Results: A total of 24 studies were identified and included; of these, 17 included studies were cost identification studies. The remaining 7 studies were cost utility analyses that used economic models to investigate the effect of variables such as the cost of allograft tissue, fixation devices, and physical therapy, the percentage and timing of revision surgery, and the cost of revision surgery. Of the 24 studies, there were 3 studies with level 1 evidence, 8 with level 2 evidence, 6 with level 3 evidence, and 7 with level 4 evidence. The following economic comparisons were demonstrated: (1) ACLR is more cost-effective than nonoperative treatment with rehabilitation only (per 3 cost utility analyses); (2) autograft use had lower total costs than allograft use, with operating room supply costs and allograft costs most significant (per 5 cost identification studies and 1 cost utility analysis); (3) results on hamstring versus BPTB graft source are conflicting (per 2 cost identification studies); (4) there is significant cost reduction with an outpatient versus inpatient setting (per 5 studies using cost identification analyses); (5) bilateral ACLR is more cost efficient than 2 unilateral ACLRs in separate settings (per 2 cost identification studies); (6) there are lower costs with similarly successful outcomes between single- and double-bundle technique (per 3 cost identification studies and 2 cost utility analyses). Conclusion: Results from this review suggest that early single-bundle, single (endoscopic)-incision outpatient ACLR using either BPTB or HS autograft provides the most value. In the setting of bilateral ACL rupture, single-setting bilateral ACLR is more cost-effective than staged unilateral ACLR. Procedures using CANS technology do not yet yield results that are superior to the results of a standard surgical procedure, and CANS has substantially greater costs.

Current Status of Evidence-Based Sports Medicine

Background: There has been recent increased emphasis on the publication quality and levels of evidence in orthopaedic sports medicine clinical research. The American Journal of Sports Medicine (AJSM) began publishing levels of evidence in the abstracts of clinical articles in 2005. Purpose: To analyze trends in the characteristics and levels of evidence of articles published in AJSM. Study Design: Meta-analysis. Methods: All articles in AJSM from 1996, 2001, 2006, and 2011 were analyzed. Articles were analyzed for type: clinical original research, basic science, current concepts review, and case report. Clinical articles were assigned a level of evidence from 1 to 4 and categorized as therapeutic, prognostic, diagnostic, or economic. Descriptive information was collected regarding funding, authorship, and study characteristics. Statistics were calculated using χ2 tests. Results: A total of 795 articles were analyzed. From 1996 to 2011, there has been a significant increase in the percentage of level 1 and 2 articles (9.4% to 23.0%; P = .007) and a significant decrease in the percentage of level 3, 4, and 5 articles (55.1% to 45.1%; P = .037). There was a significant increase in the percentage of therapeutic studies (46.8% to 68.6%; P = .004) and a decrease in prognostic studies (36.7% to 22.2%; P = .03). Publishing authors were from 31 countries, notable for a significant increase in the percentage of studies published by authors from outside the United States from 1996 to 2011 (20.3% to 53.0%; P < .001). The percentage of articles reporting a financial conflict of interest significantly increased during this time (26.1% to 42.2%; P = .006). Conclusion: From 1996 to 2011, the proportion of level 1 and 2 evidence studies published in AJSM has increased significantly. There has been an increase in therapeutic studies and a decrease in prognostic studies. There has been an increase in the number of international studies published.