Updates on Management of Avascular Necrosis Using Hip Arthroscopy for Core Decompression.

Osteonecrosis of the femoral head (ONFH) is caused when circulation within the femoral head is disrupted. Etiology of this disease is characterized by either traumatic events or atraumatic risk factors, such as chronic alcohol consumption or glucocorticoid use. ONFH commonly presents as pain in the groin, gluteus muscles, and/or knee with reductions in internal rotation range of motion of the hip. ONFH pathology can be confirmed with radiographic or advanced imaging and characterized by stage, size and location of the lesion. Treatment for ONFH consists of conservative and therapeutic methods as well as surgical intervention. Historically, ONFH has been treated using total hip arthroplasty (THA), but with increasing incidence in a younger, active population, measures to preserve the native hip joint have been explored. Recent advancements in hip arthroscopy and arthroscopy-assisted core decompression have led to improved outcomes, reduced pain and higher hip survival rate for early onset ONFH compared with more invasive approaches such as THA. Biologic treatments combined with arthroscopic core decompression have also shown improved outcomes and quality of life in few reports, suggesting a potential role for biologic adjuncts. The current study provides a comprehensive review and update on the literature surrounding arthroscopy-assisted core decompression for patients with ONFH.

Seasonal and monthly trends in elbow ulnar collateral ligament injuries and surgeries: a national epidemiological study.

Background: Monthly incidence of elbow ulnar collateral ligament (UCL) injuries and surgeries is relatively unknown. Defining seasonal peaks of UCL injuries and surgeries may identify opportunities for injury-prevention strategies. The purpose of this study is to analyze seasonal and monthly variations in UCL injuries and surgeries across the United States with emphasis on the timing of baseball season. Methods: The Truven Health MarketScan database (2013-2015) was queried for patients younger than 40 years with a diagnosis code of elbow UCL sprain and a procedural code for UCL repair or reconstruction. Differences in patient characteristics were evaluated using chi-square and Mann-Whitney U-tests. Negative binomial regression models were calculated for UCL injuries and surgeries to assess monthly trends. Results: UCL injuries were sustained by 13,894 patients, with 1404 (10.1%) patients having undergone surgery. The median age at first diagnosis was 17 years, and the median age of patients requiring surgery decreased from 20 to 18 years from 2013 to 2015 (P = .75). Most UCL injuries (n = 3785) and surgeries (n = 438) occurred during the spring season (March 21-June 20), and spring injuries were most likely to result in surgical management (11.6%). During the baseball season (March to September), the number of UCL injuries peaked in April/May, then declined, except for a second peak in September/October (incidence rate ratio 0.97; confidence interval 0.95, 0.99; P = .01). The number of UCL surgeries steadily increased from March (n = 116) to June (n = 152), followed by a gradual decline (incidence rate ratio 1.00; confidence interval 0.96, 1.04; P = .99). Conclusion: Athletes frequently experienced UCL injuries and surgeries in the early months (April-June) of the baseball season. More emphasis should be paid to rehabilitative strategies at the beginning of a baseball season to help mitigate injury risk.

Patient-Reported Outcomes and Factors Associated with Achieving the Minimal Clinically Important Difference After ACL Reconstruction: Results at a Mean 7.7-Year Follow-up.

BACKGROUND: Analyzing outcomes and the minimal clinically important difference (MCID) after anterior cruciate ligament reconstruction (ACLR) is of increased interest in the orthopaedic literature. The purposes of this study were to report outcomes after ACLR at medium to long-term follow-up, identify the threshold preoperative outcome values that would be predictive of achieving the MCID postoperatively, and analyze outcome maintenance at medium to long-term follow-up after ACLR. METHODS: Active athletes who underwent ACLR were identified in an institutional ACL registry. Patient-reported outcome measures (PROMs) were administered preoperatively and at the 2-year and >5-year postoperative follow-up; measures included the International Knee Documentation Committee (IKDC) form, the 12-item Short Form Health Survey (SF-12) Physical Component Summary (PCS) and Mental Component Summary (MCS), and Lysholm scale. We calculated the MCID from baseline to each of the 2 follow-up periods (2-year and mean 7.7-year). Logistic regression was performed to investigate factors associated with achievement of the MCID. RESULTS: A total of 142 patients (mean follow-up, 7.7 years [range, 6.6 to 9.1 years]) underwent ACLR. The mean age and body mass index at the time of surgery were 27.2 ± 13.0 years and 23.2 ± 3.0 kg/m2, respectively. Final postoperative outcome scores improved significantly from baseline for the IKDC (50.9 ± 14.7 to 87.9 ± 11.2), SF-12 PCS (41.6 ± 8.9 to 55.6 ± 3.2), and Lysholm scale (62.2 ± 17.6 to 90.5 ± 10.3) (p < 0.0001), while the SF-12 MCS did not improve significantly (54.2 ± 8.0 to 54.4 ± 6.0) (p = 0.763). Between 2- and >5-year follow-up, the SF-12 PCS showed significant improvement (54.6 ± 4.5 to 55.6 ± 3.2; p = 0.036), while no change was noted in the IKDC (87.6 ± 11.1 to 87.9 ± 11.2), SF-12 MCS (55.5 ± 5.3 to 54.4 ± 6.0), and Lysholm scale (89.8 ± 10.6 to 90.5 ± 10.3) (p ≥ 0.09). At the time of final follow-up, the MCID was achieved by 94.7% of patients for the IKDC, 80.8% for the Lysholm, 79.0% for the SF-12 PCS, and 28.2% for the SF-12 MCS. At 2-year follow-up, 95.3% of patients were either "very" or "somewhat" satisfied with their surgery, compared with 88.6% at the time of final follow-up. CONCLUSIONS: We found a high level of maintained function following ACLR. The IKDC, SF-12 PCS, and Lysholm scores improved significantly after ACLR at the time of final follow-up and were not significantly different between follow-up periods. Approximately 95% and 89% of patients reported being satisfied with the outcome of surgery at the 2-year and final follow-up, respectively. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Multiyear Factor VIII Expression after AAV Gene Transfer for Hemophilia A.

BACKGROUND: The goal of gene therapy for patients with hemophilia A is to safely impart long-term stable factor VIII expression that predictably ameliorates bleeding with the use of the lowest possible vector dose. METHODS: In this phase 1-2 trial, we infused an investigational adeno-associated viral (AAV) vector (SPK-8011) for hepatocyte expression of factor VIII in 18 men with hemophilia A. Four dose cohorts were enrolled; the lowest-dose cohort received a dose of 5 × 1011 vector genomes (vg) per kilogram of body weight, and the highest-dose cohort received 2 × 1012 vg per kilogram. Some participants received glucocorticoids within 52 weeks after vector administration either to prevent or to treat a presumed AAV capsid immune response. Trial objectives included evaluation of the safety and preliminary efficacy of SPK-8011 and of the expression and durability of factor VIII. RESULTS: The median safety observation period was 36.6 months (range, 5.5 to 50.3). A total of 33 treatment-related adverse events occurred in 8 participants; 17 events were vector-related, including 1 serious adverse event, and 16 were glucocorticoid-related. Two participants lost all factor VIII expression because of an anti-AAV capsid cellular immune response that was not sensitive to immune suppression. In the remaining 16 participants, factor VIII expression was maintained; 12 of these participants were followed for more than 2 years, and a one-stage factor VIII assay showed no apparent decrease in factor VIII activity over time (mean [±SD] factor VIII activity, 12.9±6.9% of the normal value at 26 to 52 weeks when the participants were not receiving glucocorticoids vs. 12.0±7.1% of the normal value at >52 weeks after vector administration; 95% confidence interval [CI], -2.4 to 0.6 for the difference between matched pairs). The participants had a 91.5% reduction (95% CI, 88.8 to 94.1) in the annualized bleeding rate (median rate, 8.5 events per year [range, 0 to 43.0] before vector administration vs. 0.3 events per year [range, 0 to 6.5] after vector administration). CONCLUSIONS: Sustained factor VIII expression in 16 of 18 participants who received SPK-8011 permitted discontinuation of prophylaxis and a reduction in bleeding episodes. No major safety concerns were reported. (Funded by Spark Therapeutics and the National Heart, Lung, and Blood Institute; ClinicalTrials.gov numbers, NCT03003533 and NCT03432520.).

The use of biologics to improve patient-reported outcomes in hip preservation.

Despite lack of clear understanding, the use of biologic treatment methods has increased in the United States. Therapeutic methods, including platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC) and hyaluronic acid (HA) among other biologics, are commonly associated with relief of pain in a number of different orthopedic conditions. Within the past two decades, hip preservationists have investigated the roles of these biologic treatments in both non-operative and surgical management of common hip conditions. The purpose is to review the published literature surrounding the application and efficacy of biologics, most notably PRP, BMAC and HA, in the clinical management of hip conditions. The hip conditions examined in this review include hip osteoarthritis, femoroacetabular impingement syndrome and associated labral tear pathology, avascular necrosis of the femoral head and gluteal/hamstring tendinopathy. While our review of the literature suggests that there is support for the implementation of biologics to relieve pain and improve function for hip conditions. Through further research efforts, it is important to stay updated with the clinical efficacy of biologics in hip preservation.

PROMIS Global-10 poorly correlates with legacy outcomes for patients undergoing hip arthroscopy.

The Patient-Reported Outcomes Measurement Information System (PROMIS) Global-10 assesses generic-related quality of life, but has not been well studied in the orthopaedic literature. The purpose was to compare PROMIS Global-10 and legacy hip-specific patient-reported outcome measures (PROMs) in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS). This study included patients who underwent primary hip arthroscopy with complete preoperative and 6-month post-operative follow-up. PROMIS Global-10 Physical (PROMIS-P) and Mental (PROMIS-M) components, as well as the modified Harris hip score (mHHS) and International Hip Outcome Tool-33 (iHOT-33) were assessed. PROM analysis included: post-operative changes, correlations, floor and ceiling effects and responsiveness. Final analysis included 112 patients. Average age and body mass index were 36.1±11.7 years and 24.8±3.9 kg/m2, respectively. All 6-month PROMs, except PROMIS-M, were significantly improved compared to preoperative level (P<0.02). Preoperatively, PROMIS-P was poorly correlated with mHHS and iHOT-33 (r s <0.4) whereas PROMIS-M was only poorly correlated with iHOT-33 (r s <0.4, 95% CI of 0.02-0.37). Post-operatively, the iHOT-33 was poorly correlated with both PROMIS measures (r s <0.4). The mHHS was fairly correlated with both PROMIS measures (r s <0.6) post-operatively. The effect sizes for mHHS and iHOT-33 were high (d=1.2 and 1.40, respectively), whereas the effect sizes for PROMIS Global-10 were small (d<0.3). PROMIS Global-10 demonstrated lower effect sizes and poor to fair correlation with legacy hip-specific PROMs, and appears to have a limited role in the assessment of patients undergoing hip arthroscopy for FAIS. Therefore, the PROMIS Global-10 may have a limited role in assessing patients with FAIS.

Comparison of Different Functional Tests for Leg Power and Normative Bilateral Asymmetry Index in Healthy Collegiate Athletes.

BACKGROUND: Bilateral leg power is being increasingly investigated as a proxy for the recovery of muscle performance after injury. Functional tests like the single leg hop for distance (SLHD) and single leg vertical jump (SLVJ) are often used to determine symmetry and return to play (RTP) readiness. As an injury predictor, leg power is accurately measured with the Keiser Air420 seated leg press. PURPOSE: To measure and analyze lower leg asymmetry in healthy collegiate athletes across each test battery. METHODS: Eighty-eight healthy student-athletes (44 males, 44 females) across 14 varsity teams at Wake Forest University performed the SLHD, SLVJ, and the Keiser. Horizontal and vertical displacement were measured via the SLHD and SLVJ, respectively. Peak power was recorded via the Keiser Air420 leg press. Pearson correlations and repeated measures ANOVA were used to calculate associations and compare bilateral asymmetry indices (BAI) and raw scores. RESULTS: There was a significant effect on each test's raw BAI (P < 0.01). The mean absolute BAI were 5.42 ± 4.9%, 6.64 ± 4.9% and 5.36 ± 4.7% for the SLHD, SLVJ and Keiser, respectively. The SLVJ and Keiser (dominant leg r = 0.832, nondominant leg r = 0.826) were more highly correlated than the SLHD and Keiser (dominant leg r = 0.645, nondominant leg r = 0.687), all of which were statistically significant (P < 0.01). CONCLUSION: At the 90th percentile, healthy collegiate athletes attained <15% BAI. We recommend the implementation of a battery of tests to determine normative lower limb asymmetry. A battery of functional tests may present different asymmetry indices as opposed the 10% reference asymmetry.

Predicting the Risk of Subsequent Hip Surgery Before Primary Hip Arthroscopy for Femoroacetabular Impingement Syndrome: A Machine Learning Analysis of Preoperative Risk Factors in Hip Preservation.

BACKGROUND: The number of patients requiring reoperation has increased as the volume of hip arthroscopy for femoroacetabular impingement syndrome (FAIS) has increased. The factors most important in determining patients who are likely to require reoperation remain elusive. PURPOSE: To leverage machine learning to better characterize the complex relationship across various preoperative factors (patient characteristics, radiographic parameters, patient-reported outcome measures [PROMs]) for patients undergoing primary hip arthroscopy for FAIS to determine which features predict the need for future ipsilateral hip reoperation, namely, revision hip arthroscopy, total hip arthroplasty (THA), hip resurfacing arthroplasty (HRA), or periacetabular osteotomy (PAO). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A cohort of 3147 patients undergoing 3748 primary hip arthroscopy procedures were included from an institutional hip preservation registry. Preoperative computed tomography of the hip was obtained for each patient, from which the following parameters were calculated: the alpha angle; the coronal center-edge angle; the neck-shaft angle; the acetabular version angle at 1, 2, and 3 o'clock; and the femoral version angle. Preoperative PROMs included the modified Harris Hip Score (mHHS), the Hip Outcome Score (HOS)-Activities of Daily Living subscale (HOS-ADL) and the Sport Specific subscale, and the international Hip Outcome Tool (iHOT-33). Random forest models were created for revision hip arthroscopy, the THA, the HRA, and the PAO. Area under the curve (AUC) for the receiver operating characteristic curve and accuracy were calculated to evaluate each model. RESULTS: A total of 171 patients (4.6%) underwent subsequent hip surgery after primary hip arthroscopy for FAIS. The AUC and accuracy, respectively, were 0.77 (fair) and 76% for revision hip arthroscopy (mean, 26.4-month follow-up); 0.80 (good) and 81% for THA (mean, 32.5-month follow-up); 0.62 (poor) and 69% for HRA (mean, 45.4-month follow-up); and 0.76 (fair) and 74% for PAO (mean, 30.4-month follow-up). The most important factors in predicting reoperation after primary hip arthroscopy were higher body mass index (BMI) and lower preoperative HOS-ADL for revision hip arthroscopy, greater age and lower preoperative iHOT-33 for THA, increased BMI for HRA, and larger neck-shaft angle and lower preoperative mHHS for PAO. CONCLUSION: Despite the low failure rate of hip arthroscopy for FAIS, our study demonstrated that machine learning has the capability to identify key preoperative risk factors that may predict subsequent ipsilateral hip surgery before the index hip arthroscopy. Knowledge of these demographic, radiographic, and patient-reported outcome data may aid in preoperative counseling and expectation management to better optimize hip preservation.

Revision Hip Arthroscopy in the Native Hip: A Review of Contemporary Evaluation and Treatment Options.

Hip arthroscopy is a reproducible and efficacious procedure for the treatment of femoroacetabular impingement syndrome (FAIS). Despite this efficacy, clinical failures are observed, clinical entities are challenging to treat, and revision hip arthroscopy may be required. The most common cause of symptom recurrence after a hip arthroscopy that leads to a revision arthroscopy is residual cam morphology as a result of inadequate femoral osteochondroplasty and restoration of head-neck offset, though several other revision etiologies including progressive chondral and labral pathologies also exist. In these cases, it is imperative to perform a comprehensive examination to identify the cause of a failed primary arthroscopy as to assess whether or not a revision hip arthroscopy procedure is indicated. When a secondary procedure is indicated, approaches may consist of revision labral repair, complete labral reconstruction, or labral augmentation depending on labral integrity. Gross instability or imaging-based evidence of microinstability may necessitate capsular augmentation or plication. If residual cam or pincer morphology is present, additional resection of the osseous abnormalities may be warranted. This review article discusses indications, the evaluation of patients with residual symptoms after primary hip arthroscopy, and the evaluation of outcomes following revision hip arthroscopy through an evidence-based discussion. We also present a case example of a revision hip arthroscopy procedure to highlight necessary intraoperative techniques during a revision hip arthroscopy.

Defining Minimal Clinically Important Difference After Open Hip Abductor Repair.

BACKGROUND: Open repair for gluteus medius and minimus tears is a common surgical treatment for patients with lateral hip pain associated with abductor tears; however, clinically meaningful outcomes have not been described after open surgical treatment. PURPOSE: To define the minimal clinically important difference (MCID) in patient-reported outcome measures (PROMs) in patients undergoing open gluteus medius or minimus repair, and to identify preoperative patient characteristics predictive of achieving MCID postoperatively. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective review of prospectively collected data from a consecutive series of patients undergoing open abductor repair between July 2010 and April 2019 was conducted. Perioperative patient data collected included patient characteristics and preoperative and postoperative modified Harris Hip Score (mHHS) and International Hip Outcome Tool (iHOT-33) score. Paired t tests were utilized to compare preoperative and postoperative PROMs and MCID was calculated for both PROMs. Multivariate logistical regression analysis was used to assess the association between preoperative variables and the likelihood for achieving MCID. RESULTS: A total of 47 patients were included in the study. The majority of patients were female (78.7%), with an average age of 63 ± 10.7 years. The average follow-up for both the mHHS and the iHOT-33 surveys was 37.8 ± 27.9 months (range, 10-102 months). Patients demonstrated statistically significant improvements on the mHHS and iHOT-33 postoperatively (P < .001 for both). The MCIDs of mHHS and iHOT-33 were calculated to be 9.9 and 14.3, respectively. Overall, 82.9% of patients achieved MCID for mHHS and 84.1% of patients achieved MCID for iHOT-33 postoperatively. Multivariate logistical analysis demonstrated younger patients were less likely to achieve MCID for both outcome measures. Four patients (8.5%) suffered postoperative complications after open repair. CONCLUSION: This study defined MCID for mHHS and iHOT-33 for patients undergoing open repair of hip abductor tears, with a large percentage of patients (>80%) achieving meaningful outcomes for both outcome measures. There was a low complication rate. Younger patients were less likely to achieve MCID compared with older patients.

The modern reverse shoulder arthroplasty and an updated systematic review for each complication: part II.

BACKGROUND: Globally, reverse shoulder arthroplasty (RSA) has moved away from the Grammont design to modern prosthesis designs. The purpose of this study was to provide a focused, updated systematic review for each of the most common complications of RSA by limiting each search to publications after 2010. In this part II, the following were examined: (1) instability, (2) humerus/glenoid fracture, (3) acromial/scapular spine fractures (AF/SSF), and (4) problems/miscellaneous. METHODS: Four separate PubMed database searches were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Overall, 137 studies for instability, 94 for humerus/glenoid fracture, 120 for AF/SSF, and 74 for problems/miscellaneous were included in each review, respectively. Univariate analysis was performed with chi-square and Fisher exact tests. RESULTS: The Grammont design had a higher instability rate vs. all other designs combined (4.0%, 1.3%; P < .001), and the onlay humerus design had a lower rate than the lateralized glenoid design (0.9%, 2.0%; P = .02). The rate for intraoperative humerus fracture was 1.8%; intraoperative glenoid fracture, 0.3%; postoperative humerus fracture, 1.2%; and postoperative glenoid fracture, 0.1%. The rate of AF/SSF was 2.6% (371/14235). The rate for complex regional pain syndrome was 0.4%; deltoid injury, 0.1%; hematoma, 0.3%; and heterotopic ossification, 0.8%. CONCLUSIONS: Focused systematic reviews of recent literature with a large volume of shoulders demonstrate that using non-Grammont modern prosthesis designs, complications including instability, intraoperative humerus and glenoid fractures, and hematoma are significantly reduced compared with previous studies. As the indications continue to expand for RSA, it is imperative to accurately track the rate and types of complications in order to justify its cost and increased indications.

Surgical Treatment of Labral Tears: Debridement, Repair, and Reconstruction.

Advances in hip preservation surgery have to lead to increased utilization of hip arthroscopy. With this, there has also been a growth in the understanding of various hip conditions, therefore, leading to an increase in hip conditions amenable to arthroscopic intervention. The acetabular hip labrum has been at the forefront of arthroscopic advances in the hip. The labrum is important for hip stability, provision of the suction seal, and joint proprioception. Given the labrum's central role in hip biomechanics, there is increasing emphasis on labral preservation in the form of debridement and repair. In revision settings, advanced techniques such as labral augmentation and reconstruction may play a role in the management of labral pathology. Appropriate management of the hip labrum at the time of surgery can be an important mediator of the outcome. As such, an understanding of the evolving evidence base and surgical indications and techniques are integral to the treatment and management of labral pathology.

Current Orthopaedic Health Economic Literature: Quality Is High but Ethical and Societal Perspectives Are Lacking.

PURPOSE: To evaluate the quality of orthopaedic cost-effectiveness analyses (CEAs) in accordance with the 2016 recommendations by the Second Panel on Cost-Effectiveness in Health and Medicine. METHODS: A systematic review of all CEAs from September 2017 to September 2019 in the 10 highest impact orthopaedic surgery journals was performed. Quality scoring used the Quality of Health Economic Studies (QHES) instrument and the Second Panel checklist. QHES scores ≥80 were considered high quality and <50 poor quality. Mann-Whitney U and independent samples Kruskal-Wallis tests compared individual and multiple groups, respectively. Linear regression analysis was performed to correlate QHES score, checklist item fulfillment, and impact factor. RESULTS: The 10 highest impact orthopaedic journals published 6,323 articles with 35 (0.55%) meeting inclusion criteria. Total joint arthroplasty (TJA) and sports medicine articles comprised 65.7% of included studies. Overall mean QHES score was 89.0 ± 7.6, with 82.8% considered high quality. Mean proportion of Second Panel checklist items fulfilled was 82.1% ± 13.3%, but no studies performed an impact inventory accounting for consequences within and outside the health care sector or discussed ethical implications. Mean QHES score and satisfied checklist items were significantly different by journal (P = .025 and P = .01, respectively). In addition, there was a moderate positive correlation between QHES score and impact factor (r = 0.446, P = .007). TJA CEAs satisfied a higher number of checklist items compared with spine surgery CEAs. CONCLUSIONS: Recent orthopaedic CEAs have generally been high quality according to updated Second Panel guidelines but consistently miss checklist items relating to societal impact and ethics. TJA and sports medicine continue to be the most frequently studied orthopaedic subspecialties in health economics, and the breadth of orthopaedic procedures analyzed by CEAs has improved. STUDY DESIGN: Level IV, systematic review.

Achievement of the minimal clinically important difference following open proximal hamstring repair.

There is a paucity of literature on patient-reported outcome measures (PROMs) following proximal hamstring repair beyond return to play, patient satisfaction and pain improvement. The minimal clinically important difference (MCID) defines the minimum degree of quantifiable improvement that a patient can perceive, but the MCID and predictors of this measure have not been defined for this patient population. This study aimed to define the MCID and determine the efficacy of open proximal hamstring repair through achievement of MCID and identify characteristics predictive of achieving MCID. A retrospective cohort review of an institutional hip registry was conducted, analyzing the modified Harris Hip Score (mHHS) and International Hip Outcome Tool (iHOT-33). MCID was calculated using a distribution-based method. Demographic and clinical variables predictive of achieving MCID were analyzed using univariable and multivariate logistic regression analyses. Thirty-nine patients who underwent open proximal hamstring repair were included. The mean patient age was 48.5 ± 12.4 years, with a mean follow-up of 37.1 ± 28 months. The MCID was determined for each PROM (mHHS-11.8; iHOT-33-12.6). A high percentage of patients achieved MCID for both PROMs (mHHS-85.7%; iHOT-33-91.4%). Univariate logistical regression demonstrated increased age (P = 0.163), increased body mass index (BMI; P = 0.072), requirement for inpatient admission (P = 0.088) and pre-operative iHOT-33 (P = 0.104) trended towards clinically significant predictors of not achieving MCID. A high percentage of patients achieved MCID while age, BMI, inpatient admission and pre-operative iHOT-33 appear to influence the achievement of clinically significant outcome in patients undergoing open proximal hamstring repair.

PROMIS Global-10 performs poorly relative to legacy shoulder instruments in patients undergoing total shoulder arthroplasty for glenohumeral arthritis.

BACKGROUND: The PROMIS Global-10 is a 10-item questionnaire that assesses general health-related quality of life. There is a paucity of research on the utility of the PROMIS Global-10 in the evaluation of orthopedic conditions. The aim of this study is to compare PROMIS Global-10 and legacy shoulder-specific patient-reported outcome measures (PROMs) in patients undergoing total shoulder arthroplasty (TSA) for shoulder arthritis. METHODS: This retrospective cohort study included patients who underwent TSA for shoulder arthritis and completed preoperative and 1-year postoperative surveys. Primary outcome measures were the physical (PROMIS-P) and mental (PROMIS-M) components of PROMIS Global-10. The legacy PROMs included the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score, the Single Assessment Numeric Evaluation (SANE), and the Shoulder Activity Scale (SAS). Analyses included postoperative changes for each outcome, correlations between measures and a responsiveness assessment. RESULTS: A total of 170 patients met inclusion criteria. Average age and body mass index were 67.7 ± 7.8 years and 28.0 ± 4.9, respectively. All legacy PROMs and PROMIS-P were significantly higher at 1-year follow-up compared with the preoperative level (P < .0001), whereas PROMIS-M did not change (P = .06). Preoperatively, both PROMIS components were either poorly correlated with all legacy PROMs (r < .04, P < .05) or not correlated at all (P > .05). Postoperatively, PROMIS-M was poorly correlated with all legacy PROMs (r < .04, P < .01), whereas PROMIS-P had fair correlation with ASES (r = .5, P < .0001) and poor correlation with SANE and SAS (r < .04, P < .01). A floor effect was observed for SANE, and SANE and ASES had a ceiling effect. The effect sizes for SANE and ASES were high (d = 2.01 and 2.39 respectively), whereas the effect size for SAS was moderate (d = 0.65), and the effect sizes for the PROMIS measures were small (d < .5). ASES was the most responsive measure and PROMIS-M was the least responsive. CONCLUSION: PROMIS Global-10 had limited correlation with legacy PROMs and was less responsive at 1-year follow-up in patients following TSA. The Global-10 appears to have limited utility in the evaluation of patients with shoulder arthritis both preoperatively and after TSA.

Radiographic Indices Are Not Predictive of Clinical Outcomes Among 1735 Patients Indicated for Hip Arthroscopic Surgery: A Machine Learning Analysis.

BACKGROUND: The relationship between the preoperative radiographic indices for femoroacetabular impingement syndrome (FAIS) and postoperative patient-reported outcome measure (PROM) scores continues to be under investigation, with inconsistent findings reported. PURPOSE: To apply a machine learning model to determine which preoperative radiographic indices, if any, among patients indicated for the arthroscopic correction of FAIS predict whether a patient will achieve the minimal clinically important difference (MCID) for 1- and 2-year PROM scores. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 1735 consecutive patients undergoing primary hip arthroscopic surgery for FAIS were included from an institutional hip preservation registry. Patients underwent preoperative computed tomography of the hip, from which the following radiographic indices were calculated by a musculoskeletal radiologist: alpha angle, beta angle, sagittal center-edge angle, coronal center-edge angle, neck shaft angle, acetabular version angle, and femoral version angle. PROM scores were collected preoperatively, at 1 year postoperatively, and at 2 years postoperatively for the modified Harris Hip Score (mHHS), the Hip Outcome Score (HOS)-Activities of Daily Living (HOS-ADL) and -Sport Specific (HOS-SS), and the International Hip Outcome Tool (iHOT-33). Random forest models were created for each PROM at 1 and 2 years' follow-up, with each PROM's MCID used to establish clinical meaningfulness. Data inputted into the models included ethnicity, laterality, sex, age, body mass index, and radiographic indices. Comprehensive and separate models were built specifically to assess the association of the alpha angle, femoral version angle, coronal center-edge angle, McKibbin index, and hip impingement index with respect to each PROM. RESULTS: As evidenced by poor area under the curves and P values >.05 for each model created, no combination of radiographic indices or isolated index (alpha angle, coronal center-edge angle, femoral version angle, McKibbin index, hip impingement index) was a significant predictor of a clinically meaningful improvement in scores on the mHHS, HOS-ADL, HOS-SS, or iHOT-33. The mean difference between 1- and 2-year PROM scores compared with preoperative values exceeded the respective MCIDs for the cohort. CONCLUSION: In patients appropriately indicated for FAIS corrective surgery, clinical improvements can be achieved, regardless of preoperative radiographic indices, such as the femoral version angle, coronal center-edge angle, and alpha angle. No specific radiographic parameter or combination of indices was found to be predictive of reaching the MCID for any of the 4 studied hip-specific PROMs at either 1 or 2 years' follow-up.

Patient-Reported Outcomes Measurement Information System Physical Function Has a Lower Effect Size and is Less Responsive Than Legacy Hip Specific Patient Reported Outcome Measures Following Arthroscopic Hip Surgery.

PURPOSE: To compare the use and responsiveness of Patient Reported Outcomes Measurement Information System (PROMIS) to legacy patient-reported outcome measures (PROMs) in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS) at 6-month follow-up. METHODS: Data from patients who underwent primary hip arthroscopy with routine capsular closure between August 2018 and January 2019 for the treatment of FAIS were analyzed. Preoperative outcomes, 6-month postoperative outcomes, and demographics were recorded. Primary outcome measures included PROMIS Physical Function (PROMIS-PF), PROMIS Pain Interference (PROMIS-PI), and PROMIS Depression. The legacy PROMs included Hip Outcome Score Activities of Daily Living (HOS-ADL), Hip Outcome Score Sport Subscale (HOS-SS), and the international hip outcome tool 12 questions (iHOT-12). Floor and ceiling effects along with the responsiveness and Cohen's d effect size of each PROM tool were calculated. RESULTS: Ninety-six patients with an average age and body mass index of 32.4 ± 11.9 years and 25.9 ± 6.1 kg/m2, respectively, were included in the final analysis. All outcomes were significantly higher at 6 months compared with the preoperative level (P < .001) except for PROMIS Depression (P = .873). PROMIS-PF demonstrated excellent correlation with HOS-SS (r = 0.81; P < .001), very good correlation with HOS-ADL (r = 0.73; P < .001), and good correlation with iHOT-12 (r = 0.68; P < .001). No floor was observed for any measure. The effect size was large for all outcomes, except PROMIS Depression (d = 0.04), but largest for iHOT12 (d = 1.87) followed by HOS-ADL (d = 1.29). The iHOT-12 was more responsive than PROMIS-PI (relative efficiency [RE] = 3.95), PROMIS-PF (RE = 4.13), HOS-ADL (RE = 2.26), and HOS-SS (RE = 3.84). HOS-SS was similarly responsive to PROMIS-PI (RE=1.03) and PROMIS-PF (RE=1.08). However, PROMIS-PF was overall the least responsive. CONCLUSIONS: In patients at 6 months postoperatively from hip arthroscopy for FAIS, iHOT-12 was the most responsive and had the largest effect size. In contrast, PROMIS-PF had a lower effect size compared with legacy hip-specific PROMs. Additionally, PROMIS-PF did not correlate as well with iHOT-12 compared with HOS-SS. LEVEL OF EVIDENCE: Level IV, case series.

Infused factor VIII-expressing platelets or megakaryocytes as a novel therapeutic strategy for hemophilia A.

B-domainless factor VIII (FVIII) ectopically expressed in megakaryocytes (MKs) is stored in α granules of platelets (pFVIII) and is capable of restoring hemostasis in FVIIInull mice, even in the presence of circulating inhibitors. However, our prior studies have shown that this ectopically expressed pFVIII can injure developing MKs. Moreover, the known risks of prolonged thrombocytopenia after bone marrow transplantation are significant challenges to the use of this strategy to treat individuals with severe hemophilia A and particularly those with intractable clinically relevant inhibitors. Because of these limitations, we now propose the alternative therapeutic pFVIII strategy of infusing pFVIII-expressing MKs or platelets derived from induced pluripotent stem cells (iPSCs). pFVIII-expressing iPSC-derived MKs, termed iMKs, release platelets that can contribute to improved hemostasis in problematic inhibitor patients with hemophilia A. As proof of principle, we demonstrate that hemostasis can be achieved in vitro and in vivo with pFVIII-expressing platelets and show prolonged efficacy. Notably, pFVIII-expressing platelets are also effective in the presence of inhibitors, and their effect was enhanced with recombinant FVIIa. Human pFVIII-expressing iMKs improved hemostasis in vitro, and derived platelets from infused human pFVIII-expressing iMKs improved hemostasis in FVIIInull mice. These studies indicate the potential therapeutic use of recurrent pFVIII-expressing MK or platelet infusions with prolonged hemostatic coverage that may be additive with bypassing agents in hemophilia A patients with neutralizing inhibitors.

Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant.

BACKGROUND: The prevention of bleeding with adequately sustained levels of clotting factor, after a single therapeutic intervention and without the need for further medical intervention, represents an important goal in the treatment of hemophilia. METHODS: We infused a single-stranded adeno-associated viral (AAV) vector consisting of a bioengineered capsid, liver-specific promoter and factor IX Padua (factor IX-R338L) transgene at a dose of 5×1011 vector genomes per kilogram of body weight in 10 men with hemophilia B who had factor IX coagulant activity of 2% or less of the normal value. Laboratory values, bleeding frequency, and consumption of factor IX concentrate were prospectively evaluated after vector infusion and were compared with baseline values. RESULTS: No serious adverse events occurred during or after vector infusion. Vector-derived factor IX coagulant activity was sustained in all the participants, with a mean (±SD) steady-state factor IX coagulant activity of 33.7±18.5% (range, 14 to 81). On cumulative follow-up of 492 weeks among all the participants (range of follow-up in individual participants, 28 to 78 weeks), the annualized bleeding rate was significantly reduced (mean rate, 11.1 events per year [range, 0 to 48] before vector administration vs. 0.4 events per year [range, 0 to 4] after administration; P=0.02), as was factor use (mean dose, 2908 IU per kilogram [range, 0 to 8090] before vector administration vs. 49.3 IU per kilogram [range, 0 to 376] after administration; P=0.004). A total of 8 of 10 participants did not use factor, and 9 of 10 did not have bleeds after vector administration. An asymptomatic increase in liver-enzyme levels developed in 2 participants and resolved with short-term prednisone treatment. One participant, who had substantial, advanced arthropathy at baseline, administered factor for bleeding but overall used 91% less factor than before vector infusion. CONCLUSIONS: We found sustained therapeutic expression of factor IX coagulant activity after gene transfer in 10 participants with hemophilia who received the same vector dose. Transgene-derived factor IX coagulant activity enabled the termination of baseline prophylaxis and the near elimination of bleeding and factor use. (Funded by Spark Therapeutics and Pfizer; ClinicalTrials.gov number, NCT02484092 .).

FLI1 level during megakaryopoiesis affects thrombopoiesis and platelet biology.

Friend leukemia virus integration 1 (FLI1), a critical transcription factor (TF) during megakaryocyte differentiation, is among genes hemizygously deleted in Jacobsen syndrome, resulting in a macrothrombocytopenia termed Paris-Trousseau syndrome (PTSx). Recently, heterozygote human FLI1 mutations have been ascribed to cause thrombocytopenia. We studied induced-pluripotent stem cell (iPSC)-derived megakaryocytes (iMegs) to better understand these clinical disorders, beginning with iPSCs generated from a patient with PTSx and iPSCs from a control line with a targeted heterozygous FLI1 knockout (FLI1+/-). PTSx and FLI1+/- iMegs replicate many of the described megakaryocyte/platelet features, including a decrease in iMeg yield and fewer platelets released per iMeg. Platelets released in vivo from infusion of these iMegs had poor half-lives and functionality. We noted that the closely linked E26 transformation-specific proto-oncogene 1 (ETS1) is overexpressed in these FLI1-deficient iMegs, suggesting FLI1 negatively regulates ETS1 in megakaryopoiesis. Finally, we examined whether FLI1 overexpression would affect megakaryopoiesis and thrombopoiesis. We found increased yield of noninjured, in vitro iMeg yield and increased in vivo yield, half-life, and functionality of released platelets. These studies confirm FLI1 heterozygosity results in pleiotropic defects similar to those noted with other critical megakaryocyte-specific TFs; however, unlike those TFs, FLI1 overexpression improved yield and functionality.