William W. Schairer

Background: Numerous clinical risk factors and moderate heritability have been reported for meniscus injury. However, the genetic etiology of meniscus injury remains understudied. This study was a multiancestry genome-wide association study (GWAS) of meniscus injury aimed at identifying genomic variants that influence risk and elucidating the mechanisms by which they may exert their effects. Questions/purposes: (1) Which single nucleotide polymorphisms (SNPs), genes, and molecular pathways are associated with meniscus injury? (2) How do independent SNPs with genome-wide significance alter the expression of genes within cells related to the meniscus? (3) Can a polygenic risk score (PRS) for meniscus injury discriminate between patients with meniscus injury and controls? (4) Does obesity increase the risk of meniscus injury using a Mendelian randomization framework? Methods: A meta-analysis of 38,062 patients with meniscus injury and 700,343 control participants was performed using GWAS summary statistics from the NIH’s All of Us and FinnGen cohorts. All of Us provided an ancestrally diverse cohort for a multiancestry GWAS. Functional Mapping and Annotation of Genetic Variants (FUMA) and Meta-Analysis Gene-Set Mining of GWAS (MAGMA) platforms were used to identify genes of interest and perform expression quantitative trait loci and chromatin interaction mapping of SNPs with genome-wide significance. A PRS was developed for European individuals using the FinnGen GWAS and was validated on a European cohort from All of Us. Mendelian randomization assesses putative causal associations between an exposure and outcomes given random assortment of alleles during meiotic recombination and was used to analyze the risk of obesity and meniscus injury. Results: Twelve independent genome-wide significant loci (p < 5 × 10 ^-8 ) were identified, and genes UQCC1 , BMP6 , EGR2 , CAPZB , SMG6 were associated with meniscus injury after Bonferroni correction for all identified genes (p < 2.6 × 10 ^-6 ). A subset of genes identified through MAGMA were enriched in the transforming growth factor-β (TGF-β) signaling pathway. Independent SNPs altered expression of genes related to the TGF-β pathway, including GDF5 , BMP6 , MMP24 , and UQCC1 . As an independent intronic SNP of UQCC1 , rs2425055 was in chromosomal contact with GDF5OS in mesenchymal stem cells and decreased the expression of GDF5OS . A PRS for meniscus injury demonstrated differences in genetic risk between patients with meniscus injury and control participants (area under the curve 0.53 [95% confidence interval (CI) 0.51 to 0.54], OR per SD increase 1.10 [95% CI 1.05 to 1.15]; p = 3.34 × 10 ^-5 ). Mendelian randomization demonstrated that genetic predisposition to obesity increased the risk of meniscus injury (OR 1.29 [95% CI 1.24 to 1.34]; p = 9.58 × 10 ^-38 ). Conclusion: The 12 independent genetic variants identified suggest a genetic contribution to meniscus injury risk across multiple ancestries. These SNPs may modulate meniscus injury risk by modifying genetic expression of key upstream regulators of the TGF-β signaling pathway ( GDF5, BMP6, TGF-β2 ) and related genes ( UQCC1, EGR2, MMP24 ). Although previous studies have implicated BMP6 and EGR2 in meniscus fibrochondrocyte differentiation and adaptive stress responses, our results demonstrate that genetic variation related to these genes modifies meniscus injury risk at a population level. In addition to demonstrating a putative causal relationship between obesity and meniscus injury through Mendelian randomization, we present a validated PRS that predicted risk of meniscal injury. Clinical Relevance: The genes related to meniscus injury identified in this GWAS are promising therapeutic targets for studies on meniscus regeneration. Our validated PRS presents an opportunity to develop screening and prevention strategies for individuals at high risk of meniscus injury.

The utilization of hip arthroscopy to treat femoroacetabular impingement has continued to grow year after year. Clinical studies and cost-effectiveness analyses have repeatedly shown the benefits of hip arthroscopy in improving quality of life, offering much promise to this patient population. Through years of research, a more comprehensive understanding of impingement pathologies has brought improving surgical techniques. However, predictors of poor outcomes are still not entirely understood. Although many patients attain significant relief, some patients do not attain meaningful improvement. Meaningful improvement can be found even years after hip arthroscopy, but this is a long road for patients who do not find sustained relief. Thus, as with defining appropriate indications for hip arthroscopy, it is equally important to identify factors that may instead suggest alternative treatment regimens for patients with hip pathology who may not benefit from arthroscopic intervention. However, rather than exclude large groups entirely based on the presence of certain factors such as increased age or arthritis, the goal should be to understand the nuances among patients in these higher-risk groups to identify those who may still find success with hip arthroscopy.

Purpose: To perform a population‐level analysis of the shifts in use of hip arthroscopy by different age groups and to describe the proportion of hip arthroscopy procedures performed by high‐volume surgeons. Methods: The Statewide Planning and Research Cooperative System database was combined with New York State census data to calculate changes in annual hip arthroscopy incidence by age and gender (2004‐16). Annual (January to January) surgeon volumes were calculated and stratified into 4 thresholds that have been associated with significant differences in revision hip surgery rates to calculate changes in hip arthroscopy rates by surgeon volume over time. Results: There was a 495% increase in hip arthroscopies from 2004 to 2016, from 2.35 to 15.47 per 100,000 residents in New York State. The largest increase was in the 10‐19 years age group—a 2,150% increase for female patients (= 1.26, P < . 001) and a 1,717% increase for male patients (incident rate ratio = 1.21, P < . 001). The number of labral repairs performed with femoroplasty increased 52.8% ( P < . 001). The number of hip arthroscopy surgeons increased from 3.4 to 6.5 per 1 million residents. The number of hip arthroscopies performed by high‐volume surgeons increased from 0% in 2004 to 24.7% in 2016. Conclusions: The use of hip arthroscopy has increased over the past 10 years, especially in the adolescent population ages 10‐19. Over the same time period, there has been an emergence of high‐volume hip arthroscopy surgeons and an increased proportion of procedures performed by these surgeons. Patients of high‐volume surgeons tend to be younger, while lower volume surgeons tend to have older patients. Level of Evidence: Level IV, case series.

Purpose: The purpose of this study was to use a novel scoring system to evaluate the content and grade the quality of websites that patients may use to learn about rotator cuff repair. Methods: Two search terms (“rotator cuff repair” and “rotator cuff surgery”) were entered into 3 Internet search engines (Google, Yahoo, and Bing). We scored the quality of information using a novel scoring system. Website quality was further assessed by the Journal of the American Medical Association (JAMA) benchmark criteria and Health on the Net Foundation (HON) code certification. The readability of the websites was evaluated with the Flesch‐Kincaid score. Results: We evaluated 47 websites. The average quality for all websites was 6.47 ± 5.21 (maximum 20 points). There was a large difference in scores between the top 5 websites and the remaining websites (16.30 vs 5.51, P < .001). There was no difference in scores when comparing the 3 different search engines ( P = .85). The mean reading level was 10.17 ± 2.24. Reading level was not significantly correlated with quality (r _s = 0.14, P = .36). The average JAMA benchmark criteria score for all websites was 2.34 ± 1.11 (maximum 4 points). JAMA criteria score was not significantly correlated with quality (r _s = 0.02, P = .91). Sites without HONcode certification had higher quality scores (8.33 ± 4.80) than sites with HONcode certification (6.18 ± 4.66), but this difference was not statistically significant ( P = .15). Conclusion: The quality of patient‐level information on rotator cuff repair on the Internet is both incomplete and written at a reading level higher than current recommendations. Information quality is not significantly correlated with reading level or JAMA criteria, and does not depend on the search term used or HONcode certification. Clinical Relevance: Patients having rotator cuff repair may seek information on the Internet; the information may require surgeon clarification.

Background: Recent studies have shown that intra-articular injections ≤3 months before total knee arthroplasty increase the risk of periprosthetic joint infection. We are aware of no previous study that has differentiated the risk of periprosthetic joint infection on the basis of the type of medication injected. In addition, we are aware of no prior study that has evaluated whether hyaluronic acid injections increase the risk of infection after total knee arthroplasty. In this study, we utilized pharmaceutical data to compare patients who received preoperative corticosteroid or hyaluronic acid injections and to determine whether a specific injection type increased the risk of periprosthetic joint infection. Methods: Patients undergoing unilateral primary total knee arthroplasty were selected from a nationwide private insurer database. Ipsilateral preoperative injections were identified and were grouped by medication codes for corticosteroid or hyaluronic acid. Patients who had received both types of injections ≤1 year before total knee arthroplasty were excluded. The outcome of interest was periprosthetic joint infection that occurred ≤6 months following the total knee arthroplasty. The risk of periprosthetic joint infection was compared between groups (no injection, corticosteroid, hyaluronic acid) and between patients who received single or multiple injections. Statistical comparisons were performed using logistic regression controlling for age, sex, and comorbidities. Results: A total of 58,337 patients underwent total knee arthroplasty during the study period; 3,249 patients (5.6%) received hyaluronic acid and 16,656 patients (28.6%) received corticosteroid ≤1 year before total knee arthroplasty. The overall infection rate was 2.74% in the no-injection group. Multivariable logistic regression showed independent periprosthetic joint infection risk for both corticosteroid (odds ratio [OR], 1.21; p = 0.014) and hyaluronic acid (OR, 1.55; p = 0.029) given ≤3 months before total knee arthroplasty. There was no increased risk with injections >3 months prior to total knee arthroplasty. Direct comparison of corticosteroid and hyaluronic acid showed no significant difference (p > 0.05) between medications or between single and multiple injections. Conclusions: Preoperative corticosteroid or hyaluronic acid injection ≤3 months before total knee arthroplasty increased the risk of periprosthetic joint infection. There was no difference in infection risk between medications or between multiple and single injections. On the basis of these data, we recommend avoiding both injection types in the 3 months prior to total knee arthroplasty. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Purpose: The purpose of this study was to perform a population‐level analysis to evaluate the effect of socioeconomic markers on the use of meniscus surgery in patients with meniscus tears. Methods: We queried all hospital‐based clinic visits from 2011 to 2014 in the Statewide Planning and Research Cooperative System database, which also contains all New York inpatient/outpatient visits. Patients with known prior knee surgery, meniscus tear before 2011, or other ligament injuries were excluded. The primary outcome was a meniscus procedure (meniscectomy or meniscus repair). Survival analysis was used to calculate the rate of meniscus surgery within 6 months. A multivariate model identified patient factors (age, sex, race, and payer) associated with surgical intervention. Results: There were 32,012 patients identified who met the inclusion criteria. The rate of meniscus procedure within 6 months of diagnosis was 49.6%. Meniscectomy was performed in 98.8% of cases compared with 1.2% for meniscus repair. Rates of meniscus procedures were higher in patients who were older, male, and white, as well as those first diagnosed by a surgeon. The highest rates of meniscus procedures were in those with private, worker's compensation, or other insurance types. Multivariable analysis showed that female sex, non‐white race, and public or self‐pay insurance were independently associated with lower rates of meniscus surgery. Conclusions: These results suggest both insurance‐based and race‐based disparities regarding surgical treatment. Additionally, the strongest variable for surgical management was a meniscus tear being first diagnosed by a surgeon. Level of Evidence: Level of Evidence IV, retrospective case‐control study.

Background: The aim of this study was to perform a population-level analysis on the effect of different types of anticoagulation on postoperative stiffness after total knee replacement, requiring manipulation under anesthesia. We hypothesized that patients receiving warfarin would have a higher rate of manipulation under anesthesia compared with patients receiving low-molecular-weight heparin. We also hypothesized that aspirin, direct factor Xa inhibitors, and fondaparinux would have no effect on the rate of manipulation under anesthesia. Methods: Using the PearlDiver patient database, we analyzed 32,320 patients who underwent a primary unilateral total knee replacement from 2007 to 2015. Patients were included if they filled a prescription for anticoagulation medication within 2 days of their discharge and were excluded if they were taking a prescription anticoagulation medication (except for aspirin) in the 3 months before total knee replacement. The primary outcome was manipulation under anesthesia performed within 6 months after a primary total knee replacement. Results: The most commonly prescribed postoperative anticoagulation was warfarin (38.0%), followed by low-molecular-weight heparin (33.8%). There were 1,178 patients (3.64%) who underwent manipulation under anesthesia within 6 months of total knee replacement. In multivariable analysis using low-molecular-weight heparin as a comparison group and accounting for age, sex, comorbidities, and length of stay, there was a significant increase in the risk of manipulation under anesthesia for patients who received warfarin (hazard ratio [HR], 1.17 [95% confidence interval (CI), 1.01 to 1.36]; p = 0.032), direct factor Xa inhibitors (HR, 1.42 [95% CI, 1.20 to 1.66]; p < 0.001), or fondaparinux (HR, 1.33 [95% CI, 1.01 to 1.72]; p = 0.038). Although patients who received aspirin had the same risk estimate as patients who received warfarin, there was not a significantly increased risk of manipulation under anesthesia in patients who received aspirin compared with low-molecular-weight heparin (HR, 1.17 [95% CI, 0.72 to 1.80]; p = 0.493). Conclusions: We found an increased rate of manipulation under anesthesia after total knee replacement in patients who received oral anticoagulants including warfarin, direct factor Xa inhibitors, and fondaparinux, in comparison with patients who received aspirin or low-molecular-weight heparin. We recommend that patients receiving oral anticoagulants after total knee replacement should be counseled about associated stiffness. Furthermore, surgeons should take these data into account when selecting thromboprophylaxis for patients after total knee replacement. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Purpose: To use a population‐level dataset to evaluate the rate of 30‐day complications after rotator cuff repair, and to evaluate the risk factors for complication and unplanned hospital readmission. Methods: We used the American College of Surgeons National Surgical Quality Improvement Program from 2011 to 2015 to identify patients who underwent rotator cuff repair and concomitant procedures using Current Procedural Terminology codes. Postoperative complications and unplanned hospital readmissions were identified. Patient demographics, medical comorbidities, and perioperative variables were used in a multivariate logistic regression model to identify the risk factors for infection, any complication, and unplanned hospital readmission. Results: A total of 23,741 patients were identified who underwent rotator cuff repair. Overall, 1.39% of patients experienced at least 1 complication, with 0.66% minor complications and 0.85% major complications. Unplanned readmission occurred in 1.16% of patients. Infection was the most common complication, occurring in 0.3% of patients (n = 72), and was the most common reason for return to the operating room. Open rotator cuff repair and male gender were independent risk factors for all outcomes. Increased age and numerous medical comorbidities were associated with the risk of any complication or unplanned hospital readmission. Conclusions: Rotator cuff repair has a low incidence of short‐term complications. Infection was the most common complication. Open repair, male gender, increased age, and medical comorbidities all significantly increased the risk of complications and hospital readmission. Level of Evidence: Level IV, case series.