ASES and UCLA Are Responsive Patient-Reported Outcome Measures After Rotator Cuff Repair: A Systematic Review and Meta-analysis.

BACKGROUND: Multiple patient-reported outcome measures (PROMs) have been used to assess shoulder function, but it is unknown which are the most effective. PURPOSE/HYPOTHESIS: The purpose of this study was to report the multiple PROMs used after rotator cuff repair (RCR) and to compare the responsiveness between them. It was hypothesized that the Western Ontario Rotator Cuff PROM would be the most responsive and commonly used in patients undergoing RCR. STUDY DESIGN: Meta-analysis; Level of evidence, 4. METHODS: A systematic review was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and PRISMA-Searching extension guidelines via PubMed/MEDLINE, Embase (Elsevier), and Web of Science (Clarivate). Patient and study characteristics were extracted. From the studies that met inclusion criteria for responsiveness analysis (≥2 PROMs reported, 1-year minimum follow-up, and pre- and postoperative PROM means and standard deviations reported), the authors compared the responsiveness between PROM instruments using effect size and relative efficiency (RE) if a PROM could be compared with another in ≥10 articles. RESULTS: A total of 252 studies met inclusion criteria (32,072 patients; mean age, 59.6 years; mean body mass index, 28.7; mean follow-up time, 27.8 months). Range of motion was reported in 131 (52%) studies and imaging findings were reported in 123 (49%) studies. There were 67 PROM instruments identified; the most commonly used were the American Shoulder and Elbow Surgeon (ASES) (n = 183; 73%), Visual Analog Scale (VAS) (n = 163; 65%), and Constant (n = 118; 47%) scores. The 3 PROMs with the highest effect sizes were the University of California, Los Angeles (UCLA) (2.51), Western Ontario Rotator Cuff (2.42), and ASES (2.00) scores. Overall, UCLA and ASES scores were the most responsive PROMs. The ASES PROM was more responsive than the VAS (RE, 1.70), Constant (RE, 2.76), Simple Shoulder Test (RE, 1.67), and Single Assessment Numeric Evaluation (RE, 2.14) scores. The UCLA PROM was more responsive than the ASES (RE, 1.03), VAS (RE, 3.66), Constant (RE, 1.72), and Simple Shoulder Test (RE, 1.66) scores. CONCLUSION: ASES and UCLA scores were the most responsive PROMs after RCR. The authors recommend widespread adoption of ASES and UCLA scores for clinical and research standardization; however, the UCLA PROM requires in-person range of motion and strength testing, which is a practical limitation and barrier to long-term follow-up.

Editorial Commentary: Routine Use of Suture Tape Augmentation for Primary Anterior Cruciate Ligament Reconstruction Surgery Is Not Justified.

High rates of graft failure after primary anterior cruciate ligament reconstruction (ACLR) and the need for revision ACLR continue to be a challenge. Multiple studies demonstrate graft failure rates and the need for revision ACLR in 10% to 15% of young patients participating in pivot sporting activities. Currently, a wide range of strategies to mitigate this is problem being investigated, including extra-articular augmentation (with modified lateral extra-articular tenodesis or anterolateral ligament reconstruction) and intra-articular fixation (that aim for primary anterior cruciate ligament healing or augmentation of an ACLR with suture tape). While the early data on suture tape augmentation of primary ACLR seem optimistic, it does not justify its routine use.

GDF8 inhibition enhances musculoskeletal recovery and mitigates posttraumatic osteoarthritis following joint injury.

Musculoskeletal disorders contribute substantially to worldwide disability. Anterior cruciate ligament (ACL) tears result in unresolved muscle weakness and posttraumatic osteoarthritis (PTOA). Growth differentiation factor 8 (GDF8) has been implicated in the pathogenesis of musculoskeletal degeneration following ACL injury. We investigated GDF8 levels in ACL-injured human skeletal muscle and serum and tested a humanized monoclonal GDF8 antibody against a placebo in a mouse model of PTOA (surgically induced ACL tear). In patients, muscle GDF8 was predictive of atrophy, weakness, and periarticular bone loss 6 months following surgical ACL reconstruction. In mice, GDF8 antibody administration substantially mitigated muscle atrophy, weakness, and fibrosis. GDF8 antibody treatment rescued the skeletal muscle and articular cartilage transcriptomic response to ACL injury and attenuated PTOA severity and deficits in periarticular bone microarchitecture. Furthermore, GDF8 genetic deletion neutralized musculoskeletal deficits in response to ACL injury. Our findings support an opportunity for rapid targeting of GDF8 to enhance functional musculoskeletal recovery and mitigate the severity of PTOA after injury.

The Combination of Depression and Obesity was Associated with Increased Incidence of Subsequent Total Knee Arthroplasty.

OBJECTIVE: Compare the incidence of total knee arthroplasty (TKA) within the first 5 years after knee OA diagnoses between matched groups of individuals with or without comorbid diagnoses of obesity and/or depression. We hypothesized that the greatest incidence of TKA within 5 years of OA diagnosis would be in the cohort of individuals with combined obesity and depression. METHODS: The PearlDiver Mariner Ortho157 database was used to identify four cohorts of individuals with knee OA based on diagnosis codes that were matched by age, sex, and Charlson Comorbidity Index: a group without diagnoses associated with depression or obesity (Control), those with obesity but not depression (Obesity), those with depression but not obesity (Depression), and those with diagnoses of both obesity and depression (Depression+Obesity). The incidence of subsequent TKA within the first 5 years after the index OA diagnosis were compared between the four matched cohorts. RESULTS: Each cohort was comprised of 274,403 unique individuals (180,563 females, 93,840 males; age=55±7 y). The incidence of TKA was greatest for the Depression+Obesity group (11.9%) when compared to the Control group (8.3%, p<0.0001, RR=1.43 [95%CI:1.41,1.45]), the Obesity group (10.2%, p<0.0001, RR=1.13 [95%CI:1.11,1.14], p<0.0001) or Depression (7.8%, p<0.0001, RR=1.53 [95%CI:1.50,1.55], p<0.0001). CONCLUSION: The incidence of subsequent TKA was greatest for those with the combination of obesity and depression when compared to the Control group and those with individual diagnosis of obesity or depression.

Comparison of Physical Therapy Utilization and Motion-Related Re-operations Between Isolated Anterior Cruciate Ligament and Multi-Ligament Knee Injuries.

The increased prevalence of postoperative arthrofibrosis after multi-ligament knee injuries (MLKI) compared to isolated anterior cruciate ligament (ACL) injuries has been proposed to be due, in part, to patient factors limiting physical therapy utilization. The purpose of this study was to compare demographic factors, pre- and postoperative physical therapy utilization, and the need for motion-restoring surgery between MLKI and ACL-injured patients. Using the PearlDiver Mariner 151 database, two cohorts matched by age and sex were identified using current procedural terminology (CPT) codes and included those age 16 or greater that underwent isolated ACL (n=3801) vs. MLKI reconstruction (n=3801). The number of pre- and postoperative physical therapy visits was recorded, as was the need for motion-restoring surgery (arthroscopic lysis of adhesions or manipulation under anesthesia). Demographic factors, physical therapy utilization, and the prevalence of motion-restoring surgery were compared between the MLKI and ACL groups using t-tests or chi-square tests, as appropriate. A significantly greater proportion of those with MLKI underwent subsequent motion-restoring surgery (MLKI=412/3081 (13.4%) vs. ACL=84/3081 (2.7%), p<0.001; odds ratio = 5.5 (95% CI: 4.3, 7.0), p<0.0001). Following surgery, less than half of those with MLKI that underwent subsequent motion-restoring surgery attended physical therapy, which was significantly lower than those who did not require motion-restoring surgery (p<0.0001). The prevalence of motion-restoring surgery was significantly greater after MLKI when compared to an isolated ACL injury. While the etiology of arthrofibrosis after MLKI is likely complex, the current results suggest that demographic factors and physical therapy utilization are not solely responsible for the increased risk of arthrofibrosis after MLKI.

Patients With Depression and/or Anxiety Having Arthroscopic Rotator Cuff Repair Show Decreased Number of Prescriptions and Number of Psychotherapy Sessions in the Year After Surgery.

PURPOSE: To determine whether the utilization of psychological treatments changes after arthroscopic rotator cuff repair (RCR) for patients with preoperative depression and/or anxiety. METHODS: The Truven Healthcare Marketscan database was used to identify patients who underwent arthroscopic RCR between January 2009 and December 2016. We included all patients with diagnosis codes associated with either depression or anxiety before RCR. Patients were excluded if they did not have complete insurance coverage for 1 year before or after surgery, or if they had arthroscopic RCR in the year before the index surgical procedure. We compared the proportion of patients with preoperative depression or anxiety who filled a prescription and had psychotherapy procedural codes in the year before and the year after arthroscopic RCR. RESULTS: A total of 170,406 patients who underwent RCR were identified, of which depression and/or anxiety was found in 46,737 patients (43.7% male). Of the 46,737 patients, 19.6% filled a prescription for a depression/anxiety medication at least once in the year before surgery. Of this subset of patients, 41.5% did not fill a prescription for depression or anxiety medication after surgery, whereas 32.6% continued medication use but demonstrated a median 30-day reduction in the number of days' worth of medication. Similarly, 13.1% of patients were attending psychotherapy sessions preoperatively, but 76.6% of those patients either stopped or reduced the amount of psychotherapy sessions in the year following RCR. CONCLUSIONS: The number of prescriptions and psychotherapy sessions decreased in the year after RCR for patients with preoperative diagnoses of depression and/or anxiety. LEVEL OF EVIDENCE: Level IV, case series.

Increased Effusion Synovitis for Those With a Dysregulated Inflammatory Response After an Anterior Cruciate Ligament Injury.

Introduction The progression to posttraumatic osteoarthritis (PTOA) after an anterior cruciate ligament (ACL) injury is likely multifactorial, involving biological, mechanical, and psychosocial factors. Following acute joint trauma, there appears to be a subset of patients that demonstrate a dysregulated inflammatory response. This pro-inflammatory phenotype, or "Inflamma-type," is characterized by an amplified pro-inflammatory response combined with a lack of attendant anti-inflammatory response and has been observed following both an ACL injury and an intra-articular fracture. The aims of this study were to: 1) compare magnetic resonance imaging (MRI)-measured effusion synovitis between those with vs. without a dysregulated inflammatory response, and 2) assess the correlations between effusion synovitis and synovial fluid concentrations of proinflammatory cytokines, degradative enzymes, and synovial fluid biomarkers of cartilage degradation. Methods A cluster analysis was previously performed with synovial fluid concentrations of biomarkers of inflammation and cartilage degradation from 35 patients with acute ACL injuries. Patients were then categorized into two groups: a pro-inflammatory phenotype ("Inflamma-type") and those with a more normal inflammatory response to injury (NORM). Effusion synovitis measured from each patient's preoperative clinical MRI scan was compared between the Inflamma-type and NORM groups using an independent, two-tailed t-test. In addition, Spearman's rho non-parametric correlations were calculated to evaluate the relationship between effusion synovitis and each of the synovial fluid concentrations of pro-inflammatory cytokines, degradative enzymes, and biomarkers of cartilage degradation and bony remodeling. Results Effusion synovitis was significantly greater for the Inflamma-type (10.9±3.8 mm) than the NORM group (7.4±4.4 mm, p=0.04, Cohen's d=0.82). Effusion synovitis significantly correlated with matrix metalloproteinase-3 (rho=0.63, p<0.001), matrix metalloproteinase-1 (rho=0.50, p=0.003), and sulfated glycosaminoglycan (rho=0.42, p=0.01). No other significant correlations were present. Conclusion Effusion synovitis was significantly greater for those that demonstrated a dysregulated inflammatory response after acute ACL injury than those with a more normal response to injury. Effusion synovitis was also found to significantly correlate with synovial fluid concentrations of degradative enzymes and a biomarker of early cartilage degradation. Future work is needed to determine if non-invasive methods, such as MRI or ultrasound, may accurately identify patients within this pro-inflammatory phenotype and whether this subset is more prone to more rapid PTOA changes after injury.

Leveraging Insurance Claims Data to Identify Risk Factors for Posttraumatic Osteoarthritis After Multiligament Knee Reconstruction.

BACKGROUND: The incidence of subsequent posttraumatic osteoarthritis (OA) diagnosis after surgery and the associated risk factors have been well reported after single-ligament anterior cruciate ligament (ACL) reconstruction; however, to date, the incidence of posttraumatic OA for those who have experienced multiligament knee injury (MLKI) has been reported only in relatively small, single-center studies. PURPOSE: To compare the incidence of OA diagnoses between patients with ACL injury versus patients with MLKI and to identify risk factors for OA diagnosis after MLKI. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study used the PearlDiver Mariner database, which contains insurance claims information on >151 million orthopaedic patients. We identified 2 cohorts for this study by using Current Procedural Terminology codes. The cohorts included patients between the ages of 16 and 60 who underwent either isolated ACL reconstruction (n = 114,282) or MLKI reconstruction (n = 3325) between July 1, 2010, and August 30, 2016. MLKI reconstruction was operationally defined as ACL reconstruction plus concurrent surgical treatment of ≥1 additional ligaments. Demographic factors, concomitant meniscal and cartilage procedures, and subsequent reoperation to restore motion were recorded, as was the incidence of knee OA diagnosis within 5 years of the index surgical procedure. OA incidence and demographic and surgical factors were compared (1) between ACL and MLKI groups and (2) between patients with MLKI either with or without OA diagnosis. RESULTS: A significantly greater proportion of patients with MLKI were diagnosed with knee OA within 5 years of surgery (MLKI = 299/3325 [9.0%] vs ACL = 6955/114,282 [6.1%]; P < .0001) (odds ratio [OR], 1.52; 95% CI, 1.35-1.72; P < .001). Factors associated with increased odds of OA diagnosis after MLKI included age ≥30 years (OR, 5.90), reoperation to restore motion (OR, 2.54), obesity (OR, 1.96), mood disorder diagnoses (OR, 1.85), partial meniscectomy (OR, 1.85), and tobacco use (OR, 1.72). Concomitant meniscal repair was protective against OA diagnosis (OR, 0.06). CONCLUSION: OA incidence was greater after MLKI reconstruction than after isolated ACL reconstruction. Potentially modifiable risk factors for OA after MLKI were identified and include obesity, tobacco use, depression, and the need for motion-restoring surgery.

Synovial Fluid Inflammatory Profiles did not Differ between Isolated Anterior Cruciate Ligament and Multi-ligament Knee Injuries.

Objective and design: The purpose of this study was to compare synovial concentrations of pro- and anti-inflammatory cytokines between multiple-ligament knee injured (MLKI) and anterior cruciate ligament (ACL)-injured patients. Subjects: 14 patients with MLKI and 10 patients with isolated ACL injury. Methods: Synovial fluid was aspirated from the operative knee at the time of surgery and the concentrations of pro- and anti-inflammatory markers in the synovial fluid were determined. Structures injured, the time between injury and surgery, and demographic factors were collected. Linear regressions were used to determine the association between injury pattern and synovial inflammatory markers when controlling for age, BMI, and time between injury and surgery. Results: When adjusting for group differences in age, BMI and the time between injury and surgery, no group differences were detected (interferon gamma (p = 0.11), interleukin-1beta (IL-1b, p = 0.35), IL-2 (p = 0.28), IL-4 (p = 0.64), IL-6 (p = 0.37), IL-8 (p = 0.54), IL-10 (p = 0.25), IL-12p70 (p = 0.81), IL-13 (p = 0.31), and tumor necrosis factor-alpha (p = 0.90)). Conclusion: Synovial fluid inflammatory markers did not differ between MLKI and isolated ACL injuries. MLKIs have a greater prevalence of postoperative arthrofibrosis when compared to isolated ACL injuries; however, this may be due in part to factors other than the inflammatory status of the joint.

Association of Osteoarthritis and Functional Limitations With Cognitive Impairment Among Older Adults in the United States.

Objective: Given overlapping pathophysiology, this study sought to assess the association between osteoarthritis (OA), functional impairment, and cognitive impairment in the aging population. Methods: The National Health and Nutrition Examination Survey was used to identify participants >60 years of age. We analyzed multivariable associations of grouped participants that underwent cognitive function testing using linear and logistic regression, adjusting for sex, age, race, and ethnicity. Results: Of 2776 identified participants representing a population of 50,242,917, 40% did not report OA or functional limitations; 21% had OA but not functional limitations; 15% did not have OA but had functional limitations; 17% had OA and related functional limitations; and 7% had OA and non-arthritic functional limitations. OA was not independently associated with cognitive impairment. Contrarily, functional limitations were associated with cognitive impairment regardless of OA diagnosis. Discussion: Cognitive impairment is not associated with OA, but rather functional limitations, potentially guiding future intervention.

Human synovial fluid interleukin-6, but not type II collagen breakdown, positively correlated with pain after anterior cruciate ligament injury and reconstruction.

Anterior cruciate ligament (ACL) injury initiates a biochemical cascade thought to contribute to the onset and progression of posttraumatic osteoarthritis (PTOA). Interleukin-1ß (IL-1ß), IL-6, and C-telopeptide fragments of type II collagen (CTX-II) are implicated in joint inflammation and cartilage degradation following ACL injury; however, their association with pain is still being explored. The purpose of this study was to evaluate the associations between synovial fluid concentrations of IL-1ß, IL-6, and CTX-II with pain following ACL injury and reconstruction. We hypothesized that greater IL-1ß, IL-6, and CTX-II would correlate with greater Pain Visual Analogue Scale (VAS) scores. This was a secondary analysis of 23 patients (mean age = 18.4 years, BMI = 27.4, 13 females/10 males) with acute ACL tears who participated in a pilot randomized trial. Synovial fluid and VAS scores were collected on the day of initial presentation, at ACL reconstruction, and 1 and 4 weeks after surgery. Synovial fluid concentrations of IL-1ß, IL-6, and CTX-II were assessed using enzyme-linked immunoabsorbent assays, and repeated measures correlations were used to assess the relationships between pain and synovial IL-1ß, IL-6, or CTX-II after ACL injury and reconstruction. Pain was positively correlated with synovial fluid IL-6 concentrations (r = 0.52, p < 0.001); however, pain was inversely correlated with CTX-II (r = -0.39, p = 0.002). IL-1ß had no significant correlation with pain. Statement of clinical relevance: PTOA has been described as a "silent killer" and these results suggest that early PTOA may have pro-inflammatory pathways that are not primarily associated with pain but still lead to progressive cartilage loss.

Pain Early After Anterior Cruciate Ligament Reconstruction is Associated With 6-Month Loading Mechanics During Running.

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) results in persistent altered knee biomechanics, but contributing factors such as pain or patient function, leading to the altered loading, are unknown. HYPOTHESIS: Individuals with worse self-reported pain after ACLR would have poorer biomechanics during running, and poor loading mechanics would be present in the ACLR limb compared with contralateral and control limbs. STUDY DESIGN: Cohort pilot study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 20 patients after ACLR (age, 18.4 ± 2.7 years; height, 1.7 ± 0.1 m; mass, 84.2 ± 19.4 kg) completed visual analog scale and Knee Injury and Osteoarthritis Outcomes Score (KOOS) at 1 and 6 months postsurgery. At 6 months postsurgery, patients underwent biomechanical testing during running. A total of 20 control individuals also completed running biomechanical analyses. Associations between patient outcomes and biomechanics were conducted, and differences in running biomechanics between groups were analyzed. RESULTS: KOOS pain score 1 month after surgery was associated with peak ACLR knee abduction moment (R2 = 0.35;P = 0.01). At 6-months, KOOS sport score was related to peak abduction moment in the ACLR limb (R2 = 0.23; P = 0.05). For change scores, the improvement in pain scores related to ACLR limb peak knee abduction moment (R2 = 0.55; P = 0.001). The ACLR limb had lower knee excursion, extension moments, and ground-reaction forces compared with the uninvolved and control limb. The uninvolved limb also had higher ground-reaction forces compared with the ACLR limb and control limb. CONCLUSION: These results suggest that patient-reported outcomes 1 and 6 months after surgery are associated with running mechanics 6 months after ACLR. Further, the underloading present in the ACLR limb and overloading in the uninvolved limb indicates greater need for running rehabilitation after ACLR. CLINICAL RELEVANCE: Understanding pain and how it may be linked to movement dysfunction is important for improving long-term outcomes.

Periostin regulation and cartilage degradation early after anterior cruciate ligament reconstruction.

OBJECTIVE AND DESIGN: The purpose of this study was to explore pathological processes during the first 4 weeks after anterior cruciate ligament reconstruction (ACLR). SUBJECTS: Sixteen ACL-injured patients (8 females/8 males, mean age = 19.1, mean BMI = 28.6). METHODS: Arthrocentesis was performed 1 and 4 weeks after ACLR. Proteins in the synovial fluid were identified using nanoLC-ESI-MS/MS. Differentially up- or down-regulated proteins were identified and quantified, and a pathway analysis was performed. All identified proteins were mapped into a protein-protein interaction (PPI) network, and networks of PPIs with a combined score > 0.9 were then visualized. RESULTS: Seven pathways were upregulated after ACLR: PI3K-AKT signaling pathway, extracellular matrix (ECM)-receptor interaction, focal adhesion, protein digestion and absorption, ameobiasis, and platelet activation. Network analyses identified 8 proteins that were differentially upregulated with strong PPI interactions (periostin and 7 collagen-related proteins). Increases in periostin moderately correlated with increases in a synovial fluid biomarker of type II cartilage degradation (ρ = 0.51, p = 0.06). CONCLUSION: Pro-inflammatory pathways and periostin were upregulated after ACLR. Periostin demonstrated strong network connections with markers of collagen breakdown, and future work is needed to determine whether periostin may offer a biomarker of early cartilage degradation after ACLR and/or play an active role in early post-traumatic osteoarthritis (PTOA) progression.

Balancing after randomization in orthopedic trials: Are we even or even paying attention?

A cornerstone of evidence-based medicine is the randomized controlled trial (RCT). While randomization seeks to balance study groups on potential confounders, this is not always achieved. Especially in orthopedic research where RCTs are often of modest size, imbalances can exist and may be a significant issue. We sought to describe whether orthopedic RCTs assess balancing between study groups, use statistical hypothesis testing to compare baseline characteristics between groups, and have balanced baseline characteristics between groups. All RCTs from four leading orthopedic journals published between July 2019 and June 2020 were identified and those reporting original trial results reviewed for discussion of balancing, use of statistical significance testing to compare baseline characteristics, and patient reported outcome measures (PROMs) at baseline. Standardized mean differences of baseline PROMs were calculated to assess balancing. Of 86 orthopedic RCTs reviewed, 59 (69%) assessed balancing and 50 (58%) used statistical significance testing to compare baseline characteristics. Of 74 articles specifying a primary outcome, 33 (45%) used a PROM with 23 (70%) reporting baseline PROM values. Of these articles, 17 (74%) had a difference of less than 0.25 standard deviations (SDs) between groups, 4 (17%) had a difference of between 0.25 and 0.50 SDs, and 3 (13%) had a difference greater than 0.5 SDs. Orthopedic RCTs usually assess balancing after randomization though there is room for improvement with over half of articles using hypothesis testing to assess baseline differences as opposed to a measure of the magnitude of the difference.

Mood Disorders Are Associated with Increased Perioperative Opioid Usage and Health Care Costs in Patients Undergoing Knee Cartilage Restoration Procedure.

OBJECTIVE: To identify the prevalence of mood disorder diagnoses in patients undergoing cartilage transplantation procedures and determine the relationship between mood disorders, opioid usage, and postoperative health care costs. DESIGN: Patients with current procedural terminology (CPT) codes for osteochondral autograft transplantation (OAT), osteochondral allograft transplantation (OCA), and autologous chondrocyte implantation (ACI) were identified in the Truven Health Marketscan database (January 2009-September 2014). Patients were grouped based on having a preoperative mood disorder diagnosis (preMDD). Preoperative opioids, postoperative opioids ≥90 days, and health care costs within the year postoperative were compared for those with and without mood disorders. Costs were analyzed, adjusting for preoperative cost, sex, age, and opioid usage, for those with and without mood disorders. RESULTS: A total of 3,682 patients were analyzed (ACI: 690, OAT: 1,294, OCA: 1,698). A quarter of patients had preMDD (ACI: 25.4%, OAT: 20.6%, OCA: 22.7%). Postoperative opioid use was more prevalent in preMDD patients (OAT: 37.1% vs. 24.1%, P < 0.001; OCA: 30.4% vs. 24.8%, P = 0.032; ACI: 33.7% vs. 26.2%, P = 0.070) (odds ratio [OR] ranged from 1.29 to 1.86). First-year postoperative log-transformed costs were significantly greater for preMDD patients (ACI: $7,733 vs. $5,689*, P = 0.012; OAT: $5,221 vs. $3,823*, P < 0.001; OCA: $6,973 vs. $3,992*, P < 0.001; *medians reported). The estimated adjusted first postoperative year cost increase for preMDD OCA patients was 41.7% (P < 0.001) and 28.0% for OAT patients (P = 0.034). There was no statistical difference for ACI patients (P = 0.654). CONCLUSION: Cartilage transplantation patients have a high prevalence of preoperative mood disorders. Opioid use and health care costs were significantly greater for patients with preoperative mood disorder diagnoses. LEVEL OF EVIDENCE: Level III, retrospective therapeutic study.

MOntelukast as a potential CHondroprotective treatment following Anterior cruciate ligament reconstruction (MOCHA Trial): study protocol for a double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: After anterior cruciate ligament (ACL) reconstruction, patient-reported outcomes are improved 10 years post-surgery; however, cytokine concentrations remain elevated years after surgery with over 80% of those with combined ACL and meniscus injuries having posttraumatic osteoarthritis (PTOA) within 10-15 years. The purpose of this multicenter, randomized, placebo-controlled trial is to assess whether a 6-month course of oral montelukast after ACL reconstruction reduces systemic markers of inflammation and biochemical and imaging biomarkers of cartilage degradation. METHODS: We will enroll 30 individuals undergoing primary ACL reconstruction to participate in this IRB-approved multicenter clinical trial. This trial will target those at greatest risk of a more rapid PTOA onset (age range 25-50 with concomitant meniscus injury). Patients will be randomly assigned to a group instructed to take 10 mg of montelukast daily for 6 months following ACL reconstruction or placebo. Patients will be assessed prior to surgery and 1, 6, and 12 months following surgery. To determine if montelukast alters systemic inflammation following surgery, we will compare systemic concentrations of prostaglandin E2, monocyte chemoattractant protein-1, and pro-inflammatory cytokines between groups. We will also compare degradative changes on magnetic resonance imaging (MRI) collected 1 and 12 months following surgery between groups with reductions in early biomarkers of cartilage degradation assessed with urinary biomarkers of type II collagen breakdown and bony remodeling. DISCUSSION: There is a complex interplay between the pro-inflammatory intra-articular environment, underlying bone remodeling, and progressive cartilage degradation. PTOA affects multiple tissues and appears to be more similar to rheumatoid arthritis than osteoarthritis with respect to inflammation. There is currently no treatment to delay or prevent PTOA after ACL injury. Since there is a larger and more persistent inflammatory response after ACL reconstruction than the initial insult of injury, treatment may need to be initiated after surgery, sustained over a period of time, and target multiple mechanisms in order to successfully alter the disease process. This study will assess whether a 6-month postoperative course of oral montelukast affects multiple PTOA mechanisms. Because montelukast administration can be safely sustained for long durations and offers a low-cost treatment option, should it be proven effective in the current trial, these results can be immediately incorporated into clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04572256 . Registered on October 1, 2020.

Pitch break and performance metrics remain unchanged in pitchers who returned to the same level of play after ulnar collateral ligament reconstruction in Major League Baseball pitchers.

BACKGROUND: The ulnar collateral ligament is commonly injured in overhead-throwing athletes, particularly baseball pitchers. Pitch movement (break) is a critical aspect to pitching performance. The primary purpose of this study was to determine the changes in pitch velocity, pitch break, angle of break, and pitch performance metrics before and after ulnar collateral ligament reconstruction (UCLR) in Major League Baseball (MLB) pitchers. The secondary purpose was to determine changes in pitch performance metrics before and after UCLR. We hypothesized that pitch break and pitch performance metrics would be unchanged following UCLR. MATERIALS AND METHODS: This was a retrospective case-series study of pitchers who had undergone primary UCLR between 2008 and 2014. Velocity, horizontal movement (Hmov), and vertical movement (Vmov) of each pitch were collected from the PITCHf/x system for each pitcher 12-24 months before surgery, 12-24 months after surgery, and 24-36 months after surgery. Overall break was calculated by taking the Pythagorean sum of Hmov and Vmov. Angle of break was determined by taking the inverse tangent of Vmov divided by Hmov. Repeated-measures analysis of covariance was performed to determine differences in pitch velocity, movement, angle of movement, and performance metrics between preoperative and postoperative time frames. Performance metrics included balls, strikes, swings, fouls, swings and misses, ground balls, line drives, pop-ups, fly balls, and home runs. Covariates included age at surgery, time from MLB debut to surgery, innings pitched as a starter, innings pitched as a reliever, and total pitches thrown. RESULTS: In a cohort of 46 pitchers who underwent UCLR between 2008 and 2014, pitch velocity, movement, and angle were not significantly changed with respect to preoperative or postoperative time frames. In addition, postoperative time frames had clinically insignificant differences in pitch performance metrics. CONCLUSION: Pitch break and performance metrics are not significantly affected in pitchers who return after UCLR.

A Comparison of Neuromuscular Electrical Stimulation Parameters for Postoperative Quadriceps Strength in Patients After Knee Surgery: A Systematic Review.

CONTEXT: Postoperative quadriceps strength weakness after knee surgery is a persistent issue patients and health care providers encounter. OBJECTIVE: To investigate the effect of neuromuscular electrical stimulation (NMES) parameters on quadriceps strength after knee surgery. DATA SOURCES: CINAHL, MEDLINE, SPORTDiscus, and PubMed were systematically searched in December 2018. STUDY SELECTION: Studies were excluded if they did not assess quadriceps strength or if they failed to report the NMES parameters or quadriceps strength values. Additionally, studies that applied NMES to numerous muscle groups or simultaneously with other modalities/treatments were excluded. Study quality was assessed with the Physiotherapy Evidence Database (PEDro) scale for randomized controlled trials. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 1. DATA EXTRACTION: Treatment parameters for each NMES treatment was extracted for comparison. Quadriceps strength means and standard deviations were extracted and utilized to calculate Hedge g effect sizes with 95% CIs. RESULTS: Eight RCTs were included with an average Physiotherapy Evidence Database scale score of 5 ± 2. Hedge g effect sizes ranged from small (-0.37; 95% CI, -1.00 to 0.25) to large (1.13; 95% CI, 0.49 to 1.77). Based on the Strength of Recommendation Taxonomy Quality of Evidence table, the majority of the studies included were low quality RCTs categorized as level 2: limited quality patient-oriented evidence. CONCLUSION: Because of inconsistent evidence among studies, grade B evidence exists to support the use of NMES to aid in the recovery of quadriceps strength after knee surgery. Based on the parameters utilized by studies demonstrating optimal treatment effects, it is recommended to implement NMES treatment during the first 2 postoperative weeks at a frequency of ≥50 Hz, at maximum tolerable intensity, with a biphasic current, with large electrodes and a duty cycle ratio of 1:2 to 1:3 (2- to 3-second ramp).

Tetracycline use in treating osteoarthritis: a systematic review.

BACKGROUND AND AIMS: The purpose of the review was to synthesize the current literature regarding tetracyclines in the treatment of osteoarthritis. METHODS: Using multiple databases, a systematic review was performed with customized search terms crafted to identify studies examining doxycycline or minocycline in the treatment of osteoarthritis. Results were classified into basic science mechanistic studies, in vivo animal studies, and human clinical trials. A total of 1446 potentially relevant studies were reviewed, and after exclusion criteria were applied, 23 investigations were included in the final analysis. RESULTS: From 12 basic science mechanistic studies, we report on three main mechanisms by which tetracyclines may exert benefit in osteoarthritis progression: matrix metalloproteinase inhibition, immunomodulation, and nitric oxide synthase inhibition. Seven animal studies showed generally encouraging results. Four articles reported human clinical studies, showing mixed results in the treatment of osteoarthritis, potentially related to the choice of patient population, primary outcomes, and timing of treatment. CONCLUSION: Tetracyclines have the potential to benefit osteoarthritis patients via multiple mechanisms. Further study is warranted to examine the optimal dose and timing of tetracycline treatment in osteoarthritis.

Anterior cruciate ligament reconstruction reinitiates an inflammatory and chondrodegenerative process in the knee joint.

Anterior cruciate ligament (ACL) injury leads to a sustained increase in synovial fluid concentrations of inflammatory cytokines and biomarkers of cartilage breakdown. While this has been documented post-injury, it remains unclear whether ACL reconstruction surgery contributes to the inflammatory process and/or cartilage breakdown. This study is a secondary analysis of 14 patients (nine males/five females, mean age = 9, mean BMI = 28) enrolled in an IRB-approved randomized clinical trial. Arthrocentesis was performed at initial presentation (mean = 6 days post-injury), immediately prior to surgery (mean = 23 days post-injury), 1-week post-surgery, and 1-month post-surgery. Enzyme-linked immunosorbant assay kits were used to determine concentrations of carboxy-terminal telopeptides of type II collagen (CTXII), interleukin-6 (IL-6), and IL-1ß in the synovial fluid. The log-transformed IL-1ß was not normally distributed; therefore, changes between time points were evaluated using a non-parametric Kruskal-Wallis one-way ANOVA. IL-1ß concentrations significantly increased from the day of surgery to the first postoperative time point (P ≤ .001) and significantly decreased at the 4-week postoperative visit (P = .03). IL-1ß concentrations at the 4-week postoperative visit remained significantly greater than both preoperative time points (P > .05). IL-6 concentrations at 1-week post-surgery were significantly higher than at initial presentation (P = .013), the day of surgery (P < .001), and 4 weeks after surgery (P = .002). CTX-II concentrations did not differ between the first three-time points (P > .99) but significantly increased at 4 weeks post-surgery (P < .01). ACL reconstruction appears to reinitiate an inflammatory response followed by an increase in markers for cartilage degradation. ACL reconstruction appears to initiate a second "inflammatory hit" resulting in increased chondral breakdown suggesting that post-operative chondroprotection may be needed.