Gunshot-Induced Humeral Head Osteochondral Defect Treated with an Osteochondral Allograft: A Case Report.

CASE: A 25-year-old right-hand dominant male police officer presented to the emergency department with a gunshot wound to his left shoulder. Magnetic resonance imaging demonstrated an osteochondral defect overlying the humeral head along the mid to lower aspect of the glenohumeral joint. A staged operation with shoulder arthroscopy followed by an osteochondral allograft (OCA) of the humeral head was performed. During his 6-month postoperative visit, he had returned to full work duty with no restrictions and reported that his pain was well controlled. CONCLUSION: Humeral head OCA transplantation may be an effective treatment option for traumatic osteochondral lesions of the glenohumeral joint.

Return to Activity Following Isolated Ulnar Nerve Surgery: A Systematic Review.

Ulnar neuropathy is one of the more commonly diagnosed mononeuropathies; despite this, a definitive surgical treatment strategy has not been widely agreed upon. In this study, we systematically review the literature and assess return to play or activity outcomes in patients with neuritis or neuropathy undergoing in situ decompression, subcutaneous transposition, or submuscular transposition of the ulnar nerve. We hypothesized that ulnar nerve transposition or decompression in the absence of concomitant ulnar collateral ligament (UCL) pathology would have a high rate of return to activity. Relevant studies were generated from 1975 to 2023 using PubMed, Academic Search Complete, CINAHL (Cumulative Index to Nursing and Allied Health Literature), MEDLINE, and SPORTDiscus. Articles reporting on return to play or activity outcomes following isolated ulnar nerve transposition or decompression for ulnar neuritis were included. Studies evaluating patients with concomitant UCL injury or revision surgery were excluded. A total of 12 studies met the inclusion criteria, ranging from 1977 to 2021. There were a total of 358 patients with a reported return to play or activity status across all studies with an average age of 27.2 years (range, 11-75). Successful return to play, activity, or work was reported in 303 patients (84.6%). Patients undergoing transposition, subcutaneous (n = 232) and submuscular (n = 20), had return rates of 87.9% and 95%, respectively. Patients undergoing in situ decompression (n = 106) had return rates of 75.5%. This systematic review found an 84.6% return to activity rate following ulnar nerve transposition or decompression in the absence of concomitant UCL pathology. Overall, transposition or decompression of the ulnar nerve provides a favorable return to activity rates and with appropriate indications and surgical technique will likely yield a successful return.

Management of Capitellar Osteochondritis Dissecans: A Critical Analysis Review.

¼ Osteochondritis dissecans of the capitellum is a localized compromise of bone that may lead to subchondral collapse with articular cartilage damage and loose body formation.¼ The etiology is multifactorial; proposed mechanisms include repetitive microtrauma, vascular insufficiency, and genetic predisposition.¼ Diagnosis is based on patient presentation, clinical examination, diagnostic imaging, and intraoperative findings.¼ Management is dependent on lesion characteristics, with stable lesions amenable to nonoperative treatment and unstable lesions managed with surgical intervention.¼ Adolescent athletes can expect a return to their preinjury level of activity or competition following indicated surgical intervention.

Spectral averaging with outlier rejection algorithms to increase identifications in top-down proteomics.

The identification of proteoforms by top-down proteomics requires both high quality fragmentation spectra and the neutral mass of the proteoform from which the fragments derive. Intact proteoform spectra can be highly complex and may include multiple overlapping proteoforms, as well as many isotopic peaks and charge states. The resulting lower signal-to-noise ratios for intact proteins complicates downstream analyses such as deconvolution. Averaging multiple scans is a common way to improve signal-to-noise, but mass spectrometry data contains artifacts unique to it that can degrade the quality of an averaged spectra. To overcome these limitations and increase signal-to-noise, we have implemented outlier rejection algorithms to remove outlier measurements efficiently and robustly in a set of MS1 scans prior to averaging. We have implemented averaging with rejection algorithms in the open-source, freely available, proteomics search engine MetaMorpheus. Herein, we report the application of the averaging with rejection algorithms to direct injection and online liquid chromatography mass spectrometry data. Averaging with rejection algorithms demonstrated a 45% increase in the number of proteoforms detected in Jurkat T cell lysate. We show that the increase is due to improved spectral quality, particularly in regions surrounding isotopic envelopes.

Lysholm and KOOS QoL Demonstrate High Responsiveness in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

BACKGROUND: There have been a large number of patient-reported outcome measures (PROMs) used to assess outcomes after anterior cruciate ligament (ACL) reconstruction (ACLR). PURPOSE/HYPOTHESIS: The purpose was to determine which PROMs are being commonly used in randomized clinical trials (RCTs) to assess patients undergoing ACLR and to compare the responsiveness between them. It was hypothesized that the International Knee Documentation Committee (IKDC) score would be the most commonly used and responsive PROM among patients undergoing ACLR. STUDY DESIGN: Meta-analysis. Level of evidence, 2. METHODS: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed, and relevant studies were extracted from the PubMed/MEDLINE and Web of Science databases. The inclusion criteria were English-language RCTs reporting on PROMs after ACLR. For articles meeting our inclusion criteria for responsiveness analysis (≥2 PROMs reported, 1 year minimum follow-up, and reported pre- and postoperative PROM means and standard deviations), the responsiveness between PROMs was compared using effect size (ES) and relative efficiency (RE). RESULTS: A total of 108 articles met the inclusion criteria, comprising 9034 patients (mean age, 29.9 years; mean body mass index, 24.3; mean follow-up time, 36.1 months). There were 34 PROMs identified. The top 3 most commonly reported PROMs were the IKDC (n = 68; 63.0%), Lysholm (n = 65; 60.2%), and Tegner (n = 47; 43.5%) scores. The 2 PROMs with the highest ES were the ACL-Quality of Life (QoL) (3.37) and Knee Injury and Osteoarthritis Outcome Score (KOOS) QoL (2.07) scores. Compared with other PROMs, Lysholm and KOOS QoL scores had the greatest RE values. The Lysholm score had a greater RE than the KOOS Pain (RE, 1.17), KOOS Symptoms (RE, 1.22), KOOS Activities of Daily Living (ADL) (RE, 1.42), KOOS Sport/Recreation (RE, 1.55), KOOS QoL (RE, 1.41), and Tegner (RE, 2.89) scores. KOOS QoL had a greater RE than the IKDC (RE, 1.32), KOOS Pain (RE, 1.60), KOOS Symptoms (RE, 2.12), KOOS ADL (RE, 3.03), KOOS Sport/Recreation (RE, 1.27), and Tegner (RE, 2.06) scores. CONCLUSION: The IKDC score is the most commonly reported PROM in RCTs after ACLR; however, the Lysholm and KOOS QoL scores demonstrated the highest responsiveness in patients undergoing ACLR compared with other PROMs.

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.

Randomized Controlled Trials on Platelet-Rich Plasma for Knee Osteoarthritis Poorly Adhere to the Minimum Information for Studies Evaluating Biologics in Orthopaedics (MIBO) Guidelines: A Systematic Review.

BACKGROUND: Platelet-rich plasma (PRP) treatment for knee osteoarthritis has grown exponentially over the past decade; however, its scientific evaluation is highly variable. The American Academy of Orthopaedic Surgeons addressed the need for the standardization of orthobiologics studies by publishing the Minimum Information for Studies Evaluating Biologics in Orthopaedics (MIBO) guidelines in May 2017. In total, the MIBO guidelines are divided into 12 categories, encompassing 23 checklist items. HYPOTHESIS/PURPOSE: The purpose of this study was to analyze how well randomized controlled trials (RCTs) on PRP interventions for knee osteoarthritis adhered to the MIBO guidelines. We hypothesized that most articles would report <80% of the MIBO criteria. STUDY DESIGN: Systematic review; Level of evidence, 1. METHODS: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were used to perform a systematic review in the PubMed/MEDLINE and Web of Science databases. Inclusion criteria included English-language RCTs that assessed PRP interventions for knee osteoarthritis and reported beginning patient enrollment in June 2017 or later. The original 23 MIBO checklist items were separated and modified into a 44-point checklist. Adherence was determined by calculating the total percentage of checklist items that each article adequately and clearly reported from the 44-point checklist. RESULTS: A total of 25 RCTs (2356 patients) were included in this study. The weighted mean age was 57.7 ± 4.4 years, with 42.9% being male. On average, only 53.1% ± 10.4% (range, 31.8%-77.3%) of the 44-point MIBO checklist items were reported per article. No articles had adherence rates ≥80%, 5 (20.0%) had rates between 60% and 79.9%, and 20 (80.0%) had rates ≤59.9%. Categories fluctuated in adherence, with "Intervention" having the greatest adherence (100.0%) and "Activation" having the lowest (14.0%). Additionally, 4 (33.3%) categories had adherence rates ≥80%, 0 had rates from 60% to 79.9%, and 8 (66.7%) had rates ≤59.9%. CONCLUSION: The overall mean adherence to MIBO guidelines by RCTs on PRP interventions for knee osteoarthritis was 53.1%. To increase the reproducibility, improve transparency, and assess the treatment efficacy of future PRP studies, reporting of MIBO guidelines should be improved.

Responsiveness of Patient-Reported Outcome Measures After Large Knee Articular Cartilage Transplantation: A Systematic Review and Meta-analysis.

BACKGROUND: Cartilage transplantation is commonly used to treat large (>4 cm2) articular cartilage defects of the knee. The 2 most common transplants are osteochondral allograft transplantation and autologous chondrocyte implantation. Several patient-reported outcome measures (PROMs) have been used to determine the efficacy of treatment, but it is unknown which measures are the most effective. PURPOSE: To report the multiple PROMs used after large knee articular cartilage transplantation surgery and to compare the responsiveness between them. STUDY DESIGN: Meta-analysis; Level of evidence, 4. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search of the PubMed/MEDLINE and Web of Science databases was performed. A total of 181 articles met inclusion criteria. Patient and study characteristics were extracted, including pre- and postoperative means for PROMs. From the articles that met inclusion criteria for responsiveness analysis (2+ PROMs reported, 1-year minimum follow-up, reported pre- and postoperative means and standard deviations; n = 131), 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 10,015 patients (10,093 knees; mean age, 34.8 years; mean body mass index, 26.1) were included in this study. The mean follow-up time was 58.3 months (range, 1.5-247.2 months), imaging findings were reported in 80 articles (44.2%), patient satisfaction was reported in 39 articles (21.5%), and range of motion was reported in 10 articles (5.5%). There were 58 unique PROM instruments identified, with the most used being the International Knee Documentation Committee (IKDC) score (n = 118; 65.2%), followed by Knee injury and Osteoarthritis Outcome Score (KOOS) Pain (n = 58; 32.0%), KOOS Sport and Recreation (n = 58; 32.0%), KOOS Quality of Life (n = 57; 31.5%), KOOS Activities of Daily Living (n = 57; 31.5%), and KOOS Symptoms (n = 57; 31.5%). Overall, IKDC was found to have the greatest effect size (1.68) and the best responsiveness of the other PROMs, which include KOOS Pain (RE, 1.38), KOOS Symptoms (RE, 3.06), KOOS Activities of Daily Living (RE, 1.65), KOOS Sport and Recreation (RE, 1.44), Lysholm (RE, 1.76), and Tegner (RE, 1.56). CONCLUSION: The IKDC is the most responsive PROM after large knee articular cartilage transplantation surgery. The IKDC score is recommended for assessing outcomes after cartilage transplantation surgery.

Erratum: Proteomic pathways to metabolic disease and type 2 diabetes in the pancreatic islet.

[This corrects the article DOI: 10.1016/j.isci.2021.103099.].

Orthopaedic Sports Medicine Randomized Controlled Trials Infrequently Report on the Social Determinants of Health Factors of Their Patient Cohorts.

PURPOSE: To describe the prevalence of randomized controlled trials (RCTs) in orthopaedic sports medicine-related journals reporting on the social determinants of health (SDOH) of their patient cohorts, including factors receiving less attention, such as education level, employment status, insurance status, and socioeconomic status. METHODS: The PubMed/MEDLINE database was used to search for RCTs between 2020 and 2022 from 3 high-impact orthopaedic sports medicine-related journals: American Journal of Sports Medicine, Arthroscopy, and Journal of Shoulder and Elbow Surgery. The following information was extracted from each article: age, sex/gender, body mass index, year published, corresponding author country, and self-reported SDOH factors (race, ethnicity, education level, employment status, insurance status, and socioeconomic status). RESULTS: A total of 189 articles were analyzed. Articles originated from 34 different countries, with the United States (n = 66) producing the greatest number of articles. Overall, age (n = 186; 98.4%) and sex/gender (n = 184; 97.4%) were the factors most commonly reported, followed by body mass index (n = 112; 59.3%), race (n = 17; 9.0%), ethnicity (n = 10; 5.3%), employment status (n = 9; 4.8%), insurance status (n = 7; 3.7%), and education level (n = 5; 2.6%). Socioeconomic status was not reported in any of the articles analyzed. Articles from the United States report on SDOH factors more frequently than international articles, most notably race (24.2% vs 0.8%, respectively) and ethnicity (15.2% and 0%, respectively). CONCLUSIONS: RCTs from 3 high-impact orthopaedic sports medicine journals infrequently report on SDOH. CLINICAL RELEVANCE: Better understanding patient SDOH factors in RCTs is important to help orthopaedic surgeons and other practitioners best apply study results to their patients, as well as help researchers and our field ensure that research is being done transparently with relevance to as many patients as possible.

Case-Based Understanding of the Role of the Scapula in Common Shoulder Pathologies.

Scapular dyskinesis is an extremely common component of shoulder pathology, especially in the overhead athlete; despite its prevalence, proper diagnosis and management of scapular disorders remains an enigma for many clinicians. An understanding of the contribution of the scapula to pathomechanics and clinical symptoms is necessary to optimize both surgical and nonsurgical treatment of shoulder disorders. Without correction of scapular dysfunction, even effective management of the pathoanatomy is unlikely to produce optimal results. It is important to examine the role of the scapula in common shoulder pathologies and elucidate a case-based treatment strategy for both surgical and nonsurgical shoulder disorders.

Risk Factors Associated With Prolonged Opioid Use After Revision Total Shoulder Arthroplasty.

INTRODUCTION: The purpose of this study was to determine which preoperative factors are associated with prolonged opioid use after revision total shoulder arthroplasty (TSA). METHODS: The M157Ortho PearlDiver database was used to identify patients undergoing revision TSA between 2010 and 2021. Opioid use for longer than 1 month after surgery was defined as prolonged opioid use. Postoperative opioid use from 1 to 3 months was independently assessed. Multivariable logistic regression was used to evaluate the association between preoperative patient-related risk factors (age, Charlson Comorbidity Index, sex, depression, anxiety, substance use disorder, opioid use between 12 months to 1 week of surgery, tobacco use, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, osteoporosis, previous myocardial infarction, and chronic ischemic heart disease) with prolonged postoperative opioid use. Odds ratios (OR) and their associated 95% confidence intervals (CI) were calculated for each risk factor. RESULTS: A total 14,887 patients (mean age = 67.1 years) were included. Most of the patients were female (53.3%), and a large proportion were opioid familiar (44.1%). Three months after revision TSA, older age (OR = 0.96, CI 0.96 to 0.97) and male sex (OR = 0.90, CI 0.81 to 0.99) were associated with a decreased risk of prolonged postoperative opioid usage. Patients with preexisting depression (OR = 1.21, CI 1.08 to 1.35), substance use disorder (OR = 1.47, CI 1.29 to 1.68), opioid use (OR = 16.25, CI 14.27 to 18.57), and chronic obstructive pulmonary disorder (OR = 1.24, CI 1.07 to 1.42) were at an increased risk of prolonged postoperative opioid use. DISCUSSION: Older age and male sex were associated with a decreased risk of prolonged opioid use after revision TSA. Depression, substance use disorder, opioid familiarity, and COPD were associated with prolonged opioid use after revision TSA.

Evaluation of Patient Adherence to Vaccine and Screening Recommendations during Community Pharmacist-led Medicare Annual Wellness Visits in a Family Medicine Clinic.

Background: The Centers for Medicare and Medicaid Services initiated annual wellness visits (AWV) to reduce healthcare costs and improve preventive healthcare for beneficiaries. Provider time constraints and varying preferences to perform AWVs have limited its clinical implementation in some areas, affording pharmacists an opportunity to expand their role. Objective: To evaluate patient adherence to pharmacist recommendations for vaccinations and preventive screenings in an annual wellness visit service at a family medicine clinic in northeast Mississippi. Methods: This study included patients receiving at least one vaccination or screening recommendation during an AWV. Investigators provided vaccination (influenza, pneumococcal and herpes zoster) and screening (mammograms, DEXA, and colorectal cancer) recommendations based on current guidelines. For services not provided in-clinic, investigators contacted outside facilities 45 days post-visit to confirm adherence to recommendations. Primary endpoints included the composite adherence rate of all recommendations and percentage of patients achieving the 60% goal composite adherence rate. Secondary endpoints included individual vaccination and screening adherence rates. Results: Investigators recommended 715 interventions to a total of 254 patients, of which 239 were completed within 45 days for a 33.4 percent composite adherence rate. 20.1 percent of all participants achieved the goal composite adherence rate (60%). Overall, participants were 30.5 and 41 percent adherent to all vaccinations and preventive screening recommendations, respectively. Conclusion: Pharmacists providing AWVs increased patient access to preventive health recommendations. Although, adherence to recommendations remains a challenge and warrants further study. The findings and limitations observed in this study have identified opportunities for future research to evaluate pharmacist-led AWV services.

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.

Prevalence and Predictors of Postoperative Depression and Anxiety After Anterior Cruciate Ligament Reconstruction.

PURPOSE: Preoperative mood disorders influence postoperative outcomes after anterior cruciate ligament (ACL) reconstruction (ACLR), but the prevalence and risk factors associated with postoperative depression/anxiety development remain unknown. The purposes of this study were to quantify the prevalence of postoperative diagnoses of depression or anxiety following ACLR in patients under the age of 25 and assess the interplay between patient sex and ACL reoperation on the prevalence of a depression or anxiety diagnosis following ACLR. METHODS: ACLR patients under the age of 25 years old were identified in the Truven Healthcare Marketscan database. Patients with incomplete coverage +/- one year of the index surgical procedure were excluded. Patients were categorized by the presence of preoperative, postoperative, or no depression/anxiety using the International Classification of Diseases, Ninth Revision (ICD-9) codes. We compared patient demographics and reoperation rates following the index ACLR between the depression and anxiety categories. Additionally, logistic regression was fit to assess the interaction between sex and either ipsilateral or contralateral ACL surgery on postoperative depression/anxiety diagnosis. RESULTS: Of the 42,174 patients, 10.7% had a new depression/anxiety diagnosis after ACLR. Postoperative depression/anxiety was nearly twice as prevalent for females (F: 14.4%, M: 7.6%) despite having similar rates of secondary ACLR (F: 15.5%, M: 13.0%). Those with postoperative depression/anxiety had a considerably greater prevalence of reoperation (18.8%) than those without depression/anxiety (13.7%) and those with pre-existing preoperative depression/anxiety (12.9%). Sex and reoperation were independently associated with postoperative depression/anxiety diagnosis. CONCLUSION: Female sex and secondary ACL surgery are independently associated with an increased prevalence of postoperative depression/anxiety. Nearly one in seven young females are diagnosed with depression/anxiety after ACLR. Similarly, a greater proportion of patients who suffer a secondary ACL surgery are subsequently diagnosed with depression/anxiety. The orthopedic community must be cognizant of the increased risk of postoperative depression/anxiety for females and those who suffer a secondary ACL surgery, and screening for depression/anxiety in these at-risk populations with referrals to mental health professionals may be warranted.

Comprehensive Characterization of Endogenous Phospholamban Proteoforms Enabled by Photocleavable Surfactant and Top-down Proteomics.

Top-down mass spectrometry (MS)-based proteomics has become a powerful tool for analyzing intact proteins and their associated post-translational modifications (PTMs). In particular, membrane proteins play critical roles in cellular functions and represent the largest class of drug targets. However, the top-down MS characterization of endogenous membrane proteins remains challenging, mainly due to their intrinsic hydrophobicity and low abundance. Phospholamban (PLN) is a regulatory membrane protein located in the sarcoplasmic reticulum and is essential for regulating cardiac muscle contraction. PLN has diverse combinatorial PTMs, and their dynamic regulation has significant influence on cardiac contractility and disease. Herein, we have developed a rapid and robust top-down proteomics method enabled by a photocleavable anionic surfactant, Azo, for the extraction and comprehensive characterization of endogenous PLN from cardiac tissue. We employed a two-pronged top-down MS approach using an online reversed-phase liquid chromatography tandem MS method on a quadrupole time-of-flight MS and a direct infusion method via an ultrahigh-resolution Fourier-transform ion cyclotron resonance MS. We have comprehensively characterized the sequence and combinatorial PTMs of endogenous human cardiac PLN. We have shown the site-specific localization of phosphorylation to Ser16 and Thr17 by MS/MS for the first time and the localization of S-palmitoylation to Cys36. Moreover, we applied our method to characterize PLN in disease and reported the significant reduction of PLN phosphorylation in human failing hearts with ischemic cardiomyopathy. Taken together, we have developed a streamlined top-down targeted proteomics method for comprehensive characterization of combinatorial PTMs in PLN toward better understanding the role of PLN in cardiac contractility.

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.

Older Age, Female Sex, Anxiety, Substance Use Disorder, Osteoarthritis, Tibial Tubercle Osteotomy, and Opioid Familiarity Are Risk Factors for Prolonged Opioid Use Following Medial Patellofemoral Ligament Reconstruction.

Purpose: To determine which preoperative factors are associated with prolonged opioid use after medial patellofemoral ligament reconstruction (MPFLR). Methods: The M151Ortho PearlDiver database was queried for patients who underwent MPFLR between 2010 and 2020. Inclusion criteria included patients who underwent MPFLR using Current Procedural Terminology codes 27420, 27422, and 27427 and had a patellar instability diagnosis. Prolonged opioid use was defined as opioid use greater than 1 month after surgery. Postoperative opioid use from 1 month to 6 months was assessed. Multivariable logistic regression was used to evaluate the association between patient-related risk factors (age, sex, Charlson Comorbidity Index, anxiety, depression, substance use disorder, osteoarthritis, tibial tubercle osteotomy [TTO], and previous opioid use within 3 months to 1 week of surgery) with prolonged postoperative opioid use. Odds ratios (OR) and their associated 95% confidence intervals (CI) were calculated for each risk factor. Results: A total of 23,249 patients were included. There was a higher proportion of female patients compared to male patients (67.8% vs 32.2%) in our cohort, as well as a large proportion of patients who had preoperative opioid use (23.9%). In total, 14.3% of patients had a concomitant TTO. Three months post-MPFLR, male patients were at a decreased risk of opioid usage (OR 0.75; CI 0.67-0.83; P ≤ .001). Older age (OR 1.01, CI 1.00-1.01; P ≤ .001), patients with pre-existing anxiety (OR 1.30, CI 1.15-1.47; P ≤ .001), substance use disorder (OR 2.04, CI 1.80-2.31; P ≤ .001), knee osteoarthritis (OR 1.70, CI 1.49-1.94; P ≤ .001), concomitant TTO (OR 1.91, CI 1.67-2.17; P ≤ .001), and opioid familiarity (OR 7.68, CI 6.93-8.52; P ≤ .001) were at a significantly increased risk of postoperative opioid usage. Conclusions: Older age, female sex, anxiety, substance use disorder, osteoarthritis, tibial tubercle osteotomy, and opioid familiarity are risk factors for prolonged opioid use following MPFLR. Level of Evidence: Level III, retrospective cohort study.

International Knee Documentation Committee (IKDC) Is the Most Responsive Patient Reported Outcome Measure After Meniscal Surgery.

Purpose: To report the variability in outcome measures after meniscal surgery and to compare responsiveness between patient-reported outcome measures (PROMs). Methods: A systematic search of the PubMed/MEDLINE and Web of Science databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A total of 257 studies met inclusion criteria. Patient and study attributes were extracted, including pre- and postoperative means for PROMs. Of the studies that met inclusion criteria for responsiveness analysis (2+ PROMs reported, 1-year minimum follow-up; n = 172), we compared the responsiveness between PROM instruments using effect size and relative efficiency (RE) if a PROM could be compared with another in at least 10 articles. Results: In total, 18,612 patients (18,690 menisci, mean age = 38.6 years, mean body mass index = 26.3) were included in this study. Radiographic measures were reported in 167 (65.0%) studies, range of motion was reported in 53 (20.6%) studies, and 35 different PROM instruments were identified. The mean number of PROMs in each article was 3.6 and 83.8% reported 2 or more PROMs. The most used PROMs were Lysholm (74.5%) and IKDC (51.0%). IKDC was found to be more responsive than other PROMs, which include Lysholm (RE = 1.03), Tegner (RE = 3.90), and Knee Injury and Osteoarthritis Outcome Score (KOOS) Activities of Daily Living (ADL) (RE = 1.12). KOOS Quality of Life (QoL) was also more responsive than other PROMs, such as IKDC (RE = 1.45) and KOOS ADL (RE = 1.48). Lysholm was more responsive compared with KOOS QoL (RE = 1.14), KOOS ADL (RE = 1.96), and Tegner (RE = 3.53). Conclusions: Our study found that IKDC, KOOS QoL, and Lysholm were the most responsive PROMs. However, because of the previously reported risks of either floor effects (KOOS QoL) or ceiling effects (Lysholm), the IKDC may offer a more complete psychometric profile when quantifying outcomes after meniscus procedures. Clinical Relevance: To improve clinical outcomes, surgical decision-making, and research methodology, it is important to determine which PROMs are the most responsive after meniscal surgery.

Return to Play and Performance After Anterior Cruciate Ligament Reconstruction in the National Women's Soccer League.

Background: The anterior cruciate ligament (ACL) is commonly injured in elite-level female athletes, which usually requires ACL reconstruction (ACLR). Purpose: To analyze return to play (RTP) and changes in performance of players in the National Women's Soccer League (NWSL) after ACLR. Study Design: Descriptive epidemiology study. Methods: NWSL players who sustained an ACL tear and underwent surgery between the 2013 and 2020 seasons were identified by multiple online resources. Players were classified as forwards, defenders, midfielders, and goalkeepers. RTP was assessed according to games played, games started, percentage of minutes played, plus/minus net per 90 minutes (a measure of a player's contribution to their team's performance while on the field), goals scored, and assists. A subanalysis was performed based on the median age at the time of the injury (≤24 vs ≥25 years). Nonparametric testing methods were used throughout the analysis. Results: A total of 30 NWSL athletes were included. Midfielders had the highest percentage of injuries (n = 11; 36.7%), followed by forwards (n = 10; 33.3%). Overall, 27 players returned to the NWSL at a median of 12.1 months (IQR, 10.9-14.3 months), constituting a 90.0% RTP rate. There was a significant decrease in the percentage of minutes played from 1 year before the injury to 1 year after the injury (median, 87.9% [IQR, 80.7%-90.6%] vs 25.1% [IQR, 16.3%-57.2%], respectively; P = .031). Forwards and midfielders had a significant decrease in the number of assists from 1 year before the injury to 1 year after the injury (median, 3.0 [IQR, 1.0-3.0] vs 0.0 [IQR, 0.0-1.0], respectively; P = .037) as well as the number of goals scored when averaging across 2 seasons before the injury to 2 seasons after the injury (median, 3.0 [IQR, 1.5-5.5] vs 1.0 [IQR, 0.5-3.5], respectively; P = .031). On subanalysis, older players started in significantly more games (median, 12.0 [IQR, 3.8-18.5] vs 3.0 [IQR, 0.5-6.0], respectively; P = .048) and had a higher percentage of minutes played (median, 63.0% [IQR, 18.8%-77.3%] vs 14.9% [IQR, 2.0%-21.2%], respectively; P = .046) at 1 year after the injury versus younger players. Conclusion: There was a 90.0% RTP rate after ACLR in the NWSL. Players who returned to the NWSL had a lower percentage of minutes played in their first year after RTP, with older players starting in more games and having a greater percentage of minutes played. Compared with preinjury performance, forwards and midfielders had a significant decrease in the number of assists at 1 year after the injury as well as the number of goals scored at 2 years after the injury.