Sparsentan for Focal Segmental Glomerulosclerosis in the DUET Open-Label Extension: Long-term Efficacy and Safety.

Rationale & Objective: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist (DEARA) examined in the ongoing phase 2 DUET trial for focal segmental glomerulosclerosis (FSGS). In the DUET 8-week double-blind period, sparsentan resulted in greater proteinuria reduction versus irbesartan. We report the long-term efficacy and safety of sparsentan during the open-label extension over more than 4 years. Study Design: Patients were examined from their first sparsentan dose (double-blind period or open-label extension) through 4.6 years. Setting & Participants: Patients with FSGS, excluding secondary FSGS. Intervention: Sparsentan (200, 400, and 800 mg/d). Outcomes: Urinary protein-creatinine ratio, FSGS partial remission endpoint (urinary protein-creatinine ratio ≤1.5 g/g and >40% reduction from baseline), estimated glomerular filtration rate, and blood pressure approximately every 12 weeks. Treatment-emergent adverse events by year and cases/100 patient-years. Results: 109 patients were enrolled; 108 received ≥1 sparsentan dose; 103 entered the open-label extension (68 sparsentan, 35 irbesartan during the double-blind period). Sparsentan was ongoing in 45/108 patients (41.7%); median time to treatment discontinuation was 3.9 years (95% CI, 2.6-5.2). Mean percent proteinuria reduction from baseline was sustained through follow-up. Achieving partial remission within 9 months of first sparsentan dose (52.8% of patients) versus not achieving (47.2%) was associated with significantly slower rate of estimated glomerular filtration rate decline over the entire treatment period (-2.70 vs -6.56; P = 0.03) and in the first 2 years (-1.69 vs -6.46; P = 0.03). The most common treatment-emergent adverse events (>9 cases/100 patient-years) were headache, peripheral edema, upper respiratory infection, hyperkalemia, and hypotension. Peripheral edema and hypotension declined from year 1 (13.9% and 15.7% of patients, respectively) to ≤4% in years ≥2. There were no cases of heart failure and no patient deaths. Limitations: The open-label extension does not include a comparison group. Conclusions: Long-term sparsentan treatment showed sustained proteinuria reduction and a consistent safety profile.

There is substantial unmet clinical need for safe and effective treatments for focal segmental glomerulosclerosis (FSGS), a kidney lesion with varied causes. Sparsentan is being studied for treatment of FSGS and targets 2 important pathways (endothelin-1 and angiotensin II) that lead to the loss of kidney function. In the 8-week randomized, double-blind DUET study in patients with FSGS, sparsentan reduced the amount of protein in the urine better than irbesartan (a blood pressure medicine often used to treat FSGS). We examined long-term treatment with sparsentan over >4 years in the DUET open-label extension. We found sustained proteinuria reduction in patients who continued treatment with sparsentan and a consistent safety profile with no new or unexpected adverse effects.

Comparable Clinical and Functional Outcomes Between Osteochondral Allograft Transplantation and Autologous Chondrocyte Implantation for Articular Cartilage Lesions in the Patellofemoral Joint at a Mean Follow-up of 5 Years.

PURPOSE: To assess clinical outcomes and return to sport (RTS) rates among patients that undergo osteochondral allograft (OCA) transplantation and autologous chondrocyte implantation (ACI) or matrix-induced autologous chondrocyte implantation (MACI), for patellofemoral articular cartilage defects. METHODS: A retrospective review of patients who underwent an OCA or ACI/MACI from 2010-2020 was conducted. Patient-reported outcomes (PROs) collected included: Visual Analog Scale for pain/satisfaction, Knee Injury and Osteoarthritis Outcome Score (KOOS), and RTS. The percentage of patients that met the Patient Acceptable Symptom State (PASS) for KOOS was recorded. Logistic regression was used to identify predictors of worse outcomes. RESULTS: A total of 95 patients were included (78% follow-up) with ACI or MACI performed in 55 cases (57.9%) and OCA in 40 (42.1%). A tibial tubercle osteotomy was the most common concomitant procedure for OCA (66%) and ACI/MACI (98%). Overall, KOOS pain was significantly poorer in OCA than ACI/MACI (74.7, 95% CI [68.1, 81.1] vs 83.6, 95% CI [81.3, 88.4], p= 0.012), while the remaining KOOS subscores were non-significantly different (all p>0.05). Overall, RTS rate was 54%, with no significant difference in return between OCA or ACI/MACI (52% vs 58%, p= 0.738). There were 26 (27%) reoperations and 5 (5%) graft failures in the entire group. Increasing age was associated with lower satisfaction in OCA and poorer outcomes in ACI/MACI, while larger lesion area was associated with lower satisfaction and poorer outcomes in ACI/MACI. CONCLUSION: Clinical and functional outcomes were similar in patients that underwent OCA or ACI/MACI for patellofemoral articular cartilage defects at a mean follow-up of 5 years. Patients who received OCA had a higher proportion of degenerative cartilage lesions and, among those with trochlear lesions, reported higher pain at final follow-up than their ACI/MACI counterparts. Overall, increasing age and a larger lesion size were associated with worse patient-reported outcomes.

Podocyte-targeted therapies - progress and future directions.

Podocytes are the key target cells for injury across the spectrum of primary and secondary proteinuric kidney disorders, which account for up to 90% of cases of kidney failure worldwide. Seminal experimental and clinical studies have established a causative link between podocyte depletion and the magnitude of proteinuria in progressive glomerular disease. However, no substantial advances have been made in glomerular disease therapies, and the standard of care for podocytopathies relies on repurposed immunosuppressive drugs. The past two decades have seen a remarkable expansion in understanding of the mechanistic basis of podocyte injury, with prospects increasing for precision-based treatment approaches. Dozens of disease-causing genes with roles in the pathogenesis of clinical podocytopathies have been identified, as well as a number of putative glomerular permeability factors. These achievements, together with the identification of novel targets of podocyte injury, the development of potential approaches to harness the endogenous podocyte regenerative potential of progenitor cell populations, ongoing clinical trials of podocyte-specific pharmacological agents and the development of podocyte-directed drug delivery systems, contribute to an optimistic outlook for the future of glomerular disease therapy.

Cytokine Receptor-like Factor 1 (CRLF1) and Its Role in Osteochondral Repair.

BACKGROUND: Since cytokine receptor-like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. METHODS: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow-derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno-associated virus (AAV) or AAV containing CRLF1 was determined by morphological, histological, and micro computer tomography (CT) analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were determined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes using real-time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. RESULTS: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondrogenic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and cardiotrophin-like Cytokine (CLC) stimulated catabolic events via STAT3 activation. CONCLUSION: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.

Integrated multiomics implicates dysregulation of ECM and cell adhesion pathways as drivers of severe COVID-associated kidney injury.

COVID-19 has been a significant public health concern for the last four years; however, little is known about the mechanisms that lead to severe COVID-associated kidney injury. In this multicenter study, we combined quantitative deep urinary proteomics and machine learning to predict severe acute outcomes in hospitalized COVID-19 patients. Using a 10-fold cross-validated random forest algorithm, we identified a set of urinary proteins that demonstrated predictive power for both discovery and validation set with 87% and 79% accuracy, respectively. These predictive urinary biomarkers were recapitulated in non-COVID acute kidney injury revealing overlapping injury mechanisms. We further combined orthogonal multiomics datasets to understand the mechanisms that drive severe COVID-associated kidney injury. Functional overlap and network analysis of urinary proteomics, plasma proteomics and urine sediment single-cell RNA sequencing showed that extracellular matrix and autophagy-associated pathways were uniquely impacted in severe COVID-19. Differentially abundant proteins associated with these pathways exhibited high expression in cells in the juxtamedullary nephron, endothelial cells, and podocytes, indicating that these kidney cell types could be potential targets. Further, single-cell transcriptomic analysis of kidney organoids infected with SARS-CoV-2 revealed dysregulation of extracellular matrix organization in multiple nephron segments, recapitulating the clinically observed fibrotic response across multiomics datasets. Ligand-receptor interaction analysis of the podocyte and tubule organoid clusters showed significant reduction and loss of interaction between integrins and basement membrane receptors in the infected kidney organoids. Collectively, these data suggest that extracellular matrix degradation and adhesion-associated mechanisms could be a main driver of COVID-associated kidney injury and severe outcomes.

Urinary Plasminogen as a Marker of Disease Progression in Human Glomerular Disease.

RATIONALE & OBJECTIVE: Glomerular disorders have a highly variable clinical course, and biomarkers that reflect the molecular mechanisms underlying their progression are needed. Based on our previous work identifying plasminogen as a direct cause of podocyte injury, we designed this study to test the association between urine plasmin(ogen) (ie, plasmin and its precursor plasminogen) and end-stage kidney disease (ESKD). STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 1,010 patients enrolled in the CureGN Cohort with biopsy-proven glomerular disease (focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A nephropathy). PREDICTORS: The main predictor was urine plasmin(ogen) at baseline. Levels were measured by an electrochemiluminescent immunoassay developed de novo. Traditional clinical and analytical characteristics were used for adjustment. The ratio of urine plasmin(ogen)/expected plasmin(ogen) was evaluated as a predictor in a separate model. OUTCOME: Progression to ESKD. ANALYTICAL APPROACH: Cox regression was used to examine the association between urinary plasmin(ogen) and time to ESKD. Urinary markers were log2 transformed to approximate normal distribution and normalized to urinary creatinine (Log2uPlasminogen/cr, Log2 urinary protein/cr [UPCR]). Expected plasmin(ogen) was calculated by multiple linear regression. RESULTS: Adjusted Log2uPlasminogen/cr was significantly associated with ESKD (HR per doubling Log2 uPlasminogen/cr 1.31 [95% CI, 1.22-1.40], P<0.001). Comparison of the predictive performance of the models including Log2 uPlasminogen/cr, Log2 UPCR, or both markers showed the plasmin(ogen) model superiority. The ratio of measured/expected urine plasmin(ogen) was independently associated with ESKD: HR, 0.41 (95% CI, 0.22-0.77) if ratio<0.8 and HR 2.42 (95% CI, 1.54-3.78) if ratio>1.1 (compared with ratio between 0.8 and 1.1). LIMITATIONS: Single plasmin(ogen) determination does not allow for the study of changes over time. The use of a cohort of mostly white patients and the restriction to patients with 3 glomerular disorders limits the external validity of our analysis. CONCLUSIONS: Urinary plasmin(ogen) and the ratio of measured/expected plasmin(ogen) are independently associated with ESKD in a cohort of patients with glomerular disease. Taken together with our previous experimental findings, urinary plasmin(ogen) could be a useful biomarker in prognostic decision making and a target for the development of novel therapies in patients with proteinuria and glomerular disease. PLAIN-LANGUAGE SUMMARY: Glomerular diseases are an important cause of morbidity and mortality in patients of all ages. Knowing the individual risk of progression to dialysis or transplantation would help to plan the follow-up and treatment of these patients. Our work studies the usefulness of urinary plasminogen as a marker of progression in this context, since previous studies indicate that plasminogen may be involved in the mechanisms responsible for the progression of these disorders. Our work in a sample of 1,010 patients with glomerular disease demonstrates that urinary plasminogen (as well as the ratio of measured to expected plasminogen) is associated with the risk of progression to end-stage kidney disease. Urine plasminogen exhibited good performance and, if further validated, could enable risk stratification for timely interventions in patients with proteinuria and glomerular disease.

Segond fracture: an indicator for increased risk of lateral meniscus injury in patients with acute anterior cruciate ligament ruptures.

PURPOSE: The purpose of this study was to investigate the incidence and anatomic distribution of meniscus injury in patients who have sustained acute ACL injuries with and without concomitant Segond fracture. We hypothesized that patients who have sustained a torn ACL with a concomitant Segond fracture would have a higher incidence of lateral meniscal injuries than patients with an isolated ACL injury. METHODS: Patients who underwent ACL reconstruction from 2012 to 2022 were retrospectively reviewed. Segond fractures were identified on knee radiographs. Inclusion criteria were age 18-40, injury during sports activity, and reconstruction within 90 days of injury. Sports activity, anatomic location of meniscus injury, and meniscus treatment were documented. Multivariable regression was used to identify predictors of meniscus injury/treatment. RESULTS: There were 25 of 603 (4.1%) patients who had an ACL tear with concomitant Segond fracture. The incidence of lateral meniscus injury in the Segond group (72%) was significantly higher than in the non-Segond cohort (49%; p = 0.024). A significantly smaller proportion of medial meniscus injuries among patients with Segond fractures were repaired (23.1%) compared to the non-Segond group (54.2%; p = 0.043). Multivariate analysis found patients with Segond fractures to have increased odds of lateral meniscus injury (OR 2.68; [1.09, 6.60], p = 0.032) and were less likely to have medial meniscus injuries repaired (OR 0.35; [0.15, 0.81], p = 0.014). Additionally, males had increased odds of lateral meniscus injury (OR 1.54; [1.08 - 2.91], p = 0.017), which were more likely to require repair (OR 1.48; [1.02, 2.14], p = 0.038). CONCLUSIONS: Among acute ACL injuries, the incidence of lateral meniscus injury is greater among patients with Segond fractures. Patients with Segond fracture were less likely to undergo repair of medial meniscal injuries.

Medial quadriceps tendon femoral ligament reconstruction and medial patellofemoral ligament reconstruction have no significant differences in clinical outcomes for treatment of lateral patellar instability: a matched-cohort study.

OBJECTIVES: The purpose of this study was to compare clinical outcomes of medial quadriceps tendon-femoral ligament reconstruction (MQTFLR) and medial patellofemoral ligament reconstruction (MPFLR) among patients with recurrent lateral patellar instability. METHODS: A retrospective matched-cohort study was conducted involving patients who underwent MQTFLR or MPFLR with or without tibial tubercle osteotomy (TTO) from 2019 to 2021. Subjects were matched 1:1 on age, concomitant osteochondral allograft (OCA), concomitant TTO, and follow-up time. Measured outcomes included 90-day complications, Visual Analog Scale (VAS) knee pain, return to sport/work, Kujala score, Tegner score, and MPFL-Return to Sport after Injury (MPFL-RSI) score. Outcomes were compared between groups using Mann-Whitney U-test for continuous variables and Fisher's exact test for categorical variables. P-values <0.05 were considered significant. RESULTS: Ten MQTFLR patients (mean age 28.7 years, 80% female, mean follow-up 19.7 months) and ten MPFLR patients (mean age 29.1 years, 90% female, mean follow-up 28.3 months) were included in the study. One MQTFLR patient (10%) and three MPFLR patients (30%) underwent reoperation for postoperative arthrofibrosis. Postoperative VAS resting pain was not significantly different between the groups (MQTFLR mean 1.1, MPFLR mean 0.6, p â€‹= â€‹0.31). There were no significant differences in rates of recurrent subluxations (MQTFLR 20%, MPFLR 0%, p â€‹= â€‹0.47), return to sport (MQTFLR 50%, MPFLR 75%, p â€‹= â€‹0.61), return to work (MQTFLR 100%, MPFLR 88%, p â€‹= â€‹1.00), or MPFL-RSI pass rate (MQTFLR 75% vs. MPFLR 38%, p â€‹= â€‹0.31). CONCLUSION: There were no significant differences in knee pain and function, return to work, and rates of recurrent patellar instability between patients who underwent MQTFLR versus MPFLR, though these results should be interpreted with caution given the small sample size and potential selection bias. LEVEL OF EVIDENCE: III.

Arthroscopic Bankart repair versus nonoperative management for first-time anterior shoulder instability: A cost-effectiveness analysis.

Purpose: Arthroscopic Bankart repair (ABR) may be more effective than nonoperative management for patients with anterior shoulder instability following first-time dislocation. The purpose of the study was to determine the most cost-effective treatment strategy by evaluating the incremental cost-effectiveness ratio (ICER) for ABR versus nonoperative treatment. Methods: This cost-effectiveness study utilized a Markov decision chain and Monte Carlo simulation. Probabilities, health utility values, and outcome data regarding ABR and nonoperative management of first-time shoulder instability derived from level I/II evidence. Costs were tabulated from Centers for Medicaid & Medicare Services. Probabilistic sensitivity analysis was performed using >100,000 repetitions of the Monte Carlo simulation. A willingness-to-pay (WTP) threshold was set at $50,000. Results: The expected cost for operative management higher than nonoperative management ($32,765 vs $29,343). However, ABR (5.48 quality-adjusted life years (QALYs)) was the more effective treatment strategy compared to nonoperative management (4.61 QALYs). The ICER for ABR was $3943. Probabilistic sensitivity analysis showed that ABR was the most cost-effective strategy in 100% of simulations. Discussion: ABR is more cost-effective than nonoperative management for first-time anterior shoulder dislocation. The threshold analysis demonstrated that when accounting for WTP, ABR was found to be the more cost-effective strategy.

Psychological Readiness to Return to Sport (RTS) and RTS Rates Are Similar in Patients After Either Bilateral or Unilateral Anterior Cruciate Ligament Reconstruction.

Purpose: To compare psychological readiness to return to sport (RTS), RTS rate, level of return, and time to return between patients who underwent bilateral anterior cruciate ligament reconstruction (ACLR) and those who underwent unilateral ACLR. Methods: The electronic medical record at a single academic medical center was queried for patients who underwent ACLR from January 2012 to May 2020. The inclusion criteria were skeletally mature patients who underwent either single or sequential bilateral ACLR and who had undergone either the primary ACLR or second contralateral ACLR at least 2 years earlier. Bilateral ACLRs were matched 1:3 to unilateral reconstructions based on age, sex, and body mass index. Psychological readiness to RTS was assessed using the validated ACL Return to Sport After Injury (ACL-RSI) scale. This, along with time to return and level of RTS, was compared between the 2 cohorts. Results: In total, 170 patients were included, of whom 44 underwent bilateral ACLR and 132 underwent unilateral ACLR. At the time of the first surgical procedure, patients in the unilateral cohort were aged 28.8 ± 9.4 years and those in the bilateral cohort were aged 25.7 ± 9.8 years (P = .06). The average time difference between the first and second surgical procedures was 28.4 ± 22.3 months. There was no difference in psychological readiness to RTS (50.5 in bilateral cohort vs 48.1 in unilateral cohort, P = .66), RTS rate (78.0% in unilateral cohort vs 65.9% in bilateral cohort, P = .16), percentage of return to preinjury sport level (61.2% in unilateral cohort vs 69.0% in bilateral cohort, P = .21), or time to return (41.2 ± 29.3 weeks in unilateral cohort vs 35.2 ± 23.7 weeks in bilateral cohort, P = .31) between the 2 cohorts. Conclusions: Compared with patients who undergo unilateral ACLR, patients who undergo bilateral ACLR are equally as psychologically ready to RTS, showing equal rates of RTS, time to return, and level of return. Level of Evidence: Level III, retrospective cohort study.

Examining the Trajectory of Health-Related Quality of Life among Coronavirus Disease Patients.

BACKGROUND: Recent studies have reported a reduction in health-related quality of life (HR-QoL) among post-coronavirus disease 2019 (COVID-19) patients. However, there remains a gap in research examining the heterogeneity and determinants of HR-QoL trajectory in these patients. OBJECTIVE: To describe and identify factors explaining the variability in HR-QoL trajectories among a cohort of patients with history of COVID-19. DESIGN: A prospective study using data from a cohort of COVID-19 patients enrolled into a registry established at a health system in New York City. PARTICIPANTS: Participants were enrolled from July 2020 to June 2022, and completed a baseline evaluation and two follow-up visits at 6 and 12 months. METHODS: We assessed HR-QoL with the 29-item Patient Reported Outcomes Measurement Information System instrument, which was summarized into mental and physical health domains. We performed latent class growth and multinomial logistic regression to examine trajectories of HR-QoL and identify factors associated with specific trajectories. RESULTS: The study included 588 individuals with a median age of 52 years, 65% female, 54% White, 18% Black, and 18% Hispanic. We identified five physical health trajectories and four mental health trajectories. Female gender, having pre-existing hypertension, cardiovascular disease, asthma, and hospitalization for acute COVID-19 were independently associated with lower physical health. In addition, patients with increasing body mass index were more likely to experience lower physical health over time. Female gender, younger age, pre-existing asthma, arthritis and cardiovascular disease were associated with poor mental health. CONCLUSIONS: We found significant heterogeneity of HR-QoL after COVID-19, with women and patients with specific comorbidities at increased risk of lower HR-QoL. Implementation of targeted psychological and physical interventions is crucial for enhancing the quality of life of this patient population.

Patients who undergo tibial tubercle anteromedialization with medial patellofemoral ligament reconstruction demonstrate similar rates of return to sport compared to isolated MPFL reconstruction.

PURPOSE: To investigate the rate of return to sports and sport psychological readiness between patients who underwent isolated MPFLR (iMPFLR) compared to a matched cohort of patients who underwent MPFLR with anteromedializing tibial tubercle osteotomy (MPFLR/TTO). METHODS: Patients who underwent primary MPFLR with or without TTO for recurrent patellar instability were retrospectively reviewed from 2012 to 2020 at a single institution. Preinjury sport and work information, Kujala, Tegner, Visual Analogue Score for pain, satisfaction and MPFL-Return to Sport after Injury (MPFL-RSI) score were collected. Two readers independently measured the tibial tuberosity-trochlear groove distance, Caton-Deschamps index and Dejour classification for trochlear dysplasia. Patients in iMPFLR and MPFLR/TTO groups were matched 1:1 on age, sex, body mass index and follow-up length. Multivariate regression analysis was performed to determine whether the MPFL-RSI was associated with a return to sport. RESULTS: This study included 74 patients at mean follow-up of 52.5 months (range: 24-117). These groups returned to sport at similar rates (iMPFLR: 67.6%, MPFLR/TTO: 73.0%, not significant [ns]), though iMPFLR patients returned more quickly (8.4 vs. 12.8 months, p = 0.019). Rates of return to preinjury sport level were also similar (45.9% vs. 40.5%, ns). Patients with Dejour B/C took more time to return to sport compared to patients with mild/no trochlear pathology (13.8 vs. 7.9 months, p = 0.003). Increasing MPFL-RSI score was significantly predictive of the overall return to sport (odds ratio [OR]: 1.08, 95% confidence interval [CI] [1.03, 1.13], p < 0.001) and return to preinjury level (OR: 1.07, 95% CI [1.04, 1.13], p < 0.001). Most patients in iMPFLR and MPFLR/TTO groups resumed work (95.7% vs. 88.5%, ns), though iMPFLR patients who returned to preinjury work levels did so more quickly (1.7 vs. 4.6 months, p = 0.005). CONCLUSION: Patients who underwent MPFLR with anteromedializing TTO demonstrated similar rates of return to sport and psychological readiness compared to an isolated MPFLR matched comparison group, though iMPFLRs returned more quickly. Patients with more severe trochlear pathology required more time to return to sports. LEVEL OF EVIDENCE: Level III.

Increased kinesiophobia leads to lower return to sport rate and clinical outcomes following osteochondral allograft transplantation of the knee.

PURPOSE: The purpose of this study is to describe the postoperative psychological state of patients following osteochondral allograft (OCA) transplantation in the knee and to determine whether patient-perceived kinesiophobia is associated with the rate of return to sport (RTS). METHODS: A retrospective review of the electronic medical record at a single institution was conducted for all patients that underwent OCA transplantation from January 2010 to 2020. Patient-reported outcomes including the visual analog scale (VAS), knee injury and osteoarthritis outcome score (KOOS) and the Tampa scale of kinesiophobia-11 (TSK-11) were collected. Patients were surveyed regarding their postoperative RTS status. RESULTS: A total of 38 patients (52.6% female) were included in our analysis. Overall, 24 patients (63.2%) returned to sport with 12 (50%) of these patients returning at a lower level of play. When comparing patients that return to sport to those that did not, patients that return had significantly superior KOOS pain (p = 0.019) and KOOS QOL (p = 0.011). Measures of kinesiophobia (TSK-11) were significantly higher among patients that did not return to sport (p = 0.014), while satisfaction (n.s.) and pain intensity (n.s.) were comparable between groups. Logistic regression models controlling for demographic factors, VAS pain scores and lesion size showed that for every one-point increase in TSK-11 kinesiophobia score, patients were 1.33 times more likely to return to sport at a lower level (p = 0.009). For every one-point increase in TSK-11 scores KOOS QOL decreased by 2.4 points (p < 0.001). CONCLUSION: Fear of reinjury decreases the likelihood that patients will return to their preoperative level of sport after OCA transplantation. Patients that do not return to sport report significantly greater fear of reinjury and inferior clinical outcomes, despite similar levels of satisfaction and pain compared to those that return. LEVEL OF EVIDENCE: Level III.

The 50 Most Cited Publications in Adipose-Derived "Stem Cell Therapies" with Application in Orthopaedic Surgery.

Stem cell therapies have become widely popular in orthopaedic surgery, with a recent interest in adipose-derived therapeutics. Adipose-derived mesenchymal signaling cells (ADSCs) and micronized adipose tissue (MAT) are unique therapies derived from different processing methods. Characterizing the most influential studies in lipoaspirate research can help clarify controversies in definitions, identify core literature, and further collective knowledge for educational purposes. The Science Citation Index Expanded subsection of the Web of Science Core Collection was systematically searched to identify the top 50 most cited publications (based on citation/year) on orthopaedic ADSCs or MAT research. Publication and study characteristics were extracted and reported using descriptive statistics. Level of evidence was assessed for applicable studies, and Spearman correlations were calculated to assess the relationship between citation data and level of evidence. The top 50 articles were published between the years 2003 and 2020, with 78% published in the year 2010 or later. The mean number of citations was 103.1 ± 81.1. The mean citation rate was 12.4 ± 6.0 citations per year. Of the 21 studies for which level of evidence was assessed, the majority were level III (10, 47.6%). The single study design most common among the top 50 cited articles was in vitro basic science studies (17 studies, 34%). Twenty-nine articles (58%) were classified as basic science or translational. Application to treat knee osteoarthritis was the most common focus of studies (14 studies, 28%), followed by in vitro analysis of growth factor and cell signaling markers (11 studies, 22%). No correlation was found between rank, citation rate, or year of publication and level of evidence. This study provides a current landscape on the most cited articles in lipoaspirates in orthopaedic surgery. With the expansion of ADSCs and MAT in the past two decades, this study provides the first historical landmark of the literature and a launching point for future research. Studies should explicitly state their processing methodology and whether their study investigates ADSCs or MAT to avoid misinformation.

Patients With Segond Fracture Demonstrate Similar Rates of Return to Sport and Psychological Readiness After Anterior Cruciate Ligament Reconstruction: A Matched Cohort Study at Minimum 2-Year Follow-Up.

PURPOSE: To compare clinical outcomes, rate of return to sports, and psychological readiness among patients undergoing anterior cruciate ligament reconstruction (ACLR) with and without concomitant Segond fracture. METHODS: We retrospectively identified patients who underwent primary ACLR from January 2012 to December 2020 with minimum 2-year follow-up. Exclusion criteria were additional ligamentous injury, age <16 years, or a concomitant lateral augmentation procedure. Preoperative knee radiographs were reviewed to identify Segond fractures. Identified patients were matched 1:2 to controls by age/sex/body mass index/graft type. Charts were reviewed for pre- and postoperative knee stability. Surveys administered included preinjury sport participation and return status, Lysholm score, Tegner activity scale, and ACL-Return to Sport Index (ACL-RSI), a metric of psychological sport readiness. Multivariable logistic regression was conducted to identify predictors of return to sport. RESULTS: There were 120 patients who were included in the final analysis (40 Segond, 80 controls) at a mean follow-up of 5.7 ± 2.4 years. A total of 52.5% of patients received bone-patellar tendon-bone autograft. The overall rate of return to sport was 79.5% in the Segond group compared with an 83.8% rate of return in the control group (P = .569). In total, 48.7% of the Segond group and 56.8% of the control group returned to their preinjury level of sport (P = .415). Lysholm (89.6 ± 10.3 vs 85.4 ± 16.7, P = .296), Tegner (5.7 ± 1.8 vs 6.1 ± 2.2, P = .723), and ACL-RSI (62.2 ± 25.4 vs 56.6 ± 25.4, P = .578) scores were similar between Segond and control groups. There was a single graft failure in the Segond group 5 years' postoperatively. Increasing ACL-RSI score was significantly predictive of return to sport (P < .001). CONCLUSIONS: Patients who had an ACL tear and a concomitant Segond fracture who underwent isolated ACLR without lateral augmentation procedures had similar clinical outcomes and rates of return sport compared with a matched isolated ACLR control group at minimum 2-year follow-up. There was no significant difference in psychological readiness between groups as measured by the ACL-RSI. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

High Rate of Patient Satisfaction with Either Telemedicine or Traditional Office-Based Follow-Up Visit After Arthroscopic Shoulder Surgery.

Background: The purpose of this study was to determine if any differences exist in patient satisfaction with office-based visits versus telemedicine visits following arthroscopic shoulder surgery. Methods: Patients undergoing shoulder arthroscopy were prospectively enrolled for 1 year. Patient demographic and clinical data (including complication events) and second postoperative visit satisfaction data were recorded and analyzed for statistical significance. Results: Ninety-six (n = 96) patients met inclusion criteria. Fifty-four patients (56.3%) participated in a traditional in-person office visit, and 42 participated in a video visit (43.8%). No significant differences were found between office and video appointments in terms of overall care satisfaction (9.46 ± 0.9 vs. 9.55 ± 1.0, p = 0.67). Females were significantly less satisfied with their second postoperative visit compared with males (8.3 ± 2.3 vs. 9.3 ± 1.5, p = 0.035). Significantly more females would also have preferred a traditional in person office visit compared with males (91% vs. 67%, p = 0.009). Video appointment patients spent significantly more time with their surgeon than office visit patients (57.64 mean rank vs. 41.39 mean rank, p = 0.003). Discussion: Video visit patients required significantly less time overall for their visit and spent significantly more time with their surgeon, although did not demonstrate differences in satisfaction.

Patient-reported outcomes and return to pre-injury activities after surgical treatment of multi-ligamentous knee injuries in patients over 40-years-old: Average 5-years follow-up.

BACKGROUND: Multi-ligamentous knee injuries (MLKI) are potentially devastating injuries, though existing prognostic research among older patients who sustain MLKI is limited. The purpose was to investigate clinical outcomes and rates of return to pre-injury activities following surgical treatment of MLKI in patients at least 40 years old. METHODS: This study was a multi-center retrospective case series of patients who underwent surgical treatment for MLKI from 2013-2020 and were ≥ 40 years old at time of injury. Outcomes were assessed via e-mail and telephone using the International Knee Documentation Committee (IKDC) score, Lysholm score, Tegner activity scale, a satisfaction rating, and return to pre-injury sport and work surveys. Stepwise linear regression was used to assess the impact of preoperative characteristics on IKDC and Lysholm scores. RESULTS: Of 45 patients eligible for inclusion, 33 patients (mean age: 48.6 years [range: 40-72]) were assessed at a mean follow-up of 59.1 months (range 24-133). The cohort reported a mean IKDC of 63.4 ± 23.5, Lysholm of 72.6 ± 23.6, and Tegner of 3.8 ± 2.0. There was a 41.2% rate of return to sports, and 82.1% returned to work. Documented knee dislocation was predictive of poorer IKDC (ß:-20.05, p = 0.025) and Lysholm (ß:-19.99, p = 0.030). Patients aged > 50 were more satisfied compared to those 40-50 years old (96.2 ± 4.9 vs 75.6 ± 23.3, p = 0.012). CONCLUSIONS: Patients who sustained MLKI aged at least 40 at injury demonstrated fair clinical outcomes at a mean 5-year follow-up. Older patients who sustained MLKI reported a relatively high rate of return to work but were less likely to return to sports. LEVEL OF EVIDENCE: IV, Case series.

Patient-reported allergies are associated with increased rate of postoperative stiffness after arthroscopic rotator cuff repair.

BACKGROUND: Several risk factors have been identified for the development of postoperative shoulder stiffness, and there has been increasing interest in orthopedic literature regarding patient-reported allergy (PRA) as an identifiable risk factor for adverse outcomes. The purpose of this study is to determine whether PRAs are associated with subsequent rates of diagnosis of adhesive capsulitis (AC) or return to the operating room for postoperative shoulder stiffness within 2 years after arthroscopic rotator cuff repair (ARCR). METHODS: Current Procedural Terminology surgical billing codes were used to retrospectively identify patients who underwent ARCR at a single urban academic institution from January 2012 to December 2020 with minimum 2-year follow-up. Lysis of adhesions (LOA), manipulation under anesthesia (MUA), and AC of the shoulder were further queried within 2 years postoperatively for the ipsilateral shoulder. Patients were excluded if they had undergone ipsilateral MUA/LOA or received a diagnosis of AC before the index procedure. Demographic characteristics and medical comorbidities (hypertension, diabetes, hyperlipidemia, and hypothyroidism) were extracted from electronic medical records. Baseline characteristics were compared between patients with and without PRAs. Multivariate logistic regression analyses were performed to determine the association of the presence of PRAs overall, as well as the presence of 1, 2, or 3 or more PRAs, with subsequent MUA/LOA or diagnosis of AC within 2 years postoperatively. RESULTS: Of 7057 patients identified in the study period, 6583 were eligible for the final analysis. The mean age was 56.6 ± 11.7 years, and the mean body mass index was 29.1 ± 5.6. Overall, 19.3% of patients (n = 1271) reported at least 1 allergy, and 7.1% (n = 469) had >1 PRA. A total of 44 patients (0.7%) underwent subsequent ipsilateral MUA/LOA within 2 years postoperatively, whereas 93 patients (1.4%) received a diagnosis of ipsilateral AC in the same time frame. PRAs were significantly associated with subsequent diagnosis of AC (odds ratio [OR]: 2.39; 95% confidence interval [CI]: 1.45-3.92; P < .001), but not MUA/LOA (OR: 1.97, 95% CI: 1.26-3.61; P = .133). Patients with 2 PRAs had greater odds of being diagnosed with AC than patients with 1 PRA (OR: 2.74; 95% CI: 1.14-5.99; P = .012). Although this association was nonsignificant for MUA/LOA, patients with 2 PRAs (OR: 2.67; 95% CI: 0.96-8.80; P = .059) demonstrated a similar statistical trend. CONCLUSION: PRAs are associated with increased odds of receiving a diagnosis of AC within 2 years after ARCR but were not found to be associated with return to the operating room for postoperative stiffness.