Morrey, Mark E.

Platelet-rich plasma (PRP) is a revolutionary treatment that harnesses the regenerative power of the body's own platelets to promote healing and tissue regeneration. While PRP therapy has emerged as a promising option for augmenting biologic healing in the shoulder, the complexity of shoulder disorders makes it difficult to draw definitive conclusions about the efficacy of PRP across different conditions and stages of disease. Our comprehensive review of twenty-four studies highlights the current state of PRP therapy in shoulder pathologies, revealing a wide variety of number of patients, control groups and results. Despite these challenges, the regenerative potential of PRP therapy is moderate in some conditions, with numerous studies demonstrating the positive effects. In conclusion, the authors of this study recommend the use of PRP therapy for adhesive capsulitis and rotator cuff repair of medium to large tears. However, they do not recommend the use of PRP for subacromial impingement or rotator cuff tears. It is up to the clinician's discretion to decide whether PRP therapy is appropriate for individual cases. However, there is still insufficient evidence to support the inclusion of PRP therapy in treatment protocols for other shoulder disorders. Therefore, further research is needed to fully explore the potential of PRP therapy in the treatment of various shoulder conditions.

Objectives: Osteochondritis dissecans (OCD) of the humeral capitellum is an often painful condition that typically affects the adolescent athlete. There is little consensus on treatment and a scarcity of long-term outcomes data. The purpose of this study was to (1) report the long-term outcomes associated with both operative and non-operative management of capitellar OCD, (2) identify factors associated with failure of non-operative management, and (3) determine whether delay in surgery affects final outcomes. Methods: All patients diagnosed with OCD of the capitellum from 1995-2020 within a defined geographic cohort were included. Medical records, imaging studies, and operative reports were manually reviewed to record demographic data, treatment strategies, and outcomes. Surgical treatment was considered delayed if it occurred more than 6 months after symptom onset. Results: A total of 50 elbows with a mean follow-up of 9.4 years were included. Of these, 7 (14%) were treated non-operatively and never underwent surgery during follow-up, while 43 (86%) underwent surgical intervention: 27 had early surgery and 16 underwent delayed surgery after ≥ 6 months of non-operative treatment. When compared to non-operative management, surgical management resulted in superior MEPI scores (90 vs 83, p=0.05), decreased persistence of mechanical symptoms (9% vs 50%, p<0.01), and better elbow flexion (141° vs 131°, p=0.01) at long-term follow up. Older patients had a trend toward increased failure of non-operative management (p=0.06). The presence of an intra-articular loose body strongly predicted failure of non-operative management (p=0.01; OR 13). Plain radiography and MRI had poor sensitivities for identifying loose bodies (27% and 40%, respectively). Differences in outcomes following early versus delayed surgical management were not demonstrated. Conclusions: Patients with capitellar OCD initially treated nonoperatively failed nonoperative management 70% of the time. Elbows that did not undergo surgery had slightly increased symptoms and decreased functional outcomes compared to those treated surgically. In this cohort, the greatest predictors for failure of non-operative treatment were older age and presence of a loose body; however, an initial trial of non-operative treatment did not adversely impact the success of future surgery at long term follow-up. [Table: see text][Table: see text][Table: see text][Table: see text]

Purpose To (1) report the long‐term outcomes associated with both operative and nonoperative management of capitellar osteochondritis dissecans (OCD), (2) identify factors associated with failure of nonoperative management, and (3) determine whether delay in surgery affects final outcomes. Methods All patients who received a diagnosis of capitellar OCD from 1995‐2020 within a geographic cohort were included. Medical records, imaging studies, and operative reports were manually reviewed to record demographic data, treatment strategies, and outcomes. The cohort was divided into 3 groups: (1) nonoperative management, (2) early surgery, and (3) delayed surgery. Delayed surgery (surgery ≥6 months after symptom onset) was considered failure of nonoperative management. Results Fifty elbows with a mean follow‐up period of 10.5 years (median, 10.3 years; range, 1‐25 years) were studied. Of these, 7 (14%) were definitively treated nonoperatively, 16 (32%) underwent delayed surgery after at least 6 months of failed nonoperative treatment, and 27 (54%) underwent early surgical intervention. When compared with nonoperative management, surgical management resulted in superior Mayo Elbow Performance Index pain scores (40.1 vs 33, P = .04), fewer mechanical symptoms (9% vs 50%, P < .01), and better elbow flexion (141° vs 131°, P = .01) at long‐term follow‐up. Older patients trended toward increased failure of nonoperative management ( P = .06). The presence of an intra‐articular loose body predicted failure of nonoperative management ( P = .01; odds ratio, 13). Plain radiography and magnetic resonance imaging had poor sensitivities for identifying loose bodies (27% and 40%, respectively). Differences in outcomes after early versus delayed surgical management were not observed. Conclusions Nonoperative management of capitellar OCD failed 70% of the time. Elbows that did not undergo surgery had slightly more symptoms and decreased functional outcomes compared with those treated surgically. The greatest predictors of failure of nonoperative treatment were older age and presence of a loose body; however, an initial trial of nonoperative treatment did not adversely impact the success of future surgery. Level of Evidence Level III, retrospective cohort study.

AbstractArthrofibrosis, which is characterized by excessive scar tissue and limited motion, can complicate the daily functioning of patients after total knee arthroplasty (TKA). Molecular hallmarks of arthrofibrosis include pathologic accumulation of myofibroblasts and disproportionate collagen deposition. Epigenetic mechanisms, including posttranslation modification of histones, control gene expression and may regulate fibrotic events. This study assessed the role of the bromodomain and extra‐terminal (BET) proteins on myofibroblast differentiation. This group of epigenetic regulators recognize acetylated lysines and are targeted by a class of drugs known as BET inhibitors. RNA‐seq analysis revealed robust mRNA expression of three BET members (BRD2, BRD3, and BRD4) while the fourth member (BRDT) is not expressed in primary TKA knee outgrowth fibroblasts. RT‐qPCR and western blot analyses revealed that BET inhibition with the small molecule JQ1 impairs TGFβ1‐induced expression of ACTA2, a key myofibroblast marker, in primary outgrowth knee fibroblasts. Similarly, JQ1 administration also reduced COL3A1 mRNA levels and collagen deposition as monitored by picrosirius red staining. Interestingly, the inhibitory effects of JQ1 on ACTA2 mRNA and protein expression, as well as COL3A1 expression and collagen deposition, were paralleled by siRNA‐mediated depletion of BRD4. Together, these data reveal that BRD4‐mediated epigenetic events support TGFβ1‐mediated myofibroblast differentiation and collagen deposition as seen in arthrofibrosis. To our knowledge, these are the first studies that assess epigenetic regulators and their downstream events in the context of arthrofibrosis. Future studies may reveal clinical utility for drugs that target epigenetic pathways, specifically BET proteins, in the prevention and treatment of arthrofibrosis.

Aims As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA). Methods Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections. Results Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. Conclusion This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies. Cite this article: Bone Joint Res 2023;12(1):58–71.

Background: Arthroscopic debridement for osteochondritis dissecans (OCD) lesions of the capitellum is a relatively common and straightforward surgical option for failure of nonoperative management. However, the long-term outcomes of this procedure remain unknown. Hypothesis: Arthroscopic debridement of capitellar OCD would provide satisfactory long-term improvement in patient-reported outcomes. Study Design: Case series; Level of evidence, 4. Methods: Patients aged ≤18 years who underwent arthroscopic debridement procedures for OCD lesions (International Cartilage Repair Society grades 3 and 4) were identified. Procedures included loose body removal when needed and direct debridement of the lesion; marrow stimulation with drilling or microfracture was added at the discretion of each surgeon. The cohort consisted of 53 elbows. Patient evaluation included visual analog scale for pain; motion; subjective satisfaction; Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) scores; reoperation; and rate of return to sports. Results: At a mean 11 years of follow-up (range, 5-23 years), the median visual analog scale score for pain was 0, and 96% of patients reported being improved as compared with how they were before surgery. The mean ± SD QuickDASH score was 4 ± 9 points (range, 0-52 points), and 80% of patients returned to their sports of interest. The arc of motion significantly improved from 115°± 28° preoperatively to 130°± 17° at latest follow-up ( P = .026). Seven elbows (13%) required revision surgery for OCD lesions, resulting in high rates of overall survivorship free of revision surgery: 90% (95% CI, 80%-96%) at 5 years and 88% (95% CI, 76%-94%) at 10 years. At final follow-up, 7 all-cause reoperations were performed without revision surgery on the OCD lesion. Conclusion: Arthroscopic debridement of grade 3 or 4 OCD lesions of the capitellum produced satisfactory patient-reported outcomes in a majority of elbows, although a subset of patients experienced residual symptoms. The inherent selection bias of our cohort should be considered when applying these results to the overall population with OCD lesions, as we do not recommend this procedure for all patients.

Background: There are limited data on the incidence of capitellar osteochondritis dissecans (OCD) in the United States (US) population. Purpose: To determine the incidence of symptomatic capitellar OCD in a representative US subpopulation and identify changes in its incidence over time and to investigate the relationship between the incidence of capitellar OCD and patient sex and age. Study Design: Descriptive epidemiology study. Methods: A retrospective review was performed of patients aged ≤24 years from Olmsted County, Minnesota, with symptomatic capitellar OCD over a 25-year period (1995-2019). Patients with acute osteochondral injuries, Panner disease, and hereditary arthropathy were excluded. Poisson regression was utilized to identify the predictors of a capitellar OCD diagnosis. Incidence rates (per 100,000) were assessed for changes over time. Age groups of younger (10-15 years) versus older (16-24 years) patients were compared. Results: A total of 45 patients (78% male) were identified. The mean age was 14.5 years (range, 10-24 years); 31 patients were in the younger group, and 14 patients were in the older group. Sport participation was seen in 89%of patients; 90% were overhead athletes, and 58% were throwing athletes. The incidence of capitellar OCD was 6.0 per 100,000 overall, 9.5 per 100,000 for male patients, and 2.6 per 100,000 for female patients. The incidence was highest for male patients in the younger group (15.3/100,000) and lowest for female patients in the older group (0.8/100,000). The estimated incidence rate ratio for younger versus older patients was 3.3 ( P < .001), and the incidence rate ratio for male versus female patients was 3.5 ( P < .001). There were no changes in the incidence of capitellar OCD over time as a continuous or 5-year categorical variable ( P = .290 and P = .460, respectively). Overall, 82% of patients were treated surgically. There were no significant changes in surgical rates over time. Conclusion: In this US subpopulation, the overall incidence of symptomatic capitellar OCD between the ages of 10 and 24 years was 6.0 per 100,000 over the 25-year period studied, which is higher than previously reported US estimates. Incidence rates and treatment strategies did not change significantly over time.

Background: Continuous passive motion (CPM) has been used for decades, but we are not aware of any randomized controlled trials (RCTs) in which CPM has been compared with physical therapy (PT) for rehabilitation following release of elbow contracture. Methods: In this single-blinded, single-center RCT, we randomly assigned patients undergoing arthroscopic release of elbow contracture to a rehabilitation protocol involving either CPM or PT. The primary outcomes were the rate of recovery and the arc of elbow motion (range of motion) at 1 year. The rate of recovery was evaluated by measuring range of motion at 6 weeks and 3 months. The secondary outcomes included other range-of-motion-related outcomes, patient-reported outcome measures (PROMs), flexion strength and endurance, grip strength, and forearm circumference at multiple time points. Results: A total of 24 patients were assigned to receive CPM, and 27 were assigned to receive PT. At 1 year, CPM was superior to PT with regard to the range of motion, with an estimated treatment difference of 9° (95% confidence interval [CI], 3° to 16°; p = 0.007). Similarly, the use of CPM led to a greater range of motion at 6 weeks and 3 months than PT. The percentage of lost motion recovered at 1 year was higher in the CPM group (51%) than in the PT group (36%) (p = 0.01). The probability of restoring a functional range of motion at 1 year was 62% higher in the CPM group than in the PT group (risk ratio for functional range of motion, 1.62; 95% CI, 1.01 to 2.61; p = 0.04). PROM scores were similar in the 2 groups at all time points, except for a difference in the American Shoulder and Elbow Surgeons (ASES) elbow function subscale, in favor of CPM, at 6 weeks. The use of CPM decreased swelling and reduced the loss of flexion strength, flexion endurance, and grip strength on day 3, with no between-group differences thereafter. Conclusions: Among patients undergoing arthroscopic release of elbow contracture, those who received CPM obtained a faster recovery and a greater range of motion at 1 year, with a higher chance of restoration of functional elbow motion than those who underwent routine PT. Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

AbstractArthrofibrosis is characterized by excessive extracellular matrix (ECM) deposition that results in restricted joint motion after total knee arthroplasties (TKAs). Currently, treatment options are limited. Therefore, an in vitro model of knee‐related myofibroblastogenesis is valuable to facilitate investigation of the arthrofibrotic process, diagnostic and therapeutic options. In this study, we obtained intraoperative posterior capsule (PC), quadriceps tendon (QT), and suprapatellar pouch (SP) tissues from the knees of four patients undergoing primary TKAs for osteoarthritis. From these tissues, we isolated primary cells by the outgrowth method and subsequently characterized these cells in the absence and presence of the pro‐myofibroblastic cytokine, transforming growth factor beta 1 (TGFβ1). Light microscopy of knee outgrowth cells revealed spindle‐shaped cells, and immunofluorescence (IF) analysis demonstrated staining for the fibroblast‐specific markers TE‐7 and vimentin (VIM). These knee outgrowth fibroblasts differentiated readily into myofibroblasts as reflected by enhanced α‐smooth muscle actin (ACTA2) mRNA and protein expression and increased mRNA expression of collagen type 1 (COL1A1) and type 3 (COL3A1) with collagenous matrix deposition in the presence of TGFβ1. Outgrowth knee fibroblasts were more sensitive to TGFβ1‐mediated myofibroblastogenesis than adipose‐derived mesenchymal stromal/stem cells (MSCs). While outgrowth knee fibroblasts isolated from three anatomical regions in four patients exhibited similar gene expression, these cells are distinct from other fibroblastic cell types (i.e., Dupuytren's fibroblasts) as revealed by RNA‐sequencing. In conclusion, our study provides an in vitro myofibroblastic model of outgrowth knee fibroblasts derived from patients undergoing primary TKA that can be utilized to study myofibroblastogenesis and assess therapeutic strategies for arthrofibrosis.