Morrey, Mark E.

Aims Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein). Results At the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001). Conclusion Collectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis. Cite this article: Bone Joint Res 2020;9(6):302–310.

AbstractThe dense formation of abnormal scar tissue after total knee arthroplasty results in arthrofibrosis, an unfortunate sequela of inflammation. The purpose of this study was to use a validated rabbit model to assess the effects on surgically‐induced knee joint contractures of two combined pharmacological interventions: celecoxib (CXB) loaded on an implanted collagen membrane, and subcutaneously (SQ) injected ketotifen. Thirty rabbits were randomly divided into five groups. The first group received no intervention after the index surgery. The remaining four groups underwent intra‐articular implantation of collagen membranes loaded with or without CXB at the time of the index surgery; two of which were also treated with SQ ketotifen. Biomechanical joint contracture data were collected at 8, 10, 16, and 24 weeks. At the time of necropsy (24 weeks), posterior capsule tissue was collected for messenger RNA and histopathologic analyses. At 24 weeks, there was a statistically significant increase in passive extension among rabbits in all groups treated with CXB and/or ketotifen compared to those in the contracture control group. There was a statistically significant decrease in COL3A1, COL6A1, and ACTA2 gene expression in the treatment groups compared to the contracture control group (P < .001). Histopathologic data also demonstrated a trend towards decreased fibrous tissue density in the CXB membrane group compared to the vehicle membrane group. The present data suggest that intra‐articular placement of a treated collagen membrane blunts the severity of contracture development in a rabbit model of arthrofibrosis, and that ketotifen and CXB may independently contribute to the prevention of arthrofibrosis. Statement of clinical significance: Current literature has demonstrated that arthrofibrosis may affect up to 5% of primary total knee arthroplasty patients. For that reason, novel pharmacologic prophylaxis and treatment modalities are critical to mitigating reoperations and revisions while improving the quality of life for patients with this debilitating condition.

Purpose To systematically evaluate the outcomes and complications of osteochondral autograft transfer (OAT) and osteochondral allograft transplantation (OCA) for the surgical treatment of capitellar osteochondritis dissecans (OCD). Methods A literature search was conducted across 3 databases (PubMed, Cochrane, and CINAHL [Cumulative Index to Nursing and Allied Health Literature]) from database inception through December 2019 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines. Individual study quality was assessed using the Methodological Index for Non‐randomized Studies scale. Studies were published between 2005 and 2019. Results Eighteen studies consisting of 446 elbow OCD lesions treated with OAT surgery were included. There was a single OCA study eligible for inclusion. Patient ages ranged from 10 to 45 years. Of the OAT studies, 4 used autologous costal grafts whereas the remainder used autografts from the knee. Outcome measures were heterogeneously reported. A significant improvement in Timmerman‐Andrews scores from preoperatively to postoperatively was reported in 9 of 10 studies. Return‐to‐play rates to the preinjury level of competitive play ranged from 62% to 100% across 16 studies. Significant improvement in motion, most often extension, was noted in most studies. Reported complication, reoperation, and failure rates ranged from 0% to 11%, 0% to 26%, and 0% to 20%, respectively. When used, knee autografts resulted in low donor‐site morbidity (Lysholm scores, 70‐100). Conclusions OAT surgery for large, unstable OCD lesions of the capitellum reliably produced good outcomes, few complications, and a high rate of return to competitive play. Complications are relatively uncommon, and donor‐site morbidity is low. Less is known about the performance of OCA given the paucity of available literature. Level of Evidence Level IV, systematic review of Level II to IV studies.

Background Despite good reported outcomes with open reduction and internal fixation of intra-articular distal humerus fractures, complication rates remain high. The objective of this work is to identify factors associated with reoperation. Methods Sixty-three patients treated with open reduction and internal fixation for intra-articular ( Arbeitsgemeinschaft für Osteosynthesefragen type C) distal humerus fractures between 2004 and 2010 were identified using an institutional trauma registry, 62 of which were followed for a minimum of six months. Age, gender, fracture subclassification, open fracture presence, Injury Severity Score, time to definitive surgery, length of postoperative immobilization, and type of approach were recorded. Multivariate analysis was utilized to identify factors independently associated with reoperation. Results Complications requiring reoperation developed in 25 (40.3%) elbows. The most common reasons were wound dehiscence or infection in nine elbows (14.5%) and symptomatic hardware in six (9.6%). During multivariate analysis, only olecranon osteotomy remained an independent predictor for reoperation ( P = 0.043). Discussion Despite improved internal fixation techniques, a high proportion of elbows require reoperation after open reduction and internal fixation for distal humerus fractures. Higher complication rates in fractures fixed through an olecranon osteotomy may reflect additional reoperations due to nonunion of the osteotomy or need to remove hardware from the ulna. Level of evidence Prognostic Level III.

ABSTRACTArthrofibrosis is a common complication following total knee arthroplasty caused by pathologic fibroblast activation and excessive collagen deposition around a synovial joint leading to debilitating loss of motion. Treatment options are limited because the pathologic mechanisms remain to be characterized. Dysregulation of the inflammatory cascade may lead to communication between myofibroblasts and immune cells triggering tissue metaplasia, and excessive collagen deposition described clinically as arthrofibrosis. We explored the novel use of celecoxib (selective cyclooxygenase‐2 [COX‐2] inhibitor) to disrupt the downstream effects of the post‐traumatic inflammatory cascade and inhibit scar tissue formation in a validated rabbit model of arthrofibrosis combined with new parameters for quantifying the stiffness of the posterior capsule. Biomechanical and molecular analyses, of contracted rabbit knee posterior capsule tissue after COX‐2 inhibition revealed increased maximal passive extension and down‐regulation of collagen messenger RNA compared with controls. Histopathologic examination suggested a trend of decreased quantities of dense fibrous connective tissue with COX‐2 inhibition. These data may suggest that inhibiting the inflammatory cascade could potentially reduce pathologic myofibroblast activation, thereby reducing scar tissue formation and increasing the range of motion in arthrofibrotic joints. Implementing a multi‐modal pharmacologic approach may simultaneously target numerous cellular components contributing to the complex process of arthrofibrogenesis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2609–2620, 2019

ABSTRACTTrauma, surgery, and other inflammatory conditions can lead to debilitating joint contractures. Adjunct pharmacologic modalities may permit clinical prevention and treatment of recalcitrant joint contractures. We investigated the therapeutic potential of rosiglitazone by intra‐articular delivery via oligo[poly(ethylene glycol)fumarate] (OPF) hydrogels in an established rabbit model of arthrofibrosis. OPF hydrogels loaded with rosiglitazone were characterized for drug elution properties upon soaking in minimum essential media (MEM) with 10% fetal bovine serum and measurements of drug concentrations via High Performance Liquid Chromatography (HPLC). Drug‐loaded scaffolds were surgically implanted into 24 skeletally mature female New Zealand White rabbits that were divided into equal groups receiving OPF hydrogels loaded with rosiglitazone (1.67 mg), or vehicle control (10 µl DMSO). After 8 weeks of joint immobilization, rabbits were allowed unrestricted cage activity for 16 weeks. Contracture angles of rabbit limbs treated with rosiglitazone showed statistically significant improvements in flexion compared to control animals (mean angles, respectively, 64.4° vs. 53.3°, p < 0.03). At time of sacrifice (week 24), animals in the rosiglitazone group continued to exhibit less joint contracture than controls (119.0° vs. 99.5°, p = 0.014). The intra‐articular delivery of rosiglitazone using implanted OPF hydrogels decreases flexion contractures in a rabbit model of arthrofibrosis without causing adverse effects (e.g., gross inflammation or arthritis). Statement of Clinical Significance: Post‐traumatic joint contractures are common and debilitating, with limited available treatment options. Pharmacologic interventions can potentially prevent and treat such contractures. This study is translational in that a commercially approved medication has been repurposed through a novel delivery device. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2949–2955, 2018.

Introduction Primary reverse shoulder arthroplasty has been reported to provide good outcomes. The majority of designs utilize a large portion of the glenoid. Some studies have reported worrisome rates of notching and stress fractures of the acromion or scapular spine. The purpose of this study was to determine the outcome and complications of a bone-preserving reverse prosthesis with limited ingrowth glenoid surface paired with an onlay humeral component. Materials and methods Between 2014 and 2015, 96 reverse arthroplasties were implanted using a bone-preserving reverse with a 135° onlay humeral bearing. Six patients died. The remaining 87 patients (90 shoulders) were followed for 2 years or until revision. Mean age was 69.3 years. The underlying diagnosis was cuff tear arthropathy (13), irreparable cuff tear (39), osteoarthritis (32), and other (6). Shoulders were followed for 2 years or until revision surgery. Results Reverse shoulder arthroplasty resulted in significant improvements in pain, motion, and function. At most recent follow-up, 74 shoulders had no or mild pain. Elevation was 131° ± 31° and external rotation 46° ± 21°. The mean American Shoulder and Elbow Surgeons (ASES) score was 76. There were 4 reoperations for deep infection (2), periprosthetic fracture, and glenoid loosening. None of the remaining arthroplasties were loose. There was one stress fracture of the acromion and one of the spine of the scapula. No radiographic notching or dislocation was observed. Discussion Primary reverse arthroplasty using a bone-preserving glenoid component and an anatomic onlay humeral bearing provides satisfactory clinical outcomes with a very low rate of failure and complications.

ABSTRACTThe current method of measuring arthrofibrosis in live rabbits is critically limited. Specifically, this method involves radioactive fluoroscopy, error‐prone goniometric measurements, and static joint angle outcomes that fail to approximate the compliance of tissues surrounding the joint. This study aims to validate a novel method of capturing the compliance of contracted tissues surrounding the joint without the use of fluoroscopy or animal sacrifice. Surgically induced contractures of one‐hundred and eight rabbits were measured using the current standard of contracture measurement (a pulley system) as well as a newly designed dynamic load cell (DLC) device. The DLC device was highly reliable when compared to the pulley system (r = 0.907, p < 0.001). Finally, the DLC device produced joint stiffness hysteresis curves capable of approximating the compliance of stiff joint tissues, ultimately calculating a mean joint stiffness of 1.57 ± 1.31 N · m · rad−1 (range, 0.33–6.37 N · m · rad−1). In conclusion, the DLC device represents a valid method for measuring joint contractures. Further, the DLC device notably improves current techniques by introducing the capacity to approximate the compliance of contracted tissues in living rabbits. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2186–2192, 2018.

Background: High rates of radiographic loosening have been reported with various glenoid designs. Many available designs sacrifice most of the bone at the central portion of the glenoid vault, creating large areas of deficiency when revision becomes necessary. The purpose of this study was to report the 2- to 5-year outcome of shoulder arthroplasty using a bone-preserving all-polyethylene glenoid components with self-pressurizing pegs. Methods: Between August 2011 and December 2014, 202 consecutive anatomic total shoulder arthroplasties (TSAs) were performed by a single surgeon with implantation of a self-pressurizing cemented pegged glenoid component in 190 patients (12 patients had both shoulders replaced). Patients were followed up prospectively and evaluated for pain, motion, strength, American Shoulder and Elbow Surgeons (ASES) scores, and radiographic changes. The mean follow-up time was 2.7 (2–5) years. Results: TSA improved pain and function reliably. At the most recent follow-up, 94% of the shoulders had no or mild pain. Motion included 154 ± 25° of elevation, 68 ± 18° of external rotation, and median internal rotation to T10 (range, iliac crest to T4). The most recent average ASES score was 82 ± 15 points. Early postoperative radiographs showed no radiolucent lines. No humeral or glenoid component was considered radiographically loose at the most recent follow-up. Complications requiring reoperation included subscapularis insufficiency (4), posterior instability (2), deep infection (1), stiffness (1), and a painful loose body (1). No components were revised for loosening. Conclusions: Anatomic TSA using a cemented bone-preserving all-polyethylene pegged self-pressurizing glenoid component provided satisfactory clinical outcomes and survival at 2 to 5 years.