AdipoRon reduces TGFß1-mediated collagen deposition in vitro and alleviates knee stiffness in vivo.

Arthrofibrosis, which causes joint motion restrictions, is a common complication following total knee arthroplasty (TKA). Key features associated with arthrofibrosis include myofibroblast activation, knee stiffness, and excessive scar tissue formation. We previously demonstrated that adiponectin levels are suppressed within the knee tissues of patients affected by arthrofibrosis and showed that AdipoRon, an adiponectin receptor agonist, exhibited anti-fibrotic properties in human mesenchymal stem cells. In this study, the therapeutic potential of AdipoRon was evaluated on TGFß1-mediated myofibroblast differentiation of primary human knee fibroblasts and in a mouse model of knee stiffness. Picrosirius red staining revealed that AdipoRon reduced TGFß1-induced collagen deposition in primary knee fibroblasts derived from patients undergoing primary TKA and revision TKA for arthrofibrosis. AdipoRon also reduced mRNA and protein levels of ACTA2, a key myofibroblast marker. RNA-seq analysis corroborated the anti-myofibrogenic effects of AdipoRon. In our knee stiffness mouse model, 6 weeks of knee immobilization, to induce a knee contracture, in conjunction with daily vehicle (DMSO) or AdipoRon (1, 5, and 25 mg/kg) via intraperitoneal injections were well tolerated based on animal behavior and weight measurements. Biomechanical testing demonstrated that passive extension angles (PEAs) of experimental knees were similar between vehicle and AdipoRon treatment groups in mice evaluated immediately following immobilization. Interestingly, relative to vehicle-treated mice, 5 mg/kg AdipoRon therapy improved the PEA of the experimental knees in mice that underwent 4 weeks of knee remobilization following the immobilization and therapy. Together, these studies revealed that AdipoRon may be an effective therapeutic modality for arthrofibrosis.

Comparison of reconstructive techniques for nonprimary malignancies in the proximal humerus.

BACKGROUND: Endoprostheses (EPC) are often utilized for reconstruction of the proximal humerus with either hemiarthroplasty (HA) or reverse arthroplasty (RA) constructs. RA constructs have improved outcomes in patients with primary lesions, but no studies have compared techniques in metastatic disease. The aim of this study is to compare functional outcomes and complications between HA and RA constructs in patients undergoing endoprosthetic reconstruction for proximal humerus metastases. METHODS: We retrospectively reviewed our institutional arthroplasty database to identify 66 (56% male; 38 HA and 28 RA) patients with a proximal humerus reconstruction for a non-primary malignancy. The majority (88%) presented with pathologic fracture, and the most common diagnosis was renal cell carcinoma (48%). RESULTSS: Patients with RA reconstructions had better postoperative forward elevation (74° vs. 32°, p < 0.01) and higher functional outcome scores. HA patients had more complications (odds ratio 13, p < 0.01), with instability being the most common complication. CONCLUSIONS: Patients with nonprimary malignancies of the proximal humerus had improved functional outcomes and fewer complications after undergoing reconstruction with a reverse EPC compared to a HA EPC. Preference for reverse EPC should be given in patients with good prognosis and ability to complete postoperative rehabilitation.

Open and Arthroscopic Elbow Contracture Release: Tips and Pearls.

Elbow stiffness is a common consequence of trauma and can significantly limit the functionality of the affected arm. Intervention may be necessary for those with a motion arc less than 100°, but the decision to intervene should be based on individual patient needs. Restoration of joint motion in a stiff elbow can be challenging, time consuming, and costly. Nonsurgical treatment is the primary management option, and surgical intervention is considered for refractory stiffness. However, recurrent stiffness is a common issue following surgical elbow contracture release. An overview of relevant elbow anatomy, principles and technical pearls of arthroscopic and open contracture release, and postoperative rehabilitation methods to reduce the risk of recurrent stiffness is provided. It is important to tailor the treatment plan to each patient's unique needs and functional expectations.

Complications After Reverse Shoulder Arthroplasty for Proximal Humerus Nonunion.

BACKGROUND: Proximal humerus nonunion is a challenging complication of fractures that can be treated surgically with either open reduction internal fixation (ORIF) or reverse total shoulder arthroplasty (RTSA). The few studies published on this subject have shown high rates of complications and revision surgery when RTSA has been performed for proximal humerus nonunion. The purpose of this study was to determine the rates of complications and revision of this procedure at our institution, as well as to identify any variables that may impact risks of complications and reoperations. METHODS: A single-institution retrospective review of all patients who underwent RTSA for proximal humerus nonunion between 2005 and 2021 was performed. Nonunion was defined as imaging evidence of lack of union, at least 90 days after the index fracture. Patients with less than one year of clinical follow-up were excluded. Fifty patients were included, with the majority being female (78%). The mean age at time of RTSA was 71 (range: 54-86) years and most patients were initially treated nonoperatively (74%). Mean total follow-up was 49 (range: 11-130) months. Demographic and surgical variables were recorded. Primary outcomes were complications and reoperations. Complications were divided into surgical (those directly related to RTSA), or other (those unrelated to RTSA). Secondary outcomes included VAS pain scores and range of motion. RESULTS: A total of 17 shoulders (34%) sustained complications after RSA, with 10 (20%) requiring reoperation. Six patients (12%) sustained dislocations and 5 (10%) had radiographic evidence of humeral loosening. No variables examined, including nonoperative vs surgical management of the index fracture, prosthesis type, or management of tuberosities, influenced the risk of dislocation. Survivorship free from reoperation at 2 years was 73%. Younger age at time of RTSA and the presence of diabetes mellitus both increased the risk of reoperation significantly (p=0.013 and p=0.037, respectively). There was a trend towards increased risk of reoperation in patients who were treated with initial ORIF (HR=2.95); however, this did not reach statistical significance (p=0.088). Three patients (6%) sustained a periprosthetic fracture after a fall. CONCLUSION: RTSA provides improved pain and function for properly selected patients with proximal humerus nonunion. Dislocation, humeral loosening, and reoperation rates remain high when RTSA is performed for nonunion compared to other diagnoses. In this study, younger age and diabetes mellitus increased the odds of reoperation. Every effort must be made to optimize implant stability and humeral component fixation when RTSA is performed for proximal humerus nonunion.

Operative Treatment of Acromial and Scapular Spine Fracture Nonunions Complicating Reverse Total Shoulder Arthroplasty.

BACKGROUND: Fractures of the acromion and spine can have a major impact on the outcome of reverse shoulder arthroplasty (RSA) with respect to pain, motion, and function. Reports on internal fixation for these fractures are isolated to small series or case reports with variable outcomes. The purpose of this study was to report on the outcome of open reduction and internal fixation (ORIF) of acromion or spine fractures encountered before or after RSA and describe our evolution of fixation techniques. METHODS: Between 2011 and 2023, 22 fractures or nonunions of the acromion or spine of the scapula underwent ORIF at a single institution and were followed for a minimum of 1 year. In 16 shoulders, fractures occurred after RSA, whereas 5 shoulders underwent ORIF prior to RSA. One shoulder had undergone prior failed ORIF elsewhere and revision ORIF was performed at our institution. There were 10 males and 12 females with a mean age of 67 (SD=15.1) years. Fixation strategies included single (n=11) and double plate fixation (n=11). Kruskal-Wallis one-way analyses of variance were used to analyze continuous variables and Chi-square tests employed for categorical variables. RESULTS: Of the 5 fractures treated with ORIF pre-RSA, 1 shoulder suffered an additional fracture medial to the hardware and 1 required additional bone grafting for incomplete union at the time of RSA. These 5 shoulders all underwent RSA uneventfully, but one fracture experienced late displacement of the scapular spine nonunion, leading to plate removal. Of the 16 post-RSA ORIF shoulders, radiographic union was confirmed in 14 and substantial residual inferior angulation identified in 3. New fractures occurred after ORIF in 5 shoulders. For patients who underwent ORIF after RSA, pain scores improved from a mean of 8 to 1.9 points, with more modest elevation gains (58.2° to 91.3° pre- and postoperatively, respectively). CONCLUSIONS: ORIF of acromion and scapular spine fractures or nonunions in the setting of RSA have the potential to lead to union. When these fractures and nonunions are encountered prior to RSA, ORIF allows for uneventful RSA implantation, but secondary displacement may occur. ORIF seems to lead to improvements in pain, but more modest improvements in motion and function. Our fixation strategy has evolved to (1) dual plating, (2) spanning the whole length of the spine with one of the plates, (3) use of hook features under the acromion or os trigonum if possible, and (4) liberal use of bone graft.

Complications of antibiotic cement spacers used for elbow infections.

BACKGROUND: Antibiotic cement spacers have been widely used in the treatment of joint infections. There are no commercially available antibiotic spacers for the elbow. Instead, they are typically fashioned by the surgeon at the time of surgery using cement alone or a combination of cement with sutures, Steinmann pins, external fixator components, or elbow arthroplasty components. There is no consensus regarding the ideal elbow antibiotic spacer and no previous studies have examined the complications associated with these handmade implants in relation to their unique structural design. METHODS: We retrospectively reviewed 55 patients who had 78 static antibiotic cement spacers implanted between January 1998 and February 2021 as part of a 2-stage treatment plan for infection of an elbow arthroplasty, other elbow surgery, or primary elbow infection. Several antibiotic spacer structures were used during the study period. For analysis purposes, the spacers were classified into linked and unlinked spacers based on whether there was a linking mechanism between the humerus and the ulna. Complications related to these spacers that occurred either during the implantation, between implantation and removal, or during removal were recorded and analyzed from chart review and follow-up x rays. Reoperations due to spacer-related complications were also recorded. RESULTS: Among the 55 patients (78 spacers), there were 23 complications, including 17 minor and 6 major complications. The most common complication of unlinked spacers (intramedullary [IM] dowels, beads and cap spacer) was spacer displacement. Other complications included IM dowel fracture and difficulty locating beads during spacer removal. The major complications of linked cement spacers included two periprosthetic humerus fractures after internal external fixator cement spacers and re-operation due to breakage and displacement of one bushing cement spacer. The major complications of unlinked cement spacers included two reoperations due to IM dowel displacement and one reoperation due to displacement of beads. Among patients who had removal of all components and those with native joints, there was no statistically significant difference between internal external fixator cement spacers and unlinked cement spacers in minor complication rates (30% vs. 16%, P = .16), major complication rates (7% vs. 8%, P = .85) and reoperation rates (0% vs. 8%, P = .12). CONCLUSIONS: Static handmade antibiotic elbow spacers have unique complications related to their structural designs. The most common complication of linked and nonlinked cement spacers were failure of the linking mechanism and displacement, respectively. Surgeons should keep in mind the possible complications of different structures of cement spacers when choosing 1 antibiotic spacer structure over another.

Reverse shoulder arthroplasty megaprosthesis for surgical management of severe proximal humeral bone loss.

BACKGROUND: Shoulder arthroplasty in the setting of severe proximal humerus bone loss can be challenging. The purpose of this study was to evaluate the outcomes of a modular segmental megaprosthesis when implanted in a reverse configuration for complex primary arthroplasty, reconstruction at the time of oncologic resection, and revision shoulder arthroplasty. MATERIALS AND METHODS: A Joint Registry Database was queried to identify all shoulder arthroplasties performed at a single institution using the Comprehensive Segmental Revision System reverse shoulder arthroplasty (SRS-RSA; Zimmer Biomet). A retrospective review of electronic medical records and radiographs was performed to record demographic data, indication, outcomes, complications, and revision surgery. RESULTS: Between February 2012 and October 2022, a total of 76 consecutive SRS-RSAs were implanted. An analysis of patients with minimum 12-month follow-up yielded 53 patients with a mean follow-up of 4.1 ± 2.43 years. Surgical complication rate in this cohort was observed in 41.5% (22 of 53) of cases. Overall, the revision rate at final follow-up was 26.4% (14 of 53), with a significant difference between the primary and revision cohorts. The number of prior surgeries was a significant risk factor for revision surgery, with a hazard ratio of 1.789 (95% confidence interval 1.314-2.436, P < .001). When analyzing aseptic humeral loosening rates across study cohorts, a significant difference was found between the primary arthroplasty (0%, n = 0) and the revision arthroplasty cohorts (22.2%, n = 6) (P = .04). DISCUSSION: Reverse shoulder arthroplasty using a modular segmental megaprosthesis remains a reasonable salvage option for shoulder reconstruction in the setting of proximal humeral bone loss. Because of the substantial bone loss and soft tissue deficiencies typically present in these cases, surgeons should educate patients on the relatively high complication rate, particularly when used in the setting of a previous failed arthroplasty.

Proximal Humerus Reconstruction for Bone Sarcomas: A Critical Analysis.

¼ The proximal humerus is a common location for primary bone tumors, and the goal of surgical care is to obtain a negative margin resection and subsequent reconstruction of the proximal humerus to allow for shoulder function.¼ The current evidence supports the use of reverse total shoulder arthroplasty over hemiarthroplasty when reconstructing the proximal humerus after resection of a bone sarcoma if the axillary nerve can be preserved.¼ There is a lack of high-quality data comparing allograft prosthetic composite (APC) with endoprosthetic reconstruction of the proximal humerus.¼ Reverse APC should be performed using an allograft with donor rotator cuff to allow for soft-tissue repair of the donor and host rotator cuff, leading to improvements in shoulder motion compared with an endoprosthesis.

Optimal antibiotics duration following surgical management of septic olecranon bursitis: a 12-year retrospective analysis.

Introduction: The absence of a standardized postoperative antibiotic treatment approach for patients with surgically treated septic bursitis results in disparate practices. Methods: We retrospectively reviewed charts of adult patients with surgically treated septic olecranon bursitis at Mayo Clinic sites between 1 January 2000 and 20 August 2022, focusing on their clinical presentation, diagnostics, management, postoperative antibiotic use, and outcomes. Results: A total of 91 surgically treated patients were identified during the study period. Staphylococcus aureus was the most common pathogen (64 %). Following surgery, 92 % (84 of 91 patients) received systemic antibiotics. Excluding initial presentations of bacteremia or osteomyelitis (n=5), the median duration of postoperative antibiotics was 21 d (interquartile range, IQR: 14-29). Postoperative complications were observed in 23 % (21 of 91) of patients, while cure was achieved in 87 % (79 of 91). Active smokers had 4.53 times greater odds of clinical failure compared with nonsmokers (95 % confidence interval, 95 % CI: 1.04-20.50; p=0.026). The highest odds of clinical failure were noted in cases without postoperative antibiotic administration (odds ratio, OR: 7.4). Conversely, each additional day of antibiotic treatment, up to 21 d, was associated with a progressive decrease in the odds of clinical failure (OR: 1 at 21 d). Conclusion: The optimal duration of antibiotics postoperatively in this study was 21 d, which was associated with a 7.4-fold reduction in the odds clinical failure compared with cases without postoperative antibiotics. Further validation through a randomized controlled trial is needed.

Efficacy of ADIPOR1 and ADIPOR2 peptide-agonist AdipoRon in preventing contracture in a rabbit model of arthrofibrosis.

AdipoRon is an adiponectin receptor 1, 2 (ADIPOR1 and ADIPOR2) agonist with potential antifibrotic effects. Whether AdipoRon can mitigate joint stiffness in a rabbit model of arthrofibrosis is unknown. We examined the efficacy of intravenous (IV) AdipoRon at mitigating contracture in a rabbit model of knee arthrofibrosis. Fifty-six female New Zealand White rabbits were divided into three dosing groups: vehicle (dimethyl sulfoxide, DMSO), 2.5 mg/kg AdipoRon, and 5 mg/kg AdipoRon. AdipoRon, in DMSO, was administered IV preoperatively and for 5 days postoperatively (30 rabbits, Aim 1). AdipoRon was again dosed similarly after Kirschner wire (K-wire) removal at 8 weeks (26 rabbits; Aim 2). The primary outcome of joint passive extension angle (PEA,°) was measured at 8, 10, 12, 16, and 24 weeks following index surgery. At 24 weeks, rabbits were euthanized and limbs were harvested to measure posterior capsular stiffness (N cm/°). In Aim 1, the 5 mg/kg treated rabbits had a significant increase in PEA when compared to controls at 16-week (p < 0.05). In Aim 2, the 5 mg/kg treated rabbits had a significant increase in PEA when compared to controls at 10-week (p < 0.05). In both aims, no significant differences were observed at later time points. Capsular stiffness was no different in any group. We are the first to report the efficacy of IV AdipoRon in a rabbit model of arthrofibrosis. We identified a significant dose-dependent decrease in joint PEA at early time points; however, no differences were observed between groups at later time points. Clinical Significance: The present investigation provided the first assessment of AdipoRon's efficacy in mitigating knee stiffness in the current gold standard rabbit model of arthrofibrosis. Results of this investigation provided further evidence as to the potential role of AdipoRon as a preventative for arthrofibrosis in large mammals.