Michael P. Leslie

Matrix-matrix interaction of cartilage oligomeric matrix protein and fibronectin

Recent work indicates that cartilage oligomeric matrix protein (COMP) plays an important role in extracellular matrix assembly and matrix-matrix protein interactions. In order to identify the proteins in extracellular matrix that interact with COMP, we used an ELISA-based solid-phase binding assay, which revealed a specific, high-affinity interaction between COMP and fibronectin. This interaction is concentration-dependent and saturable, and appears to occur under physiologically relevant conditions. Electron microscopy after negative staining and fragment binding analysis using the solid-phase assay revealed a predominant binding site for the COMP C-terminal globular domain to a molecular domain approximately 14 nm from the N-terminal domain of fibronectin, which can be inhibited by the presence of a polyclonal antibody specific for the C-terminal heptadecapeptide of COMP. This interaction is further demonstrated in vivo by colocalization of both COMP and fibronectin in the chondrocyte pericellular matrix by laser confocal microscopy of chondrocytes grown in agarose culture, and by appositional and colocalization of these proteins in the growth plate of primates by immunohistochemistry.

Expression of cartilage oligomeric matrix protein by human synovium

Human synovium was analyzed for the possible expression of cartilage oligomeric matrix protein (COMP). Immunostaining with polyclonal antiserum to COMP demonstrated positive staining within the synovial cells and immediately subjacent connective tissue, with less intense staining in the deeper connective tissue. Western blot analysis using either polyclonal or monoclonal antibodies to human COMP confirmed the presence of COMP by immunoreactive bands with the same molecular mass (approximately 110 kDa) as purified articular cartilage COMP. PCR using oligonucleotides that span human COMP exons 7–13 revealed identical amplification products from cDNA prepared from either human chondrocytes or synovium. Northern blot analysis using a biotinylated‐probe to human COMP, spanning exons 12–13, also reveal an identical hybridization product to either human chondrocyte or synovium total RNA. Human synovium should be considered as a potential tissue source of COMP in any investigation of biological markers of cartilage metabolism.

Tissue distribution and measurement of cartilage oligomeric matrix protein in patients with magnetic resonance imaging‐detected bone bruises after acute anterior cruciate ligament tears

Histologic and immunostaining analyses were performed on articular cartilage/subchondral bone biopsy specimens overlying MRI‐detected bone bruises in 12 patients with anterior cruciate ligament (ACL) tears. Staining with toluidine blue for proteoglycan revealed loss of staining from the superficial portion of the articular cartilage. Immunostaining for cartilage oligomeric matrix protein (COMP) showed an increased staining in the superficial matrix of the articular cartilage. Using polyclonal antisera against COMP, the authors performed a competitive enzyme‐linked immunosorbent assay (ELISA) on the synovial fluid from the injured and uninjured knees. There was an approximately 10‐fold higher synovial fluid COMP levels in injured knees. The COMP levels were greater in those patients who had synovial fluid samples harvested closer to the date of initial injury. Western blot analysis of the synovial fluid showed an increased presence of COMP degradation fragments from injured knees. These results are indicative of a significant injury to the articular cartilage, and may represent preclinical posttraumatic osteoarthritic lesions.

Postoperative length of stay and 30-day readmission after geriatric hip fracture: an analysis of 8434 patients.

Objectives: To identify factors associated with increased postoperative length of stay (LOS) and readmission after surgical repair of geriatric hip fractures. Methods: Patients aged 70 years and older who underwent hip fracture surgery from January 2011 through December 2012 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. Patient characteristics were tested for association with postoperative LOS and readmission using bivariate and multivariate analyses. Results: For the 8434 patients with hip fracture identified, the average age was 83.8 ± 5.9 years (mean ± SD), and 26.9% were male. Average postoperative LOS was 5.6 ± 6.0 days. Ten percent were readmitted within the first 30 postoperative days. Increased postoperative LOS of at least 1 full day was associated with increased time from admission to surgery, non–general anesthesia, and procedure type on multivariate analysis. Readmission was associated with increased age, male sex, body mass index ≥35 kg/m2, American Society of Anesthesiologists class ≥3, pulmonary disease, hypertension, steroid use, dependent functional status, and discharge to a facility on multivariate analysis. Conclusions: Ten percent of patients were readmitted after hip fracture repair in this national sample. Preoperative time to surgery, anesthesia type, and implant selection are 3 risk factors for increased LOS that can potentially be modified. A clinically significant risk factor for readmission was body mass index ≥35 kg/m2, which was not associated with increased postoperative LOS. The identified risk factors illuminate opportunities for optimizing care for hip fracture patients aged 70 and older. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Is It Possible to Train Patients to Limit Weight Bearing on a Lower Extremity

Orthopedic patients are often instructed on how much weight to bear on an injured or postoperative extremity. Although specific weight-bearing instructions are given to a majority of lower-extremity orthopedic patients, the ability of patients to comply with these instructions is questioned in the medical literature. This study compared the effectiveness of new forms of clinical interventions designed to train patients on weight bearing, focusing on the use of biofeedback devices designed to offer real-time feedback to partial weight-bearing patients. Twenty healthy patients aged 20 to 30 years completed 3 interventions: (1) verbal instructions on weight bearing, (2) training with a bathroom scale, and (3) training with a biofeedback device.Patients given touchdown weight-bearing instructions (25 lb) initially bore an average of 63.57±6.24 lb when given verbal instructions. This was reduced to 44.75±5.69 lb after training with a bathroom scale (P<.001), and was further reduced to 26.2±1.57 lb with biofeedback training (P=.011). Likewise, patients given partial weight-bearing instructions (75 lb) initially bore an average of 92.28±7.85 lb. No improvement occurred with the use of a bathroom scale (at 75 lb), which showed an average of 90.82±7.19 lb (P=1.000). Training with a biofeedback device improved the average weight bearing to 69.67±3.18 lb (P=.014).Biofeedback training led to superior compliance with touchdown and partial weight-bearing instructions. Because partial weight-bearing instructions are commonly given to orthopedic patients, training with such a device may be appropriately considered.

Preoperative factors and early complications associated with hemiarthroplasty and total hip arthroplasty for displaced femoral neck fractures.

Displaced femoral neck fractures are common injuries in the elderly individuals. There is controversy about the best treatment with regard to total hip arthroplasty (THA) versus hemiarthroplasty. This study uses the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database to evaluate the preoperative risk factors associated with the decision to perform THA over hemiarthroplasty. We also evaluate the risk factors associated with postoperative complications after each procedure. Patients older than 50 years undergoing hemiarthroplasty or THA after fracture in the NSQIP database from 2007 to 2010 were compared to each other in terms of preoperative medical conditions, postoperative complications, and length of stay. Multivariate logistic regression models were used to adjust for preoperative risk factors for undergoing a THA versus a hemiarthroplasty and for complications after each procedure. In all, 783 patients underwent hemiarthroplasty and 419 underwent THA for fracture. Hemiarthroplasty patients had longer hospital stays. On multivariate logistic regression, the only significant predictor for having a THA after fracture over hemiarthroplasty was being aged 50 to 64 years. The patient characteristics/comorbidities that favored having a hemiarthroplasty were age >80 years, hemiplegia, being underweight, having a dependent functional status, being on dialysis, and having an early surgery. High body mass index, American Society of Anesthesiologists (ASA) class, gender, and other comorbidities were not predictors of having one procedure over another. Disseminated cancer and diabetes were predictive of complications after THA while being overweight, obese I, or a smoker were protective. High ASA class and do-not-resuscitate status were significant predictors of complications after a hemiarthroplasty. This study identified clinical factors influencing surgeons toward performing either THA or hemiarthroplasty for elderly patients after femoral neck fractures. Younger, healthier patients were more likely to receive THA. Patients particularly at higher risks of complications after hemiarthroplasty should be monitored closely.

Haptic Biofeedback for Improving Compliance With Lower-Extremity Partial Weight Bearing

After lower-extremity orthopedic trauma and surgery, patients are often advised to restrict weight bearing on the affected limb. Conventional training methods are not effective at enabling patients to comply with recommendations for partial weight bearing. The current study assessed a novel method of using real-time haptic (vibratory/vibrotactile) biofeedback to improve compliance with instructions for partial weight bearing. Thirty healthy, asymptomatic participants were randomized into 1 of 3 groups: verbal instruction, bathroom scale training, and haptic biofeedback. Participants were instructed to restrict lower-extremity weight bearing in a walking boot with crutches to 25 lb, with an acceptable range of 15 to 35 lb. A custom weight bearing sensor and biofeedback system was attached to all participants, but only those in the haptic biofeedback group were given a vibrotactile signal if they exceeded the acceptable range. Weight bearing in all groups was measured with a separate validated commercial system. The verbal instruction group bore an average of 60.3±30.5 lb (mean±standard deviation). The bathroom scale group averaged 43.8±17.2 lb, whereas the haptic biofeedback group averaged 22.4±9.1 lb (P<.05). As a percentage of body weight, the verbal instruction group averaged 40.2±19.3%, the bathroom scale group averaged 32.5±16.9%, and the haptic biofeedback group averaged 14.5±6.3% (P<.05). In this initial evaluation of the use of haptic biofeedback to improve compliance with lower-extremity partial weight bearing, haptic biofeedback was superior to conventional physical therapy methods. Further studies in patients with clinical orthopedic trauma are warranted.

Lower-extremity Weight-bearing Compliance Is Maintained Over Time After Biofeedback Training

Previous studies have shown immediate compliance with weight-bearing instructions to be better after biofeedback training than after verbal or scale training. This study assessed retention of biofeedback training to determine potential clinical applicability. Twelve participants were enrolled in a prospective clinical study at an academic orthopedic center. Participants were trained with a biofeedback device to comply with touch-down weight-bearing instructions (25 lb). Immediately following the training session, weight bearing was assessed for each participant. The retention of this training was then reassessed at 2 to 4, 6 to 8, and 22 to 24 hours. Two control participants were given no biofeedback training (verbal instructions only) and were followed similarly. Following initial biofeedback training at 25 lb, participants bore an average of 20.4±2.12 lb. Retention tests during the 24-hour period showed no significant difference from the original testing, with 2- to 4-hour retention of 19.98±4.75 lb, 6- to 8-hour retention of 25.07±6.60 lb, and 22- to 24-hour retention of 21.75±4.58 lb. Participants who only received verbal instructions consistently bore several-fold greater weight than instructed. Biofeedback training has previously been shown to have a strong immediate effect on partial weight-bearing compliance. This study demonstrated that this effect lasts up to 24 hours. This maintained weight-bearing compliance after biofeedback training suggests that this method may be an effective way to train patients to comply with given instructions for limited weight bearing.

Implant options for the treatment of intertrochanteric fractures of the hip: rationale, evidence, and recommendations.

Aims The aim of this paper is to review the evidence relating to the anatomy of the proximal femur, the geometry of the fracture and the characteristics of implants and methods of fixation of intertrochanteric fractures of the hip. Materials and Methods Relevant papers were identified from appropriate clinical databases and a narrative review was undertaken. Results Stable, unstable, and subtrochanteric intertrochanteric fractures vary widely in their anatomical and biomechanical characteristics, as do the implants used for their fixation. The optimal choice of implant addresses the stability of the fracture and affects the outcome. Conclusion The treatment of intertrochanteric fractures of the hip has evolved along with changes in the design of the implants used to fix them, but there remains conflicting evidence to guide the choice of implant. We advocate fixation of 31A1 fractures with a sliding hip screw and all others with an intramedullary device.

Osteoporotic Pelvic Ring Injuries

As with most fractures associated with osteoporosis, the incidence of pelvic ring injuries in this population of patients is rising rapidly. Osteoporotic pelvic ring injuries are exceedingly different in their etiology, natural history, and treatment from the more recognizable patterns in young patients with high-energy pelvic ring injuries. Recognition of a potentially unstable fracture pattern, careful evaluation of the ambulatory and functional status of each patient before injury, and the potential pitfalls and benefits of operative versus nonoperative care are critical to the effective treatment.