Search

Purpose To compare the efficacy of a single, intra-articular, nonconcentrated bone marrow aspirate (BMA) injection in comparison to cortisone for the treatment of glenohumeral joint osteoarthritis (GHJ OA). Methods Inclusion criteria were patients between the ages of 18 and 75 with a diagnosis of GHJ OA on radiograph. Patients were randomized to receive an ultrasound-guided, intra-articular cortisone injection or BMA injection (without concentration). The primary outcome measure was the Western Ontario Osteoarthritis of the Shoulder (WOOS) index at 12 months. Secondary outcome measures were the QuickDASH, EuroQOL 5-dimensions 5-level questionnaire (EQ-5D-5L) and visual analogue scale. Results The study included 25 shoulders of 22 patients who completed baseline and 12 months’ patient-reported outcome measures (12 shoulders received cortisone, 13 shoulders received BMA) after the study was terminated early by changes in Health Canada regulations. Baseline characteristics demonstrated a significant difference in the ages of the 2 groups, with the BMA group being older (61.6 vs 53.8 mean years, P = 0.021). For the BMA group, a significant improvement was seen in the WOOS index (P = 0.002), the QuickDASH (P < 0.001), and the EQ-5D-5L pain dimension (P = 0.004) between baseline and 12 months. No significant difference was seen for any outcome in the cortisone group between baseline and 12 months. No significant difference was demonstrated between changes in the WOOS scores from baseline to 12 months when compared between groups (P = 0.07). However, a significant difference in changes in scores was seen in the QuickDASH (P = 0.006) and the EQ-5D-5L pain scores (P = 0.003) and the EQ-5D-5L health scores (P = 0.032) in favor of BMA. Conclusions The results of this study demonstrate that patients with GHJ OA treated with BMA have superior changes in the QuickDASH and EQ-5D-5L pain and health scores but not in the WOOS outcomes measures at 12 months post injection when compared to patients treated with cortisone. However, because of the limited number of patients as a result of the early termination of the study, larger randomized studies are required to confirm these findings. Level of Evidence Level II, randomized controlled trial.

Ehlers-Danlos Syndrome (EDS) are a heterogeneous group of genetic connective tissue disorders, and typically manifests as weak joints that subluxate/dislocate, stretchy and/or fragile skin, organ/systems dysfunction, and significant widespread pain. Historically, this syndrome has been poorly understood and often overlooked. As a result, people living with EDS had difficulty obtaining an accurate diagnosis and appropriate treatment, leading to untold personal suffering as well as ineffective health care utilization. The GoodHope EDS clinic addresses systemic gaps in the diagnosis and treatment of EDS. This paper describes a leap forward—from lack of awareness, diagnosis, and treatment—to expert care that is tailored to meet the specific needs of patients with EDS. The GoodHope EDS clinic consists of experts from various medical specialties who work together to provide comprehensive care that addresses the multi-systemic nature of the syndrome. In addition, EDS-specific self-management programs have been developed that draw on exercise science, rehabilitation, and health psychology to improve physical and psychosocial wellbeing and overall quality of life. Embedded into the program are research initiatives to shed light on the clinical presentation, underlying mechanisms of pathophysiology, and syndrome management. We also lead regular educational activities for community health care providers to increase awareness and competence in the interprofessional management of EDS beyond our doors and throughout the province and country.

OBJECTIVE The influence of sex on post-total knee arthroplasty (TKA) outcomes has been variable in the literature. Though sex is often reported as an averaged effect, we undertook this study to investigate whether sex modified the influence of presurgery characteristics on post-TKA knee pain. METHODS This was a prospective study with data derived from 477 TKA osteoarthritis patients (279 women, 198 men). Questionnaires were completed presurgery and at 3 months postsurgery. The association between 3-month post-TKA knee pain and presurgery covariates (body mass index, comorbidity count, symptomatic joint count, low back pain, knee pain, and depressive symptoms) was assessed by linear regression. Sex-specific effects were evaluated using interactions. RESULTS Women had significantly worse presurgery knee pain, joint count, and depressive symptoms, and worse postsurgery knee pain, than men. With simple covariate adjustment, no sex effect on pain was found. However, sex was found to moderate the effects of comorbidities (worse for women [P = 0.013]), presence of low back pain (worse for men [P = 0.003]), and depressive symptoms (worse for men [P < 0.001]) on postsurgery pain. Worse presurgery pain was associated with worse postsurgery pain similarly for women and men. CONCLUSION The influence of some patient factors on early post-TKA pain cannot be assumed to be the same for women and men; average effects may mask underlying associations. Results suggest a need to consider sex differences in understanding TKA outcomes, which may have important implications for prognostic tool development in TKA.

As a result of the coronavirus disease 2019 (COVID-19) pandemic, tele-health for orthopedic care is expanding rapidly. The authors sought to identify the evidence describing the effectiveness, barriers, and clinical applications of telehealth for orthopedic assessments and consultations. MEDLINE, PubMed, EMBASE, and the Cochrane Library were searched from inception to March 2020. Forty-seven studies were included, with the most common conditions evaluated being trauma related and the primary modality being videoconferencing. Available literature supports the use of telehealth for orthopedic consultations and assessments because it yields moderate-to-high patient and provider satisfaction, accurate examinations, cost-effectiveness, and reduced wait times. Most commonly reported concerns were professional liability, network security, and technical issues. Given the COVID-19 pandemic, rapid implementation and uptake of virtual assessment for patient care has occurred. The current evidence suggests that telehealth is capable of providing prompt access to quality, cost-efficient orthopedic consultations and assessments. [ Orthopedics . 2021;44(4):198––206.]

Good Life with osteoArthritis in Denmark (GLA:D®) is a program for the management of patients with hip and knee osteoarthritis (OA). Adapted for the Canadian population, the GLA:DTM Canada program implements evidence-based strategies to support the prevention, early diagnosis and effective management of hip and knee OA. GLA:D assists local communities in implementing OA strategies across the spectrum of disease severity. An integral part of this program is a national quality and outcomes registry, which includes data concerning participant characteristics and both patient-reported and functional outcomes. This registry helps healthcare providers and healthcare decision makers ensure that individuals with OA receive effective, high-quality care through the GLA:D Canada program.

Objective: MicroRNAs act locally and systemically to impact osteoarthritis (OA) pathophysiology, but comprehensive profiling of the circulating miRNome in early vs late stages of OA has yet to be conducted. Sequencing has emerged as the preferred method for microRNA profiling since it offers high sensitivity and specificity. Our objective was to sequence the miRNome in plasma from 91 patients with early [Kellgren–Lawrence (KL) grade 0 or 1 (n = 41)] or late [KL grade 3 or 4 (n = 50)] symptomatic radiographic knee OA to identify unique microRNA signatures in each disease state. Design: MicroRNA libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the Illumina NextSeq 550. Counts were produced for microRNAs captured in miRBase and for novel microRNAs. Statistical, bioinformatics, and computational biology approaches were used to refine and interpret the final list of microRNAs. Results: From 215 differentially expressed microRNAs (FDR < 0.01), 97 microRNAs showed an increase or decrease in expression in ≥85% of samples in the early OA group as compared to the median expression in the late OA group. Increasing this threshold to ≥95%, seven microRNAs were identified: hsa-miR-335-3p, hsa-miR-199a-5p, hsa-miR-671-3p, hsa-miR-1260b, hsa-miR-191-3p, hsa-miR-335-5p, and hsa-miR-543. Four novel microRNAs were present in ≥50% of early OA samples and had 27 predicted gene targets in common with the prioritized set of predicted gene targets from the 97 microRNAs, suggesting common underlying mechanisms. Conclusion: Sequencing of well-characterized patient cohorts produced unbiased profiling of the circulating miRNome and identified a unique panel of 11 microRNAs in early radiographic knee OA.

Summary Objective There are suggestions that the relationship between inflammation and pain in osteoarthritis (OA) may differ by sex, yet studies have been limited. We investigated whether the relationship between knee-specific OA pain and systemic inflammatory markers differs by sex. Design 196 patients scheduled for knee arthroplasty for OA were included. Questionnaires were completed and blood samples drawn pre-surgery. Questionnaire data: knee pain (WOMAC), sex, age, height, weight, comorbidities, depressive symptoms, and symptomatic joint count. Systemic inflammatory markers (cytokines IL-6, IL-8, IL-10, IL-1β and TNF-α) were measured by multiplex ELISA. A series of regression models with interaction terms between sex and ln-transformed inflammatory markers were estimated with pain score as the outcome. The adjusted relationship between pain and inflammatory markers, by sex, were presented graphically. Results Mean age was 64 years (range 43–89); females comprised 58.7% of the sample. In adjusted analyses, similar relationships between knee pain and lnIL-10 (negative: β ​= ​−1.28, 95%CI (−1.97, −0.58)) and lnTNF-α (positive: β ​= ​0.92, 95%CI (0.11, 1.76)) were found for females and males. In contrast, relationships between knee pain and lnIL-1β, lnIL-6 and lnIL-8 differed in direction for females and males. Specifically, for lnIL-1β and lnIL-8 they were positive for males, negative for females. The opposite was found with lnIL-6, negative for males, positive for females. Conclusion These findings provide some evidence of sex-specific relationships between individual inflammatory markers and knee OA pain. They expose a need for further exploration of sex-differences in this context, with potential future implications for treatment or drug development in OA.

The procedure for aspiration of bone marrow from the femur of patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) may vary from an OR (operating room) to OR based on the surgeon’s skill and may lead to varied extent of clotting of the marrow and this, in turn, presents difficulty in the isolation of mesenchymal stem cells (MSCs) from such clotted bone marrow. We present a simple detailed protocol for aspirating bone marrow from such patients, isolation, and characterization of MSCs from the aspirated bone marrow specimens and show that the bone marrow presented no clotting or exhibited minimal clotting. This represents an economical source and convenient source of MSCs from bone marrow for use in regenerative medicine. Also, we presented the detailed protocol and showed that the MSCs derived from such bone marrow specimens exhibited MSCs characteristics and generated micromass cartilages, the recipe for regenerative medicine for osteoarthritis. The protocols we presented can be used as standard operating procedures (SOPs) by researchers and clinicians.

OBJECTIVE To evaluate rates of prescription opioid use among patients with presurgical knee, hip, and spine osteoarthritis (OA) and associations between use and sociodemographic and health status characteristics. METHODS Participants were patients with presurgical, end-stage OA of the knee (n = 77), hip (n = 459), and spine (n = 168). Data were collected on current use of opioids and other pain medications, as well as measures of sociodemographic and health status variables and depression and pain (0-10 numeric rating scale). Rates of opioid use were calculated by sex, age, and surgical site. Multivariable logistic regression was used to examine associations between opioid use (sometimes/daily versus never) and other study variables. RESULTS The mean age of participants was 65.6 years; 55.5% were women, 15% of patients reported "sometimes" using opioids, and 15% reported "daily use." Use of opioids was highest among patients with spine OA (40%) and similar among patients with knee and hip OA (28% and 30%, respectively). Younger women (ages

Adult articular cartilage lacks significant regenerative capacity, and damage to this tissue often leads to progressive joint degeneration (osteoarthritis). We developed strategies to generate articular cartilage from human pluripotent stem cells (hPSCs) as a source of clinically relevant tissues for joint repair1. Previously, we demonstrated that these chondrocytes retain cartilage forming potential following subcutaneous implantation in mice. In this report, we evaluated the potential of human embryonic stem cell (hESC)-derived articular cartilage tissue to repair osteochondral defects created in the rat knee. Following implantation, the hESCderived cartilage maintained a proteoglycan and type II collagen-rich matrix, and was well integrated with native rat tissue at the basal and lateral surfaces. The ability to generate cartilage tissue with integrative and reparative properties from an unlimited and robust cell source represents a significant clinical advance for cartilage repair that can be applied to large animal models and ultimately to patient care.

Summary Objective We investigated whether pain at rest and pain on activity were differentially associated with neuropathic pain scores in individuals with end-stage hip and knee OA. Design Study participants were 843 patients with hip or knee OA scheduled for total joint arthroplasty. In pre-surgery questionnaires, measures of socio-demographics, health status, medication use, neuropathic pain (painDETECT), pain at rest and pain on activity (WOMAC pain items), depression (HADS) and pain catastrophizing (PCS) were collected. Multivariable linear regression models were estimated for men and women separately to examine the association between neuropathic pain scores (outcome) and study measures, entered in blocks. Results Sample mean age was 65.1 years (SD: 9.6); 57.1% were women. Mean painDETECT scores were significantly higher ( P ≤ 0.001) for women (11.2 ± 6.6 out of 38) than men (9.3 ± 7.0), with 35.6% of women and 27.7% of men meeting cut-offs for possible or likely neuropathic pain. In the final regression model for women, the coefficients for both types of pain were statistically significant, although the coefficient for pain at rest was 1.6 times greater than that for pain on activity. For men, only pain at rest was significantly associated with neuropathic pain scores. Conclusions Findings support that possible neuropathic pain is experienced by a notable proportion of patients with end-stage hip and knee OA and is more strongly associated with pain at rest than pain on activity, particularly in men. Clinical presentation of pain at rest may warrant more thorough evaluation for potential neuropathic pain and have implications for appropriate pain management.

Background Multijoint involvement in osteoarthritis (OA) has long been documented clinically and in the literature. Even so, the vast majority of OA research has focused on OA in individual joints, particularly the knees, hips or hands. In many “joint-specific” studies, the presence of multijoint symptoms are either ignored or peripherally considered in descriptive and analytical work. The implicit assumption is often that OA is OA, irrespective of whether a single joint or several joints are involved. Objectives To document the occurrence of multijoint symptoms in a clinical sample of individuals with knee and hip OA scheduled for orthopaedic surgery. To examine the joint sites involved and investigate whether the extent of joint involvement is related to demographic and health characteristics. Methods Patients scheduled for total knee or hip replacement for end-stage OA were consecutively recruited from an academic hospital in Toronto, Canada. A health questionnaire completed prior to surgery captured demographic characteristics (age, sex), symptomatic joints other than the surgical joint (right and left shoulders, elbows, wrists, hands, hips, knees, feet, ankle, neck and back), body mass index (BMI), comorbidities (hypertension, depression, diabetes, migraine headaches, cancer, respiratory disease, heart disease, stomach/bowel disease, stroke) and WOMAC hip- and knee-specific pain and function. Results Study questionnaires were completed by 366 hip and 407 knee patients. The mean age of the sample was 65 years (SD=9.2; range 38–89 years), 57% were female. The most frequently reported symptomatic joints among knee patients were the contralateral knee (53.2%), one or both hands (32.1%), and the upper-, mid- or lower-back (31.0%), and among hip patients were one or both knees (49.4%), the back (36.6%), and the contralateral hip (21.3%). The overall mean number of symptomatic joints other than the surgical joint was 3.0 (SD=3.2; range 0–17). Only 19.0% reported the surgical joint as the only symptomatic joint; 23.0% reported 5 or more additional symptomatic joints. Mean hip/knee-specific pain and function scores were significantly worse with increasing symptomatic joint count (p Conclusions In this clinical OA sample, the “average” patient reported multiple symptomatic joints. Increasing age was not associated with increasing frequency of symptomatic joints. Irrespective of age and obesity, multiple symptomatic joints were the rule, not the exception. It was notable that the frequency of co-occurring conditions increased with increasing symptomatic joint count. This may suggest a need to re-examine how OA is characterized and perhaps its underlying etiology as it relates to single vs. multi-joint involvement. Disclosure of Interest None declared

Background: Reoperation rates following open reduction and internal fixation (ORIF) of midshaft clavicle fractures have been described, but reported rates of nonunion, malunion, infection, and implant removal have varied. We sought to establish baseline rates of, and risk factors for, reoperations following clavicle ORIF in a large population cohort. Methods: Administrative databases were used to identify patients sixteen to sixty years of age who had undergone an ORIF of a closed, midshaft clavicle fracture from April 2002 to April 2010. The primary outcome was a reoperation within two years (isolated implant removal, irrigation and debridement [deep infection], pseudarthrosis reconstruction [nonunion], or clavicle osteotomy [malunion]). The secondary outcome was rare perioperative complications, including pneumothorax, subclavian vasculature injury, and brachial plexus injury. A multivariable logistic regression analysis was performed to determine the influence of patient and provider factors on these outcomes. Results: We identified 1350 patients who underwent midshaft clavicle ORIF (median age, thirty-two years [interquartile range, twenty-one to forty-four years]; 81.3% male). One in four patients (24.6%) underwent at least one clavicle reoperation. The most common procedure was isolated implant removal (18.8%), and females were at highest risk (odds ratio [OR], 1.7; p = 0.002). The median time to implant removal was twelve months. A reoperation secondary to nonunion, deep infection, and malunion occurred in 2.6%, 2.6%, and 1.1% of the patients after a median of six, five, and fourteen months, respectively. Risk factors for clavicle nonunion included female sex (OR, 2.2; p = 0.04) and a high comorbidity score (OR, 2.8; p = 0.009). For surgeons, fewer years in practice was associated with a small risk of the patient developing an infection (OR, 1.1; p < 0.001). Sixteen pneumothoraces (1.2%) were identified; however, brachial plexus and subclavian vessel injuries were each found in five or fewer patients. Conclusions: Following clavicle ORIF, one in four patients underwent a reoperation. The most common procedure was implant removal, and although the rates of reoperations secondary to nonunion, malunion, and infection were low they were higher than previously reported. Pneumothoraces and neurovascular injuries were infrequent and should continue to be considered rare complications of clavicle ORIF. Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Objectives: The existing medial meniscectomy (MMx) procedure in rodents involves transection of MCL and wide opening of the knee capsule followed by meniscus transection that results into articular cartilage degeneration and causes significant changes in subchondral bone at specific post-MMx period. These animals serve as experimental osteoarthritis (OA) models. Structurally, knee is very complex. There may be a need to uncouple articular cartilage degenerative changes from subchondral bone degenerative changes in experimental OA models. Therapeutical drugs/agents, designed to treat articular cartilage degenerative changes of OA knee, may not be effective to treat subchondral bone degenerative changes or vice versa. The purpose of the study was to modify the existing MMx procedure to a less invasive procedure so that it causes only articular cartilage degenerative OA changes and no subchondral bone changes. This will serve as an early OA model to target degenerative changes in articular cartilage in human. Methods: Ten 8-9 weeks old male athymic nude rats underwent less invasive MMx on right knee; the left knee served as unoperated control. The surgery involved no transection of MCL and opening of knee capsule wide. The medial meniscus was pulled out from a slit made on the medial aspect of the knee capsule, and was transected. At 10 weeks post-MMx, animals were sacrificed and knees were assessed. Results: There was no significant alteration in bone strength parameters (BV/TV, Tb.Th, Tb.Sp, Tb.N, Tb.Pf, cortical wall thickness) in subchondral bone in the less invasive MMx knee as analyzed by μCT. X-ray radiography did not indicate the presence of any osteophyte at the knee margins. On the other hand, the less invasive MMx caused degenerative changes in articular cartilage as follows: fibrillation and thinning in the medial tibia; narrowing of medial knee joint; reduced proteoglycans shown by safranin-O staining; decreased metachromasia by PSR staining; alteration in collagen fibril thickness under cross-polarization light. Immunohistochemical expression was reduced (COL-II, aggrecan), increased (NITEGE, Col2-3/4m, COL-X, and MMP13) or imbalanced (lubricin) in articular cartilage thickness of less invasive MMx knee. Conclusion: The less invasive MMx procedure, in rat, can be a model for early or less severe human OA due to articular cartilage degenerative changes only and with no subchondral bone degenerative changes in the knee synovial joint. The therapeutical drugs/agents designed to repair articular cartilage may be suitable for this model and may lead to treatment of early or less severe human OA.

Shoulder Shoulder osteoarthritis (OA) is common. Primary shoulder OA is the most common form. The most common type of secondary shoulder OA is rotator cuff arthropathy and is believed to be related to a decoupling of forces about the humeral head. Typical presentation is activity-related shoulder pain and loss of shoulder range of motion. Physical exam should include an assessment of the rotator cuff and axillary nerve. Standard radiographs are often sufficient to make diagnosis, but cross-sectional imaging may be indicated to identify bone loss (CT) or soft tissue deficiencies (MRI/ultrasound). Nonoperative care can include physical therapy, pharmacotherapy, and intra-articular injections (cortisone and hyaluronic acid), but evidence for or against these treatments is limited. Surgical management of end-stage shoulder OA includes arthroscopic debridement, interposition arthroplasty (glenoid resurfacing), humeral head resurfacing, hemiarthroplasty, anatomic total shoulder arthroplasty, and, in low demand patients with a deficient rotator cuff, reverse total shoulder arthroplasty. In young patients with end-stage shoulder OA, arthroplasty has high failure rates secondary to either glenoid erosion (hemiarthroplasty) or glenoid component loosening (anatomic total shoulder arthroplasty). For older patients with end-stage shoulder OA and an intact rotator cuff, anatomic total shoulder arthroplasty is recommended.

Background Simple elbow dislocations are often treated with closed reduction (CR); however, the rate of CR failure and factors that may predict failure have been largely underinvestigated. The objectives of this study were (1) to determine the incidence of elbow dislocations treated by CR in a universal health care system and (2) to identify patient characteristics associated with failed CR, defined as the subsequent need for open reduction. Methods Patients ≥16 years old who underwent elbow CR by a physician between 1994 and 2010 were identified from administrative databases. Concurrent elbow fractures were excluded. The incidence density rate (IDR) of CR per 100,000 eligible person-years among the general population was calculated. Failed CR was defined as subsequent open reduction with or without ligament repair or reconstruction within 90 days. Patient and provider characteristics were modeled in a multivariate logistic regression for failure. Results The cohort consisted of 4878 patients (median age, 41 years) who underwent CR (IDR, 2.65 per 100,000 person-years), and 75 (1.5%) underwent subsequent open reduction with or without ligament repair or reconstruction (median time, 15 days). Young men (≤20 years) had the highest IDR (7.45 per 100,000 person-years), twice that of young women ( P = .005). Patient characteristics associated with failed CR included older age ( P = .001), admission to the hospital ( P 1 attempted CR ( P = .001), and new orthopedic consultation in the 4 weeks after the CR ( P = .02). Conclusion Young men are at highest risk for CR for simple elbow dislocations; however, older patients are more likely to require open intervention, as are those with markers of a difficult reduction signifying potentially greater soft tissue damage. A comprehensive understanding of the epidemiology of simple elbow dislocation will aid management decisions.

BACKGROUND: The prevalence of obesity in the United States has increased in recent decades. The aim of this study was to evaluate the influence of obesity in patients undergoing primary total elbow arthroplasty. METHODS: From 1987 to 2006, 723 primary semiconstrained, linked total elbow arthroplasties were performed in 654 patients. The average patient age (and standard deviation) at the time of surgery was 62.3 ± 13.7 years, with 550 total elbow arthroplasties (76%) performed in women. Total elbow arthroplasties were used to treat inflammatory conditions in patients undergoing 378 total elbow arthroplasties (52%) and to treat acute traumatic or posttraumatic conditions in patients undergoing 310 total elbow arthroplasties (43%). Patients were classified as non-obese (having a body mass index of

Background. Ligament injuries of the knee are common and, if severe, can predispose to joint pain, instability, reinjury, and, ultimately, osteoarthritis. Xenograft replacement of ligaments could have potential; however, a limited understanding of the immunology of ligament xenograft rejection has inhibited their use. The purpose of this study was to characterize the antigenic elements of a fresh porcine tendon xenograft in a rabbit model and to provide a better understanding of what would need to be done to either block or extract these antigenic elements. Methods. Three experimental situations were evaluated in a pig to rabbit ligament transplantation model: subcutaneous implantation of fresh porcine patellar tendon (PPT), implantation of fresh PPT into a medial collateral ligament midsubstance gap, and replacement of the entire medial collateral ligament complex with either fresh or guanidinium hydrochloride-extracted PPT. Preimmune and immune sera were collected from rabbits and used to localize antigenic targets in PPT, meniscus, and cartilage with indirect immunofluorescence techniques. The reactivities of the same rabbit sera towards tissue extracts of PPT, meniscus, and cartilage by Western immunoblot analyses were used to characterize the antigenic components. Results. Indirect immunofluorescence with preimmune rabbit sera on PPT showed staining of tendon fibroblasts. Immune sera from rabbits transplanted with xenografts stained regions of the extracellular matrix of PPT. Fresh PPT induced antibodies that consistently recognized six extracellular matrix components with molecular masses of >200 kDa, 180 kDa, 135 kDa, 108 kDa, 63 kDa, and 59 kDa. Conclusions. Our results suggest that naturally occurring rabbit anti-pig antibodies of the IgG isotype recognize immunogenic components on tendon fibroblasts, whereas induced rabbit anti-pig antibodies recognize a specific subset of six extracellular matrix components of PPT. PPT xenografts appeared to induce a similar humoral immune response irrespective of graft location. Finally, our results indicate that selective extraction of PPT xenograft components before implantation altered the induced rabbit anti-pig antibody response; however, such extraction did not change the ultimate fate of the transplant tissue. Ligament injuries are common and, if severe, can result in on-going joint pain, instability, reinjury, and, ultimately, osteoarthritis. Various surgical treatments for such injuries have evolved, with the most common techniques now involving attempts at anatomic replacement of damaged ligaments with free dense connective tissue grafts being taken from elsewhere in that individual (an autograft) or from another

FROM THE ORIGINAL ARTICLE BACKGROUND: Nonunion is a challenging and not uncommon complication of distal humeral fractures. Our long-term experience with linked semiconstrained total elbow arthroplasty as a salvage procedure for patients with distal humeral nonunion not amenable to internal fixation was investigated. METHODS: Ninety-one consecutive patients (ninety-two elbows) underwent total elbow arthroplasty for the treatment of a distal humeral nonunion, and the results were reviewed at a mean of 6.5 years postoperatively. Patients' charts and anteroposterior and lateral radiographs made prior to and immediately after the joint replacement and at the time of the latest follow-up were reviewed to identify intraoperative and postoperative complications, and radiographic evidence of loosening or bushing wear. The outcome measures consisted of prosthetic survival, with implant removal as the end point for failure, and the Mayo Elbow Performance Score (MEPS). RESULTS: At the time of the most recent follow-up, joint stability had been initially restored in all patients, including nine who had had a grossly flailed elbow. Sixty-seven (74%) of the patients had no pain or mild pain at the time of the latest follow-up, whereas seventy-nine patients (87%) had had moderate or severe pain prior to the surgery. While 85% (seventy-seven) of the ninety-one patients rated the outcome as better or much better, twenty patients (22%) had a fair or poor MEPS. A total of forty-four complications occurred in forty elbows, and there were thirty-two reoperations, twenty-three of which involved implant revision or removal. Factors that increased the risk of implant failure were a patient age of less than sixty-five years, two or more prior surgical procedures, and a history of infection. The rate of prosthetic survival without removal or revision for any reason was 96% at two years, 82% at five years, and 65% at both ten and fifteen years. CONCLUSIONS: Linked semiconstrained total elbow arthroplasty is a salvage procedure that can provide pain relief and restore motion and function in patients with a distal humeral nonunion that is not amenable to internal fixation. Substantial risk factors for failure include an age of less than sixty-five years, multiple previous surgical procedures, and any history of infection. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence. ORIGINAL ABSTRACT CITATION: “Linked Elbow Replacement: A Salvage Procedure for Distal Humeral Nonunion” (2008;90:1939-50).

Advances in the understanding of bone repair and improved biotechnology have led to the introduction of new strategies for orthopedic surgeons to control and modulate bone healing using growth factors. However, many orthopedic surgeons are uncertain about the current levels of evidence supporting the use of materials that possess these properties and their therapeutic role in the management of skeletal problems such as fracture, long-bone nonunion, and spine fusion. In particular, the differences amongst osteoinductive factors synthesized by recombinant gene technology, or derived from demineralized bone matrix or platelet rich plasma requires clarification.

Background MicroRNAs (miRNAs) are a novel class of non-coding small RNAs. They are 19-22 nucleotides in length and negatively regulate gene expression through mRNA cleavage or translation suppression. miRNAs have been implicated in various physiological and pathological conditions including OA. OA is a chronic degenerative disease characterized by cartilage degradation, subchondral bone remodelling and synovial inflammation. Identification of OA biomarkers is critical as current image-based detection is of suboptimal accuracy and sensitivity. The presence and high stability of circulating miRNAs in synovial fluid make them attractive as potential OA biomarkers. Objectives The objectives of our study were, (1) To identify differentially expressed miRNAs in synovial fluid from endstage OA patients compared to early-stage OA patients, and (2) To explore the use of these differentially expressed miRNAs as potential OA biomarkers. Methods miRNA profiling of knee synovial fluid from 4 endstage (patients scheduled to undergo knee replacement surgery for OA) and 4 early-stage (patients undergoing arthroscopic surgery for knee OA) OA patients was undertaken using miRCURY LNA Universal RT microRNA PCR Human panel I+II arrays. Validation work was based on knee synovial fluid samples from 27 endstage OA and 24 early-stage OA patients. Quantitative real-time PCR was used for validation. Results The miRCURY LNA PCR arrays contained 752 miRNAs and we identified 14 differentially expressed miRNAs in end stage OA compared to early-stage OA. Among these, expression of three miRNAs (miR-27a-3p, miR-378 and miR-101) was only detected in endstage OA, six miRNAs (miR-23a, miR-24, miR-29c, miR-34a, miR-186, miR-27b) were up-regulated and five miRNAs (miR-934, miR-329, miR-655, miR-27a-5p and miR-708-3p) were down-regulated. At second stage of the study, we validated the expression of these 14 miRNAs. Nine miRNAs (miR-23a, miR-24, miR-29c, miR-34a, miR-186, miR-27b, miR-27a-3p, miR-27a-5p and miR-378) remained significantly differentially expressed irrespective of gender. Specifically, miR-378 was detected in majority of endstage OA but rarely in early stage OA synovial fluid. Conclusions We identified and validated 9 miRNAs differentially expressed in knee synovial fluid in endstage compared to early-stage knee OA patients. Importantly this is the first study to profile miRNA expression in OA synovial fluid and 3 miRNAs identified in our study have never been reported to be associated with OA. Current work is underway investigating the source of these miRNAs and if the identified miRNAs exhibit any pathophysiological role in OA. Based on the current data, these miRNAs have the potential to serve as minimally invasive OA biomarkers. Acknowledgements This work is supported by Dr. Kapoor9s Start-up funds provided by the UHN Arthritis Program, Toronto Western Research Institute, Toronto Western Hospital. Disclosure of Interest None declared