MRI and Clinical Risk Indicators for Osteomyelitis.

Introduction. The sensitivity and specificity for magnetic resonance imaging (MRI) diagnosis of osteomyelitis is 90% and 80%, respectively; findings include bone marrow edema, T2-weighted image hyperintensity (HI-T2WI), T1-weighted image confluent signal(CS-T1WI), and cortical erosion (CE). The goal is to determine which risk factors and MRI findings are most predictive of osteomyelitis. Materials and Methods. After institutional review board approval, records of patients who underwent bone biopsy of the foot/ankle between 2015 and 2017 were reviewed. Diagnosis was determined histologically. Blinded MRI review identified indicators of osteomyelitis: HI-T2WI, CS-T1WI, ulcer depth, and CE. Bivariate and multivariate regression determined an association between osteomyelitis and radiographic indicators. Results. Of 59 subjects, 41 (69.5%) and 18 (30.5%) had pathologic evidence of osteomyelitis or were indeterminate. The sensitivity and specificity by radiologist diagnosis was 51.4% and 91.7%, respectively. Diabetes (relative risk [RR]=2.9, 95% CI = 1.0.8-7.77, P = .034), CS-T1WI (RR = 1.6, 95% CI = 1.23-2.20, P < .001), and CE (RR = 1.8, 95% CI = 1.34-2.28, P < .001) were risk factors on bivariate analysis. Ulcer depth demonstrated a trend toward statistical significance. Diabetes (RR = 2.4, 95% CI = 1.00-5.69, P = .049) and CE (RR = 1.7, 95% CI = 1.27-2.37, P < .001) were independent risk factors on multivariate analysis. Discussion. Diabetes and CS-T1WI are independent risk factors for pedal osteomyelitis. Patients with diabetes, CS-T1WI, and CE should be evaluated for osteomyelitis with recommendation for bone biopsy in appropriate clinical settings.Levels of Evidence: Level III Retrospective Comparative Study.

Radiographic evaluation of reconstructive surgery for segmental bone defects: What the radiologist should know about distraction osteogenesis and bone grafting.

Radiologists work in conjunction with orthopedic surgeons to evaluate the progression of bone healing and identify potential problems during bone reconstruction. Accurate evaluation and identification of healing progression or complications are critical to optimizing successful patient outcomes with either distraction osteogenesis or bone grafting. Therefore, radiologists must understand the fundamental concepts behind these surgical reconstructive techniques in order to provide accurate postoperative radiographic assessments. The cases and discussion within this review aim to provide this foundational knowledge.

Self-Complementary Adeno-Associated Virus-Mediated Interleukin-1 Receptor Antagonist Gene Delivery for the Treatment of Osteoarthritis: Test of Efficacy in an Equine Model.

The authors are investigating self-complementary adeno-associated virus (scAAV) as a vector for intra-articular gene-delivery of interleukin-1 receptor antagonist (IL-1Ra), and its therapeutic capacity in the treatment of osteoarthritis (OA). To model gene transfer on a scale proportional to the human knee, a frequent site of OA incidence, studies were focused on the joints of the equine forelimb. Using AAV2.5 capsid and equine IL-1Ra as a homologous transgene, a functional ceiling dose of ∼5 × 1012 viral genomes was previously identified, which elevated the steady state levels of eqIL-1Ra in synovial fluids by >40-fold over endogenous production for at least 6 months. Here, using an osteochondral fragmentation model of early OA, the functional capacity of scAAV.IL-1Ra gene-delivery was examined in equine joints over a period of 12 weeks. In the disease model, transgenic eqIL-1Ra expression was several fold higher than seen previously in healthy joints, and correlated directly with the severity of joint pathology at the time of treatment. Despite wide variation in expression, the steady-state eqIL-1Ra in synovial fluids exceeded that of IL-1 by >400-fold in all animals, and a consistent treatment effect was observed. This included a 30-40% reduction in lameness and ∼25% improvement in total joint pathology by both magnetic resonance imaging and arthroscopic assessments, which included reduced joint effusion and synovitis, and improved repair of the osteochondral lesion. No vector-related increase in eqIL-1Ra levels in blood or urine was noted. Cumulatively, these studies in the equine model indicate scAAV.IL-1Ra administration is reasonably safe and capable of sustained therapeutic IL-1Ra production intra-articularly in joints of human scale. This profile supports consideration for human testing in OA.

Gene Therapy for Osteoarthritis: Pharmacokinetics of Intra-Articular Self-Complementary Adeno-Associated Virus Interleukin-1 Receptor Antagonist Delivery in an Equine Model.

Toward the treatment of osteoarthritis (OA), the authors have been investigating self-complementary adeno-associated virus (scAAV) for intra-articular delivery of therapeutic gene products. As OA frequently affects weight-bearing joints, pharmacokinetic studies of scAAV gene delivery were performed in the joints of the equine forelimb to identify parameters relevant to clinical translation in humans. Using interleukin-1 receptor antagonist (IL-1Ra) as a secreted therapeutic reporter, scAAV vector plasmids containing codon-optimized cDNA for equine IL-1Ra (eqIL-1Ra) were generated, which produced eqIL-1Ra at levels 30- to 50-fold higher than the native sequence. The most efficient cDNA was packaged in AAV2.5 capsid, and following characterization in vitro, the virus was injected into the carpal and metacarpophalangeal joints of horses over a 100-fold dose range. A putative ceiling dose of 5 × 1012 viral genomes was identified that elevated the steady-state eqIL-1Ra in the synovial fluids of injected joints by >40-fold over endogenous levels and was sustained for at least 6 months. No adverse effects were seen, and eqIL-1Ra in serum and urine remained at background levels throughout. Using the 5 × 1012 viral genome dose of scAAV, and green fluorescent protein as a cytologic marker, the local and systemic distribution of vector and transduced cells following intra-articular injection scAAV.GFP were compared in healthy equine joints and in those with late-stage, naturally occurring OA. In both cases, 99.7% of the vector remained within the injected joint. Strikingly, the pathologies characteristic of OA (synovitis, osteophyte formation, and cartilage erosion) were associated with a substantial increase in transgenic expression relative to tissues in healthy joints. This was most notable in regions of articular cartilage with visible damage, where foci of brilliantly fluorescent chondrocytes were observed. Overall, these data suggest that AAV-mediated gene transfer can provide relatively safe, sustained protein drug delivery to joints of human proportions.

Risk of bleeding associated with interventional musculoskeletal radiology procedures. A comprehensive review of the literature.

This review compiles the current literature on the bleeding risks in common musculoskeletal interventional procedures and attempts to provide guidance for practicing radiologists in making decisions regarding the periprocedural management of patients on antithrombotic therapy. The practitioner must weigh the risk of bleeding if therapy is continued against the possibility a thromboembolic occurring if anticoagulation therapy is withheld or reversed. Unfortunately, there is little empirical data to guide evidence-based decisions for many musculoskeletal interventions. However, a review of the literature shows that for low-risk procedures, such as arthrograms/arthrocenteses or muscle/tendon sheath injections, bleeding risks are sufficiently small that anticoagulants and antiplatelet therapies need not be withheld. Additionally, relatively higher-risk procedures, such as needle biopsies of bone and soft tissue, may be safely performed without holding antithrombotic therapy, provided pre-procedural INR is within therapeutic range. Thus, while a patient's particular clinical circumstances should dictate optimal individualized management, anticoagulation alone is not a general contraindication to most interventional musculoskeletal radiology procedures.