Novel genetic loci associated with osteoarthritis in multi-ancestry analyses in the Million Veteran Program and UK Biobank.

Osteoarthritis is a common progressive joint disease. As no effective medical interventions are available, osteoarthritis often progresses to the end stage, in which only surgical options such as total joint replacement are available. A more thorough understanding of genetic influences of osteoarthritis is essential to develop targeted personalized approaches to treatment, ideally long before the end stage is reached. To date, there have been no large multiancestry genetic studies of osteoarthritis. Here, we leveraged the unique resources of 484,374 participants in the Million Veteran Program and UK Biobank to address this gap. Analyses included participants of European, African, Asian and Hispanic descent. We discovered osteoarthritis-associated genetic variation at 10 loci and replicated findings from previous osteoarthritis studies. We also present evidence that some osteoarthritis-associated regions are robust to population ancestry. Drug repurposing analyses revealed enrichment of targets of several medication classes and provide potential insight into the etiology of beneficial effects of antiepileptics on osteoarthritis pain.

A Clinicoradiological and Functional Evaluation of Lapidus Surgery for Moderate to Severe Bunion Deformity Shows Excellent Stable Correction and High Long-Term Patient Satisfaction.

Background. Lapidus surgery involving arthrodesis of the first metatarsocuneiform (MTC) joint is an effective procedure for the correction of moderate to severe hallux valgus. The aim of this study was to collect and analyze radiographic data from our institution and determine the extent of first metatarsal shortening associated with the Lapidus procedure. Materials and Methods. A total of 53 patients (54 feet) who underwent arthrodesis of the first MTC joint combined with modified McBride bunionectomy for correction of moderate to severe hallux valgus deformity, between 2010 and 2015 were included in this study. Complete radiographic evaluation and AOFAS (American Orthopaedic Foot and Ankle Surgery) scoring was available for 54 feet. The average preoperative hallux valgus angulation (HVA) was 32° and the average intermetatarsal angle (IMA) was 16°. Results. Excluding 2 patients with postoperative hallux varus the average postoperative HVA correction at last follow-up was 14°. Average postoperative IMA was 9°. Although there was minimal bone resection during preparation of the MTC joint, no significant shortening of the first metatarsal was observed with this procedure. The relative length of the first metatarsal to the second metatarsal changed only 1.3%. Nonunion of the first MTC joint occurred in 10.3%, but only 1 foot was symptomatic requiring revision. The average postoperative hallux AOFAS score was 80.8. In sum, 63% of patients were very satisfied, 27% satisfied with reservations, and 10% were dissatisfied. Conclusion. The Lapidus bunion procedure offers excellent stable correction of moderate to severe hallux valgus deformity with minimal shortening of the first metatarsal and thereby higher patient satisfaction.Levels of Evidence: Level IV: Retrospective case series.

A Case Report and Literature Review to Aid in the Management of Trunnion Failure in Hip Arthroplasty Patients: Can Trunnionosis and Prosthetic Joint Infection Co-Exist?

Trunnionosis is a type of corrosion and wear at the head-neck taper junction of the femoral implant, and it can be a slow and silent catastrophe. Simultaneous prosthetic joint infection (PJI) is occasionally possible based on the fulfillment of a few of the minor criteria from the Musculoskeletal Infection Society (MSIS), but the existing literature lacks adequate evidence to support that the infection actually exists. We are presenting a case of an 82-year-old man with right total hip arthroplasty performed over a decade prior to presenting to the emergency room with a sudden-onset pop followed by groin pain and difficulty in walking. Radiographs showed a dissociated femoral implant at the level of trunnion with malalignment and heterotopic ossification. Metal Artifact Reduction Sequence MRI of the right hip showed mixed type-two and type-three pseudotumors, and atrophy of surrounding abductor muscles. The erythrocyte sedimentation rate was within normal limits, C-reactive protein was borderline raised, and serum cobalt-chromium levels were elevated without any signs of systemic metal toxicity. Hip joint aspirate revealed blood-stained fluid flooded with red blood cells, leukocytes and neutrophils, and a positive alpha-defensin assay. These findings were interpreted as positive for prosthetic joint infection. Intraoperatively, there was severe wear of the inferomedial aspect of the femoral head-neck junction and extensive metallosis throughout the right hip. Tissue and fluid specimens were sent for cultures, sensitivities, and histopathology for pseudotumor and infection evaluation. An articulating antibiotic spacer was then placed with the intent to perform a staged reconstruction of the femur and right acetabulum. Final synovial, bone, and soft tissue cultures, as well as histopathological photomicrograph of the tissue slides, were negative for infection. This case demonstrates the striking features of metallosis associated with trunnion failure of a metal-on-polyethylene total hip joint prosthesis that was simultaneously showing signs of prosthetic infection by satisfying the minor criteria according to the latest guidelines by the MSIS with a strikingly high cell count of red blood cells in the synovial fluid exam, indicating inflamed hyper-vascular pseudotumors vs. hemarthrosis vs. bloody tap. Diagnostic dilemma led by positive synovial fluid alpha defensin, high synovial neutrophil and white cell count results with negative final cultures or infection on histological slides raises concern that infection was not present and two-stage revision arthroplasty with six weeks of antibiotics was not necessary along with increased risk of morbidity, mortality as well as cost of care.

Daptomycin-Tobramycin Cement Beads have Lethal Local Antibacterial Effect in Resistant Periprosthetic Joint Infections.

Background Resistant periprosthetic joint infection (PJI) can be a devastating complication of surgery and is difficult to treat. We attempted to identify the utility of Daptomycin/Tobramycin-impregnated polymethylmethacrylate (PMMA) beads in resistant PJIs. Methods Charts of patients with hip or knee PJI at a single academic medical center, with surgeries performed from May 2008 through May 2018, were reviewed retrospectively. The diagnosis of PJI was consistent with the Musculoskeletal Infection Society recommendations. Prosthetic joints underwent radical anterior-posterior synovectomy and placement of antibiotic cement beads in the infected joint. Clinical cure rate and local intraarticular antibiotic concentration were measured. Results Forty-four patients experienced 53 episodes of PJI, requiring 88 surgeries. There was a fairly even split between hip and knee PJI. The cure rate was 92% (11/12) for patients who had any infection with methicillin-resistant staphylococci during the evaluation period, compared with 62% (13/21) for patients with methicillin-susceptible Staphylococci. On days one and seven, the addition of tobramycin increased daptomycin concentrations by 47% and 3374%, respectively, for beads made onsite compared to elution of daptomycin alone. Elution increased by 44% and 8394%, respectively, for commercial beads compared to beads fabricated onsite. Conclusions Daptomycin-Tobramycin-loaded PMMA beads are safe and powerful bactericidal agents in prosthetic joint infections.

Elusive Differential of a Painful Unstable Total Knee Arthroplasty - Metal on Cement Disease.

Particle disease from the release of metal, cement, ceramic, or polyethylene particles is a rare condition in total knee replacement. Wear, fracture, or corrosion of the components leads to foreign body reaction in the joint, followed by pain, swelling, limited motion, difficulty in walking, functional disability, and occasional systemic disease. This paper presents two cases of metal-on-cement disease as an etiology for the implant failure wherein the metal particles were shed off from the implant, along with cement and polyethylene particles, leading to a complex foreign body reaction in the failed total knee. We have coined this phenomenon as "cementallosis." Initial symptoms and signs from implant failure in both patients were mild, intermittent mediolateral knee pain that was aggravated after walking but no pain at rest or at night. The pain was associated with a 'buckling' sensation, recurrent knee swelling, and gradually worsening knee range of motion. Clinical examination in both cases was suggestive of a well-healed anterior midline surgical scar, mild to moderate effusion, mild diffuse tenderness over the entire joint, limited functional range of motion, grade 1+ laxity throughout the range of motion, and intact distal neurovascular status. Routine blood and synovial fluid workup were inconclusive for identifying the exact etiology of the patient's symptoms. Radiographs, computed tomography (CT) scans, as well as bone scans, were negative for prosthetic joint infection, component malalignment, polyethylene wear, maltracking, or loosening of the components but showed mild to moderate effusions, synovial hypertrophy, and mild scattered periprosthetic osteolysis. Intraoperatively, there was significant synovial hypertrophy with dark pigment deposition and apparent dissociation of the femoral and tibial components from the underlying cement mantle, although the cement was well-adhered to the underlying bone. Synovial fluid and multiple tissue specimens were suggestive of complex foreign body granulomas with metal, cement, and polyethylene particles. These patients had undergone surgery by the same surgery team in the community using the same implant. These cases demonstrate the failure of a total knee arthroplasty implant at the metal-cement interface with features of adverse local tissue reactions that resemble a pseudotumor from the metal-on-metal disease in the knee joint. We have compared and contrasted the clinical presentations, laboratory, imaging, histopathological, and intraoperative study findings in these cases. Knowing what to look for will aid in early diagnosis, ordering necessary investigations, better surgery planning, reducing operative time, as well as improving outcomes and cost of care. The aim of this paper is to educate the audience about this new phenomenon as a cause of knee prosthesis failure produced by a complex pseudotumor-like foreign body reaction that involves metal, cement, and polyethylene particles.

Serum interleukin 6 could be a valuable initial diagnostic tool in prosthetic knee joint infections.

BACKGROUND: Accurate preoperative diagnosis of prosthetic joint infection (PJI) in the absence of obvious clinical signs or laboratory findings is challenging. Interleukin 6 (IL-6) has been proposed as an infection marker but supportive data are limited. We studied the diagnostic utility of serum IL-6 in infected total knee arthroplasty (TKA). METHODS: A prospective cohort study was done in 52 patients (59 knees) with a painful TKA. The abnormal limits for serum IL-6, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), synovial fluid white cell counts (WBC) and synovial fluid neutrophils (PMN) were determined from receiver operating characteristic curves. An infection was defined as the presence of sinus tract or positive culture > two separate tissue or fluid samples. We utilized Mann-Whitney test, Spearman's correlation and Fischer's exact test to determine the sensitivity, specificity, positive predictive value, negative predictive value (NPV) and accuracy of serum IL-6. RESULTS: The optimal threshold concentration of serum IL-6 was 9.14 pg/ml. Independently, this yielded a sensitivity, specificity and NPV of 81%, 63% and 85%, respectively, and when combined with synovial fluid WBC, values were 100%, 90%, 100%, respectively. The sensitivity and specificity of ESR (70%, 63.6%), CRP (66.7%, 66.7%), synovial WBC (66.7%, 81%) and synovial PMN (82.4%, 73.7%) were also calculated. Serum IL-6 levels strongly correlate with all markers in PJI. CONCLUSIONS: Serum IL-6 improves the diagnosis of PJI over existing methods, especially when combined with synovial fluid WBC. Its optimal usage is as an excellent screening test to rule out infected total knee arthroplasty. LEVEL OF EVIDENCE: Diagnostic Level II.