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Objective. Rheumatoid arthritis (RA) is classically thought of as a Th1, T lymphocyte-driven disease of the adaptive immune system. However, cells of the innate immune system, including neutrophils, are prevalent within the diseased joint, and accumulate in large numbers. This study was undertaken to determine whether cells of the rheumatoid stromal microenvironment could establish an inflammatory environment in which endothelial cells are conditioned in a diseasespecific manner to support neutrophil recruitment.Methods. Human umbilical vein endothelial cells (ECs) and fibroblasts isolated from the synovium or skin of RA patients were established in coculture on opposite sides of porous transwell filters. After 24 hours of EC conditioning, the membranes were incorporated into a parallel-plate, flow-based adhesion assay and levels of neutrophil adhesion to ECs were measured.Results. ECs cocultured with synovial, but not skin, fibroblasts could recruit neutrophils in a manner that was dependent on the number of fibroblasts. Antibody blockade of P-selectin or E-selectin reduced neutrophil adhesion, and an antibody against CD18 (the ␤2 integrin) abolished adhesion. Blockade of CXCR2, but not CXCR1, also greatly inhibited neutrophil recruitment. Interleukin-6 (IL-6) was detectable in coculture supernatants, and both IL-6 and neutrophil adhesion were reduced in a dose-dependent manner by hydrocortisone added to cocultures. Antibody blockade of IL-6 also effectively abolished neutrophil adhesion.Conclusion. Synovial fibroblasts from the rheumatoid joint play an important role in regulating the recruitment of inflammatory leukocytes during active disease. This process may depend on a previously unsuspected route of IL-6-mediated crosstalk between fibroblasts and endothelial cells.

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Objective. The role of chemokines and their transporters in rheumatoid arthritis (RA) is poorly described. Evidence suggests that CXCL5 plays an important role, because it is abundant in RA tissue, and its neutralization moderates joint damage in animal models of arthritis. Expression of the chemokine transporter Duffy antigen receptor for chemokines (DARC) is also up-regulated in early RA. The aim of this study was to investigate the role of CXCL5 and DARC in regulating neutrophil recruitment, using an in vitro model of RA synovium.Methods. To model RA synovium, RA synovial fibroblasts (RASFs) were cocultured with endothelial cells (ECs) for 24 hours. Gene expression in cocultured cells was investigated using TaqMan gene arrays. The roles of CXCL5 and DARC were determined by incorporating cocultures into a flow-based adhesion assay, in which their function was demonstrated by blocking neutrophil recruitment with neutralizing reagents.Results. EC-RASF coculture induced chemokine expression in both cell types. Although the expression of CXC chemokines was modestly up-regulated in ECs, the expression of CXCL1, CXCL5, and CXCL8 was greatly increased in RASFs. RASFs also promoted the recruitment of flowing neutrophils to ECs. Anti-CXCL5 antibody abolished neutrophil recruitment by neutralizing CXCL5 expressed on ECs or when used to immunodeplete coculture-conditioned medium. DARC was also induced on ECs by coculture, and anti-Fy6 antibody or small interfering RNA targeting of DARC expression effectively abolished neutrophil recruitment.Conclusion. This study is the first to demonstrate, in a model of human disease, that the function of DARC is essential for editing the chemokine signals presented by ECs and for promoting unwanted leukocyte recruitment.

Antiviral therapy for the treatment of hepatitis C virus (HCV) infection is used before and after liver transplantation. The objective of this study was to determine the most cost-effective timing for pegylated interferon/ribavirin therapy in patients with advanced liver disease infected with genotype 1 HCV. A Markov model was constructed to compare treatment strategies: (1) no treatment, (2) antiviral therapy in patients with compensated cirrhosis, (3) antiviral therapy in patients with decompensated cirrhosis, and (4) antiviral therapy in patients with progressive fibrosis due to recurrent HCV post-transplantation. Outcomes of interest included the total cost per patient, number of quality-adjusted life years (QALYs) saved, cost per QALY saved, number of deaths and hepatocellular carcinomas (HCCs), and number of transplants required. Compared to the no-antiviral treatment strategy, treatment during compensated cirrhosis increased QALYs by 0.950 and saved $55,314. Treatment during decompensated cirrhosis increased QALYs by 0.044 and saved $5511. Treatment during posttransplant advanced recurrence increased QALYs by 0.061 and saved $3223. Treatment of patients with compensated cirrhosis resulted in 119 fewer deaths, 54 fewer HCCs, and 66 fewer transplants with respect to the no-treatment strategy. The model was sensitive to the rate of graft failure in patients with and without sustained virological response. The model was otherwise robust to all variables tested in sensitivity analysis. In conclusion, the treatment of patients with compensated cirrhosis was found to be the most cost-effective strategy and resulted in improved survival and decreased cost in comparison with all other strategies. This study provides pharmacoeconomic evidence in support of treating HCV in patients with compensated cirrhosis before progression to more advanced liver disease. Liver Transpl 16:748-759,

Background:Acellular dermal matrices (ADMs) have been used in the treatment of shoulders with massive rotator cuff tears (MRCTs). Despite clinical improvement, correlation of clinical findings with ADM integrity on imaging has not been investigated.Hypothesis:The pain in shoulders with MRCTs is partially due to bone-to-bone contact between the tuberosity and acromion. Coverage of the tuberosity with an intact graft or a graft that is torn in a way that the tuberosity remains covered will act as an interpositional tissue, preventing bone-to-bone contact and leading to clinical improvement.Study Design:Case series; Level of evidence, 4.Methods:Between 2006 and 2016, a total of 25 shoulders with MRCTs underwent a procedure with an ADM. Pre- and postoperative visual analog scale (VAS) results, American Shoulder and Elbow Surgeons (ASES) score, Hamada grade, and Goutallier classification were reviewed. A postoperative magnetic resonance imaging (MRI) was obtained in 22 (88%) shoulders. The status of the graft was divided into the following categories: type I, intact graft; type II, graft tear with tuberosity covered; and type III, graft tear with tuberosity uncovered (bare).Results:The mean patient age was 61 years (range, 49-73 years), and the mean follow-up was 25.6 months (range, 10-80 months). Mean length from surgery to postoperative MRI was 13.9 months (range, 6-80 months). The graft was torn in 59% (13/22 shoulders). Significant improvements were found in VAS and ASES scores (7 vs 0.7 and 32.6 vs 91.2, respectively; P < .01) for type I grafts and in VAS and ASES scores (8.1 vs 1.3 and 26.3 vs 84.6, respectively; P < .01) for type II grafts. No difference was found in postoperative VAS and ASES (0.7 vs 1.3 and 91.2 vs 84.6, respectively; P = .8) between type I and type II grafts. No improvement was seen in VAS (7.3 vs 5.7; P = .2) or ASES (30.6 vs 37.2; P = .5) for type III grafts.Conclusion:MRI appearance of the graft has a significant impact on functional outcomes. Patients with an intact graft or a graft tear leaving the tuberosity covered have lower pain and higher functional scores than those in whom the torn graft leaves the tuberosity uncovered.

Lumbar muscle quantity and quality showed specific correlation with age and spine disorders. Additionally, LL can be predicted by the muscle quantity, but not the quality. These time-saving evaluation tools potentially accelerate the study of lumbar muscles. These slides can be retrieved under Electronic Supplementary Material.

Upper extremity gunshot wounds result in notable morbidity for the orthopaedic trauma patient. Critical neurovascular structures are particularly at risk. The fractures are often comminuted and may be associated with a variable degree of soft-tissue injury. The literature lacks consensus regarding antibiotic selection and duration, and indications for surgical débridement. Bullets and/or bullet fragments should be removed in cases of plumbism, intra-articular location, nerve impingement, location within a vessel, and location in a subcutaneous position within the hand and/or wrist. Gunshot fractures generally do not follow common fracture patterns seen in blunt injuries, and the complexity of certain gunshot fractures can often be a challenge for the treating orthopaedic surgeon. Common plate and screw constructs may not adequately stabilize these injuries, and innovative fixation techniques may be required. The treatment for bone defects varies by location and severity of injury, and typically requires staged treatment. Nerve injuries after gunshot wounds are common, but spontaneous nerve recovery is expected in most cases.