Search

Objective: To evaluate the association between ultrasound (US) detected inflammation at baseline and the subsequent development of new bone erosions at follow-up in patients with hand osteoarthritis (HOA).Method: 32 of the 35 (10 controls, 12 patients with non erosive HOA (non-EHOA), 13 with EHOA subjects originally studied were re-evaluated 3.9 years after the initial study, by means of standard radiography and US examination. Kellgren-Lawrence (K-L) and Kallman scores were utilized to evaluate 576 interphalangeal (IP) joints. US detected synovial inflammation features were scored as present/absent. US detected bone erosions were also investigated. The association between synovial inflammation features at baseline and the development of new bone erosions was evaluated using the generalized linear mixed model (GLMM) after adjustment for patient effect, age, gender, body mass index.Results: In HOA patients, radiographic scores worsened and bone erosions progressed. In HOA patients similar percentages of joints with Power Doppler Signal (PDS) and gray scale (GS) synovitis were found comparing baseline and follow-up examinations, whilst a significant increase was found in the joints with effusions. Only a minority of joints were positive on both occasions (between 2 and 6 %), the majority fluctuated between positive and negative and vice versa. PDS positivity was associated with new radiographic central erosions and US-detected bone erosions, whereas GS synovitis and effusion were not.Conclusions: Radiographic scores and bone erosions increased over a period of about 4 years. Synovial inflammation as detected by PDS was associated with the appearance of new bone erosions. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To examine ultrasound (US) features of synovitis in hand osteoarthritis (OA) joints, and to evaluate their relationship with radiological damage severity and US-detected cartilage thickness. Methods: US examination was carried out on 14 joints of both hands of 25 patients with symptomatic hand OA (HOA) and 10 age- and sex-matched control subjects. US-detected features were: synovial hypertrophy, effusion, power Doppler signal (PDS), cartilage thickness. Conventional hand radiographs were scored utilizing the Kellgren–Lawrence and Kallman systems. HOA patients were divided into two subsets: non-erosive and erosive. Results: Among the three groups of subjects studied, erosive OA showed the highest values of radiological scores and the highest prevalence of US-detected synovitis. Joints positive for US synovitis features (above all PDS) had higher radiological scores and lower cartilage thickness, while joints with X-ray detected central erosions [the hallmark of erosive HOA were more likely to present PDS positivity. US measured cartilage thickness inversely correlated with radiological damage scores. Conclusions: US-detected synovitis is present in about 10% of HOA finger joints and is associated with more severe radiological damage and reduced cartilage thickness. PDS and cartilage thickness (mm) may represent two innovative additional information tools provided by ultrasonography in HOA evaluation. [ABSTRACT FROM AUTHOR]

Summary: Objective: IL-13/IL-4/IL-4R system has strong chondroprotective activity. We investigated polymorphisms in these genes as potential hand osteoarthritis (OA) susceptibility loci by performing a case–control association study. Methods: Eighteen common single nucleotide polymorphisms (SNPs) (nine in IL-4R, five in IL-4 and four in IL-13) were genotyped in 403 patients (380 females) with hand OA and 322 healthy controls (308 females). Results: Two SNPs (rs1805013 and rs1805015), mapping to the IL-4R gene, were associated with P-values of 0.0116 and 0.0305 respectively in the whole sample. As far as the non-erosive hand OA group (n =159) is concerned, the significance level of association of SNP rs1805013 is increased. After correction for multiple testing (correction for the 54 tests) the significance was not retained. None of the IL-13 SNPs analyzed showed association with hand OA. Some of the analyzed SNP within the IL-4 gene showed significant association with hand OA only when considering subgroups of patients. With respect to the CMC1 OA group, two SNPs in IL-4 (rs2243250 and rs2243274) showed association with a P-value of 0.027 and 0.018 respectively. None of these associations remained after correction for multiple testing. Conclusions: The present study shows a trend to an association between non-erosive hand OA in Caucasian population and a genetic variant in the coding region of IL-4R gene. Our results, in keeping with previous data on hip OA, confirm the suggestion that IL-4/IL-4R system plays a role in OA pathogenesis. Further confirmation studies on different populations are necessary. [Copyright &y& Elsevier]

Abstract: The literature on hepatitis B virus (HBV) in immunocompromised patients is heterogeneous and referred mainly to the pre-antivirals era. Today a rational approach to the problem of hepatitis B in these patients provides for: (a) the evaluation of HBV markers and of liver condition in all subjects starting immunosuppressive therapies (baseline), (b) the treatment with antivirals (therapy) of active carriers, (c) the pre-emptive use of antivirals (prophylaxis) in inactive carriers, especially if they are undergoing immunosuppressive therapies judged to be at high risk, (d) the biochemical and hepatitis B surface antigen (HBsAg) monitoring (or universal prophylaxis, in case of high risk immunosuppression) in subjects with markers of previous contact with HBV (HBsAg negative and anti-HBc positive), in order to prevent reverse seroconversion. Moreover it is suggested a strict adherence to criteria of allocation based on the virological characteristics of both recipients and donors in the general setting of transplants and in liver transplantation the universal prophylaxis with nucleos(t)ides analogues (frequently combined with specific anti-HBV immunoglobulins) in HBsAg positive candidates and in HBsAg negative recipients of anti-HBc positive grafts. [Copyright &y& Elsevier]

Objective: To test the importance of the interleukin-4 (IL-4)/IL-4 receptor (IL-4R) system in osteoarthritis (OA) we evaluated soluble IL-4R (sIL-4R) levels in sera of patients with different forms of OA and healthy individuals.Methods: We recruited: 141 patients with hand OA, 70 with nodal and 71 with erosive hand OA; 64 patients undergoing total joint replacement, 34 with hip and 30 with knee OA; and 38 ethnically and geographically age-matched healthy individuals [normal controls (NC)].Results: Serum sIL-4R concentration was found to be significantly higher in all OA patients than that in NC. When patients were divided into four subgroups (nodal, erosive, hip and knee OA) significant differences were present when comparing NC with each subgroup. This was true also when small-joint OA groups were compared with large-joint OA groups, the latter being associated with higher IL-4R levels.Conclusions: We found increased levels of sIL-4R in OA patients compared with healthy individuals. We speculate that this reduces availability of IL-4, and its effects on chondrocytes. [ABSTRACT FROM AUTHOR]

Adipose mesenchymal stromal cells (ASC) are commonly utilized in various cell therapies and recently in phase I clinical trials to counteract the development of knee osteoarthritis. Administered-ASC in the knee joints enter in close contact with the OA inflammatory milieu and hypoxic environment,which could modulate their characteristics.Little is known about the OA milieu factors that could enhance the migration and tissue specific engraftment of exogenously injected ASC for successful regenerative cell therapy.Therefore,we tested the effect of OA milieu on good manufactured practice (GMP)-ASC,both in normoxic and hypoxic conditions and evaluated their migration properties and cytokine receptors. We analyzed IL8, IP10,SDF-1,MCP1,MIP1α, MIP1β,RANTES and IL6 cytokines in two different OA milieu:OA synovial fluid (SF) and OA-conditioned medium (CM) from synoviocytes.These milieu adequately represent the OA environment for ASC injection and the milieu containing all the soluble factors released by the target tissue of ASC, respectively. The same cytokines were analyzed also on basal GMP-ASC,both in normoxic and hypoxic conditions. Afterwards, GMP-ASC were treated either with OA-SF or OA-CM for 48hours and tested for migration and cytokine receptors expression, as well as the cytokine secretion, both in normoxia or hypoxia (1,5%O 2). Healthy SF was used as control. In OA-SF we detected higher amount of IP10 than in OA-CM while MCP1 and MIP1β were higher in OA-CM compared to OA-SF.All the other cytokines were detected in the same amounts in both OA milieu. We demonstrated that GMP-ASC show an increase in proliferation, migration, no changes in the amount of cytokines released and modulation of CXCR1,CXCR3,CCR1 and CCR5 receptors in hypoxic condition. Moreover,GMP-ASC migration increased 15-fold when treated either with OA-SF or OA-CM compared to healthy SF,both in normoxic and hypoxic conditions.GMP-ASC treated in OA milieu showed an increase of CXCR3, CCR3 and IL6R and a decrease of CCR1,CCR2 receptors. IP10 was the only chemokine of the OA milieu down-modulated after treatment with GMP-ASC.We demonstrated specific effects of OA milieu on both GMP-ASC migration and cytokine receptor expression that were strictly dependent by the inflammatory and hypoxic environment.The use of characterized OA milieu might contributes to define the therapeutic effects of GMP-ASC and indicates that IP10-CXCR3 axis is partially involved in GMP-ASC effect on synovial macrophages. [ABSTRACT FROM AUTHOR]