Prediction of clinical outcomes in Crohn’s disease by using confocal laser endomicroscopy: results from a prospective multicenter study

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Use of biosimilars in inflammatory bowel disease: Statements of the Italian Group for Inflammatory Bowel Disease

The introduction of biological therapies, particularly anti-TNFα agents, has revolutionized the management of inflammatory bowel disease in those cases which are refractory to conventional treatment; however these drugs are not risk-free and their use has substantially increased the cost of treatment. As marketing protection expires for original, first-generation biopharmaceuticals, lower-cost “copies” of these drugs produced by competitor companies—referred to as biosimilars—are already entering the market. In September 2013, the European Medicines Agency approved two infliximab biosimilars for treatment of adult and paediatric inflammatory bowel disease patients, a decision based largely on efficacy and safety data generated in studies of patients with ankylosing spondylitis and rheumatoid arthritis. For many clinicians, extrapolation practices and the general question of interchangeability between biosimilars and reference biologics are cause for concern. In the present paper, the Italian Group for inflammatory bowel disease presents its statements on these issues, with emphasis on the peculiar clinical characteristics of inflammatory bowel disease and the importance of providing physicians and patients with adequate information and guarantees on the safety and efficacy of these new drugs in the specific setting of inflammatory bowel disease.     

Hepatitis Status and Mortality in Hemodialysis Population

The role of hepatitis B (HBV) and C (HCV) virus infection in mortality among MHD patients is poorly understood. Recent studies have shown that HCV positivity is associated with significantly higher cardiovascular mortality, especially in dialysis patients younger than 65 years. However, little information is available in European renal registries about mortality among HBV and HCV positive MHD patients. We prospectively followed all patients (prevalents and incidents) attending the dialysis center in the Sicilian region since January 1, 1999, up to December 31, 2000. Those who died for any cause after the starting point were identified and included in the cases population. In all, 698 eligible cases were found. For each case, three controls extracted from the Registry were matched by age at death (within five years) and sex. We calculated the sample size of 698 cases and three controls for each case, assuming the power of the study to be 80%, with an estimated prevalence of exposure among controls of 3.0%. The χ² and the t-test were used to evaluate possible differences among cases and controls for the different variables under investigation. The ORs of the association between hepatitis infection and mortality, adjusted for each of the possible confounding factors, was calculated using the Mantel-Haenszel test. The prevalence of Hepatitis C (HCV) was much higher among case compared with controls, both in males (23.4%?vs. 17.7?%) and females (25.0%?vs. 22.4%). In the multivariate model, the association between HCV and mortality maintained a significant association only among women aged?<65 years with an OR of 1.77 (95%?CI: 1.12–2.79). We also observed a correlation between increased risk of mortality in hemodialysis and HCV-positive patients with a longer time on dialysis. Our results suggest that HCV positivity among MHD patients is associated with significantly higher mortality in female aged?<65 years. For this reason we should be more aggressive in identifying, preventing, and treating HCV infection among patients with end stage renal disease.     

Changes in serum fetuin-A and inflammatory markers levels in end-stage renal disease (ESRD): effect of a single session haemodialysis.

BACKGROUND: The aim of the present study was to evaluate the effect of a single haemodialysis (HD) session on serum fetuin-A levels, considered a negative acute phase response marker; moreover, we evaluated the behaviour of fibrinogen and high sensitivity C-reactive protein (hsCRP) as acute phase response and chronic/subclinical inflammation markers, respectively, after a single HD session. METHODS: Serum fetuin-A, albumin, hsCRP and fibrinogen were measured in 72 patients before and after a single HD session. RESULTS: After a single HD session, we observed a significant increase in fibrinogen levels, while fetuin-A levels decreased (p<0.05). Also, hsCRP levels were significantly increased. CONCLUSIONS: The significant decrease of fetuin-A levels after a single HD session is consistent with the hypothesis of HD-induced inflammation; activated acute phase response and fetuin-A deficiency might account for increased cardiovascular risk and accelerated atherogenesis in dialysis patients.     

Increased inflammation in mice deficient for the chemokine decoy receptor D6

Chemokines are chemotactic cytokines with a key role in the control of cell trafficking and positioning under homeostatic and inflammatory conditions. D6 is a promiscuous 7-transmembrane-domain receptor expressed on lymphatic vessels which recognizes most inflammatory, but not homeostatic, CC chemokines. In vitro experiments demonstrated that D6 is unable to signal after ligand engagement, and it is structurally adapted to sustain rapid and efficient ligand internalization and degradation. These unique functional properties lead to the hypothesis that D6 may be involved in the control of inflammation by acting as a decoy and scavenger receptor for inflammatory chemokines. Consistent with this hypothesis, here we report that D6(-/-) mice showed an anticipated and exacerbated inflammatory response in a model of skin inflammation. Moreover, the absence of D6 resulted in increase cellularity and inflammatory-chemokine levels in draining lymph nodes. Thus, D6 is a decoy receptor structurally adapted and strategically located to tune tissue inflammation and control transfer of inflammatory chemokines to draining lymph nodes.     

Favorable outcome of ex-vivo purging of monocytes after the reintroduction of treatment after interruption in patients infected with multidrug resistant HIV-1

In multidrug resistant patients treatment interruptions allow the selection of archived wild-type drug-susceptible viruses that compete for the less fit drug-resistant strains. However, the selection of viruses with increased replicative capacity is often followed by a loss of CD4+ T cells. In addition, drug resistant variants later re-emerge limiting the overall clinical benefit of treatment interruption. Blood monocytes are a key component of the HIV reservoir and can be partially removed by a system for purging of myeloid cells (MYP). This study tested the safety and efficacy of MYP on multidrug resistant patients who underwent treatment interruption. Twelve patients were randomized to receive or not six cycles of MYP during treatment interruption. An optimized antiretroviral regimen was reintroduced after the reappearance of a drug susceptible genotype. Following therapy reintroduction, a long lasting increase in CD4+ T cell counts was observed only in the treatment interruption + MYP patients but not in the control patients. Five/six treatment interruption + MYP patients never experienced virological rebound during a median follow up period of 98 weeks. In contrast, 4/6 patients who did not receive MYP never reached complete viral suppression and had a virological rebound after a median of 16.5 weeks after treatment reintroduction. The difference between the two groups in the time to virological rebound was statistically significant (P = 0.021). A consistent decrease of HIV DNA load in CD14+ purified cells was observed only in treatment interruption + MYP patients. These data suggest that MYP can improve the immunological and virological response to treatment interruption.     

Uncoupling of inflammatory chemokine receptors by IL-10: generation of functional decoys

As originally demonstrated for the interleukin 1 (IL-1) type II receptor, some primary proinflammatory cytokines from the IL-1 and tumor necrosis factor families are regulated by decoy receptors that are structurally incapable of signaling. Here we report that concomitant exposure to proinflammatory signals and IL-10 generates functional decoy receptors in the chemokine system. Inflammatory signals, which cause dendritic cell (DC) maturation and migration to lymphoid organs, induce a chemokine receptor switch, with down-regulation of inflammatory receptors (such as CCR1, CCR2, CCR5) and induction of CCR7. Concomitant exposure to lipopolysaccharide (LPS) and IL-10 blocks the chemokine receptor switch associated with DC maturation. LPS + IL-10-treated DCs showed low expression of CCR7 and high expression of CCR1, CCR2 and CCR5. These receptors were unable to elicit migration. We provide evidence that uncoupled receptors, expressed on LPS + IL-10-treated cells, sequester and scavenge inflammatory chemokines. Similar results were obtained for monocytes exposed to activating signals and IL-10. Thus, in an inflammatory environment, IL-10 generates functional decoy receptors on DC and monocytes, which act as molecular sinks and scavengers for inflammatory chemokines.     

Antiadhesive and antibiofilm activity of hyaluronic acid against bacteria responsible for respiratory tract infections

To address the problem of limited efficacy of existing antibiotics in the treatment of bacterial biofilm, it is necessary to find alternative remedies. One candidate could be hyaluronic acid; this study therefore aimed to evaluate the in vitro antiadhesive and antibiofilm activity of hyaluronic acid toward bacterial species commonly isolated from respiratory infections. Interference exerted on bacterial adhesion was evaluated by using Hep‐2 cells, while the antibiofilm activity was assessed by means of spectrophotometry after incubation of biofilm with hyaluronic acid and staining with crystal violet. Our data suggest that hyaluronic acid is able to interfere with bacterial adhesion to a cellular substrate in a concentration‐dependent manner, being notably active when assessed as pure substance. Moreover, we found that Staphylococcus aureus biofilm was more sensitive to the action of hyaluronic acid than biofilm produced by Haemophilus influenzae and Moraxella catarrhalis. In conclusion, hyaluronic acid is characterized by notable antiadhesive properties, while it shows a moderate activity against bacterial biofilm. As bacterial adhesion to oral cells is the first step for colonization, these results further sustain the role of hyaluronic acid in prevention of respiratory infections.