Evidence-based recommendations for the management of ankylosing spondylitis: systematic literature search of the 3E Initiative in Rheumatology involving a broad panel of experts and practising rheumatologists

Objective. Recommendations and/or guidelines represent a popularway of integrating evidence-based medicine into clinical practice.The 3E Initiatives is a multi-national effort to develop recommendationsfor the management of rheumatic diseases, which involves a largenumber of experts combined with practising rheumatologists addressingspecific questions relevant to clinical practice. Methods. Ten countries participated in three rounds of discussionsand votes concerning the management of AS. A set of nine questionswas formulated in the domains of diagnosis, monitoring and treatment,after a Delphi procedure. A literature search in MedLine wasconducted. Predefined outcome parameters for the domains ofdiagnosis, monitoring and treatment were assessed. The evidenceto support each proposition was evaluated and scored. Afterdiscussion and votes, the final recommendations were presentedusing brief statements by each national group, following whichthe final international recommendations were formulated. Results. A total of 2699 papers were found and 467 were selectedfor analysis. Twelve key recommendations were developed: threein the domain of diagnosis addressing general diagnostic considerations,early AS diagnosis and general practitioners’ referralrecommendations; three concerning monitoring of AS disease activity,severity and prognosis; six concerning pharmacological treatment(except biologics): non-steroidal anti-inflammatory drugs/COX-IIinhibitors, bisphosphonates and treatment of enthesitis. Thecompiled agreement among experts ranged from 72% to 93%. Conclusion. Recommendations for the management of AS were developedusing an evidence-based approach followed by expert/physicianconsensus with high level of agreement. Involvement of a largerand more representative group of rheumatologists may improvetheir dissemination and implementation in daily clinical practice. KEY WORDS: Ankylosing spondylitis, Systemic literature search, Recommendations, Non-steroidal anti-inflammatory drugs, COX-II inhibitors, Monitoring, Diagnosis, Treatment     

Quantitative testing of liver function in patients with cirrhosis due to chronic hepatitis C to assess disease severity

BACKGROUND/AIMS: Quantitative testing of liver function (QTLF) may allow a prognostic assessment of patients with various liver diseases. However, there are insufficient data about patients with liver cirrhosis due to hepatitis C. PATIENTS/METHODS: 86 consecutive patients (58 males, 28 females, age: 48.3 +/- 11.7 years) with chronic hepatitis C (HCV RNA pos.) underwent sonographically guided liver biopsy to confirm the diagnosis of cirrhosis. QTLF included aminopyrine breath test (microsomal liver function), galactose elimination capacity (cytosolic liver function), sorbitol clearance (liver plasma flow) and indocyanine green clearance (liver perfusion). Values were correlated with the Child-Pugh classification. RESULTS: 55% of the patients (n=47) had cirrhosis of Child-Pugh grade A, 28% of grade B (n=24) and 17% of grade C (n=15). QTLF showed a steady decrease from Child-Pugh grade A to grade B and to grade C. Contrary to markedly reduced tests of metabolic liver function in Child-Pugh grade patients, surrogate tests of hepatic perfusion were at the lower normal limit. All QTLF were significantly reduced in Child-Pugh grade B and C patients compared to healthy controls. Differences between the three Child grades were significant. CONCLUSION: In patients with cirrhosis due to hepatitis C, QTLF correlated inversely with Child-Pugh grades. Since in cirrhosis of grade A, surrogate tests of hepatic perfusion remained at the lower normal limit, whereas those of metabolic function were decreased, QTLF may be a tool to predict prognosis or complications in early cirrhosis due to chronic hepatitis C.     

Toxicity and response to high-dose ifosfamide+mesna as salvage therapy for advanced breast cancer

Summary Twenty-six cycles of high-dose ifosfamide+mesna (HD-IFO+M) were applied to seven female patients with advanced breast cancer refractory to prior treatment, using three different durations of continuous infusion (4, 24, and 48 h) every 3 weeks. To evaluate the most tolerable time schedule, the duration of the infusions was changed periodically in each patient. Toxicity was low in general, but continuous infusion of HD-IFO+M over 24 h appeared to be the best tolerated. On partial response lasting 27 weeks was achieved and four patients achieved stable disease lasting from 9 to 12 weeks.     

Bone disease in vitamin D-deficient patients with Crohn's disease

Vitamin D deficiency is frequently observed in patients with Crohn's disease and may be associated with an increased risk of development of metabolic bone disease. To estimate the incidence of metabolic bone disease by noninvasive methods, 31 patients (17–75 years old) with Crohn's disease and low 25-hydroxy vitamin D (25-OHD) levels in winter were investigated in the following summer by measuring the bone mineral content (BMC) of the distal radius by single photon absorptiometry and the cortical area ratio (CAR) calculated from radiographs of the right hand and by x-ray of the lumbar spine. Forty-five percent of the patients showed signs of metabolic bone disease. BMC and CAR correlated with 25-OHD serum levels (P<0.05), especially in men. Furthermore, the amount of sun exposure has an influence not only on 25-OHD serum levels both in summer and in winter (P=0.0006), but also on the BMC (P=0.07). Consequently, vitamin D deficiency is of major importance for the development of metabolic bone disease in patients with Crohn's disease. Vitamin D deficiency can be prevented by increasing sun exposure and long-term vitamin D supplementation.     

Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens

Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/miniICE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-alpha. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/miniICE.     

Inhibition of BMP activity protects epithelial barrier function in lung injury

Epithelial injury is a central finding in pulmonary disease and is accompanied by disruption of epithelial barrier function, leading to pulmonary oedema and inflammation. Injured epithelial cells lose their properties and gain mesenchymal characteristics, a phenotypic switch that contributes to lung remodelling after injury. Here we studied bone morphogenetic protein (BMP) signalling and, in particular, the role of BMP2 and the BMP modulator BMPER in injured lung epithelium. Increased BMP activity, reflected by up‐regulation of the Smad1/5–Id1 axis, is detected after injury of lung epithelium in vitro and in vivo. Two members of the BMP family, BMP2 and BMPER, have opposing effects. BMP2 is up‐regulated after epithelial injury and causes epithelial dysfunction and hyperpermeability, mediated by the Smad1/5–Id1‐dependent down‐regulation of E‐cadherin. In contrast, BMPER expression is decreased following injury, which in turn impairs epithelial integrity, characterized by reduction of E‐cadherin and epithelial leakage in vitro and in vivo. High levels of BMPER antagonized BMP2‐Smad5–Id1 signalling and prevented BMP2‐mediated decrease of E‐cadherin and hyperpermeability, suggesting that BMPER restores epithelial homeostasis. Supporting this notion, pharmacological inhibition of BMP signalling by LDN193189 prevented reduction of E‐cadherin and disruption of epithelial barrier function. Inhibition of excessive BMP activation could be a new approach to restore epithelial integrity and prevent disruption of epithelial barrier function after lung injury. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

How to report the antinuclear antibodies (anti-cell antibodies) test on HEp-2 cells: guidelines from the ICAP initiative

Immunologic Research - Results of the anti-nuclear antibodies-indirect immunofluorescence assay (anti-cell antibodies test) on HEp-2 cell substrates should be communicated to clinicians in a...