Exploring IL-17 in spondyloarthritis for development of novel treatments and biomarkers

Spondyloarthritis (SpA) is an umbrella term describing a family of chronic inflammatory rheumatic diseases. These diseases are characterised by inflammation of the axial skeleton, peripheral joints, and entheseal insertion sites throughout the body which can lead to structural joint damage including formation of axial syndesmophytes and peripheral osteophytes. Genetic evidence, preclinical and clinical studies indicate a clear role of interleukin (IL)- 23 and IL-17 as mediators in SpA pathogenesis. Targeting the IL-23/?17 pathways seems an efficient strategy for treatment of SpA patients, and despite the remaining challenges the pathway holds great promise for further advances and improved therapeutic opportunities. Much research is focusing on serological markers and imaging strategies to correctly diagnose patients in the early stages of SpA. Biomarkers may facilitate personalised medicine tailored to each patient's specific disease to optimise treatment efficacy and to monitor therapeutic response. This narrative review focuses on the IL-17 pathway in SpA-related diseases with emphasis on its role in pathogenesis, current approved IL-17 inhibitors, and the need for biomarkers reflecting core disease pathways for early diagnosis and measurement of disease activity, prognosis, and response to therapy.     

Einstellungen und Hinderungsgründe bezüglich Telemedizin bei Epilepsien: Eine Umfrage in neurologischen Praxen

Clinical Epileptology - In Anbetracht ihres bedeutenden Potenzials zur Verbesserung der medizinischen Versorgung wird Telemedizin weiterhin zu wenig genutzt. Trotz einiger erfolgreicher...     

Inhibition of mTOR in combination with doxorubicin in an experimental model of hepatocellular carcinoma

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is resistant to chemotherapy. We reported that sirolimus, an mTOR inhibitor, has antiangiogenic properties in HCC. Since antiangiogenic therapy may enhance chemotherapy effects, we tested the antitumorigenic properties of sirolimus combined with doxorubicin in experimental HCC. METHODS: Morris Hepatoma (MH) cells were implanted into livers of syngeneic rats. Animals were assigned to sirolimus, pegylated liposomal doxorubicin, both combined or control groups. Tumoral growth was followed by MRI. Antiangiogenic effects were assessed by CD31 immunostaining and capillary tube formation assays. Cell proliferation was monitored in vitro by thymidine incorporation. Expression of p21 and phosphorylated MAPKAP kinase-2 was quantified by immunoblotting. RESULTS: Animals treated with the combination developed smaller tumors with decreased tumor microvessel density compared to animals that received monotherapies. In vitro, inhibition of mTOR further impaired capillary formation in the presence of doxorubicin. Doxorubicin reduced endothelial cell proliferation; inhibition of mTOR accentuated this effect. Doxorubicin stimulated p21 expression and the phosphorylation of MAPKAP kinase-2 in endothelial cells. Addition of mTOR inhibitor down-regulated p21, but did not decrease MAPKAP kinase-2 phosphorylation. CONCLUSIONS: Sirolimus has additive antitumoral and antiangiogenic effects when administered with doxorubicin. These findings offer a rationale for combining mTOR inhibitors with chemotherapy in HCC treatment.     

Biochemical marker discovery,testing and evaluation for facilitating OA drug discovery and development

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Item reduction based on rigorous methodological guidelines is necessary to maintain validity when shortening composite measurement scales

ObjectiveTo review current practice and update guidelines for the methodology of shortening composite measurement scales (CMSs).Study Design and SettingA literature review gathered data on 91 shortening processes from 1995 to 2009. The validity of the initial CMS, the shortening methods, and the validity of the derived short-form scales were examined. The results were compared with those from a previous literature review (articles from 1985 to 1995) to develop updated guidelines for CMS shortening.ResultsThe literature review revealed a persisting lack of use of rigorous methodology for CMS shortening. Of the 91 cases of CMS shortening, 36 combined a content approach and a statistical approach; 45 used only a statistical approach and 10 (11%) only a content approach. The updated guidelines deal with the validity and conceptual model of the initial CMS, the preservation of content and psychometric properties during shortening, the selection of items, and the validation of the short form.ConclusionItem reduction based on a rigorous methodology is necessary if the short-form instrument aims to maintain the validity and other measurement properties of the parent instrument, which in turn supports application in research and clinical practice.     

Reticular erythema signalling the onset of episodes of hereditary angioedema in a child

INTRODUCTION: Hereditary angioedema is characterized by episodes of subcutaneous, digestive or laryngeal edema. In some cases, non-pruritic reticular erythema may precede the episodes of edema. OBSERVATION: Every 4 to 6 weeks since infancy, a girl presented non-pruritic widespread reticular erythema, sparing the face. Two or three times every year, abdominal pain or edema of the lower limb joints followed the skin eruption. At 12 years of age, she was hospitalized because of an edema of the face associated with the eruption. Exploration of the complement confirmed the diagnosis of type I hereditary angioedema. DISCUSSION: The mean delay before diagnosis of hereditary angioedema is of 7 years. Reticular erythema in hereditary angioedema is frequent (40p. 100 of cases) and it usually occurs early in childhood, even in the absence of any episode of angioedema. When present, these eruptions usually precede an episode of angioedema. Recognition of this eruption as a symptom of hereditary angioedema would shorten the delay before diagnosis and anticipate appropriate management of the episodes.     

Improvement in cognitive function and cerebral perfusion after bur hole surgery in an adult with moyamoya disease. Case report

Recent studies have suggested that cognitive impairment may be a common complication in adults with moyamoya disease (MMD). However, the mechanisms of cognitive dysfunction have not been clarified. Whether cognitive impairment may occur as a consequence of cerebral hypoperfusion and may improve after revascularization surgery has not been determined. A 39-year-old West Indian woman with subacute dysexecutive cognitive syndrome and no history of stroke was diagnosed with MMD. Magnetic resonance imaging showed an old, small cerebral infarction in the left frontal white matter and no evidence of recent cerebral ischemia. Perfusion MR imaging with acetazolamide challenge demonstrated a reduced cerebrovascular reserve in both frontal lobes. Revascularization with bur hole surgery was performed, which resulted in complete regression of initial cognitive impairment. Improvement in cognitive function correlated with the development of transdural collaterals on angiography and improvement in cerebral perfusion on MR imaging. This case suggests a relationship between cognitive dysfunction and cerebral hypoperfusion in MMD. Cognitive impairment may be potentially reversible after bur hole surgery and cerebral perfusion improvement.