Expanding the clinical spectrum of STIP1 homology and U-box containing protein 1-associated ataxia

Journal of Neurology - STUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1...     

Meta-analysis: hyperhomocysteinaemia in inflammatory bowel diseases

Aliment Pharmacol Ther 2011; 34: 1173–1184

Summary

Background The magnitude of association between homocysteine metabolism and inflammatory bowel diseases (IBD) remains unknown, whereas the association between hyperhomocysteinaemia and thrombosis remains controversial in IBD. Aim To conduct a systematic review and meta‐analysis to examine these issues. Methods The literature search was conducted using MEDLINE database and international conference abstracts from January 1966 to April 2011 and included all studies that evaluated plasma homocysteine level in IBD. Results Twenty‐eight studies evaluated the plasma homocysteine level and/or hyperhomocysteinaemia risk in IBD patients. Five studies assessed the association of hyperhomocysteinaemia with thrombosis. The mean plasma homocysteine level was significantly higher in IBD patients when compared with controls (weighted mean difference (WMD) = 3.75 μmol/L; 95% CI, 2.23–5.26 μmol/L; P < 0.0001; reference ranges for plasma homocysteine level: 5–12 μmol/L). The mean plasma homocysteine level did not differ between ulcerative colitis (UC) and Crohn’s disease (CD) (WMD = 0.41 μmol/L; 95% CI, −2.45 to 3.06 μmol/L; P = 0.76). The risk of hyperhomocysteinaemia was significantly higher in IBD patients when compared with controls [odds ratio (OR) = 4.65; 95% CI, 3.04–7.09; P < 0.0001]. The risk of hyperhomocysteinaemia was not higher among IBD patients who experienced thromboembolic complications (OR = 1.97; 95% CI, 0.83–4.67; P = 0.12). Plasma folate level was inversely correlated with IBD risk associated with MTHFR C677T polymorphism (P = 0.006). Conclusions The risk of hyperhomocysteinaemia is significantly higher in IBD patients when compared with controls. The risk assessment of hyperhomocysteinaemia–related thrombosis in IBD requires further investigation. Deficient folate status is associated with a higher impact of MTHFR C677T polymorphism on IBD risk.

     

The use of azathioprine in Crohn's disease during pregnancy and in the post-operative setting: a worldwide survey of experts

Aliment Pharmacol Ther 2011; 33: 707–713

Summary

Background Although thiopurines are considered safe in humans, they are still pregnancy FDA category D drugs. Prevention of post‐operative recurrence is a challenge in clinical practice in Crohn’s disease. The European Crohn’s and Colitis Organisation consensus states that thiopurines should be considered in high‐risk patients. Aim To perform a worldwide survey for evaluating the extent to which gastroenterologists who are experts in the field of IBD are utilising thiopurines during pregnancy and in the post‐operative setting in Crohn’s disease. Methods This was a Web‐based cross‐sectional, statement‐based survey, which was conducted among experts who have published at least once in the field of thiopurines in IBD. Results Between 20 December 2009 and 9 April 2010, 175 questionnaires were received. The median number of IBD patients per physician per year was 400 (IQR 25–75th, 188–600) and the total number of IBD patients followed by all responders was 82 379. In a pregnant woman with a history of severe Crohn’s disease in clinical remission after 1 year on azathioprine, 89% of experts usually continue azathioprine until delivery and 9% of physicians never administrate azathioprine during pregnancy. After ileocecal resection for Crohn’s disease, 39% of physicians initiate azathioprine only in high‐risk patients, 28% of practitioners prescribe azathioprine according to endoscopic evaluation, 20% of gastroenterologists systematically initiate azathioprine and 13% have a different attitude. Conclusions Almost 9 of 10 physicians continue azathioprine throughout pregnancy. About 7 of 10 physicians prescribe azathioprine in the post‐operative setting according to the European Crohn’s and Colitis Organisation recommendations, whereas one‐fifth of practitioners systematically initiate azathioprine after surgery.     

Additional benefit of procalcitonin to C-reactive protein to assess disease activity and severity in Crohn's disease

Aliment Pharmacol Ther 2010; 32: 1135–1144

Summary

Background Serum procalcitonin level may reflect non‐infectious inflammation. Aim To assess the correlation of serum procalcitonin level with clinical, biological, endoscopic and radiological markers of disease activity in inflammatory bowel diseases (IBD), and to evaluate the additional diagnostic benefit of measuring serum procalcitonin level to that of C‐reactive protein (CRP) for disease activity appraisal. Methods We performed a prospective observational study. Spearman’s rank correlation and receiver operating characteristic analysis were used to evaluate correlation and diagnostic accuracy respectively. Results In Crohn’s disease (CD) (n = 30), serum procalcitonin level was strongly correlated with clinical, biological, endoscopic and radiological disease activity markers. In CD, the serum procalcitonin level >0.14 μg/L demonstrated a high accuracy for detecting severe disease (Sensitivity = 100%; Specificity = 96%; AUROC = 0.963; P = 0.0001). The diagnostic accuracy of the ‘serum procalcitonin level‐CRP strategy’ (CRP >5 mg/L and serum procalcitonin level >0.05 μg/L) was significantly superior to that of CRP alone for diagnosing severe CD (AUROC = 0.783 vs. 0.674; P = 0.01). In ulcerative colitis (UC) (n = 27), serum procalcitonin level was correlated with CRP and with endoscopic and radiological disease activity markers. Conclusions In CD, the serum procalcitonin level was correlated with all disease activity markers and a cut‐off of 0.14 μg/L could distinguish severe forms of the disease. The ‘serum procalcitonin level‐CRP strategy’ was superior to CRP alone for diagnosing active or severe CD.