Re-bleeding events in patients with obscure gastrointestinal bleeding after negative capsule endoscopy

AIM: To investigate long-term re-bleeding events after a negative capsule endoscopy in patients with obscure gastrointestinal bleeding(OGIB) and the risk factors associated with the procedure.METHODS: Patients referred to Hospital Egas Moniz(Lisboa, Portugal) between January 2006 and October 2012 with OGIB and a negative capsule endoscopy were retrospectively analyzed. The following study variables were included: demographic data, comorbidities, bleeding-related drug use, hemoglobin level, indication for capsule endoscopy, post procedure details, work-up and follow-up. Re-bleeding rates and associated factors were assessed using a Cox proportional hazard analysis. The Kaplan-Meier method was used to estimate the cumulative incidence of re-bleeding at 1, 3 and 5 years, and the differences between factors were evaluated.RESULTS: The study population consisted of 640 patients referred for OGIB investigation. Wireless capsule endoscopy was deemed negative in 113 patients(17.7%). A total of 64.6% of the population was female, and the median age was 69 years. The median follow-up was forty-eight months(interquartile range 24-60). Re-bleeding occurred in 27.4% of the cases. The median time to re-bleeding was fifteen months(interquartile range 2-33). In 22.6%(n = 7) of the population, small-bowel angiodysplasia was identified as the culprit lesion. A univariate analysis showed that age > 65 years old, chronic kidney disease, aortic stenosis, anticoagulant use and overt OGIB were risk factors for re-bleeding; however, on a multivariate analysis, there were no risk factors for re-bleeding. The cumulative risk of re-bleeding at 1, 3 and 5 years of follow-up was 12.9%, 25.6% and 31.5%, respectively.Patients who presented with overt OGIB tended to rebleed sooner(median time for re-bleeding: 8.5 mo vs 22 mo).CONCLUSION: Patients with OGIB despite a negative capsule endoscopy have a significant re-bleeding risk; therefore, these patients require an extended follow-up strategy.

Monoclonal gammopathy of renal significance:Diagnostic workup

The clinical spectrum of diseases associated withmonoclonal gammopathies is wide and they are most commonly the consequence of renal deposition of monoclonal immunoglobulin or its components. The differential diagnosis is difficult and renal biopsy is essential. To distinguish many of these pathologies is necessary to use techniques that are not always avai-lable, even in tertiary central hospitals. This review will discuss the clinical presentation, pathologic features, treatment, prognosis and common diagnostic diffculties of these entities.

Impact of preformed donor-specific antibodies against HLA class Ⅰ on kidney graft outcomes:Comparative analysis of exclusively anti-Cw vs anti-A and/or-B antibodies

AIM To analyze the clinical impact of preformed antiH LA-Cw vs antiH LA-A and/or-B donor-specific antibodies(DSA) in kidney transplantation.METHODS Retrospective study, comparing 12 patients transplanted with DSA exclusively antiH LA-Cw with 23 patients with preformed DSA antiH LA-A and/or B.RESULTS One year after transplantation there were no differencesin terms of acute rejection between the two groups(3 and 6 cases, respectively in the DSA-Cw and the DSA-A-B groups; P = 1). At one year, eG FR was not significantly different between groups(median 59 mL /min in DSA-Cw group, compared to median 51 mL /min in DSA-A-B group, P = 0.192). Moreover, kidney graft survival was similar between groups at 5-years(100% in DSA-Cw group vs 91% in DSA-A-B group, P = 0.528). The sole independent predictor of antibody mediated rejection(AMR) incidence was DSA strength(HR = 1.07 per 1000 increase in MFI, P = 0.034). AMR was associated with shortened graft survival at 5-years, with 75% and 100% grafts surviving in patients with or without AMR, respectively(Log-rank P = 0.005).CONCLUSION Our data indicate that DSA-Cw are associated with an identical risk of AMR and impact on graft function in comparison with "classical" class I DSA.

Penicillamine and auto-immunity:Relationship or coincidence?

Drug induced lupus is an established and recognised entity,and penicillamine is one of the drugs that induce it.But the uncertainty remains:Could penicillamine trigger autoimmunity in a broad-spectrum or in a particular way?

Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity

T-cell development ensures the formation of diverse repertoires of T-cell receptors(TCRs)that recognize a variety of antigens.Glycosylation is a major posttranslational modification present in virtually all cells,including T-lymphocytes,that regulates activity/functions.Although these structures are known to be involved in TCR-selection in DP thymocytes,it is unclear how glycans regulate other thymic development processes and how they influence susceptibility to disease.Here,we discovered stage-specific glycome compositions during T-cell development in human and murine thymocytes,as well as dynamic alterations.After restricting the N-glycosylation profile of thymocytes to high-mannose structures,using specific glycoengineered mice(Rag1CreMgat1fl/fl),we showed remarkable defects in key developmental checkpoints,includingß-selection,regulatory T-cell generation andγδT-cell development,associated with increased susceptibility to colon and kidney inflammation and infection.We further demonstrated that a single N-glycan antenna(modeled in Rag1CreMgat2fl/fl mice)is the sine-qua-non condition to ensure normal development.In conclusion,we revealed that mannosylated thymocytes lead to a dysregulation in T-cell development that is associated with inflammation susceptibility.