Are xenogeneic anti-tissue transglutaminase antibodies the holy grail for celiac patients?

Celiac disease is an immune mediated disorder, the only one with a well-established origin, resulting from a permanent gluten intolerance. Although a gluten-free diet is currently the "safe" and appropriate therapy for celiac disease, this is not always an easy and simple option as "harmful" gluten may contaminate food during the processing and preparation phases. There are also further social pressures, which might be more pressing for young celiac patients, in following a strict gluten-free diet. Therefore, a new therapeutic approaches are sought which would permit celiacs to "peacefully" coexist with gluten. Presently, the most promising looks search for genetically modified wheat lacking toxic gluten peptides and the use of oral endopeptidases in attempt to curb gluten toxicity. Recently discovered role of anti-tissue transglutaminase antibodies in celiac pathogenesis has brought a prospect for a new hypothetical therapeutic approach, an oral immunization of celiacs with xenogeneic anti-tissue transglutaminase antibodies.     

The additive prognostic value of restrictive pattern and dipyridamole-induced contractile reserve in idiopathic dilated cardiomyopathy

BACKGROUND: Diastolic dysfunction and lack of contractile reserve are unfavorable prognostic predictors in patients with dilated cardiomyopathy (DCM). AIMS: This study aims to assess whether diastolic dysfunction and lack of dipyridamole-induced contractile reserve were additive predictors of poor outcome in patients with DCM. METHODS: A total of 116 patients with DCM and ejection fraction (EF<35%) were studied by dipyridamole echo (0.84 mg/kg over 10 min). At rest, a restrictive filling pattern was defined as: E/A ratio >2 and an E-wave deceleration time of <140 ms on transmitral flow velocity profile. RESULTS: Rest wall motion score index (WMSI) was 2.2+/-0.3 and decreased to 1.9+/-0.41 after dipyridamole (p<0.001). During follow-up (median 26.5 months), 22 cardiac deaths occurred. At multivariate analysis, dipyridamole-induced contractile reserve yielded significant incremental prognostic value (RR=0.275, p<0.006) over NYHA class (RR=1.971, p<0.03), angiotensin-converting enzyme inhibitor therapy (RR=0.173, p<0.001), and left ventricular end-diastolic diameter (RR=1.131, p<0.001). The worst prognostic combination was the presence of restrictive pattern at rest and the absence of contractile reserve (deltaWMSI<0.15). CONCLUSION: In patients with DCM, the ominous combination of restrictive transmitral flow pattern and lack of contractile reserve during dipyridamole stress predicts an unfavourable outcome.     

Treatment of iron deficiency anemia in pediatric inflammatory bowel disease

Opinion statement Anemia is a frequent extraintestinal manifestation of inflammatory bowel disease (IBD) that is commonly overlooked, despite its significant impact on quality of life. Characteristic symptoms include chronic fatigue, headache, and subtle impairment of cognitive function, although some less common symptoms include dyspnea, dizziness, pica, angular stomatitis, shortened attention span, and esophageal webs. Several types of anemia are associated with IBD, but iron deficiency anemia (IDA) accounts for the majority of cases and others include anemia of chronic disease, anemia associated with vitamin deficiency (vitamin B₁₂ and folate), autoimmune anemia, and anemia caused by medication used to treat IBD. The diagnosis of IDA relies on laboratory blood tests. Therefore, these tests should be obtained on a regular basis because characteristic symptoms may be absent or not readily recognized by patients and their clinicians. Complete blood count may suffice; however, iron studies and serum vitamin levels may be necessary to differentiate between specific types of anemia. During the diagnostic process, it is important to consider coexistence of different types of anemia, especially if no response to therapy is noted. The therapy for anemia is directed towards treatment of the underlying inflammatory process and supplemental therapy, depending on the type of deficiency. Iron deficiency anemia is treated with iron preparations, first orally, and if unresponsive or if associated with untoward adverse events leading to decrease in adherence with the therapeutic regimen, with intravenous preparations. Intramuscular therapy has been abandoned due to high rate of complications. Intravenous therapy may be administered as a multiple-dose regimen (intravenous iron sucrose and gluconate) or as a single intravenous dose (iron dextran), which is associated with a higher risk of allergic infusion reactions and requires obligatory test dose administration. Treatment with erythropoietin is reserved for a select subgroup of patients with anemia of chronic disease. With appropriate treatment, the majority of patients with IBD will have significant improvement or resolution of anemia, which can lead to a better quality of life. However, a high index of suspicion should be maintained in order to identify the precise cause of anemia and to prescribe the appropriate therapy.