Systematic review with meta-analysis: pharmacological interventions for eosinophilic oesophagitis.

BACKGROUND: Eosinophilic oesophagitis (EoE) is a growing cause of dysphagia. Current therapies include dietary manipulation, steroids and biological drugs. AIM: To perform a systematic review and summarise the effect of different medical interventions on EoE. METHODS: Two reviewers searched Pubmed and Embase for studies on treatment for EoE. We included randomised controlled trials (RCT) limited to pharmacological interventions. Two reviewers selected studies. Meta-analysis was done using random effects model to estimate odds ratio (OR). Heterogeneity was determined by Cochran's Q statistic and I(2) . RESULTS: Seventeen references met our inclusion criteria. Eleven RCTs involving 455 participants were included in the meta-analysis. 325 participants were evaluated for symptomatic improvement and 330 were evaluated for histological remission. Symptomatic improvement with topical steroids (7 studies, 250 participants) compared to the control group (placebo or PPI) was noted (OR: 3.03, 95% confidence interval, CI: 1.57-5.87). Histological remission was also noted in nine studies involving 330 participants (OR: 13.66, 95% CI: 2.65-70.34) comparing topical steroids to a control (placebo or PPI). There was no difference between anti-IL-5 drugs and placebo in terms of symptomatic improvement (OR: 0.69, 95% CI: 0.34-1.42). CONCLUSIONS: Topical steroids induce significant symptomatic and histological remission, and should be considered as a first line treatment. Anti-IL-5 therapy has a minor effect on eosinophilic oesophagitis. Future research in eosinophilic oesophagitis should standardise methodology according to published guidelines to improve quality and allow direct comparison between therapies.

Meta-analysis: vitamin D and non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition. Emerging evidence suggests that vitamin D may play a role in the pathogenesis of NAFLD. AIM: To review systematically the association between vitamin D levels, measured as serum 25-hydroxy vitamin D [25(OH)D], and NAFLD. METHODS: We used PubMed and EMBASE databases to identify all studies that assessed the association between vitamin D and NAFLD up until 22 April 2013, without language restrictions. We included studies that compared vitamin D levels between NAFLD cases and controls and also those that compared the odds of vitamin D deficiency by NAFLD status. Pooled standardised differences and odds ratios were calculated using an inverse variance method. RESULTS: Seventeen cross-sectional and case-control studies have evaluated the association between vitamin D and NAFLD. NAFLD was diagnosed using biopsy (4 studies), ultrasound or CT (10 studies) and liver enzymes (3 studies). Nine studies provided data for a quantitative meta-analysis. Compared to controls, NAFLD patients had 0.36 ng/mL (95% CI: 0.32, 0.40 ng/mL) lower levels of 25(OH)D and were 1.26 times more likely to be vitamin D deficient (OR 1.26, 95% CI: 1.17, 1.35). CONCLUSIONS: NAFLD patients have decreased serum 25(OH)D concentrations, suggesting that vitamin D may play a role in the development of NAFLD. The directionality of this association cannot be determined from cross-sectional studies. Demonstration of a causal role of hypovitaminosis D in NAFLD development in future studies could have important therapeutic implications.

Estudio colaborativo de abortos espontáneos: empleo de técnicas moleculares en muestras cuyo resultado citogenético no puede ser establecido / Colaborative study of spontaneus abortion: use of molecular techniques in failure culture samples

Introducción. El conocimiento de la causa de abortopermite ofrecer un adecuado consejo genético, además dereducir el estrés psicológico y el sentimiento de culpabilidadgenerado en la mujer tras sufrir un aborto. En la actualidadel estudio de abortos se realiza mediante técnicas citogenéticas,aunque muchas veces no es posible ofrecer un diagnósticodebido al fracaso de cultivo que acontece entre el5-42 % de los casos. En este trabajo se pretende evaluar lasensibilidad de las técnicas moleculares para el estudio dealteraciones cromosómicas en aquellos casos cuyo resultadocitogenético no puede ser establecido.Metodología. Se han estudiado 70 muestras de abortosdel primer y segundo trimestre de gestación mediante citogenéticay genética molecular (Quantitative FluorescentPolymerase chain Reaction [QF-PCR] y Multiplex ligationdependentProbe Amplification [MLPA]).Resultados. No se pudo establecer un resultado citogenéticoen el 37,2 % de las muestras. 44 fueron cariotipadas,obteniéndose 37 cariotipos normales y 7 anómalos. El estudiomolecular permitió establecer una dotación cromosómicaen el 100% de los casos, se encontraron alteraciones en10, de los cuales 3 carecían de resultado citogenético.Conclusiones. Se propone incluir en el protocolo de estudiode abortos el empleo de las técnicas citadas en casode fracaso del cultivo celular. La colaboración entre laboratoriosde citogenética y genética molecular especializados,permitiría ofrecer un resultado a la mayoría de las pacientes,esencial a la hora de poder establecer un adecuado consejogenético(AU)

Introduction. The knowledge of miscarriage causepermits offering an appropriate genetic counselling andmoreover, reduces psychological distress and self blamefeelings in women with a miscarriage. Nowadays, chromosomalstudy of abortions is mostly performed usingcytogenetic techniques. In few cases, no diagnosis can beestablished due to the high rate of culture failure (5-42%). Here, we try to evaluate the usefulness of moleculartechniques for the chromosomal study of those casesin which a cytogenetic result can not be established.Methods. A total of 70 miscarriage samples from thefirst and second trimesters of gestation have been studiedby karyotyping and molecular techniques (QF-PCRy MLPA).Results. The karyotype could not be established in37.2% of cases. Karyotype could be obtained in 44 samples,being 37 normal and 7 chromosomally abnormal.Molecular studies permitted to obtain a result in 100% ofthe cases, finding abnormalities in 10 of them, including3 in which the karyotype had not been established.Conclusions. We propose the use of molecular techniquesin those cases in which the culture fails. The collaborationbetween cytogenetic and molecular laboratorieswould permit to establish a result in the majority ofcases, which would represent an improvement for the offeringof an appropriate genetic counselling(AU)

Transforming growth factor beta at clinical onset of Type 1 diabetes mellitus. A pilot study.

AIMS: The aims of the study were to determine whether transforming growth factor beta1 TGF-beta1 levels are raised at diagnosis of Type 1 diabetes mellitus and are related to blood glucose. SUBJECTS AND METHODS: Fourteen patients (mean age 24.3 +/- 4.9 years) admitted to hospital for onset of Type 1 diabetes were studied. On the first day of hospitalization, before insulin therapy, and at 1, 4 and 16 weeks, fasting blood glucose, HbA(1c), lipid profile and TGF-beta1 levels and TGF-beta1 levels in 24-h urine were determined. The control group included 14 non-diabetic subjects with similar characteristics to those of the diabetic group. RESULTS: Plasma and urinary TGF-beta1 levels were significantly lower in controls (4.7 (1.6-6.8) ng/ml P < 0.001; 5.7 (1.5-8.5) ng/mg urinary creatinine, P < 0.01) than in patients with Type 1 diabetes mellitus [10.5 (1.8-24.9) ng/ml; 10.1 (4.2-29.8) ng/mg urinary creatinine]. On study completion, HbA(1c) fell from 11.6 +/- 2.0 to 5.4 +/- 0.6% (P < 0.001). Improved metabolic control was not associated with changes in plasma (9.4 (2.6-19.5)/5.9 (1.6-21.5)/7.0 (2.3-30.2)/10.5 (1.8-24.9) ng/ml at baseline, 1, 4 and 16 weeks, respectively) or urinary (12.0 (4.7-29.5)/10.9 (1.5-20.5)/8.7 (4.3-16.9)/10.1 (4.2-29.8) ng/mg urinary creatinine) TGF-beta1 levels. A statistically significant correlation was observed between plasma TGF-beta1 and insulin dosage (U/kg/day) (r = 0.52, P = 0.037). CONCLUSIONS: The increased TGF-beta1 production observed herein was not modulated by glycaemic reduction and could be a response to immuno-inflammatory activation present at the onset of Type 1 diabetes.

Dominant T- and B-cell epitopes in an autoantigen linked to Chagas' disease.

In Chagas' disease caused by Trypanosoma cruzi, a paradigm of autoimmune disease, both autoantibodies and autoreactive T cells have been described. We have identified a novel dominant autoantigen, named Cha, recognized by the majority of sera from T. cruzi-infected humans and mice. We noted significant homologies between amino acids 120-129 of Cha, where the B-cell epitope maps, and an expressed sequence tag from T. cruzi, and also between amino acids 254-273 of Cha and a repeated amino acid sequence from the shed acute-phase antigen (SAPA) of T. cruzi. Moreover, T. cruzi-infected mice contain autoreactive T cells that can cross-react with Cha and the SAPA homologous peptides. Transfer of T cells from infected mice triggered anti-Cha (120-129) Ab production in naive recipients. Interestingly, heart tissue sections from those adoptive transferred mice showed cardiac pathology similar to T. cruzi-infected mice. Our results demonstrate the presence of both T- and B-cell cross-reactive epitopes in the Cha antigen. This dual mimicry may lead to T/B cell cooperation and give rise to a pathological immunodominant response against Cha in T. cruzi infected animals.