Factors related to gastric neuroendocrine tumors. / Factores relacionados a tumores neuroendocrinos gástricos.

INTRODUCTION AND AIMS: An association between long-term use of proton pump inhibitors and the development of gastric neuroendocrine tumors has been reported, but it is still a subject of debate. The aims of the present study were to determine the presence of this association in a Mexican population and to identify the risk factors for developing gastric neuroendocrine tumors. MATERIALS AND METHODS: A case-control study was conducted, in which the cases were patients with a histopathologic diagnosis of gastric neuroendocrine tumor and the controls were patients evaluated through upper endoscopy. The controls were paired by age, sex, and endoscopic examination indication. Proton pump inhibitor use was considered prolonged when consumption was longer than 5 years. RESULTS: Thirty-three patients with gastric neuroendocrine tumor and 66 controls were included in the study. Eighteen (54.5%) patients in the case group were women, as were 39 (59%) of the patients in the control group. The median age of the patients in the case group was 55 years (minimum-maximum range: 24-82) and it was 54 years (minimum-maximum range:18-85) in the control group. A greater number of patients in the gastric neuroendocrine tumor group presented with gastric atrophy (p<0.0001) and autoimmune atrophic gastritis (p=0.0002), compared with the control group. No association between gastric neuroendocrine tumor and prolonged proton pump inhibitor use, sex, smoking, gastroesophageal reflux disease, Helicobacter pylori infection, diabetes mellitus, or autoimmune diseases was found in the univariate analysis. CONCLUSIONS: The results of our study showed no association between proton pump inhibitor use for more than 5 years and the development of gastric neuroendocrine tumor. The presence of gastric atrophy and autoimmune atrophic gastritis was associated with gastric neuroendocrine tumor development.

How to improve the diagnosis of eosinophilic esophagitis: Experience from a case series in Mexico. / Cómo mejorar el diagnóstico de esofagitis eosinofílica: experiencia de una serie de casos en México.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic, immune disorder mediated largely by food antigens. It shares nonspecific symptoms with gastroesophageal reflux disease (GERD). EoE is rarely reported in Mexico, perhaps due to the racial characteristics of the population or because of insufficient diagnostic suspicion. AIMS: Our aim was to describe a Mexican cohort with EoE and evaluate the usefulness of the clinical history and endoscopy in the EoE diagnosis, in comparison with GERD patients. MATERIALS AND METHODS: A retrospective study was carried out on the clinical characteristics and endoscopic and histopathologic findings in patients with EoE, along with a case-control study on patients with GERD. The endoscopic images obtained were interpreted in a blind and randomized manner by 4 gastroenterologists, before and after providing them with information on the characteristic alterations of EoE. The esophageal biopsies were also blinded to 2 pathologists that evaluated their diagnostic correlation. The Fisher's exact test and Mann-Whitney U test were used in the statistical analysis. RESULTS: Fourteen patients with EoE were included in the study. Ten (71%) of them were men and the mean age of the patients was 35 years. There were more subjects with a personal history of asthma (p=0.0023) and food impaction (p=0.04) in the EoE group. The initial evaluation of the endoscopic findings showed 53% correct EoE interpretations and rose to 96% in the second revision (sensitivity 100%, specificity 71%, PPV 65%, NPV 100%). CONCLUSIONS: Mexican patients with EoE have similar characteristics to those of patients in western case series. Clinical awareness of the disorder increases endoscopic diagnosis in up to 40% of cases.

Quantitative T cell subsets profile in peripheral blood from patients with idiopathic inflammatory myopathies: tilting the balance towards proinflammatory and pro-apoptotic subsets.

The role of T cells in idiopathic inflammatory myopathies (IIM) is not yet clear. Some alterations in certain subsets have been reported in inflamed muscle cells. However, a broad quantitative assessment of peripheral T cell subsets has not been evaluated. The aim of this study was to address the quantitative profile of potential pathogenic T cell subsets, namely follicular helper T cells (Tfh), T helper type 17 (Th17), CD28(null) and regulatory T cells (Tregs ) in peripheral blood from IIM patients. Thirty IIM patients and 30 age- and gender-matched healthy donors were included. Peripheral blood mononuclear cells were isolated. T cell subsets were evaluated by flow cytometry, as follows: Tfh (CD4(+) CXCR5(+) ) and its subsets Tfh1 (CXCR3(+) CCR6(-) ), Tfh2 (CXCR3(-) CCR6(-) ), Tfh17 (CXCR3(-) CCR6(+) ), Th17 (CD4(+) IL17A(+) ), CD28(null) (CD4(+) CD28(-) CD244(+) ) and Tregs (CD4(+) CD25(high) forkhead box protein 3 (FoxP3(+) ); CD8(+) CD25(high) FoxP3(+) ). Percentage, absolute numbers and mean fluorescence intensity were analysed. We found increased numbers of total Tfh cells (28 ± 8.16 versus 6.64 ± 1.29, P=0.031) in IIM patients when compared to healthy controls. Moreover, this increment was dependent upon Tfh2 and Tfh17 (Tfh2:9.49 ± 2.19 versus 1.66 ± 0.46, P=0.005; Tfh17 9.48 ± 2.83 versus 1.18 ± 0.21, P=0.014). Also, IIM patients showed higher numbers of Th17 cells (30.25 ± 6.49 versus 13.46 ± 2.95, P=0.031) as well as decreased number of Tregs (5.98 ± 1.61 versus 30.82 ± 8.38, P=0.009). We also found an expansion of CD28(null) cells (162.88 ± 32.29 versus 64 ± 17.35, P=0.015). Our data suggest that IIM patients are characterized by an expansion of peripheral proinflammatory T cells, such as Tfh and Th17, as well as pro-apoptotic CD28 null cells and a deficiency of suppressor populations of Tregs (CD4(+) and CD8(+) ).

Interferon regulatory factor 3 as key element of the interferon signature in plasmacytoid dendritic cells from systemic lupus erythematosus patients: novel genetic associations in the Mexican mestizo population.

Many genetic studies have found an association between interferon regulatory factors (IRF) single nucleotide polymorphisms (SNPs) and systemic lupus erythematosus (SLE); however, specific dendritic cell (DC) alterations have not been assessed. The aim of the present study was to address the expression of IRF3 and IRF5 on different DC subsets from SLE patients, as well as their association with interferon (IFN)-α production and novel SNPs. For the genetic association analyses, 156 SLE patients and 272 healthy controls from the Mexican mestizo population were included. From these, 36 patients and 36 controls were included for functional analysis. Two IRF3 SNPs - rs2304206 and rs2304204 - were determined. We found an increased percentage of circulating pDC in SLE patients in comparison to controls (8.04 ± 1.48 versus 3.35 ± 0.8, P = 0.032). We also observed enhanced expression of IRF3 (64 ± 6.36 versus 36.1 ± 5.57, P = 0.004) and IRF5 (40 ± 5.25 versus 22.5 ± 2.6%, P = 0.010) restricted to this circulating pDC subset from SLE patients versus healthy controls. This finding was associated with higher IFN-α serum levels in SLE (160.2 ± 21 versus 106.1 ± 14 pg/ml, P = 0.036). Moreover, the IRF3 rs2304206 polymorphism was associated with increased susceptibility to SLE [odds ratio (OR), 95% confidence interval (CI) = 2.401 (1.187-4.858), P = 0.021] as well as enhanced levels of serum type I IFN in SLE patients who were positive for dsDNA autoantibodies. The IRF3 rs2304204 GG and AG genotypes conferred decreased risk for SLE. Our findings suggest that the predominant IRF3 expression on circulating pDC is a key element for the increased IFN-α activation based on the interplay between the rs2304206 gene variant and the presence of dsDNA autoantibodies in Mexican mestizo SLE patients.

Lymphopenia as risk factor for development of severe infections in patients with systemic lupus erythematosus: a case-control study.

OBJECTIVES: Hematological abnormalities, particularly lymphopenia, are common in patients with systemic lupus erythematosus (SLE), whether the disease is active or not. The aim of this study is to assess whether lymphopenia (blood counts ≤1000 K/µl) is a risk factor for severe infections in patients with SLE. METHODS: A retrospective case-control study was performed. We reviewed the clinical records of 167 SLE patients throughout a 5-year period. SLE patients with severe infections were compared with those without infection and the presence of lymphopenia was obtained from the blood count previous to the infection date. Also, other clinical and laboratory features as well as immunosuppressive therapy and SLE disease activity index (SLEDAI) were recorded. RESULTS: Univariate analysis shows multiple risk factors for severe infections in SLE, such as lymphopenia, high SLEDAI index, prednisone (PDN) and mycophenolate mofetil treatment and low levels of C3 and C4. Moreover, hydroxychloroquine treatment conferred protection. However, after multivariate analysis, only lymphopenia [odds ratio (OR) 5.2, 95% confidence interval (CI) 2.39-11.3], PDN treatment (OR 4.8, 95% CI 2.1-11.9) and low levels of C3 (OR 2.97, 95% CI 1.1-7.9) remained as independent risk factors. CONCLUSIONS: Our data suggest that lymphopenia, PDN treatment and low levels of C3 are independent risk factors for the development of severe infections in SLE patients, including diverse microorganisms, not only opportunistic infections.