Robot-assisted minimally invasive esophagectomy (RAMIE): tips and tricks from the bedside assistant view-expert experiences.

The role of bedside assistants in robot-assisted minimally invasive esophagectomy is important. It includes knowledge of the procedure, knowledge of the da Vinci Surgical System, skills in laparoscopy, and good communicative skills. An experienced bedside assistant will likely improve efficiency and safety of robot-assisted minimally invasive esophagectomy.

The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease.

OBJECTIVE: Intestinal dysbiosis has been associated with coeliac disease (CD), but whether the alterations are cause or consequence of the disease is unknown. This study investigated whether the human leukocyte antigen (HLA)-DQ2 genotype is an independent factor influencing the early gut microbiota composition of healthy infants at family risk of CD. DESIGN: As part of a larger prospective study, a subset (n=22) of exclusively breastfed and vaginally delivered infants with either high genetic risk (HLA-DQ2 carriers) or low genetic risk (non-HLA-DQ2/8 carriers) of developing CD were selected from a cohort of healthy infants with at least one first-degree relative with CD. Infant faecal microbiota was analysed by 16S rRNA gene pyrosequencing and real time quantitative PCR. RESULTS: Infants with a high genetic risk had significantly higher proportions of Firmicutes and Proteobacteria and lower proportions of Actinobacteria compared with low-risk infants. At genus level, high-risk infants had significantly less Bifidobacterium and unclassified Bifidobacteriaceae proportions and more Corynebacterium, Gemella, Clostridium sensu stricto, unclassified Clostridiaceae, unclassified Enterobacteriaceae and Raoultella proportions. Quantitative real time PCR also revealed lower numbers of Bifidobacterium species in infants with high genetic risk than in those with low genetic risk. In high-risk infants negative correlations were identified between Bifidobacterium species and several genera of Proteobacteria (Escherichia/Shigella) and Firmicutes (Clostridium). CONCLUSIONS: The genotype of infants at family risk of developing CD, carrying the HLA-DQ2 haplotypes, influences the early gut microbiota composition. This finding suggests that a specific disease-biased host genotype may also select for the first gut colonisers and could contribute to determining disease risk.

The R30Q DLG5 variant is not associated with celiac disease or inflammatory bowel disease in the Spanish population.

Alterations in intestinal epithelial permeability could underlie inflammatory bowel disease (IBD) and celiac disease (CeD) etiology, as supported by previous association studies. One related gene, DLG5 [discs, large homologue 5 (Drosophila)], has been associated with IBD in several populations and with CeD in the Dutch population. We tried to confirm the involvement of DLG5 in CeD performing a case-control study (725 CeD patients and 803 controls) by analysing the R30Q variant (rs1248696). Genetic frequencies did not significantly differ between groups (P > 0.80) and the meta-analysis with the Dutch data did not show any association. Additionally, we evaluated the effect of R30Q in IBD risk (858 patients), as discordant results were previously obtained. No association was detected. Our study does not support the effect of the R30Q DLG5 variant in CeD or IBD predisposition in the Spanish population.

Interplay between human leukocyte antigen genes and the microbial colonization process of the newborn intestine.

Coeliac disease (CD) development involves genetic (HLA-DQ2/DQ8) and environmental factors. Herein, the influence of the HLA-DQ genotype on the gut colonization process of breast-fed children was determined. A cohort of 20 newborns, with at least one first-degree relative with CD, were classified according to their HLA-DQ genotype into high, intermediate and low genetic risk groups, showing 24-28%, 7-8% and less than 1% probability to develop CD, respectively. Faecal microbiota was analysed at 7 days, 1 and 4 months of children's age by fluorescence in situ hybridization. When considering all data, Gram-negative bacteria and Bacteroides-Prevotella group proportions were higher (P<0.05) in the high than in the intermediate and low genetic risk groups. E. coli, Streptococcus-Lactococcus, E. rectale-C. coccoides, sulphate-reducing bacteria, C. lituseburense and C. histolyticum group proportions were also significantly higher (P<0.05) in the high than in the low genetic risk group. Correlations between these bacterial groups and the genetic risk were also detected (P<0.05). In addition, the number and type of CD relative seemed to influence (P<0.050) these bacterial proportions in children at CD risk. At 4 months of age, similar relationships were established between the high genetic risk to develop CD and the proportions of Streptococcus-Lactococcus (P<0.05), E. rectale-C. coccoides (P<0.05), C. lituseburense (P<0.05), C. histolyticum (P<0.05), Bacteroides-Prevotella (P<0.10) groups and total Gram-negative bacteria (P<0.05). The results suggest a relationship between HLA-DQ genes and the gut microbial colonization process that could lead to a change in the way this disorder is investigated.

The effect of a partially hydrolysed formula based on rice protein in the treatment of infants with cow's milk protein allergy.

Infants diagnosed with allergy to cow's milk protein (CMP) are fed extensively hydrolysed cow's milk formulas, modified soy formulas or even amino acid-based formulas. Hydrolysed rice protein infant formulas have become available and have been shown to be well tolerated by these infants. A prospective open, randomized clinical study to compare the clinical tolerance of a new hydrolysed rice protein formula (HRPF) with an extensively hydrolysed CMP formula (EHF) in the feeding of infants with IgE-mediated cow's milk allergy. Ninety-two infants (46 boys and 46 girls, mean age 4.3 months, range 1.1-10.1 months) diagnosed with IgE-mediated cow's milk allergy were enrolled in the study. Clinical tolerance to the formula products was tested. Clinical evaluation included skin prick tests with whole cow's milk, soya and rice as well as antigens of CMP (beta-lactoglobulin, alpha-lactalbumin, casein and bovine seroalbumin), HRPF and EHF and specific IgE determinations to CMP using CAP technology. Patients were randomized to receive either an EHF based on CMP or a new HRPF. Follow-up was at 3, 6, 12, 18 and 24 months. Growth parameters were measured at each visit. One infant showed immediate allergic reaction to EHF, but no reaction was shown by any infant in the HRPF group. The number of infants who did not become tolerant to CMP during the study was not statistically different between the two groups. Measurement of IgE levels of infants allergic to CMP during the study showed no significant differences between the two formula groups. Growth parameters were in the normal range and similar between groups. In this study, the HRPF was well tolerated by infants with moderate to severe symptoms of IgE-mediated CMP allergy. Children receiving this formula showed similar growth and development of clinical tolerance to those receiving an EHF. In accordance with current guidelines, this HRPF was tolerated by more than 90% of children with CMP allergy and therefore could provide an adequate and safe alternative to CMP-hydrolysed formulas for these infants.

Association of IL18RAP and CCR3 with coeliac disease in the Spanish population.

BACKGROUND AND AIMS: Genome-wide association studies in coeliac disease (CD) have resulted in the finding of eight new genetic regions associated with disease susceptibility. However, a replication study performed in the Italian population could not confirm two of those new regions: 2q12 (IL18RAP) and 3p21 (CCR3). The aim of this study was to investigate the role of those regions in CD risk in a different Mediterranean population, the Spanish population. METHODS: A case-control study with 722 patients with CD and 794 ethnically matched healthy controls was performed. Two single-nucleotide polymorphisms, rs917997 (2q12) and rs6441961 (3p21), were genotyped and their genetic frequencies were compared between both groups using the chi(2) test. RESULTS: An association was found with rs6441961 (p = 0.0004, OR = 1.32, 95% CI 1.13 to 1.54). A non-significant result (but concordant with the initial study) was obtained for rs917997. CONCLUSION: The association of the 3p21 genetic region with CD susceptibility in the Spanish population was confirmed. In 2q12, the initially described OR is most probably overestimated and therefore the real situation may be the existence of a genuine but weak risk factor, which generates statistical power limitations.

Lack of replication of celiac disease risk variants reported in a Spanish population using an independent Spanish sample.

Celiac disease (CD) is an inflammatory condition affecting small bowel and triggered by gluten (or related proteins) ingestion in genetic susceptible individuals. Polymorphisms in three genes, SERPINE2, PPP6C and PBX3, have recently been associated with CD in the Spanish population. However, this association could not be replicated in the UK population using imputed data. As this second study analyzed a different population, we aimed at reevaluating the role of those polymorphisms using an independent Spanish sample. We genotyped three single nucleotide polymorphisms: rs6747096 in SERPINE2, rs458046 in PPP6C and rs7040561 in PBX3, in 417 CD patients, 527 ethnically matched healthy controls and parents of 304 CD patients. A case-control study using the chi(2)-test and a familial study using the transmission disequilibrium test were performed. No association was detected in those analyses. Therefore, our results seem to discard the role of the previously described polymorphisms in SERPINE2, PPP6C and PBX3 in CD susceptibility.

Autoimmune disease association signals in CIITA and KIAA0350 are not involved in celiac disease susceptibility.

Celiac disease (CD) is a multifactorial disease characterized by intestinal inflammation after gluten exposure in genetically susceptible individuals. A strong influence of certain human leukocyte antigen (HLA) alleles (those coding the HLA-DQ2 and DQ8 heterodimers) is well established, but they cannot explain the overall genetic risk. CIITA could be a good candidate gene for CD because it is mainly transcriptionally regulated, and it encodes the master regulator of major histocompatibilty complex class II gene transcription. CIITA is located in 16p13, a region also containing KIAA0350 (CLEC16A), associated with two autoimmune diseases in genome-wide association studies. We aimed at studying the involvement of polymorphisms in CIITA and KIAA0350 in CD susceptibility, with special attention to evaluate the possible presence of more than one risk factor in the region. We performed a case-control study with 607 CD patients and up to 794 healthy controls, all Spaniards. All samples were genotyped for five single nucleotide polymorphisms: rs3087456 (-168A/G) and rs4774 in CIITA and rs7203459, rs6498169 and rs2903692 in KIAA0350. No significant results were obtained when comparing genotypic, allelic or haplotypic frequencies between patients and controls. Our results seem to discard the influence in CD susceptibility of CIITA and KIAA0350 markers previously associated with other autoimmune diseases.

[Comparison of dietary reference intakes (DRI) between different countries of the European Union, The United States and the World Health Organization]. / Comparativa de las Ingestas Dietéticas de Referencia (IDR) de los diferentes países de la Unión Europea, de Estados Unidos (EEUU) y de la Organización Mundial de la Salud (OMS).

BACKGROUND: In Spain, there are some organizations and scientific societies that have edited reference values of recommended nutrient intake, but whose data does not always agree in terms of format and content. AIMS: To review the definitions, data and methodology that other countries or groups of countries have followed to obtain and document their own reference values in order to offer basic information to facilitate the establishment of the best reference values for the Spanish population. FIELD: Review of the available information in different countries (or groups of countries) from the European Union, the United States and World Health Organization. The analysed data concerned to healthy populations. CONCLUSIONS: Reference intakes differ among the examined countries according to population groups, included nutrients, methodology and frequency of published reviews. However, most of the countries define major concepts in the same way, although with different names in each country. On the other hand, most of the studied cases represent only a scientific organization in charge of the publication and update of the values of dietary reference intakes, but not in Spain. In that context, it looks convenient to reach a consensus among all Spanish organizations and scientific societies that are involved in this task, in order to establish an acceptable reference values.