P3‐145: HEREDITARY SPASTIC PARAPLEGIA AND ALZHEIMER'S DISEASE: CLINICAL AND GENETIC STUDY OF A BRAZILIAN FAMILY

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Laparoscopic treatment of a yolk sac tumor. Case report and literature review

We report the case of a yolk sac tumor of the ovary in a 26 years old woman. The laparoscopic approach and the BEP chemotherapy were fundamental to have a minimally invasive treatment and to preserve fertilit

Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Dysregulated systemic inflammation is the primary driver of mortality in severe COVID-19 pneumonia. Current guidelines favor a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg·day-1. A comparative RCT with a higher dose and a longer duration of intervention was lacking

Disease-associated DNA methylation signatures in esophageal biopsies of children diagnosed with Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a leading cause of dysphagia and food impaction in children and adults. The diagnosis relies on histological examination of esophageal mucosal biopsies and requires the presence of > 15 eosinophils per high-powered field. Potential pitfalls include the impact of biopsy sectioning as well as regional variations of eosinophil density. We performed genome-wide DNA methylation analyses on 30 esophageal biopsies obtained from children diagnosed with EoE (n = 7) and matched controls (n = 13) at the time of diagnosis as well as following first-line treatment. Analyses revealed striking disease-associated differences in mucosal DNA methylation profiles in children diagnosed with EoE, highlighting the potential for these epigenetic signatures to be developed into clinically applicable biomarkers

Disease-associated DNA methylation signatures in esophageal biopsies of children diagnosed with Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a leading cause of dysphagia and food impaction in children and adults. The diagnosis relies on histological examination of esophageal mucosal biopsies and requires the presence of > 15 eosinophils per high-powered field. Potential pitfalls include the impact of biopsy sectioning as well as regional variations of eosinophil density. We performed genome-wide DNA methylation analyses on 30 esophageal biopsies obtained from children diagnosed with EoE (n = 7) and matched controls (n = 13) at the time of diagnosis as well as following first-line treatment. Analyses revealed striking disease-associated differences in mucosal DNA methylation profiles in children diagnosed with EoE, highlighting the potential for these epigenetic signatures to be developed into clinically applicable biomarkers

Does Azathioprine induce endoscopic and histologic healing in pediatric inflammatory bowel disease? A prospective, observational study

Background: The new concept of disease remission for pediatric inflammatory bowel diseases (IBD) implies the achievement of mucosal healing. Aims: We aimed to evaluate endoscopic and histologic healing in children with Ulcerative Colitis (UC) and Crohn's disease (CD) in clinical remission after 52 weeks of Azathioprine. Methods: From December 2012 to July 2015 we prospectively enrolled IBD children starting Azathioprine. Enrolled patients in clinical remission underwent colonoscopy after 52 weeks. Macroscopic assessment was described with Mayo score and the simplified endoscopic score for UC and CD, respectively. For microscopic assessment, an average histology score was used. Data on inflammatory markers and fecal calprotectin were also collected. Results: Fourty-seven patients were included in the analysis. Endoscopic healing was detected in 20/26 (76.9%) UC children and 10/21 (47.6%) CD patients. Median Mayo score and simplified endoscopic score were significantly decreased at week 52 (p < 0.001; p = 0.005). Median average histology score was not significantly different at week 52 in both diseases. Fecal calprotectin was directly correlated with simplified endoscopic score (T0: r = 0.4, p = 0.05; T52: r = 0.5, p = 0.01), but not with Mayo score. No correlation was found between endoscopic and histologic scores. Conclusions: IBD children under Azathioprine reach endoscopic healing, but not histological remission

Bifidobacteria enhance antigen sampling and processing by dendritic cells in pediatric inflammatory bowel disease

Bifidobacteria have been reported to reduce inflammation and contribute to intestinal homeostasis. However, the interaction between these bacteria and the gut immune system remains largely unknown. Because of the central role played by dendritic cells (DCs) in immune responses, we examined in vitro the effects of a Bifidobacteria mixture (probiotic) on DC functionality from children with inflammatory bowel disease. DCs obtained from peripheral blood monocytes of patients with Crohn's disease (CD), ulcerative colitis, and noninflammatory bowel disease controls (HC) were incubated with fluorochrome-conjugated particles of Escherichia coli or DQ-Ovalbumin (DQ-OVA) after a pretreatment with the probiotic, to evaluate DC phenotype, antigen sampling and processing. Moreover, cell supernatants were collected to measure tumor necrosis factor alpha, interferon gamma, interleukin 17, and interleukin 10 production by enzyme-linked immunosorbent assay. DCs from CD children showed a higher bacteria particles uptake and DQ-OVA processing after incubation with the probiotic; in contrast, DC from both ulcerative colitis and HC showed no significant changes. Moreover, a marked tumor necrosis factor alpha release was observed in DC from CD after exposure to E. coli particles, whereas the probiotic did not affect the production of this proinflammatory cytokine. In conclusion, the Bifidobacteria significantly improved the antigen uptake and processing by DCs from patients with CD, which are known to present an impaired autophagic functionality, whereas, in DCs from ulcerative colitis and HC, no prominent effect of probiotic mixture was observed. This improvement of antigen sampling and processing could partially solve the impairment of intestinal innate immunity and reduce uncontrolled microorganism growth in the intestine of children with inflammatory bowel disease

T300A variant of autophagy ATG16L1 gene is associated with decreased antigen sampling and processing by dendritic cells in pediatric Crohn's disease

The single-nucleotide polymorphism T300A of ATG16L1, a Crohn's disease (CD)-associated gene, is responsible for decreased autophagy. This study aimed to investigate the effects of this single-nucleotide polymorphism on the uptake and processing of antigens by dendritic cells (DCs) and the interaction between DC and intestinal epithelium in pediatric patients with CD. Pediatric patients who homozygously carry either the protective (wild type, n = 7) or risk allele (risk, n = 13) of ATG16L1, as well as heterozygous patients (het, n = 13) were enrolled. The monocyte-derived DC were analyzed for phenotype, antigen sampling, and processing by flow cytometry, whereas the capability of DC to form transepithelial protrusions was determined by confocal microscopy. DC generated from wild type patients showed higher bacteria sampling and antigen processing compared with risk patients. Additionally, after exposure to either bacteria particles or the antigen DQ-ovalbumin, wild type DC showed a significant increase in the expression of the HLA-DR and CD86 when compared with risk DC. Interestingly, also het patients showed an impairment in bacteria uptake and expression of activation marker when compared with the wild type. In the Caco2/DC coculture, the formation of transepithelial protrusions were less numerous in risk DC compared with wild type and the antigen uptake decreased. DC of pediatric patients with CD carrying the T300A allele showed a marked impairment of antigen uptake and processing and defective interactions between DC and intestinal epithelium. Collectively, our results suggest that an autophagy defect is associated with an impairment of intestinal innate immunity in pediatric C