HLA-DQ typing in the diagnostic algorithm of celiac disease.

Objective: celiac disease (CD) is an immune-mediated chronic inflammatory disease associated with HLA-DQ2 and DQ8 molecules. We evaluated the role of HLA in the CD diagnostic algorithm in order to contribute to the development of practical indications for the use of HLA typing. Material and methods: we selected 317 subjects typed for DR-DQ genes. CD was present in 123 patients, and 89 were included in the study; a control sample of 70 healthy individuals was recruited. Results: 64% of patients with CD carried DQ2 heterodimer (α5β2), 13.5% carried DQ8 heterodimer without DQ2, 21.4% only showed β2 chain and 1.1% were positive for DQ2 α5 chain. The only presence of α5 chain did not predispose to CD, while DQB1*02 allele resulted more frequent than in other reports, pointing out the intrinsic correlation between β2 chain and CD. In the case-control study we observed a progression of increased risk, ranging from 1:7 for HLA-DQ2 homozygous to 1:85 for DQ8 heterozygous subjects. Overall, 8,6% of first degree family members were affected, exclusively in presence of HLA-DQ2, -DQ8 or DQB1*02, and CD was significantly more frequent among siblings than parents. Finally, considering the different patterns of clinical presentation among the HLA-DQ risk classes identified we found no relationship between CD clinical presentation and HLA-DQ risk categories. Conclusions: our results strengthen the evidence that HLA-DQ status strongly influences the development of CD and demonstrate that knowledge of a patient's HLA-DQ genotype allows to establish clinically relevant genetic risk profiles

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Petechial rash associated with Parvovirus B19 in children: case report and literature review

Human Parvovirus B19 (B19V) infection usually causes erythema infectiosum (EI). In recent decades, several uncommon exanthems have been described in association with B19V. Recently, haemorrhagic manifestations such as purpuric-petechial rash have been reported. We describe an unusual paediatric case of B19V associated with generalized petechial eruption, and a review of the recent literature

Testing for fecal gluten immunogenic peptides: a useful tool to evaluate compliance with gluten-free diet by celiacs

Background: Although experts agree that strict dietary compliance is fundamental for the health of celiac patients, there are no evidence-based recommendations on the best way to assess dietary compliance. Detection of gluten immunogenic peptides (GIPs) in feces was recently proposed as an effective method of assessing the dietary compliance of celiac patients. Methods: Fifty-five consecutive celiac patients (27 adults and 28 children, age 6-72 years), who had been on a gluten-free diet for at least 2 years, were enrolled. All patients were evaluated clinically for symptoms, physical parameters and laboratory parameters. Dietary compliance was assessed with the Biagi questionnaire and serum anti-tissue transglutaminase (tTG) IgA antibodies were measured. GIPs were determined by immunoenzymatic assay on an automated Chorus analyzer (DIESSE Diagnostica Senese), after extraction of fecal samples by the method developed by DIESSE. Results: Eight patients tested positive for GIPs (GIPs+); 71.4% of GIP-positive patients were asymptomatic; tTG antibodies were detected in 3/8 GIP+ patients. The Biagi score was significantly associated with fecal positivity for GIPs (P=0.02). However, according to the Biagi score, 57.1% of GIP+ patients followed the diet strictly and 5.4% of GIP- subjects did not comply with the diet or made substantial mistakes. Conclusions: Assay of fecal GIPs identified more patients who did not comply with the diet than did the Biagi questionnaire, evaluation of symptoms or anti-tTG antibodies. Detection of fecal GIPs offers a direct, objective, quantitative assessment of even occasional exposure to gluten and is confirmed as a practical way to check dietary compliance. © 2020, Hellenic Society of Gastroenterology. All rights reserved

HLA-DQ typing in the diagnostic algorithm of celiac disease

Objective: celiac disease (CD) is an immune-mediated chronic inflammatory disease associated with HLA-DQ2 and DQ8 molecules. We evaluated the role of HLA in the CD diagnostic algorithm in order to contribute to the development of practical indications for the use of HLA typing. Material and methods: we selected 317 subjects typed for DR-DQ genes. CD was present in 123 patients, and 89 were included in the study; a control sample of 70 healthy individuals was recruited. Results: 64% of patients with CD carried DQ2 heterodimer (α5β2), 13.5% carried DQ8 heterodimer without DQ2, 21.4% only showed β2 chain and 1.1% were positive for DQ2 α5 chain. The only presence of α5 chain did not predispose to CD, while DQB1*02 allele resulted more frequent than in other reports, pointing out the intrinsic correlation between β2 chain and CD. In the case-control study we observed a progression of increased risk, ranging from 1:7 for HLA-DQ2 homozygous to 1:85 for DQ8 heterozygous subjects. Overall, 8,6% of first degree family members were affected, exclusively in presence of HLA-DQ2, -DQ8 or DQB1*02, and CD was significantly more frequent among siblings than parents. Finally, considering the different patterns of clinical presentation among the HLA-DQ risk classes identified we found no relationship between CD clinical presentation and HLA-DQ risk categories. Conclusions: our results strengthen the evidence that HLA-DQ status strongly influences the development of CD and demonstrate that knowledge of a patient's HLA-DQ genotype allows to establish clinically relevant genetic risk profiles

HLA-DQ typing in the diagnostic algorithm of celiac disease Tipificación HLA-DQ en el algoritmo diagnóstico de la enfermedad celíaca

Objective: celiac disease (CD) is an immune-mediated chronic inflammatory disease associated with HLA-DQ2 and DQ8 molecules. We evaluated the role of HLA in the CD diagnostic algorithm in order to contribute to the development of practical indications for the use of HLA typing. Material and methods: we selected 317 subjects typed for DR-DQ genes. CD was present in 123 patients, and 89 were included in the study; a control sample of 70 healthy individuals was recruited. Results: 64% of patients with CD carried DQ2 heterodimer (&#945;5&#946;2), 13.5% carried DQ8 heterodimer without DQ2, 21.4% only showed &#946;2 chain and 1.1% were positive for DQ2 &#945;5 chain. The only presence of &#945;5 chain did not predispose to CD, while DQB1*02 allele resulted more frequent than in other reports, pointing out the intrinsic correlation between &#946;2 chain and CD. In the case-control study we observed a progression of increased risk, ranging from 1:7 for HLA-DQ2 homozygous to 1:85 for DQ8 heterozygous subjects. Overall, 8,6% of first degree family members were affected, exclusively in presence of HLA-DQ2, -DQ8 or DQB1*02, and CD was significantly more frequent among siblings than parents. Finally, considering the different patterns of clinical presentation among the HLA-DQ risk classes identified we found no relationship between CD clinical presentation and HLA-DQ risk categories. Conclusions: our results strengthen the evidence that HLA-DQ status strongly influences the development of CD and demonstrate that knowledge of a patient's HLA-DQ genotype allows to establish clinically relevant genetic risk profiles

Overlapping microdeletions involving 15q22.2 narrow the critical region for intellectual disability to NARG2 and RORA

Microdeletions in the 15q22 region have not been well documented. We collected genotype and phenotype data from five patients with microdeletions involving 15q22.2, which were between 0.7 Mb and 6.5 Mb in size; two were of de novo origin and one was of familial origin. Intellectual disability and epilepsy are frequently observed in patients with 15q22.2 deletions. Genotype-phenotype correlation analysis narrowed the critical region for such neurologic symptoms to a genomic region of 654 Kb including the NMDA receptor-regulated 2 gene (NARG2) and the PAR-related orphan receptor A gene (RORA), either of which may be responsible for neurological symptoms commonly observed in patients with deletions in this region. The neighboring regions, including the forkhead box B1 gene (FOXB1), may also be related to the additional neurological features observed in the patients with larger deletions

Coffin-Siris and Nicolaides-Baraitser syndromes are a common well recognizable cause of intellectual disability

Nicolaides-Baraitser and Coffin-Siris syndromes are emerging conditions with overlapping clinical features including intellectual disability and typical somatic characteristics, especially sparse hair, low frontal hairline, large mouth with thick and everted lips, and hands and feet anomalies. Since 2012, mutations in genes encoding six proteins of the BAF complex were identified in both conditions.publisher: Elsevier articletitle: Coffin–Siris and Nicolaides–Baraitser syndromes are a common well recognizable cause of intellectual disability journaltitle: Brain and Development articlelink: http://dx.doi.org/10.1016/j.braindev.2014.08.009 content_type: article copyright: Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.status: publishe