Celiac disease: Prevalence, diagnosis, pathogenesis and treatment

Celiac disease(CD) is one of the most common diseases,resulting from both environmental(gluten) and genetic factors [human leukocyte antigen(HLA) and nonHLA genes].The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world.However,the population with diabetes,autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD,at least in part,because of shared HLA typing.Gliadin gains access to the basal surface of the epithelium,and interact directly with the immune system,via both trans-and para-cellular routes.From a diagnostic perspective,symptoms may be viewed as either "typical" or "atypical".In both positive serological screening results suggestive of CD,should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet(GFD) to confirm the diagnosis.Positive anti-tissue transglutaminase antibody or antiendomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy.Currently,the only treatment available for CD individuals is a strict life-long GFD.A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide,prevent toxic gliadin peptide absorption,blockage of selective deamidation of specific glutamine residues by tissue,restore immune tolerance towards gluten,modulation of immune response to dietary gliadin,and restoration of intestinal architecture.     

Fate of the aortic root after arterial switch operation.

OBJECTIVE: Concerns have been voiced about possible dilation and insufficiency of the neo-aortic valve after the arterial switch operation (ASO). AIMS: To determine growth of the neo-aortic valve and the aortic anastomosis after ASO and the prevalence of insufficiency or stenosis. PATIENTS AND METHODS: Since 1977, 144 consecutive patients (pts) underwent ASO for transposition of the great arteries (TGA). Median follow-up was 8.65 years (0.1--22.5 years). Simple TGA was present in 97 pts and 47 had TGA with ventricular septal defect (VSD). Detailed echocardiography included measurements of aortic diameter at four levels. The 608 measurements were compared with published normal values. RESULTS: The mean aortic valve z-score was 1.5, without significant change with age (P=0.75). Under 4 months, mean valve z-score was 0.63+/-2.20, between 5 and 12 months 2.56+/-2.30 (P<0.0001). Gradual growth occurs thereafter. The aortic sinus follows an identical growth pattern. The aorta at the anastomosis, is initially smaller than normal (z-score -0.64). After 4 months the z-score is 0.83, followed by continued growth of 0.1 z-score per year. At the last visit, the aortic valve z-score was above 2 in 51 patients, between -2 and 2 in 72 and less than -2 in six patients, none of whom had a flow velocity above 2 m/s. z-score of patients with VSD remained above those without VSD (P<0.0001).Aortic insufficiency was grade 2/4 in three patients, grade 3/4 in one and grade 4/4 in one. No patient developed aortic stenosis. CONCLUSION: After ASO the neo-aortic valve and sinus are larger than normal, representing the natural size difference in the prenatal situation and influence of associated cardiac malformations. In the first year of life, rapid dilatation of the new aorta is observed, followed by growth towards normalization of the valve and sinus size. Stenosis at the anastomosis was not observed. Aortic dilatation by itself is rarely associated with significant insufficiency.     

High Rate of Mutational Events in SARS-CoV-2 Genomes across Brazilian Geographical Regions,February 2020 to June 2021

Brazil was considered one of the emerging epicenters of the coronavirus pandemic in 2021, experiencing over 3000 daily deaths caused by the virus at the peak of the second wave. In total, the country had more than 20.8 million confirmed cases of COVID-19, including over 582,764 fatalities. A set of emerging variants arose in the country, some of them posing new challenges for COVID-19 control. The goal of this study was to describe mutational events across samples from Brazilian SARS-CoV-2 sequences publicly obtainable on Global Initiative on Sharing Avian Influenza Data-EpiCoV (GISAID-EpiCoV) platform and to generate indexes of new mutations by each genome. A total of 16,953 SARS-CoV-2 genomes were obtained, which were not proportionally representative of the five Brazilian geographical regions. A comparative sequence analysis was conducted to identify common mutations located at 42 positions of the genome (38 were in coding regions, whereas two were in 5′ and two in 3′ UTR). Moreover, 11 were synonymous variants, 27 were missense variants, and more than 44.4% were located in the spike gene. Across the total of single nucleotide variations (SNVs) identified, 32 were found in genomes obtained from all five Brazilian regions. While a high genomic diversity has been reported in Europe given the large number of sequenced genomes, Africa has demonstrated high potential for new variants. In South America, Brazil, and Chile, rates have been similar to those found in South Africa and India, providing enough “space” for new mutations to arise. Genomic surveillance is the central key to identifying the emerging variants of SARS-CoV-2 in Brazil and has shown that the country is one of the “hotspots” in the generation of new variants.     

Potential Additional Indicators for Pacemaker Requirement in Isolated Congenital Atrioventricular Block

Low heart rate is the predominantly used indication for pacemaker intervention in patients with isolated congenital atrioventricular block (CAVB). The aim of this study was to compare the difference in heart rates recorded with ECG and Holter monitoring between paced (PM) and nonpaced (NPM) patients with isolated CAVB before pacemaker implantation to identify additional predictors for future PM need. Retrospective evaluation of atrial and ventricular rates (electrocardiography) and minimal and maximal (Holter) heart rates in 129 CAVB patients prior to PM implantation (n = 93) was performed, and results are expressed in V adjusted for age and sex. The average V score for the atrial rate was 0.51 (n = 50) in the PM group and 0.60 (n = 22) in the NPM group (not-significant). The average z score for the ventricular (average) rate was −0.91 (n = 83) in the PM group and −0.93 (n = 33) in the NPM group (not-significant). Minimal heart rate was −0.94 (n = 61) in the PM group and −0.86 (n = 25) in the NPM group (not significant). Maximal heart rate was −0.96 (n = 61) in the PM group and −0.95 (n = 26) in the NPM group (not significant). Initial recordings of the average heart rate and the minimal and maximal heart rate recorded during Holter monitoring do not seem to predict future pacemaker need in patients with CAVB. Studies with exercise stress tests are needed to confirm these findings.     

Prenatal ultrasound diagnosis of clubfoot

Five cases of congenital clubfoot diagnosed prenatally by ultrasound are reported. The incidence of clubfoot may be higher within an affected family and may be associated with other structural anomalies or chromosomal abnormalities. Identifying a clubfoot in utero should therefore alert the sonographer that other anomalies may be present and should lead to a detailed structural survey.     

Respiratory distress syndrome treated with human surfactant: radiographic findings

Chest radiographs of 18 newborns treated with endotracheal instillation of human surfactant for respiratory distress syndrome (RDS) were compared with those of 18 similar but untreated infants. In the treated infants, severity of RDS significantly improved after surfactant administration. Most treated infants (16/18) exhibited a left-to-right shunt, presumably through a patent ductus arteriosus; similar findings were noted in untreated infants (17/18). Complications of respiratory assistance in the treated infants included transient pulmonary interstitial emphysema (n = 1), pneumothorax (n = 1), and mild (n = 4) to moderate (n = 2) bronchopulmonary dysplasia; the incidences of these complications did not exceed those in untreated infants. In three treated infants, a transient interstitial lung disease developed 3-4 days after surfactant administration.