European registry on the management of helicobacter pylori infection (HP-EUREG protocol): The first results of Russian centers

Aim: To assess the clinical practice of diagnosis and treatment in patients with Helicobacter pylori infection and to compare this practice with the international guidelines in the European Registry on the management of Helicobacter pylori infection, Hp-EuReg protocol), a multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group. Materials and methods: The data of 813 patients infected with H. pylori and entered in the Hp-EuReg register by the Russian centers in 2013-2015 were analyzed. Results: The most common methods for the primary diagnosis of H. pylori infection are histology (40.3%), rapid urease test (35.7%), and serology (17.2%). The duration of H. pylori eradication therapy was 7, 10, and 14 days in 18.0, 49.3, and 25.1%, respectively. To monitor the effectiveness of treatment, the investigators used a histological examination (34%), a urea breath test (27.3%), H. pylori stool antigen (22.8%), and a rapid urease test (16.3%). A serological test was carried out in 2.5% of the cases. No monitoring was done in 13.5% of the patients. The average eradication efficiency was 82.6%. If the therapy was ineffective, 80% of physicians did not intend to prescribe a new cycle of treatment. Conclusion: Significant differences were found between clinical practice and the current guidelines

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Subclincal Atherosclerosis as Measured by CIMT Is Present in Patients with Hodgkin’s Disease

Abstract Cardiovascular disease is a well-described late effect of treatment for Hodgkin’s Disease (HD), generally attributed to high dose radiation therapy (RT) to the mediastinum and neck. Increased carotid artery intima-media thickness (CIMT), measured by ultrasound, is a valid marker of subclinical atherosclerosis and is associated with an increased risk of future vascular disease. We evaluated CIMT in 31 patients with HD, (22 males, 9 females), mean age 21 (range 9–39) years, between 2 and 241 months from diagnosis. Thirty patients received chemotherapy, including anthracyclines. Sixteen patients were treated with RT to the bilateral neck and mediastinum; 4 received high dose (36Gy) RT and 12 received lower dose (21–25Gy) RT. One patient received lower dose RT only to the bilateral neck. Fourteen patients were treated with chemotherapy alone. CIMT was assessed using a standardized scanning and reading protocol. The CIMT was calculated as the mean of the maximum measurement at 12 sites; near and far walls of the common carotid, bifurcation and internal carotid arteries bilaterally. The mean CIMT for the total cohort was 0.757mm. Among 5 patients (mean age 13, range 9–16 years), evaluated while actively receiving therapy or within one year from completion of therapy, mean CIMT was 0.715, equivalent to the mean CIMT found in healthy 30 year old adults (Stein, Stroke 2004). In a multivariate linear regression analysis CIMT was significantly associated with increasing time since diagnosis (p=0.035), age (p=0.016), and male gender (p=0.014). There was no difference in CIMT between those patients treated with chemotherapy alone vs. chemotherapy and radiation therapy. Subclinical atherosclerosis in patients with HD may evolve early in the course of treatment and survivorship and then increase with age and time from diagnosis. Type of treatment was not a significant predictor of CIMT in our cohort suggesting that factors other than RT play a role in the development of subclinical atherosclerosis. Further studies are needed to better elucidate the etiology of atherosclerotic disease in HD survivors. Screening with CIMT may detect subclinical atherosclerosis and allow for earlier intervention to prevent cardiovascular disease in this population