Background: Diagnostic evidence of the accuracy of a test for identifying a target condition of interest can be estimated using systematic approaches following standardized methodologies. Statistical methods for the meta-analysis of diagnostic test accuracy (DTA) studies are relatively complex, presenting a challenge for reviewers without extensive statistical expertise. In 2006, we developed Meta-DiSc, a free user-friendly software to perform test accuracy meta-analysis. This statistical program is now widely used for performing DTA meta-analyses. We aimed to build a new version of the Meta-DiSc software to include statistical methods based on hierarchical models and an enhanced web-based interface to improve user experience. Results: In this article, we present the updated version, Meta-DiSc 2.0, a web-based application developed using the R Shiny package. This new version implements recommended state-of-the-art statistical models to overcome the limitations of the statistical approaches included in the previous version. Meta-DiSc 2.0 performs statistical analyses of DTA reviews using a bivariate random effects model. The application offers a thorough analysis of heterogeneity, calculating logit variance estimates of sensitivity and specificity, the bivariate I-squared, the area of the 95% prediction ellipse, and the median odds ratios for sensitivity and specificity, and facilitating subgroup and meta-regression analyses. Furthermore, univariate random effects models can be applied to meta-analyses with few studies or with non-convergent bivariate models. The application interface has an intuitive design set out in four main menus: file upload; graphical description (forest and ROC plane plots); meta-analysis (pooling of sensitivity and specificity, estimation of likelihood ratios and diagnostic odds ratio, sROC curve); and summary of findings (impact of test through downstream consequences in a hypothetical population with a given prevalence). All computational algorithms have been validated in several real datasets by comparing results obtained with STATA/SAS and MetaDTA packages. Conclusion: We have developed and validated an updated version of the Meta-DiSc software that is more accessible and statistically sound. The web application is freely available at www.metadisc.es.

Background: Whether immunosuppressed (IS) patients have a worse prognosis of COVID-19 compared to non-IS patients is not known. The aim of this study was to evaluate the clinical characteristics and outcome of IS patients hospitalized with COVID-19 compared to non-IS patients.Methods: We designed a retrospective cohort study. We included all patients hospitalized with laboratory-confirmed COVID-19 from the SEMI-COVID-19 Registry, a large multicentre national cohort in Spain, from March 27^thuntil June 19^th, 2020. We used multivariable logistic regression to assess the adjusted odds ratios (aOR) of in-hospital death among IS compared to non-IS patients.Results: Among 13 206 included patients, 2 111 (16.0%) were IS. A total of 166 (1.3%) patients had solid organ (SO) transplant, 1081 (8.2%) had SO neoplasia, 332 (2.5%) had hematologic neoplasia, and 570 (4.3%), 183 (1.4%) and 394 (3.0%) were receiving systemic steroids, biological treatments, and immunosuppressors, respectively. Compared to non-IS patients, the aOR (95% CI) for in-hospital death was 1.60 (1.43–1.79) for all IS patients, 1.39 (1.18–1.63) for patients with SO cancer, 2.31 (1.76–3.03) for patients with haematological cancer and 3.12 (2.23–4.36) for patients with SO transplant. The aOR (95% CI) for death for patients who were receiving systemic steroids, biological treatments and immunosuppressors compared to non-IS patients were 2.16 (1.80–2.61), 1.97 (1.33–2.91) and 2.06 (1.64–2.60), respectively. IS patients had a higher odds than non-IS patients of in-hospital acute respiratory distress syndrome, heart failure, myocarditis, thromboembolic disease and multiorgan failure.Conclusions: IS patients hospitalized with COVID-19 have a higher odds of in-hospital complications and death compared to non-IS patients.

Xanthine oxidoreductase (XOR) catalyzes the final two reactions that lead to uric acid formation. XOR is a complex molibdoflavoenzyme present in two different functional forms: dehydrogenase and xantine oxidase (XO). XO is a critical source of reactive oxygen species (ROS) that contribute to vascular inflammation. Under normal physiological conditions, it is mainly found in the dehydrogenase form, while in inflammatory situations, posttranslational modification converts the dehydrogenase form into XO. These inflammatory conditions lead to an increase in XO levels and thus an increased ROS generation by the enzymatic process, finally resulting in alterations in vascular function. It has also been shown that XO secondarily leads to peroxynitrite formation. Peroxynitrite is one of the most powerful ROS that is produced by the reaction of nitric oxide and superoxide radicals, and is considered to be a marker for reactive nitrogen species, accompanied by oxidative stress. Febuxostat is a novel nonpurine XO-specific inhibitor for treating hyperuricemia. As febuxostat inhibits both oxidized and reduced forms of the enzyme, it inhibits the ROS formation and the inflammation promoted by oxidative stress. The administration of febuxostat has also reduced nitro-oxidative stress. XO serum levels are significantly increased in various pathological states such as inflammation, ischemia-reperfusion or aging and that XO-derived ROS formation is involved in oxidative damage. Thus, it may be possible that the inhibition of this enzymatic pathway by febuxostat would be beneficial for the vascular inflammation. In animal models, febuxostat treatment has already demonstrated anti-inflammatory effects, together with the reduction in XO activity. However, the role of febuxostat in humans requires further investigation.

Hereditary hemorrhagic telangiectasia is an inherited disease related to an alteration in angiogenesis, manifesting as cutaneous telangiectasias and epistaxis. As complications, it presents vascular malformations in organs such as the lung, liver, digestive tract, and brain. Currently, diagnosis can be made using the Curaçao criteria or by identifying the affected gene. In recent years, there has been an advance in the understanding of the pathophysiology of the disease, which has allowed the use of new therapeutic strategies to improve the quality of life of patients. This article reviews some of the main and most current evidence on the pathophysiology, clinical manifestations, diagnostic approach, screening for complications, and therapeutic options, both pharmacological and surgical.