Clinical and economic impact of current ALK rearrangement testing in Spain compared with a hypothetical no-testing scenario

Background: Currently biomarkers play an essential role in diagnosis, treatment, and management of cancer. In non-small cell lung cancer (NSCLC) determination of biomarkers such as ALK, EGFR, ROS1 or PD-L1 is mandatory for an adequate treatment decision. The aim of this study is to determine the clinical and economic impact of current anaplastic lymphoma kinase testing scenario in Spain. Methods: A joint model, composed by decision-tree and Markov models, was developed to estimate the long-term health outcomes and costs of NSCLC patients, by comparing the current testing scenario for ALK in Spain vs a hypothetical no-testing. The current distribution of testing strategies for ALK determination and their sensitivity and specificity data were obtained from the literature. Treatment allocation based on the molecular testing result were defined by a panel of Spanish experts. To assess long-term effects of each treatment, 3-states Markov models were developed, where progression-free survival and overall survival curves were extrapolated using exponential models. Medical direct costs (expressed in €, 2019) were included. A lifetime horizon was used and a discount rate of 3% was applied for both costs and health effects. Several sensitivity analyses, both deterministic and probabilistic, were performed in order test the robustness of the analysis. Results: We estimated a target population of 7628 NSCLC patients, including those with non-squamous histology and those with squamous carcinomas who were never smokers. Over the lifetime horizon, the current ALK testing scenario produced additional 5060 and 3906 life-years and quality-adjusted life-years (QALY), respectively, compared with the no-testing scenario. Total direct costs were increased up to € 51,319,053 for testing scenario. The incremental cost-effectiveness ratio was 10,142 €/QALY. The sensitivity analyses carried out confirmed the robustness of the base-case results, being the treatment allocation and the test accuracy (sensitivity and specificity data) the key drivers of the model. Conclusions: ALK testing in advanced NSCLC patients, non-squamous and never-smoker squamous, provides more than 3000 QALYs in Spain over a lifetime horizon. Comparing this gain in health outcomes with the incremental costs, the resulting incremental cost-effectiveness ratio reinforces that testing non-squamous and never-smoker squamous NSCLC is a cost-effective strategy in Spain

Gender-Based Differences by Age Range in Patients Hospitalized with COVID-19: A Spanish Observational Cohort Study

There is some evidence that male gender could have a negative impact on the prognosis and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of the present study was to compare the characteristics of coronavirus disease 2019 (COVID-19) between hospitalized men and women with confirmed SARS-CoV-2 infection. This multicenter, retrospective, observational study is based on the SEMI-COVID-19 Registry. We analyzed the differences between men and women for a wide variety of demographic, clinical, and treatment variables, and the sex distribution of the reported COVID-19 deaths, as well as intensive care unit (ICU) admission by age subgroups. This work analyzed 12,063 patients (56.8% men). The women in our study were older than the men, on average (67.9 vs. 65.7 years; p < 001). Bilateral condensation was more frequent among men than women (31.8% vs. 29.9%; p = 0.007). The men needed non-invasive and invasive mechanical ventilation more frequently (5.6% vs. 3.6%, p < 0.001, and 7.9% vs. 4.8%, p < 0.001, respectively). The most prevalent complication was acute respiratory distress syndrome, with severe cases in 19.9% of men (p < 0.001). In men, intensive care unit admission was more frequent (10% vs. 6.1%; p < 0.001) and the mortality rate was higher (23.1% vs. 18.9%; p < 0.001). Regarding mortality, the differences by gender were statistically significant in the age groups from 55 years to 89 years of age. A multivariate analysis showed that female sex was significantly and independently associated with a lower risk of mortality in our study. Male sex appears to be related to worse progress in COVID-19 patients and is an independent prognostic factor for mortality. In order to fully understand its prognostic impact, other factors associated with sex must be considered

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

Desarrollo de un nuevo aceite de soja enriquecido en antioxidantes derivados de la industria olivícola con el fin de prevenir su degradación oxidativa.

El aceite de soja es uno de los más consumidos en Uruguay, con un alto contenido de ácidos grasos esenciales como el linoleico y linolénico. El aceite de oliva, una de las principales fuentes de grasas en la dieta mediterránea, está asociada a beneficios para la salud, debido a su contenido de ácidos grasos monoinsaturados y a los polifenoles. En condiciones gástricas, los compuestos fenólicos del aceite de oliva, ademas, promueven la formación de ácidos grasos nitrados (NO -FA), los cuales son potentes moléculas citoprotectoras. El alperujo es un subproducto de la producción del aceite de oliva (80%), rico en polifenoles, que posee carácter fitotóxico y de difícil degradación. Objetivo generar un aceite de soja enriquecido en polifenoles a partir del alperujo de diferentes variedades de olivo, empleando métodos basados en química verde y evaluando la formación de NO -FA como nuevo indicador de calidad del aceite, junto con la estabilidad oxidativa. Como resultados y conclusiones: Incremento de estabilidad oxidativa al enriquecer los aceites, siendo mayor con el alperujo de la variedad Coratina. Además se incrementó en la concentración de compuestos bioactivos, pero no se observa mayor formación durante la condición gástrica de NO -FA, siendo mayor en el aceite de oliva.Agencia Nacional de Investigación e Innovacio

Carbon Data Obtained During the R/V Sarmiento de Gamboa CAIBOX-2009 Cruise in the Atlantic Ocean (25 July - 13 August, 2009)

The item is made of 2 files, of which 1 is the dataset and the other include a small description of the measured variables.-- Dataset contributed to the Project CarbochangeThis dataset gathers discrete measurements of CO2 (pH and alkalinity) and hydrographic variables (salinity, temperature, dissolved oxygen, nitrate, phosphate and silicate) obtained during the cruise CAIBOX 2009 carried out from 25 July to 13 August 2009. pH was measured spectrophotometrically following the Clayton and Byrne (1993). This method consists on adding a dye solution to the seawater sample, so that the ratio between two absorbances at two different wavelengths is proportional to the sample pH. Alkalinity was measured using an automatic potentiometric titrator Titrando 809 Metrohm, with a Metrohm 6.0232.100 combination glass electrode and a Pt-1000 probe for temperature measurement following the methodology given by Pérez and Fraga (1987). Dissolved oxygen was analyzed following the widely applied Winkler method. Determinations of nitrate, phosphate and silicate were carried out following methods described by Hansen and Grassoff (1983) Salinity and Temperature were recorded with a CTD probeSpanish Project CAIBEX supported by Ministerio de Eduación y Ciencia (CTM2007–66408–C02–01/MAR), CARBOOCEAN (511176GOCE)N

EARLY AND LATE ASSESSMENT OF ESOPHAGOCARDIOPLASTY IN THE SURGICAL TREATMENT OF ADVANCED RECURRENT MEGAESOPHAGUS

ABSTRACT Background Since Chagas disease has esophageal manifestations with different degrees of involvement, the best surgical option is controversial, especially for patients with advanced chagasic megaesophagus and recurrent symptoms after previous treatment. Objective To assess the early and late outcomes of esophagocardioplasty in a series of patients with advanced recurrent chagasic megaesophagus. Methods This descriptive study included 19 older patients with recurrent megaesophagus grade III/IV and positive immunofluorescence for Chagas disease. They had undergone cardiomyotomy with anterior fundoplication a mean of 16.5 years ago. Serra-Doria esophagocardioplasty was selected to treat the recurrence. The patients were followed to assess postoperative and late complications and the incidence of symptom recurrence. Results In early assessment, five (26.3%) patients presented clinical complications. One (5.2%) patient had a gastrointestinal fistula secondary to esophagogastric anastomotic leak, which responded well to conservative treatment. In the one-year follow-up, 18 (94.7%) patients could swallow normally and had no vomiting. Three years after surgery, 10 (62.5%) of 16 patients could swallow normally, and 3 (19.3%) patients complained of vomiting. Five years after surgery, only 5 (38.4%) of 13 patients could swallow normally and 7 (53.8%) had vomiting. Conclusion Serra-Doria esophagocardioplasty for the treatment of advanced recurrent megaesophagus had mild postoperative complications and good success rate in the short-term follow-up. In the long-term follow-up, it proved to be a poor surgery choice because of the high incidence of symptom recurrence, compromising quality of life. This procedure should be indicated only for patients with advanced recurrent megaesophagus without clinical conditions to undergo esophageal resection