Current clinical spectrum of common variable immunodeficiency in Spain: The multicentric nationwide GTEM-SEMI-CVID registry

Common variable immunodeficiency (CVID) constitutes a heterogenic group of primary immunodeficiency disorders with a wide-ranging clinical spectrum. CVID-associated non-infectious morbidity constitutes a major challenge requiring a full understanding of its pathophysiology and its clinical importance and global variability, especially considering the broad clinical, genetic, and regional heterogeneity of CVID disorders. This work aimed to develop a nationwide, multicenter, retrospective study over a 3-year period describing epidemiological, clinical, laboratory, therapeutic, and prognostic features of 250 CVID patients in Spain. The mean diagnostic delay was around 10 years and most patients initially presented with infectious complications followed by non-infectious immune disorders. However, infectious diseases were not the main cause of morbimortality. Non-infectious lung disease was extraordinarily frequent in our registry affecting approximately 60% of the patients. More than one-third of the patients in our cohort showed lymphadenopathies and splenomegaly in their follow-up, and more than 33% presented immune cytopenias, especially Evans' syndrome. Gastrointestinal disease was observed in more than 40% of the patients. Among biopsied organs in our cohort, benign lymphoproliferation was the principal histopathological alteration. Reaching 15.26%, the global prevalence of cancer in our registry was one of the highest reported to date, with non-Hodgkin B lymphoma being the most frequent. These data emphasize the importance of basic and translational research delving into the pathophysiological pathways involved in immune dysregulation and diffuse lymphocytic infiltration. This would reveal new tailored strategies to reduce immune complications, and the associated healthcare burden, and ensure a better quality of life for CVID patients

First Colombian Multicentric Newborn Screening for Congenital Toxoplasmosis

Congenital toxoplasmosis can result in permanent sequel as blindness or neurological damage in children and it seems to be more severe in South America than in other continents. There is a lack of information about this frequency in Colombia, where no control program is established, although it is a recognized cause of potentially preventable congenital blindness. We propose the first Colombian multicentric study to determine the frequency and impact of congenital toxoplasmosis. More than 15,000 newborns in seven cities were studied. Newborns were tested at birth by doing a cord blood test for toxoplasmosis. Additionally, children from mothers with history of toxoplasmosis acquired during pregnancy were recalled for a follow-up. The program identified fifteen children otherwise undiagnosed; three of these children died as consequence of congenital toxoplasmosis. The frequency of the congenital infection varied significantly between cities, being higher in Armenia and Florencia, intermediate in Bogota, Bucaramanga and Barranquilla and very low in western cities such as Cucuta and Riohacha. For the first time a significant correlation was found between mean rainfall at the city and the incidence of this congenital infection

Manual de Buenas Prácticas para el manejo de plantaciones forestales en el noroeste de la Patagonia

El presente manual sistematiza y propone las técnicas de manejo más apropiadas para la planificación, conducción y aprovechamiento sustentable de plantaciones forestales en la Patagonia Andina. Para su elaboración se ha recopilado la información existente las experiencias aplicadas en la región a través de numerosos técnicos, investigadores, extensionistas, prestadores de servicios y propietarios forestales. Por lo tanto este manual ordena y propone un conjunto de criterios y técnicas para el manejo sustentable de las plantaciones forestales en la zona de secano de la región noroeste patagónica acordes con el estado actual de conocimientos, que promueva la producción de bienes y servicios en un paisaje multiproductivo y en un marco de conservación de la biodiversidadFil: Attis Beltran, Hernan. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Barroetaveña, Carolina. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bava, Jose E.. Centro de Investigación y Extensión Forestal Andino Patagónico; ArgentinaFil: Bonino, Never Antonio. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; ArgentinaFil: Bulgarelli, Luciano. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte; ArgentinaFil: Caballe, Gonzalo Omar. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; ArgentinaFil: Calvi, Francisco. No especifíca;Fil: Castañeda, Sara Rita. No especifíca;Fil: Chauchards, Luis Mario. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; ArgentinaFil: Chavat, Florencia. No especifíca;Fil: Claps, Leonardo Luis. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche. Grupo de Genética Forestal; ArgentinaFil: Contardi, Liliana. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentina. Centro de Investigación y Extensión Forestal Andino Patagónico; ArgentinaFil: Danklmaiert, Christine. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Davel, Miguel M.. Centro de Investigación y Extensión Forestal Andino Patagónico; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: de Errasti, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Administración de Parques Nacionales; ArgentinaFil: Defossé, Guillermo Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales. Universidad Nacional del Comahue. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales; ArgentinaFil: Del Vas, Javier. No especifíca;Fil: Alejandro, Dezzotti. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; ArgentinaFil: Diez, Juan P.. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; ArgentinaFil: Dillon, Yanina. No especifíca;Fil: Fernandez, Maria Elena. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Felicetti, Augusto. No especifíca;Fil: Frugoni, Maria Cristina Margarita. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; ArgentinaFil: Focarazzo, Silvia. No especifíca;Fil: Fontana, Virginia. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; ArgentinaFil: Godoy, M. Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales. Universidad Nacional del Comahue. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales; ArgentinaFil: Gonda, Héctor Eduardo. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentina. Centro de Investigación y Extensión Forestal Andino Patagónico; ArgentinaFil: Greslebin, Alina Gabriela. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Departamento de Biología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guglielmin, Dante A.. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Gyenge, Javier Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Lantschner, María Victoria. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Letourneau, Federico Jorge. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Loguercio, Gabriel Ange. Centro de Investigación y Extensión Forestal Andino Patagónico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Martinez, Andrés. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mattes Fernández, Hernán. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; ArgentinaFil: Mele, Uriel. No especifíca;Fil: Melzner, Guillermo E.. Ministerio de Agricultura Ganaderia y Pesca de la Nacion.; ArgentinaFil: Mondino, Victor Alejandro. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Sur. Estación Experimental Agropecuaria Esquel; ArgentinaFil: Mortoro, Ariel Mario. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; ArgentinaFil: Novak, Carla. Centro de Investigación y Extensión Forestal Andino Patagónico; ArgentinaFil: Nuñez, Cecilia Inés. Universidad Nacional del Comahue; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nuñez, Martin Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Orellana, Ivonne. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Pantaenius, Pedro Maximiliano. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentina. Centro de Investigación y Extensión Forestal Andino Patagónico; ArgentinaFil: Pastorino, Mario Juan. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rajchenberg, Mario. Centro de Investigación y Extensión Forestal Andino Patagónico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Rusch, Verónica. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; ArgentinaFil: Salvador, Gustavo. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Sur. Estación Experimental Agropecuaria Esquel; ArgentinaFil: Sarasola, Mauro Miguel. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; ArgentinaFil: Sbrancia, Renato Ernesto. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; ArgentinaFil: Stecher, Gabriel Andre. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; ArgentinaFil: Troncoso, Oscar Alberto. Universidad Nacional de la Patagonia "san Juan Bosco". Secretaria de Ciencia y Tecnica. Instituto Biotecnologico Esquel.; ArgentinaFil: Urretavizcaya, M. Florencia. Centro de Investigación y Extensión Forestal Andino Patagónico; ArgentinaFil: Varela, Santiago Agustín. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; ArgentinaFil: Velásquez, Abel. Universidad Nacional del Comahue. Asentamiento Universidad San Martín de Los Andes; ArgentinaFil: Villacide, José María. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; ArgentinaFil: Weigandt, Mariana Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; ArgentinaFil: Zalazar, Gabriel. Ministerio de Agricultura Ganaderia y Pesca de la Nacion.; Argentin

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%–80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old