Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) a-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions

El COVID-19 y la crisis socioeconómica en América Latina y el Caribe: Revista CEPAL, Edición Especial No. 132,

La edición especial de la Revista CEPAL que presentamos ha sido elaborada en el contexto de la crisis sanitaria ocasionada en 2020 por la propagación de la enfermedad por coronavirus (COVID-19) a escala mundial. Junto con esta pandemia se ha desencadenado también la más aguda crisis económica del capitalismo global desde la Gran Depresión de la década de 1930. En términos más amplios, se trata de una grave crisis humanitaria que ha costado millones de vidas humanas, truncadas por el contagio del virus, así como pérdidas de producción y empleo que se han traducido también en deterioro de las condiciones de bienestar material de vastos segmentos de la población mundial (sobre todo en materia de salud, educación y nutrición) y, por lo mismo, en fuertes retrocesos en materia de pobreza y distribución de los ingresos. En esta sombría escena mundial, América Latina ha resultado ser una de las regiones más afectadas por la pandemia, situación que no es casual en el marco de las asimetrías internas y externas que configuran su disfuncional estilo de desarrollo, patrón que las literaturas estructuralista y neoestructuralista han descrito en numerosos escritos en los que se analiza la dinámica socioeconómica y ambiental de la región en diferentes estadios históricos.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Instituto de Investigaciones Sociales (IIS

Early Use of Sarilumab in Patients Hospitalized with COVID-19 Pneumonia and Features of Systemic Inflammation: the SARICOR Randomized Clinical Trial.

The objective of this study was to investigate the efficacy and safety of early treatment with sarilumab, added to standard of care (SOC), in hospitalized adults with COVID-19. Methods included phase II, open-label, randomized, controlled clinical trial of hospitalized patients with COVID-19 pneumonia and interleukin (IL)-6 levels ≥ 40 pg/mL and/or d-dimer > 1,500 ng/mL. Participants were randomized (1:1:1) to receive SOC (control group), SOC plus a single subcutaneous dose of sarilumab 200 mg (sarilumab-200 group), or SOC plus a single subcutaneous dose of sarilumab 400 mg (sarilumab-400 group). The primary outcome variable was the development of acute respiratory distress syndrome (ARDS) requiring high-flow nasal oxygenation (HFNO), non-invasive mechanical ventilation (NIMV) or invasive mechanical ventilation (IMV) at day 28. One-hundred and 15 participants (control group, n = 39; sarilumab-200, n = 37; sarilumab-400, n = 39) were included. At randomization, 104 (90%) patients had supplemental oxygen and 103 (90%) received corticosteroids. Eleven (28%) patients in the control group, 10 (27%) in sarilumab-200, and five (13%) in sarilumab-400 developed the primary outcome (hazard ratio [95% CI] of sarilumab-400 vs control group: 0.41 [0.14, 1.18]; P = 0.09). Seven (6%) patients died: three in the control group and four in sarilumab-200. There were no deaths in sarilumab-400 (P = 0.079, log-rank test for comparisons with the control group). In patients recently hospitalized with COVID-19 pneumonia and features of systemic inflammation, early IL-6 blockade with a single dose of sarilumab 400 mg was safe and associated with a trend for better outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT04357860.)

Anales de Edafología y Agrobiología Tomo 48 Número 3-4

Determinación del pH en suelos de carga variable de Galicia. Por M. Urrutia Mera, E. García-Rodeja y F. Macías.-- Estudio de los principales factores que intervienen en la estabilidad estructural de los suelos de Galicia. Por E. Benito Rueda y F. Díaz-Fierros Viqueira.-- Contribución al estudio de suelos de alta montaña (Provincia de Teruel). l. Morfología, datos analíticos y clasificación. Por M. a L. Palomar Careza-Villamil, J. Hernando Costa y Mª T. de la Cruz Caravaca.-- Contribución al estudio de suelos de alta montaña (Provincia de Teruel). II. Estudio químico y mineralógico. Génesis. Por Mª L. Palomar Carda-Villamil, J. Hernando Costa y Ma T. de la Cruz Caravaca.-- Comparación de diferentes métodos de medida de la estabilidad estructural al agua. Por E. Benito Rueda y F. Díaz-Fierros Viqueira.-- Mineralogía de arcillas de los suelos de la Sierra de Ascoy (Cieza, Murcia) y su piedemonte. Por L . J. Alzas, C. Careta y J. Martínez.-- Las reacciones lentas del fósforo en suelos gallegos: l. Estudio cinético de la adsorción del fósforo. Por E. de Blas Varela, F. Gil Sotres y F. Guitián Ojea. Compostaje de resíduos sólidos urbanos en bruto. Producción y análisis del coropost. Por S. Mato, D. Otero, M. Carda y D. Trigo.-- Las reacciones lentas del fósforo en suelos gallegos: 2. Variación de las isotermas de sorción con el tiempo de contacto. Por E. de Bias Varela, F. Gil Sotres y F. Guitián Ojea.-- Efecto de diversos res íduos urbanos sobre el rendimiento y contenido mineral de plantas de Ray-grass y lechuga. Por S. Hernando, M. A. Díaz-Burgos y A. Polo.-- Mineralogía de suelos desarrollados sobre sedimentos fluviomarinos recientes en la ría de Betanzos. Por P. Bescansa y E. Barragán.-- Las reacciones lentas del fósforo en suelos gallegos. 3. Experiencias de incubación:A) Test de utilización de la técnica de electroultrafiltración para el estudio de la desorción del fósforo adsorbido. Por E. de Blas Varela, F. Gil Sotres y F. Guitián Ojea.-- Estudio de la capacidad nutriente de dos oxisoles desarrollados sobre bosque tropical de Amazonia. Por J. A. Díez, A. Polo, C. Cerri y F. Andreux.-- Determinación de potasio en suelos mediante contador Geiger-Müller. Por P. Beneitez, T. Calderón y R. Jiménez Ballesta.-- Tipificación de prados de siega en base a la producción de las especies. Por R. García, M. Villafañe, A. Moro ,J. E. Pérez-Pinto y A. Calleja.-- Heterogeneidad edáfica inducida por el adehesamiento del bosque mediterráneo. Por J. J. Jbáñez, A. Carcía y F. Monturiol.-- Supervivencia e inhibición de una cepa de Rhizobium meliloti en distintos perfiles de suelos. Por C. Ducos, M. A. Gómez y M. A. Sagardoy.-- Efecto de la variedad sobre el ritmo de absorción de nutrientes en plantas de berenjena. Por E. Molla, R. M. Esteban, P. Zornoza y F. J. López-Andréu.--Enraizamiento de estaquillas de castaño: efecto de la variación estacional y tratamiento auxínico. Por T. Díaz, E. González, J. Iglesias y V. Mosquera.-- Influencia de las interacciones IAA-NH¡ sobre el crecimiento de Nicotiana rustica L. Por M. A. Pérez Cerezo, M. S. Martín y J. BaztanPeer reviewe

Prospective comparative multi-centre study on imported Plasmodium ovale wallikeri and Plasmodium ovale curtisi infections

BACKGROUND: Few previous retrospective studies suggest that Plasmodium ovale wallikeri seems to have a longer latency period and produces deeper thrombocytopaenia than Plasmodium ovale curtisi. Prospective studies were warranted to better assess interspecies differences. METHODS: Patients with imported P. ovale spp. infection diagnosed by thick or thin film, rapid diagnostic test (RDT) or polymerase chain reaction (PCR) were recruited between March 2014 and May 2017. All were confirmed by DNA isolation and classified as P. o. curtisi or P. o. wallikeri using partial sequencing of the ssrRNA gene. Epidemiological, analytical and clinical differences were analysed by statistical methods. RESULTS: A total of 79 samples (35 P. o. curtisi and 44 P. o. wallikeri) were correctly genotyped. Males predominate in wallikeri group (72.7%), whereas were 48.6% in curtisi group. Conversely, 74.3% of curtisi group were from patients of African ethnicity, whilst 52.3% of Caucasians were infected by P. o. wallikeri. After performing a multivariate analysis, more thrombocytopaenic patients (p = 0.022), a lower number of platelets (p = 0.015), a higher INR value (p = 0.041), and shorter latency in Caucasians (p = 0.034) were significantly seen in P. o. wallikeri. RDT sensitivity was 26.1% in P. o. curtisi and 42.4% in P. o. wallikeri. Nearly 20% of both species were diagnosed only by PCR. Total bilirubin over 3 mg/dL was found in three wallikeri cases. Two patients with curtisi infection had haemoglobin under 7 g/dL, one of them also with icterus. A wallikeri patient suffered from haemophagocytosis. Chemoprophylaxis failed in 14.8% and 35% of curtisi and wallikeri patients, respectively. All treated patients with various anti-malarials which included artesunate recovered. Diabetes mellitus was described in 5 patients (6.32%), 4 patients of wallikeri group and 1 curtisi. CONCLUSIONS: Imported P. o. wallikeri infection may be more frequent in males and Caucasians. Malaria caused by P. o. wallikeri produces more thrombocytopaenia, a higher INR and shorter latency in Caucasians and suggests a more pathogenic species. Severe cases can be seen in both species. Chemoprophylaxis seems less effective in P. ovale spp. infection than in P. falciparum, but any anti-malarial drug is effective as initial treatment. Diabetes mellitus could be a risk factor for P. ovale spp. infection