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Background: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a relatively common complication. Multiple studies described this relationship in critical patients, however its incidence and outcome in other risk groups such as immunosuppressed patients remains unknown. In this sense, we aimed to evaluate the rates and outcomes of CAPA in hematological patients and according to the different hematological malignances, comparing to invasive pulmonary aspergillosis (IPA) in non-COVID-19 ones. Methods: Nationwide, population-based and retrospective observational cohort study including all adult patients with hematological malignancies admitted in Spain since March 1, 2020 to December 31, 2021. The main outcome variable was the diagnosis of IPA during hospitalization in hematological patients with or without COVID-19 at admission. The rate of CAPA compared to IPA in non-COVID-19 patients in each hematological malignancy was also performed, as well as survival curve analysis. Findings: COVID-19 was diagnosed in 3.85 % (4367 out of 113,525) of the hematological adult inpatients. COVID-19 group developed more fungal infections (5.1 % vs. 3 %; p

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.

Acute kidney injury (AKI) is the most common complication of cardiac surgery. Cardiac surgery-associated AKI (CSA-AKI) is caused by systemic and renal hemodynamic impairment and parenchymal injury. Prophylaxis of CSA-AKI remains an unmet priority, for which preventive strategies based on drug therapies, hydration procedures, and remote ischemic preconditioning (RIPC) have been tested in pre-clinical and clinical studies, with variable success. Contradicting reports and scarce or insufficiently pondered information have blurred conclusions. Therefore, with an aim to contribute to consolidating the available information, we carried out a wide scope, pan-comparative meta-analysis including the accessible information about the most relevant nephroprotective approaches assayed. After a thorough examination of 1892 documents retrieved from PubMed and Web of Science, 150 studies were used for the meta-analysis. Individual odds ratios of efficacy at reducing AKI incidence, need for dialysis, and plasma creatinine elevation were obtained for each alleged protectant. Also, the combined class effect of drug families and protective strategies was also meta-analyzed. Our results show that no drug family or procedure affords substantial protection against CSA-AKI. Only, a mild but significant reduction in the incidence of CSA-AKI by preemptive treatment with dopaminergic and adrenergic drugs, vasodilators, and the RIPC technique. The integrated analysis suggests that single-drug approaches are unlikely to cope with the variety of individual pathophysiological scenarios potentially underlying CSA-AKI. Accordingly, a theragnostic approach involving the etiopathological diagnosis of kidney frailty is necessary to guide research towards the development of pharmacological combinations concomitantly and effectively addressing the key mechanisms of CSA-AKI.

Reseña de: Brochner, G., Pinto Tortosa, A.J. y Sansó-Rubert Pascual, D. (dirs.) (2023). ¿Hacia un nuevo Telón de Acero? 30 años de geopolítica en la posguerra fría. Tirant Lo Blanch, 376 pp.

IntroductionPrevalence and mortality of the acute respiratory distress syndrome (ARDS) in intensive care units (ICU) are unacceptably high. There is scarce literature on post-operative sepsis-induced ARDS despite that sepsis and major surgery are conditions associated with ARDS. We aimed to examine the impact of post-operative sepsis-induced ARDS on 60-day mortality.MethodsWe performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups depending on whether they met criteria for ARDS. Primary outcome was 60-day mortality of post-operative sepsis-induced ARDS. Secondary outcome measures were potential risk factors for post-operative sepsis-induced ARDS, and for 60-day mortality.ResultsHigher SOFA score (OR 1.1, 95% CI 1.0–1.3, p = 0.020) and higher lactate (OR 1.9, 95% CI 1.2–2.7, p = 0.004) at study inclusion were independently associated with ARDS. ARDS patients (n = 45) had higher ICU stay [14 (18) vs. 5 (11) days, p < 0.001] and longer need for mechanical ventilation [6 (14) vs. 1 (5) days, p < 0.001] than non-ARDS patients (n = 409). Sixty-day mortality was higher in ARDS patients (OR 2.7, 95% CI 1.1–6.3, p = 0.024). Chronic renal failure (OR 4.0, 95% CI 1.2–13.7, p = 0.026), elevated lactate dehydrogenase (OR 1.7, 95% CI 1.1–2.7, p = 0.015) and higher APACHE II score (OR 2.7, 95% CI 1.3–5.4, p = 0.006) were independently associated with 60-day mortality.ConclusionPost-operative sepsis-induced ARDS is associated with higher 60-day mortality compared to non-ARDS post-operative septic patients. Post-operative septic patients with higher severity of illness have a greater risk of ARDS and worse outcomes. Further investigation is needed in post-operative sepsis-induced ARDS to prevent ARDS.

Abstract Background Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide association study (GWAS) of 28-day survival in adult patients with sepsis. Methods This study was conducted in two stages. The first stage was performed on 687 European sepsis patients from the GEN-SEP network and 7.5 million imputed variants. Association testing was conducted with Cox regression models, adjusting by sex, age, and the main principal components of genetic variation. A second stage focusing on the prioritized genetic variants was performed on 2,063 ICU sepsis patients (1362 European Americans and 701 African-Americans) from the MESSI study. A meta-analysis of results from the two stages was conducted and significance was established at p

IntroductionCOVID-19 transmission has been characterized by the presence of asymptomatic patients. Additionally, most studies evaluating costs focus on symptomatic COVID-19 cases.ObjectiveTo describe the prevalence, characteristics, and costs of asymptomatic COVID-19 cases at admission in Spanish hospitals in 2020.MethodsA nationwide study was performed, and data of hospitalized patients were collected of the Minimum Basic Data Set in Spain during 2020. Patients with COVID-19 codes as a primary and as a secondary diagnosis at admission were selected. Variables collected included age, sex, length of stay, in-hospital death, admission, length of stay and death in intensive care unit, mechanical ventilation and ventilatory assistance. COVID-19 related hospital costs were calculated using diagnosis-related groups from the Minimum Basic Data Set. Patients and costs were disaggregated by sex, age group, intensive care unit admission and epidemic wave (first or second) and main diagnosis.ResultsA total of 14,742 patients were admitted with asymptomatic COVID-19 in Spanish hospitals representing 6.35% of all COVID-19 admitted patients. The total cost of admissions with asymptomatic COVID-19 was €105,933,677.6 with a mean cost per patient of €7,185.8 with higher mean cost in the first wave despite only 2.7% of cases were found during that time. Based on primary diagnosis, the higher number of cases of asymptomatic COVID-19 were found in “Pregnancy, childbirth and the puerperium” followed by “diseases of the circulatory system”.ConclusionsThere was a high prevalence of asymptomatic cases during screening at admission process in Spanish hospitals in 2020. The highest number of cases was found among the group of “pregnancy, childbirth, and puerperium” followed by “diseases of the circulatory system.” The higher costs might be due not only to the main pathology at admission but to the associated healthcare provisions needed in case of positive COVID-19 testing.

We carried out a retrospective exploratory study on 173 patients who underwent major surgery and developed septic shock after surgery. Our findings suggest that CEACAM7 rs1001578, rs10409040, and rs889365 polymorphisms could influence septic shock-related death in individuals who underwent major surgery.

El objetivo de este número de LOCUS fue el de contribuir a la investigación y la discusión sobre la historia reciente de la política exterior latinoamericana, a través de la publicación de artículos de reflexión y análisis en torno a los procesos de democratización y elitización de la política exterior. Fueron priorizadas, con ello, aquellas contribuciones que abordan la historia de la política exterior latinoamericana, incluyendo sustento teórico-crítico con enfoque regional o transnacional, y que analizan, discuten y profundizan tanto acerca de los factores ideacionales e ideológicos de la política exterior, como en relación con la praxis entre las élites tradicionales, la sociedad civil, las fuerzas transnacionales y la influencia de otros actores y espacios alternativos de articulación. Tal problematización fue respondida por cuatro importantes contribuciones originales e inéditas.

Reseña del libro: Manfredi, Juan Luis. Diplomacia. Historia y presente. Madrid: Síntesis, 2021.

Estudio de la historia de la política exterior latinoamericana y española: entrevistas a Ricardo Scavone y Lorenzo Delgado

Abstract Background Despite growing interest in treatment strategies that limit oxygen exposure in ICU patients, no studies have compared conservative oxygen with standard oxygen in postsurgical patients with sepsis/septic shock, although there are indications that it may improve outcomes. It has been proven that high partial pressure of oxygen in arterial blood (PaO2) reduces the rate of surgical-wound infections and mortality in patients under major surgery. The aim of this study is to examine whether PaO2 is associated with risk of death in adult patients with sepsis/septic shock after major surgery. Methods We performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups whether they had hyperoxemia, defined as PaO2 > 100 mmHg (n = 216), or PaO2 ≤ 100 mmHg (n = 238) at the day of sepsis/septic shock onset according to SEPSIS-3 criteria maintained during 48 h. Primary end-point was 90-day mortality after diagnosis of sepsis. Secondary endpoints were ICU length of stay and time to extubation. Results In patients with PaO2 ≤ 100 mmHg, we found prolonged mechanical ventilation (2 [8] vs. 1 [4] days, p 19. These findings were confirmed when patients with severe hypoxemia at the time of study inclusion were excluded. Conclusions Oxygenation with a PaO2 above 100 mmHg was independently associated with lower 90-day mortality, shorter ICU stay and intubation time in critically ill postsurgical sepsis/septic shock patients. Our findings open a new venue for designing clinical trials to evaluate the boundaries of PaO2 in postsurgical patients with severe infections.

BackgroundHigh cytokine levels have been associated with severe COVID-19 disease. Although many cytokine studies have been performed, not many of them include combinatorial analysis of cytokine profiles through time. In this study we investigate the association of certain cytokine profiles and its evolution, and mortality in SARS-CoV2 infection in hospitalized patients.MethodsSerum concentration of 45 cytokines was determined in 28 controls at day of admission and in 108 patients with COVID-19 disease at first, third and sixth day of admission. A principal component analysis (PCA) was performed to characterize cytokine profiles through time associated with mortality and survival in hospitalized patients.ResultsAt day of admission non-survivors present significantly higher levels of IL-1α and VEGFA (PC3) but not through follow up. However, the combination of HGF, MCP-1, IL-18, eotaxine, and SCF (PC2) are significantly higher in non-survivors at all three time-points presenting an increased trend in this group through time. On the other hand, BDNF, IL-12 and IL-15 (PC1) are significantly reduced in non-survivors at all time points with a decreasing trend through time, though a protective factor. The combined mortality prediction accuracy of PC3 at day 1 and PC1 and PC2 at day 6 is 89.00% (p

Abstract Background The presence of headache during the acute phase of COVID-19 could be associated with the innate response and the cytokine release. We aim to compare the cytokine and interleukin profile in hospitalized COVID-19 patients at the moment of admission with and without headache during the course of the disease. Methods An observational analytic study with a case control design was performed. Hospitalized patients from a tertiary hospital with confirmed COVID-19 disease were included. Patients were classified into the headache or the control group depending on whether they presented headache not better accounted for by another headache disorder other than acute headache attributed to systemic viral infection. Several demographic and clinical variables were studies in both groups. We determined the plasmatic levels of 45 different cytokines and interleukins from the first hospitalization plasma extraction in both groups. Results One hundred and four patients were included in the study, aged 67.4 (12.8), 43.3% female. Among them, 29 (27.9%) had headache. Patients with headache were younger (61.8 vs. 69.5 years, p = 0.005) and had higher frequency of fever (96.6 vs. 78.7%, p = 0.036) and anosmia (48.3% vs. 22.7%, p = 0.016). In the comparison of the crude median values of cytokines, many cytokines were different between both groups. In the comparison of the central and dispersion parameters between the two groups, GROa, IL-10, IL1RA, IL-21, IL-22 remained statistically significant. After adjusting the values for age, sex, baseline situation and COVID-19 severity, IL-10 remained statistically significant (3.3 vs. 2.2 ng/dL, p = 0.042), with a trend towards significance in IL-23 (11.9 vs. 8.6 ng/dL, p = 0.082) and PIGF1 (1621.8 vs. 110.6 ng/dL, p = 0.071). Conclusions The higher levels of IL-10 -an anti-inflammatory cytokine- found in our sample in patients with headache may be explained as a counteract of cytokine release, reflecting a more intense immune response in these patients.

el objetivo de este artículo fue detectar, analizar y explicar la relación de la ideología nacionalista paraguaya reciente con el proceso de mestizaje hispano-guaraní del periodo de conquista y colonización castellana, así como la valoración del carácter femenino —entendido como subordinación— de la parte paraguayo-guaraní de dicho proceso de mestizaje, carácter sobreexplotado por el nacionalismo paraguayo actual. El objetivo concierne, por tanto, a dos unidades políticas contemporáneas —Paraguay y España— separadas tras la Independencia; sin embargo, el nacionalismo paraguayo quedó imbuido de un fuerte sesgo hispano en el relato de su construcción nacional, el cual fue aprovechado también por España como elemento de vínculo histórico al Paraguay (favoreciéndose el relacionamiento político). Para comprender la relación entre ambas unidades políticas durante el periodo dictatorial de ambos países en la segunda mitad del siglo XX se analizó una fuente fundamental: los escritos del que embajador español en Parauay, Ernesto Giménez Caballero (particularmente su libro Revelación del Paraguay, 1958); además, el análisis del relato implícito en esta fuente se confrontó con varios trabajos recientes de otros investigadores acerca de estos mismos elementos. El artículo derivó los principales elementos del discurso imperialista de Ernesto Giménez Caballero —hispanidad, mestizaje, catolicidad— y varias referencias o aproximaciones de la perspectiva político-ideológica de este escritor de vanguardia, intelectual fascista y diplomático franquista español, al relato nacional hegemónico de su Paraguay imaginado; un Giménez Caballero que no solo fue un servidor leal a la causa de la hispanidad desplegada por el régimen dictatorial de Francisco Franco, sino que mantuvo una estrecha relación con su homólogo paraguayo —Alfredo Stroessner—, afinidad y simpatía que reflejaron también una notable sintonía ideológica.

Cadenas productivas en la economía-mundo antes de 1800.

Los problemas vinculados al acceso al agua en el contexto de la crisis sociosanitaria de la covid-19. Entrevista a Miguel Ángel Pérez Martín.

El agua y el Paraguay indígena: identidad, cultura, sociedad y políticas públicas. Entrevistas a Sara Mabel Villalba, Manuel Chamorro y Julio de Torres.

El agua en el contexto de la transición ecológica. Entrevista a Pedro Arrojo Agudo.

Probablemente existan pocos elementos que disciplinariamente sean tan transversales y que se relacionen con tantos aspectos de la vida —natural y social— como el agua. Esta circunstancia ha supuesto que el estudio de este elemento haya sido abordado desde diversos campos disciplinarios y que exista una gama de aproximaciones cada vez más amplia en torno al agua, priorizándose diversos aspectos en su investigación. Es precisamente esa diversidad teórica la que se pretende resaltar en este documento. Siendo ampliamente reduccionista, en términos generales se podría decir que mientras las aproximaciones dominantes suelen tener enfoques más bien cientificistas y tienden a acercarse al agua desde perspectivas también dominantes de la economía, el desarrollo, la cooperación o el conflicto, otros enfoques —más críticos— tienden a problematizar el conjunto de relaciones sociales, relaciones de poder, igualdad y desigualdad en torno al agua, e incluso la forma en que las sociedades entienden y se relacionan con ella. Desde esta perspectiva, el objetivo de este documento es iniciar esta publicación especial sobre el estudio del agua esbozando un estado de la cuestión, en el que reconocidos académicos presentan los principales aspectos de sus enfoques y aproximaciones al agua, así como las líneas generales de los debates actuales y futuros de este campo de investigación. Para su desarrollo, la Coordinación de este número de la revista Relaciones Internacionales —formada por Eduardo Tamayo Belda, Aída Cecilia Acosta y Ana Isabel Carrasco Vintimilla— ha planteado a los autores y autoras entrevistados algunas cuestiones de esos debates, recogiendo los diferentes enfoques y propuestas de análisis que estos investigadores han devuelto en sus respectivas entrevistas. La compilación y la traducción de estas respuestas para su publicación en el número ha estado al cuidado de Ana Isabel Carrasco Vintimilla. En lo que sigue, los investigadores Mark Zeitoun, Naho Mirumachi, Jamie Linton y Aziza Akhmouch dan respuesta a los planteamientos propuestos para el debate por los coordinadores del dossier; se pueden ver sus currículums y principales líneas de investigación al final de este documento. Así, las respuestas de Mark Zeitoun se refieren especialmente al campo los conflictos hídricos y de las relaciones de poder en torno al agua; la investigadora Naho Mirumachi —que profundiza desde su trabajo conjunto con Zeitoun— incluye aspectos más específicos de la cooperación, la gobernanza y la hidrohegemonía. Jamie Linton, por su parte, aborda las preguntas manteniendo la perspectiva crítica de los autores anteriores, aunque centrándose con especial atención en el análisis del discurso y en el estudio de las relaciones sociales y políticas en torno al agua. Finalmente, Aziza Akhmouch presenta los principales enfoques y aspectos que priorizan algunos organismos internacionales como, en su caso, la Organización para la Cooperación y Desarrollo Económicos (OCDE). No obstante, es preciso hacer notar al lector que estas respuestas, en todo caso, planteamientos generales que proponen un escenario de debate amplio —mas no exhaustivo— del estudio del agua y de los aspectos que se discuten e investigan en torno a este elemento.

Agua y energía: la disputa por la soberanía en Paraguay. Entrevista a Sara Costa.

Trabajar a destajo sin acceso garantizado al agua: la dura realidad de muchos trabajadores migrantes en el sur de España. Entrevista a José Manuel Velázquez Mazuecos.

Reseña de: Lanceros, P. y Barja, J. (eds.) (2017). Leonardo da Vinci. El libro del agua. Madrid: Abada Editores, 260 pp.

La certeza de que el agua —y en particular el agua dulce— es un elemento transversal a todos los aspectos de la vida humana está adquiriendo en los últimos decenios el cariz de inquietud global por los trascendentes aspectos geopolíticos, económicos, socioculturales o normativos de su situación; asimismo, existe una creciente preocupación internacional por el acceso a la misma, sus usos, el derecho a su explotación, su capacidad de renovación y uso sostenible, e incluso en torno a la propia naturaleza del elemento. Las coordinadoras de esta publicación hemos querido contribuir modestamente en este dossier —número 45 de la revista Relaciones Internacionales— a centrar la atención en el debate en torno al agua —particularmente, aunque no de manera exclusiva, sobre el agua dulce—, y a abordar desde una multiplicidad de enfoques —la mayoría de ellos con marcada perspectiva crítica— los fenómenos y circunstancias que rodean este elemento fundamental para la vida sobre la Tierra. A pesar de la gran abundancia de agua que existe en nuestro planeta, apenas el 0’3% es apto para el consumo humano, y de esta provisión mundial de agua dulce la mayor parte se encuentra contenida en los polos y en la atmósfera, de manera que es menos de una quinta parte de estas reservas lo que conforma los acuíferos subterráneos, los lagos y los ríos del planeta; es en estos espacios geográficos de donde tanto seres humanos como el resto de animales extraemos las cantidades necesarias de agua para vivir y para producir energía y alimentos. Los sistemas de producción del desarrollo capitalista y el crecimiento demográfico global han colocado a este elemento natural en una situación comprometida, y podemos afirmar que en la actualidad el agua se sitúa en el epicentro de algunos de los grandes debates de relaciones internacionales del siglo XXI, en concreto de aquellos que se producen en torno a la discusión sobre la condición y categoría de los recursos naturales, de sus usos, y de su relación con los ámbitos político y sociocultural humanos. Es también notorio que los procesos económicos globales contemporáneos han agudizado el problema del agua; todos los procesos de producción basan alguna de sus etapas en su utilización, lo que sumado a los sistemas de extracción o acumulación masivos de este recurso está generando local y globalmente tensiones de diversa índole —política, social, económica, ideológica, cultural, discursiva o identitaria—, provocadas tanto por el exceso de la extracción de agua como por las consecuencias de ello en los ecosistemas donde se encuentra dicho elemento. Así, los problemas de contaminación ambiental —ya sea del agua o del entorno de las bases productivas y extractivas—, la gestión política inadecuada o excluyente del recurso —debido principalmente a las fuertes presiones e intereses privatizadores—, o el desigual reparto de los beneficios de su explotación y uso —que recrudecen la disparidad global entre los actores internacionales enriquecidos y aquellos subalternos del sistema capitalista—, representan una posibilidad de conflictos latentes y plantean una serie de dilemas y contradicciones que, en nuestra opinión, deben ser atendidos con urgencia, y deben ser abordados —además— en una dirección concreta: en pro del beneficio colectivo global, con carácter equilibrado, ecológico, sostenible y respetuoso con los usos y culturas tradicionales locales. Partiendo de la consideración básica del agua como un elemento disponible en la naturaleza, resulta sin embargo evidente que en la sociedad capitalista contemporánea conviven múltiples concepciones de este elemento, perspectivas diferentes sobre sus usos, y enfoques incluso contradictorios acerca del futuro de la naturaleza sociopolítica del mismo. Este dossier contempla una problematización política del elemento, afrontando con ello un más que necesario debate interdisciplinar sobre la geopolítica global del agua, con una discusión teórica en torno a las perspectivas, tensiones, conflictos y oportunidades suscitados por la confluencia de intereses, valores, cosmovisiones y consideraciones del agua en el sistema internacional.

Cuestión de supervivencia: agua y solidaridad en la frontera. Entrevistas a Tania García Barajas y Eduardo Erasmo Osornio García.

Cuando el plástico llega por el grifo de su casa. Desigualdad global en la contaminación del agua. Entrevista a Miguel Tamayo Belda.

Background: Oxidative stress may be a key player in COVID-19 pathogenesis due to its significant role in response to infections. A defective redox balance has been related to viral pathogenesis developing a massive induction of cell death provoked by oxidative stress. The aim of this study is to perform a complete oxidative stress profile evaluation regarding antioxidant enzymes, total antioxidant capacity and oxidative cell damage in order to characterize its role in diagnosis and severity of this disease. Methods: Blood samples were obtained from 108 COVID-19 patients and 28 controls and metabolites representative of oxidative stress were assessed. The association between lipid peroxidation and 28-day intubation/death risk was evaluated by multivariable regression analysis. Probability of intubation/death to day-28 was analyzed by using Kaplan-Meier curves and tested with the log-rank test. Results: Antioxidant enzymes (Superoxide dismutase (SOD) and Catalase) and oxidative cell damage (Carbonyl and Lipid peroxidation (LPO)) levels were significantly higher in COVID-19 patients while total antioxidant capacity (ABTS and FRAP) levels were lower in these patients. The comparison of oxidative stress molecules’ levels across COVID-19 severity revealed that only LPO was statistically different between mild and intubated/death COVID-19 patients. COX multivariate regression analysis identified LPO levels over the OOP (LPO>1948.17 μM) as an independent risk factor for 28-day intubation/death in COVID-19 patients [OR: 2.57; 95% CI: 1.10–5.99; p = 0.029]. Furthermore, Kaplan-Meier curve analysis revealed that COVID-19 patients showing LPO levels above 1948.17 μM were intubated or died 8.4 days earlier on average (mean survival time 15.4 vs 23.8 days) when assessing 28-day intubation/death risk (p

Recent works have demonstrated a significant reduction in cholesterol levels and increased oxidative stress in patients with coronavirus disease 2019 (COVID-19). The cause of this alteration is not well known. This study aimed to comprehensively evaluate their possible association during the evolution of COVID-19. This is an observational prospective study. The primary endpoint was to analyze the association between lipid peroxidation, lipid, and inflammatory profiles in COVID-19 patients. A multivariate regression analysis was employed. The secondary endpoint included the long-term follow-up of lipid profiles. COVID-19 patients presented significantly lower values in their lipid profile (total, low, and high-density lipoprotein cholesterol) with greater oxidative stress and inflammatory response compared to the healthy controls. Lipid peroxidation was the unique oxidative parameter with a significant association with the total cholesterol (OR: 0.982; 95% CI: 0.969–0.996; p = 0.012), IL1-RA (OR: 0.999; 95% CI: 0.998–0.999; p = 0.021) IL-6 (OR: 1.062; 95% CI: 1.017–1.110; p = 0.007), IL-7 (OR: 0.653; 95% CI: 0.433–0.986; p = 0.042) and IL-17 (OR: 1.098; 95% CI: 1.010–1.193; p = 0.028). Lipid abnormalities recovered after the initial insult during long-term follow-up (IQR 514 days); however, those with high LPO levels at hospital admission had, during long-term follow-up, an atherogenic lipid profile. Our study suggests that oxidative stress in COVID-19 is associated with derangements of the lipid profile and inflammation. Survivors experienced a recovery in their lipid profiles during long-term follow-up, but those with stronger oxidative responses had an atherogenic lipid profile.

Influenza B is accountable for an important burden during flu epidemics, causing special impact in children and the elderly. Vaccination is the best approach to address influenza infections. However, one of the main problems of this virus is that two different lineages circulate together, Victoria and Yamagata; and trivalent vaccines, that only contain one of these lineages, are still in use. For that reason, if during an epidemic, the lineage not included in the vaccine predominates, a mismatch would occur, and the vaccine effectiveness will be very poor. In this work, we evaluated the cross-protection given by the trivalent Influenza vaccine and compared serological profiles based on age, sex, and the type of vaccine used. We performed a retrospective analysis of serum samples obtained before and after seasonal influenza vaccination during 20 seasons (1998–2018). The results showed that heterotypic reactivity between both influenza B lineages is common, but always lower than the homologous response. Age is a relevant factor for this cross-reactivity between both lineages, while the sex and the type of vaccine not. Vaccination with trivalent influenza vaccines elicits cross-reactive antibodies against both lineages, however, this response might not be enough to provide an appropriate serological protection in case of mismatch.

Severe status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank: p = 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064–8.665), p < 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540–50.878), p = 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.

Non-alcoholic fatty liver disease (NAFLD) is characterised by an excess of hepatic fat that can progress to steatohepatitis, fibrosis, cirrhosis and hepatocarcinoma. The imbalance between lipid uptake/lipogenesis and lipid oxidation/secretion in the liver is a major feature of NAFLD. Given the lack of a non-invasive and reliable methods for the diagnosis of non-alcoholic steatohepatitis (NASH), it is important to find serum markers that are capable of discriminating or defining patients with this stage of NASH. Blood samples were obtained from 152 Caucasian subjects with biopsy-proven NAFLD due to persistently elevated liver enzyme levels. Metabolites representative of oxidative stress were assessed. The findings derived from this work revealed that NAFLD patients with a NASH score of ≥ 4 showed significantly higher levels of lipid peroxidation (LPO). Indeed, LPO levels above the optimal operating point (OOP) of 315.39 μM are an independent risk factor for presenting a NASH score of ≥ 4 (OR: 4.71; 95% CI: 1.68–13.19; p = 0.003). The area under the curve (AUC = 0.81, 95% CI = 0.73–0.89, p < 0.001) shows a good discrimination ability of the model. Therefore, understanding the molecular mechanisms underlying the basal inflammation present in these patients is postulated as a possible source of biomarkers and therapeutic targets in NASH.

Although the COVID-19 disease has developed into a worldwide pandemic, its pathophysiology remains to be fully understood. Insulin-degrading enzyme (IDE), a zinc-metalloprotease with a high affinity for insulin, has been found in the interactomes of multiple SARS-CoV-2 proteins. However, the relevance of IDE in the innate and adaptative immune responses elicited by circulating peripheral blood mononuclear cells is unknown. Here, we show that IDE is highly expressed on the surface of circulating monocytes, T-cells (both CD4+ and CD4−), and, to a lower extent, in B-cells from healthy controls. Notably, IDE’s surface expression was upregulated on monocytes from COVID-19 patients at diagnosis, and it was increased in more severe patients. However, IDE’s surface expression was downregulated (relative to healthy controls) 3 months after hospital discharge in all the studied immune subsets, with this effect being more pronounced in males than in females, and thus it was sex-dependent. Additionally, IDE levels in monocytes, CD4+ T-cells, and CD4− T-cells were inversely correlated with circulating insulin levels in COVID-19 patients (both at diagnosis and after hospital discharge). Of note, high glucose and insulin levels downregulated IDE surface expression by ~30% in the monocytes isolated from healthy donors, without affecting its expression in CD4+ T-cells and CD4− T-cells. In conclusion, our studies reveal the sex- and metabolism-dependent regulation of IDE in monocytes, suggesting that its regulation might be important for the recruitment of immune cells to the site of infection, as well as for glucometabolic control, in COVID-19 patients.

BackgroundSex differences in immune responses are well known. However, the humoral response in males and females in the case of influenza vaccination is yet to be characterized since studies have shown uneven results.MethodsA retrospective study was conducted in 2,243 individuals (46.9% males) divided by age (15–64 and ≥65 years old). A serological analysis was performed by hemagglutination inhibition assay (HI) just before and 28 days after annual vaccination against seasonal influenza viruses in people vaccinated during the 2006–2018 seasons. A comparison of the humoral responses against influenza A and B viruses contained in the vaccine, between male and female individuals in young adults and elderly was conducted.ResultsSignificative higher humoral response against classical influenza A (H1N1), A(H1N1)pdm09 subtype and B/Victoria lineage in terms of seroconversion rate were found in elderly women. No significant differences were found in the case of A(H3N2) subtype.ConclusionsElderly women seem to display a greater humoral response against classical A(H1N1), pandemic A(H1N1)pmd09 and B/Victoria lineage than elderly men. Sex dimorphism does not affect young adults.

Introduction: One of the worst clinical outcomes of the coronavirus disease 2019 (COVID-19) pandemic was acute kidney injury (AKI).Methods: This manuscript presents results from a population-based registry study assessing treatment, comorbidities, and predictors of hospital death among COVID-19 patients with AKI from March 1st to May 31th, 2020. Death, oxygen delivery and ventilation, acute dialysis need, use of medications, and various clinical outcomes, in addition to the length of stay in the hospital and intensive care unit (ICU), were evaluated.Results: In Castile and Leon, the largest region of Spain, 10.87% of the patients admitted for COVID-19 (n = 7,307) developed AKI. These patients were known by having hypertension (57.93%), cardiovascular disease (48.99%), diabetes (26.7%) and chronic kidney disease (14.36%), and they used antibiotics (90.43%), antimalarials (60.45%), steroids (48.61%), antivirals (33.38%), anti-systemic inflammatory response syndrome (SIRS) drugs (9.45%), and tocilizumab (8.31%). Mortality among patients with AKI doubled that observed in patients without AKI (46.1 vs. 21.79%). Predictors of hospital death in COVID-19 patients with AKI were ventilation needs (OR = 5.9), treatment with steroids (OR = 1.7) or anti-SIRS (OR = 2.4), severe acute respiratory syndrome (SARS) occurrence (OR = 2.8), and SIRS occurrence (OR = 2.5).Conclusions: Acute kidney injury is a frequent and serious complication among COVID-19 patients, with a very high mortality, that requires more attention by treating physicians, when prescribing medications, by looking for manifestations particular to the disease, such as SARS or SIRS.

Abstract Background In regard to obstetrical analgesia management there are different results related to the use of epidural analgesia versus mechanical adverse outcomes at delivery. Methods Cohort study of 23,183 consecutive, term, singleton vaginal deliveries, including spontaneous and induced labours, at a single institution from January 2004 to June 2016 to determine the association between epidural analgesia and different mechanical complications affecting maternal health such as severe perineal tears (SPT), abnormal foetal head position at delivery, instrumental delivery and caesarean section (CS). Multivariate logistic regression models were constructed to evaluate the risk factors of these mechanical complications with respect to possible cofounders. Results Epidural analgesia was used in 15,821 (68.24%) women. The logistic regression model showed a non-significant association between the use of epidural analgesia and SPT (odds ratio [OR], 078; 95% confidence interval [CI], 0.48–1.26; p = 0.310). Instrumental delivery and CSs were more frequently performed in cases than controls (p =

Background and Objectives: One of the most serious clinical outcomes in hospitalized patients with COVID-19 is severe acute respiratory syndrome (SARS). The aim is to analyze pharmacological treatment, survival and the main mortality predictors. Materials and Methods: A real-world data study from COVID-19-hospitalized patients with SARS from 1 March to 31 May 2020 has been carried out. Variables such as hospital length of stay, ventilation type and clinical outcomes have been taken into account. Results: In Castile and Leon, 14.03% of the 7307 in-hospital COVID-19 patients developed SARS, with a mortality rate of 42.53%. SARS prevalence was doubled in males compared to females, and 78.54% had an age of 65 years or more. The most commonly used medicines were antibiotics (89.27%), antimalarials (68.1%) and corticosteroids (55.9%). Survival of patients developing SARS was lower compared to patients without this complication (12 vs. 13 days). The main death predictors were disseminated intravascular coagulation (DIC) (OR: 13.87) and age (>65 years) (OR: 7.35). Conclusions: Patients older than 65 years who develop DIC have a higher probability of hospital death. Tocilizumab and steroids have been linked to a lower incidence of hospital death, being the main treatment for COVID-19 hospitalized patients with SARS.

Interferon lambda 3 (IFNL3, previously called IL-28B) is a cytokine with effects against viral and bacterial pathogens. We aimed to analyze the IFNL3 rs12980275 SNP in patients who underwent major surgery, in order to establish its relationship with susceptibility to septic shock and septic shock-related death in these patients. We performed a case-control study on 376 patients to establish the association between IFNL3 rs12980275 SNP and the susceptibility to develop septic shock. Besides, we performed a longitudinal study among 172 septic shock patients using survival analysis with one censoring point of 28-days mortality. The IFNL3 rs12980275 polymorphism was genotyped by Agena Bioscience's MassARRAY platform. IFNL3 rs12980275 polymorphism was not associated with higher susceptibility to infection and septic shock development. Regarding survival analysis, the Kaplan–Meier analysis showed that patients with IFNL3 rs12980275 AA genotype had higher survival than patients with GG genotype (p = 0.003). The Cox regression analysis adjusted by the most relevant clinical and epidemiological characteristics showed that the GG genotype (recessive model) and the presence of the G allele (additive model) were associated with higher risk of death [adjusted hazard ratio (aHR) = 2.15, p = 0.034; aHR = 1.50, p = 0.030, respectively]. In conclusion, IFNL3 rs12980275 polymorphism was associated with septic shock-related death in patients who underwent major surgery. The A allele was linked to protection, and the G allele was associated with an increased risk of death. This is a first preliminary study that suggests for the first time a role of IFNL3 polymorphisms in the prognosis of septic shock.

Abstract Early recognition of sepsis is a key factor to improve survival to this disease in surgical patients, since it allows prompt control of the infectious source. Combining pro-inflammatory and immunosupression biomarkers could represent a good strategy to improve sepsis detection. Here we evaluated the combination of procalcitonin (PCT) with gene expression levels of HLA-DRA to detect sepsis in a cohort of 154 surgical patients (101 with sepsis and 53 with no infection). HLA-DRA expression was quantified using droplet digital PCR, a next-generation PCR technology. Area under the receiver operating curve analysis (AUROC) showed that the PCT/HLA-DRA ratio outperformed PCT to detect sepsis (AUROC [CI95%], p): PCT: 0.80 [0.73–0.88],

Sepsis is characterized by deregulated host response to infection. Efficient therapies are still needed but a limitation for sepsis treatment is the heterogeneity in patients. Here Sweeney et al. generate prognostic models based on gene expression to improve risk stratification classification and prediction for 30-day mortality of patients.

Abstract Background Sepsis has represented a substantial health care and economic burden worldwide during the previous several decades. Our aim was to analyze the epidemiological trends of hospital admissions, deaths, hospital resource expenditures, and associated costs related to sepsis during the twenty-first century in Spain. Methods We performed a retrospective study of all sepsis-related hospitalizations in Spanish public hospitals from 2000 to 2013. Data were obtained from records in the Minimum Basic Data Set. The outcome variables were sepsis, death, length of hospital stay (LOHS), and sepsis-associated costs. The study period was divided into three calendar periods (2000–2004, 2005–2009, and 2010–2013). Results Overall, 2,646,445 patients with sepsis were included, 485,685 of whom had died (18.4%). The incidence of sepsis (events per 1000 population) increased from 3.30 (2000–2004) to 4.28 (2005–2009) to 4.45 (2010–2013) (p

A high percentage of patients with COVID-19 (coronavirus disease 2019) have previous cardiovascular disease (CVD). The findings presented here came from an epidemiological population-based registry study (real-world data) that enrolled all in-hospital COVID-19 patients with previous CVD from 1 March to 31 May 2020. Death, other comorbidities, hospital stay variables, ventilation type, and main clinical outcomes were evaluated. In Castile and Leon, 35.83% of the 7307 in-hospital COVID-19 patients who participated in this study had previous CVD, particularly arrhythmias (48.97%), cerebrovascular disease (25.02%), ischemic heart disease (22.8%), and chronic heart failure (20.82%). Of the patients, 21.36% were men and more than 90% were over 65 years of age, and the mortality rate achieved 32.93%. The most used medicines were antibiotics (91.41%), antimalarials (73.3%), steroids (46.64%), and antivirals (43.16%). The main predictors of death were age over 65 years (OR: 5), ventilation needs (OR: 2.81), treatment with anti-SIRS (systemic inflammatory response syndrome) medicines (OR: 1.97), antivirals (OR: 1.74) or steroids (OR: 1.68), SIRS (OR: 5.75), SARS (severe acute respiratory syndrome) (OR: 2.44), or AKI (acute kidney injury) (OR: 1.63) occurrence. Chronic heart failure and cerebrovascular disease were associated with a worse clinical course of COVID-19, especially in men older than 65 years with diabetes who developed SIRS, SARS, or AKI.

Sepsis is a major health problem worldwide. It is a time-dependent disease, with a high rate of morbidity and mortality. In this sense, an early diagnosis is essential to reduce these rates. The progressive increase of both the incidence and prevalence of sepsis has translated into a significant socioeconomic burden for health systems. Currently, it is the leading cause of noncoronary mortality worldwide and represents one of the most prevalent pathologies both in hospital emergency services and in intensive care units. In this article, we review the role of both endothelial dysfunction and neutrophil dysregulation in the physiopathology of this disease. The lack of a key symptom in sepsis makes it difficult to obtain a quick and accurate diagnosis of this condition. Thus, it is essential to have fast and reliable diagnostic tools. In this sense, the use of biomarkers can be a very important alternative when it comes to achieving these goals. Both new biomarkers and treatments related to endothelial dysfunction and neutrophil dysregulation deserve to be further investigated in order to open new venues for the diagnosis, treatment and prognosis of sepsis.

Abstract Background Pre-evaluation of endogenous immunoglobulin levels is a potential strategy to improve the results of intravenous immunoglobulins in sepsis, but more work has to be done to identify those patients who could benefit the most from this treatment. The objective of this study was to evaluate the impact of endogenous immunoglobulins on the mortality risk in sepsis depending on disease severity. Methods This was a retrospective observational study including 278 patients admitted to the ICU with sepsis fulfilling the SEPSIS-3 criteria, coming from the Spanish GRECIA and ABISS-EDUSEPSIS cohorts. Patients were distributed into two groups depending on their Sequential Organ Failure Assessment score at ICU admission (SOFA

The concept of healthcare-associated infections (as opposed to hospital-acquired infections) in intraabdominal infections (IAIs) is scarcely supported by data in the literature. The aim of the present study was to analyse community-onset IAIs (non-postoperative/non-nosocomial) in patients admitted to intensive care units (ICUs), to investigate differences in resistance patterns linked to healthcare exposure and mortality-associated factors. A one-year prospective observational study (17 Spanish ICUs) was performed distributing cases as healthcare-associated infections (HCAI), community-acquired infections (CAI) and immunocompromised patients (ICP). Bacteria producing extended-spectrum β-lactamases (ESBL) and/or carbapenemase (CPE), high-level aminoglycoside- and/or methicillin- and/or vancomycin- resistance were considered antimicrobial resistant (AMR). Mortality-associated factors were identified by regression multivariate analysis. Of 345 patients included (18.8% HCAI, 6.1% ICP, 75.1% CAI), 51.6% presented generalized peritonitis; 32.5% were >75 years (55.4% among HCAI). Overall, 11.0% cases presented AMR (7.0% ESBL- and/or CPE), being significantly higher in HCAI (35.4%) vs. CAI (5.8%) (p75 years (OR = 6.67, 95%CI = 2.56-17.36,p75 years, severity and Candida isolation but not with AMR.

Diphtheria antitoxin for therapeutic use is in limited supply. A potential source might be affinity-purified antibodies originally derived from plasma of adults who received a booster dose of a vaccine containing diphtheria toxoid. These antibodies might be useful for treating even severe cases of diphtheria.