Enhanced Catalytic Hydrogenation of Olefins in Sulfur-Rich Naphtha Using Molybdenum Carbide Supported on γ-Al2O3 Spheres under Steam Conditions: Simulating the Hot Separator Stream Process.

Spheres comprising 10 wt.% Mo2C/γ-Al2O3, synthesized through the sucrose route, exhibited unprecedented catalytic activity for olefin hydrogenation within an industrial naphtha feedstock that contained 23 wt.% olefins, as determined by supercritical fluid chromatography (SFC). The catalyst demonstrated resilience to sulfur, exhibiting no discernible deactivation signs over a tested 96 h operational period. The resultant hydrogenated naphtha from the catalytic process contained only 2.5 wt.% olefins when the reaction was conducted at 280 °C and 3.44 × 106 Pa H2, subsequently blended with Athabasca bitumen to meet pipeline specifications for oil transportation. Additionally, the carbide catalyst spheres effectively hydrogenated olefins under steam conditions without experiencing any notable hydrogenation in the aromatics. We propose the supported carbide catalyst as a viable alternative to noble metals, serving as a selective agent for olefin elimination from light petroleum distillates in the presence of steam and sulfur, mitigating the formation of gums and deposits during the transportation of diluted bitumen (dilbit) through pipelines.

Safety and effectiveness of isavuconazole in real-life non-neutropenic patients.

OBJECTIVES: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. METHODS: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. RESULTS: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. CONCLUSION: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.

Temperature variability and metabolic adaptation in terrestrial and aquatic ectotherms.

Thermodynamics is a major factor determining rates of energy expenditure, rates of biochemical dynamics, and ultimately the biological and ecological processes linked with resilience to global warming in ectothermic organisms. Nonetheless, whether ectothermic organisms exhibit general adaptive metabolic responses to cope with worldwide variation in thermal conditions has remained as an open question. Here we combine a model comparison approach with a global dataset of standard metabolic rates (SMR), including 1,160 measurements across 788 species of aquatic invertebrates, insects, fishes, amphibians and reptiles, to investigate the association between metabolic rates and environmental temperatures in their respective habitats. Our analyses suggest that variation in SMR after removing allometric and thermodynamic effects is best explained by the temperature range encountered across seasons, which always provided a better fit than the average temperature for the hottest and coldest month and mean annual temperatures. This pattern was consistent across taxonomic groups and robust to sensitivity analyses. Nonetheless, aquatic and terrestrial lineages responded differently to seasonality, with SMR declining - 6.8% °C-1 of thermal range across seasons in aquatic organisms and increasing 2.8% °C-1 in terrestrial organisms. These responses may reflect alternative strategies to mitigate the impact of increments in warmer temperatures on energy expenditure, either by means of metabolic reduction in thermally homogeneous water bodies or effective behavioral thermoregulation to exploit temperature heterogeneity on land.

A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study.

BACKGROUND: The identification of critically ill COVID-19 patients at risk of fatal outcomes remains a challenge. Here, we first validated candidate microRNAs (miRNAs) as biomarkers for clinical decision-making in critically ill patients. Second, we constructed a blood miRNA classifier for the early prediction of adverse outcomes in the ICU. METHODS: This was a multicenter, observational and retrospective/prospective study including 503 critically ill patients admitted to the ICU from 19 hospitals. qPCR assays were performed in plasma samples collected within the first 48 h upon admission. A 16-miRNA panel was designed based on recently published data from our group. RESULTS: Nine miRNAs were validated as biomarkers of all-cause in-ICU mortality in the independent cohort of critically ill patients (FDR < 0.05). Cox regression analysis revealed that low expression levels of eight miRNAs were associated with a higher risk of death (HR from 1.56 to 2.61). LASSO regression for variable selection was used to construct a miRNA classifier. A 4-blood miRNA signature composed of miR-16-5p, miR-192-5p, miR-323a-3p and miR-451a predicts the risk of all-cause in-ICU mortality (HR 2.5). Kaplan‒Meier analysis confirmed these findings. The miRNA signature provides a significant increase in the prognostic capacity of conventional scores, APACHE-II (C-index 0.71, DeLong test p-value 0.055) and SOFA (C-index 0.67, DeLong test p-value 0.001), and a risk model based on clinical predictors (C-index 0.74, DeLong test-p-value 0.035). For 28-day and 90-day mortality, the classifier also improved the prognostic value of APACHE-II, SOFA and the clinical model. The association between the classifier and mortality persisted even after multivariable adjustment. The functional analysis reported biological pathways involved in SARS-CoV infection and inflammatory, fibrotic and transcriptional pathways. CONCLUSIONS: A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.

Effect of viral storm in patients admitted to intensive care units with severe COVID-19 in Spain: a multicentre, prospective, cohort study.

BACKGROUND: The contribution of the virus to the pathogenesis of severe COVID-19 is still unclear. We aimed to evaluate associations between viral RNA load in plasma and host response, complications, and deaths in critically ill patients with COVID-19. METHODS: We did a prospective cohort study across 23 hospitals in Spain. We included patients aged 18 years or older with laboratory-confirmed SARS-CoV-2 infection who were admitted to an intensive care unit between March 16, 2020, and Feb 27, 2021. RNA of the SARS-CoV-2 nucleocapsid region 1 (N1) was quantified in plasma samples collected from patients in the first 48 h following admission, using digital PCR. Patients were grouped on the basis of N1 quantity: VIR-N1-Zero (<1 N1 copies per mL), VIR-N1-Low (1-2747 N1 copies per mL), and VIR-N1-Storm (>2747 N1 copies per mL). The primary outcome was all-cause death within 90 days after admission. We evaluated odds ratios (ORs) for the primary outcome between groups using a logistic regression analysis. FINDINGS: 1068 patients met the inclusion criteria, of whom 117 had insufficient plasma samples and 115 had key information missing. 836 patients were included in the analysis, of whom 403 (48%) were in the VIR-N1-Low group, 283 (34%) were in the VIR-N1-Storm group, and 150 (18%) were in the VIR-N1-Zero group. Overall, patients in the VIR-N1-Storm group had the most severe disease: 266 (94%) of 283 patients received invasive mechanical ventilation (IMV), 116 (41%) developed acute kidney injury, 180 (65%) had secondary infections, and 148 (52%) died within 90 days. Patients in the VIR-N1-Zero group had the least severe disease: 81 (54%) of 150 received IMV, 34 (23%) developed acute kidney injury, 47 (32%) had secondary infections, and 26 (17%) died within 90 days (OR for death 0·30, 95% CI 0·16-0·55; p<0·0001, compared with the VIR-N1-Storm group). 106 (26%) of 403 patients in the VIR-N1-Low group died within 90 days (OR for death 0·39, 95% CI 0·26-0·57; p<0·0001, compared with the VIR-N1-Storm group). INTERPRETATION: The presence of a so-called viral storm is associated with increased all-cause death in patients admitted to the intensive care unit with severe COVID-19. Preventing this viral storm could help to reduce poor outcomes. Viral storm could be an enrichment marker for treatment with antivirals or purification devices to remove viral components from the blood. FUNDING: Instituto de Salud Carlos III, Canadian Institutes of Health Research, Li Ka-Shing Foundation, Research Nova Scotia, and European Society of Clinical Microbiology and Infectious Diseases. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Molecular Docking and In Vitro Studies of Ochratoxin A (OTA) Biodetoxification Testing Three Endopeptidases.

Ochratoxin A (OTA) is considered one of the main mycotoxins responsible for health problems and considerable economic losses in the feed industry. The aim was to study OTA's detoxifying potential of commercial protease enzymes: (i) Ananas comosus bromelain cysteine-protease, (ii) bovine trypsin serine-protease and (iii) Bacillus subtilis neutral metalloendopeptidase. In silico studies were performed with reference ligands and T-2 toxin as control, and in vitro experiments. In silico study results showed that tested toxins interacted near the catalytic triad, similar to how the reference ligands behave in all tested proteases. Likewise, based on the proximity of the amino acids in the most stable poses, the chemical reaction mechanisms for the transformation of OTA were proposed. In vitro experiments showed that while bromelain reduced OTA's concentration in 7.64% at pH 4.6; trypsin at 10.69% and the neutral metalloendopeptidase in 8.2%, 14.44%, 45.26% at pH 4.6, 5 and 7, respectively (p < 0.05). The less harmful α-ochratoxin was confirmed with trypsin and the metalloendopeptidase. This study is the first attempt to demonstrate that: (i) bromelain and trypsin can hydrolyse OTA in acidic pH conditions with low efficiency and (ii) the metalloendopeptidase was an effective OTA bio-detoxifier. This study confirmed α-ochratoxin as a final product of the enzymatic reactions in real-time practical information on OTA degradation rate, since in vitro experiments simulated the time that food spends in poultry intestines, as well as their natural pH and temperature conditions.

Management of patients with suspected or confirmed antibiotic allergy. Executive summary of guidance from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Allergy and Clinical Immunology (SEAIC), the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Intensive Medicine and Coronary Care Units (SEMICYUC).

Suspected or confirmed antibiotic allergy is a frequently encountered clinical circumstance that influences antimicrobial prescribing and often leads to the avoidable use of less efficacious and/or more toxic or costly drugs than first-line antimicrobials. Optimizing antimicrobial therapy in patients with antibiotic allergy labels has become one of the priorities of antimicrobial stewardship programs (ASP) in several countries. This guidance document aims to make recommendations for the systematic approach to patients with suspected or confirmed antibiotic allergy based on current evidence. A panel of eleven members of involved Scientific Societies with expertise in the management of patients with suspected or confirmed antibiotic allergy formulated questions about the management of patients with suspected or confirmed antibiotic allergy. A systematic literature review was performed by a medical librarian. The questions were distributed among panel members who selected the most relevant references, summarized the evidence and formulated graded recommendations when possible. The answers to all questions were finally reviewed by all panel members. A systematic approach to patients with suspected or confirmed antibiotic allergy is recommended to improve antibiotic selection and, consequently clinical outcomes. A clinically oriented, 3-category risk-stratification strategy was recommended for patients with suspected antibiotic allergy. Complementary assessments should consider both clinical risk category and preferred antibiotic agent. Empirical therapy recommendations for the most relevant clinical syndromes in patients with suspected or confirmed ß-lactam allergy were formulated. Recommendations on the implementation and monitoring of the impact of the guidelines were formulated. ASP and allergists should design and implement activities that facilitate the most adequate antibiotic use in these patients.

Evaluation of trefoil factor 3 as a non-invasive biomarker of gastric intestinal metaplasia and gastric cancer in a high-risk population.

BACKGROUND: Adenocarcinoma is preceded by chronic atrophic gastritis, gastric intestinal metaplasia and dysplasia. Trefoil factor 3 (TFF3) is a peptide secreted by goblet cells, which is abundantly present in intestinal metaplasia. AIM: To evaluate the utility of serum TFF3 as a non-invasive biomarker for the diagnosis of intestinal metaplasia and gastric cancer. METHODS: Single-center, cross-sectional study of 274 patients who consecutively underwent upper gastrointestinal endoscopy with gastric biopsies (updated Sydney system). TFF3 levels were measured in serum by a commercial ELISA kit. Patients with normal histology or chronic atrophic gastritis without intestinal metaplasia comprised the control group. In addition, 14 patients with invasive gastric cancer were included as a reference group. The association between TFF3 levels and intestinal metaplasia was assessed by logistic regression. RESULTS: Patients with intestinal metaplasia (n=110) had a higher median TFF3 level as compared to controls (n=164), 13.1 vs. 11.9ng/mL, respectively (p=0.024). Multivariable logistic regression showed a no significant association between TFF3 levels and intestinal metaplasia (OR=1.20; 95%CI: 0.87-1.65; p-trend=0.273). The gastric cancer group had a median TFF3 level of 20.5ng/mL, and a significant association was found (OR=3.26; 95%CI: 1.29-8.27; p-trend=0.013). CONCLUSION: Serum levels of TFF3 do not discriminate intestinal metaplasia in this high-risk Latin American population. Nevertheless, we confirmed an association between TFF3 levels and invasive gastric cancer.

Uso de endoprótesis para el tratamiento de enfermedades no neoplásicas de la rodilla / Use of endoprosthesis for the treatment of non-neoplastic pathologies of the knee

Introducción: Las endoprótesis son el método de elección para la reconstrucción luego de las resecciones oncológicas. Los avances en los materiales y diseños permitieron expandir las indicaciones a enfermedades no neoplásicas. Su montaje intraoperatorio simple y rápido, y su estabilidad mecánica inmediata permiten una rehabilitación y una recuperación funcional tempranas. Sin embargo, la tasa de fallas es elevada, aunque distinta de la de las enfermedades oncológicas. Las causas predominantes son diferentes. Objetivos: Analizar nuestra experiencia con el uso de endoprótesis de rodilla y compararla con los estudios publicados, evaluando los resultados funcional y radiográfico, la supervivencia del implante y las causas de su eventual falla. Materiales y Métodos: Se seleccionaron pacientes con enfermedad no neoplásica compleja de rodilla que requirieran una reconstrucción con endoprótesis. Para el examen clínico y la evaluación funcional se utilizó el puntaje de la Musculoskeletal Tumor Society, y para las fallas de los implantes, la clasificación de Henderson y cols. modificada. Resultados:Se estudiaron 12 endoprótesis, con un seguimiento promedio de 3.8 años. Se registraron 2 fallas (18%), con un tiempo promedio hasta la falla de 47.5 meses. Una fue tipo 2 (aflojamiento aséptico) y la otra, tipo 4 (infección). No hubo otras complicaciones. En la evaluación funcional, el puntaje final medio fue del 76,6%. Conclusión: Nuestros resultados respaldan el uso de endoprótesis para enfermedades complejas no neoplásicas de rodilla en pacientes cuidadosamente seleccionados, pese a ser un procedimiento quirúrgico complejo y con muchas complicaciones. Nivel de Evidencia: IV

Introduction: Endoprosthesis is the gold standard for reconstruction after oncological resections. The advances regarding its materials and designs allowed for the expansion of the indications to non-neoplastic pathologies. Its simple and fast intraoperative assembly and its immediate mechanical stability allow for early rehabilitation and functional recovery. However, the failure rate is high, although it is different from oncological pathologies. The predominant causes are varied. Objectives: To analyze our experience in the use of knee endoprosthesis and compare it with the literature, evaluating functional outcomes, radiographic outcomes, implant survival and causes of eventual failure. Materials and Methods: Patients with complex non-neoplastic knee pathology that required reconstruction with endoprosthesis were selected. Clinical history, anamnesis, physical examination, and radiographs were reviewed. For clinical examination and functional evaluation, the MusculoSkeletal Tumor Society Score (MSTS Score) was used. For implant failures, the modified Henderson et al. classification was used. Results: 12 endoprostheses were studied, with an average follow-up of 3.8 years. Failures were recorded in 2 (18%), with a mean time to failure of 47.5 months. One type 2 failure (aseptic loosening) and one type 4 failure (infection) were recorded. No other complications were noted. For the functional evaluation, the mean final score was 76.6%. Conclusion: Our results support the use of endoprostheses for complex non-neoplastic knee diseases in carefully selected patients, despite being a complex surgical procedure with many complications.Keywords: Endoprosthesis; knee; infection; complications. Level of Evidence: IV

The wild plant Gnaphalium lavandulifolium as a sentinel for biomonitoring the effects of environmental heavy metals in the metropolitan area of México Valley.

Biomonitoring is a valuable tool for assessing the presence and effects of air pollutants such as heavy metals (HM); due to their toxicity and stability, these compounds can affect human health and the balance of ecosystems. To assess its potential as a sentinel organism of HM pollution, the wild plant Gnaphalium lavandulifolium was exposed to four sites in the metropolitan area of México Valley (MAMV): Altzomoni (ALT) Coyoacán (COY), Ecatepec (ECA), and Tlalnepantla (TLA) during 2, 4, and 8 weeks, between October and November 2019. Control plants remained under controlled conditions. The chemical analysis determined twelve HM (Al, As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, V, and Zn) in the leaves. Macroscopic damage to the leaves, later determined in semi-thin sections under light microscopy, lead to a finer analysis. Transmission electron microscope (TEM) showed major structural changes: chromatin condensation, protoplast shrinkage, cytoplasm vacuolization, cell wall thinning, decreased number and size of starch grains, and plastoglobules in chloroplasts. All these characteristics of stress-induced programed cell death (sPCD) were related to the significant increase of toxic HM in the leaves of the exposed plants compared to the control (p < 0.05). Immunohistochemistry revealed a significant amount of proteases with caspase 3-like activity in ECA and TLA samples during long exposure times. Ultrastructural changes and sPCD features detected confirmed the usefulness of G. lavandulifolium as a good biomonitor of HM contamination. They supported the possibility of considering subcellular changes as markers of abiotic stress conditions in plants.

Research on metallic glasses at the atomic scale: a systematic review.

Metallic glasses (MGs) have been long investigated in material science to understand the origin of their remarkable properties. With the help of computational simulations, researchers have delved into structure-property relationships, leading to a large number of reports. To quantify the available literature, we employed systematic review and bibliometric analysis on studies related to MGs and classical molecular dynamics simulations from 2000 to 2021. It was found that the total number of articles has increased remarkably, with China and the USA producing more than half of the reports. However, high-impact articles were mainly conducted in the latter. Collaboration networks revealed that top contributor authors are strongly connected with other researchers, which emphasizes the relevance of scientific cooperation. In regard to the evolution of research topics, according to article keywords, plastic behavior has been a recurrent subject since the early 2000s. Nevertheless, the traditional approach of studying monolithic MGs at the short-range order evolved to complex composites with characterizations at the medium-range order, including topics such as nanoglasses, amorphous/crystalline nanolaminates, rejuvenation, among others. As a whole, these findings provide researchers with an overview of past and current trends of research areas, as well as some of the leading authors, productivity statistics, and collaboration networks.

Immunomodulatory therapy for the management of critically ill patients with COVID-19: A narrative review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. AIM: To describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of hyperinflammation and abnormal immune responses to disease progression together with a complete narrative review of the different immunoadjuvant treatments used so far in COVID-19 and their indication in severe and life-threatening subsets. METHODS: A comprehensive literature search was developed. Authors reviewed the selected manuscripts following the PRISMA recommendations for systematic review and meta-analysis documents and selected the most appropriate. Finally, a recommendation of the use of each treatment was established based on the level of evidence of the articles and documents reviewed. This recommendation was made based on the consensus of all the authors. RESULTS: A brief rationale on the SARS-CoV-2 pathogenesis, immune response, and inflammation was developed. The usefulness of 10 different families of treatments related to inflammation and immunopathogenesis of COVID-19 was reviewed and discussed. Finally, based on the level of scientific evidence, a recommendation was established for each of them. CONCLUSION: Although several promising therapies exist, only the use of corticosteroids and tocilizumab (or sarilumab in absence of this) have demonstrated evidence enough to recommend its use in critically ill patients with COVID-19. Endotypes including both, clinical and biological characteristics can constitute specific targets for better select certain therapies based on an individualized approach to treatment.

Current Positioning against Severe Infections Due to Klebsiella pneumoniae in Hospitalized Adults.

Infections due to Klebsiella pneumoniae have been increasing in intensive care units (ICUs) in the last decade. Such infections pose a serious problem, especially when antimicrobial resistance is present. We created a task force of experts, including specialists in intensive care medicine, anaesthesia, microbiology and infectious diseases, selected on the basis of their varied experience in the field of nosocomial infections, who conducted a comprehensive review of the recently published literature on the management of carbapenemase-producing Enterobacterales (CPE) infections in the intensive care setting from 2012 to 2022 to summarize the best available treatment. The group established priorities regarding management, based on both the risk of developing infections caused by K. pneumoniae and the risk of poor outcome. Moreover, we reviewed and updated the most important clinical entities and the new antibiotic treatments recently developed. After analysis of the priorities outlined, this group of experts established a series of recommendations and designed a management algorithm.

Autoimmune hepatitis triggered by COVID-19.

We present the case of a 60-year-old female with no drug allergies or toxic habits, with hypothyroidism, and receiving treatment with levothyroxine. She was admitted in February 2021 and presented with choluria of 72 hours duration; there were no abdominal or respiratory clinical symptoms, and no related fever. Medical examination findings included mucocutaneous jaundice and a recorded oxygen saturation of 97 % in ambient air. There was a notable pattern of cytolysis compatible with acute hepatitis, and no history hepatotoxic drugs. Screening was performed for acute hepatitis in addition to serology testing, determination of autoantibodies and immunoglobulins, a PCR test for COVID, and a radiologic study.

Thiopurine adherence: a high prevalence with low impact on UC outcomes.

INTRODUCTION: thiopurines are used as maintenance therapy in patients with ulcerative colitis (UC). There are contradictory results regarding the relationship between adherence to treatment and risk of relapse. OBJECTIVES: to quantify and evaluate the trends in thiopurine prescription rates, and to determine the impact and risk factors of non-adherence. METHODS: analytical, observational, retrospective study of UC patients taking thiopurines included in the ENEIDA single-center registry from October 2017 to October 2019. Adult patients in clinical remission at the beginning of the study on thiopurines maintenance treatment for at least 6 months before recruitment were included. Adherence was evaluated with an electronic pharmaceutical prescription system. Adherence was considered when 80 % or more of the prescribed medication was dispensed at the pharmacy. Kaplan-Meier curves and a regression model were used to examine year-to-year treatment dispensation, and to identify factors associated with non-adherence. RESULTS: a total of 41 patients were included, of whom 71 % were males with a mean age of 44 (14), and 26.8 % were concomitantly managed with biological therapy. Overall, 22 % were non-adherent to thiopurines. No predictive factors of non-adherence were identified. Adherence rate did not correlate with disease activity during two years of follow-up (OR 1.6; 95 % CI = 0.3-9.1). Left-sided colitis and concomitant biological treatment were related with disease relapse (p ≤ 0.01). CONCLUSION: adherence to thiopurines in UC patients is high (78 %). Non-adherence is not related to clinical or pharmacological factors. Adherence rate was not associated with disease activity.

Corticosteroid treatment and mortality in mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients: a multicentre cohort study.

BACKGROUND: Some unanswered questions persist regarding the effectiveness of corticosteroids for severe coronavirus disease 2019 (COVID-19) patients. We aimed to assess the clinical effect of corticosteroids on intensive care unit (ICU) mortality among mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients. METHODS: This was a retrospective study of prospectively collected data conducted in 70 ICUs (68 Spanish, one Andorran, one Irish), including mechanically ventilated COVID-19-associated ARDS patients admitted between February 6 and September 20, 2020. Individuals who received corticosteroids for refractory shock were excluded. Patients exposed to corticosteroids at admission were matched with patients without corticosteroids through propensity score matching. Primary outcome was all-cause ICU mortality. Secondary outcomes were to compare in-hospital mortality, ventilator-free days at 28 days, respiratory superinfection and length of stay between patients with corticosteroids and those without corticosteroids. We performed survival analysis accounting for competing risks and subgroup sensitivity analysis. RESULTS: We included 1835 mechanically ventilated COVID-19-associated ARDS, of whom 1117 (60.9%) received corticosteroids. After propensity score matching, ICU mortality did not differ between patients treated with corticosteroids and untreated patients (33.8% vs. 30.9%; p = 0.28). In survival analysis, corticosteroid treatment at ICU admission was associated with short-term survival benefit (HR 0.53; 95% CI 0.39-0.72), although beyond the 17th day of admission, this effect switched and there was an increased ICU mortality (long-term HR 1.68; 95% CI 1.16-2.45). The sensitivity analysis reinforced the results. Subgroups of age < 60 years, severe ARDS and corticosteroids plus tocilizumab could have greatest benefit from corticosteroids as short-term decreased ICU mortality without long-term negative effects were observed. Larger length of stay was observed with corticosteroids among non-survivors both in the ICU and in hospital. There were no significant differences for the remaining secondary outcomes. CONCLUSIONS: Our results suggest that corticosteroid treatment for mechanically ventilated COVID-19-associated ARDS had a biphasic time-dependent effect on ICU mortality. Specific subgroups showed clear effect on improving survival with corticosteroid use. Therefore, further research is required to identify treatment-responsive subgroups among the mechanically ventilated COVID-19-associated ARDS patients.

Detection of SARS-CoV-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 patients.

COVID-19 has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection in serum as a severity biomarker in COVID-19. Retrospective observational study including 193 patients admitted for COVID-19. Detection of SARS-CoV-2 RNA in serum (viremia) was performed with samples collected at 48-72 h of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19. Viremia was detected in 50-60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p < 0.001). Patients with viremia were older (p = 0.006), had poorer baseline oxygenation (PaO2/FiO2; p < 0.001), more severe lymphopenia (p < 0.001) and higher LDH (p < 0.001), IL-6 (p = 0.021), C-reactive protein (CRP; p = 0.022) and procalcitonin (p = 0.002) serum levels. We defined "relevant viremia" when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35% specificity. Relevant viremia predicted death during hospitalization (OR 9.2 [3.8-22.6] for Roche, OR 10.3 [3.6-29.3] for TFS; p < 0.001). Cox regression models, adjusted by age, sex and Charlson index, identified increased LDH serum levels and relevant viremia (HR = 9.87 [4.13-23.57] for TFS viremia and HR = 7.09 [3.3-14.82] for Roche viremia) as the best markers to predict mortality. Viremia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 patients. Viremia is highly reproducible with two different techniques (TFS and Roche), has a good consistency with other severity biomarkers for COVID-19 and better predictive accuracy.

Prognostic Value of Procalcitonin and C-Reactive Protein in 1608 Critically Ill Patients with Severe Influenza Pneumonia.

Background: Procalcitonin (PCT) and C-Reactive protein (CRP) are well-established sepsis biomarkers. The association of baseline PCT levels and mortality in pneumonia remains unclear, and we still do not know whether biomarkers levels could be related to the causative microorganism (GPC, GNB). The objective of this study is to address these issues. Methods: a retrospective observational cohort study was conducted in 184 Spanish ICUs (2009-2018). Results: 1608 patients with severe influenza pneumonia with PCT and CRP available levels on admission were included, 1186 with primary viral pneumonia (PVP) and 422 with bacterial Co-infection (BC). Those with BC presented higher PCT levels (4.25 [0.6-19.5] versus 0.6 [0.2-2.3]ng/mL) and CRP (36.7 [20.23-118] versus 28.05 [13.3-109]mg/dL) as compared to PVP (p < 0.001). Deceased patients had higher PCT (ng/mL) when compared with survivors, in PVP (0.82 [0.3-2.8]) versus 0.53 [0.19-2.1], p = 0.001) and BC (6.9 [0.93-28.5] versus 3.8 [0.5-17.37], p = 0.039). However, no significant association with mortality was observed in the multivariate analysis. The PCT levels (ng/mL) were significantly higher in polymicrobial infection (8.4) and GPC (6.9) when compared with GNB (1.2) and Aspergillus (1.7). The AUC-ROC of PCT for GPC was 0.67 and 0.32 for GNB. The AUROC of CRP was 0.56 for GPC and 0.39 for GNB. Conclusions: a single PCT/CRP value at ICU admission was not associated with mortality in severe influenza pneumonia. None of the biomarkers have enough discriminatory power to be used for predicting the causative microorganism of the co-infection.