Deploying unsupervised clustering analysis to derive clinical phenotypes and risk factors associated with mortality risk in 2022 critically ill patients with COVID-19 in Spain

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Fenotips; Factors de risc; Infecció greu per SARS-CoV-2Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Fenotipos; Factores de riesgo; Infección grave por SARS-CoV-2Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Phenotypes; Risk factors; Severe SARS-CoV-2 infectionBackground The identification of factors associated with Intensive Care Unit (ICU) mortality and derived clinical phenotypes in COVID-19 patients could help for a more tailored approach to clinical decision-making that improves prognostic outcomes. Methods Prospective, multicenter, observational study of critically ill patients with confirmed COVID-19 disease and acute respiratory failure admitted from 63 ICUs in Spain. The objective was to utilize an unsupervised clustering analysis to derive clinical COVID-19 phenotypes and to analyze patient’s factors associated with mortality risk. Patient features including demographics and clinical data at ICU admission were analyzed. Generalized linear models were used to determine ICU morality risk factors. The prognostic models were validated and their performance was measured using accuracy test, sensitivity, specificity and ROC curves. Results The database included a total of 2022 patients (mean age 64 [IQR 5–71] years, 1423 (70.4%) male, median APACHE II score (13 [IQR 10–17]) and SOFA score (5 [IQR 3–7]) points. The ICU mortality rate was 32.6%. Of the 3 derived phenotypes, the A (mild) phenotype (537; 26.7%) included older age ( 65 years), high severity of illness and a higher likelihood of development shock. Crude ICU mortality was 20.3%, 25% and 45.4% for A, B and C phenotype respectively. The ICU mortality risk factors and model performance differed between whole population and phenotype classifications. Conclusion The presented machine learning model identified three clinical phenotypes that significantly correlated with host-response patterns and ICU mortality. Different risk factors across the whole population and clinical phenotypes were observed which may limit the application of a “one-size-fits-all” model in practice.This study was supported by the Spanish Intensive Care Society (SEMICYUC) and Ricardo Barri Casanovas Foundation. The study sponsors have no role in the study design, data collection, data analysis, data interpretation, or writing of the report

Investigating the Influence of Au Nanoparticles on Porous SiO2-WO3 and WO3 Methanol Transformation Catalysts

"This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Physical Chemistry C, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021%2Facs.jpcc.6b08125Analyzing the structural and chemical properties of materials at the interface of metal nanoparticles and metal oxide supports is important for catalytic applications. Tungsten oxide (WO3) is a widely studied catalyst, but changing the catalytic reactivity at the surface of this oxide with metal nanoparticles is of interest. In this work, we sought to modify the redox properties of porous WO3 and SiO2 WO3 catalysts with sonochemically deposited gold nanoparticles (Au NPs) in order to access and study this reaction pathway. Characterization using powder X-ray diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma optical emission spectroscopy (ICP-OES) confirmed that crystalline Au NPs with diameters of 5-12 nm were distributed throughout the catalysts. Temperature-programmed desorption (TPD) was used to probe the surface acidity of the catalysts. The physico-chemical characteristics of catalysts have been also discussed by considering the catalytic performance of these materials in the aerobic transformation of methanol. Catalysts containing nanocrystalline WO3 but no Au NPs displayed very high selectivity to DME (>60%) at all conversions with minor oxidation reactivity, which highlighted the acidic nature of these catalysts. No effect on the acidity of the catalysts was observed by TPD when Au NPs were loaded in the catalysts. The reducibility of the crystalline WO3 species, however, increased significantly due to the interaction with Au NPs, as observed by temperature-programmed reduction (TPR). In the gas-phase transformation of MeOH under aerobic conditions, catalysts modified with Au NPs showed greater activity compared to nonmodified catalysts. In addition, oxidation selectivity to products such as methyl formate as well as formaldehyde, dimethoxymethane, and carbon oxides became heavily favored with only minor dehydration selectivity. The redox properties of these WO3 catalysts could be tuned by changing the Au loading. More labile lattice oxygen and enhanced redox properties at the surface of WO3 modified with Au NPs clearly altered these traditional dehydration catalysts to potential oxidation catalysts. Thus, modification of WO3 with Au is an effective way to expand the MeOH transformation product distribution beyond DME to other useful, oxidized products not typically observed over pure WO3.The authors would like to thank the University of Vermont and the DGICYT in Spain (CTQ2015-68951-C3-1-R, CTQ2012-37925-C3-3-R, and SEV-2012-0267 Severo Ochoa Projects) for financial support and David M. Parker for assistance with catalyst synthesis.Depuccio, DP.; Ruiz-Rodríguez, L.; Rodriguez-Castellon, E.; Botella Asuncion, P.; López Nieto, JM.; Landry, CC. (2016). Investigating the Influence of Au Nanoparticles on Porous SiO2-WO3 and WO3 Methanol Transformation Catalysts. Journal of Physical Chemistry C. 120(49):27954-27963. https://doi.org/10.1021/acs.jpcc.6b08125S27954279631204

COVID-19: Some unresolved issues

Two years after the COVID-19 pandemic, many uncertainties persist about the causal agent, the disease and its future. This document contains the reflection of the COVID-19 working group of the Official College of Physicians of Madrid (ICOMEM) in relation to some questions that remain unresolved. The document includes considerations on the origin of the virus, the current indication for diagnostic tests, the value of severity scores in the onset of the disease and the added risk posed by hypertension or dementia. We also discuss the possibility of deducing viral behavior from the examination of the structure of the complete viral genome, the future of some drug associations and the current role of therapeutic resources such as corticosteroids or extracorporeal oxygenation (ECMO). We review the scarce existing information on the reality of COVID 19 in Africa, the uncertainties about the future of the pandemic and the status of vaccines, and the data and uncertainties about the long-term pulmonary sequelae of those who suffered severe pneumonia.post-print462 K

New variants of SARS-CoV-2

The emergence and spread of new variants of SARS-CoV-2 has produced enormous interest due to their possible implication in the improved transmissibility of the virus, their consequences in the individual evolution of the infection, as well as in the possible escape from the immunity generated by the current vaccines. The variants that attract most attention are those of public health concern, including B.1.1.7 (UK), P.1 (Brazilian) and B.1.351 (South African). This list is extended by the variants of interest that emerge and are expanding in certain countries but are found sporadically in others, such as B.1.427 and B.1.429 (Californians) or B.1.617 (Indian). Whole genome sequencing or strategies specifically targeting the spicule gene are used in the microbiology laboratories for characterization and detection. The number of infected individuals, the sanitary situation of each country, epidemiological measures and vaccination strategies influence its dispersion and new variants are expected to emerge. This emergence can only be avoided today by increasing the vaccinated population in all countries and by not relaxing epidemiological containment measures. It is not excluded that in the future it will be necessary to revaccinate against new variants.post-print186 K

Persistence and viability of SARS-CoV-2 in primary infection and reinfections

Since the beginning of the SARS-CoV-2 epidemic, virus isolation in the infected patient was only possible for a short period of time and it was striking that this occurred constantly and did not provide guidance on the clinical course. This fact led to confusion about the efficacy of some of the drugs initially used, which seemed to have a high efficiency in viral clearance and proved ineffective in modifying the course of the disease. The immune response also did not prove to be definitive in terms of evolution, although most of the patients with very mild disease had a weak or no antibody response, and the opposite was true for the most severe patients. With whatever the antibody response, few cases have been re-infected after a first infection and generally, those that have, have not reproduced a spectrum of disease similar to the first infection. Among those re-infected, a large number have been asymptomatic or with very few symptoms, others have had a moderate picture and very few have had a poor evolution. Despite this dynamic of rapid viral clearance, laboratory tests were still able to generate positive results in the recovery of genomic sequences and this occurred in patients who were already symptom-free, in others who were still ill and in those who were very seriously ill. There was also no good correlate. For this reason and with the perspective of this year and the half of pandemic, we compiled what the literature leaves us in these aspects and anticipating that, as always in biology, there are cases that jump the limits of the general behavior of the dynamics of infection in genera

Actions and attitudes on the immunized patients against SARS-CoV-2

The access to COVID vaccines by millions of human beings and their high level of protection against the disease, both in its mild and severe forms, together with a plausible decrease in the transmission of the infection from vaccinated patients, has prompted a series of questions from the members of the College of Physicians of Madrid (ICOMEM) and the society. The ICOMEM Scientific Committee on this subject has tried to answer these questions after discussion and consensus among its members. The main answers can be summarized as follows: The occurrence of new SARS-CoV-2 infections in both vaccinated and previously infected patients is very low, in the observation time we already have. When breakthrough infections do occur, they are usually asymptomatic or mild and, purportedly, should have a lower capacity for transmission to other persons. Vaccinated subjects who have contact with a SARS-CoV-2 infected patient can avoid quarantine as long as they are asymptomatic, although this decision depends on variables such as age, occupation, circulating variants, degree of contact and time since vaccination. In countries with a high proportion of the population vaccinated, it is already suggested that fully vaccinated persons could avoid the use of masks and social distancing in most circumstances. Systematic use of diagnostic tests to assess the immune response or the degree of protection against reinfection after natural infection or vaccination is discouraged, since their practical consequences are not known at this time. The existing information precludes any precision regarding a possible need for future revaccination. This Committee considers that when mass vaccination of health care workers and the general population is achieved, SARS-CoV-2 screening tests could be avoided at least in out-patient care and in the case of exploratory procedures that do not require hospitalizatio

A body weight loss- and health-promoting gut microbiota is established after bariatric surgery in individuals with severe obesity

Obesity has reached an epidemic level worldwide, and bariatric surgery (BS) has been proven to be the most efficient therapy to reduce severe obesity-related comorbidities. Given that the gut microbiota plays a causal role in obesity development and that surgery may alter the gut environment, investigating the impact of BS on the microbiota in the context of severe obesity is important. Although, alterations at the level of total gut bacteria, total gene content and total metabolite content have started to be disentangled, a clear deficit exists regarding the analysis of the active fraction of the microbiota, which is the fraction that is most reactive to the BS. Here, active gut microbiota and associated metabolic functions were evaluated using shotgun proteomics and metabolomics in 40 severely obese volunteers. Samples from each volunteer were obtained under basal conditions, after a short high protein and calorie-restricted diet, and 1 and 3 months after BS, including laparoscopic surgery through Roux-en-Y Gastric Bypass or Sleeve Gastrectomy. The results revealed for the first time the most active microbes and metabolic flux distribution pre- and post-surgery and deciphered main differences in the way sugars and short-fatty acids are metabolized, demonstrating that less energy-generating and anaerobic metabolism and detoxification mechanisms are promoted post-surgery. A comparison with non-obese proteome data further signified different ways to metabolize sugars and produce short chain fatty acids and deficiencies in proteins involved in iron transport and metabolism in severely obese individuals compared to lean individuals.This work was funded by grants SAF2015-65878-R, BIO2017-85522-R, PID2019-105969GB-I00 and RTI2018-095166-B-I00 from the Ministry of Science, Innovation and Universities, by the Ministry of Science and Innovation, by the Instituto de Salud Carlos III (projects PIE14/00045 and AC17/00022), Fundación Agencia Española contra el Cáncer and Instituto de Salud Carlos III(projects ERA NET TRANSCAN-2 AC17/00022 and AECC 2017-1485), Generalitat Valenciana (project Prometeo/2018/A/133) and co-financed by the European Regional Development Fund (ERDF). The proteomic analysis was performed in the Proteomics Facility of The Spanish National Center for Biotechnology (CNB-CSIC) that belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019.Peer reviewe

Vacunación anti-COVID-19: la realidad tras los ensayos clínicos.

Tras el comienzo de la vacunación frente a SARS-CoV-2, se está acumulando ya suficiente experiencia clínica, en el mundo real y fuera de los ensayos clínicos, para resolver algunas de las cuestiones que siguen pendientes sobre este problema. El Comité Científico sobre COVID-19 del Colegio de Médicos de Madrid ha discutido y revisado algunos de estos temas con una aproximación multidisciplinar. El documento que sigue es un intento de responder a algunas de dichas cuestiones con la información disponible hasta el momento. Este documento se ha estructurado en preguntas sobre distintos aspectos de las indicaciones, eficacia y tolerancia de la vacunación anti- COVID-19.post-print214 K

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio