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Risk factors for mortality in patients with COVID-19 needing extracorporeal respiratory support.
No full textWhen indicating ECMO in patients with COVID-19, centre case volume, age, driving pressure and the duration of symptoms (not the length of MV) should be taken into account. Large drainage cannula and high PEEP levels during the first days are recommended. https://bit.ly/3DGjGk
Evaluation of coagulation function by rotation thromboelastometry in critically ill patients with severe Covid-19 Pneumonia
No full textBeta-blocker use in patients with heart failure with preserved ejection fraction and sinus rhythm.
No full textBeta-adrenergic receptor blockers (beta-blockers) are frequently used for patients with heart failure (HF) with preserved ejection fraction (HFpEF), although evidence-based recommendations for this indication are still lacking. Our goal was to assess which clinical factors are associated with the prescription of beta-blockers in patients discharged after an episode of HFpEF decompensation, and the clinical outcomes of these patients. We assessed 1078 patients with HFpEF and in sinus rhythm who had experienced an acute HF episode to explore whether prescription of beta-blockers on discharge was associated with one-year all-cause mortality or the composite endpoint of one-year all-cause death or HF readmission. We also examined the clinical factors associated with beta-blocker discharge prescription for such patients. At discharge, 531 (49.3%) patients were on beta-blocker therapy. Patients on beta-blockers more often had a prior diagnosis of hypertension and more comorbidity (including ischemic heart disease) and a better functional status, but less often a prior diagnosis of chronic obstructive pulmonary disease. These patients had a lower heart rate on admission and more often used angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors and loop diuretics. One year after the index admission, 161 patients (15%) had died and 314 (29%) had experienced the composite endpoint. After multivariate adjustment, beta-blocker prescription was not associated with either all-cause mortality (HR=0.83 [95% CI 0.61-1.13]; p=0.236) or the composite endpoint (HR=0.98 [95% CI 0.79-1.23]; p=0.882). In patients with HFpEF in sinus rhythm, beta-blocker use was not related to one-year mortality or mortality plus HF readmission.S
In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against Mpro, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature.
No full textIn the work described here, a number of sesquiterpenes and benzoxazinoids from natural sources, along with their easily accessible derivatives, were evaluated against the main protease, RNA replicase and spike glycoprotein of SARS-CoV-2 by molecular docking. These natural products and their derivatives have previously shown remarkable antiviral activities. The most relevant compounds were the 4-fluoro derivatives of santamarine, reynosin and 2-amino-3H-phenoxazin-3-one in terms of the docking score. Those compounds fulfill the Lipinski's rule, so they were selected for the analysis by molecular dynamics, and the kinetic stabilities of the complexes were assessed. The addition of the 4-fluorobenzoate fragment to the natural products enhances their potential against all of the proteins tested, and the complex stability after 50 ns validates the inhibition calculated. The derivatives prepared from reynosin and 2-amino-3H-phenoxazin-3-one are able to generate more hydrogen bonds with the Mpro, thus enhancing the stability of the protein-ligand and generating a long-term complex for inhibition. The 4-fluoro derivate of santamarine and reynosin shows to be really active against the spike protein, with the RMSD site fluctuation lower than 1.5 Å. Stabilization is mainly achieved by the hydrogen-bond interactions, and the stabilization is improved by the 4-fluorobenzoate fragment being added. Those compounds tested in silico reach as candidates from natural sources to fight this virus, and the results concluded that the addition of the 4-fluorobenzoate fragment to the natural products enhances their inhibition potential against the main protease, RNA replicase and spike protein of SARS-CoV-2.This paper is affectionately dedicated in the memory of Mariola Macías (1984–2020) on her second anniversary. She was an excellent professional, an emergency doctor at Hospital Punta Europa, Algeciras (Cadiz), Spain, a Doctor in Immunology and, above all, a great person. She worked intensively not only in clinical functions but also in research against SARS- CoV-2 and was passionate about Natural Products. Her humanity, kindness, special and unmistakable smile, generosity, dedication and professionalism will never be forgotten. All simulations were performed using computational facilities at the ‘Servicio de Supercomputación of Área de Sistemas de Información′ of the University of Cádiz. F.J.R.M thanks Iván Carrillo-Berdugo for his MD comments and advice.S
Carbapenem Combinations for Infections Caused by Carbapenemase-Producing Pseudomonas aeruginosa: Experimental In Vitro and In Vivo Analysis.
No full textIn the context of difficult-to-treat carbapenem-resistant Pseudomonas aeruginosa infections, we evaluated imipenem, meropenem, and doripenem combinations against eleven carbapenemase-producing P. aeruginosa isolates. According to the widespread global distribution of high-risk clones and carbapenemases, four representative isolates were selected: ST175 (OXA-2/VIM-20), ST175 (VIM-2), ST235 (GES-5), and ST111 (IMP-33), for efficacy studies using a sepsis murine model. Minimum inhibitory concentration (mg/L) ranges were 64-256 for imipenem and 16-128 for meropenem and doripenem. In vitro, imipenem plus meropenem was synergistic against 72% of isolates and doripenem plus meropenem or imipenem against 55% and 45%, respectively. All combinations were synergistic against the ST175, ST235, and ST155 clones. In vivo, meropenem diminished the spleen and blood bacterial concentrations of four and three isolates, respectively, with better efficacy than imipenem or doripenem. The combinations did not show efficacy compared with the more active monotherapies, except for imipenem plus meropenem, which reduced the ST235 bacterial spleen concentration. Mortality decreased with imipenem plus meropenem or doripenem for the ST175 isolate. Results suggest that carbapenem combinations are not an alternative for severe infections by carbapenemase-producing P. aeruginosa. Meropenem monotherapy showed in vivo efficacy despite its high MIC, probably because its dosage allowed a sufficient antimicrobial exposure at the infection sites.S
Editorial: Systems Biology Approach to the Immunology of Asthma and Allergy.
No full textTheprevalence of allergic diseases as well as their severity have risen progressively during the last decades, affecting a considerable percentage of the population worldwide. Asthma and allergies as a whole are heterogeneous and show acomplexpatternof disease endotypes, a complicated balance between immune tolerance and allergic sensitization, and a progression of allergic diseases. The application of highthroughput technologies enables the profiling of genomes, epigenomes, transcriptomes, microbiomes and metabolomestogainabetter understandingoftheimmunemechanismsunderlyingasthmaandallergies. The use of systems biology aims at combining and connecting the information on the different molecular components on the cell, tissue, or organ level to discover the properties of the full system. A system’s level understanding of the complex allergic diseases will then assist in implementing personalized medicine strategies for the treatment of allergic and asthmatic patients.This work was supported by ISCIII (PI18/01467), cofounded by FEDER “Investing in your future” for the thematic network and co-operative research centres ARADyAL RD16/0006/0015; as well as by the grant from Ministerio de Ciencia, Innovación y Universidades co-financed with FEDER RTI2018-095166-B-I00.S
No evidence of brown adipose tissue activation after 24 weeks of supervised exercise training in young sedentary adults in the ACTIBATE randomized controlled trial.
No full textExercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise, n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX n = 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control; n = 35, MOD-EX; n = 31, and VIG-EX; n = 31). We observed no changes in BAT volume (Δ Control: -22.2 ± 52.6 ml; Δ MOD-EX: -15.5 ± 62.1 ml, Δ VIG-EX: -6.8 ± 66.4 ml; P = 0.771) or 18F-fluorodeoxyglucose uptake (SUVpeak Δ Control: -2.6 ± 3.1 ml; Δ MOD-EX: -1.2 ± 4.8, Δ VIG-EX: -2.2 ± 5.1; p = 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.The authors thank all the participants who took part in the study, as well as those researchers who contributed to the study design (Drs. Barbara Cannon, Jan Nedergaard, José A Lopez Calbet, John Blundell, Graham Finlayson, Catherine Gibbons, Jose Antonio Jimenez-Rios, Emilio Martinez de Vitoria, and Maria Dolores Ruiz), data collection (Dr. Carlos de Teresa, Socorro Navarrete, Rosa Lozano, Esther Brea, Dr. Jose Rubio Lopez, Dr. Jose M Pascual, Dr. Josune Olza, Dr. Francisco Ruiz Ojeda, Amalia Cano Nieto, María Ruiz Ruiz, Laura Frutos, Marina Bórrallo, Miguel Angel Contreras Gomez, Juan Prados-Ruiz, Abdel-Karim Ruiz, Dr. Yolanda García Rivero, and Dr. Ángel Ramirez Navarro), and to the discussion of the results (Brooks Leitner and Dr. Mariëtte Boon). This study was funded by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393; J.R.R.) and PTA-12264I, Retos de la Sociedad (DEP2016-79512-R; J.R.R.) and European Regional Development Funds (ERDF; J.R.R.), the Spanish Ministry of Education (FPU13/04365 (G.S.D.), FPU14/04172 (F.A.G.), FPU15/04059 (J.M.A.), FPU16/03653 (A.M.G.), FPU16/02828 (F.J.O.P.), FPU16/05159 (H.X.), FPU17/01523 (L.O.A.), FPU19/01609 (L.J.F.)), International Doctoral Studies Scholarship no. 440575 from the Mexican National Council of Science and Technology (CONACYT; WDMA), the Fundación Iberoamericana de Nutrición (FINUT; JRR), the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022; J.R.R.), the AstraZeneca HealthCare Foundation (J.R.R.), the University of Granada Plan Propio de Investigación 2016 -Excellence actions: Unit of Excellence on Exercise and Health (UCEES) (J.R.R.)- and Plan Propio de Investigación 2018 - Programa Contratos-Puente and Programa Perfecionamiento de Doctores (G.S.D.), the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (ERDF; ref. SOMM17/6107/UGR; JRR), the Junta de Andalucía, Consejería de Economía, Conocimiento, Empresas y Universidad (ref. P18-RT-4455; J.R.R.), the Fundación Alfonso Martín Escudero (B.M.T. and G.S.D.), the Maria Zambrano fellowship by the Ministerio de Universidades y la Unión Europea–NextGenerationEU (RR_C_2021_04; B.M.T.), and the Novo Nordisk Foundation (NNF18OC0032394; M.S.). This study was performed as part of a PhD thesis conducted within the Biomedicine Doctoral Studies Program of the University of Granada, Spain. The funding agencies had no role in study design, data collection and analysis or manuscript writing.S
Dexamethasone as risk-factor for ICU-acquired respiratory tract infections in severe COVID-19.
No full textDexamethasone is the only drug that has consistently reduced mortality in patients with COVID-19, especially in patients needing oxygen or invasive mechanical ventilation. However, there is a growing concern about the relation of dexamethasone with the unprecedented rates of ICU-acquired respiratory tract infections (ICU-RTI) observed in patients with severe COVID-19. This was a multicenter, prospective cohort study; conducted in ten countries in Latin America and Europe. We included patients older than 18 with confirmed SARS-CoV-2 requiring ICU admission. A multivariate logistic regression and propensity score matching (PSM) analysis was conducted to determine the relation between dexamethasone treatment and ICU-RTI. A total of 3777 patients were included. 2065 (54.7%) were treated with dexamethasone within the first 24 h of admission. After performing the PSM, patients treated with dexamethasone showed significantly higher proportions of VAP (282/1652 [17.1%] Vs. 218/1652 [13.2%], p = 0.014). Also, dexamethasone treatment was identified as an adjusted risk factor of ICU-RTI in the multivariate logistic regression model (OR 1.64; 95%CI: 1.37-1.97; p Patients treated with dexamethasone for severe COVID-19 had a higher risk of developing ICU-acquired respiratory tract infections after adjusting for days of invasive mechanical ventilation and ICU length of stay, suggesting a cautious use of this treatment
Differences in early-onset vs. late-onset psoriatic arthritis: data from the respondia and regisponser studies.
No full textBackground The prevalence of late-onset psoriatic arthritis (PsA) is increasing in parallel with the progressive aging of the population. The elderly population presents a greater functional deterioration and a greater number of comorbidities than the young people. With this study we aim to find clinically relevant differences to predict the evolution and prognosis of the disease depending on the onset of the symptoms to carry out a more exhaustive follow-up. Objectives To evaluate the association of the age at onset of PsA symptoms with the characteristics and burden of the disease. Methods Observational study that includes a subgroup of 231 patients with Psoriatic Arthritis (PsA) from the REGISPONSER study (Registry of Spondyloarthritis of Spanish Rheumatology) and the RESPONDIA study (Ibero-American Registry of Spondyloarthropathies). Patients with less than 10 years of disease duration (since the first symptom) were selected so that the sample was homogeneous. Patients were divided into two groups according to the age of PsA onset (early-onset: ≤40 years old and late-onset: ≥60 years old). The characteristics and burden of the disease were compared using the Student’s t-test/Mann-Whitney U test for quantitative variables or using the chi-square/Fisher test for qualitative variables.S
MASS CYTOMETRY DATA RECLASSIFY SYSTEMIC AUTOIMMUNE DISEASE PATIENTS IN PHENOTYPICALLY DISTINCTIVE GROUPS
No full textSystemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSC), Sjögren’s syndrome (SJS), mixed connective tissue disease (MCTD), primary antiphospholipid syndrome (PAPS) and undifferentiated connective tissue disease (UCTD) are classified as systemic autoimmune diseases (SADs). They are diagnosed based on different clinical and laboratory criteria. Due to their high internal heterogeneity and overlapping symptoms, SADs are difficult to diagnose. Therefore, molecular and cellular-based studies need to be undertaken to precisely classify the patients. Mass cytometry is a single-cell proteomics technology that measures approximately 50 markers per cell, thus it is a suitable tool to perform deep-phenotyping studies in SADs