Diferencias clínicas y pronósticas de los pacientes con infarto de miocardio y arterias coronarias sin lesiones obstructivas significativas frente a los que presenta síndrome de takotsubo

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de Lectura: 25-04-202

Psycho-emotional disorders as incoming risk factors for myocardial infarction with non-obstructive coronary arteries

  Background: There is an emerging field underlying the myocardial infarction (MI) with non-obstruc­tive coronary arteries (MINOCA). The aim of this study was to evaluate the impact of psycho-emotional disorders and social habits in MINOCA patients. Methods: The study included 95 consecutive patients diagnosed of MINOCA and 178 patients with MI and obstructive lesions. MINOCA patients were included when they fulfilled the three main criteria: accomplishment of the Third Universal Definition of Myocardial Infarction, absence of obstructive coronary arteries and no clinically overt specific cause for the acute presentation. Results: MINOCA patients had a higher frequency of previous psychiatric illnesses than the obstructive coronary arteries group (29.7% vs. 12.9%, p = 0.001). MINOCA patients recognized emotional stress in 75.7% of the cases, while only 32.1% of the obstructive related group did (p < 0.001). The relation­ship remained after excluding takotsubo syndrome from the analysis (26 cases, 27.4%): psychiatric diseases (27.9% vs. 12.9%, p < 0.01) and recognition of emotional stress (70.8% vs. 32.1%, p < 0.001). Social habits which could act as stress modulating showed no significant relation with MINOCA. Conclusions: Psycho-emotional disorders are related to MINOCA and they could act as risk fac­tor. This relationship is maintained after excluding takotsubo from the analysis. (Cardiol J 2018; 25, 1: 24–31

CILAIR-Based Secretome Analysis of Obese Visceral and Subcutaneous Adipose Tissues Reveals Distinctive ECM Remodeling and Inflammation Mediators

In the context of obesity, strong evidences support a distinctive pathological contribution of adipose tissue depending on its anatomical site of accumulation. Therefore, subcutaneous adipose tissue (SAT) has been lately considered metabolically benign compared to visceral fat (VAT), whose location is associated to the risk of developing cardiovascular disease, insulin resistance, and other associated comorbidities. Under the above situation, the chronic local inflammation that characterizes obese adipose tissue, has acquired a major role on the pathogenesis of obesity. In this work, we have analyzed for the first time human obese VAT and SAT secretomes using an improved quantitative proteomic approach for the study of tissue secretomes, Comparison of Isotope-Labeled Amino acid Incorporation Rates (CILAIR). The use of double isotope-labeling-CILAIR approach to analyze VAT and SAT secretomes allowed the identification of location-specific secreted proteins and its differential secretion. Additionally to the very high percentage of identified proteins previously implicated in obesity or in its comorbidities, this approach was revealed as a useful tool for the study of the obese adipose tissue microenvironment including extracellular matrix (ECM) remodeling and inflammatory status. The results herein presented reinforce the fact that VAT and SAT depots have distinct features and contribute differentially to metabolic disease

Clinical Profile and Determinants of Mortality in Patients with Interstitial Lung Disease Admitted for COVID-19.

BACKGROUND Concern has risen about the effects of COVID-19 in interstitial lung disease (ILD) patients. The aim of our study was to determine clinical characteristics and prognostic factors of ILD patients admitted for COVID-19. METHODS Ancillary analysis of an international, multicenter COVID-19 registry (HOPE: Health Outcome Predictive Evaluation) was performed. The subgroup of ILD patients was selected and compared with the rest of the cohort. RESULTS A total of 114 patients with ILDs were evaluated. Mean ± SD age was 72.4 ± 13.6 years, and 65.8% were men. ILD patients were older, had more comorbidities, received more home oxygen therapy and more frequently had respiratory failure upon admission than non-ILD patients (all p < 0.05). In laboratory findings, ILD patients more frequently had elevated LDH, C-reactive protein, and D-dimer levels (all p < 0.05). A multivariate analysis showed that chronic kidney disease and respiratory insufficiency on admission were predictors of ventilatory support, and that older age, kidney disease and elevated LDH were predictors of death. CONCLUSIONS Our data show that ILD patients admitted for COVID-19 are older, have more comorbidities, more frequently require ventilatory support and have higher mortality than those without ILDs. Older age, kidney disease and LDH were independent predictors of mortality in this population.S

In Vitro Antifungal Activity of Ibrexafungerp (SCY-078) Against Contemporary Blood Isolates From Medically Relevant Species of Candida: A European Study

BackgroundIbrexafungerp (SCY-078) is the newest oral and intravenous antifungal drug with broad activity, currently undergoing clinical trials for invasive candidiasis. ObjectiveThe aim of this study was to assess the in vitro activity of ibrexafungerp and comparators against a collection of 434 European blood isolates of Candida. MethodsIbrexafungerp, caspofungin, fluconazole, and micafungin minimum inhibitory concentrations (MICs) were collected from 12 European laboratories for 434 blood isolates, including 163 Candida albicans, 108 Candida parapsilosis, 60 Candida glabrata, 40 Candida tropicalis, 29 Candida krusei, 20 Candida orthopsilosis, 6 Candida guilliermondii, 2 Candida famata, 2 Candida lusitaniae, and 1 isolate each of Candida bracarensis, Candida catenulata, Candida dubliniensis, and Candida kefyr. MICs were determined by the EUCAST broth microdilution method, and isolates were classified according to recommended clinical breakpoints and epidemiological cutoffs. Additionally, 22 Candida auris from different clinical specimens were evaluated. ResultsIbrexafungerp MICs ranged from 0.016 to >= 8 mg/L. The lowest ibrexafungerp MICs were observed for C. albicans (geometric MIC 0.062 mg/L, MIC range 0.016-0.5 mg/L) and the highest ibrexafungerp MICs were observed for C. tropicalis (geometric MIC 0.517 mg/L, MIC range 0.06->= 8 mg/L). Modal MICs/MIC(50)s (mg/L) against Candida spp. were 0.125/0.06 for C. albicans, 0.5/0.5 for C. parapsilosis, 0.25/0.25 for C. glabrata, 0.5/0.5 for C. tropicalis, 1/1 for C. krusei, 4/2 for C. orthopsilosis, and 0.5/0.5 for C. auris. Ibrexafungerp showed activity against fluconazole- and echinocandin-resistant isolates. If adopting wild-type upper limits, a non-wild-type phenotype for ibrexafungerp was only observed for 16/434 (3.7%) isolates: 11 (4.6%) C. parapsilosis, 4 (5%) C. glabrata, and 1 (2.5%) C. tropicalis. ConclusionIbrexafungerp showed a potent in vitro activity against Candida.This study received funding from SCYNEXIS. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of the article, or the decision to submit it for publication. CM-A is a recipient of a grant from Fundació n ONCE (Oportunidad al Talento). EE, AG, NJ, CM-A, and GQ have received grant support from Consejerı́a de Educación, Universidades e Investigación del Gobierno Vasco (GIC15 IT-990-16), Fondo de Investigación Sanitaria del Gobierno de España (FIS PI11/00203), and UPV/EHU (UFI 11/25). All authors declare no other competing interests

Prevalence and prognosis of anxiety, insomnia, and type D personality in patients with myocardial infarction: A Spanish cohort

Background: It has been suggested that patients with myocardial infarction and non-obstructive coronary arteries (MINOCA) have more psycho-emotional disorders than patients with obstructive coronary artery disease (MICAD). The aim of this study is to compare the prevalence of anxiety, insomnia, and type D personality between MINOCA and MICAD and their impact on prognosis. Methods: Patients with myocardial infarction undergoing coronary angiography were prospectively enrolled. Psychological questionnaires were completed by each patient during admission. Results: Among a total of 533 patients, 56 had MINOCA and 477 had MICAD. There were no differences in the prevalence of anxiety and insomnia between both groups: trait anxiety median value (M) MINOCA = 18 (11–34) vs. MICAD M = 19 (12–27), p = 0.8; state anxiety MINOCA M = 19 (11–29) vs. MICAD M = 19 (12.2–26), p = 0.6; and insomnia MINOCA M = 7 (3–11) vs. MICAD M = 7 (3–12), p = 0.95. More MINOCA patients had type D personality (45.0% vs. 28.5%, p = 0.03). At 3-year follow-up, there were no differences in mortality between MINOCA and MICAD (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.28–2.17) in major adverse cerebral or cardiovascular events (MACCE) (HR 0.71, 95% CI 0.38–1.31). Scores of trait anxiety and negative affectivity were significantly associated with MACCE (HR 1.65, 95% CI [1.05–2.57]; HR 1.75, 95% CI [1.11–2.77], respectively). High insomnia levels were associated with greater mortality (HR 2.72, 95% CI [1.12–6.61]). Conclusions: Anxiety and insomnia levels were similar between patients with MINOCA and those with MICAD, whilst the prevalence of type D personality was higher in the MINOCA than in the MICAD group. Higher scores in trait anxiety, insomnia, and negative affectivity were related to a worse prognosis at 3-year follow-up

Daptomycin plus Fosfomycin versus Daptomycin Alone for Methicillin-Resistant Staphylococcus 2 aureus Bacteremia and Endocarditis. A Randomized Clinical Trial

Background We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. Methods A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. Results Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). Conclusions Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events

Impact of the presence of heart disease, cardiovascular medications and cardiac events on outcome in COVID-19

Background: Cardiovascular risk factors and usage of cardiovascular medication are prevalent among coronavirus disease 2019 (COVID-19) patients. Little is known about the cardiovascular implications of COVID-19. The goal herein, was to evaluate the prognostic impact of having heart disease (HD) and taking cardiovascular medications in a population diagnosed of COVID-19 who required hospitalization. Also, we studied the development of cardiovascular events during hospitalization. Methods: Consecutive patients with definitive diagnosis of COVID-19 made by a positive real time- -polymerase chain reaction of nasopharyngeal swabs who were admitted to the hospital from March 15 to April 14 were included in a retrospective registry. The association of HD with mortality and with mortality or respiratory failure were the primary and secondary objectives, respectively. Results: A total of 859 patients were included in the present analysis. Cardiovascular risk factors were related to death, particularly diabetes mellitus (hazard ratio in the multivariate analysis: 1.810 [1.159– –2.827], p = 0.009). A total of 113 (13.1%) patients had HD. The presence of HD identified a group of patients with higher mortality (35.4% vs. 18.2%, p &lt; 0.001) but HD was not independently related to prognosis; renin–angiotensin–aldosterone system inhibitors, calcium channel blockers, diuretics and beta-blockers did not worsen prognosis. Statins were independently associated with decreased mortality (0.551 [0.329–0.921], p = 0.023). Cardiovascular events during hospitalization identified a group of patients with poor outcome (mortality 31.8% vs. 19.3% without cardiovascular events, p = 0.007). Conclusions: The presence of HD is related to higher mortality. Cardiovascular medications taken before admission are not harmful, statins being protective. The development of cardiovascular events during the course of the disease is related to poor outcome

Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial.

INTRODUCTION: Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. METHODS AND ANALYSIS: A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. ETHICS AND DISSEMINATION: The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License