Test whether high dose corticosteroid pulse therapy (HDCPT) with either methylprednisolone or dexamethasone is associated with increased survival in COVID-19 patients at risk of hyper-inflammatory ...response. Provide some initial diagnostic criteria using laboratory markers to stratify these patients.
This is a prospective observational study, 318 met the inclusion criteria. 64 patients (20.1%) were treated with HDCPT by using at least 1.5mg/kg/24h of methylprednisolone or dexamethasone equivalent. A multivariate Cox regression (controlling for co-morbidities and other therapies) was carried out to determine whether HDCPT (among other interventions) was associated with decreased mortality. We also carried out a 30-day time course analysis of laboratory markers between survivors and non-survivors, to identify potential markers for patient stratification.
HDCPT showed a statistically significant decrease in mortality (HR = 0.087 95% CI 0.021-0.36; P < 0.001). 30-day time course analysis of laboratory marker tests showed marked differences in pro-inflammatory markers between survivors and non-survivors. As diagnostic criteria to define the patients at risk of developing a COVID-19 hyper-inflammatory response, we propose the following parameters (IL-6 > = 40 pg/ml, and/or two of the following: C-reactive protein > = 100 mg/L, D-dimer > = 1000 ng/ml, ferritin > = 500 ng/ml and lactate dehydrogenase > = 300 U/L).
HDCPT can be an effective intervention to increase COVID-19 survival rates in patients at risk of developing a COVID-19 hyper-inflammatory response, laboratory marker tests can be used to stratify these patients who should be given HDCPT. This study is not a randomized clinical trial (RCT). Future RCTs should be carried out to confirm the efficacy of HDCPT to increase the survival rates of COVID-19.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
CE has been a continuously evolving analytical methodology since its first introduction in the 1980s of the last century. The development of new CE separation procedures, the coupling of these ...systems to more sensitive and versatile detection systems, and the advances in miniaturization technology have allowed the application of CE to the resolution of new and complex analytical problems, overcoming the traditional disadvantages associated with this method. In the present work, different recent trends in CE and their application to the determination of high complexity samples (as biological fluids, individual cells, etc.) will be reviewed: capillary modification by different types of coatings, microfluidic CE, and online microextraction CE. The main advantages and disadvantages of the different proposed approaches will be discussed with examples of most recent applications.
For the first time, a novel and versatile microfluidic device was developed to achieve the possibility of combining different extraction principles using a miniaturized approach for the extraction of ...different classes of analytes. This novel microchip is composed of a sandwich of three poly(methyl methacrylate) (PMMA) layers. Four channels allowed the combination of electromembrane extraction (EME) and liquid-phase microextraction (LPME) in three different ways: (I) EME and LPME, (II) EME and EME, or (III) LPME and LPME. The microchip can be used either (a) using a common acceptor phase (for both extractions) for the simultaneous extraction of drugs from different nature in a single step, or (b) a common sample solution (for both extractions) and two acceptor solutions for simultaneous drug separation. In this work, the performance of this novel microchip was demonstrated by simultaneous integration of EME and LPME using a common acceptor phase for both extractions. This configuration reduces the time of analysis allowing direct analysis in a single chip. The microchip was tested for extracting two different classes of analytes: five fluoroquinolones and four parabens as model analytes. All effective variables were optimized for EME and LPME. Under the optimized conditions, the reusable microchip enables simultaneous μ-EME/LPME with extraction efficiencies over 77% in only 8 min extraction and sample volume consumption lower than 40 μL. The optimized procedure was successfully applied to urine samples obtaining recoveries over 90% for all analytes.
Background and Purpose
Organisms, including humans, are subjected to the simultaneous action of a wide variety of pollutants, the effects of which should not be considered in isolation, as many ...synergies and antagonisms have been found between many of them. Therefore, this work proposes an in vivo study to evaluate the effect of certain metal contaminants on the bioavailability and metabolism of pharmacologically active compounds. Because the most frequent entry vector is through ingestion, the influence of the gut microbiota and the possible protective effects of selenium has been additionally evaluated.
Experimental Approach
A controlled exposure experiment in mammals (Mus musculus) to a “chemical cocktail” consisting of metals and pharmaceuticals (diclofenac and flumequine). The presence of selenium has also been evaluated as an antagonist. Mouse plasma samples were measured by UPLC‐QTOF. A targeted search of 48 metabolites was also performed.
Key Results
Metals significantly affected the FMQ plasma levels when the gut microbiota was depleted. Hydroxy FMQ decreased if metals were present. Selenium minimized this decrease. The 3‐hydroxy DCF metabolite was not found in any case. Changes in some metabolic pathways are discussed.
Conclusions and Implications
The presence of metals in the mouse diet as well as the prior treatment of mice with an antibiotic mixture (Abxs), which deplete the gut microbiota, has a decisive effect on the bioavailability and metabolism of the tested pharmaceuticals and dietary selenium minimize some of their effects.
Background
The aim of this study was to compare the ability to predict 30‐day in‐hospital mortality of lactate versus the modified Rapid Emergency Medicine Score (mREMS) versus the arithmetic sum of ...the mREMS plus the numerical value of lactate (mREMS‐L).
Methods
A prospective, multicentric, emergency department delivery, pragmatic study was conducted. To determine the predictive capacity of the scales, lactate was measured and the mREMS and mREMS‐L were calculated in adult patients (aged>18 years) transferred with high priority by ambulance to the emergency department in five hospitals of Castilla y Leon between 1 January 2020 and 31 December 2021. The area under the receiver operating characteristic (ROC) curve of each of the scales was calculated in terms of mortality for 30 days.
Results
A total of 5371 participants were included, and the in‐hospital mortality rate at 30 days was of 11.4% (615 cases). The best cut‐off point determined in the mREMS was 7.0 points (sensitivity of 67% and specificity of 84%), and for lactate, the cut‐off point was 1.4 mmol/L (sensitivity of 88% and specificity of 67%). Finally, the combined mREMS‐L showed a cut‐off point of 7.9 (sensitivity of 83% and a specificity of 83%). The area under the ROC curve of the mREMS, lactate and mREMS‐L for 30‐day mortality was 0.851, 0.853, and 0.903, respectively (p < 0.001 in all cases).
Conclusions
The new score generated, mREMS‐L, obtained better statistical results than its components (mREMS and lactate) separately.
The prevalence and management of coronary artery disease (CAD) in liver transplantation (LT) candidates are not well characterized. The aims of this study were to evaluate the impact on clinical ...outcomes of a specifically designed protocol for the management of asymptomatic CAD in LT candidates and to investigate noninvasive risk profiles for obstructive and nonobstructive CAD for 202 LT candidates. Those with high baseline cardiovascular risk (CVR; defined by the presence of classic CVR factors and/or decreased ejection fraction) received coronary angiography and significant arterial stenosis and were treated with percutaneous stents. Patients were followed up after LT until death or coronary event (CE). There were 78 patients who received coronary evaluation (62 direct angiography, 14 computed tomography coronary angiography, and 2 both). Of them, 39 (50%) patients had CAD of any severity, and 6 (7.7%) had significant lesions (5 were amenable to be treated with stents, whereas 1 patient had diffuse lesions which contraindicated the LT). Insulin‐dependent diabetes was the only factor related to CAD of any severity (odds ratio, 3.44; 95% confidence interval CI, 1.00‐11.97). A total of 69 patients (46 with coronary evaluation) received LT. The incidence of CEs and overall survival after LT were similar between patients with and without coronary evaluation. Furthermore, no differences occurred between these groups in a multivariate competing risk model (subhazard ratio, 0.84; 95% CI, 0.27‐2.61; P = 0.76). In conclusion, the application of an angiographic screening protocol of CAD in a selected high‐risk Mediterranean population is safe and effective. The short‐ and medium‐term incidence rates of CEs and death after LT in this population are similar to that observed in low‐risk patients.
Bicuspid aortic valve (BAV) is the most common human congenital cardiac malformation. Although the etiology is unknown for most patients, formation of the 2 main BAV anatomic types (A and B) has been ...shown to rely on distinct morphogenetic mechanisms. Animal models of BAV include 2 spontaneous hamster strains and 27 genetically modified mouse strains. To assess the value of these models for extrapolation to humans, we examined the aortic valve anatomy of 4340 hamsters and 1823 mice from 8 and 7 unmodified strains, respectively. In addition, we reviewed the literature describing BAV in nonhuman mammals. The incidences of BAV types A and B were 2.3% and 0.03% in control hamsters and 0% and 0.3% in control mice, respectively. Hamsters from the spontaneous model had BAV type A only, whereas mice from 2 of 27 genetically modified strains had BAV type A, 23 of 27 had BAV type B, and 2 of 27 had both BAV types. In both species, BAV incidence was dependent on genetic background. Unlike mice, hamsters had a wide spectrum of aortic valve morphologies. We showed interspecific differences in the occurrence of BAV between humans, hamsters, and mice that should be considered when studying aortic valve disease using animal models. Our results suggest that genetic modifiers play a significant role in both the morphology and incidence of BAV. We propose that mutations causing anomalies in specific cardiac morphogenetic processes or cell lineages may lead to BAV types A, B, or both, depending on additional genetic, environmental, and epigenetic factors.
Smoking and second‐hand smoke (SHS) exposure have been recently linked to a higher risk of breast cancer in women. The aim of this work is to estimate the number of deaths and disability‐adjusted ...life years (DALYs) from breast cancer attributable to these two risk factors in the European Union (EU‐28) in 2017. The comparative risk assessment method was used. Data on prevalence of smoking and SHS exposure were extracted from the Eurobarometer surveys, relative risks from a recent meta‐analysis, and data on mortality and DALYs from breast cancer were estimated from the Global Burden of Disease, Injuries and Risk Factors Study. In 2017, 82 239 DALYs and 3354 deaths from breast cancer in the EU‐28 could have been avoided by removing exposure to these two risk factors (smoking and SHS exposure). The proportion of DALYs from breast cancer lost respectively from smoking and SHS exposure was 2.6% and 1.0%, although geographically distributed with significant heterogeneity. These results represent the first estimates of breast cancer burden in women attributable to smoking and SHS exposure for the EU‐28. It is important to increase awareness among women, health professionals and wider society of the association between smoking, SHS exposure and breast cancer, a relationship that is not widely recognised or discussed.
What's new?
Smoking and exposure to secondhand smoke are not considered a major risk factor for breast cancer risk in Europe. Here, the authors publish the first analysis estimating how many deaths and years of disability can be attributed to smoking. Using the comparable risk assessment method, they determined that eliminating smoking could have saved 60 733 years of life with disability and 2719 deaths from breast cancer. Given the burden of disease from breast cancer attributable to smoking, it is important to increase awareness among health professionals and public.
AbstractOur aim was to provide a systematic review of studies on the burden of disease due to second-hand smoke (SHS) exposure, reviewing methods, exposure assessment, diseases causally linked to ...SHS, health outcomes, and estimates available to date. A literature review of studies on the burden of disease from SHS exposure, available in PubMed and SCOPUS, published 2007–2018 in English language, was carried out following the PRISMA recommendations. Overall, 588 studies were first identified, and 94 were eligible. Seventy-two studies were included in the systematic review. Most of them were based on the comparative risk assessment approach, assessing SHS exposure using mainly surveys on exposure at home/workplaces. Diseases more frequently studied were: lung cancer, ischemic heart disease, stroke, chronic obstructive pulmonary disease, asthma and breast cancer in adults; lower respiratory tract infection, otitis media, asthma, sudden infant death syndrome and low birth weight in children. The SHS exposure assessment and the reported population attributable fractions (PAF) were largely heterogeneous. As an example, the PAF from lung cancer varied between 0.6% and 20.5%. Moreover, PAF were estimated applying relative risks and SHS exposures with no consistent definitions or with different age classes. The research gap on the SHS exposure burden is shrinking. However, estimates are not yet available for a number of countries, particularly the Middle Eastern and African countries, and not all diseases with the strongest evidence of causation, such as sudden infant death syndrome, have been explored. Moreover, in some cases the applied methodology revealed relatively low quality of data.
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