Бронхиальная астма и COVID-19 у пожилых пациентов: особенности течения, выживаемость, предикторы летальности

Bronchial asthma occurs in 0.9 – 17% of patients hospitalized with COVID-19. However, it is not clear whether asthma is a risk factor for the development and severity of COVID-19. Studies have shown that patients with asthma appear to be more susceptible to COVID-19 infection, but severe disease progression is not related to medication use, including asthma biologics, but rather to older age and comorbidities.Aim. To evaluate the clinical course of SARS-CoV-2 infection in elderly patients with asthma, to examine the effect of asthma and comorbidities on COVID-19related outcomes, and to determine predictors of mortality.Methods. Elderly patients [WHO, 2020] (> 60 years, n = 131, median age 74 (67; 80) years; 59 men, 72 women) with asthma hospitalized for COVID-19 were included in the study. COVID-19 was confirmed by laboratory tests (PCR smear) and/or clinical and radiological examinations. All patients had a history of a documented diagnosis of asthma (GINA, 2020).Results. Out of 131 patients, 30 (22.9%) died in the hospital, and 15 (14.9%) died after discharge from the hospital (within 90 days). The group of patients with lethal outcome showed the following differences from those who recovered: values of Charlson index, respiration rate, degree of lung damage on CT scan, absolute number of leukocytes, neutrophils and neutrophils-to-lymphocytes ratio, C-reactive protein on the 5th day of hospitalization, and LDH were statistically significantly higher, while absolute number of eosinophils, total protein content, SpO2 and SpO2/FiO2 levels were lower; steroid intake during the year and non-atopic asthma were more common. Multivariate and ROC analysis revealed the most significant predictors of hospital mortality and their thresholds: Charlson comorbidity index ≥ 6 points, neutrophil/lymphocyte ratio ≥ 4.5, total protein ≤ 60 g/l, eosinophil level ≤ 100 cells/μL.Conclusion. The most significant predictors of hospital mortality in elderly patients with severe COVID-19 against asthma are Charlson comorbidity, neutrophil/lymphocyte ratio; lower eosinophil and total protein levels. Survival time of patients has an inverse correlation with the number of mortality risk factors present.Бронхиальная астма (БА) встречается у 0,9–17 % пациентов, госпитализированных с COVID-19, однако остается неясным, является ли БА фактором риска развития и тяжести COVID-19. По-видимому, пациенты с БА более восприимчивы к заражению COVID-19, но тяжелое прогрессирование заболевания связано не с использованием лекарств, включая биопрепараты от БА, а скорее с пожилым возрастом и сопутствующими заболеваниями.Целью исследования явились оценка клинического течения инфекции SARS-CoV-2 у пожилых пациентов с БА, а также изучение влияния БА и сопутствующих заболеваний на исходы, связанные с COVID-19, и определение предикторов летальности. Материалы и методы. В исследование включены пожилые (старше 60 лет) пациенты с БА (n = 131: 59 мужчин, 72 женщины; средний возраст – 74 (67; 80) года), госпитализированные по поводу COVID-19 (рекомендации Всемирной организации здравоохранения, 2020). Наличие COVID-19 подтверждалось лабораторными исследованиями (по результатам полимеразной цепной реакции) и / или рентгенологически. У всех пациентов в анамнезе документально подтвержден диагноз БА в соответствии с рекомендациями Глобальной инициативы по бронхиальной астме (Global Initiative for Asthma – GINA, 2020). . Результаты. В стационаре из 131 пациента умерли 30 (22,9 %), после выписки из стационара (в течение 90 дней) – 15 (14,9 %). По сравнению с выздоровевшими у умерших больных перед летальным исходом статистически значимо отмечались более высокие индекс Чарлсона, частота дыхания, степень поражения легких по данным компьютерной томографии, абсолютное число лейкоцитов, нейтрофилов и показатель соотношения нейтрофилы / лимфоциты, уровни C-реактивного белка на 5-е сутки госпитализации и лактатдегидрогеназы, более низкие показатели абсолютного числа эозинофилов, общего белка, пульсоксиметрии (SpO2) и альтернативного индекса оксигенации (показатель соотношения SpO2 и фракции вдыхаемого кислорода); они также чаще принимали глюкокортикостероиды в течение 1 года, у них чаще отмечался неатопический вариант БА. По данным многофакторного и ROC-анализа выявлены наиболее значимые предикторы госпитальной летальности и их пороговые значения – индекс коморбидности Чарлсона ≥ 6 баллов, соотношение нейтрофилы / лимфоциты ≥ 4,5, уровень общего белка ≤ 60 г / л, уровень эозинофилов ≤ 100 кл. / мкл. Заключение. Наиболее значимыми предикторами госпитальной летальности у пожилых больных с тяжелой формой COVID-19 на фоне БА являются коморбидность по Чарлсону, показатель соотношения нейтрофилы / лимфоциты; более низкие уровни эозинофилов и общего белка. Время дожития пациентов имеет обратную зависимость от количества имеющихся факторов риска летальности

Conversion of rice straw to bio-based chemicals: an integrated process using Lactobacillus brevis

Commercialization of lignocellulosic biomass as a feedstock for bio-based chemical production is problematic due to the high processing costs of pretreatment and saccharifying enzymes combined with low product yields. Such low product yield can be attributed, in large part, to the incomplete utilization of the various carbohydrate sugars found in the lignocellulosic biomass. In this study, we demonstrate that Lactobacillus brevis is able to simultaneously metabolize all fermentable carbohydrates in acid pre-processed rice straw hydrolysate, thereby allowing complete utilization of all released sugars. Inhibitors present in rice straw hydrolysate did not affect lactic acid production. Moreover, the activity of exogenously added cellulases was not reduced in the presence of growing cultures of L. brevis. These factors enabled the use of L. brevis in a process termed simultaneous saccharification and mixed sugar fermentation (SSMSF). In SSMSF with L. brevis, sugars present in rice straw hydrolysate were completely utilized while the cellulase maintained its maximum activity due to the lack of feedback inhibition from glucose and/or cellobiose. By comparison to a sequential hydrolysis and fermentation process, SSMSF reduced operation time and the amount of cellulase enzyme necessary to produce the same amount of lactic acid

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Erythropoietin content in correction by 3-hydroxypyridine derivative the acute stress with various degree of erythron system damage

В експериментах на 46 білих щурах-самцях відтворювали гострий анемічний або іммобілізаційний стрес. З метою фармакологічної корекції тваринам вводили 2-етил-6-метил-3-гідроксипіридину сукцинат (мексидол) інтраперитонеально в дозі 100 мг/кг маси відразу після крововтрати або початку іммобілізації. Уміст еритропоетину (ЕПО) у плазмі крові визначали методом імуноферментного аналізу. Показано, що розвиток стрес-синдрому супроводжується підвищенням вмісту ЕПО, яке реєструється при анемічному стресі (крововтраті) через 72 год, а при іммобілізаційному стресі – через 3 та 72 год від початку дії стресорного фактора. Мексидол підтримує підвищену концентрацію ЕПО у плазмі крові при крововтраті та зменшує її при іммобілізації, тобто демонструє регуляторну дію на рівень цього гормону залежно від ступеня ушкодження еритрону під час ініціації стрес-синдромe; Известно, что стресс приводит к изменениям концентрации эритропоэтина (ЭПO) в организме, что обеспечивает развитие постстрессорной активации эритропоэза, а также реализацию нейропротекторного действия ЭПО, но влияние лекарственных препаратов на вышеуказанные процессы исследовано слабо. Цель исследования – изучить особенности влияния 2-этил-6-метил-3гидроксипиридина сукцината (мексидола) на содержание ЭПО в условиях двух видов стресса с различной степенью повреждения системы эритрона. Острый анемический стресс (как кровопотерю) и иммобилизационный стресс воспроизводили у 46 белых крыс-самцов линии Вистар. Мексидол вводили внутрибрюшинно в дозе 100 мг/кг сразу же после кровопотери или начала иммобилизации. Крысы контрольных групп получали инъекцию растворителя. Через 3 и 72 часа от начала действия стрессора животных подвергали эвтаназии. Содержание ЭПО в плазме крови определяли с помощью иммуноферментного анализа. Показано, что развитие стресс-синдрома сопровождается повышением уровней ЭПО в 2–2,4 раза (р < 0,01–0,001) по сравнению с интактными животными, что регистрируется через 72 часа при анемическом стрессе (кровопотере) и через 3 и 72 часа при иммобилизационном стрессе. По-видимому, гемодилюция, как нормальная компенсаторная реакция, объясняет отсутствие достоверных изменений концентрации ЭПО в ранний период после кровопотери. Введение мексидола поддерживает повышенное содержание ЭПO при острой кровопотере. В то же время препарат уменьшает этот параметр в 1,6 раза (р < 0,01) при иммобилизации, то есть проявляет регулирующее действие на уровень ЭПО в зависимости от степени повреждения эритрона во время инициации стресс-синдрома. Предполагается, что потеря железа и прямое взаимодействие производного 3-гидроксипиридина с этим элементом может быть ключевой причиной наблюдаемых особенностей; It is known that stress leads to the changes in concentration of erythropoietin (EPO) in the organism that provides the development of post-stress activation of erythropoiesis as well as realization of EPO’s neuroprotective action, but the influence of medicinal drugs on the mentioned processes is investigated poorly. The goal of this paper was to study the peculiarities of 2-ethyl-6-methyl-3-hydroxypyridine succinate (mexidol) influence on the EPO content under the conditions of two kinds of stress with different damage of erythron system. Acute anemic stress as blood loss and immobilization stress were designed in 46 albino male Wistar rats. The animals were administered with mexidol intraperitoneally in the dose of 100 mg/kg immediately after the blood loss or beginning of immobilization. Rats of control groups received the injection of solvent. After 3 or 72 h from the start of stressor’s action they were euthanized. EPO content in blood plasma was determined by enzyme-linked immunosorbent assay. It is shown that development of stress syndrome is accompanied by enhance of EPO levels in 2–2,4 times (p < 0,01– 0,001) as compared to intact animals that is registered within 72 h in anemic stress (blood loss), and within 3 and 72 h in the immobilization stress. Hemodilution, as a normal compensatory reaction, probably, is the reason for the absence of significant changes in EPO concentration in the early period after the blood loss. Mexidol’s administration maintains enhanced EPO concentration in acute blood loss. At the same time, the drug reduces this parameter in 1,6 time in the immobilization, i.e. exhibits a regulatory effect on the level of EPO depending on the degree of erythron damage during stress syndrome initiation. It is supposed that the loss of iron and direct interaction of 3-hydroxipiridine derivative with this mineral in the body may be the key factor for the observed peculiarities

One-step synthesis of ZnO nanosheets: a blue-white fluorophore

Zinc oxide is synthesised at low temperature (80°C) in nanosheet geometry using a substrate-free, single-step, wet-chemical method and is found to act as a blue-white fluorophore. Investigation by atomic force microscopy, electron microscopy, and X-ray diffraction confirms zinc oxide material of nanosheet morphology where the individual nanosheets are polycrystalline in nature with the crystalline structure being of wurtzite character. Raman spectroscopy indicates the presence of various defects, while photoluminescence measurements show intense green (centre wavelength approximately 515 nm) blue (approximately 450 nm), and less dominant red (approximately 640 nm) emissions due to a variety of vacancy and interstitial defects, mostly associated with surfaces or grain boundaries. The resulting colour coordinate on the CIE-1931 standard is (0.23, 0.33), demonstrating potential for use as a blue-white fluorescent coating in conjunction with ultraviolet emitting LEDs. Although the defects are often treated as draw-backs of ZnO, here we demonstrate useful broadband visible fluorescence properties in as-prepared ZnO