Atorvastatin: old friend in the light of novel coronavirus infection’s pandemia

The COVID-19 (COronaVIrus Disease 2019) pandemic caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2) continues to be a global threat to people and health systems. As of March 21, 2022, there are more than 460 million cases and more than 6 million deaths worldwide, and more than 17 million and 360,000 respectively in the Russian Federation. Due to the rapid spread of the new coronavirus infection, since the beginning of the pandemic, tremendous efforts have been made to create new pharmacological agents to reduce morbidity and mortality, and tactics have been used to repurpose existing medications in treatment regimens for patients with COVID-19, particularly statins. Statins represent one of the most widely used and prescribed classes of drugs in the world. The hypolipidemic properties of statins are actively used to treat hyperlipidemia and primary and secondary prevention of cardiovascular diseases and their complications. Statins have a known safety profile, are inexpensive and accessible. In addition to their hypolipidemic effects, statins have a wide range of pleiotropic anti-inflammatory, antiviral, and antithrombotic effects potentially useful in the treatment of COVID-19. Presumably, the use of statins can reduce SARS-CoV-2-induced organ and tissue damage and improve lung function. The use of statins, particularly atorvastatin, as one of the most effective, widely prescribed and studied drugs in this class, as a safe, affordable and relatively inexpensive therapy may be a promising therapeutic approach in the fight against a new coronavirus infection

Outpatient Practice of Lipid-Lowering Therapy Prescription (According to the ARGO-3 Study)

Aim. To study the frequency of prescriptions of various types of lipid-lowering therapy and their effectiveness in outpatient clinical practice based on the results of a questionnaire of primary care physicians.Material and methods. The study was performed in 2022 in 75 constituent entities of the Russian Federation with the participation of 1117 doctors working in outpatient clinics. Most of the doctors had work experience of 10-20 years or more. Doctors of polyclinics (therapists and cardiologists, etc.) before the start of the study received instructions, questionnaires for filling out, developed by the National Atherosclerosis Society. The frequency of prescriptions by primary care physicians of various types of lipid-lowering therapy and their effectiveness in terms of the frequency of achieving target levels of low-density lipoprotein cholesterol (LDL-C) was studied based on the results of a questionnaire.Results. Monotherapy with statins was prescribed in 55.2% of cases, free combination of rosuvastatin with ezetimibe – in 17.2%, single pill combination of rosuvastatin with ezetimibe – in 23.2%, combination therapy with PCSK9 inhibitors – in 4.1% of cases. Target levels of LDL-C ˂ 1.8 mmol/l and ˂ 1.4 mmol/l were achieved with statin monotherapy in 42.6% and 28.2% of cases, respectively, free combination of rosuvastatin with ezetimibe – in 61.7% and 39 .5%, a fixed combination of rosuvastatin with ezetimibe – in 67.8% and 48.5%, combination therapy with PCSK9 inhibitors – in 96.8% and 92.8% of cases.Conclusion. The single pill combination of rosuvastatin with ezetimibe is more effective in achieving target levels of LDL-C compared with statin monotherapy and therapy with free combination of statin with ezetimibe. Despite the fact that the target values of LDL-C when prescribing a combination with PCSK9 inhibitors were achieved in 96.8% and 92.8% of cases, they were used quite rarely at the outpatient stage of treatment in the Russian Federation

Magnetization and specific heat of TbFe3(BO3)4: Experiment and crystal field calculations

We have studied the thermodynamic properties of single-crystalline TbFe3(BO3)4. Magnetization measurements have been carried out as a function of magnetic field (up to 50 T) and temperature up to 350K with the magnetic field both parallel and perpendicular to the trigonal c-axis of the crystal. The specific heat has been measured in the temperature range 2-300K with a magnetic field up to 9 T applied parallel to the c-axis. The data indicate a structural phase transition at 192 K and antiferromagnetic spin ordering at 40 K. A Schottky anomaly is present in the specific heat data around 20 K, arising due to two low-lying energy levels of the Tb3+ ions being split by f-d coupling. Below TN magnetic fields parallel to the c-axis drive a spin-flop phase transition, which is associated with a large magnetization jump. The highly anisotropic character of the magnetic susceptibility is ascribed mainly to the Ising-like behavior of the Tb3+ ions in the trigonal crystal field. We describe our results in the framework of an unified approach which is based on mean-field approximation and crystal-field calculations.Comment: 10 pages, 10 figures, 20 references, accepted by Phys. Rev.

Associative connection of infectious and inflammatory diseases in pregnancy and severe preeclampsia

Materials and methods. This retrospective case-control study enrolled 50 women with severe preeclampsia and 50 control women with spontaneous singleton pregnancy. Median age of women ranged from 20 to 35 years. All women did not have a history of hypertension, autoimmune, metabolic, renal, or cardiac diseases, and preeclampsia before this pregnancy. We have analyzed χ2, odds ratio (OR) and its 95% confidence intervals (95% Cl). Results. We found significant association between maternal systemic infectious and severe preeclampsia (OR = 49.6; 95% Cl 13.05-188.64). The risk of severe preeclampsia were significantly lower in patients with local infections of the lower genital tract (OR = 4.5; 95% Cl 1.49-6.71). Asymptomatic bacteriuria is associated with the highest risk of severe preeclampsia (OR = 17.0; 95% Cl 4.66-61.81). Acute gravidarum pyelonephritis showed lower association with severe preeclampsia (OR = 5.4; 95% Cl 1.69-10.54). We did not observe increased risk of severe preeclampsia with acute respiratory infections (OR = 2.0; 95% Cl 0.71-4.69). Acute non-specific bacterial vaginitis and acute candidiasis vulvovaginitis were found to be risk factors of severe preeclampsia (OR = 6.7; 95% Cl 1.90-11.02 and OR = 4.3; 95% Cl 1.45-9.99 respectively). Cytomegalovirus infection (2 %), toxoplasmosis (2 %), Chlamydia trachomatis cervicitis (4 %), acute Trichomonas colpitis (2 %) and bacterial vaginosis (4 %) were found only in patients with severe preeclampsia. Conclusion. Our data support that acute maternal infection is associated with an increased risk of severe preeclampsia in healthy women with singleton pregnancy. Systemic inflammatory response might be the main potential mechanisms related to infections and enhanced development of severe preeclampsia. Further research is required to elucidate the underlying mechanism of this association

Эффективность высокоинтенсивной терапии розувастатином для вторичной профилактики сердечно-сосудистых осложнений у пациентов очень высокого риска

According to the latest international and Russian guidelines for the treatment of dyslipidemias, statins are defined as the main group of drugs that significantly reduce the level of low-density lipoprotein cholesterol (LDL-C) effectively prevent atherosclerotic cardiovascular diseases (CVD) and complications and can slow down the progression of atherosclerosis. The principle “the lower LDL-C, the better” is especially relevant in categories of patients with very high and extreme cardiovascular risk, and therefore, in order to achieve target LDL-C values (≤1.4 is optimal ≤1.0) in this category of patients, high-intensity lipid-lowering therapy should be used. Rosuvastatin remains the most effective statin. Its use makes possible to achieve target lipid values at the starting dose of treatment, enhances adherence to treatment, and also reduces the frequency of side effects associated with the use of high doses of other statins. In addition, the proven ability of rosuvastatin to reduce the volume of atherosclerotic plaque, by reducing the level of pro-inflammatory cytokines and C-reactive protein, normalizing endothelial function, antiplatelet action, that is, rosuvastatin, in addition to its powerful lipid-lowering effect, has anti-inflammatory and anti-ischemic effects. Also, rosuvastatin can be successfully used in the presence of comorbidities, including chronic kidney disease and chronic heart failure. Taking into consideration the urgency of the fight against the COVID-19 pandemic (coronavirus Disease 2019), which covered 220 countries, due to the lack of effective etiotropic drugs, the possibility of using statins, including rosuvastatin, for the treatment of comorbid patients with COVID-19, was evaluated.Согласно последним международным и российским рекомендациям по лечению дислипидемий, статины определены в качестве основной группы лекарственных препаратов, значимо снижающих уровень холестерина липопротеидов низкой плотности (ХС ЛНП) крови, эффективных для профилактики сердечно-сосудистых заболеваний (ССЗ) и сердечно-сосудистых осложнений (ССО), позволяющих затормозить прогрессирование атеросклероза. Принцип «чем ниже ХС ЛНП, тем лучше» особенно актуален у категорий пациентов очень высокого и экстремального сердечно-сосудистого риска, в связи с чем для достижения целевых значений ХС ЛНП (≤ 1,4 оптимально ≤ 1,0) у этой категории пациентов должна применяться высокоинтенсивная гиполипидемическая терапия. Наиболее эффективным представителем статинов остается розувастатин. Его применение позволяет добиваться целевых значений липидов на стартовой дозе лечения, способствует повышению приверженности к лечению, а также уменьшению частоты побочных эффектов, связанных с применением высоких доз других статинов. Кроме того, доказанной является способность розувастатина уменьшать объем атеросклеротической бляшки за счет снижения уровня провоспалительных цитокинов и С-реактивного белка, нормализации функции эндотелия, дезагрегантного действия, т. е. розувастатин, помимо мощного гиполипидемического воздействия, обладает противовоспалительным и антиишемическим эффектами. Также розувастатин может успешно применяться при наличии сопутствующей патологии, включая хроническую болезнь почек и хроническую сердечную недостаточность. Учитывая актуальность борьбы с пандемией COVID-19 (COronaVIrus Disease 2019), охватившей 220 стран, в связи с отсутствием эффективных этиотропных препаратов оценена возможность применения статинов, в т. ч. и розувастатина, для лечения коморбидных пациентов с COVID-19

Studying of the Polylactide or Polyglycylidactide Surface Layer Biodegradation in Neutral Media for the Subsequent Layered Composite Creation

  The processes of biodegradation in phosphate buffer with pH 7.4 and 0.9 wt.% NaCl of polymer polylactide or polyglycylidactide films for the subsequent creation of a layered composite with a biodegradable layer on the basis of a nickel-free shape memory alloy TiNbTaZr were studied. The structure of the samples was determined by SEM and an optical microscope. For polylactide films the rate of biodegradation did not depend on the mass of the film. A gradual decrease in the rate of biodegradation at any mass with a similar dependence on time is noted. With an increase in the mass of films based on poly(glycolide-lactide) the rate of biodegradation increased. And even at the initial stage the dissolution rate is 2-3 times higher than in pure polylactide. On day 180, complete dissolution of the polyglycolidelactide was observed (even a precipitate was not observed) and completely entire polylactide films, however, lost  their transparency, was noted

Новая мутация в гене TYMP: клинико-морфологическая характеристика пациента с синдромом MNGIE

Mitochondrial neurogastrointestinal encephalomyopathy is an extremely rare (1–9:1 000 000, Orphanet, 2021) multisystem genetic disease caused by mutations in the TYMP gene encoding the enzyme thymidine phosphorylase.The article presents the data of a thirteen‑year survey on 40‑year‑old patient D. with clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy syndrome associated with the previously undescribed missense mutation c.1301G>T (p.Gly434Val) of the TYMP gene. Detailed clinical picture (gastrointestinal dysfunction, cachexia, blepharoptosis, ophthalmoparesis, peripheral polyneuropathy and leukoaraiosis), electroneuromyography data (demyelination with secondary axonopathy), high blood serum level of dihydrothymine together with normal levels of thymidine and deoxyuridine made it possible to verify the diagnosis. Histopathological examination revealed atrophy of the longitudinal (outer) muscle layer of the small and large intestines and a significant decrease in the number of CD117+ cells (telocytes), signs of damage to the striated skeletal muscles of a mixed nature with a predominance of the myogenic pattern, as well the destruction of the myelin sheaths of peripheral nerves. Histochemical examination did not reveal “ragged red fibers” characteristic of mitochondrial pathology. Transmission electron microscopy demonstrated the presence of megalomitochondria in the myocardium.Синдром митохондриальной нейрогастроинтестинальной энцефаломиопатии – редкое (1–9:1000000, Orphanet, 2021) генетическое мультисистемное заболевание, обусловленное мутациями в ядерном гене TYMP, кодирующем фермент тимидинфосфорилазу.Представлены данные 13‑летнего наблюдения пациентки Д., 40 лет, с синдромом митохондриальной нейрогастроинтестинальной энцефаломиопатии, связанным с ранее не описанной миссенс‑заменой c.1301G>T (p.Gly434Val) в гене TYMP. Диагноз синдрома митохондриальной нейрогастроинтестинальной энцефаломиопатии был поставлен на основании клинических проявлений (дисфункция желудочно‑кишечного тракта, кахексия, блефароптоз, офтальмопарез, периферическая полинейропатия и лейкоэнцефалопатия), результатов электронейромиографии (демиелинизация с вторичной аксонопатией), а также повышения уровня дигидротимина в сыворотке крови при нормальных уровнях тимидина и дезоксиуридина. Патогистологическое исследование выявило атрофию продольного (наружного) мышечного слоя тонкой и толстой кишок и значимое уменьшение количества CD117+‑клеток (телоцитов), поражение скелетных мышц смешанного характера с преобладанием миогенного паттерна, а также деструкцию миелиновых оболочек периферических нервов. Исследование S100‑положительных вегетативных образований кишечной стенки не выявило патологических изменений. При гистохимическом исследовании не были обнаружены «рваные красные волокна», характерные для митохондриопатий. Трансмиссионная электронная микроскопия продемонстрировала наличие полиморфизма митохондрий кардиомиоцитов и мегаломитохондрий лейомиоцитов кишечника

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

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