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© 2021, The Author(s). Background: Sleep-disordered breathing (SDB) is highly prevalent in acute ischaemic stroke and is associated with worse functional outcome and increased risk of recurrence. Recent meta-analyses suggest the possibility of beneficial effects of nocturnal ventilatory treatments (continuous positive airway pressure (CPAP) or adaptive servo-ventilation (ASV)) in stroke patients with SDB. The evidence for a favourable effect of early SDB treatment in acute stroke patients remains, however, uncertain. Methods: eSATIS is an open-label, multicentre (6 centres in 4 countries), interventional, randomized controlled trial in patients with acute ischaemic stroke and significant SDB. Primary outcome of the study is the impact of immediate SDB treatment with non-invasive ASV on infarct progression measured with magnetic resonance imaging in the first 3 months after stroke. Secondary outcomes are the effects of immediate SDB treatment vs non-treatment on clinical outcome (independence in daily functioning, new cardio-/cerebrovascular events including death, cognition) and physiological parameters (blood pressure, endothelial functioning/arterial stiffness). After respiratory polygraphy in the first night after stroke, patients are classified as having significant SDB (apnoea-hypopnoea index (AHI) > 20/h) or no SDB (AHI < 5/h). Patients with significant SDB are randomized to treatment (ASV+ group) or no treatment (ASV− group) from the second night after stroke. In all patients, clinical, physiological and magnetic resonance imaging studies are performed between day 1 (visit 1) and days 4–7 (visit 4) and repeated at day 90 ± 7 (visit 6) after stroke. Discussion: The trial will give information on the feasibility and efficacy of ASV treatment in patients with acute stroke and SDB and allows assessing the impact of SDB on stroke outcome. Diagnosing and treating SDB during the acute phase of stroke is not yet current medical practice. Evidence in favour of ASV treatment from a randomized multicentre trial may lead to a change in stroke care and to improved outcomes. Trial registration: ClinicalTrials.gov NCT02554487, retrospectively registered on 16 September 2015 (actual study start date, 13 August 2015), and www.kofam.ch (SNCTP000001521).

© 2021, The Author(s). Background: Sleep-disordered breathing (SDB) is highly prevalent in acute ischaemic stroke and is associated with worse functional outcome and increased risk of recurrence. Recent meta-analyses suggest the possibility of beneficial effects of nocturnal ventilatory treatments (continuous positive airway pressure (CPAP) or adaptive servo-ventilation (ASV)) in stroke patients with SDB. The evidence for a favourable effect of early SDB treatment in acute stroke patients remains, however, uncertain. Methods: eSATIS is an open-label, multicentre (6 centres in 4 countries), interventional, randomized controlled trial in patients with acute ischaemic stroke and significant SDB. Primary outcome of the study is the impact of immediate SDB treatment with non-invasive ASV on infarct progression measured with magnetic resonance imaging in the first 3 months after stroke. Secondary outcomes are the effects of immediate SDB treatment vs non-treatment on clinical outcome (independence in daily functioning, new cardio-/cerebrovascular events including death, cognition) and physiological parameters (blood pressure, endothelial functioning/arterial stiffness). After respiratory polygraphy in the first night after stroke, patients are classified as having significant SDB (apnoea-hypopnoea index (AHI) > 20/h) or no SDB (AHI < 5/h). Patients with significant SDB are randomized to treatment (ASV+ group) or no treatment (ASV− group) from the second night after stroke. In all patients, clinical, physiological and magnetic resonance imaging studies are performed between day 1 (visit 1) and days 4–7 (visit 4) and repeated at day 90 ± 7 (visit 6) after stroke. Discussion: The trial will give information on the feasibility and efficacy of ASV treatment in patients with acute stroke and SDB and allows assessing the impact of SDB on stroke outcome. Diagnosing and treating SDB during the acute phase of stroke is not yet current medical practice. Evidence in favour of ASV treatment from a randomized multicentre trial may lead to a change in stroke care and to improved outcomes. Trial registration: ClinicalTrials.gov NCT02554487, retrospectively registered on 16 September 2015 (actual study start date, 13 August 2015), and www.kofam.ch (SNCTP000001521).

© 2020 Elsevier Inc. Objective: Conflicting data exist on the effect of dexmedetomidine on delirium. For the present study, a randomized trial was performed to investigate the effect of perioperative dexmedetomidine on the rate of postoperative delirium after cardiac surgery. Design: A randomized controlled trial. Setting: University hospital. Participants: Patients (n = 169) undergoing elective cardiac surgery (coronary artery bypass graft surgery, valve surgery, or combined surgery) with cardiopulmonary bypass. Interventions: Patients received a sevoflurane-based general anesthesia and were randomly assigned 1:1 to receive a dexmedetomidine infusion that started in the operating room (0.7 μg/kg/h) and continued into the intensive care unit (0.4 μg/kg/h) or an equivolume infusion of placebo. Measurements and Main Results: A decrease in the rate of delirium in the dexmedetomidine group compared with the placebo group was demonstrated (6 of 84 [7.1%] v 16 of 85 [18.8%]; p = 0.02; odds ratio [OR] 0.33 [95% confidence interval {CI} 0.12-0.90]). Reduced intensive care unit and hospital lengths of stay also were observed (18 [18-22] hours v 22 [18-39] hours; p = 0.002 and 17 [7-20] days v 19 [8-21] days; p = 0.04, respectively). Mortality at 30 days was 2 (2.4%) in both groups. On multivariate analysis, only dexmedetomidine administration (OR 0.24 [95% CI 0.08-0.74]) and cardiopulmonary bypass time (OR 1.02 [95% CI 1.01-1.03] for increases of 1 min) were independent predictors of delirium development. Conclusions: Dexmedetomidine administered during and after general anesthesia for cardiac surgery with cardiopulmonary bypass decreased the rate of postoperative delirium and intensive care unit and hospital lengths of stay.

© 2020 Elsevier B.V. Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) are crucial for the peripheral and central nervous system development, respectively, and differential brain and blood levels in Intra Uterine Growth Restriction (IUGR) and prematurity have been found. As reduced growth of brain regions, measured at 30−40 days of postnatal period, has been demonstrated in preterm and IUGR neonates who showed impaired neuro-development at two years of age, in this study, the levels of NGF and BDNF were evaluated in the urine samples of 30−40 day-old subjects who were full-term, preterm and IUGR and showed a normal or an abnormal neuro-development at follow up after two years. Neurotrophins were measured concurrently with volumes of whole brain, thalamus, frontal cortex and cerebellum. Values were then correlated with later neuro-developmental outcome. Biochemical parameters and cerebral volumes were assessed using colorimetric ELISA kits and three-dimensional ultra-sonography (3DUS), respectively. Neuro-development was estimated using the Griffiths-II test. Urinary NGF and brain volumes significantly correlated and were lower in preterm and IUGR subjects characterized by poor neuro-development. No differences were seen in the case of BDNF. The present investigation demonstrates, for the first time, the strong and direct association of NGF with brain growth at the initial phase of the postnatal period and with neuro-developmental outcome in later life. Remarkably, urinary NGF may be suggested as an early prognostic indicator of high long-term risk of motor and cognitive impairment in IUGR and preterm neonates.

© 2020 Elsevier B.V. Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) are crucial for the peripheral and central nervous system development, respectively, and differential brain and blood levels in Intra Uterine Growth Restriction (IUGR) and prematurity have been found. As reduced growth of brain regions, measured at 30−40 days of postnatal period, has been demonstrated in preterm and IUGR neonates who showed impaired neuro-development at two years of age, in this study, the levels of NGF and BDNF were evaluated in the urine samples of 30−40 day-old subjects who were full-term, preterm and IUGR and showed a normal or an abnormal neuro-development at follow up after two years. Neurotrophins were measured concurrently with volumes of whole brain, thalamus, frontal cortex and cerebellum. Values were then correlated with later neuro-developmental outcome. Biochemical parameters and cerebral volumes were assessed using colorimetric ELISA kits and three-dimensional ultra-sonography (3DUS), respectively. Neuro-development was estimated using the Griffiths-II test. Urinary NGF and brain volumes significantly correlated and were lower in preterm and IUGR subjects characterized by poor neuro-development. No differences were seen in the case of BDNF. The present investigation demonstrates, for the first time, the strong and direct association of NGF with brain growth at the initial phase of the postnatal period and with neuro-developmental outcome in later life. Remarkably, urinary NGF may be suggested as an early prognostic indicator of high long-term risk of motor and cognitive impairment in IUGR and preterm neonates.

© 2019 Background: Iron (Fe), copper (Cu), and manganese (Mn) play a significant role in female reproduction and fetal development. At the same time, high levels of metals may exert toxic effects. Correspondingly, both excess and deficiency of essential trace elements were shown to be associated with female infertility and adverse pregnancy outcome, although the existing data are rather contradictory. Therefore, the objective of the present study was to reveal the potential role of altered iron, copper, and manganese status in female reproductive health problems through assessment of serum metal levels in healthy non-pregnant and pregnant women, as well as patients with miscarriage and primary infertility. Methods: A total of 150 healthy controls, 169 pregnant women (II trimester of pregnancy), 75 women with miscarriage, and 91 patients with primary infertility were enrolled. Serum metal levels were assessed using ICP-MS. Results: Pregnant women are characterized by a significant increase in serum Cu an Mn levels by 40% (p < 0.001) and 16% (p = 0.043) as compared to the controls, respectively. Serum Cu levels in women with miscarriage and infertility were 30% and 35% lower than those in pregnant women (p < 0.001). No significant difference in serum iron levels were observed between the control and pregnant women. Women who had miscarriage were characterized by 13% (p = 0.042) higher serum Fe levels as compared to the pregnant ones. Multiple regression analysis demonstrated that serum copper levels was significantly associated both with pregnancy (β = 0.436; p < 0.001) and reproductive health problems in women (β = −0.272; p < 0.001). The latter was improved significant after adjustment for serum Fe and Mn levels, age, and BMI (β = −0.431; p < 0.001). The model incorporating serum Cu, Fe, Mn, and anthropometric parameters accounted for 23% of variability in reproductive status (p < 0.001). Conclusions: It is proposed that the lack of pregnancy-associated increase in metal levels in miscarriage and infertility may be indicative of at least partial role of metal insufficiency in impaired pregnancy and reproductive function in general. However, detailed clinical studies as well as experimental investigations are required for assessment of the potential causes and mechanisms of the observed associations.

© 2019 John Wiley  &  Sons, Ltd. Management guidelines continue to identify metformin as initial pharmacologic antidiabetic therapy of choice for people with type 2 diabetes without contraindications, despite recent randomized trials that have demonstrated significant improvements in cardiovascular outcomes with newer classes of antidiabetic therapies. The purpose of this review is to summarize the current state of knowledge of metformin's therapeutic actions on blood glucose and cardiovascular clinical evidence and to consider the mechanisms that underlie them. The effects of metformin on glycaemia occur mainly in the liver, but metformin-stimulated glucose disposal by the gut has emerged as an increasingly import site of action of metformin. Additionally, metformin induces increased secretion of GLP-1 from intestinal L-cells. Clinical cardiovascular protection with metformin is supported by three randomized outcomes trials (in newly diagnosed and late stage insulin-treated type 2 diabetes patients) and a wealth of observational data. Initial evidence suggests that cotreatment with metformin may enhance the impact of newer incretin-based therapies on cardiovascular outcomes, an important observation as metformin can be combined with any other antidiabetic agent. Multiple potential mechanisms support the concept of cardiovascular protection with metformin beyond those provided by reduced blood glucose, including weight loss, improvements in haemostatic function, reduced inflammation, and oxidative stress, and inhibition of key steps in the process of atherosclerosis. Accordingly, metformin remains well placed to support improvements in cardiovascular outcomes, from diagnosis and throughout the course of type 2 diabetes, even in this new age of improved outcomes in type 2 diabetes.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Purpose of Review: Sleep-wake disorders (SWD) are common not only in the general population but also in stroke patients, in whom SWD may be pre-existent or appear “de novo” as a consequence of brain damage. Despite increasing evidence of a negative impact of SWD on cardiocerebrovascular risk, cognitive functions, and quality of life, SWD are insufficiently considered in the prevention and management of patients with stroke. This narrative review aims at summarizing the current data on the bidirectional link between SWD and stroke. Recent Findings: Several studies have demonstrated that sleep-disordered breathing (SDB) is an independent risk factor for stroke and has a detrimental effect on stroke recovery. Short and long sleep duration and possibly other SWD (e.g., insomnia, circadian rhythm disorders) may also increase the risk of stroke and influence its outcome. Data on SDB treatment increasingly indicate a benefit on stroke risk and evolution while treatment of other SWD is still limited. Summary: A systematic search for SWD in stroke patients is justified due to their high frequency and their negative impact on stroke outcomes. Clinicians should actively consider available treatment options.

© 2018 Wiley-VCH Verlag GmbH  &  Co. KGaA, Weinheim Phosphorolytic transglycosylation catalyzed by nucleoside phosphorylases is an important biotechnological process. The reaction is reversible, and the yield of the target nucleoside depends on its concentration at the equilibrium state. We have shown that initial concentrations of the starting compounds and the phosphorolysis equilibrium constants of starting and final glycosides determine concentrations of all the components at the equilibrium state. Based on that, we developed a novel quantitative approach for the prediction of yields in transglycosylation reactions. This method simplifies the choice of reagent concentrations and their ratios for the maximization of the target nucleoside yield. It is advantageous over widely applied blind and cumbersome trial-and-error approach and can reduce the required chemical and energy resources. The described algorithm could also be applied for other equilibrium transfer reactions. (Figure presented.).

© 2018 National Research University Higher School of Economics. All rights reserved. The aim of this study was to identify predictors of poor outcomes in patients hospitalized for severe acute exacerbation of COPD (AECOPD). Methods. This retrospective, observational cohort study was conducted in Pulmonology Department of a city hospital in 2015 - 2016 and involved patients hospitalized for severe AECOPD. Patients were divided according to outcomes. Poor outcomes included at least one of the followings: the need in invasive (IMV) or non-invasive (NIV) ventilation, admission to ICU, in-hospital death and COPD-related readmission during 2 months. Demographic, clinical, laboratory parameters, pulmonary function tests and blood gas analysis were analyzed; different multidimensional prognostic scores were also evaluated and compared. Results. Of 121 patients included, a poor outcome had occurred in 45 patients (37%). Among them, NIV was required in 21 (17%), IMV in 8 (6%), and admission to ICU in 16 patients (13%); death was registered in 6 patients (5%) and readmission in 27 (22%) of the patients. Patients with poor outcomes were admitted more frequently by ambulance (62% vs 40%; p = 0.003), more often were admitted to a hospital for AECOPD in the previous year (69% vs 45%; p = 0.0006), and had lower pH (p = 0.001), lower PaO2 (p = 0.001), higher PaCO2 (p = 0.001), and a worse score on several prognostic scales such as APACHE II (13.9 ± 5.4 vs 7.8 ± 3.6; p = 0.001), DECAF (2.4 ± 0.6 vs 1.5 ± 0.6; p = 0.001), BODEx (5.6 ± 1.8 vs 3.9 ± 1.1; p = 0.001), DOSE (2.9 ± 1.5 vs 2.2 ± 1.2; p = 0.029), and ADO (4.9 ± 1.5 vs 4.3 ± 1.3; p = 0.015) at admission. They more frequently received O2 therapy (87% vs 46%; p = 0.001) and had longer hospital stay (19.2 ± 6.2 days vs 12.5 ± 1.8 days; p = 0.001). Conclusions. Hypercapnia, hypoxemia and worse prognostic scores on admission predicted poor outcome in patients hospitalized for AECOPD during the previous year.

© Bionika Media Ltd. Objective. To evaluate the efficiency of methodological approaches to optimizing the care of pregnant women with gestational diabetes mellitus (GDM) under the present-day conditions of a progressive increase in the incidence of this disease in case of a specialized obstetric hospital. Materials and methods. The statistical data on the 2015–2016 activities of the Outpatient Department and the Maternity Department, Moscow City Clinical Hospital Twenty-Nine, were retrospectively analyzed. Results. GDM was diagnosed in two thirds of the pregnant women at more than 30 weeks’ gestation in primary outpatient care services. In the management of pregnant women with untimely detected GDM, the sensitivity of ultrasound fetometry using the specific markers of diabetic fetopathy (DF) was 65.5%. Programmed labor (PL) was one of the leading methods during childbirth. Conclusion. Ultrasound fetometry using specific markers for DF and the strict continuity of outpatient and inpatient care permitted the frequency of DF to be reduced about 1.5-fold. The use of PL methods in GDM contributed to a two-fold decrease in the cesarean delivery rate without deteriorating the perinatal outcomes of labor.

© 2018, Pediatria Ltd.. All rights reserved.  Objective of the research – to reveal the correlation between neurochemical criteria in the neonatal period and the consequences of severe hypoxic hemorrhagic CNS lesions in children according to catamnesis data. Materials and methods: researchers analyzed 54 cases of newborns of different gestational age (GA) that were in the ICU after birth due to severe condition; all newborns had combined hypoxic hemorrhagic brain lesion detected by neurosonography – periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH) of various severity. Catamnesis follow-up was performed up to 2–2,5 years of age. The control group consisted of 20 newborns, comparable in GA, body weight at birth, with an Apgar score of at least 6 points in the 1st minute of life and without changes in neurosonography. In the neonatal period, serum concentrations of S100, BDNF, VEGF, ALCAM, DR5 were studied in dynamics using the quantitative ELISA (Enzyme Linked Immuno Sorbent Assay) according to a standard protocol. Results: the concentration of factors contributing to destructive changes in tissues (S100, DR5, ALCAM) in the serum, was in inverse correlation with the level of VEGF and BDNF. The latter had a direct correlation relationship. VEGF directly correlated with CNTF by the end of the 2 nd week of life. Results of catamnesis follow-up: 43 children diagnosed with cerebral palsy, 25 with spastic diplegia, 18 with spastic tetraparesis, and 11 without evident motor disorders. In 28 children I–III level of motor disorders was determined according to GMFS, in 26 children – IV–V level. At the age of 2 years, all children underwent MRI of the brain and gliio-atrophic changes were detected. Significant differences in the implementation of neurological consequences were found between the number of children with grade I and II IVH and PVL and III–IV degree IVH and PVL. Conclusion: children with PVL and IVH III–IV degree have a high risk of severe neurological outcomes – spastic tetraparesis, impaired motor activity by GMFS IV–V level, mental retardation and symptomatic epilepsy.

© 2018 Lippincott Williams and Wilkins. All rights reserved. The objective - of the present work was to develop the forensic medical criteria for the evaluation of the unfavourable outcomes of the roentgeno-endovascular operations (REVO) on the arteries of the lower extremities. The study included the analysis of the conclusions based on the results of the commission forensic medical examinations, attorney inquiry reports, query response, medical histories of the hospitalized patients who had undergone the roentgeno-endovascular operations on the arteries of the lower extremities. The criteria for the forensic medical evaluation of the unfavourable outcomes of the roentgeno-vascular operations on the arteries of the lower extremities have been proposed together with the indications for REVO, methods and tools for the performance of these surgical procedures. Particular attention was given to the identification of the signs and prognostics of the unfavourable outcomes of the roentgeno-endovascular operations (both intraoperatively and during the early postoperative period and the subsequent stay in the hospital) and to the risks of the development of the unfavourable outcomes of the surgical interventions following the technically adequate REVO. Special emphasis is placed on the cause-and-effect relationship between the actions or a failure to act on the part of an emergency physician and/or an attending surgeon/cardiovascular surgeon and the possibility of the unfavourable outcomes of the roentgeno-endovascular operations.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To study clinico-epidemiological characteristics of patients with CHC and to evaluate clinical, economic and other parameters related to their treatment. Patients and methods. The study is conducted in 10 countries in Central and Eastern Europe involving 1.500-2000 patients with chronic HCV infection, aged 18 years and older not current receiving treatment for hepatitis and seeking for care in a routine clinical visit to physician. After enrollment, patients are observed until the end of HCV treatment. The study includes three consecutive phases. At the phase 1 epidemiological data for the patients seeking for care is being collected at the single visit. Patients for whom antiviral IFN-containing treatment is planned to be started within 12 weeks from the first visit were included into the second phase. During phase 2 patients are being assessed on-treatment for HRQoL changes over time, the impact of HCV and treatment on work productivity, activities of daily living and resource utilization. Interim results presented in this paper reflect epidemiologic characteristics of HCV patients collected during the first phase of MOSAIC study on the territory of Russia. Results. Data from 492 patients were collected in 15 study centers in Russia. 441 patients (377 treatment naïve, 64 experienced) entered the study, 51 patients were considered non-participants. 161 patients did not start treatment within 12 weeks after enrollment. Patients were of white race, 57% males and 43% females, aged between 19 and 74 years, with median age 37.0 (IQR 31-47 years). Median time since HCV diagnosis was 2.0 years. 30 (6.8%) patients had clinically compensated liver cirrhosis, 40% of patients had unknown cirrhosis status. The most common viral genotypes were Gt1 and Gt3 – 55.6% and 37.6% of patients, respectively. Among patients with known viral load HCV RNA level at enrollment was ≤ 800.000 IU/ml in 53% of patients and > 800.000 IU/ml in 47% of patients. Twelve (4.3%) treated patients had extra-hepatic symptoms of liver disease, no association was found between liver cirrhosis and presence of extra-hepatic manifestations (p = 0.3534). 14.5% of patients were treatment experienced, 88.9% of them had only one course of antiviral therapy in the past. Relapse was the most common reason of therapy failure observed in 50% (32/64) patients.17.5% of HCV patients have concomitant diseases; the most common are cardiovascular diseases (5,7%), other liver diseases (5%) and diabetes mellitus (2,9%), the latter is associated with the presence of liver cirrhosis (p = 0.0125). Among studied parameters (gender, age, HCV genotype and pre-treatment status) age was an only significant predictor of liver cirrhosis development, odds increase with every 10 years of increment (OR 2.005 [95% CI 1.407; 2.858], ROC 0.732, p = 0.0001). Conclusion. Epidemiology of patients with HCV infection was investigated in the first phase of MOSAIC international observational study on the territory of Russia and described in the present article. Сlinical, humanistic and economic burden of anti-HCV treatment based on MOSAIC data will be presented in future publications.