Influence of COVID-19 on anemia in patients on program hemodialysis

The aim of the study - to study changes in the level of hemoglobin, iron and the volume of erythropoietin therapy in patients on program hemodialysis during the COVID-19 pandemic.Цель исследования - изучить изменения уровня гемоглобина, железа и объема терапии эритропоэтином у пациентов, находящихся на программном гемодиализе, в период пандемии COVID-1

Мутации в геноме вирусов гриппа птиц подтипов Н1 и Н5, ответственные за адаптацию к млекопитающим

Avian influenza viruses of H1 and H5 subtypes were involved in the formation of highly pathogenic viruses that caused pandemics and panzootics in the 20th–21st centuries. In order to assess the zoonotic potential of viruses of these subtypes, two viruses of H1N1 and H5N3 have been isolated from wild ducks in Moscow and adapted to growth in mouse lungs. Their phenotypic properties were studied, and the genetic changes that occurred during adaptation were identified. The original A/duck/Moscow/4970/2013 (H1N1) and A/duck/Moscow/4182-C/2010 (H5N3) viruses were apathogenic for mice but became pathogenic after 7–10 passages in mouse lungs. Complete genome sequencing revealed 2 amino acid substitutions in the proteins of the H1N1 mouse-adapted variant (Glu627Lys in PB2 and Asp35Asn in hemagglutinin (HA) – numbering according to H3) and 6 mutations in the proteins of H5N3 virus (Glu627lys in PB2, Val113Ala in PB1, Ser82Pro in PB1-F2, Lys52Arg in HA2, Arg65Lys in NP, and Ser59Ile in NA). The increase in virulence is most likely due to a common substitution in the protein PB2 Glu627Lys as revealed in both viruses. The replacement of Asp35Asn in HA of the mouse-adapted H1N1 virus is associated with an increase in the pH value of the HA transition from 5.0 for 5.5 in comparison to the HA of parent virus. The found mutations in HA, NA, and PB1-F2 proteins of the adapted H5N3 variant are unique. The mutations Glu627Lys in PB2, Arg65Lys in NP, and Val113Ala in PB1 are most likely host adaptive.Вирусы гриппа птиц подтипов Н1 и Н5 участвовали в формировании высокопатогенных вариантов вирусов, вызвавших пандемии и  панзоотии в  XX–XXI  веках. С  целью оценки зоонозного потенциала вирусов этих подтипов, выделенных от диких уток в черте Москвы, была проведена адаптация вирусов к размножению в легких мышей, изучены их фенотипические свойства и идентифицированы генетические изменения, возникшие при адаптации. Изначально апатогенные для мышей вирусы A/duck/Moscow/4970/2013 (H1N1) и A/duck/Moscow/4182‑C/2010 (H5N3) после 7–10 пассажей через легкие мышей изменили фенотип на патогенный. Полногеномное секвенирование выявило в адаптированных к мышам вирусах 2 аминокислотные замены в вирусе гриппа H1N1 (Glu627Lys в белке PB2 и Asp35Asn в гемагглютинине (HA) — нумерация по H3) и 6 мутаций в белках вируса H5N3 (Glu627Lys в PB2, Val113Ala в PB1, Ser82Pro в PB1‑F2, Lys52Arg в HA2, Arg65Lys в NP и Ser59Ile в NA). Возрастание вирулентности для мышей, скорее всего, обусловлено общей для обоих вирусов заменой – Glu627Lys в  белке PB2. Замена Asp35Asn в  HA адаптированного к  мышам вируса гриппа H1N1  ассоциирована с возрастанием значения рН конформационного перехода HA с 5.0 до 5.5 относительно HA дикого вируса. Обнаруженные в адаптированном варианте H5N3 мутации в белках НА, NA и PB1‑F2 — уникальные. Мутации Glu627Lys в PB2, Arg65Lys в NP и Val113Ala в PB1, скорее всего, носят адаптационный характер

НЕЙРОПСИХОЛОГИЧЕСКИЙ СТАТУС ПАЦИЕНТОВ СО СТАБИЛЬНОЙ ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦА И ФАКТОРЫ, НА НЕГО ВЛИЯЮЩИЕ

The purpose. To assess neuropsychological status of patients with stable coronary artery disease (CAD) and to determine the factors affecting it.Material and methods. 272 male patients aged 45-69 years were included in the study. Neuropsychological status of patients with coronary artery disease was assessed and presented as an integrated index.Results. The integrated index of neuropsychological status was reported to be 2 times less than those in healthy subjects matched for age (0.47 [0.35; 0.59] vs. 0.8 [0.72; 0.87, (p <0.0001)). The most significant factors affecting neuropsychological status of patients with coronary artery disease were as follows: age (p = 0.00271), number of years of education (p = 0.033), left ventricular ejection fraction (LVEF) (p = 0.018), as well as plasma triglyceride levels (TG) (p = 0.003). Conclusion. The integrated approach to the assessment of neuropsychological status in patients with CAD allows not only presenting it as a single index, but also determining the extent to which the index deviate from neuropsychological status of healthy subjects. The factors affecting neuropsychological status in patients with coronary artery disease were as follows: age, number of years of education, LVEF and plasma triglyceride levels.Цель. Оценить состояние нейропсихологического статуса пациентов со стабильной ишемической болезнью сердца (ИБС) и определить факторы, на него влияющие.Материал и методы. Обследовано 272 мужчины в возрасте 45-69 лет. Нейропсихологический статус пациента с ИБС комплексным способом был представлен в виде его интегрального показателя.Результаты. Выявлено, что интегральный показатель нейропсихологического статуса почти в 2 раза ниже данного показателя здоровых лиц того же возраста (0,47 [0,35; 0,59] и 0,8 [0,72; 0,87, (p<0,0001)). Установлено, что наиболее значимыми факторами, влияющими на нейропсихологический статус пациента с ИБС, являются возраст (p=0,00271), количество лет обучения (p=0,033), фракции выброса левого желудочка (p=0,018), а также концентрация в плазме триглицеридов (ТГ) (p=0,003).Выводы. Комплексный способ оценки нейропсихологического статуса у пациентов с ИБС позволяет оценить и представить его в виде единого показателя, а также определить степень его отклонения от статуса здоровых лиц. Факторами, негативно влияющими на состояние нейропсихологического статуса у пациентов с ИБС, являются возраст, количество лет образования, ФВ ЛЖ и концентрация в плазме крови ТГ

Дифференциальная диагностика токсического эпидермального некролиза (синдрома Лайелла) в ОРИТ: клинические наблюдения

Toxic epidermal necrolysis (TEN) is a critical life-threating condition developing as the total detachment of epidermidis and characterized by severe pathological reactions of all body systems. The current article describes two cases of TEN with similar clinical and laboratory signs. In one case the diagnosis of TEN was subsequently refused.The objective: analysis of methods of clinical and differential diagnostics of conditions accompanied with massive epidermidis detachment in ICU patients.Results. The immunomorphological evaluation of skin specimen obtained from the patient with a torpid form of TEN showed linear IgG fixation in the intercellular space of stratum basale, stratum spinosum and stratum granulosum and C3 fixation in the intercellular space of stratum basale.Conclusion. The complex of anamnesis data and pathomorphological evaluation of skin are crucial for the diagnosis and treatment of patients with atypical TEN.Токсический эпидермальный некролиз (ТЭН) – критическое жизнеугрожающее состояние, развивающееся в виде тотального отслоения эпидермиса и характеризующееся тяжелыми реакциями со стороны всех систем организма. Приведено описание двух клинических случаев со сходной клинико-лабораторной симптоматикой, в одном из которых диагноз ТЭН впоследствии был опровергнут.Цель: анализ методов клинической и лабораторной дифференциальной диагностики состояний, сопровождающихся массивной отслойкой эпидермиса, у пациентов, пребывающих в ОРИТ.Результаты. При иммуноморфологическом исследовании биоптата кожи, полученного от пациентки с торпидным течением ТЭН, обнаружена четкая линейная фиксация IgG в межклеточной связывающей субстанции (МСС) базального, шиповатого и зернистого слоев эпидермиса, а также фиксация С3-компонента комплемента в МСС базального слоя эпидермиса.Заключение. Совокупность анамнестических сведений и результатов патоморфологического исследования методом прямой иммунофлюоресценции имеет критически важное значение для установления диагноза и выбора лечебной тактики у пациентов с атипичным течением ТЭН

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

The formation of human populations in South and Central Asia

By sequencing 523 ancient humans, we show that the primary source of ancestry in modern South Asians is a prehistoric genetic gradient between people related to early hunter-gatherers of Iran and Southeast Asia. After the Indus Valley Civilization’s decline, its people mixed with individuals in the southeast to form one of the two main ancestral populations of South Asia, whose direct descendants live in southern India. Simultaneously, they mixed with descendants of Steppe pastoralists who, starting around 4000 years ago, spread via Central Asia to form the other main ancestral population. The Steppe ancestry in South Asia has the same profile as that in Bronze Age Eastern Europe, tracking a movement of people that affected both regions and that likely spread the distinctive features shared between Indo-Iranian and Balto-Slavic languages