Pulmonary embolism and atrial fibrillation: analysis of data from the SIRENA Russian registry

Aim. To present the clinical characteristics and in-hospital prognosis in patients with pulmonary embolism (PE) and atrial fibrillation (AF).Material and methods. On the initiative of a working group of physicians, the basic principles of an observational prospective study (SIRENA registry) have been developed.Results. Among the 660 patients included in the registry, AF was diagnosed in almost every fourth patient — in 22,9% of cases (n=151), which reflects its high incidence in relation to PE. The prevalence of AF corresponded to such conditions as heart failure (HF) (23,2%; n=153), diabetes (15,6%; n=103), and hypertension (HTN) (65,7% n=400). The diagnosis of AF in most patients is based on the history data (n=144; 95,4%), while the first registered AF episode was verified in 7 patients (4,6%). Patients with AF were characterized by older age, significantly higher prevalence of HF (51,2%), HTN (80,8%), chronic kidney disease (18,5%), stroke or transient ischemic attack (23,2%). It is important to note the low prevalence of anticoagulant therapy (15,3%) in the group of patients with previously diagnosed AF (n=144). The prevalence of thrombolytic therapy in patients with AF was significantly lower than among patients without AF (13,9 vs 25,8% (p=0,026)), which is due to contraindications and underdiagnosis of PE. Given the predominantly senile age, high comorbidity rate in patients with AF, as well as the absence of outpatient anticoagulant therapy, in-hospital mortality in patients with PE and AF was 31,1%, and significantly differed from that in those without AF 12,6% (p=0,001). In the general group, post-mortem diagnosis of PE was noted in 7,7% of cases (n=51), of which the proportion of patients with AF was 54,9% (n=28). A possible explanation for the underestimation of PE in AF patients was an erroneous explanation of its manifestations (tachypnea, tachycardia, lower limb edema) due to concomitant HF.Conclusion. Suspicion for PE in elderly patients with AF and manifestations of HF decompensation, as well as the timely administration of anticoagulant therapy, will prevent both arterial and venous embolism

Paradoxical embolism with the development of ischemic stroke on the background of pulmonary embolism: comparative analysis of two clinical cases

The development of a neurological deficit clinic in patients with pulmonary embolism (PE) requires a diagnostic search aimed at excluding the phenomenon of paradoxical embolism in the form of transcranial dopplerography (TCDG) with a bubble test, and to clarify the features of intracardiac hemodynamics – transesophageal echocardiography (TEE). Material and methods. The article presents two clinical examples of the development of PE in the form of embolic ischemic stroke (IS) against the background of deep vein thrombosis of the lower extremities, PE, patent foramen ovale (PFO) in combination with an atrial septal aneurysm. Results and discussion. In the first case, the right-left shunt was confirmed by TKDG with a bubble test, in the second example, during routine transthoracic echocardiography, a ribbon thrombus prolapsing through the PFO was visualized. In our opinion, PE is a possible mechanism of IS in patients with venous thromboembolic events. Consequently, it is necessary to plan a “bubble test” for verifying the cause of a stroke. Conclusions. The management of patients with PE and IS was individual and required a team approach, including the use of thrombolytic therapy, the selection of an anticoagulant therapy regimen, choice of conservative/invasive tactics for the treatment of patients

The Flow Cytometry Study of Cellular Immunity in Rhesus Monkeys after Experimental Infection with SARS CoV 2 Virus

Cellular immunity plays an important role in the pathogenesis and formation of protective immune defense against the SARS‑CoV‑2 virus.The aim of the work was to study the cellular immunity of rhesus monkeys applying flow cytometry after experimental infection with the SARS‑CoV‑2 virus.Materials and methods. Male rhesus monkeys were intranasally inoculated with the SARS‑CoV‑2 virus, Isolate B strain and hCoV-19/Russia/SP48-1226/2020 strain (abbreviated name U-2), at a dose of 5.0 lg PFU. Using flow cytometry, the levels of 21 populations/subpopulations of mononuclear cells in the peripheral blood of animals were determined before experimental infection with the pathogen and on day 14 after infection. SARS‑CoV‑2 coronavirus RNA was assessed using real-time polymerase chain reaction. Determination of the titer of virus-neutralizing antibodies to the SARS‑CoV‑2 virus in the blood sera of animals was conducted through neutralization test evaluating the ability to suppress negative colonies.Results and discussion. Infection with Isolate B strain culture has led to an increase in the relative content of total T-lymphocytes (p˂0.2), cytotoxic T-lymphocytes (p˂0.1), as well as monocytes expressing the early activation marker CD25 (p˂0.2). The decrease in levels has been observed for total B-lymphocytes (p˂0.2) and T-helper cells (p˂0.1). Infection with the U-2 strain culture revealed an increase in the relative content of monocytes expressing the early activation marker CD25 (p˂0.2). Thus, for the first time in the Russian Federation, flow cytometry was used to study the cellular immunity of rhesus monkeys before and after experimental infection with the SARS‑CoV‑2 virus. The obtained information can be used for studying the pathogenesis of SARS‑CoV‑2 infection, course, and outcome of the disease, and developing strategies for vaccination and treatment

Свойства гетерологичного иммуноглобулина против лихорадки Эбола после длительного хранения

Ebola outbreak in eastern parts of the Democratic Republic of the Congo in 2018–2020 proved that the virus remains highly hazardous for humans, and the outbreak in West Africa in 2014–2016, which was the largest Ebola outbreak in history, showed that it could be imported to other continents, including Russia. In 1993 the Federal State Budgetary Institution “48th Central Scientific Research Institute” of the Russian Ministry of Defence developed a specific equine immunoglobulin for emergency prophylaxis of Ebola in risk groups. The evaluation and improvement of the product’s properties is an important area in the development of biological defence technologies.The aim of the study was to examine the properties of the equine anti-Ebola immunoglobulin which had been stored for a long time at 2–8 °C.Materials and methods: the authors studied batches of heterologous anti-Ebola immunoglobulin that had been stored for 17–22 years. The properties of the product were evaluated according to the requirements of the State Pharmacopoeia of the Russian Federation, 14th ed. (Ph. Rus. 14 ed.). The specific activity of the product was determined in a plaque reduction neutralisation test using Ebola virus and African green monkey kidney cells (GMK-AH-1(D)). Immunoglobulin molecular parameters were determined by size-exclusion high-performance liquid chromatography using the test methods described in the European Pharmacopoeia 9.6 and Ph. Rus. 14 ed.Results: the storage of anti-Ebola immunoglobulin for 17–22 years at 2–8 °C resulted in a four-fold reduction of the level of virus-neutralising antibodies against Ebola, decrease in the proportion of monomers from 98 to 74–90%, increase in the proportion of dimers and polymers, and formation of immunoglobulin molecules’ fragments. Signs of toxicity for mice were observed in one of the three product batches. Conclusions: the obtained results suggest the need to perform more studies to test the quality of antiEbola immunoglobulin batches that were stored for shorter periods of time in order to assess the stability of their initial characteristics.Вспышка геморрагической лихорадки Эбола в восточных районах Демократической Республики Конго в 2018–2020 гг. показала сохраняющуюся высокую опасность вируса для человечества, а вспышка в Западной Африке в 2014–2016 гг., самая крупная с момента обнаружения вируса – возможность его ввоза в другие страны, в том числе в Россию. В ФГБУ «48 ЦНИИ» Минобороны России в 1993 г. разработан специфический лошадиный иммуноглобулин для экстренной профилактики лихорадки Эбола в группах риска. Изучение и совершенствование его защитных свойств является актуальным направлением разработки средств биологической защиты. Цель работы: оценить свойства иммуноглобулина против лихорадки Эбола из сыворотки крови лошадей после длительного хранения при температуре от 2 до 8 °С. Материалы и методы: серии гетерологичного иммуноглобулина против лихорадки Эбола, хранившиеся от 17 до 22 лет. Свойства иммуноглобулина оценивали согласно требованиям Государственной фармакопеи Российской Федерации XIV издания (ГФ РФ XIV изд.). Специфическую активность препарата определяли в реакции нейтрализации с вирусом Эбола в культуре клеток почки африканской зеленой мартышки (GМК-АН-1(Д)) методом подавления образования негативных колоний (бляшкообразования). Определение молекулярных параметров иммуноглобулина проводили методом эксклюзионной высокоэффективной жидкостной хроматографии согласно методикам, представленным в Европейской фармакопее 9.6 и ГФ РФ XIV изд. Результаты: хранение препарата иммуноглобулина против лихорадки Эбола в течение 17–22 лет при температуре от 2 до 8 °С привело к снижению уровня вируснейтрализующих антител к вирусу Эбола в 4 раза, уменьшению доли мономеров c 98 до 74–90%, увеличению доли димеров и полимеров, а также появлению фрагментов молекул иммуноглобулина. В одной из трех серий препарата была выявлена токсичность для белых нелинейных мышей. Выводы: полученные результаты свидетельствуют о целесообразности проведения дальнейших исследований по определению показателей качества серий иммуноглобулина против лихорадки Эбола, хранившихся менее продолжительные сроки, с целью оценки стабильности их исходных характеристик

Oral anticoagulant therapy in patients after intracerebral hemorrhage

The presence of indications for long-term oral anticoagulant (OAC) therapy in a patient who has experienced an intracerebral hemorrhage (IUD) poses a difficult clinical dilemma for the physician. The article discusses the vectors of recurrence for different types of IUD and their neuroimaging markers. It describes approaches to the global assessment of risk factors for IUD in patients taking OACs. Detailed consideration is given to the situation of IUD concurrent with atrial fibrillation as the most common reason for prescribing OACs. There are data on the safety of restating OACs after IUD and on the risk of the latter in patients taking warfarin and direct OACs. The optimal OAC start or restart time after IUD, including that in patients with prosthetic valves, is discussed. An algorithm for decision making is recommended

Biomarkers of atrial cardiopathy in patients with different pathogenetic subtypes of ischemic stroke

Studies of the biomarkers of atrial cardiopathy seem to be promising for identifying patients with cryptogenic stroke (CS), in which an intensive search for atrial fibrillation is indicated. Nevertheless, the diagnostic value of these markers and their threshold values require clarification.Objective: to present the characteristics of echocardiographic markers for atrial cardiopathy and the serum concentration of N-terminal pro-Btype natriuretic peptide (NT-proBNP) in embolic CS versus cardioembolic stroke (CES) and non-cardioembolic stroke (non-CES) to determine the threshold values of parameters with the highest sensitivity and specificity in differentiating CES and non-CES.Patients and methods. A total of 259 patients with ischemic stroke were examined. The standard examination additionally involved calculation of the parameters that reflected left atrial LA) function (LAF): LA emptying fraction (LAEF), and LA functional index (LAFI). The serum NT-proBNP concentration was also determined in 75 patients.Results and discussion. The patients with CES versus those with CS and non-CES were characterized by a considerable increase in LA diameter (4.3 [3.5; 4.5] cm vs 3.7 [3.4; 4.0] cm vs 3.7 [3.4; 3.9] cm; p=0.005 and p=0.009, respectively), LAVI (35.7 [30.5; 39.9] ml/m2 vs 28.5 [25.6; 34.6] ml/m2 vs 27.1 [24.5; 31.2] ml/m2 ; p< 0.001) and NT-proBNP level (559 [409; 1144] pg/ml vs 164 [65; 308] pg/ml vs 191 [63; 446] pg/ml; p=0.002 and p=0.019, respectively), as well as by a lower LAEF value [50.3 [48.5; 51.1]% vs 54.7 [51.6; 56.6]% vs 54.9 [52.5; 56.8]%; p< 0.001). The only parameter that showed significant differences between all the three groups (CES, CS, and nonCES) was LAFI (0.24 [0.2; 0.32] units vs 0.37 [0.3; 0.47] units vs 0.40 [0.34; 0.47] units; p<0.00 1), while maintaining the differences in the values for the two groups (CS and non-CES) (p=0.004). The following threshold values of biomarkers were obtained for CES and nonCES; these were a LA diameter of 41.5 mm (p< 0.001), a LAVI of 36.3 ml/m2 (p< 0.001), a LAEF of 51.8% (p< 0.001), a LAFI of 0.28 units (p< 0.001), and an NT-proBNP of 316 pg/ml (p< 0.001). Analysis of the ROC curves and the area under the curve (AUC) revealed that the most informative criteria for sensitivity and specificity were LAEF (79 and 88%, AUC 0.89), NT-proBNP (67 and 91%, AUC 0.89) and LAFI (93 and 72%, AUC 0.81).Conclusion. The CS group and non-CES one are comparable in the echocardiographic manifestations of atrial cardiopathy and in serum NTproBNP values. LAEF and NT-proBNP concentrations are promising biomarkers to classify CS patients into potential arterio- and cardioembolic types

Complicated upper extremity deep vein thrombosis (Paget-Schroetter disease): a case report

We report the case of the development of pulmonary embolism in a patient with Paget-Schroetter disease

Capabilities of perfusion ASPECTS in predicting the efficiency of intravenous thrombolytic therapy

Perfusion computed tomography (PCT) is increasingly used to diagnose ischemic stroke (IS), as well as to identify candidates for thrombolytic therapy (TLT). The feasibility of using this technique in all patients within the therapeutic window has not yet been established. Objective: to investigate cerebral blood flow according to PCT findings and its relationship to clinical and instrumental indicators and functional status of patients who had received TLT in the acute period of IS.Patients and methods. 62 patients with acute IS who had received TLT were examined. All the patients underwent clinical, laboratory, and instrumental examinations and PCT, by assessing cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) in 10 brain regions in accordance with the Alberta Score Program Early CT Score (ASPECTS). The total result of perfusion ASPECTS was calculated separately for CBV, CBF and MTT, as well as combinations of these parameters. The penumbra size was calculated as CBV minus MTT (CBV - MTT) ASPECTS, the infarct core size was measured as CBV + MTT ASPECTS.Results. There was an increase in MTT in most regions of interest of the affected hemisphere as compared to the intact one and a predominance of reversible perfusion disorders. The averaged penumbra size constituted three zones according to ASPECTS. No relationship was found between ASPECTS scores and time after the onset of symptoms prior to hospital admission. Perfusion parameters, particularly penumbra size (CBV - MTT), were associated with the degree of stenosis in the contralateral common carotid artery, body mass index, and blood triglyceride level. Cerebral blood flow indices were also influenced by red blood cell counts and heart ejection fraction. The scores of the perfusion scales were correlated with those of the non-contrast scale. The data of the investigated ASPECTS variants correlated with the level of neurological deficit in patients, its course, and the functional outcome of acute IS.Conclusion. The perfusion variants of ASPECTS have a high predictive value for patients' neurologic and functional status upon completion of the first treatment stage. The penumbra size (CBV - MTT ASPECTS) is a marker for the expected regression of neurological impairment during TLT. The infarct core size (CBV + MTT ASPECTS) determines the degree of neurologic deficit at a patient's discharge

Properties of Heterologous anti-Ebola Immunoglobulin after Long Storage

Ebola outbreak in eastern parts of the Democratic Republic of the Congo in 2018–2020 proved that the virus remains highly hazardous for humans, and the outbreak in West Africa in 2014–2016, which was the largest Ebola outbreak in history, showed that it could be imported to other continents, including Russia. In 1993 the Federal State Budgetary Institution “48th Central Scientific Research Institute” of the Russian Ministry of Defence developed a specific equine immunoglobulin for emergency prophylaxis of Ebola in risk groups. The evaluation and improvement of the product’s properties is an important area in the development of biological defence technologies.The aim of the study was to examine the properties of the equine anti-Ebola immunoglobulin which had been stored for a long time at 2–8 °C.Materials and methods: the authors studied batches of heterologous anti-Ebola immunoglobulin that had been stored for 17–22 years. The properties of the product were evaluated according to the requirements of the State Pharmacopoeia of the Russian Federation, 14th ed. (Ph. Rus. 14 ed.). The specific activity of the product was determined in a plaque reduction neutralisation test using Ebola virus and African green monkey kidney cells (GMK-AH-1(D)). Immunoglobulin molecular parameters were determined by size-exclusion high-performance liquid chromatography using the test methods described in the European Pharmacopoeia 9.6 and Ph. Rus. 14 ed.Results: the storage of anti-Ebola immunoglobulin for 17–22 years at 2–8 °C resulted in a four-fold reduction of the level of virus-neutralising antibodies against Ebola, decrease in the proportion of monomers from 98 to 74–90%, increase in the proportion of dimers and polymers, and formation of immunoglobulin molecules’ fragments. Signs of toxicity for mice were observed in one of the three product batches. Conclusions: the obtained results suggest the need to perform more studies to test the quality of antiEbola immunoglobulin batches that were stored for shorter periods of time in order to assess the stability of their initial characteristics