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Background: Macrophage activation syndrome (MAS) can be regarded as a key factor determining the severity of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C), and often requires treatment in the intensive care unit (ICU) to avoid life-threatening complications. No reputable specific criteria for the diagnosis of MAS in MIS-C patients have yet been identified, and criteria currently used for the diagnosis of hemophagocytic syndromes, such as HLH-2004, MAS-2005, and MAS-2016, are not sufficient for MAS in MIS-C. Our goal in this study was to work out the criteria for the early diagnosis of MAS in MIS-C. Methods: One hundred and sixty-six (166) patients with MIS-C were assessed retrospectively. The two most experienced experts independently identified patients with MAS. The patients were divided into three cohorts: MAS (n = 19), without MAS (n = 78), and probable MAS (n = 67). The latter included patients diagnosed with MAS by only one expert, and it was excluded from the analysis. Results: The age of patients with MAS was much higher, and they more frequently had edematous syndrome, hypotension and/or shock, splenomegaly, and CNS involvement. In their blood tests, thrombocytopenia, hypoalbuminemia, and hypertriglyceridemia occurred more often. The level of biomarkers of inflammation, such as ferritin, CRP, troponin, AST, and ALT, was also higher in this group. Increased fibrinogen and D-dimer were also found, demonstrating hypercoagulation in the MAS-MIS-C group. We chose 21 continuous and categorical variables with statistical significance, out of which 2—ferritin > 469 μg/L or platelets < 114 × 109/L—allowed us to discriminate MAS patients. Conclusions: Ferritin > 469 μg/L or platelets < 114 × 109/L can be regarded as key signs to differentiate MAS in MIS-C patients with a sensitivity of 100% and specificity of 94.9%, and they can be used along with other diagnostic methods.

Background. Detailed knowledge of the splenic arterial vasculature is essential for the minimally invasive surgery. A promising area of research in this regard is the quantitative analysis of the vasculatures of parenchymatous organs as a fractal or quasi-fractal system." Purpose. to determine the morphometric features in different groups of dichotomies (‘optimal’/’non-optimal’) of the splenic arterial vasculature in individuals of different sex and age. Materials and methods. The morphometric features of ‘optimal’ and ‘non-optimal’ dichotomies (according to C.D. Murray’s and H.B.M Ulings’ criteria) were studies using corrosion casts of splenic arterial vasculature (67 individuals, 1st and 2nd adulthood period, both sexes). Results. The ‘optimal’ dichotomies equaled 1% according to C.D. Murray’s criteria and 9% by H.B.M. Ulings criteria out of total number of dichotomies investigated in splenic arterial vasculature corrosion casts. The relative amount of ‘optimal’ dichotomies in slightly higher in men than in female. Whereas relative number of ‘optimal’ dichotomies is lower in 1st adulthood period that in 2nd adulthood. ‘Optimal’ dichotomies are mainly located at the proximal generation and division level of splenic arterial vasculature. They are bigger in size, less symmetrical in comprising with ‘non-optimal’ ones. Conclusion. Morphometric parameters vary significantly in different sex and age groups which should be considered for numerical modelling of splenic arterial vasculature.

Background. Insight into blood viscosity in terms of its physical and biochemical properties carries significant clinical value. By understanding the relationship between the physical properties of blood and physiology, a potentially powerful tool for diagnosing early signs of many diseases can be discovered. Purpose. To identify the effect of fibrinogen on tensio- and rheometric characteristics of blood plasma and serum in patients with coronary heart disease and with mitral and/or aortic valve disease. Materials and methods. Prospective non-randomized study. The study of dynamic, equilibrium surface tension and viscoelastic modulus was performed by the pendant drop method using a PAT-1 device (Sinterface Technologies, Germany). We measured parameters characterizing the surface tension and dilatation rheology of blood serum such as: dynamic surface tension at an adsorption time of 100 s (γ), equilibrium surface tension (γ ∞) (adsorption time 2500 s), viscoelastic modulus |E|, and phase angle (φ) at frequencies of 0.1 and 0.01 Hz. All patients under study were divided into 3 groups. The healthy volunteers (30 subjects) without chronic diseases and active complaints aged 49 to 78 years (mean age, 61.1±1.1 years) comprised the comparison group (group 1). Group 2 - 40 patients with coronary heart disease (CHD) aged 49 to 77 years (mean age 62.2±1.3 years) who underwent bypass surgery to treat atherosclerotic coronary vessels (2 to 5 bypasses). Group 3 - 30 patients with cardiac mitral and/or aortic valve lesions aged 52 to 78 years (mean age 61.3±1.2 years). They underwent mitral and/or aortic valve replacement with mechanical prostheses. The most common pathophysiological syndrome in patients due to coronary artery or heart valve lesions was chronic heart failure (CHF) (stage 2A-2B according to Vasilenko-Strazhesko classification). Results. Characteristic γ100s of blood serum and plasma had significant difference in both patients’ groups, possibly due to the role of coagulation and anti-coagulation system proteins’ role in dynamic surface tension of plasma in a shorter timeframe (up to 100 s.). The increase in Δγ100s in both patients’ groups by day 7 of the postoperative period indicates an increasing dynamic surface tension of serum compared to plasma. Plasma of perioperative patients does not differ from the comparison group by its surface-equilibrium properties. Accordingly, the Δγ∞s values in groups 1 and 2 both before surgery and on days 1 and 7 of the postoperative period are almost identical, pointing to no difference in the amount of surfactants tending to adsorb on the droplet surface. Alterations of viscoelastic modulus |E| and phase angle (φ) at 0.1 and 0.01 Hz in the perioperative period indicate changes in qualitative and quantitative characteristics of circulating blood with variation in individual homeostasis characteristics, resulting in an increase in surface elasticity combined with an almost unchanged surface viscosity. Conclusion. Dynamic and equilibrium surface tension parameters in patients’ plasma differ from those in serum due to the presence of fibrinogen and other proteins of the blood coagulation system.

The fall of Angkor in the 15th century marked a turning point in the Cambodian history leading to the downfall of the Khmer civilization and the start of the so-called “post-Angkor period” which is also often referred to as the “Dark Age of Cambodia”. Local epigraphical sources almost completely disappear from the 13th up to the 16th centuries while the Royal Chronicles dealing with this timeframe were compiled much later, mostly in the 18th and 19th centuries. Therefore, primary sources of this era are very scarce. While it is commonly accepted among the modern researchers that the fall of Angkor was a continuous process and was not a result of a single Siamese attack or a natural calamity (moreover, various reasons for this gradual downfall have been outlined), the perception of this process by other political powers in the region, especially China, has been significantly understudied. In this work the author made an attempt to trace the transformation of depiction of Cambodia in the Chinese sources of the Yuan and early Ming dynasties (both official and private).

Aim. Analysis of the dynamics of different stages of clot formation and its lysis in patients with different COVID-19 severity. Materials and methods. We prospectively included 58 patients with COVID-19 (39 patients with moderate disease severity and 18 patients with severe disease) and 47 healthy volunteers as a control group. All participants underwent the assessment of flow-mediated dilation (FMD) of brachial artery, impedance aggregometry, rotational thromboelastometry and thrombodynamics. Von Willebrand factor antigen (vWF:Ag) quantification was also performed in patients with COVID-19. Measurements were repeated on the 3rd and 9th day of hospitalization. Results. Compared to the control group, patients with COVID-19 showed reduced values of platelet aggregation and greater values of the clot growth rate, as well as its size and density. On the first day of hospitalization, we found no differences in the activity of plasma hemostasis and endogenous fibrinolysis between subgroups of patients. With the progression of the disease, the growth rate and size of the clot were higher in the severe subgroup, even despite higher doses of anticoagulants in this subgroup. An increase in platelet aggregation was noted during the progression of the disease, especially in the severe subgroup. There were no differences in the results of the FMD test by subgroups of patients. The vWF:Ag level was significantly higher in the severe subgroup. Conclusion. Thus, plasma hemostasis followed by secondary platelet activation correlates with the severity of COVID-19. Patients with moderate to severe coronavirus infection have predominantly local rather than generalized endothelial dysfunction.

Background: Macrophage activation syndrome (MAS) can be regarded as a key factor determining the severity of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C), and often requires treatment in the intensive care unit (ICU) to avoid life-threatening complications. No reputable specific criteria for the diagnosis of MAS in MIS-C patients have yet been identified, and criteria currently used for the diagnosis of hemophagocytic syndromes, such as HLH-2004, MAS-2005, and MAS-2016, are not sufficient for MAS in MIS-C. Our goal in this study was to work out the criteria for the early diagnosis of MAS in MIS-C. Methods: One hundred and sixty-six (166) patients with MIS-C were assessed retrospectively. The two most experienced experts independently identified patients with MAS. The patients were divided into three cohorts: MAS (n = 19), without MAS (n = 78), and probable MAS (n = 67). The latter included patients diagnosed with MAS by only one expert, and it was excluded from the analysis. Results: The age of patients with MAS was much higher, and they more frequently had edematous syndrome, hypotension and/or shock, splenomegaly, and CNS involvement. In their blood tests, thrombocytopenia, hypoalbuminemia, and hypertriglyceridemia occurred more often. The level of biomarkers of inflammation, such as ferritin, CRP, troponin, AST, and ALT, was also higher in this group. Increased fibrinogen and D-dimer were also found, demonstrating hypercoagulation in the MAS-MIS-C group. We chose 21 continuous and categorical variables with statistical significance, out of which 2—ferritin > 469 μg/L or platelets < 114 × 109/L—allowed us to discriminate MAS patients. Conclusions: Ferritin > 469 μg/L or platelets < 114 × 109/L can be regarded as key signs to differentiate MAS in MIS-C patients with a sensitivity of 100% and specificity of 94.9%, and they can be used along with other diagnostic methods. [ABSTRACT FROM AUTHOR]

Hemophagocytic syndrome is a key point in the pathogenesis of severe forms of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C). The factors associated with hemophagocytosis in patients with MIS-C were assessed in the present study of 94 boys and 64 girls ranging in age from 4 months to 17 years, each of whose HScore was calculated. In accordance with a previous analysis, patients with HScore ≤ 91 (n = 79) and HScore > 91 (n = 79) were compared. Patients with HScore > 91 had a higher frequency of symptoms such as cervical lymphadenopathy, dry cracked lips, bright mucous, erythema/swelling of hands and feet, peeling of fingers, edematous syndrome, hepatomegaly, splenomegaly, and hypotension/shock. They also had a higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and D-dimer levels, and a tendency to anemia, thrombocytopenia, and hypofibrinogenemia. They more often needed acetylsalicylic acid and biological treatment and were admitted to ICU in 70.9% of cases. Conclusion: The following signs of severe MIS-C were associated with HScore > 91: myocardial involvement, pericarditis, hypotension/shock, and ICU admission.

Abstract Background Diffuse large B‐cell lymphoma (DLBCL) is the most common (30%–35%) type of B‐cell lymphoma. Only about 60% of all newly diagnosed advanced‐stage DLBCL can be completely treated with x6 R‐CHOP. High‐dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation in the first remission (upfront auto‐HSCT) can serve as an option to improve a prognosis in these patients. Aims This trial aimed to improve prognosis in DLBCL by upfront auto‐HSCT. Methods and Results A group of 105 patients: DLBCL NOS, age 18–65, stage IV, IPI ≥2, CR/PR after x6 R‐CHOP/DA‐EPOCH‐R from 2010 to 2019 at NMRC of Oncology named after N.N.Petrov of MoH of Russia was retrospectively analyzed. The HSCT group included patients with upfront HDCT followed by auto‐HSCT (n = 35). The control group included patients with non‐invasive follow‐up after induction (n = 70). Primary endpoint was progression‐free survival (PFS). Secondary endpoints were overall survival (OS), response rate and relapse rate. The 3‐year OS (p = .013) and 3‐year PFS (p = .033) were significantly higher in the HSCT group. The 3‐year OS was decreased by the occurrence of relapse (p ≤ .001) and weight loss (B‐symptom) (p = .04). DEL was the negative prognostic factor for 3‐year PFS in all patients (p = .001) and control group (p = .001). DA‐EPOCH‐R significantly increased the 3‐year PFS (p = .041). Conclusion Upfront HDCT followed by auto‐HSCT can increase 3‐year OS and PFS and improve prognosis in DLBCL NOS, age 18–65, stage IV, IPI ≥2 patients.

Цель. Провести анализ применимости уравнений Murray C.D. для расчёта значений углов дихотомий внутриорганного артериального и венозного русел почки человека. Материал и методы. Были исследованы внутриорганные артерии и вены почек. Почки полученны на аутопсии у людей (возраст от 36 до 74 лет; 9 человек мужского пола, 8 – женского), изготовлены 17 коррозионных препаратов: 9 препаратов артериальное русло, 8 – венозное. Визуализацию проводили с помощь микротомографа BRUNKER SkyScan 1178. Для морфометрии использовали программный пакет blender с надстройкой NeuroMorph Measuring tools. Измеряли диаметры сегментов (D, dmax, dmin) и углы между ними (αmax, αmin). Для расчетов углов дихотомии пользовались уравнениями Murray C.D. Результаты. Установлено наличие четырех структурно-различных типов дихотомий, составляющих внутриорганное сосудистое русло почки. Показано, что применять уравнение Murray C.D. для расчетов величины угла αmax можно для любых структурно-различных типов сосудистых дихотомий почки человека. Однако использовать уравнение Murray C.D. для расчетов значений угла αmin нельзя для артериальных и венозных дихотомий 1-го структурно-различного типа и для 2-го типа венозных дихотомий. Заключение. Применение уравнений Murray C.D. для численного моделирования сосудистых дихотомий почки человека носит ограниченный характер. Это необходимо учитывать при создании структурных математических моделей сосудистого русла почки человека.

Multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C) is a life-threatening condition that often requires intensive care unit (ICU) admission. The aim of this study was to determine risk factors for severe/life-threatening course of MIS-C. The study included 166 patients (99 boys, 67 girls) aged 4 months–17 years (median 8.2 years). The criterion of severity was the fact of ICU admission. To conduct a comparative analysis, MIS-C patients were divided into two groups: patients hospitalized in the ICU (n = 84, 50.6%) and those who did not need ICU admission (n = 82, 49.4%). Patients with a more severe course of MIS-C were significantly older. They had a higher frequency of signs such as rash, swelling, hepatomegaly, splenomegaly, and neurological and respiratory symptoms. Hypotension/shock and myocardial involvement were much more common in patients with severe MIS-C. These patients had a more significant increase in CRP, creatinine, troponin, and D-dimer levels. Additionally, the presence of macrophage activation syndrome was higher in patients admitted to the ICU. Conclusion: Nineteen predictors of severe course of MIS-C were found, out of which hepatomegaly, splenomegaly, D-dimer > 2568 ng/mL, troponin > 10 pg/mL were mainly associated with the probability of being classified as early predictors of severe MIS-C requiring ICU admission.

This study investigated the use of cellulose nanocrystals (CNC)/chitosan (Chit) polyelectrolyte complex as a stabilizing agent for Pickering emulsions. We demonstrated that chitosan reduces the surface charge of CNC improving the emulsification process. An optimal stabilizing complex containing 1% chitosan results in emulsions with minimal zeta potential (3.2 ± 0.3 mV), droplet size (2.8 ± 0.8 μm), and creaming index (19.8 ± 1.0%) values, along with high stability during storage, a change in pH, and high centrifugal forces (up to 2000 g). The study also showed that the maximum neutralized surface charge of the CNC in the CNC-Chit complex allows for effective adsorption on the surface of sunflower oil droplets, producing a denser stabilizing layer with a smaller droplet size. Additionally, chitosan addition is linked to improved stability and higher viscosity, with little dependence on ionic strength and temperature. Potentiometric titration revealed that compared with sulfated CNCs, five times less chitosan is needed to neutralize the negative surface charge of acetylated CNC. The wettability of a hydrophilic surface depends on the surface charge of the complex, and the wettability and adhesion performance increase with increasing chitosan content. Additionally, we showed that tuning the stabilizer composition can change the bioaccessibility of lipophilic compounds during oral administration. [ABSTRACT FROM AUTHOR]

Цель. Путём численного моделирования проверить предположение о связи между типом дихотомии и особенностями движения крови в структурно-различных бифуркациях внутриорганного артериального русла сердца человека. Материал и методы. Использовали результаты морфометрии реального артериального русла сердца. Для моделирования нестационарного ламинарного течения применяли решение полной системы уравнений Навье-Стокса, полученное с помощью неявной разностной схемы в пакете ANSYS. Результаты. Установлено: дихотомия (бифуркация) первого типа (полная асимметрия) увеличивает интенсивность флуктуаций расхода и максимальную скорость потока, а также уменьшает динамическую вязкость крови в большей ветви. В меньшей ветви формируется квазистационарное течение. Дихотомия (бифуркация) второго типа (боковая асимметрия) уменьшает максимум скорости потока и значение динамической вязкости во всех ветвях. Дихотомия (бифуркация) третьего типа (односторонняя симметрия) увеличивает максимум скорости потока и уменьшает динамическую вязкость. Дихотомия (бифуркация) четвертого типа (полная симметрия) уменьшает максимум скорости потока, деформирует профиль скорости и значительно увеличивает вязкость крови. Более того зона с увеличенной вязкостью распространяется из ядра потока практически на всю область течения. Выводы. Результаты моделирования позволяют утверждать о разной функциональной роли артериальных дихотомий (бифуркаций) структурно-различных типов. После прохождения различных типов дихотомий (бифуркаций) поток крови приобретает унифицированные свойства, необходимые для течения в гемомикроциркуляторном участке русла. Выявленные особенности необходимо учитывать при численном моделировании структуры внутриорганного артериального русла сердца человека и внутриартериальной гемодинамики.

ObjectivesHeart involvement in multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C) is a new challenging problem, requiring fast and reliable diagnostics and appropriate treatment. The aim of this study is to describe heart involvement in patients with MIS-C.Study DesignIn this retrospective, multicenter cohort study, data of 122 patients were included. All patients met WHO and CDC criteria of MIS-C.ResultsVarious types of heart involvement in MIS-C patients were observed. Patients with solely coronary artery lesions (CAL, n = 10, 8.2%) had typical features of Kawasaki disease: younger age, thrombocytosis and normal ferritin level, without giant CA aneurysms, thrombosis, myocardial infarction, shock, and ICU admission. Patients with solely myocardial involvement (MI, n = 30, 24.6%) had an older onset age, elevated ferritin, LDH, the highest D-dimer, H score, and thrombocytopenia level. The following clinical signs were associated with MI: gastrointestinal and central nervous system disorder, sore throat, swelling face, splenomegaly, shock, and treatment in the intensive care unit required. Patients with a combination of CAL and MI (n = 10, 8.2%) had symptoms similar to patients with solely MI, except for impressive thrombocytopenia. Shock and ICU admission were found in 34.7% of patients without heart involvement (n = 72, 59%). One major criterion [troponin > 32 pg/ml (52 points)] or at least two minor criteria [face swelling (32 points) and D-Dimer > 1,300 ng/ml (29 points)] were associated with MI (>32 points) with a sensitivity of 67.5% and a specificity of 88.9%.ConclusionThe above-suggested criteria can be added to routine diagnostic procedures to confirm MI in MIS-C patients.

Background: Several cases of skin and central nervous system vasculopathy associated with COVID-19 in children have been published, but the information is rather limited. Our study aimed to describe these cases of vasculitis associated with COVID-19 in children. Methods: In the retrospective-prospective case series study we included information regarding four children with COVID-19-associated vasculitis. In every case, we had a morphological description and the etiology was confirmed via real-time polymerase chain reaction during a tissue biopsy. Results: The most involved systems were skin (4/4), respiratory (3/4), cardiovascular (2/4), nervous (1/4), eye (1/4), kidney (1/4), and inner year (1/4). All patients had increased inflammatory markers and thrombotic parameters (D-dimer). No patient met the criteria for multisystem inflammatory syndrome in children. Two patients met polyarteritis nodosa criteria, one met Henoch–Schonlein purpura criteria, and one met unclassified vasculitis criteria. All patients were treated with systemic glucocorticosteroids (two-pulse therapy). Non-biologic DMARDs were prescribed in all cases; 1/4 patients (25%) was treated with intravenous immunoglobuline, and 3/4 (75%) were treated with biologics (etanercept, tocilizumab, and adalimumab). Conclusions: Vasculitis associated with COVID-19 could be a life-threatening condition; SARS-CoV-2 might be a new trigger or etiological agent for vasculitis and other immune-mediated diseases. Further research and collection of similar cases are required.

Objectives: Diagnostic between multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C) and Kawasaki disease (KD) can make difficulties due to many similarities. Our study aimed to create a Kawasaki/MIS-C differentiation score (KMDscore) allowing discrimination of MIS-C and KD.Study design: The retrospective multicenter cohort study included clinical, laboratory, and instrumental information about MIS-C (n = 72) and KD (n = 147). The variables allowed to discriminate both conditions used to construct and validate the diagnostic score called the KMDscore.Results: Patients with MIS-C were older, had earlier admission to the hospital, had a shorter time before fever resolution, two times frequently had signs of GI and CNS involvement observed, and had more impressive thrombocytopenia, higher level of CRP, ferritin, ALT, AST, LDH, creatinine, triglycerides, troponin, and D-dimer compared to KD patients. Respiratory signs in MIS-C were presented with pleuritis, acute respiratory distress syndrome, oxygen dependency, lung infiltration, and ground-glass opacities in CT. The heart involvement with fast progression of myocarditis provided the severity of MIS-C and ICU admission due to 12 times higher arterial hypotension or shock and required cardiotonic. No differences in the frequency of CA lesions were seen in the majority of cases. Five criteria, CRP >11 mg/dl (18 points), D-dimer >607 ng/ml (27 points), age >5 years (30 points), thrombocytopenia (25 points), and GI involvement (28 points), were included in the KMDscore. The summa >55 points allowed to discriminate MIS-C from KD with a sensitivity of 87.5% and specificity of 89.1%.Conclusion: The KMDscore can be used to differentiate the diagnostic of MIS-C from KD.