General dynamics of the URT microbiome and microbial signs of recovery in COVID-19 patients.

COVID-19 is caused by an airborne virus, SARS-CoV-2. The upper respiratory tract (URT) is, therefore, the first system to endure the attack. Inhabited by an assemblage of microbial communities, a healthy URT wards off the invasion. However, once invaded, it becomes destabilised, which could be crucial to the establishment and progression of the infection. We examined 696 URT samples collected from 285 COVID-19 patients at three time-points throughout their hospital stay and 100 URT samples from 100 healthy controls. We used 16S ribosomal RNA sequencing to evaluate the abundance of various bacterial taxa, α-diversity, and ß-diversity of the URT microbiome. Ordinary least squares regression was used to establish associations between the variables, with age, sex, and antibiotics as covariates. The URT microbiome in the COVID-19 patients was distinctively different from that of healthy controls. In COVID-19 patients, the abundance of 16 genera was significantly reduced. A total of 47 genera were specific to patients, whereas only 2 were unique to controls. The URT samples collected at admission differed more from the control than from the samples collected at later stages of treatment. The following four genera originally depleted in the patients grew significantly by the end of treatment: Fusobacterium, Haemophilus, Neisseria, and Stenotrophomonas. Our findings strongly suggest that SARS-CoV-2 caused significant changes in the URT microbiome, including the emergence of numerous atypical taxa. These findings may indicate increased instability of the URT microbiome in COVID-19 patients. In the course of the treatment, the microbial composition of the URT of COVID-19 patients tended toward that of controls. These microbial changes may be interpreted as markers of recovery.

[Informativeness estimation for the main clinical and laboratory parameters in patients with severe COVID-19].

AIM: To conduct a retrospective assessment of the clinical and laboratory data of patients with severe forms of COVID-19 hospitalized in the intensive care and intensive care unit, in order to assess the contribution of various indicators to the likelihood of death. MATERIALS AND METHODS: A retrospective assessment of data on 224 patients with severe COVID-19 admitted to the intensive care unit was carried out. The analysis included the data of biochemical, clinical blood tests, coagulograms, indicators of the inflammatory response. When transferring to the intensive care units (ICU), the indicators of the formalized SOFA and APACHE scales were recorded. Anthropometric and demographic data were downloaded separately. RESULTS: Analysis of obtained data, showed that only one demographic feature (age) and a fairly large number of laboratory parameters can serve as possible markers of an unfavorable prognosis. We identified 12 laboratory features the best in terms of prediction: procalcitonin, lymphocytes (absolute value), sodium (ABS), creatinine, lactate (ABS), D-dimer, oxygenation index, direct bilirubin, urea, hemoglobin, C-reactive protein, age, LDH. The combination of these features allows to provide the quality of the forecast at the level of AUC=0.85, while the known scales provided less efficiency (APACHE: AUC=0.78, SOFA: AUC=0.74). CONCLUSION: Forecasting the outcome of the course of COVID-19 in patients in ICU is relevant not only from the position of adequate distribution of treatment measures, but also from the point of view of understanding the pathogenetic mechanisms of the development of the disease.

Ruxolitinib versus dexamethasone in hospitalized adults with COVID-19: multicenter matched cohort study.

BACKGROUND: Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Previously, dexamethasone demonstrated a reduction of case-fatality rate in hospitalized patients with respiratory failure. In this matched control study we compared dexamethasone to a Janus kinase inhibitor, ruxolitinib. METHODS: The matched cohort study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by main clinical and laboratory parameters predicting survival. Recruitment period was April 7, 2020 through September 9, 2020. RESULTS: Ruxolitinib treatment in the general cohort of patients was associated with case-fatality rate similar to dexamethasone treatment: 9.6% (95% CI [4.6-14.6%]) vs 13.0% (95% CI [7.5-18.5%]) respectively (p = 0.35, OR = 0.71, 95% CI [0.31-1.57]). Median time to discharge without oxygen support requirement was also not different between these groups: 13 vs. 11 days (p = 0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated a reduced case-fatality rate in ruxolitnib-treated patients with a high fever (≥ 38.5 °C) (OR 0.33, 95% CI [0.11-1.00]). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p = 0.042), ruxolitinib therapy was associated with a better safety profile due to a reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p = 0.025). For 32 patients from ruxolitinib group (21.9%) with ongoing progression of respiratory failure after 72 h of treatment, additional anti-cytokine therapy was prescribed (8-16 mg dexamethasone). CONCLUSIONS: Ruxolitinib may be an alternative initial anti-cytokine therapy with comparable effectiveness in patients with potential risks of steroid administration. Patients with a high fever (≥ 38.5 °C) at admission may potentially benefit from ruxolitinib administration. Trial registration The Ruxolitinib Managed Access Program (MAP) for Patients Diagnosed With Severe/Very Severe COVID-19 Illness NCT04337359, CINC424A2001M, registered April, 7, 2020. First participant was recruited after registration date.

[The role of myeloperoxidase, paraoxonase and nitric oxide system in blood and pericardial fluid in patients with IHD who underwent direct myocardial revascularization.]

76 patients with coronary artery disease who underwent aortocoronary bypass surgery were examined to study the role of paraoxonase, myeloperoxidase, arginase, asymmetric dimethylarginine and nitric oxide in the mechanisms of the pathogenesis of post-pericardiotomy syndrome (PPCS). Patients were divided into two groups: the 1st - patients with coronary artery disease, who did not have PPCS as a result of clinical studies; the 2nd- patients with ischemic heart disease (IHD who were diagnosed with PPCS. The results showed that the postoperative period after coronary artery bypass grafting is associated with inhibition of paraoxonase, activation of myeloperoxidase, increased activity of arginase, nitrite/nitrate level and asymmetric dimethylarginine, and may be accompanied by the development of endothelial dysfunction and increased systemic inflammatory response. In the present work, inverse correlation relationships between the arylesterase activity of paraoxonase and myeloperoxidase activity in plasma, as well as between the aryl esterase activity of paraoxonase in the blood plasma and the activity of arginase in erythrocytes of the patients of the two studied groups were established. tests were developed on basis of ratio of the enzymes activities to predict the development of post-pericardicotomy syndrome.

[Analysis of flowmetric parameters of blood flow through coronary bypass grafts in high-risk surgical patients]. / Analiz floumetricheskikh pokazatelei krovotoka koronarnykh shuntov u patsientov vysokogo khirurgicheskogo riska.

Coronary artery bypass grafting is a widely used cardiosurgical intervention which may be performed either on the arrested heart in conditions of artificial circulation or on the beating heart without artificial circulation. However, in a series of works, the results of bypass grafting using both techniques had no significant differences. In our article, we analyse the flowmetric parameters of blood flow through the coronary bypass grafts in high-surgical risk patients presenting with ischaemic heart disease and undergoing coronary artery bypass grafting in conditions of artificial circulation and on the beating heart. For this purpose, a total of 148 patients enrolled into the study were divided into 2 groups depending on the technique of surgical treatment. The obtained statistical data showed comparable results in the both groups, however, operative interventions on the beating heart made it possible to significantly decrease the risk of the development of the majority of complications.

[Prevention of gastrointestinal bleeding in patients with advanced burns]. / Profilaktika zheludochno-kishechnykh krovotechenii u patsientov s obshirnymi termicheskimi ozhogami.

AIM: To reduce the incidence of gastrointestinal bleeding in patients with advanced burns by developing a prophylactic algorithm. MATERIAL AND METHODS: The study consisted of retrospective group of 488 patients with thermal burns grade II-III over 20% of body surface area and prospective group of 135 patients with a similar thermal trauma. Standard clinical and laboratory examination was applied. Instrumental survey included fibrogastroduodenoscopy, endoscopic pH-metry and invasive volumetric monitoring (PICCO plus). Statistical processing was carried out with Microsoft Office Excel 2007 and IBM SPSS 20.0. RESULTS: New algorithm significantly decreased incidence of gastrointestinal bleeding (p<0.001) and mortality rate (p=0.006) in patients with advanced burns.

[Concentration of proinflammatory cytokines, peroxiredoxin-1 and glutathione peroxidase activity in the blood plasma of patients with coronary artery disease undergoing coronary artery bypass grafting].

76 patients with coronary heart disease (who had undergone coronary artery bypass grafting) were examined to investigate the role of pro-inflammatory cytokines and enzymes involved in redox regulation, in the mechanisms of development of systemic inflammatory response syndrome. Patients were divided into 2 groups: 1st - patients with coronary heart disease, who as a result of clinical trials has not been set postpericardiotomy syndrome; 2nd - patients with coronary heart disease who have been diagnosed postpericardiotomy syndrome. The blood plasma of both groups indicated intensification of production of interleukin-6, intrleukin-8, as well as - an imbalance in the peroxiredoxin-1 and glutathione peroxidase. These changes by patients with postpericardiotomy syndrome are observed at the earliest time and differed depth of expression. The results of this work confirm the high potential of the investigated indicators for prevention and monitoring postpericardiotomy syndrome development.

[Vascular endothelial growth factors (VEGF): role in pathological processes]. / Vaskuloéndotelial'nye faktory rosta (VEGF): rol' i mesto v patologicheskikh protsessakh.

Russian and foreign literature sources on vascular endothelial growth factors (VEGF) from different parts of the human body, their prevalence and involvement in pathological processes were analyzed. A conclusion has been drawn that further research on different types of VEGF is needed.

[OBJECTIVE CRITERIA OF PATIENT'S READINESS TO FREE AUTOPLASTY IN CASE OF GRANULATING WOUNDS (CRITERIA OF READINESS OF GRANULATING WOUNDS TO OPERATION)].

The article based on the analysis of 84 follow-up of the patients. The authors suggested using the indices of microbiological and immunological investigations and data of laser Doppler ultrasonography to determine the readiness of granulating wound to free autoplasty. The data obtained allowed developing an algorithm of treatment, patient's preparation to surgery and determination of operation terms.

[Dynamics of morphologic changes in tracheobronchial system in patients with acute carbon monoxide poisoning complicated by thermochemical damage to respiratory tract].

The authors identified three severity degrees of thermochemical damage to respiratory tract during acute carbon monoxide poisoning. Follow-up bronchoscopic studies were performed, and characteristic signs of thermochemical damage to respiratory tract in acute carbon monoxide poisoning were diagnosed. Evidence is that the signs were following certain sequence: from edema and hyperemia of respiratory tract lining to severe purulent discharge.

[Risk factors of gastroduodenal bleeding in patients with severe burns].

An experience of treatment of 133 patients with severe bums was analyzed. Bleedings from the upper parts of the gastrointestinal tract were diagnosed in 16 patients in different terms since their admission to the hospital. At the moment of carrying out of the endoscopic research all bleedings were considered as taking place. Statistically significant risk factors of the development of gastroduodenal bleedings were considered to be an alcoholic intoxication at the moment of injury and insufficient fluid therapy during the pre-admission stage and young age of the patients. The antisecretory therapy showed that the detection of risk factors in question should be regarded as an indication to the reinforced regime of preventive measures for gastroduodenal injuries.

[Influence of microbial wound dissemination and microcirculation on the results of skin engraftment].

The indices of Doppler laser flowmetery are proposed to be used for determination of the readiness of a granulating wound for free autoplasty. An analysis of capillary blood flow in the groups under test showed the information value of indicators of microcirculation obtained by Doppler laser flowmetery for determination of the granulating wound condition before autotransplantation and prediction of the results of skin engraftment. It is stated, that the disorder of microcirculation has been developed against the background of progression of wound invasive infection. The obtained data can allow the development of an algorithm of treatment and the preparation of the patients to surgery, determination of the terms of operation, the development the strategy of postoperative management of the patients, which can reduce unfavorable results of operations.

[Effect of perfluorane on the time course of changes in endogenous intoxication in victims with severe thermal injury].

The investigation was undertaken to study the effects of perfluorane on the degree of endogenous intoxication in the severely burnt. Sixty-five victims aged 20 to 55 years who had burns of the skin, involving more than 30% of the body surface area, without comorbidity (less than 9 SAPS scores), were examined. All the examinees were divided into 2 groups. They were comparable in age and burn injury degree. Perfluorane was administered in a dose of 4 ml/kg body weight within the first 24 hours after the moment of injury (a study group; n = 30). During the investigation, the authors estimated blood gas composition and acid-base balance, the level of lactate in mixed venous blood, the content of low and medium molecular-weight substances (LMMWS) in venous and arterial plasmas, on red blood cells and urine; erythrocytic deformity index; the level of reduced glutathione; total plasma antioxidative activity, and the plasma concentration of malonic dialdehyde. Blood was sampled on admission, an hour after administration of perfluorane, and onwards--on days 1, 3, 5, 7, 10, and 15. Perfluorane used in acute burn disease leads to normalization of oxygen balance, a reduction in the rate of free radical oxidation and lipid peroxidation, and a considerable decrease in LMMWS levels on the red blood cell membranes and plasma. Positive changes were recorded just an hour after administration of perfluorane and retained throughout the observation. In the study group victims, mortality was 15% less than that in the controls.

[Clinical and immunological criteria of burn sepsis].

A hundred and twenty-nine victims aged 16 to 60 years who had skin burns in the area of 15 to 60% of the body surface without severe concomitant somatic disease (SAPS less than 9 scores). The clinical symptoms of a systemic inflammatory response (SIR) and the signs of wound infection were recorded in all the examinees. The victims underwent a comprehensive clinical and laboratory examination, 55 of them were immunologically studied over time (on admission, on days 3 and 10). To reveal the predictive clinical and immunological criteria for sepsis, the examinees were divided into 3 groups. Group 1 comprised 33 burnt persons who were observed to have the symptoms of SIR and the signs of burn wound infections without impaired function of organs and systems. Group 2 included 46 victims with severe sepsis and a good outcome of burn disease. Group 3 consisted of 50 patients who had died from severe sepsis. Analysis of the results of the study has indicated that the count of formed blood elements by calculating the leukocytic intoxication index, the estimation of the level of lysosomal cation proteins in the neutrophilic granulocytes, the detection of populations of T helper cells, cytotoxic lymphocytes, as well as histomorphological and bacteriological findings are early and valid criteria for the development of infectious complications. Their use for the diagnosis and prediction of sepsis permits initiation of its treatment at early stages, without awaiting the appearance of the signs of a septic process.

[Diagnosis and intensive therapy of thermal and inhalation trauma]. / Diagnostika i intensivnaia terapiia termoingaliatsionnoi travmy.

The authors made an analysis of an experience with treatment of patients with a combined thermal inhalation injury in the Burn Center of the St. Petersburg Research Institute of emergency medical care named after I.I. Dzhanelidze for the recent years. A prognostic model with respect to the patient's life was worked out on the basis of complex estimation of the data of the depth and square of the injury of skin, severity of the inhalation trauma and age of the casualty. The authors propose a scale of estimation of the severity of the inhalation trauma with special reference to the probable outcome which allows a differentiated approach to choice of the treatment policy that finally favors reduction of lethality in the group under analysis.

[Bronchoscopic methods in complex diagnosis and treatment of burned patients with inhalation injuries]. / Bronkhoskopicheskie metody v kompleksnoi diagnostike i lechenii obozhzhennykh s ingaliatsionnymi porazheniiami.

Chromobronchoscopy was first used in treatment of 37 burned patients with inhalation injuries for better visual manifestation of the injuries of the tracheobronchial tree mucosa. The trachea and bronchi mucosa was irrigated with a viral stain--0.25% aqueous solution of methylene blue. The intensity of staining the mucosa in light blue colour showed the true limits and depth of the injury. Resulting from the clinico-endoscopic examinations supplemented with findings of chromobronchoscopy, cytological and bacteriological analyses, a working classification of inhalation injuries in burned people was developed which allowed the adequate methods of local treatment during fiber bronchoscopy to be worked out taking into account the degree of thermochemical injuries of the respiratory pathways. It resulted in 19.7% lower lethality of burned patients.

[Diagnosis, outcome prognosis and treatment strategy in inhalation trauma in patients with thermal injuries]. / Diagnostika, prognozirovanie iskhoda i lechebnaia taktika pri ingaliatsionnoi travme u postradavshikh s termicheskimi porazheniiami.

Sixty-seven therapeutic fibrobronchoscopies (FBS) were carried out in burnt patients with suspected inhalation injuries at Center for Burns at the Janelidze Institute of Emergency Care in 1996-1998. The severity of inhalation injury was assessed from the extent and severity of mucosal edema, spot hematomas and their type, erosions and ulcers, discharge, and ventilation obstruction. An original score is developed for evaluating the severity of inhalation injuries in burnt patients. Inhalation injuries were diagnosed in 63 patients. FBS was performed with tracheobronchial lavage with antibiotics, proteolysis enzymes, and repair stimulants. Mortality among burnt patients with inhalation injuries was decreased to 38%.

[Clinical variants of glaucoma in patients with acquired high myopia]. / Klinicheskie raznovidnosti glaukomy u lits s priobretennoi blizorukost'iu vysokoi stepeni.

Examinations of 88 glaucoma patients with high myopia showed three variants of glaucoma: 1) mixed form with combination of nuclear cataract and lenticular myopia, 2) open-angle form with ischemic background cerebral circulation (ocular circulation deficiency combined with a decrease in linear velocity of the bloodflow in the intracranial collateral cerebral circulation: to 21.8% in the anterior cerebral artery, to 26.1% in the middle cerebral artery, and to cerebral artery (by 8.3%) and in the orbital artery (by 4.2%). Clinical values indicate impeded venous outflow. Differential diagnostic signs of glaucoma in high myopia are defined.