CORRELATIVE ASSOCIATION OF OXYGENATION AND SEPSIS PANELS WITH THE USE OF ACE2 INHIBITORS AND WITHOUT IT IN THE CONDITIONS OF SEPTIC SHOCK IN COVID-19-INFECTED AND NON-INFECTED PATIENTS (COHORT STUDY).

Sepsis-associated hyperlactatemia (SAHL), Lactic acidosis, is a common problem in critically ill patients. The prevalence of Lactic acidosis is estimated to be approximately 1% of all hospitalized nonsurgical patients. The purpose of our study was to reveal possible associations between the level of Lactate with sepsis biomarkers: PCT, IL 6, and PO2 in the presence of ACE 2 inhibitors in Covid-19 infected and non-infected patients with Septic Shock. We conducted a cohort study, comparing outcomes of 212 critically ill patients with Septic shock, who were treated in the intensive care unit of First University Clinic of Tbilisi State Medical University during the 2020-2021 years. Inclusion criteria for the study were: Age>40ys; COVID-19 and other respiratory diseases associated with Septic shock, with respiration dysfunctions with prior exposure to ACE2 inhibitors o no history of treatment with the ACE2 inhibitors. Patients enrolled in the study were individuals who were diagnosed with COVID-19 infection and septic shock, and who were undergoing treatment with ACE2 inhibitors/not taking ACE2 inhibitors; patients with septic shock who were not infected with COVID-19, and who were undergoing treatment with ACE2 inhibitors/not taking ACE2 inhibitors. According to lactate level, the studied patients were divided into subgroups: lactate <3 mMol/l, and lactate > 3 mmol/l. In patients with septic shock who were not infected with COVID-19 the main Causative microorganisms were gram-negative bacteria. In patients' blood the Interleukin-6 (IL-6), lactate, procalcitonin (PCT), pO2, and pulmonary pressure were investigated. Results of the study show that the rise in lactate levels in COVID-19-infected and non-infected patients was accompanied by an increase in PCT content and a decrease in pO2 level in blood. Therefore, serum lactate levels can be used as a prognostic marker of the severity of septic shock in COVID-19-infected and noninfected patients. In COVID-19-infected patients together with the increased lactate level, increases the level of IL-6, which indicates the important link between the quality of immunological disorders, inflammation, and COVID-19 infection in patients with ARDS and sepsis. These alterations were not prevented by the prior use of the ACE2 inhibitors. In COVID-19-infected and noninfected patients who didn't use ACE2 inhibitors, high lactate levels were accompanied by decreased pulmonary pressure which was normalized in patients who prior used ACE2 inhibitors.

IMPACT OF THE ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS ON THE COURSE OF THE SEPTIC SHOCK DEVELOPED DURING COVID-19 AND OTHER SEVERE RESPIRATORY INFECTIONS IN PRESENCE OF HYPERFERRITINEMIA.

SARS-CoV-2 can cause sepsis regardless of the presence of secondary bacterial or fungal infections. The virus itself likely causes sepsis through a variety of possible mechanisms, including immune dysregulation, with respiratory dysfunction, which as a result of circulatory dysfunction leads to hypoxemia and metabolic acidosis. We conducted cohort study, comparing outcomes of 212 critically ill patients with Septic shock (134 men (63.3%) and 78 women (36.7%), with a mean age between 40-70 years) were evaluated, who were treated in the intensive care unit of First University Clinic during 2020-2021 years. All four groups had documented Hyperferritinemia (HF). Patients were divided according to ferritin concentrations: moderate HF (ferritin <1500ng/ml) and severe HF (ferritin >1500ng/ml). The study aimed to reveal the impact of the Angiotensin-Converting enzyme -2 (ACE2) inhibitors on the course of the Septic shock developed during COVID-19 and other severe respiratory infections in conditions of hyperferritinemia (HF). Study results show that severe HF in patients with Septic shock is associated with a high risk of mortality and can be considered an indicator of the severity of the disease. The consumption of ACE2 inhibitors plays an important role in the regulation of inflammatory processes in both COVID-19-infected and non-infected patients with Septic shock: ACE2 inhibitors reduce the levels of Ang II and C reactive protein (CRP) in the blood in both COVID-19-infected and non-infected patients with Septic shock in conditions of moderate and severe HF; regulate the activity of leukocytes and the blood pro-coagulation system in both COVID-19-infected and non-infected patients with Septic shock in conditions of moderate HF; reduce the expression of pro-inflammatory cytokines (IL-6), decrease the level of D dimer in СOVID-infected patients in conditions of moderate HF; Procalcitonin levels do not differ between COVID-19 infected and non-infected patients with Septic shock. Based on our study, we can assume that there is the important link between elevated Ang 2 and the quality of immunological disorders and inflammation. The consumption of ACE2 inhibitors plays an important role in the regulation of inflammatory processes in both COVID-19-infected and non-infected patients with Septic shock.

THE ROLE OF ANGIOTENSIN -2 IN THE PATHOGENESIS OF SEPTIC SHOCK DURING MULTIORGAN DYSFUNCTION SYNDROME (REVIEW).

Septic shock is an acute pathophysiological condition characterized by vasodilation, hypotension, decreased circulating blood volume, tissue hypoxia, organ failure, and high lethality. The causes of septic vasodilation, which can lead to vascular smooth muscle dysfunction or selective vasomotor imbalance, remain controversial. In septic vasodilation, optimal pharmacological intervention is needed. Expected vascular response to shock when various vasoconstrictors are used, requires further study of the therapeutic potential of these agents. Because of all the above, it is of great interest to study and compare the therapeutic effects of angiotensin-2 and already used catecholamine and non-catecholamine vasoconstrictors in the treatment of septic shock. Angiotensin 2, approved by the FDA in 2018, is the newest available vasopressor for the treatment of vasodilatory shock. In the setting of high-dose vasopressors, exogenously administered synthetic angiotensin 2 significantly improved mean arterial pressure, decreased background vasopressor dose, and lowered sequential organ failure assessment scores in patients with refractory septic shock, In the review, the role of angiotensin-2 and its correlation with markers of sepsis for adequate management of septic shock-induced multiorgan dysfunction and arterial hypotension with ACE inhibitors is evaluated.

EPIDEMIOLOGY OF CLINICALLY MANIFESTED ACUTE HEPATITIS C CASES IN GEORGIA.

Hepatitis C virus is responsible for the majority of persistent viral infections of the liver, chronic hepatitis, liver cirrhosis and/ or hepatocellular carcinoma. Two strategies are important to curtailing the rising prevalence of disease: efficient diagnosis of acute hepatitis and identification of the likely mode of transmission. The aim of this study was to identify the clinical and epidemiological hallmarks of acute hepatitis C. During 2013-2015, 31 patients were hospitalized with a diagnosis of acute C hepatitis. According to epidemiological data, the primary mode of transmission is during medical procedures, responsible for 14 (45.16%) of cases, followed by injection drug use 3 (9.7%) of cases and sexual transmission - 2 (6.43%) of cases. However, in 12 (38.71%) of cases the infected individual was unable identify the likely source of infection. Given that nearly half of all cases arise from nosocomial infection, it is imperative that infection control practices be reviewed and resources provided to prepare a sterile environment for patients and health care providers.

Clinical and epidemiological peculiarities of hemorrhagic colitis complicated by hemolytic-uremic syndrome.

The aim of the research: identification of etiological structure of acute diarrheas and hemorrhagic colitis in Georgia, manifestation of clinical peculiarities and predictors of hemorrhagic colitis complicated by HUS ( Hemolytic-Uremic syndrome). In 2011-2013 we studied 274 hospitalized patients at the Center of Infectious Diseases, AIDS and Clinical Immunology (160 hemorrhagic colitis and 114 non-bloody diarrhea). Causative agents of hemorrhagic colitis (160 patients) were determined in 110 (69%) cases; etiology of the non-bloody diarrhea (114 patients) was established in 46 (40%) cases. Enteronterohaemorrhagic E. coli (EHEC) strains are major causes of hemorrhagic colitis. For the confirmation of STEC infection by the bacteriological investigation some significant additional methods were used: serologic examination of feces on shiga- toxin molecular markers by ImmunoCard STAT and PCR methods. Thus, these above mentioned investigations contribute to diagnosis STEC infection at the early stage of the disease. Based on our findings we were able to reveal predictors of complications of hemorrhagic colitis by HUS. They include: Delayed hospitalization, rural residents, premorbid background, onset of the disease with low-grade fever accompanied with abdominal cramps, manifestation of bloody diarrhea on the 2-3-rd days of the disease, frequent bowl movement (>20 times a day), development of oliguria and edema on the following days, leucocytosis in hemogram, elevation of LDH, creatinine and urea, hypoalbuminemia and development of ascites.

Enterohemorrhagic E. coli and hemolytic uremic syndrome in Georgia.

It is important to consider that between Jul-October 2009 in the pathologic center of infectious diseases (Tbilisi State Medical University Department of Infectious Diseases) among hospitalized patients with hemorrhagic colitis 25 patients developed HUS syndrome. Most of patients were rural residents 20 (80%), only 5 (20%) were urban. 11 (44%) patients were children, 14 (56%) were adults. Male and female rate was equal. All the patients related the onset of the disease with the consumption of notwashed raw fruits or vegetables, nonpasteurized dairy products, food from street vendors, soft cheeses made from raw milk and untreated water in areas lacking adequate chlorination. The onset of the disease was not acute: low grade fever (37,5-37,8(0)C), severe diffuse pain in abdomen accompanied with cramps, frequent bowel movement with loose, watery stools 5-6 times a day. On the 2-3rd days of disease condition was worsened by increased of intoxication and frequent bowel movement with bloody stools about 10-15-20 times a day. On the 3-4 rd days of the onset of the diarrhea developed oliguria, anuria, edema. Among other complications important were: polyserosit - 8 (32%), encephalopathy - 2 (8%), disseminated intravascular coagulation - 3 (14%), ileus -1 (4%,) acute reactive phsycosis - 1 (4)%. In 15 (60%) cases became necessary to carry out hemodialysis. died 5 patients, lethality is - 5 (20%). Treatment options included: pathogenetic and symptomatic. Thus, increased rate of patients in the recent years indicates to circulation of shiga-toxin producing E.Coli in Georgia.