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Background and aim . This study aimed to assess the efficacy of the treatment of Kan Jang ® , a fixed combination of Andrographis paniculata (Burm. F.) Wall. ex. Nees and Eleutherococcus senticosus (Rupr. & Maxim.) Maxim extracts in patients with mild symptoms of COVID-19. Methods . One hundred and forty patients received six capsules of Kan Jang ® ( n = 68, daily dose of andrographolides-90 mg) or placebo ( n = 72) and supportive treatment (paracetamol) for 14 consecutive days in a randomized, quadruple-blinded, placebo-controlled, two-parallel-group design. The efficacy outcomes were the rate of cases turning to severe, the detection rate of coronavirus SARS-CoV-2 over the time of treatment, the duration, and the severity of symptoms (sore throat, runny nose, cough, headache, fatigue, loss of smell, taste, pain in muscles) in the acute phase of the disease. Other efficacy measures included improving cognitive and physical performance, quality of life, and the levels of inflammatory blood markers-interleukin 6 (IL-6), C-reactive protein, and D-dimer. Results . Kan Jang ® significantly ( p < 0.05) reduced the rate of cases turning to severe (5.36%) compared to the placebo (17.86%) and decreased the detection rate of SARS-CoV-2 virus over the time of the treatment. The statistical difference in the rates of patients with clinical deterioration in the Kan Jang treatment and placebo control groups was significant ( p = 0.0176) both in the 112 patients in the included-per-protocol (IPP) analysis and in the 140 patients in the intended-to-treat (ITT) analysis ( p = 0.0236); the absolute risk reduction in cases thanks to the Kan Jang treatment was 12.5%, and the number we needed to treat with Kan Jang was 8. The patient's recovery time (number of sick days at the home/clinic) was shorter in the Kan Jang group compared with the placebo group. The rate of attenuation of inflammatory symptoms in the Kan Jang ® group was significantly higher, decreasing the severity of cough, sore throat/pain, runny nose, and muscle soreness compared with the placebo group. Kan Jang ® significantly decreased the Wisconsin Upper Respiratory Symptoms scores compared to the placebo in the sample size of 140 patients. However, the relief of fatigue and headache and the decrease in IL-6 in the blood were observed only in a subset of 86 patients infected during the second three waves of the pandemic. Kan Jang ® significantly increased physical activity and workout; however, it did not affect cognitive functions (attention and memory), quality of life score, inflammatory marker D-dimer, and C-reactive protein compared with the placebo group. Conclusions . Overall, the results of this study suggest that Kan Jang ® is effective in treating mild and moderate COVID-19 irrespective of the SARS-CoV-2 variant of infection.

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.

Background: Angiotensin-converting enzyme 2 (ACE2) is not only the entry route of SARS-CoV-2 infection but also triggers a major mechanism of COVID-19 aggravation by promoting a hyperinflammatory state, leading to lung injury, hematological and immunological dysregulation. The impact of ACE2 inhibitors on the course of COVID-19 is still unclear. The effect of ACE2 inhibitors on the course of acute respiratory distress syndrome (ARDS) during COVID-19 and other severe respiratory infections in conditions of hyperferritinemia (HF) was investigated., Methods: A cohort study of critically ill patients with COVID-19 and other respiratory diseases (widespread infection, pneumonia) who underwent treatment in The Critical Care Unit of the First University Clinic (Tbilisi, Georgia) during the 2020-2021 years was conducted. The impact of the ACE2 inhibitors on the course of the ARDS developed during COVID-19 and other severe respiratory infections in conditions of different severity of HF was evaluated., Results: In COVID-19-infected (I) and uninfected (II) patients with ARDS, ACE2 inhibitors reduce the levels of Ang II, C reactive protein (CRP) and D-dimer (I: from 1508.07  ±  26.68 to 48.51  ±  24.35, from 233.92  ±  13.02 to 198.12  ±  11.88, from 7.88  ±  0.47 to 6.28  ±  0.43; II: from 1000.14  ±  149.49 to 46.23  ±  88.21, 226.48  ±  13.81 to 183.52  ±  17.32, from 6.39  ±  0.58 to 5.48  ±  0.69) at moderate HF and Ang II, CRP levels (I: from 1845.89  ±  89.37 to 49.64  ±  51.05, from 209.28  ±  14.41 to 175.37  ±  9.84; II: from 1753.29  ±  65.95 to 49.76  ±  55.74, 287.10  ±  20.50 to 214.71  ±  17.32) at severe HF, reduce interleukin-6 (IL-6) expression at moderate HF (I: from 1977.23  ±  354.66 to 899.36  ±  323.76) and cause reduction of pCO 2 index at severe HF (I: from 69.80  ±  3.22 to 60.44  ±  2.20) in COVID-19-infected patients., Conclusion: Study results show that the ACE2 inhibitors play an important role in the regulation of inflammatory processes in both COVID-19-infected and uninfected patients with ARDS. ACE2 inhibitors decrease immunological disorders, inflammation, and lung alveoli dysfunction, especially in COVID-19-infected patients., (© The Author(s) 2023.)

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.

Arterial hypertension is a highly urgent problem of modern medicine since the crisis of blood pressure control remains open, due to the increasing number of uncontrolled arterial hypertension. Today, one of the most critical problems of cardiology is the study of the mechanisms of development and progression of arterial hypertension. Therefore, our international and multidisciplinary working group presents a vision of a new therapeutic target - urotensin II in the pathogenesis of arterial hypertension. Thus, this article reflects the concept of the Armenian, Georgian and Iranian medical schools., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Kan Jang ® , the fixed combination of Andrographis paniculata (Burm. F.) Wall. ex. Nees and Eleutherococcus senticosus (Rupr. & Maxim.) Maxim extracts, is a herbal medicinal product for relieving symptoms of upper respiratory tract infections. This study aimed to assess the efficacy of Kan Jang ® /Nergecov® on duration and the relief of inflammatory symptoms in adults with mild COVID-19. 86 patients with laboratory-confirmed COVID-19 and mild symptoms for one to three days received supportive treatment (paracetamol) and six Kan Jang ® (daily dose of andrographolides-90 mg) or placebo capsules a day for 14 consecutive days in this randomized, quadruple-blinded, placebo-controlled, two-parallel-group study. The primary efficacy outcomes were the decrease in the acute-phase duration and the severity of symptoms score (sore throat, runny nose, cough, headache, fatigue, loss of smell, taste, pain in muscles), an increase in cognitive functions, physical performance, quality of life, and decrease in IL-6, c-reactive protein, and D-dimer in blood. Kan Jang ® /Nergecov ® was effective in reducing the risk of progression to severe COVID-19, decreasing the disease progression rate by almost 2.5-fold compared to placebo. Absolute risk reduction by Kan Jang treatment is 14%, the relative risk reduction is 243.9%, and the number Needed to Treat is 7.14. Kan Jang ® /Nergecov ® reduces the duration of disease, virus clearance, and days of hospitalization and accelerates recovery of patients, relief of sore throat, muscle pain, runny nose, and normalization of body temperature. Kan Jang ® /Nergecov ® significantly relieves the severity of inflammatory symptoms such as sore throat, runny nose, and muscle pain, decreases pro-inflammatory cytokine IL-6 level in the blood, and increases patients' physical performance (workout) compared to placebo. In this study, for the first time we demonstrate that Kan Jang ® /Nergecov ® is effective in treating mild COVID-19.

Aim and Objective: The establishment of the potential role of the infected people's ABO blood type in the virus infectivity and aggressivity could clarify the aspects of the various susceptibility to virus and play a key role in assessing its spreading potential in the future. We studied the possible association of risk of coronavirus disease-2019 (COVID-19) infection and severe outcomes of disease with ABO blood groups and Rh factor in the Georgian population., Materials and Methods: The effect of blood type on the severity of infection in COVID-19 positive patients admitted to the First University Clinic of Tbilisi State University (Tbilisi, Georgia) from December 2020 to September 2021 was analyzed retrospectively. The odds ratio (OR) criterion was used to determine the influence of the blood group on the risk of COVID-19 infection and of severe course of the disease., Results: The incidence of COVID-19 was 1.65-fold higher in the patients with blood group II(A), and average twice lower in patients with blood groups III(B) and IV(AB), compared with the ABO blood group distribution in healthy donors of the region. The percentage of patients transferring in ICU with I(O) and II(A) blood groups was enough high (42-40%), whereas in patients with III(B) and IV(AB) blood groups very low (12-6%). There were not revealed any statistically significant differences in the distribution of the patients with Rh+ and Rh- blood groups in healthy and COVID-19 infected individuals (including those transferred in the ICU)., Conclusion: The link between patients' ABO blood groups and receptivity to COVID-19 infection, progression and severity of the disease, has been detected. These results are relevant in terms of elucidating the mechanisms and risk factors of infecting and severity course of COVID-19 disease., How to Cite This Article: Ratiani L, Sanikidze TV, Ormotsadze G, Pachkoria E, Sordia G. Role of ABO Blood Groups in Susceptibility and Severity of COVID-19 in the Georgian Population. Indian J Crit Care Med 2022;26(4):487-490., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2022; Jaypee Brothers Medical Publishers (P) Ltd.)

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.

The aim of our study was to evaluate the effectiveness of treatment with the local antihistamine medicine Palada NS in patients with vasomotor rhinitis who have had COVID-19 infection (6 months after transfer) and have not. The diagnosis of vasomotor rhinitis was made on the basis of subjective (sneezing frequency, degree of difficulty in nasal breathing, nature, consistency, color of nasal discharge, as well as color of swelling of the nasal mucosa and turbinates, impaired olfactory function, general condition of the patient) and objective (anterior and posterior rhinoscopy, endoscopy, rhinomanometry) examination.Patients in both groups were treated with Palladium NS for 10 days (2 sprays, 2 times a day for 10 days). All studies were performed in patients before, 3-5 days after, and at the end of the treatment. The effectiveness of treatment was assessed according to patients' subjective complaints and objective indicators of instrumental examination. Symptoms before and after treatment were assessed on a 3-point scale. A positive result of treatment was revealed in the majority of patients. Which manifested itself in a decrease in the number of subjective and objective complaints. In patients who did not undergo COVID-19 infection, the subjective and objective indicators' improvement was revealed as early as on the 5th day of treatment, in patients with vasomotor rhinitis who underwent COVID-19 at least 6 months ago, the improvement was recorded only by the end of treatment. Based on the results of our studies, the proposed treatment regimen for vasomotor rhinitis with the local antihistamine medicine Palada NS can be recommended for patients with vasomotor rhinitis, both with and without COVID-19 infection.

Lipomatous Hypertrophy of the Interatrial Septum (LHIS) is an unusual and benign condition characterized by the excessive deposition of adipose tissue in the interatrial septum, which is most often detected as an incidental finding on echocardiography. The classic finding is a homogenous, bi-lobed configuration of the interatrial septum with sparing of the fossa ovalis. LHIS has been associated with various atrial arrhythmias, including multifocal atrial tachycardia, multiple premature atrial contractions, atrial fibrillation and rarely sudden death. The prevalence of LHIS is estimated to be between 1-8%. The incidence increases with age, body mass and chronic corticosteroid therapy. There may be a higher incidence in women. Here the authors describe a case report of a 73 year-old obese female who visited the cardiology department for planned cryoablation of paroxysmal atrial fibrillation. Difficulties raised during transseptal punction, a bidimensional tranthoracic echocardiography (TTE) showed the typical findings of LHIS. A 73 year-old asymptomatic woman was found to have an incidental cardiac mass, TTE findings were consistent with lipomatous hypertrophy of the interatrial septum. Given the characteristic appearance on TTE, biopsy or surgery was not indicated, the procedure of cryoablation has been stopped and the patient was managed conservatively.

Despite the multifaceted effects of the medicines provided for COVID-19treatment, the number of the infected and mortality of patients increases which demonstrates the insufficient effectiveness of drugs used to fight coronavirus infections in medical practice, and clearly shows the need to develop new treatment tactics.In this review article are summarized and analyzed the literature data concerning specific features of COVID 19. Particular attention is given to genetic characteristic of this virus ,to mechanism of its invasion into the human organism, replication and interection with ACE-2 receptors ,as well as to the basic targets for the action of existing drugs with antiviral activity against COVID-19. Currently, the following medications are used to treat COVID-19: remdesivir, chloroquine, hydroxychloroquine (HCQ), ribavirin, lopinavir/ritonavir. According to a recent theory of coronavirus treatment, the starting point for the mechanism of action of a potential etiotropic drug is the inhibition of the coronavirus main protease (Mpro/3CLpro) and the papain-like protease (PLpro). Among the drugs listed above, lopinavir acts through this mechanism but is characterized by severe side effects.It is emphasized that remdesivir as adenosine analog provides inhibitory action on RNA dependent RNA-Polymerase,but there are controversial views about reduction in mortality during using of this drug against COVID-19. The present paper discusses the mechanism of action of a potential etiotropic drug against coronavirus, which implies the replacement of the nucleotides involved in the process of translation of the virus with their analogs with the aim to "inhibit" the ribosome and block the production of viral proteins.

Vasoplegia is considered as a key factor responsible for the death of patients with septic shock, due to persistent and irreversible hypotension. The latter associated with vascular hyporeactivity to vasoconstrictors is a significant independent prognostic factor of mortality in severe sepsis. Loss of control of the vascular tone occurs through the complex, multifactorial mechanism and implicates deeply disrupted balance between vasoconstrictors and vasodilators. The aim of this review is to discuss in detail the recent suggested alternative mechanisms of vasoplegia in severe sepsis: Overproduction of nitric oxide (NO) by activation of inducible form of nitric oxide synthase (iNOS); up-regulation of prostacyclin (PG12); vasopressin deficiency; significantly elevated levels of circulating endothelin; increased concentrations of vasodilator peptides such as adrenomedulin (AM) and calcitonin gene-related peptide (CGRP); oxidative stress inducing endothelial dysfunction and vascular hyporeactivity to vasoconstrictors; inactivation of catecholamines by oxidation; over-activation of ATP-sensitive potassium channels (KATP channels) during septic shock and their involvement in vascular dysfunction. The review also discusses some therapeutic approaches based on pathogenetic mechanisms of severe sepsis and their efficacy in treatment of patients with septic shock. The loss of vascular tone control occurs through the complex, multifactorial mechanism and implicates deeply disrupted balance between vasoconstrictors and vasodilators in the pathogenesis of septic shock. Overproduction of nitric oxide (NO) by the inducible form of nitric oxide synthase (iNOS); up-regulation of prostacyclin (PG12); vasopressin deficiency; elevated levels of circulating endothelin; increased concentrations of vasodilator peptides such as adrenomedulin (AM) and calcitonin gene-related peptide (CGRP); oxidative stress inducing endothelial dysfunction and vascular hyporeactivity to vasoconstrictors; inactivation of catecholamines by oxidation; over-activation of ATP-sensitive potassium channels (KATP channels) and their involvement in vascular dysfunction - all these factors combined together lead to steady refractory shock with the lethal outcome in patients.

Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic circulatory, neurological, hematological, gastrointestinal, reproductive and immunological pathologies. The mechanism of lead induced toxicity is not fully understood. The prime targets to lead toxicity are the heme synthesis enzymes, thiol-containing antioxidants and enzymes (superoxide dismutase, catalase, glutathione peroxidase, glucose 6-phosphate dehydrogenase and antioxidant molecules like GSH). The low blood lead levels are sufficient to inhibit the activity of these enzymes and induce generation of reactive oxygen species and intensification oxidative stress. Oxidative stress plays important role in pathogenesis of lead-induced toxicity and pathogenesis of coupled disease. The primary target of lead toxicity is the central nervous system. There are different cellular, intracellular and molecular mechanisms of lead neurotoxicity: such as induction of oxidative stress, intensification of apoptosis of neurocites, interfering with Ca(2+) dependent enzyme like nitric oxide synthase. Population studies have demonstrated a link between lead exposure and subsequent development of hypertension and cardiovascular disease. The vascular endothelium is now regarded as the main target organ for the toxic effect of lead. Lead affects the vasoactive function of endothelium through the increased production of reactive oxygen species, inactivation of endogenous nitric oxide and downregulation of soluble guanylate cyclase by reactive oxygen species, leading to a limiting nitric oxide availability, impairing nitric oxide signaling. This review summarizes recent findings of the mechanism of the lead-induced toxicity and possibilities of its prevention.

Increasing of number of various therapeutic agents or medications on the world market require the development of rapid and comparatively cheap methodology for screening of these preparations, elucidation their efficacy and mechanisms of action. In article was investigated the methodology based on modeling of human lymphoblastoid T-cell line Jurkat for the modeling and correction of cell homeostasis disregulation, mitochondria-dependent apoptosis, T-lymphocyte proliferation and differentiation conditions, T-cell activity dependence on the alterations of oxidative metabolism, T cell antigen and effector specificity. This methodology gives rapid and comparatively cheap possibility to provide screening of various medical agents, assessment of their immunomodulatory, pro-and antiapoptogenic efficacy and studying mechanism of action of potentially cardioprotective, antyatherogenic medications increasing efficacy of traditional treatment of cardiovascular diseases.

Estrogens belong to more or less frequently prescribed preparations. Main fields of application of these preparations (as in monotherapy as well as in combination) are contraception and hormone replacement therapy during menopause. More uncommon indications of estrogens are growth inhibition and hypogonadism (in this case they are prescribed along with gonadotropic hormones). Synthesis and metabolism of estrogens, as well as their intracellular receptors are well studied these days, which allow us to understand physiology and pharmacology of these hormones. In pharmacology the main stage is detection of estrogen receptors inside of cells of targets. There are two types of estrogen receptors alpha- and beta- coded by different genes. A number of steroid and non-steroid compounds have characteristics of estrogens. Likely in the future their popularity will increase, as by the aging of population number of those women, who receive replacement therapy, will increase. Investigations to find an ideal elective modulator of estrogen receptors, that will possess anti-estrogenic activity in connection with mammal gland and develop indifference in connection with endometrium and at the same time will display ability to reduce hot flushes, bone resorption, atrophy of mucous membranes of vagina and urinary bladder, as well as it will favorably effect on metabolism of lipoproteins are carried out.

The paper is concerned with studies of the T- and B-immunity systems in the CSF in 37 patients, in whom the CSF was extracted in order to perform spinal anesthesia. This was necessary for surgical operations because of cryptochidism (16 patients aged from 16--30) and hypertrophy of the prostate (21 patients aged from 60 and over). The patients of both groups showed no signs of nervous system lesions. A comprehensive immunomorphological analysis of the CSF cells permitted to detect the medium indices of the T- and B-immunocompetent cells of individuals depneding upon the age.