Effectiveness of serological markers of gastric mucosal atrophy in the gastric precancer screening and in cancer prevention

BACKGROUND New markers are needed to improve the effectiveness of serological screening for atrophic gastritis.AIM To develop a cost-effective method for serological screening of atrophic gastritis with a high level of sensitivity.METHODS Of the 169 patients with atrophic gastritis,selected by the visual endoscopic Kimura-Takemoto method,165 showed histological mucosal atrophy using the updated Kimura-Takemoto method.All 169 patients were examined for postprandial levels of gastrin-17(G17)and pepsinogen-1(PG1)using Gastro-Panel®(Biohit Plc,Helsinki,Finland).RESULTS We used the histological standard of five biopsies of the gastric mucosa,in accordance with the Kimura-Takemoto classification system to assess the sensitivity of G17 in detecting gastric mucosal atrophy.We also compared the morphofunctional relationships between the detected histological degree of gastric mucosal atrophy and the serological levels of G17 and PG1,as the markers of atrophic gastritis.The sensitivity of postprandial G17 was 62.2%for serological levels of G17(range:0-4 pmol/L)and 100%for serological G17(range:0-10 pmol/L)for the detection of monofocal severe atrophic gastritis.No strong correlation was found between the levels of PG1 and degree of histological atrophy determined by the Kimura-Takemoto classification system to identify the severity of mucosal atrophy of the gastric corpus.In the presented clinical case of a 63-year-old man with multifocal atrophic gastritis,there is a pronounced positive long-term dynamics of the serological marker of atrophy-postprandial G17,after five months of rennet replacement therapy.CONCLUSION Serological screening of multifocal atrophic gastritis by assessment of postprandial G17 is a cost-effective method with high sensitivity.Postprandial G17 is an earlier marker of regression of atrophic gastritis than a morphological examination of a gastric biopsy in accordance with the Sydney system.Therefore,postprandial G17 is recommended for dynamic monitoring of atrophic gastritis after treatment.

Global strategy for prevention of gastric cancer

Global prevention of gastric cancer needs to increase its level of effectiveness.The prevention strategy should include all stages of primary and secondary prevention.The necessary steps to prevent gastric cancer are the following:Maintaining a healthy lifestyle and diet,avoiding smoking and alcohol;serological screening of Helicobacter pylori infections and eradication;serological screening of atrophic gastritis in the population over 45 years of age and identification of severe atrophic gastritis with a high risk of developing gastric cancer;verification of atrophic gastritis and precancerous changes in the gastric mucosa using modern endoscopic(confocal laser endomicroscopy,narrow-spectrum imaging,and magnifying endoscopy)and morphological methods among patients with severe atrophic gastritis who were identified using serological screening;treatment of patients with atrophic gastritis during diagnosis verification;annual endoscopic and morphological monitoring of patients with atrophic gastritis during permanent treatment;annual serological monitoring of patients with atrophic gastritis who refused endoscopic and morphological monitoring;and radical treatment of patients with verified early gastric cancer.Ways to implement the algorithm for the global strategy for the prevention of gastric cancer(protocol of practical recommendations)are:State,government,and municipal programs;departmental programs of health departments;family doctors for patients who have a contract at the initiative of the doctor;family doctors for patients with a contract at the patient’s initiative;and within private healthcare system where both doctors and patients can initiate the implementation of algorithm.

Criteria for assessing the diagnostic significance of modern methods of imaging gastrointestinal diseases in practical gastroenterology

Imaging methods are frequently used to diagnose gastrointestinal diseases and play a crucial role in verifying clinical diagnoses among all diagnostic algorithms.However,these methods have limitations,challenges,benefits,and advantages.Addressing these limitations requires the application of objective criteria to assess the effectiveness of each diagnostic method.The diagnostic process is dynamic and requires a consistent algorithm,progressing from clinical subjective data,such as patient history(anamnesis),and objective findings to diagnostics ex juvantibus.Caution must be exercised when interpreting diagnostic results,and there is an urgent need for better diagnostic tests.In the absence of such tests,preliminary criteria and a diagnosis ex juvantibus must be relied upon.Diagnostic imaging methods are critical stages in the diagnostic workflow,with sensitivity,specificity,and accuracy serving as the primary criteria for evaluating clinical,laboratory,and instrumental symptoms.A comprehensive evaluation of all available diagnostic data guarantees an accurate diagnosis.The“gold standard”for diagnosis is typically established through either the results of a pathological autopsy or a lifetime diagnosis resulting from a thorough examination using all diagnostic methods.

Mesenchymal stem cells and the neuronal microenvironment in the area of spinal cord injury

Cell-based technologies are used as a therapeutic strategy in spinal cord injury(SCI). Mesenchymal stem cells(MSCs), which secrete various neurotrophic factors and cytokines, have immunomodulatory, anti-apoptotic and anti-inflammatory effects, modulate reactivity/phenotype of astrocytes and the microglia, thereby promoting neuroregeneration seem to be the most promising. The therapeutic effect of MSCs is due to a paracrine mechanism of their action, therefore the survival of MSCs and their secretory phenotype is of particular importance. Nevertheless, these data are not always reported in efficacy studies of MSC therapy in SCI. Here, we provide a review with summaries of preclinical trials data evaluating the efficacy of MSCs in animal models of SCI. Based on the data collected, we have tried(1) to establish the behavior of MSCs after transplantation in SCI with an evaluation of cell survival, migration potential, distribution in the area of injured and intact tissue and possible differentiation;(2) to determine the effects MSCs on neuronal microenvironment and correlate them with the efficacy of functional recovery in SCI;(3) to ascertain the conditions under which MSCs demonstrate their best survival and greatest efficacy.

Possibility of non-invasive diagnosis of gastric mucosal precancerous changes

AIM: To assess the possibility of non-invasive screening of atrophic chronic gastritis for preventing further development of gastric cancer.METHODS: One hundred and seventy-eight consecutive Helicobacter pylori ( H pylori)-positive dyspeptic patients after detection of serum levels of pepsinogen-1 (PG-1) and gastrin-17 (G-17) by enzyme immunoassay were proposed for endoscopy and histology. The serologic and morphologic results were compared with estimating the sensitivity, specificity and prognostic values of the tests.RESULTS: There was statistically significant reverse dependence between the grade of stomach mucosal antral or corpus atrophy and the proper decreasing of serum G17 or PG1 levels. The serologic method was quite sensitive in the diagnosis of non-atrophic and severe antral and corpus gastritis. Also, it was characterized by the high positive and negative prognostic values.CONCLUSION: Detection of serum G-17 and PG1 levels can be offered as the screening tool for atrophic gastritis. The positive serologic results require further chromoendoscopy with mucosal biopsy, for revealing probable progressing of atrophic process with development of intestinal metaplasia, dysplasia or gastric cancer.

Updated Kimura-Takemoto classification of atrophic gastritis

BACKGROUND The Updated Sydney system for visual evaluation of gastric mucosal atrophy viaendoscopic observation is subject to sampling error and interobserver variability.The Kimura-Takemoto classification system was developed to overcome theselimitations.AIMTo compare the morphological classification of atrophic gastritis between theKimura-Takemoto system and the Updated Sydney system.METHODSA total of 169 patients with atrophic gastritis were selected according to diagnosisby the visual endoscopic Kimura-Takemoto method. Following the UpdatedKimura-Takemoto classification system, one antrum biopsy and five gastriccorpus biopsies were taken according to the visual stages of the Kimura-Takemoto system. The Updated Kimura-Takemoto classification system was thenapplied to each and showed 165 to have histological mucosal atrophy;theremaining 4 patients had no histological evidence of atrophy in any biopsy. The Updated Kimura-Takemoto classification was verified as a referencemorphological method and applied for the diagnosis of atrophic gastritis. Addingone more biopsy from the antrum to the six biopsies according to the Updated Kimura-Takemoto classification, constitutes the updated combined Kimura-Takemoto classification and Sydney system.RESULTSThe sensitivity for degree of mucosal atrophy assessed by the Updated Sydneysystem was 25% for mild, 36% for moderate, and 42% for severe, when comparedwith the Updated Kimura-Takemoto classification of atrophic gastritis formorphological diagnosis. Four types of multifocal atrophic gastritis wereidentified: sequential uniform (type 1;in 28%), sequential non-uniform (type 2;in7%), diffuse uniform (type 3;in 23%), diffuse non-uniform (type 4;in 24%), and"alternating atrophic – non-atrophic" (type 5;in 18%). The pattern of the spread ofatrophy, sequentially from the antrum to the cardiac segment of the stomach,which was described by the Updated Kimura-Takemoto system, washistologically confirmed in 82% of cases evaluated.CONCLUSIONThe Updated Sydney system is significantly inferior to the Updated Kimura-Takemoto classification for morphological verification of atrophic gastritis.

Ursodeoxycholic acid as a means of preventing atherosclerosis,steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease

BACKGROUND Atherosclerotic cardiovascular disease(ASCVD)is the leading cause of mortality in patients with nonalcoholic fatty liver disease(NAFLD).Weight loss is a key factor for successful NAFLD and CVD therapy.Ursodeoxycholic acid(UDCA),which is one of the first-line therapeutic agents for treatment of NAFLD,is reported to have a beneficial effect on dyslipidemia and ASCVD risk because of antioxidant properties.AIM To evaluate the effects of 6 mo of UDCA treatment on hepatic function tests,lipid profile,hepatic steatosis and fibrosis,atherogenesis,and ASCVD risk in men and women with NAFLD,as well as to assess the impact of>5%weight reduction on these parameters.METHODS An open-label,multicenter,international noncomparative trial was carried out at primary health care settings and included 174 patients with ultrasound-diagnosed NAFLD who received 15 mg/kg/d UDCA for 6 mo and were prescribed lifestyle modification with diet and exercise.The efficacy criteria were liver enzymes,lipid profile,fatty liver index(FLI),noninvasive liver fibrosis tests(nonalcoholic fatty liver disease fibrosis score and liver fibrosis index),carotid intima-media thickness(CIMT),and ASCVD risk score.To test statistical hypotheses,the Wilcoxon test,paired t-test,Fisher’s exact test,and Pearson's chi-squared test were used.RESULTS The alanine aminotransferase(ALT)level changed by-14.1 U/L(-31.0;-5.3)from baseline to 3 mo and by-6.5 U/L(-14.0;0.1)from 3 to 6 mo.The magnitude of ALT,aspartate transaminase,and glutamyltransferase decrease was greater during the first 3 mo of treatment compared to the subsequent 3 mo(P<0.001,P<0.01,P<0.001,respectively).At 6 mo,in the total sample,we observed a statistically significant decrease in body weight and levels of FLI:84.9±10.4 vs 72.3±17.6,P<0.001,total cholesterol:6.03±1.36 vs 5.76±1.21,Р<0.001,lowdensity lipoprotein:3.86±1.01 vs 3.66±0.91,Р<0.001,and triglyceride:3.18(2.00;4.29)vs 2.04(1.40;3.16),Р<0.001.No effect on nonalcoholic fatty liver disease fibrosis score or liver fibrosis index was found.The CIMT decreased significantly in the total sample(0.985±0.243 vs 0.968±0.237,P=0.013),whereas the highdensity lipoprotein(Р=0.036)and 10-year ASCVD risk(Р=0.003)improved significantly only in women.Fifty-four patients(31%)achieved>5%weight loss.At the end of the study,the FLI decreased significantly in patients with(88.3±10.2 vs 71.4±19.6,P<0.001)and without>5%weight loss(83.5±10.3 vs 72.8±16.7,P<0.001).The changes in ALT,aspartate transaminase,glutamyltransferase,total cholesterol,and low-density lipoprotein levels were similar between the subgroups.CONCLUSION UDCA normalizes liver enzymes greatly within the first 3 mo of treatment,improves lipid profile and hepatic steatosis independent of weight loss,and has a positive effect on CIMT in the total sample and 10-year ASCVD risk in women after 6 mo of treatment.

Consensus on management of hepatitis C virus infection in resource-limited Ukraine and Commonwealth of Independent States regions

Globally, 69.6 million individuals were infected with hepatitis C virus (HCV) infection in 2016. Of the six major HCV genotypes (GT), the most predominant one is GT1, worldwide. The prevalence of HCV in Central Asia, which includes most of the Commonwealth of Independent States (CIS), has been estimated to be 5.8% of the total global burden. The predominant genotype in the CIS and Ukraine regions has been reported to be GT1, followed by GT3. Inadequate HCV epidemiological data, multiple socio-economic barriers, and the lack of regionspecific guidelines have impeded the optimal management of HCV infection in this region. In this regard, a panel of regional experts in the field of hepatology convened to discuss and provide recommendations on the diagnosis, treatment, and pre-, on-, and posttreatment assessment of chronic HCV infection and to ensure the optimal use of cost-effective antiviral regimens in the region. A comprehensive evaluation of the literature along with expert recommendations for the management of GT1-GT6 HCV infection with the antiviral agents available in the region has been provided in this review. This consensus document will help guide clinical decision-making during the management of HCV infection, further optimizing treatment outcomes in these regions.

The Activity of Antioxidative Enzymes of Neutrophils in Patients with Unfavorable Outcome of Acute Coronary Syndrome

Background: There is a necessity for an establishment of specific markers of oxidative stress for screening in populations of high risk and an estimation of efficiency antioxidative therapies. Objective: Studying the activity of antioxidative enzymes at neutrophils in patients with acute coronary syndrome depending on outcome during the year. Methods: Intracellular metabolism of neutrophils was studied in 108 patients, of whom, in 58 persons has been diagnosed acute coronary syndrome, and 50 individuals were without coronary heart disease. Results: In patients with acute coronary syndrome, in comparison with patients without coronary heart disease, growth of production of superoxide anion on background reduction of glutathione reductase activity in neutrophils was revealed. The greatest reduction in parameters of glutathione reductase and catalase at simultaneous growth of activity of NAD(P)H oxidase and myeloperoxidase at neutrophils was observed in patients with fatal outcome during the year. Conclusion: The decrease of efficiency antioxidative protection of neutrophils associates with risk of fatal outcome in patients with acute coronary syndrome.

Influence of Antirisk Factors of Cardiovascular Diseases on Intracellular Metabolism of Neutrophils in Men with Obesity

Background: The factor promoting development of oxidative stress at obesity can be the neutro-phils. Objective: To study the influence antirisk factors of cardiovascular diseases on intracellular metabolism of neutrophils in men with peripheral obesity. Methods: In 103 male patients aged 23 to 64 years without coronary heart disease, we studied the presence obesity, antirisk factors of cardiovascular diseases, and the metabolic activity of neutrophils. Results: It is identified that obesity in men associates with more rare use of crude vegetables or fruits every day, and also low physical activity. The daily uses of crude vegetables or fruits, and also the increase of physical activity in obese men promote increase intracellular activity of antioxidative protection at neutrophils. Conclusion: The antirisk factors of cardiovascular diseases increase activity antioxidative protection of neutrophils in men with peripheral obesity, reducing the probability of development of oxidative stress.

Diagnostic Accuracy and Predictive Value of Clinical Symptoms for the Diagnosis of Mild COVID-19

Objective: To assess the diagnostic accuracy and predictive values of clinical symptoms in patients with suspected mild COVID-19 to identify target groups for self-isolation and outpatient treatment without additional testing. Methods: We conducted an open-label prospective study in patients aged 18 to 72 years with suspected mild COVID-19. The clinical diagnosis was based on the acute onset of such symptoms as olfactory dysfunction, hyperthermia, myalgia, nasal congestion, nasal discharge, cough, rhinolalia, sore throat, without pneumonia in persons in contact with a confirmed case of COVID-19. The physician assessed clinical symptoms using a 4-point scale. The patient self-assessed clinical symptoms using a ten-point visual analogue scale (VAS). All enrolled patients underwent laboratory testing to confirm the diagnosis of COVID-19. Results: Of the 120 patients underwent testing, the diagnosis of mild COVID-19 was confirmed in 96 patients and ruled out in 24 patients. When assessing symptoms by a physician according to the correlation analysis, hyperthermia, myalgia, nasal congestion and rhinolalia have a positive predictive value with a significance level of more than 0.6. When self-assessing symptoms by a patient, fever, myalgia and nasal congestion have a diagnostic accuracy with a significance level of more than 0.5. Nasal discharge, cough and sore throat have negative predictive values. Conclusion: The presence of these symptoms in patients with an acute onset of the disease can help to make a clinical diagnosis of coronavirus disease and identify target groups for self-isolation and outpatient treatment without additional testing. Highly suspect asymptomatic patients are not considered as those who have possible mild COVID-19 infection.

Tumor irradiation may facilitate the detection of tumor-specific mutations in plasma

BACKGROUND The mutation-based analysis of circulating tumor DNA(ctDNA)is a promising diagnostic tool for clinical oncology.However,it has low success rate because many cancer patients do not have detectable ctDNA in the bloodstream.AIM To evaluate whether preoperative tumor irradiation results in a transient increase of plasma ctDNA concentration due to the induction of apoptosis in radiationexposed cells.METHODS This study focused on patients with locally advanced rectal cancer,because preoperative tumor irradiation is a part of their standard treatment plan.Nine subjects,whose tumors contained KRAS,NRAS or BRAF mutations,donated serial blood samples 1 h prior to the first fraction of irradiation(at baseline),immediately after the first fraction(time 0),and 1,3,6,12,24,36,48,72 and 96 h after the first fraction.The amount of mutated gene copies was measured by droplet digital PCR.RESULTS Five out of nine patients were mutation-negative by ctDNA test at baseline;two of these subjects demonstrated an emergence of the mutated DNA copies in the bloodstream within the follow-up period.There were 4 patients,who had detectable ctDNA in the plasma at the start of the experiment;three of them showed an evident treatment-induced increase of the content of mutated RAS/RAF alleles.CONCLUSION Local tumor irradiation may facilitate the detection of tumor-specific DNA in the bloodstream.These data justify further assessment of the clinical feasibility of irradiation-assisted liquid biopsy.

Cancer risk stratification system and classification of gastritis:Perspectives

Kyoto global consensus reports that the current ICD-10 classification for gastritis is obsolete.The Kyoto classification of gastritis states that severe mucosal atrophy has a high risk of gastric cancer,while mild to moderate atrophy has a low risk.The updated Kimura-Takemoto classification of atrophic gastritis considers five histological types of multifocal corpus atrophic gastritis according to stages C2 to O3.This method of morphological diagnosis of atrophic gastritis increases sensitivity by 2.4 times for severe atrophy compared to the updated Sydney system.This advantage should be considered when stratifying the high risk of gastric cancer.The updated Kimura-Takemoto classification of atrophic gastritis should be used as a reference standard(gold standard)in studies of morphofunctional relationships to identify serological markers of atrophic gastritis with evidence-based effectiveness.The use of artificial intelligence in the serological screening of atrophic gastritis makes it possible to screen a large number of the population.During serological screening of atrophic gastritis and risk stratification of gastric cancer,it is advisable to use the Kyoto classification of gastritis with updated Kimura-Takemoto classification of atrophic gastritis.

Plasma Levels of Leukotriene B4 and Prostaglandin E2 Correlation with Endoscopic Changes after NSAID Gastropathies Pantoprazole Treatment in Patients with Cardiovascular Pathology

The article describes the pantoprazole healing effect on the gastroduodenal mucosa in patients with NSAID gastropathy. Two groups of patients were compared, depending on the treatment they have got group, which was taking 75 mg of enteric aspirin per day and the group, where pantoprazole has been added to aspirin in the usual dose. Mucosa assessment was studied using fibrogastroduodenoscopy and Lanza score. Also, the relationship between aggression factors that cause NSAID gastropathy and mucosal protection agents has been studied. It was proved that the pantoprazole influence reduces the ulcerative-erosive lesions amount. Stomach erosive lesions percentage decreased from 58.18% to 42.42%, stomach ulcers from 14.55% to 6.06%, duodenum erosive lesions decreased from 34.55% to 24.24%, duodenum ulcers deceased from 9.09% to 3.03%. A positive correlation between LTB4 and Lanza scale was checked after pantoprazole treatment, indicating an impact on the LTB4 reduction in ulcers healing in patients with NSAID gastropathy.

Blood-brain barrier and cerebral blood flow: Age differences in hemorrhagic stroke

Neonatal stroke is similar to the stroke that occurs in adults and produces a significant morbidity and long-term neurologic and cognitive deficits.There are important differences in the factors,clinical events and outcomes associated with the stroke in infants and adults.However,mechanisms underlying age differences in the stroke development remain largely unknown.Therefore,treatment guidelines for neonatal stroke must extrapolate from the adult data that is often not suitable for children.The new information about differences between neonatal and adult stroke is essential for identification of significant areas for future treatment and effective prevention of neonatal stroke.Here,we studied the development of stress-induced hemorrhagic stroke and possible mechanisms underlying these processes in newborn and adult rats.Using histological methods and magnetic resonance imaging,we found age differences in the type of intracranial hemorrhages.Newborn rats demonstrated small superficial bleedings in the cortex while adult rats had more severe deep bleedings in the cerebellum.Using Doppler optical coherent tomography,we found higher stress-reactivity of the sagittal sinus to deleterious effects of stress in newborn vs.adult rats suggesting that the cerebral veins are more vulnerable to negative stress factors in neonatal vs.adult brain in rats.However,adult but not newborn rats demonstrated the stroke-induced breakdown of blood brain barrier(BBB)permeability.The one of possible mechanisms underlying the higher resistance to stress-related stroke injures of cerebral vessels in newborn rats compared with adult animals is the greater expression of two main tight junction proteins of BBB(occludin and claudin-5)in neonatal vs.mature brain in rats.

Diastolic Dysfunction and Left Ventricle Remodeling in Men with Impaired Fasting Glucose

Background: Early disturbances of carbohydrate metabolism are an independent risk factor of development of cardiovascular diseases. Objective: The diastolic dysfunction and left ventricle remodeling depending on presence of impaired fasting glucose were examined. Methods: The characteristics of heart remodeling and fasting glucose of capillary blood were studied in 85 men aged 30 to 63 years without coronary heart disease. Results: In male patients with impaired fasting glucose in comparison of persons with level of glucose less than 5.6 mM/l, more pronounced diastolic dysfunction and left ventricle remodeling associated with more often presence III degree of peripheral obesity. Conclusion: Impaired fasting glucose in men increases probability of development of heart remodeling.

Chondroitin sulfate and glucosamine combination in patients with knee and hip osteoarthritis:A long-term observational study in Russia

BACKGROUND Oral treatment of glucosamine(GA) combined with chondroitin sulfate(CS) was reportedly effective for pain relief and function improvement in osteoarthritis patients with moderate to severe knee pain in clinical trials. While the effectiveness of GA and CS on both clinical and radiological findings has been demonstrated, only a few high-quality trials exist. Therefore, controversy regarding their effectiveness in real-world clinical practice remains.AIM To investigate the impact of GA + CS on clinical outcomes of patients with knee and hip osteoarthritis in routine clinical practice.METHODS A multicenter prospective observational cohort study included 1102 patients of both genders with knee or hip osteoarthritis(Kellgren & Lawrence grades Ⅰ-Ⅲ) in 51 clinical centers in the Russian Federation from November 20, 2017, to March 20,2020, who had started to receive oral capsules of glucosamine hydrochloride 500 mg and CS 400mg according to the approved patient information leaflet starting from 3 capsules daily for 3 wk,followed by a reduced dosage of 2 capsules daily before study inclusion(minimal recommended treatment duration is 3-6 mo). Changes in subscale scores [Pain, Symptoms, Function, and Quality of Life(QOL)] of the Knee Injury and Osteoarthritis Outcome Score(KOOS)/Hip Disability and Osteoarthritis Outcome Score(HOOS) questionnaires during the observational period(up to 54-64wk with a total of 4 visits). Patients’ treatment satisfaction, data on the combined oral use of glucosamine hydrochloride and CS, concomitant use of non-steroidal anti-inflammatory drugs(NSAIDs), and adverse events(AEs) were also evaluated.RESULTS A total of 1102 patients with knee and hip osteoarthritis were included in the study. The mean patient age was 60.4 years, most patients were women(87.8%), and their average body mass index was 29.49 kg/m2. All subscale scores(Pain, Symptoms, Function, and QOL) of the KOOS and HOOS demonstrated clinically and statistically significant improvements. In patients with knee osteoarthritis, the mean score increases from baseline to the end of Week 64 were 22.87, 20.78,16.60, and 24.87 on Pain, Symptoms, Physical Function(KOOS-PS), and QOL subscales(P < 0.001for all), respectively. In patients with hip osteoarthritis, the mean score increases were 22.81, 19.93,18.77, and 22.71 on Pain, Symptoms, Physical Function(HOOS-PS), and QOL subscales(P < 0.001for all), respectively. The number of patients using any NSAIDs decreased from 43.1% to 13.5%(P < 0.001) at the end of the observation period. Treatment-related AEs occurred in 2.8% of the patients and mainly included gastrointestinal disorders [25 AEs in 24(2.2%) patients]. Most patients(78.1%) were satisfied with the treatment.CONCLUSION Long-term oral GA + CS was associated with decreased pain, reduced concomitant NSAID therapy, improved joint function and QOL in patients with knee and hip osteoarthritis in routine clinical practice.

Hepatobiliary system and intestinal injury in new coronavirus infection(COVID-19):A retrospective study

BACKGROUND An important area of effective control of the coronavirus disease 19(COVID-19)pandemic is the study of the pathogenic features of severe acute respiratory syndrome coronavirus 2 infection,including those based on assessing the state of the intestinal microbiota and permeability.AIM To study the clinical features of the new COVID-19 in patients with mild and moderate severity at the stage of hospitalization,to determine the role of hepatobiliary injury,intestinal permeability disorders,and changes in the qualitative and quantitative composition of the microbiota in the development of systemic inflammation in patients with COVID-19.METHODS The study was performed in 80 patients with COVID-19,with an average age of 45 years,19 of whom had mild disease,and 61 had moderate disease severity.The scope of the examination included traditional clinical,laboratory,biochemical,instrumental,and radiation studies,as well as original methods for studying microbiota and intestinal permeability.RESULTS The clinical course of COVID-19 was studied,and the clinical and biochemical features,manifestations of systemic inflammation,and intestinal microbiome changes in patients with mild and moderate severity were identified.Intestinal permeability characteristics against the background of COVID-19 were evaluated by measuring levels of proinflammatory cytokines,insulin,faecal calprotectin,and zonulin.CONCLUSION This study highlights the role of intestinal permeability and microbiota as the main drivers of gastroenterological manifestations and increased COVID-19 severity.

Rebamipide and Pantoprazole Combination in NSAIDs-Gastropathy Treatment

The objective of this study was to investigate the pantoprazole and rebamipide efficiency on NSAIDs （nonsteroidal anti-inflammatory drugs）-gastropathy restoring and healing in patients with coronary heart disease, stable angina, who have been taking aspirin for a long time period. The study included three groups of patients according to the treatment they have got： ASA （acetylsalicylic acid） in the first group; ASA and pantoprazole in the second; ASA, pantoprazole and rebamipide in the third one. To obtain the results, endoscopic method and proinflammatory cytokines LTB4 and protective prostaglandin E2 determination in the blood were used. The research demonstrated no ulcer effects in the group of patients who were treated by rebamipide, and significantly fewer gastroduodenal erosions, in comparison to the group, where treatment contained ASA and pantoprazole. The LTB4 （leukotriene B4） level decreased in pantoprazole and rebamipide treatment groups, but the PGE2 （prostaglandin E2） level increased only after rebamipide therapy. Therefore, rebamipide should be included to the therapy for the better NSAIDs-gastropathy treatment, in reason of its good reparative and gastroprotective properties.

Matrix Metalloproteinases and Their Tissue Inhibitors in Patients with Nonalcoholic Fatty Liver Disease

The objective of the study is to assess the role of MMP-9, TIMP-1 ＆ 2 as non-invasive markers of liver fibrosis in the NAFLD. The 99 patients with NAFLD and different stages of fibrosis were examined. We assessed of anthropometric indicators, biochemical analysis of blood, abdominal ultrasonic studies, the levels of MMP-9, TIMP-1 ＆ 2. According of results of elastometry, patients were divided into five groups： n = 27, n = 22, n = 23, n = 14, n = 13, respectively, depending on the stage of fibrosis （0-4）. Between the groups in physical examination, no significant differences in BMI and W/H were found. 64.6% of patients had abdominal obesity （BMI： 31.5 （29.1-33.9）, W/H： 1.02 （1.01-1.05））. Obesity and abdominal obesity （BMland W/H） had a significant positive relationship of moderate streight （rs = 0.257, p 〈 0.04 and rs = 0.301, p 〈 0.02, respectively）, with the stage of liver fibrosis. The groups were significant differences in the level of glucose, total bilirubin （p 〈 0.04, p 〈 0.03, respectively）. No significant differences in the level of liver function tests （ALT and AST） in the study groups were found. Significant differences were found in level of TIMP-2 （p 〈 0.04）. TIMP-2 had a significant positive correlation with the severity of fibrosis in the hepatic tissue （rs = 0.349, p 〈 0.004）. TIMP-2 may be considered as a potential non-invasive marker for the diagnosis of liver fibrosis in patients with NAFLD.