Endotoxin Inflammatory Action on Cells by Dysregulated-Immunological-Barrier-Linked ROS-Apoptosis Mechanisms in Gut-Liver Axis.

Our study highlighted the immune changes by pro-inflammatory biomarkers in the gut-liver-axis-linked ROS-cell death mechanisms in chronic and acute inflammations when gut cells are exposed to endotoxins in patients with hepatic cirrhosis or steatosis. In duodenal tissue samples, gut immune barrier dysfunction was analyzed by pro-inflammatory biomarker expressions, oxidative stress, and cell death by flow cytometry methods. A significant innate and adaptative immune system reaction was observed as result of persistent endotoxin action in gut cells in chronic inflammation tissue samples recovered from hepatic cirrhosis with the A-B child stage. Instead, in patients with C child stage of HC, the endotoxin tolerance was installed in cells, characterized by T lymphocyte silent activation and increased Th1 cytokines expression. Interesting mechanisms of ROS-cell death were observed in chronic and acute inflammation samples when gut cells were exposed to endotoxins and immune changes in the gut-liver axis. Late apoptosis represents the chronic response to injury induction by the gut immune barrier dysfunction, oxidative stress, and liver-dysregulated barrier. Meanwhile, necrosis represents an acute and severe reply to endotoxin action on gut cells when the immune system reacts to pro-inflammatory Th1 and Th2 cytokines releasing, offering protection against PAMPs/DAMPs by monocytes and T lymphocyte activation. Flow cytometric analysis of pro-inflammatory biomarkers linked to oxidative stress-cell death mechanisms shown in our study recommends laboratory techniques in diagnostic fields.

Tissue and Circulating MicroRNA-31, MicroRNA-200b, and MicroRNA-200c Reflects Disease Activity in Crohn's Disease Patients: Results from the BIOMIR Study.

BACKGROUND AND AIMS: MicroRNAs (miR) have altered expression in multiple autoimmune disorders including inflammatory bowel disease. The aim of the study was to assess the tissue and circulating miR-31, miR-200b, and miR-200c expression levels as potential biomarkers for intestinal disease activity in patients with Crohn's disease (CD). METHODS: The study included 45 patients with histopathological confirmed CD and active disease (defined as fecal calprotectin >50 µg/g and Simple Endoscopic Score (SES) of CD >3), and 21 subjects as controls for the validation cohort. Demographic and clinical data, biomarkers (fecal calprotectin), endoscopy data, the expression levels of miR-31, miR-200b, and miR-200c in tissue and serum were assessed (by RT-PCR). Receiver operating characteristic analysis was performed to assess the miR-31, miR-200b, and miR-200c expression levels as potential biomarkers for active CD. RESULTS: Mean fecal calprotectin was 1540±890 µg/g. Mean SES-CD was 8.9±4.2. Tissue and circulating miR- 31 were significantly correlated with fecal calprotectin (r=0.81, r=0.83, p<0.01) and with SES-CD (r=0.82, r=0.79, p<0.01). The expression level of miR-31 was significantly upregulated in CD tissue cases compared to the control tissue samples (6.24±1.57 vs. 3.70±1.44; p <0.01). Similarly, serum miR-31 expression levels in CD patients were significantly upregulated compared to the control serum samples (0.78±0.42 vs. -2.07±1.00; p<0.01). The expression levels of tissue miR-200b and miR-200c were significantly upregulated in CD tissue cases compared to the control tissue samples (-5.25±0.93 vs. -4.69±0.80, p=0.03 for miR-200b, and -0.86±0.96 vs. 0.39±0.66, p<0.01 for miR-200c). Similarly, serum miR-200b and miR-200c expression levels in CD patients were significantly upregulated compared to the control serum samples (p < 0.05). Receiver operating characteristic analysis revealed that the expression levels of the selected miRNAs could help to discriminate active CD patients from healthy controls with very good specificity and sensitivity. CONCLUSIONS: Tissue and circulating miR-31, miR-200b, and miR-200c reflect disease activity in CD patients and can be used as biomarkers for active disease.

Does rifaximin offer any promise in Crohn's disease in remission and concurrent irritable bowel syndrome-like symptoms?

ABSTRACT: Microbiota plays an important role in many diseases including inflammatory bowel diseases. Inflammatory bowel disease patients can have concurrent irritable bowel syndrome symptoms similar to those associated with a flare. The potential role of gut dysbiosis in the pathogenesis of inflammatory bowel disease provides a rationale for treating such patients with rifaximin. This study aimed to assess the efficacy of rifaximin in the management of irritable bowel syndrome-like symptoms (bloating, abdominal pain, stool consistency) and quality of life in patients with Crohn's disease in remission.The present study included 86 patients with Crohn's disease in remission (fecal calprotectin <50 µg/g, C-reactive protein <0.5 mg/dL, simple endoscopic score for Crohn's disease <2) and associated irritable bowel syndrome-like symptoms (bloating, abdominal pain, diarrhea). These patients were randomly assigned to rifaximin treatment group (44 patients) and the control group (42 patients). Besides the baseline inflammatory bowel disease treatment and antispasmodics (as needed), patients in the rifaximin treatment group received 3 repeated courses of treatment, each course being represented by 1200 mg/d of rifaximin for 10 days and 20 days free of treatment (3 months consecutively); patients in the control group also received antispamodics as needed and were observed for 3 months.Monthly analyses of bloating score, abdominal pain score, stool consistency score, and quality of life score showed significant improvement after treatment in the rifaximin group in contrast with control group. Significantly more patients in the rifaximin group than in the control group met the criteria for adequate improvement of bloating score after 3 months of treatment (59.09% vs 19.04%, P = .01), adequate improvement of abdominal pain score (54.5% vs 21.4%, P = .04), stool consistency score (34.09% vs 14.2%, P = .03), and quality of life score (70.4% vs 21.4%, P < .001).Rifaximin in a dose of 1200 mg/d, 10 d/mo, 3 months consecutively is an effective medication for concurrent irritable bowel syndrome-like symptoms in patients with Crohn's disease in remission.

Genetic Antibiotic Resistance of Helicobacter pylori in South-Eastern Romania.

BACKGROUND AND AIM: Helicobacter pylori infection is very common worldwide, and it is associated with an important gastric pathology. Treatment of this infection is difficult and consists of the combination of two or three antibiotics. However, the rate of resistance to treatment is high. Antimicrobial resistance of Helicobacter pylori is based on its cultivation in the laboratory and testing of phenotypic susceptibility, a time-consuming, laborious method. This study aimed to detect the genetic resistance to antibiotics of Helicobacter pylori in the south-eastern region of Romania. METHODS: Ninety patients with positive rapid urease test gastric biopsy samples were tested. Genetic resistance to antibiotics (fluoroquinolone and clarithromycin) was tested by GenoType HelicoDR kit (Hain Lifescience GmbH, Germany). RESULTS: Clarithromycin resistance mutations were detected in 20% of patients, the commonest mutation in our study beeing A2147G (associated with high level of clarithromycin resistance and lower cure rates). Fluoroquinolones resistance mutations were detected in 30% of patients, and the most common mutations were D91N, D91G, and N87K. There was no correlation with patients gender or age, with the exception of fluoroquinolone resistance, which was detected more frequently in females.   Conclusions. Clarithromycin and fluoroquinolone resistance of Helicobacter pylori is moderately high in our study. There is a need for monitoring Helicobacter resistance patterns in Romania to provide data that can guide empirical treatment. This is the first published study on the genetic resistance of Helicobacter pylori in Romania.

Timing of paracentesis and outcomes in hospitalized patients with decompensated cirrhosis.

BACKGROUND: Ascites is one of the most common complications of cirrhosis, placing a significant burden on the healthcare system. Data regarding the optimal time of paracentesis and outcomes among patients with cirrhosis and ascites are scarce. AIM: To assess the outcomes of patients who underwent paracentesis within 12 h after admission compared to patients who underwent paracentesis later than 12 h. METHODS: The study included 185 patients with cirrhosis and ascites who underwent paracentesis. The early paracentesis group was defined as paracentesis performed < 12 h after admission (65 patients) and the delayed paracentesis group was defined as paracentesis performed > 12 h after admission (120 patients). New-onset complications of cirrhosis, length of hospital stay, weekday or weekend admission, in-hospital mortality rate, and 90-d readmission rates were assessed and compared between the groups. RESULTS: Significantly more patients in the delayed paracentesis group than in the early paracentesis group developed hepatic encephalopathy (45% vs 21.5%, P < 0.01), hepato-renal syndrome (21.6% vs 9.2%, P = 0.03) and infections (25% vs 10.7%, P = 0.02) during hospitalization. There were no statistically significant differences in the occurrence of spontaneous bacterial peritonitis and upper gastrointestinal bleeding between the two groups. Length of stay was shorter in the early paracentesis group than in the delayed paracentesis group (6.7 d vs 12.2 d) and in-hospital mortality was lower among patients in the early paracentesis group. Patients in the delayed paracentesis group had a higher risk of developing complications during hospitalization. CONCLUSION: Early paracentesis (within 12 h after admission) could be a new inpatient quality metric among patients hospitalized with cirrhosis and ascites as it is associated with fewer complications of cirrhosis, lower in-hospital mortality and shorter length of stay.

Triple Antioxidant Therapy, an Alternative for Patients with Chronic Liver Disease - A Prospective Multicenter Interventional Study.

Background: Non-alcoholic fatty liver disease (NAFLD) has increased exponentially in recent years in Western European countries, where the number of hepatitis of viral etiology has been declining, and it is thought to be the most common cause of chronic liver disease in the near future (1). Currently, NAFLD is both the second most common cause of hepatocellular carcinoma (HCC) and the second most common indication for liver transplantation (2-4). This problem is very serious, as cases of NAFLDs are increasingly in children, a population with a long life ahead, and in whom the disease has all the time to progress to cirrhosis and HCC (5, 6). Objectives: The goal of this prospective study is to determine the effect of an original formula consisting in silymarin, organic selenium and alpha lipoic acid, in reducing liver damage in patients with chronic liver disease. Material and methods: The study started in March 2018, initially with a group of patients from Bucharest, integrated in the study at St. Mary's Hospital. In October 2018 it was expanded at the national level to 1 718 patients, monitored by 145 investigating physicians from 134 centers, with an average of 11.8 patients per investigating physician. Outcomes: Taking each stage of fatty liver disease (FLD) at T0 moment (the beginning of the study), we observed that 25% of patients with grade I FLD had no sign of disease at the end of the study, 74% of those with grade II FLD recovered or improved their health, and 83% of patients with grade III FLD recovered or improved their health. There were 149 patients with no FLD detected at the end of the study (recovered). Conclusion: Based on triple antioxidant therapy, the original formula improved the evolution and prognosis of patients with chronic liver disease.

Fabry's disease.

Fabry's disease is a rare X-linked, recessive, glycolipid storage disorder. It is caused by the deficient activity of a lysosomal enzyme, alpha-galactosidase A. Deficiency of alpha-GAL causes an inability to catabolize the lipids with cellular accumulation of its most abundant substrate, globotriaosylceramide (GL-3), and other neutral glycosphingolipids in the vascular endothelium and numerous tissues throughout the body. This progressive glycosphingolipid accumulation leads to life-threatening clinical sequelae in renal, cardiac and cerebrovascular systems. Heterozygous Fabry's disease is less studied. We present a patient, 43 years old, with cardiac (hypertrophic cardiomyopathy), neurological (sensitive-motive polyneuropathy), digestive (chronic diarrheea), renal and cutaneous involvements.

The feasibility of FOBT tests in colorectal cancer screening in Dobrogea.

BACKGROUND AND AIM: The high incidence of colorectal cancer in Eastern Europe and the declining mortality due to this pathology in the Western World, where screening programs for cancer are available, prove the necessity of implementing colorectal cancer screening in Romania, too. The aim of our study was to detect colorectal cancer in asymptomatic stages, where surgical treatment could be curative. METHOD: The study was conducted in the Gastroenterology Department of Emergency Hospital, Constanta County, over a period of 18 months. We recruited apparently healthy people following all criteria recommended by the guidelines. RESULTS: From the total of 1098 patients included in the study, 162 patients with FOBT test positive followed the screening program undergoing colonoscopy or barium enema investigation. The rate of acceptance regarding the screening procedures was 70.3%. Advanced colon lesions were found in 14 patients (1.27%) and cancers in 7 cases (0.63%). According to TNM classification 5 cancers (71.4%) were surgically curative (TNM I/II/III) and 2 (28.5%) were advanced (TNM IV). The positive predictive value (PPVs) of FOBT for cancer was 4.7%. CONCLUSION: Even if the effect of screening on mortality was not demonstrated, our study results confirm the necessity of colorectal cancer screening in our country, as it is worldwide, detecting cancers in curative stages. The detection rate of FOBT positive tests for neoplasia was similar to other studies.

[Early diagnosis of lung cancer in Constanta county--preliminary results]. / Diagnosticul precoce al cancerului bronhopulmonar (CBP) în judetul Constanta--rezultate preliminarii.

Lung cancer (LC) has an increasing incidence and mortality rate in both sexes in Romania. Due to its gravity, early detection of LC (stages 0, I, II) is very important. We analyzed a group of 161 patients with LC. Early LC was present in 22% (36 patients). More than half of them were in stage II. All patients had high risk for LC: smokers, man, and age over 50. Suggestive symptomatology of early LC included: cough and its change of pattern, hemoptysis and loss of weight. In 95% of these patients radiological abnormalities were already present. Bronchoscopy (including biopsy brushing, bronchial aspiration and bronchial washing) was the main diagnostic procedure for central type LC, but was also useful in peripheral type. Sputum analysis was positive in 92% of cases. Early detection of LC needs an active diagnosis in all patients with high risk, with all available diagnostic procedures (including high resolution computed tomography).