Gut peptide changes in patients with obstructive jaundice undergoing biliary drainage: A prospective case control study.

BACKGROUND: Biliary obstruction is a relatively common condition that affects approximately 5 in 1000 people annually. Malnutrition is very common in patients with biliary obstruction and since it is associated with significant morbidity and mortality, it is important to identify factors and mechanisms involved in its development. AIM: To determine the influence of obstructive jaundice on the hormones controlling appetite and nutritive status. METHODS: This was a prospective case control study performed in a tertiary center in Zagreb, Croatia. Patients with biliary obstruction undergoing internal biliary drainage from September 2012 until August 2013 were enrolled. After excluding patients who developed procedure related complications or were lost in the follow-up, out of initial 73 patients, 55 patients were included in the analysis, including 34 with benign and 21 with malignant disease. Meanwhile, 40 non-jaundiced controls were also included. Appetite, nutritional status, and serum ghrelin, cholecystokinin (CCK), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were determined at admission, 48 h and 28 d after internal biliary drainage. Chi square test was used for categorical variables. Continuous variables were analysed for normality by Kolmogorov-Smirnov test and relevant non-parametric (Mann-Whitney, Kruskal-Wallis, and Friedman) or parametric (t-test and analysis of variance) tests were used. RESULTS: Patients with obstructive jaundice were significantly malnourished compared to controls, regardless of disease etiology. Plasma ghrelin and CCK levels were significantly higher in patients with obstructive jaundice. Serum bilirubin concentrations were negatively correlated with ghrelin levels and positively correlated with TNF-α, but had no correlation with CCK concentrations. After internal biliary drainage, a significant improvement of nutritional status was observed although serum concentrations of ghrelin, IL-6, and TNF-α remained significantly elevated even 28 d after the procedure. CCK levels in patients without malnutrition remained elevated 28 d after the procedure, but in patients with malnutrition, CCK levels decreased to levels comparable with those in the control group. We have not established any correlation between appetite and serum levels of ghrelin, CCK, IL-6, and TNF-α before and after biliary drainage. CONCLUSION: Possible abnormalities in ghrelin and CCK regulation may be associated with the development of malnutrition during the inflammatory response in patients with biliary obstruction.

IBD Patients' Perception of Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic and Satisfaction with Provided Healthcare: A Cross-Sectional Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 pandemic is affecting public health systems and mental health significantly. Patients with inflammatory bowel disease are witnessing vigorous organizational changes in inflammatory bowel disease centers and experiencing all psychosocial effects of the crisis. We conducted a single-center cross-sectional study in order to assess inflammatory bowel disease patients' concerns, behavior, and satisfaction with provided healthcare during severe acute respiratory syndrome coronavirus 2 pandemic. METHODS: All inflammatory bowel disease patients treated in our center from April 1 to June 1, 2020, were invited to fulfill an anonymous online questionnaire. RESULTS: A total of 132 participants have completed the questionnaire, 63.2% were female, 57.9% had Crohn's disease (CD) During the first wave of the pandemic, 74.2% of participants perceived themselves as a high-risk group for acquiring coronavirus disease 2019 only because they suffered from inflammatory bowel disease, and 66.2% thought inflammatory bowel disease medications make them more susceptible to coronavirus disease 2019. This especially concerned patients treated with biologics (B = 2.068, P < .01). Females were more stressed (B = -1.451, P < .01) and concerned (B = -1.488, P < .01) about the pandemic, and they also reported more potential benefits from professional psychological help (B = -2.664, P = .02). Six patients (5.3%) discontinued inflammatory bowel disease therapy on their own initiative. Seventy-eight (68.4%) patients were completely satisfied and 14 (12.3%) were partially satisfied with the quality of healthcare provided in our inflammatory bowel disease center. CONCLUSION: Female inflammatory bowel disease patients tend to be more emotionally vulnerable during severe acute respiratory syndrome coronavirus 2 pandemic. Although psychological support should be continuously available to all inflammatory bowel disease patients, female gender may warrant special attention. Providing patients with adequate and early information during pandemic probably leads to better compliance and higher satisfaction.

Role of Endoscopic Ultrasound in Liver Disease: Where Do We Stand?

As the burden of liver disease in the general populace steadily increases, so does the need for both advanced diagnostic and treatment options. Endoscopic ultrasound is a reliable diagnostic and therapeutic method that has an established role, foremost in pancreatobiliary pathology. This paper aims to summarize the growing role of endoscopic ultrasound in hepatology based on the search of the current literature. A number of applications of endoscopic ultrasound are reviewed, including both noninvasive methods and tissue acquisition in focal and diffuse liver disease, portal hypertension measurement, detection and management of gastric and esophageal varices, treatment of focal liver lesions and staging of pancreatobiliary malignancies, treatment of cystic and solid liver lesions, as well as liver abscess drainage. Both hepatologists and endoscopists should be aware of the evolving role of endoscopic ultrasound in liver disease. The inherent invasive nature of endoscopic examination limits its use to a targeted population identified using noninvasive methods. Endoscopic ultrasound is one the most versatile methods in gastroenterology, allowing immediate access with detection, sampling, and treatment of digestive tract pathology. Further expansion of its use in hepatology is immanent.

Prevalence and Prognostic Impact of Deranged Liver Blood Tests in COVID-19: Experience from the Regional COVID-19 Center over the Cohort of 3812 Hospitalized Patients.

BACKGROUND: Derangement of liver blood tests (LBT) is frequent in patients with Coronavirus disease 2019 (COVID-19). We aimed to evaluate (a) the prevalence of deranged LBT as well as their association with (b) clinical severity at admission and (c) 30-day outcomes among the hospitalized patients with COVID-19. METHODS: Consecutive patients with COVID-19 hospitalized in the regional referral center over the 12-month period were included. Clinical severity of COVID-19 at hospital admission and 30-day outcomes (need for intensive care, mechanical ventilation, or death) were analyzed. RESULTS: Derangement of LBT occurred in 2854/3812 (74.9%) of patients, most frequently due to elevation of AST (61.6%), GGT (46.1%) and ALT (33.4%). Elevated AST, ALT, GGT and low albumin were associated with more severe disease at admission. However, in multivariate Cox regression analysis, when adjusted for age, sex, obesity and presence of chronic liver disease, only AST remained associated with the risk of dying (HR 1.5081 and 2.1315, for elevations 1-3 × ULN and >3 × ULN, respectively) independently of comorbidity burden and COVID-19 severity at admission. Patients with more severe liver injury more frequently experienced defined adverse outcomes. CONCLUSIONS: Deranged LBTs are common among patients hospitalized with COVID-19 and might be used as predictors of adverse clinical outcomes.

Expression of adipokine ghrelin and ghrelin receptor in human colorectal adenoma and correlation with the grade of dysplasia.

BACKGROUND: Ghrelin is an adipokine that plays an important role in energy balance. Expression of ghrelin and ghrelin receptor has been investigated in different tissues and tumors. Studies regarding expression of ghrelin and ghrelin receptor in colorectal tumors are scarce and no data on expression of ghrelin and its receptor in colorectal adenomas has been published. Ghrelin and ghrelin receptor were highly expressed in colon carcinoma cells while expression was decreased in less differentiated tumors, presuming that ghrelin might be important in early phases of tumorigenesis. AIM: To investigate the expression of ghrelin and ghrelin receptor in human colorectal adenomas and adjacent colorectal tissue. METHODS: In this prospective study (conducted from June 2015 until May 2019) we included 92 patients (64 male and 28 female) who underwent polypectomy for colorectal adenomas in the Department of Gastroenterology and Hepatology, "Sestre milosrdnice" Clinical Hospital Center in Zagreb, Croatia. After endoscopic removal of colorectal adenoma, an additional sample of colon mucosa in the proximity of the adenoma was collected for pathohistological analysis. Adenomas were graded according to the stage of dysplasia, and ghrelin and ghrelin receptor expression were determined immunohistochemically in both adenoma and adjacent colon tissue using the polyclonal antibody for ghrelin (ab150514, ABCAM Inc, Cambridge, United States) and ghrelin receptor (ab48285, ABCAM Inc, Cambridge, United States). Categorical and nominal variables were described through frequencies and proportions and the difference between specific groups were analyzed with Fisher's and Fisher-Freeman-Halton's method respectively. Spearman's rank correlation coefficient was determined for correlation of expression of ghrelin and ghrelin receptor in adenoma and adjacent colon tissue with the grade of adenoma dysplasia. RESULTS: Among 92 patients with colorectal adenoma 43 had adenomas with high-grade dysplasia (46.7%). High expression of ghrelin was 7 times more common in high-grade adenoma compared to low-grade adenomas (13.95% to 2.04%, P = 0.048), while the expression of ghrelin in adjacent colon tissue was low. We found no correlation between ghrelin receptor expression in adenoma and adjacent colon tissue and the grade of colorectal adenoma dysplasia. The most significant correlation was found between ghrelin and ghrelin receptor expression in adenomas with high-grade dysplasia (rho = 0.519, P < 0.001). CONCLUSION: Ghrelin and ghrelin receptor are expressed in colorectal adenoma and adjacent tissue with ghrelin expression being more pronounced in high grade dysplasia as a possible consequence of increased local synthesis.

Candidemia after endoscopic therapy with lumen-apposing metal stent for pancreatic walled-off necrosis.

Necrotizing pancreatitis remains a challenging and unpredictable condition accompanied by various complications. Endoscopic ultrasound-guided transmural drainage and necrosectomy have become the standard treatment for patients with walled-off necrosis (WON). Endoscopic therapy via lumen-apposing metal stents (LAMS) with large diameters has shown success in the management of pancreatic fluid collections, but there are few data on specific complications of that therapy. We report a case of infected WON and concomitant fungemia following LAMS placement and necrosectomy. In addition, a systematic literature review of current related studies has been provided.

Bleeding Peptic Ulcer - Tertiary Center Experience: Epidemiology, Treatment and Prognosis.

The aim of this study was to demonstrate epidemiological, clinical and endoscopic characteristics of acute upper gastrointestinal bleeding (UGIB) with special reference to peptic ulcer bleeding (PUB). The study included 2198 consecutive patients referred to our emergency department due to acute UGIB from January 2008 to December 2012. All patients underwent urgent upper GI endoscopy within 24 hours of admission, and 842 patients diagnosed with PUB were enrolled and prospectively followed-up. The cumulative incidence of UGIB was 126/100,000 in the 5-year period. Two out of five patients had a bleeding peptic ulcer; in total, 440 (52.3%) had bleeding gastric ulcer, 356 (42.3%) had bleeding duodenal ulcer, 17 (2%) had both bleeding gastric and duodenal ulcers, and 29 (3.5%) patients had bleeding ulcers on gastroenteric anastomoses. PUB was more common in men. The mean patient age was 65.9 years. The majority of patients (57%) with PUB were taking agents that attenuate the cytoprotective function of gastric and duodenal mucosa. Rebleeding occurred in 77 (9.7%) patients and 47 (5.9%) patients required surgical intervention. The 30-day morality was 5.2% and 10% of patients died from uncontrolled bleeding and concomitant diseases. In conclusion, PUB is the main cause of UGIB, characterized by a significant rebleeding rate and mortality.

Glasgow Blatchford, pre-endoscopic Rockall and AIMS65 scores show no difference in predicting rebleeding rate and mortality in variceal bleeding.

OBJECTIVE: To compare the performance of the Glasgow Blatchford score (GBS), pre-endoscopic Rockall score (PRS) and AIMS65 score in predicting specific clinical endpoints following variceal upper gastrointestinal hemorrhage (UGIH). MATERIAL AND METHODS: Between January 2008 and December 2013, we retrospectively analyzed 225 consecutive hospitalized patients managed for endoscopically confirmed UGIH. RESULTS: A total of 225 patients (mean age 61.3 years), mostly diagnosed with alcoholic cirrhosis (195/86.7%), presented with variceal UGIH during the study period. Rebleeding occurred in 22 (9.8%) patients and 30-day mortality was 39 (17.3%). Initial hemostasis was achieved with N-butyl cyanoacrylate (151/79.1%) and endoscopic variceal ligation (40/20.9%), while secondary rebleeding prophylaxis in 110 (48.9%) patients was accomplished using endoscopic variceal ligation (92%). The majority of patients died from the underlying disease, while 12 (30.8%) died from bleeding. Median hospital stay was 6 (1-35) days. There was no statistically significant difference among AIMS65, GBS and PRS in predicting mortality (AUROC 0.70 vs. 0.64 vs. 0.66) or rebleeding rates (AUROC 0.74 vs. 0.60 vs. 0.67). The GBS was superior in predicting the need for blood transfusion compared to AIMS65 score (AUROC 0.75 vs. 0.61, p = 0.01) and PRS (AUROC 0.75 vs. 0.58, p = 0.009). CONCLUSIONS: The AIMS65, GBS and PRS scores are comparable but not useful for predicting outcome in patients with variceal UGIH because of poor discriminative ability. The GBS is superior in predicting the need for transfusion compared to AIMS65 score and PRS.

Hepatitis C Virus, Insulin Resistance, and Steatosis.

Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide. Liver steatosis is a common finding in many hepatic and extrahepatic disorders, the most common being metabolic syndrome (MS). Over time, it has been shown that the frequent coexistence of these two conditions is not coincidental, since many epidemiological, clinical, and experimental studies have indicated HCV to be strongly associated with liver steatosis and numerous metabolic derangements. Here, we present an overview of publications that provide clinical evidence of the metabolic effects of HCV and summarize the available data on the pathogenetic mechanisms of this association. It has been shown that HCV infection can induce insulin resistance (IR) in the liver and peripheral tissues through multiple mechanisms. Substantial research has suggested that HCV interferes with insulin signaling both directly and indirectly, inducing the production of several proinflammatory cytokines. HCV replication, assembly, and release from hepatocytes require close interactions with lipid droplets and host lipoproteins. This modulation of lipid metabolism in host cells can induce hepatic steatosis, which is more pronounced in patients with HCV genotype 3. The risk of steatosis depends on several viral factors (including genotype, viral load, and gene mutations) and host features (visceral obesity, type 2 diabetes mellitus, genetic predisposition, medication use, and alcohol consumption). HCV-related IR and steatosis have been shown to have a remarkable clinical impact on the prognosis of HCV infection and quality of life, due to their association with resistance to antiviral therapy, progression of hepatic fibrosis, and development of hepatocellular carcinoma. Finally, HCV-induced IR, oxidative stress, and changes in lipid and iron metabolism lead to glucose intolerance, arterial hypertension, hyperuricemia, and atherosclerosis, resulting in increased cardiovascular mortality.

[Etiology of erythema nodosum in rheumatology outpatient clinic]. / Etiologija nodoznog eritema u bolesnika u reumatoloskoj ambulanti.

Erythema nodosum (EN) is a skin lesion presenting with the acute appearance of red nodular eflorescences caused by a reactive immunological process. In most cases EN regresses spontaneously within 3 to 6 weeks and often recurs. This paper is based on a sample of 98 patients from Croatia which were treated in a rheumatologic outpatient clinic by the same internal medicine and rheumatology specialist. Presentation and differences between secondary and idiopathic forms of EN in the Croatian population were analyzed. The results show the final proportion of EN associated with secondary etiology as 47/98. Secondary etiology of EN included mostly infectious diseases (23/98), sarcoidosis (18/98) and IBD (4/98). Comparison of various clinical and laboratory parameters of both idiopathic and secondary EN resulted in a small number of statistically significant differences found (sore throat, recent respiratory infections, ASO titer changes, antibiotics use). The conclusion is that the approach to patients with EN starts by a careful taking of patient history, with an emphasis on recent upper respiratory tract infections and occurrence of diarrhea. A thorough physical examination, basic hematological and biochemical tests, basic inflammatory markers (ESR, CRP), chest X-ray and PPD test are required to determine which patients need further evaluation. A throat swab and/or determination of the titer ofASO on two occasions at intervals of 2-4 weeks should be done. It is important to perform regular patient follow-up. Considering literature substantiated regional differences in the etiology of EN it is recommended that for each population the prevalence of individual causes of EN is determined and the clinical approach accordingly standardized.