Melatonin as a Promising Anti-Inflammatory Agent in an In Vivo Animal Model of Sepsis-Induced Rat Liver Damage.

Melatonin (MLT), earlier described as an effective anti-inflammatory agent, could be a beneficial adjunctive drug for sepsis treatment. This study aimed to determine the effects of MLT application in lipopolysaccharide (LPS)-induced sepsis in Wistar rats by determining the levels of liver tissue pro-inflammatory cytokines (TNF-α, IL-6) and NF-κB as well as hematological parameters indicating the state of sepsis. Additionally, an immunohistological analysis of CD14 molecule expression was conducted. Our research demonstrated that treatment with MLT prevented an LPS-induced increase in pro-inflammatory cytokines TNF-α and IL-6 and NF-κB levels, and in the neutrophil to lymphocyte ratio (NLR). On the other hand, MLT prevented a decrease in the blood lymphocyte number induced by LPS administration. Also, treatment with MLT decreased the liver tissue expression of the CD14 molecule observed after sepsis induction. In summary, in rats with LPS-induced sepsis, MLT was shown to be a significant anti-inflammatory agent with the potential to change the liver's immunological marker expression, thus ameliorating liver function.

Prediction of in-hospital mortality after acute upper gastrointestinal bleeding: cross-validation of several risk scoring systems.

OBJECTIVE: We aimed to identify the clinical, biochemical, and endoscopic features associated with in-hospital mortality after acute upper gastrointestinal bleeding (AUGIB), focusing on cross-validation of the Glasgow-Blatchford score (GBS), full Rockall score (RS), and Cedars-Sinai Medical Center Predictive Index (CSMCPI) scoring systems. METHODS: Our prospective cross-sectional study included 156 patients with AUGIB. Several statistical approaches were used to assess the predictive accuracy of the scoring systems. RESULTS: All three scoring systems were able to accurately predict in-hospital mortality (area under the receiver operating characteristic curve [AUC] > 0.9); however, the multiple logistic model separated the presence of hemodynamic instability (state of shock) and the CSMCPI as the only significant predictive risk factors. In compliance with the overall results, the CSMCPI was consistently found to be superior to the other two systems (highest AUC, highest sensitivity and specificity, highest positive and negative predictive values, highest positive likelihood ratio, lowest negative likelihood ratio, and 1-unit increase in CSMCPI associated with 6.3 times higher odds of mortality), outperforming the GBS and full RS. CONCLUSIONS: We suggest consideration of the CSMCPI as a readily available and reliable tool for accurately predicting in-hospital mortality after AUGIB, thus providing an essential backbone in clinical decision-making.

The role of magnetic resonance imaging in the evaluation of endometrial carcinoma.

PURPOSE: Gynecological cancers comprise about 19% of all cancers in women whereas the endometrial cancer is the most common malignant tumor of the female reproductive organs. The application of modern imaging tools plays an important role in the preoperative assessment of disease extent and allows the selection of a proper and adequate therapeutic approach for each patient. The purpose of this review was to show the role of magnetic resonance imaging (MRI) in the evaluation of endometrial carcinoma. MRI enables the display of zonal anatomy of the uterus, detection of the anomalies as well as the detection and characterization of pathological processess. Endometrial cancer is staged with the International Federation of Gynecology and Obstetrics (FIGO) classification, which was significantly revised in 2009. The FIGO classification incorporates two of the important prognostic parameters, the depth of myometrial invasion and histological grade. The depth of myometrial invasion can be accurately assessed by MRI. MRI is not officially included in the FIGO staging system. However, it is widely accepted as a suitable imaging technique for preoperative staging, treatment planning and monitoring of patients with endometrial cancer.

Perforation of gastric cancer - What should the surgeon do?

Perforation represents a rare and severe complication of gastric cancer (GC) with a large hospital mortality (8-82%). The aim of this study is to evaluate the clinical-pathological features in patients with perforated gastric cancer (PGC) and to advise the surgical treatment options. A total of 11 patients with PGC were retrospectively reviewed among 376 consecutive cases of GC operated. The clinical-pathological features including tumor stage, survival, and the type of treatment were observed. The perforation was more frequent in stage III (8 patients) and in stage IV (3 patients), but none of the cases in stage I and II GC were observed. All the patients had serosal invasion and lymph node metastasis. Limited lymphadenectomy (D0, D1) was performed in 5 patients, and extended lymphadenectomy (D2, D3) in 3 patients. Emergency gastrectomy was performed in 8 (72.8%) patients, subtotal gastrectomy in 5 (45.5%), and total gastrectomy in 3 (27.2%) cases. Three (27.2%) patients were treated by simple closure with omental patch. The overall 30-day mortality rate was 46%. The survival rate was higher among the patients who underwent curative resection (75.77±68.88 days) than in those who underwent simple closure with omental patch (18.00±24.43 days). The difference between the treatments in these groups was significant (p < 0.05). PGC required surgical emergency. Curative resection improved long-term survival in the patients with potentially curable gastric malignancy. Unsuccessful outcomes after PGC could be attributed to the poor condition of the patients and the advanced disease stage.

Gadolinium deposition within the dentate nucleus and globus pallidus after repeated administrations of gadolinium-based contrast agents-current status.

INTRODUCTION: Gadolinium-based contrast agents (GBCAs) have been used clinically since 1988 for contrast-enhanced magnetic resonance imaging (CE-MRI). Generally, GBCAs are considered to have an excellent safety profile. However, GBCA administration has been associated with increased occurrence of nephrogenic systemic fibrosis (NSF) in patients with severely compromised renal function, and several studies have shown evidence of gadolinium deposition in specific brain structures, the globus pallidus and dentate nucleus, in patients with normal renal function. METHODS: Gadolinium deposition in the brain following repeated CE-MRI scans has been demonstrated in patients using T1-weighted unenhanced MRI and inductively coupled plasma mass spectroscopy. Additionally, rodent studies with controlled GBCA administration also resulted in neural gadolinium deposits. RESULTS: Repeated GBCA use is associated with gadolinium deposition in the brain. This is especially true with the use of less-stable, linear GBCAs. In spite of increasing evidence of gadolinium deposits in the brains of patients after multiple GBCA administrations, the clinical significance of these deposits continues to be unclear. CONCLUSION: Here, we discuss the current state of scientific evidence surrounding gadolinium deposition in the brain following GBCA use, and the potential clinical significance of gadolinium deposition. There is considerable need for further research, both to understand the mechanism by which gadolinium deposition in the brain occurs and how it affects the patients in which it occurs.

Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol.

OBJECTIVE: To evaluate correlation between cumulative dose of gadobutrol and signal intensity (SI) within dentate nucleus and globus pallidus on unenhanced T1-weighted images in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios, and renal and liver functions, were evaluated after multiple intravenous administrations of 0.1 mmol/kg gadobutrol at 27, 96-98, and 168 weeks. We compared SI ratios based on the number of administrations, total amount of gadobutrol administered, and time between injections. RESULTS: Globus pallidus-to-thalamus (p = 0.025) and dentate nucleus-to-pons (p < 0.001) SI ratios increased after multiple gadobutrol administrations, correlated with the number of administrations (ρ = 0.263, p = 0.046, respectively) and depended on the length of administration (p = 0.017, p = 0.037, respectively). Patients receiving gadobutrol at 27 weeks showed the greatest increase in both SI ratios (p = 0.006; p = 0.014, respectively, versus 96-98 weeks). GGT increased at the end of the study (p = 0.004). CONCLUSION: In patients with RRMS, SI within the dentate nucleus and globus pallidus increased on unenhanced T1-weighted images after multiple gadobutrol injections. Administration of the same total amount of gadobutrol over a shorter period caused greater SI increase. KEY POINTS: Gadolinium deposition may occur within the human brain after multiple gadolinium contrast administrations. Increasing T1W signal intensity occurs within the dentate nucleus and globus pallidus. Increasing signal intensity may be a consequence of multiple administrations of gadobutrol. Administration of gadobutrol over a shorter period causes greater signal intensity increase.

Obesity and metabolic syndrome as risk factors for the development of non-alcoholic fatty liver disease as diagnosed by ultrasound.

Introduction/Aim: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease of a broad histological spectrum, characterized by the accumulation of triglycerides in more than 5% of hepatocytes in the absence of consuming alcohol in quantities harmful to the liver. The aim of our study was to determine the importance of anthropometric and laboratory parameters as well as metabolic syndrome (MS) for the diagnosis of NAFLD and to estimate their influence on the degree of liver steatosis as evaluated by ultrasound (US). Methods: The study included 86 participants, 55 of whom had fatty liver diagnosed by ultrasound and they comprised the study group. The control group consisted of 31 control subjects. During the course of hospitalization at the Clinic of Gastroenterology and Hepatology, Clinical Centre Nis, the patients had their anamnesis taken, and anthropometric measurements as well as biochemical blood analyses and abdominal ultrasound were performed. Results: The patients with NAFLD had statistically higher values of body mass index (BMI), waist circumference (WC), systolic (SBP) and diastolic blood pressure (DBP), levels of alanin and aspartate aminotransferase (ALT, AST), gamma-glutamyl transpeptidase (GGT) (p<0.001), low-density lipoprotein cholesterole (LDL), total bilirubin (TBIL) (p<0.05), total cholesterol (p<0.01), triglycerides (TGL), urates, C-reactive protein (CRP), ferritin, fibrinogenes, fasting blood glucose (FBG), insulin and Homeostasis Model Assessment (HOMA-IR) (p<0.001), whereas the levels of high-density lipoprotein cholesterol (HDL) were higher in the control group (p<0.05). In the NAFLD group, there were statistically significantly more patients with hypertension (72.73% vs. 12.90%, p<0.001) and type 2 diabetes mellitus (DM) (47.27%). Metabolic syndrome was determined in 48 (87.27%) patients of the study group. An equal number of patients, 16 of them (29.09%), had 3, 4 and 5 components of MS. In the NAFLD group there were 17 overweight (30.91%) (BMI from 25 kg/m2 to 29.9 kg/m2) and 38 (69.09%) obese patients. (BMI ≥ 30.0 kg/m2). The largest number of patients in the obesity group, 22 (40.00%) of them, had the first degree obesity (BMI from 30 kg/m2 to 34.99 kg/m2). The largest number of the NAFLD group patients - 23 (41.82%), had an ultrasound finding of grade 3 fatty liver, 20 patients (36.36%) had grade 2 and 12 (21.82%) grade 1 fatty liver. Kruskal-Wallis test and ANOVA analysis showed statistically significant differences between groups with different US grade for insulin, LDL-cholesterol, WC, BMI (p<0.05), as well as HOMA-IR and body weight (BW) (p<0.01). Metabolic syndrome was statistically more present in patients with US finding grades 2 and 3 (p<0.01) in relation to grade 1 US finding, as well as obesity, hypertension and DM type 2 (p<0.05). Conclusion: The results of our study have confirmed that a high percentage of patients with high risk factors (DM, MS, dyslipidemia, hypertension) have NAFLD.

Can probiotics improve efficiency and safety profile of triple Helicobacter pylori eradication therapy? A prospective randomized study.

Background/Aim: Some studies suggest the benefit of applying different probiotic strains in combination with antibiotics in the eradication of Helicobacter pylori (H. pylori) infection. The aim of this study was to evaluate the effect of co-administration of multiple probiotic strains with triple H. pylori eradication therapy.This prospective study included 167 patients with dyspeptic symptoms and chronic gastritis who were diagnosed with H. pylori infection and randomized into two groups. The group I of 77 patients underwent triple eradication therapy, for 7 days, with lansoprazole, 2 × 30 mg half an hour before the meal, amoxicillin 2 × 1.000 mg per 12 hours and clarithromycin 2 × 500 mg per 12 hours. After the 7th day of the therapy, lansoprazole continued at a dose of 30 mg for half an hour before breakfast for 4 weeks. The group II of 90 patients received the same treatment as the patients of the group I, with the addition of the probiotic cultures in the form of a capsule comprising Lactobacillus Rosell-52, Lactobacillus Rosell-11, Bifidobacterium Rosell-1755 and Saccharomyces boulardii, since the beginning of eradication for 4 weeks. Eradication of H. pylori infection control was performed 8 weeks after the therapy by rapid urease test and histopathologic evaluation of endoscopic biopsies or by stool antigen test for H. pylori.Eradication of H. pylori infection was achieved in 93.3% of the patients who received probiotics with eradication therapy and in 81.8% of patients who were only on eradication therapy without probiotics. The difference in eradication success was statistically significant, (p < 0.05). The incidence of adverse effects of eradication therapy was higher in the group of patients who were not on probiotic (28.6%) than in the group that received probiotic (17.7%), but the difference was not statistically significant.Multiple probiotic strains addition to triple eradication therapy of H. pylori achieves a significantly better eradication success, with fewer side effects of antibiotics.

Imaging characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL).

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is an autosomal dominant vascular disorder. Diagnosis and follow-up in patients with CADASIL are based mainly on magnetic resonance imaging (MRI). MRI shows white matter hyperintensities (WMHs), lacunar infarcts and cerebral microbleeds (CMBs). WMHs lesions tend to be symmetrical and bilateral, distributed in the periventricular and deep white matter. The anterior temporal lobe and external capsules are predilection sites for WMHs, with higher specificity and sensitivity of anterior temporal lobe involvement compared to an external capsule involvement. Lacunar infarcts are presented by an imaging signal that has intensity of cerebrospinal fluid in all MRI sequences. They are localized within the semioval center, thalamus, basal ganglia and pons. CMBs are depicted as focal areas of signal loss on T2 images which increases in size on the T2*-weighted gradient echo planar images ("blooming effect").

De novo mutation in the NOTCH3 gene causing CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is one of the most common hereditary forms of stroke, and migraine with aura, mood disorders and dementia. CADASIL is caused by mutations of the NOTCH3 gene. This mutation is inherited as an autosomal dominant trait. Most individuals with CADASIL have a parent with the disorder. In extremely rare cases, CADASIL may occur due to a spontaneous genetic mutation that occurs for unknown reasons (de novo mutation). We report a new case of patient with de novo mutation of the NOTCH3 gene and a condition strongly suggestive of CADASIL (migraine, stroke, and white matter abnormalities), except that this patient did not have any first-degree relatives with similar symptoms.

Complications after angiogram-negative subarachnoid haemorrhage: comparative study of pretruncal and nonpretruncal hemorrhage patients.

INTRODUCTION: Subarachnoid haemorrhages (SAH) of unknown aetiology usually have a mild clinical presentation, favourable outcome and low complication rate. OBJECTIVE: The aim of this study was to analyse the complications in two forms of angiogram-negative spontaneous SAH: pretruncal (PNSAH) and nonpretruncal (NPNSAH). METHODS: The study group involved 18 patients with PNSAH and 16 patients with NPNSAH. CT scan was done within 72 hours from bleeding. All patients underwent four-vessel cerebral angiography. Repeat angiography was performed in five PNSAH and all NPNSAH patients. RESULTS: Twenty-nine patients were in grade I or II of the Hunt-Hess Scale (17 PNSAH and 12 NPNSAH). There was one case of rebleeding (NPNSAH patient), 10 cases of transient acute hydrocephalus (4 PNSAH and 6 NPNSAH). Cerebral vasospasm visualized by angiographies in two NPNSAH patients was local and mild, but was not found in PNSAH patients. Acute electrocardiography changes were found in 19 patients (significantly more frequently in NPNSAH than in PNSAH, 12 and 7 patients, respectively; p = 0.037). CONCLUSION: Cardiac problems following these types of SAH are more frequent than expected, and therefore cardiac monitoring is necessary.

The model for the end-stage liver disease and Child-Pugh score in predicting prognosis in patients with liver cirrhosis and esophageal variceal bleeding.

BACKGROUND/AIM: Esophageal variceal bleeding is one of the most frequent and gravest complications of liver cirrhosis, directly life-threatening. By monitoring certain clinical and laboratory hepatocellular insufficiency parameters (Child-Pugh score), it is possible to determine prognosis in patients who are bleeding and evaluate further therapy. Recently, the Model for the End-Stage Liver Disease (MELD) has been proposed as a tool to predict mortality risk in cirrhotic patients. The aim of the study was to evaluate survival prognosis of cirrhotic patients by the MELD and Child-Pugh scores and to analyze the MELD score prognostic value in patients with both liver cirrhosis and variceal bleeding. METHODS: We retrospectively evaluated the survival rate of a group of 100 cirrhotic patients of a median age of 57 years. The Child-Pugh score was calculated and the MELD score was computed according to the original formula for each patient. We also analysed clinical and laboratory hepatocellular insufficiency parameters in order to examine their connection with a 15-month survival. The MELD values were correlated with the Child-Pugh scores. The Student's t-test was used for statistical analysis. RESULTS: Twenty-two patients died within 15-months followup. Age and gender did not affect survival rate. The Child-Pugh and MELD scores, as well as ascites and encephalopathy significantly differed between the patients who survived and those who died (p < 0.0001). The International Normalized Ratio (INR) values, serum creatinine and bilirubin were significantly higher, and albumin significantly lower in the patients who died (p < 0.0001). The MELD score was significantly higher in the group of patients who died due to esophageal variceal bleeding (p < 0.0001). CONCLUSION: In cirrhotic patients the MELD score is an excellent survival predictor at least as well as the Child-Pugh score. Increase in the MELD score is associated with decrease in residual liver function. In the group of patients with liver cirrhosis and esophageal variceal bleeding, the MELD score identifies those with a higher intrahospital mortality risk.

Endovascular treatment of hereditary hemorrhagic telangiectases of the tongue.

Hereditary hemorrhagic telangiectasia, also known as Osler-Weber-Rendu disease, is an autosomal dominant disorder involving vascular abnormalities of various organs. Telangiectases are frequently observed, predominantly on the nasal and oral mucosa. We present a case a of 53-year-old man with the tonge hemorrhagic telangiectases and epistaxis. Selective catheterization and embolization of the right lingual artery led to size redution and no bleeding from tongue telangiectases.

[Risk and causes of gastroesophageal bleeding in patients with liver cirrhosis].

BACKGROUND/AIM: Variceal bleeding is the most life-threating complication in liver cirrhosis. The aim of this study was to analyze the sources of gastroesophageal bleeding in patients with liver cirrhosis and to ascertain the risk factors of bleeding from esophageal varices. METHODS: This prospective study included 52 patients with liver cirrhosis and portal hypertension. Severity of liver dysfunction according to Child's classification, coagulation parameters, and endoscopic findings were analyzed. In patients with varices we analyzed the size, color, location of varices, and the presence of red signs. The varices were classified as small, medium and large. RESULTS: Esophageal varices were found in 76.9% of the patients. Isolated varices were present in 36.6%, and associated with other findings in 40.3%. Small varices were present in 10%, medium in 25% and large in 65% patients. Of them 55% had variceal bleeding. Variceal bleeding was present in 50% of the patients with medium and in 65.38% of the patients with large varices. There was no bleeding in the patients with small varices. Endoscopy revealed red signs before bleeding in 85% of the patients with large varices. There was a higher incidence of variceal bleeding in the Child's group B. There were no significant differences (p > 0.05) in the coagulation parameters in patients with and without variceal bleeding. Rebleeding was present in 86.36% of the patients. Most of them (52.63%) were rebleeding between 7 weeks and 12 months after the first episode of variceal bleeding. In the patients with the most severe hepatocellular dysfunction (Child's group C) the period between the first bleeding and rebleeding was the shortest (mean, 20.8 days). CONCLUSION: Our study revealed that esophageal varices are the most frequent sources of bleeding in the patients with liver cirrhosis. There is the association between the first bleeding and large varices and the red signs. Coagulation disorders and hepatic dysfunction were not related to the initial episode of variceal bleeding. The risk of early rebleeding was higher in the patients with severe hepatic dysfunction (Child's class C).