Treating critically ill patients with probiotics: Beneficial or dangerous?

Probiotic bacteria are live microorganisms which confer to health benefits of the host. They help to maintain the integrity of the intestinal barrier function by modulating the mucosal and systemic immune response of the host. These bacteria have proven their beneficial effect in several conditions of ulcerative colitis. More recently probiotics/synbiotics have been included in the treatment of critically ill patients. However to date it remains uncertain whether probiotics/synbiotics are beneficial or even dangerous to the clinical outcome of this patient group. This article reviews the current evidence of the use of bacteria in critically ill patients in intensive care settings

Implications of growth factor alterations in the treatment of pancreatic cancer

Pancreatic cancer ranks fifth as a cause of cancer-related death in the world with an overall 5-year survival rate of less than 1% and a median survival of less than a year after tumour detection. Most of these patients have already metastases at the time of diagnosis. The oncologic strategies such as chemotherapy, radiotherapy, antihormonal modalities or the systemic use of specific monoclonal antibodies have not achieved a significant improvement in the survival of pancreatic cancer patients. Recent studies suggest that alterations in molecular pathways, particularly in growth factor mediated mechanisms, that regulate cell proliferation and differentiation play a pivotal role in the pathogenesis of this cancer. The molecular knowledge regarding changes in the expression of growth factors in pancreatic cancer has the potential to improve diagnostic and therapeutic treatment strategies in the near future

Functional and Topological Properties in Hepatocellular Carcinoma Transcriptome

Hepatocellular carcinoma (HCC) is a leading cause of global cancer mortality. However, little is known about the precise molecular mechanisms involved in tumor formation and pathogenesis. The primary goal of this study was to elucidate genome-wide molecular networks involved in development of HCC with multiple etiologies by exploring high quality microarray data. We undertook a comparative network analysis across 264 human microarray profiles monitoring transcript changes in healthy liver, liver cirrhosis, and HCC with viral and alcoholic etiologies. Gene co-expression profiling was used to derive a consensus gene relevance network of HCC progression that consisted of 798 genes and 2,012 links. The HCC interactome was further confirmed to be phenotype-specific and non-random. Additionally, we confirmed that co-expressed genes are more likely to share biological function, but not sub-cellular localization. Analysis of individual HCC genes revealed that they are topologically central in a human protein-protein interaction network. We used quantitative RT-PCR in a cohort of normal liver tissue (n = 8), hepatitis C virus (HCV)-induced chronic liver disease (n = 9), and HCC (n = 7) to validate co-expressions of several well-connected genes, namely ASPM, CDKN3, NEK2, RACGAP1, and TOP2A. We show that HCC is a heterogeneous disorder, underpinned by complex cross talk between immune response, cell cycle, and mRNA translation pathways. Our work provides a systems-wide resource for deeper understanding of molecular mechanisms in HCC progression and may be used further to define novel targets for efficient treatment or diagnosis of this disease

Inflammatory Myofibroblastic Tumor of the Pancreatic Head: An Unusual Cause of Recurrent Acute Pancreatitis – Case Presentation of a Palliative Approach after Failed Resection and Review of the Literature

Inflammatory myofibroblastic tumors (IMTs) are a rare cause of echo-poor pancreatic head enlargement. Histologically, IMTs are characterized by spindle-shaped myofibroblasts or fibroblasts accompanied by a mixed immune cell infiltration. The most common localizations of IMTs have been reported in lung, mesentery and omentum, especially in children and young adults. IMTs show infiltrating growth, multilocular appearance and also metastasis have been reported. Curative resection is the only therapeutic option so far. In the palliative situation, evident data and clear guidelines for this rare tumor entity are missing. We report on a 44-year-old male with an unresectable IMT of the pancreatic head causing recurrent episodes of acute pancreatitis that resulted in a chronic obstructive course of the disease. The patient entered a palliative therapeutic regimen including radiation therapy and antiinflammatory medication. In a regular follow-up of 12 months, he presented with stable disease after initial progression. This case of local progressive IMT of the pancreatic head was managed with a palliative therapeutic regimen and is discussed based on the current literature

Psychometric validation of the German translation of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire in patients with reflux disease

BACKGROUND: Symptoms of heartburn has an impact on health-related quality of life (HRQL). When a questionnaire is translated into a new language, a linguistic validation is necessary but not sufficient unless the psychometric characteristics have been verified. The aim is to document the psychometric characteristics of the German translation of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire. METHODS: 142 patients with symptoms of heartburn (Age: M = 47.5, ± 14.6; Males = 44.4%) completed the German translation of GSRS, the QOLRAD, the Short-Form-36 (SF-36) and the Hospital Anxiety and Depression (HAD) scale. RESULTS: The internal consistency reliability of GSRS ranged from 0.53–0.91 and of QOLRAD from 0.90–0.94, respectively. The test-retest reliability of GSRS ranged from 0.49–0.73 and of QOLRAD from 0.70–0.84. The relevant domains of the GSRS and QOLRAD domain scores significantly correlated. GSRS domains of Abdominal Pain and Constipation correlated (negatively) with most of the domains of the SF-36. The relevant QOLRAD domains significantly correlated with all SF-36 domains. CONCLUSIONS: The psychometric characteristics of the German translation of GSRS and QOLRAD were found to be good, with satisfactory reliability and validity. The reliability of the GSRS Abdominal Pain domain was moderate

The influence of gastric atrophy on Helicobacter pylori antibiotics resistance in therapy-naïve patients

Background: Antibiotic susceptibility of Helicobacter pylori to antibiotics may vary among different niches of the stomach. The progression of chronic H. pylori gastritis to atrophy changes intragastric physiology that may influence selection of resistant strains. Aim: To study the antibiotic resistance of H. pylori taking the severity of atrophic gastritis in antrum and corpus into account. Methods: Helicobacter pylori-positive patients (n = 110, m = 32, mean age 52.6 ± 13.9 years) without prior H. pylori eradication undergoing upper gastrointestinal (GI) endoscopy for dyspeptic symptoms were included in a prospective study. Patients were stratified into three groups depending on the grade of atrophy: no atrophy (OLGA Stage 0), mild atrophy (OLGA Stage I–II) and moderate/severe atrophy (OLGA Stage III–IV). Two biopsies each from the antrum and the corpus and one from the angulus were taken and assessed according to the updated Sydney system. H. pylori strains were isolated from antrum and corpus biopsies and tested for antibiotic susceptibility (AST) for amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifampicin by the agar dilution methods. A Chi-square test of independence with a 95% confidence interval was used to detect differences in the proportion of patients with susceptible and resistant H. pylori strains. Results: Among 110 patients, primary clarithromycin resistance (R) was 30.0%, both in the antrum and corpus; metronidazole resistance accounted for 36.4 and 34.5% in the antrum and corpus; and levofloxacin was 19.1 and 22.7% in the antrum and corpus, respectively. Resistance rates to amoxicillin, tetracycline, and rifampicin were below 5%. Dual antibiotic resistance rate was 21.8%, and triple resistance rate was 9.1%. There was a significant difference in the resistance rate distribution in antrum (p < 0.0001) and corpus (p < 0.0001). With increasing severity of atrophy according to OLGA stages, there was a significant increase in clarithromycin-R and metronidazole-R. Conclusion: In treatment-naïve patients, antibiotic resistance and heteroresistance were related to the severity of atrophy. The high clarithromycin resistance in atrophic gastritis suggests that H. pylori antibiotic susceptibility testing should always be performed in this condition before selecting the eradication regimen

Formulation and evaluation of floating mucoadhesive alginate beads for targetingHelicobacter pylori

Objectives: There are various obstacles in the eradication of Helicobacter.pylori (H. pylori) infections, including low antibiotic levels and poor accessibility of the drug at the site of the infection. This study describes the preparation and characterisation of novel floating-mucoadhesive alginate beads loaded with clarithromycin (CMN) for delivery to the gastric mucosa to improve the eradication of this micro-organism. Methods: Calcium alginate beads were prepared by ionotropic gelation. The formulation was modified through addition of oil and coating with chitosan in order to improve floating, mucoadhesion and modify drug release. Key findings: SEM confirmed the sphericity of the beads with X-ray microtomography (XμMT) showing the 3D structure of the beads with the layered internal structure of the bead and the even distribution of the drug within the bead. This formulation combined two gastro-retentive strategies and these formulations produced excellent in vitro floating, mucoadhesive and drug release characteristics. Enhanced stability of the beads in phosphate buffer raises a potential for the modified formulations to be targeted to regions of higher pH within the gastrointestinal tract with a higher pH. Drug release from these beads was sustained through an unstirred mucin layer simulating in vivo conditions under which the H. pylori resides in the gastric mucosa. Conclusions: This novel formulation will ensure retention for a longer period in the stomach than conventional formulations and control drug release, ensuring high local drug concentrations, leading to improved eradication of the bacteria