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Krpina K.,Clinical Hospital Center Rijeka
Urologia | Year: 2014

PURPOSE: The aim of the present study was to evaluate the prognostic value of the local NK cell count in patients with recurrent non-muscle-invasive bladder cancer.METHODS: The archival paraffin-embedded primary tumor specimens were derived from retrospectively-selected patients, who were treated between 1996 and 2001 for bladder cancer. The study group consisted of 46 patients who developed recurrent disease during their first two post-operative years. The control group consisted of 27 patients who did not develop recurrent disease during their first two post-operative years. Specimens were assessed immunohistochemically with standard "ABC" technique. The frequency of NK cells was expressed as total number, estimated for each tumor by counting the positive NK cells in 10 high-power representative fields. Statistical analysis was done using Kruskal-Wallis test.RESULTS: Patients with recurrent non-muscle invasive bladder cancer in general have significantly higher values of stromal NK cell count than the control group. Patients with single tumor and smaller tumors show a statistically significant difference in NK cell count between study and control group. There also exists a statistically significant difference in stromal NK cell count in patients with clinical stage Ta tumor.CONCLUSIONS: Our results confirm an association of the bladder wall NK cell count in bladder cancer patients with the natural history of disease. Further well-performed, reproducible, large, prospective investigation stratified by clinical parameters, such as tumor number and diameter, is needed to display the true value of this marker in the clinical work-up of bladder cancer patients.


Brncic N.,Clinical Hospital Center Rijeka | Gorup L.,Clinical Hospital Center Rijeka | Strcic M.,Clinical Hospital Center Rijeka | Abram M.,Clinical Hospital Center Rijeka | Mustac E.,University of Sfax
Journal of Clinical Microbiology | Year: 2012

Nontyphoidal salmonellae can cause breast infection only exceptionally. A case of breast abscess in a 70-year-old man due to Salmonella enterica serotype Enteritidis (Salmonella Enteritidis) is reported. The infection was successfully treated with a combination of surgical and antibiotic treatment. Copyright © 2012, American Society for Microbiology. All Rights Reserved.


Plavsic I.,Clinical Hospital Center Rijeka | Hauser G.,Clinical Hospital Center Rijeka | Tkalcic M.,University of Rijeka | Pletikosic S.,University of Rijeka | Salkic N.,University of Tuzla
Gastroenterology Research and Practice | Year: 2015

Irritable bowel syndrome is a disorder diagnosed on symptom-based criteria without inclusion of any objective parameter measurable by known diagnostic methods. Heterogeneity of the disorder and overlapping with more serious organic diseases increase uncertainty for the physician's work and increase the cost of confirming the diagnosis. This paper is an attempt to summarize the efforts to find adequate biomarkers for irritable bowel syndrome, which should shorten the time to diagnosis and reduce the cost. Most of the reviewed papers were observational studies from secondary care institutions. Since publication of the Rome III criteria in 2006, most recent studies use these for the recruitment of IBS patients. This is a positive step forward as future studies should use the same criteria, facilitating comparison of their results. Among the studied biomarkers, most evidence is provided for fecal calprotectin. Cutoff values for fecal calprotectin have still to be investigated prior to inclusion in the irritable bowel syndrome diagnostic algorithm. © 2015 Ivana Plavšić et al.


Salkic N.N.,University of Tuzla | Jovanovic P.,University of Tuzla | Hauser G.,Clinical Hospital Center Rijeka | Brcic M.,University of Tuzla
American Journal of Gastroenterology | Year: 2014

OBJECTIVES:Extent of liver fibrosis is one of the most important factors in determining prognosis and the need for active treatment in chronic hepatitis B (CHB). Noninvasive alternatives such as FibroTest/Fibrosure (FT) have been developed in order to overcome the shortcomings of liver biopsy (LB). We aimed to systematically review studies describing the diagnostic accuracy of FT for predicting CHB-related fibrosis.METHODS:MEDLINE and EMBASE searches and hand searching methods were performed to identify studies that assessed the diagnostic accuracy of FibroTest in HB patients using LB as a reference standard. We used a hierarchical summary receiver operating curves model and the bivariate model to produce summary receiver operating characteristic curves and pooled estimates of sensitivity and specificity.RESULTS:We included 16 studies (N=2494) and 13 studies (N=1754) in the heterogenous meta-analysis for liver fibrosis and cirrhosis, respectively. The area under the hierarchical summary receiver operating curve for significant liver fibrosis and for all included studies was 0.84 (95% confidence interval (CI): 0.78-0.88). At the FT threshold of 0.48, the sensitivity, specificity, and diagnostic odds ratio (DOR) of FT for significant fibrosis were 61 (48-72%), 80 (72-86%), and 6.2% (3.3-11.9), respectively. The area under the hierarchical summary receiver operating curve for liver cirrhosis and for all included studies was 0.87 (95% CI: 0.85-0.90). At the FT threshold of 0.74, the sensitivity, specificity, and DOR of FT for cirrhosis were 62 (47-75%), 91 (88-93%), and 15.7% (8.6-28.8), respectively.CONCLUSIONS:FibroTest is of value in exclusion of patients with CHB-related cirrhosis, but has suboptimal accuracy in the detection of significant fibrosis and cirrhosis. It is necessary to further improve the test or combine it with other noninvasive modalities in order to improve accuracy. © 2014 by the American College of Gastroenterology.


Bralic M.,Clinical Hospital Center Rijeka | Stemberga V.,University of Rijeka | Stifter S.,University of Rijeka
Medical Hypotheses | Year: 2012

Traumatic brain injury (TBI) is a major cause of death and disability throughout the world. In recent years, researchers focused on the pathological significance of calcium accumulation in the brain after TBI. Neuronal calcium homeostasis disturbances may result in the activation of calpain a ubiquitous calcium-sensitive protease. The calpain family has a well-established causal role in neuronal cell death following acute brain injury: their activation has been observed to progressively increase after either contusive or diffuse brain trauma in animals, suggesting calpain to be a mediator of early neuronal damage.We hypothesize that pretreatment with the calpain inhibitors in population at objective risk (military soldiers' pre combat) in appropriate dose would open therapeutic time window expected to prevent and reduce extensive brain damage by providing optimal TBI neuroprotection. Additional therapeutic strategy for TBI, based on calpain modulating actions such as pretreatment with calpain inhibitors has been proposed.Since calpain overexpression has been well established in acute neuronal injury and further subsequent neurodegeneration, from a clinical viewpoint, we speculate that if this hypothesis proves correct pretreatment inhibitors introduction may become a therapeutic option for different brain pathologies to be approached and treated with. © 2012 Elsevier Ltd.


Hauser G.,Clinical Hospital Center Rijeka | Pletikosic S.,University of Rijeka | Tkalcic M.,University of Rijeka
World Journal of Gastroenterology | Year: 2014

Irritable bowel syndrome (IBS) is considered a biopsychosocial disorder, whose onset and precipitation are a consequence of interaction among multiple factors which include motility disturbances, abnormalities of gastrointestinal sensation, gut inflammation and infection, altered processing of afferent sensory information, psychological distress, and affective disturbances. Several models have been proposed in order to describe and explain IBS, each of them focusing on specific aspects or mechanisms of the disorder. This review attempts to present and discuss different determinants of IBS and its symptoms, from a cognitive behavioral therapy framework, distinguishing between the developmental predispositions and precipitants of the disorder, and its perpetuating cognitive, behavioral, affective and physiological factors. The main focus in understanding IBS will be placed on the numerous psychosocial factors, such as personality traits, early experiences, affective disturbances, altered attention and cognitions, avoidance behavior, stress, coping and social support. In conclusion, a symptom perpetuation model is proposed. © 2014 Baishideng Publishing Group Inc. All rights reserved.


Poropat G.,Clinical Hospital Center Rijeka | Giljaca V.,Clinical Hospital Center Rijeka | Hauser G.,Clinical Hospital Center Rijeka | Stimac D.,Clinical Hospital Center Rijeka
The Cochrane database of systematic reviews | Year: 2015

BACKGROUND: Acute pancreatitis is a common and potentially lethal disease with increasing incidence. Severe cases are characterised by high mortality, and despite improvements in intensive care management, no specific treatment relevantly improves clinical outcomes of the disease. Meta-analyses suggest that enteral nutrition is more effective than conventional treatment consisting of discontinuation of oral intake with use of total parenteral nutrition. However, no systematic review has compared different enteral nutrition formulations for the treatment of patients with acute pancreatitis.OBJECTIVES: To assess the beneficial and harmful effects of different enteral nutrition formulations in patients with acute pancreatitis.SEARCH METHODS: We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Specialised Register of Clinical Trials, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 7), MEDLINE (from inception to 20 August 2013), EMBASE (from inception to 2013, week 33) and Science Citation Index-Expanded (from 1990 to August 2013); we conducted full-text searches and applied no restrictions by language or publication status.SELECTION CRITERIA: We considered randomised clinical trials assessing enteral nutrition in patients with acute pancreatitis. We allowed concomitant interventions if they were received equally by all treatment groups within a trial.DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and extracted data. We performed the analysis using Review Manager 5 (Review Manager 2013) and both fixed-effect and random-effects models. We expressed results as risk ratios (RRs) for dichotomous data, and as mean differences (MDs) for continuous data, both with 95% confidence intervals (CIs). Analysis was based on an intention-to-treat principle.MAIN RESULTS: We included 15 trials (1376 participants) in this review. We downgraded the quality of evidence for many of our outcomes on the basis of high risk of bias. Low-quality evidence suggests that immunonutrition decreases all-cause mortality (RR 0.49, 95% CI 0.29 to 0.80). The effect of immunonutrition on other outcomes from a subset of the included trials was uncertain. Subgrouping trials by type of enteral nutrition did not explain any variation in effect. We found mainly very low-quality evidence for the effects of probiotics on the main outcomes. One eligible trial in this comparison reported a higher rate of serious adverse events leading to increased organ failure and mortality due to low numbers of events and low risk of bias. When we excluded this study as a post hoc sensitivity analysis, risks of mortality (RR 0.30, 95% CI 0.10 to 0.84), organ failure (RR 0.74, 95% CI 0.59 to 0.92) and local septic complications (RR 0.40, 95% CI 0.22 to 0.72) were lower with probiotics. In one trial assessing immunonutrition with probiotics and fibres, no deaths occurred, but hospital stay was shorter with immunonutrition (MD -5.20 days, 95% CI -8.73 to -1.67). No deaths were reported following semi-elemental enteral nutrition (EN), and the effect on length of hospital stay was small (MD 0.30 days, 95% CI -0.82 to 1.42). Fibre-enriched formulations reduced the number of other local complications (RR 0.52, 95% CI 0.32 to 0.87) and length of hospital stay (MD -9.28 days, 95% CI -13.21 to -5.35) but did not significantly affect all-cause mortality (RR 0.23, 95% CI 0.03 to 1.84) and other outcomes. Very low-quality evidence from the subgroup of trials comparing EN versus no intervention showed a decrease in all-cause mortality with EN (RR 0.50, 95% CI 0.29 to 0.86).AUTHORS' CONCLUSIONS: We found evidence of low or very low quality for the effects of immunonutrition on efficacy and safety outcomes. The role of supplementation of enteral nutrition with potential immunomodulatory agents remains in question, and further research is required in this area. Studies assessing probiotics yielded inconsistent and almost contrary results, especially regarding safety and adverse events, and their findings do not support the routine use of EN enriched with probiotics in routine clinical practice. However, further research should be carried out to try to determine the potential efficacy or harms of probiotics. Lack of trials reporting on other types of EN assessed and lack of firm evidence regarding their effects suggest that additional randomised clinical trials are needed. The quality of evidence for the effects of any kind of EN on mortality was low, and further studies are likely to have an impact on the finding of improved survival with EN versus no nutritional support. Evidence remains insufficient to support the use of a specific EN formulation.


Giljaca V.,Clinical Hospital Center Rijeka
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: Methotrexate has been used to treat patients with primary biliary cirrhosis as it possesses immunosuppressive properties. The previously prepared version of this review from 2005 showed that methotrexate seemed to significantly increase mortality in patients with primary biliary cirrhosis. Since that last review version, follow-up data of the included trials have been published. OBJECTIVES: To assess the beneficial and harmful effects of methotrexate for patients with primary biliary cirrhosis. SEARCH STRATEGY: Randomised clinical trials were identified by searching The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, and EMBASE (from their inception until September 2009). Reference lists were also read through. Authors of trials were contacted. SELECTION CRITERIA: We searched to include randomised clinical trials comparing methotrexate with placebo, no intervention, or another drug irrespective of blinding, language, year of publication, or publication status. DATA COLLECTION AND ANALYSIS: Our primary outcomes were mortality, and mortality or liver transplantation combined. Dichotomous outcomes were reported as relative risks (RR) and hazard ratios (HR) if applicable. Continuous outcomes were reported as mean differences (MD). MAIN RESULTS: Five trials were included. Four trials with 370 patients compared methotrexate with placebo or no intervention (three trials added an equal dose of ursodeoxycholic acid to the intervention groups). The bias risk of these trials was high. We did not find statistically significant effects of methotrexate on mortality (RR 1.32, 95% CI 0.66 to 2.64), mortality or liver transplantation combined, pruritus, fatigue, liver complications, liver biochemistry, liver histology, or adverse events. The pruritus score (MD - 0.17, 95% CI - 0.25 to - 0.09) was significantly lower in patients receiving methotrexate. The prothrombin time was significantly worsened in patients receiving methotrexate (MD 1.60 s, 95% CI 1.18 to 2.02). One trial with 85 patients compared methotrexate with colchicine. The trial had low risk of bias. Methotrexate, when compared to colchicine, did not significantly effect mortality, fatigue, liver biopsy, or adverse events. Methotrexate significantly benefited pruritus score (MD - 0.68, 95% CI - 1.11 to - 0.25), serum alkaline phosphatases (MD - 0.41 U/l, 95% CI - 0.70 to - 0.12), and plasma immunoglobulin M (MD - 0.47 mg/dl, 95% CI - 0.74 to - 0.20) compared with colchicine. Other outcomes showed no statistical difference. AUTHORS' CONCLUSIONS: Methotrexate had no statistically significant effect on mortality in patients with primary biliary cirrhosis nor the need for liver transplantation. Although methotrexate may benefit other outcomes (pruritus score, serum alkaline phosphatase, immunoglobulin M levels), there is no sufficient evidence to support methotrexate for patients with primary biliary cirrhosis.


Poropat G.,Clinical Hospital Center Rijeka
Cochrane database of systematic reviews (Online) | Year: 2011

Primary sclerosing cholangitis is a progressive chronic cholestatic liver disease that usually leads to the development of cirrhosis. Studies evaluating bile acids in the treatment of primary sclerosing cholangitis have shown a potential benefit of their use. However, no influence on patients survival and disease outcome has yet been proven. To assess the beneficial and harmful effects of bile acids for patients with primary sclerosing cholangitis. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded generally from inception through to October 2010. Randomised clinical trials comparing any dose of bile acids or duration of treatment versus placebo, no intervention, or another intervention were included irrespective of blinding, language, or publication status. Two authors extracted data independently. We evaluated the risk of bias of the trials using prespecified domains. We performed the meta-analysis according to the intention-to-treat principle. We presented outcomes as relative risks (RR) or mean differences (MD), both with 95% confidence intervals (CI). Eight trials evaluated ursodeoxycholic acid versus placebo or no intervention (592 patients). The eight randomised clinical trials have a high risk of bias. Patients were treated for three months to six years (median three years). The dosage of ursodeoxycholic acid used in the trials ranged from low (10 mg/kg body weight/day) to high (28 to 30 mg/kg body weight/day). Ursodeoxycholic acid did not significantly reduce the risk of death (RR 1.00; 95% CI 0.46 to 2.20); treatment failure including liver transplantation, varices, ascites, and encephalopathy (RR 1.22; 95% CI 0.91 to 1.64); liver histological deterioration (RR 0.89; 95% CI 0.45 to 1.74); or liver cholangiographic deterioration (RR 0.60; 95% CI 0.23 to 1.57). Ursodeoxycholic acid significantly improved serum bilirubin (MD -14.6 μmol/litre; 95% CI -18.7 to -10.6), alkaline phosphatases (MD -506 IU/litre; 95% CI -583 to -430), aspartate aminotransferase (MD -46 IU/litre; 95% CI -77 to -16), and gamma-glutamyltranspeptidase (MD -260 IU/litre; 95% CI -315 to -205), but not albumin (MD -0.20 g/litre; 95% CI -1.91 to 1.50). Ursodeoxycholic acid was safe and well tolerated by patients with primary sclerosing cholangitis. We did not find enough evidence to support or refute the use of bile acids in the treatment of primary sclerosing cholangitis. However, bile acids seem to lead to a significant improvement in liver biochemistry. Therefore, more randomised trials are needed before any of the bile acids can be recommended for this indication.


Atalic B.,Clinical Hospital Center Rijeka
AMHA - Acta Medico-Historica Adriatica | Year: 2015

Emanuel Edward Klein (1844 - 1925) was a British microbiologist of Croatian origin. He was born in Osijek in what is currently the Republic of Croatia and which was then part of the Habsburg Monarchy, he completed his medical studies in Vienna in 1869, and went on to spend his entire career in London. Although trained as an anatomist, embryologist and histologist, his main area of research was microbiology. Due to the fact that back then it was a new and fast developing discipline, he was able to pursue his interests in many directions and make significant discoveries, such as the identification of the ‘Bacillus enteritidis sporogenes’ as a cause of summer hospital diarrhoeas. Although the overwhelming majority of his researches dealt with bacteria which attacked humans, in 1892 he published a book entitled The Etiology and Pathology of Grouse Disease, Fowl Enteritis, and Some Other Diseases Affecting Birds, which revealed the results of his experiments on the bacteria which affected birds. In the context of the general development of the microbiology, this paper tries to give an objective evaluation of this until now widely neglected book. © 2015, Croatian Scientific Society for the History of Health. All rights reserved.

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