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Düsseldorf, Germany

Weinmann A.,Johannes Gutenberg University Mainz | Sattler T.,University of Heidelberg | Unold H.-P.,Kreuznacher Diakonie Hospital | Grambihler A.,Johannes Gutenberg University Mainz | And 7 more authors.
Journal of Clinical Gastroenterology | Year: 2015

Goals: The aim of this study was to assess the long-term outcome of primary biliary cirrhosis (PBC) patients and to test the clinical value of various outcome models, such as the Mayo Risk Score (MRS), in a large single-center cohort in Germany. Background: PBC is a chronic autoimmune liver disease with a female gender predominance and a peak incidence in the fifth decade of life. PBC is characterized by portal inflammation and immune-mediated destruction of intrahepatic bile ducts in liver histology and the presence of antimitochondrial antibodies in the serum of nearly 95% of patients. In 5% to 20% of patients an overlap syndrome with autoimmune hepatitis (AIH) is diagnosed. Ursodeoxycholic acid is widely accepted as the standard medical treatment. Study: A total of 204 patients with PBC or PBC/AIH were retrospectively analyzed with regard to their clinical, biochemical, serological, and histologic features. PBC was diagnosed on the basis of the American Association for the Study of Liver Diseases criteria. Specific PBC scores, such as the MRS, the European and the Yale model, as well as nonspecific scores such as the Child-Pugh, the Model for End-stage Liver Disease, and Aspartate Aminotransferase to Platelet Ratio Index score were analyzed for their utility to predict the clinical outcome of patients. Results: One hundred eighty-four patients with PBC alone and 20 with primary biliary cirrhosis/autoimmune hepatitis overlap were followed up for an average of 7.0 (range, 0.5 to 33.2) years. Importantly, baseline values of serum bilirubin, alkaline phosphatase, immunoglobulin M (IgM) and IgG, as well as antimitochondrial antibodies titers did not allow in properly predicting patient's outcome. The MRS proved clinical applicability. Patients with an R-value <6 did not develop liver-related complications. The Aspartate Aminotransferase to Platelet Ratio Index score had a significant correlation with the histologic degree of liver fibrosis, with limited value of scores between 1.0 and 1.5. Patients with a Model for End-stage Liver Disease score ≥8 (n=17) had a significantly higher risk to undergo liver transplantation or liver-related death. Outcome was less favorable than predicted by the European model. All scores showed low positive predictive values, limiting their applicability in clinical practice. Conclusions: Herein, we demonstrate that clinical risk scores in PBC should be interpreted with care. The MRS proved to be helpful to predict a favorable outcome. Novel approaches to predict outcome are needed to identify patients who may benefit from alternative, intensified treatment regimens. © 2014 Wolters Kluwer Health, Inc.

Anlauf M.,University Clinic of Dusseldorf
Hormone and Metabolic Research | Year: 2011

Neuroendocrine neoplasms (NEN) appear homogeneous in terms of morphology, but constitute a very heterogeneous group of tumors in terms of biological and clinical features. NEN may occur in any organ, but are most commonly observed in the lung and the gastroenteropancreatic system (GEP). The European Neuroendocrine Tumor Society (ENETS) developed guidelines in the last 5 years to standardize and improve the diagnosis and therapy of GEP-NEN. Taking these guidelines into account, the TNM classification of the Union for International Cancer Control (UICC) was introduced in 2009. The new GEP-NEN classification of the World Health Organization (WHO) was presented 1 year later. According to the guidelines of the ENETS, the UICC, and the WHO, the pathology classification of NEN of GEP consists of several basic components: (1) evidence of the neuroendocrine nature of the tumor, (2) histological distinction between well and poorly differentiated tumors, (3) proliferation- based grading. (4) TNM staging (including data about vascular invasion and resection margins), (5) with reference to the clinical question: evidence of hormones and biogenic amines, and (6) optional, especially in cases of initial diagnosis of NEN: expression of the somatostatin receptor type 2A. Based on these criteria, a standardized prognostic stratification of GEP-NEN can be performed in combination with other clinical parameters. The novel classifications constitute the basis for selecting the procedures of molecular and metabolic imaging as well as for tumor- specific treatments and permit comparisons of larger tumor populations. Close interdisciplinary cooperation is a prerequisite. © Georg Thieme Verlag KG Stuttgart - New York.

Tornero E.,Bone and Joint Infection Unit | Senneville E.,Gustave Dron Hospital of Tourcoing | Euba G.,Hospital Universitari Of Bellvitge | Petersdorf S.,University Clinic of Dusseldorf | And 16 more authors.
Clinical Microbiology and Infection | Year: 2014

The objective of this study was to review the characteristics and outcome of prosthetic joint infections (PJI) due to Enterococcus sp. collected in 18 hospitals from six European countries. Patients with a PJI due to Enterococcus sp. diagnosed between January 1999 and July 2012 were retrospectively reviewed. Relevant information about demographics, comorbidity, clinical characteristics, microbiological data, surgical treatment and outcome was registered. Univariable and multivariable analyses were performed. A total of 203 patients met the inclusion criteria. The mean (SD) was 70.4 (13.6) years. In 59 patients the infection was diagnosed within the first 30 days (29.1%) from arthroplasty, in 44 (21.7%) between 31 and 90 days, in 54 (26.6%) between 91 days and 2 years and in 43 (21%) after 2 years. Enterococcus faecalis was isolated in 176 cases (89%). In 107 (54%) patients the infection was polymicrobial. Any comorbidity (OR 2.53, 95% CI 1.18-5.40, p 0.01), and fever (OR 2.65, 95% CI 1.23-5.69, p 0.01) were independently associated with failure. The only factor associated with remission was infections diagnosed later than 2 years (OR 0.25, 95% CI 0.09-0.71, p 0.009). In conclusion, prosthetic joint infections due to Enterococcus sp. were diagnosed within the first 2 years from arthroplasty in >70% of the patients, almost 50% had at least one comorbidity and infections were frequently polymicrobial (54%). The global failure rate was 44% and patients with comorbidities, fever, and diagnosed within the first 2 years from arthroplasty had a poor prognosis. © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Kruczek C.,University Clinic of Dusseldorf | Gorg B.,University Clinic of Dusseldorf | Keitel V.,University Clinic of Dusseldorf | Bidmon H.J.,Heinrich Heine University Dusseldorf | And 3 more authors.
Biological Chemistry | Year: 2011

Ammonia is a major player in the pathogenesis of hepatic encephalopathy (HE) and affects astrocyte function by triggering a self-amplifying cycle between osmotic and oxidative stress. We recently demonstrated that hypoosmotic astrocyte swelling rapidly stimulates nitric oxide (NO) production and increases intracellular free Zn 2+ concentration ([Zn 2+] i). Here we report effects of ammonia on [Zn 2+] i homeostasis and NO synthesis. In cultured rat astrocytes, NH 4Cl (5 mm) increased within 6 h both cytosolic and mitochondrial [Zn 2+]. The [Zn 2+] i increase was transient and was mimicked by the nonmetabolizable CH 3NH 3Cl, and it was dependent on NO formation, as evidenced by the sensitivity toward the nitric oxide synthase inhibitor N G-monomethyl-l-arginine. The NH 4Cl-induced NO formation was sensitive to the Ca 2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetra(acetoxymethyl) ester and increases in both NO and [Zn 2+] i were blocked by the N-methyl-d-aspartate receptor antagonist MK-801. The NH 4Cl-triggered increase in [Zn 2+] i was followed by a Zn 2+-dependent nuclear appearance of the metal response element-binding transcription factor and metallothionein messenger RNA (mRNA) induction. Metallothionein mRNA was also increased in vivo in rat cerebral cortex 6 h after an NH 4Ac challenge. NH 4Cl increased peripheral-type benzodiazepine receptor (PBR) protein expression, whereas PBR mRNA levels were decreased in a Zn 2+-independent manner. The Zn 2+-dependent upregulation of metallothionein following ammonia intoxication may reflect a cytoprotective response, whereas the increase in PBR expression may augment HE development. © 2011 by Walter de Gruyter Berlin Boston 2011.

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