Rolf Fimmers

University of Bonn, Bonn, North Rhine-Westphalia, Germany

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Publications (300)1208.33 Total impact

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    ABSTRACT: Purpose To analyze choroidal thickness (CT) in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) Methods A total of 72 eyes of 72 patients (mean age 75.97±7.09 years) with GA and 37 eyes of 37 healthy controls (73.89±6.19 years) were examined by confocal scanning-laser-ophthalmoscopy and enhanced depth imaging (EDI) spectral domain optical coherence tomography. CT was measured at 25 defined points in horizontal and vertical scans. GA size was determined in fundus-autofluorescence (FAF) images and GA subtypes were classified based on abnormal FAF in the perilesional zone. Results In GA, subfoveal CT (fCT) was significantly thinner as compared to controls (173.03±90.22 µm vs. 253.95±69.19 µm, p<0.001). Analysis of averaged measurements of all 25 points obtained per patient (mCT) revealed similar results (162.07±76.26 µm vs. 228.00±66.24 µm, p<0.001). Spatial differences in CT between both groups were largest superior to the fovea. Addressing "diffuse-trickling" (n=15) and "non-diffuse-trickling" (n=57) GA independently, fCT was 114.67±43.32 µm and 188.39±93.26 µm, respectively (p=0.002) both groups being significantly thinner than controls (p=0.001 for "diffuse-trickling" and p<0.001 for "non-diffuse-trickling"). Similar results were obtained for mCT, which was 110.21±29.66 µm in "diffuse-trickling", 175.72±79.02 µm in "non-diffuse-trickling" and 228.00±66.24 µm in controls. Differences were significant with p=0.002 between both GA groups and p≤0.001 towards controls for each GA group. Conclusions The results indicate that the choroid in eyes with GA is thinner compared to normal eyes of similar age. Hereby, the extent of thinning is most pronounced in a specific subtype of GA identified by FAF imaging ("diffuse trickling"). Such GA-subtype related differences in choroidal thickness may reflect heterogeneity in the pathogenesis of disease. Copyright © 2015 by Association for Research in Vision and Ophthalmology.
    Investigative Ophthalmology &amp Visual Science 01/2015; 56(2). DOI:10.1167/iovs.14-14933 · 3.66 Impact Factor
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    ABSTRACT: In patients undergoing transcatheter aortic valve implantation (TAVI), the high prevalence of periph- eral artery disease (PAD) limits femoral access and increases vascular complications that are associated with mortality and morbidity. Our study assessed the ability of a balloon-expandable large-bore vascular sheath to increase access-site availability and to reduce vascular complications. Methods and results: Among 257 patients from two centres, 43 patients underwent transfemoral TAVI with the use of the SoloPath balloon-expandable sheath due to complex iliofemoral access anatomy. Propensity score matching (2:1) was performed except for the sheath to femoral artery ratio (SFAR). Compared to stand- ard sheath patients, we found no significant difference in 30-day and one-year mortality (SoloPath vs. stand- ard sheath, 9.3% vs. 3.5%; p=0.2, and 18.6% vs. 23.3%; p=0.7), major vascular complications (9.3% vs. 4.7%; p=0.3), and major bleeding (9.3% vs. 10.5%; p=0.5) in the cohort with the balloon-expandable sheath. Conclusions: The use of a balloon-expandable large-bore sheath in patients with a high risk for vascular complications due to complex access-site anatomy proved to be feasible and safe. However, circumferential calcifications and sheath-to-artery ratios account for vascular access complications even in patients treated with the balloon-expandable sheath.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 01/2015; DOI:10.4244/EIJY15M01_10 · 3.17 Impact Factor
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    ABSTRACT: Hypomethylation of long interspersed element (LINE)-1 has been observed in tumorigenesis when using degenerate assays, which provide an average across all repeats. However, it is unknown whether individual LINE-1 loci or different CpGs within one specific LINE-1 promoter are equally affected by methylation changes. Conceivably, studying methylation changes at specific LINE-1 may be more informative than global assays for cancer diagnostics. Therefore, with the aim of mapping methylation at individual LINE-1 loci at single-CpG resolution and exploring the diagnostic potential of individual LINE-1 locus methylation, we analyzed methylation at 11 loci by pyrosequencing, next-generation bisulfite sequencing as well as global LINE-1 methylation in bladder, colon, pancreas, prostate, and stomach cancers compared to paired normal tissues and in blood samples from some of the patients compared to healthy donors. Most (72/80) tumor samples harbored significant methylation changes at at least one locus. Notably, our data revealed not only the expected hypomethylation but also hypermethylation at some loci. Specific CpGs within the LINE-1 consensus sequence appeared preferentially hypomethylated suggesting that these could act as seeds for hypomethylation. In silico analysis revealed that these CpG sites more likely faced the histones in the nucleosome. Multivariate logistic regression analysis did not reveal a significant clinical advantage of locus-specific methylation markers over global methylation markers in distinguishing tumors from normal tissues. Methylation changes at individual LINE-1 loci are heterogeneous, whereas specific CpGs within the consensus sequence appear to be more prone to hypomethylation. With a broader selection of loci, locus-specific LINE-1 methylation could become a tool for tumor detection.
    01/2015; 7(1):17. DOI:10.1186/s13148-015-0051-y
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    ABSTRACT: In adult and pediatric cardiology, n-terminal pro-B-type natriuretic peptide (nt-proBNP) serves as biomarker in the diagnosis and management of cardiovascular dysfunction. Elevated levels of circulating nt-proBNP are present in fetal conditions associated with myocardial pressure or volume load. Compared to fetal blood sampling, amniocentesis is technically easier and can be performed from early pregnancy onwards. We aimed to investigate amniotic fluid (AF) nt-proBNP concentrations in normal pregnancies between 10 and 34 weeks of gestation. Nt-proBNP and total protein (TP) was measured in AF by chemiluminescence assay (photometry, respectively). To adjust for a potential dilutional effect, the AF-nt-proBNP/AF-TP ratio was analyzed. Reference intervals were constructed by regression modeling across gestational age. 132 samples were analyzed. A negative correlation between AF-nt-proBNP/AF-TP ratio and gestational age was observed. Curves for the mean and the 5% and 95% reference interval between 10 and 34 weeks of gestation were established. In normal pregnancy, nt-proBNP is present in AF and decreases during gestation. Our data provide the basis for research on AF-nt-proBNP as biomarker in fetal medicine.
    PLoS ONE 12/2014; 9(12):e114416. DOI:10.1371/journal.pone.0114416 · 3.53 Impact Factor
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    ABSTRACT: Abstract Vascular endothelial cadherin and β-catenin play a key role in establishment and maintenance of the endothelial monolayer integrity, regulation of vascular barrier function, and initiation of angiogenesis. The cadherin-catenin complex has been shown to be reduced in Type 1 diabetic placenta, but the exact relationship between histopathologic findings and clinical data is not known. Immunohistochemistryof placental tissue from Type 1, Type 2 and gestational diabetes showed, that diabetes per se might be compatible with normal levels of vascular endothelial cadherin and β-catenin in fetoplacental vessels as long as the patient has not been treated with insulin. Immunoreactivity of VE-cadherin did correlate poorly with maternal glycaemic control as was investigated in this study by birthweight, body-mass-index, and HbA1c. There was no correlation found between the immunoreactivity of β-catenin and birthweight, body-mass-index, and HbA1c. However our data did show a storng correlation immunoreactivity and whether or not the patient had been treated with insulin or not. Therefore patients diagnosed with gestational diabetes, who had not been treated with insulin, had similar levels of VE-cadherin and β-catenin as the control group, thus indicating that diabetes per se must not necessarily lead to a reduction. Our study suggests that therapeutic intervention using insulin in pregnancies complicated by diabetes might have potentially harmful effects on placental morphology. Future studies should further investigate these findings.
    Pediatric and Developmental Pathology 10/2014; DOI:10.2350/13-11-1400-OA.1 · 0.86 Impact Factor
  • European Respiratory Journal 10/2014; 69(S 01). DOI:10.1183/09031936.00108914 · 7.13 Impact Factor
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    ABSTRACT: Background Inflammation, collagen deposition and tissue remodelling are involved in the pathogenesis and complications of cirrhosis with portal hypertension. CXCL9 and other chemokines play an important role in these processes and have been associated with liver injury and complications of liver disease in humans. However, their predictive value in patients with cirrhosis and portal hypertension remains to be established. Methods 103 patients with liver cirrhosis who had received TIPS (transjugular intrahepatic portosystemic shunt) were included into this study. The TIPS indication was either refractory ascites or recurrent bleeding. Before and after TIPS procedure portal and hepatic venous blood samples were obtained in 78 patients. In 25 patients blood samples were obtained from portal vein, hepatic vein, right atrium and cubital vein at TIPS insertion. Serum levels of CXCL9 were measured by cytometric bead array and correlated with clinical parameters and overall outcome. Results Portal venous levels of CXCL9 decreased after TIPS. Child-score, refractory ascites, renal dysfunction and alcoholic etiology of cirrhosis were associated with increased CXCL9 levels. Importantly, low levels of CXCL9 in portal and hepatic vein were prognostic factors for survival of patients receiving TIPS during long-time follow up. Discussion The CXCR3 ligand CXCL9 affects the liver and/or is released by the liver and thereby might contribute to hepatic and extrahepatic organ dysfunction. Elevated levels of CXCL9 are associated with shorter survival in cirrhotic patients with severe portal hypertension receiving TIPS. This chemokine should be further evaluated as a novel biomarker for the outcome in patients with cirrhosis and portal hypertension and its modulation as a new therapeutic strategy.
    Journal of Hepatology 10/2014; DOI:10.1016/j.jhep.2014.09.032 · 10.40 Impact Factor
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    ABSTRACT: Introduction There is evidence of a probable key role of the activator protein-2 γ (AP-2γ) in placental development. It is still an open question whether AP-2γ expression may be influenced by preeclampsia, which is a serious pregnancy complication, or by smoking, which has deleterious effects on trophoblastic development. Material and Methods Thus, the expression of AP-2γ was studied in trophoblastic epithelium and endothelium of placentas from patients with preeclampsia (n = 43) and smokers (n = 45) as well as placentas of healthy pregnant women (control group, n = 26) between gestational ages 23 and 43 weeks. To allow differential expression in primary, secondary and tertiary villi, AP-2γ expression (arbitrary units) was determined immunohistologically. Results In preeclamptic placentas trophoblastic as well as endothelial cells AP-2γ expression was significantly higher compared to that in control placentas. Endothelial AP-2γ expression in placentas from smokers was similar to that of healthy women while trophoblastic AP-2γ expression in smokers’ placenta was insignificantly higher compared to that of control placentas. In all three groups expression rates of AP-2γ did not differ between primary, secondary and tertiary villi. Conclusion A correlation between increased trophoblastic and endothelial AP-2γ expression in patients with preeclampsia and reduced trophoblastic invasion and migration in preeclampsia has to be discussed. Furthermore, increased AP-2γ expression may play a protective role in preeclampsia, protecting from raised blood pressure. The tendency of an enhanced trophoblastic AP-2γ expression in smokers may indicate a compensatory response to the disturbed balance between proliferation and differentiation of villi induced by smoking.
    Archives of Gynecology and Obstetrics 10/2014; 291(5). DOI:10.1007/s00404-014-3473-4 · 1.28 Impact Factor
  • Zeitschrift für Gastroenterologie 08/2014; 52(08). DOI:10.1055/s-0034-1386006 · 1.67 Impact Factor
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    ABSTRACT: Early diagnosis is the key for the successful treatment of breast cancer. A serum marker for the early detection of breast cancer could significantly reduce breast cancer morbidity and mortality by bringing the time of diagnosis at an earlier and therefore still curable stage. So far, no biomarker for the early detection is available for the clinical routine. The aim of the present study was to evaluate the use of calponin-h2 as a blood-based biomarker for the early diagnosis of this disease. Using two monoclonal antibodies against calponin-h2, we developed a sandwich ELISA to analyze the serum levels of calponin-h2. In order to evaluate the diagnostic potential of this biomarker, patients with breast cancer (n = 76), benign diseases of the breast (n = 51) and healthy females (n = 24) were analyzed. Serum levels above 10 ng/ml were only observed in patients with breast cancer (n = 8; 10.5 %). Further large-scale studies and preanalytic evaluations are necessary to clarify the definite role of calponin-h2 as a biomarker in breast cancer management.
    Tumor Biology 08/2014; 35(11). DOI:10.1007/s13277-014-2419-6 · 2.84 Impact Factor
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    ABSTRACT: To evaluate hepatobiliary magnetic resonance imaging (MRI) using Gd-EOB-DTPA in relation to various liver function tests in patients with liver disorders.
    European Radiology 07/2014; 24(10). DOI:10.1007/s00330-014-3291-x · 4.34 Impact Factor
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    ABSTRACT: Purpose To evaluate the diagnostic value of cardiac magnetic resonance (MR) imaging at 3 T in patients suspected of having acute myocarditis by using a multiparametric cardiac MR imaging approach including T1 relaxation time as an additional tool for tissue characterization. Materials and Methods Ethics commission approval was obtained for this prospective study, and written informed consent was obtained from all subjects. Twenty four patients with acute myocarditis (mean age ± standard deviation, 34.7 years ± 15.1; 75% men) and 42 control subjects (mean age, 38.7 years ± 10.2; 64% men) were included. Cardiac MR imaging approaches included relative T2 short tau inversion-recovery signal intensity ratio (T2 ratio), early gadolinium enhancement ratio, late gadolinium enhancement, native T1 relaxation times, and extracellular volume fraction. Receiver operating characteristic analysis was performed to compare diagnostic performance. The reference standard was the clinical evidence for acute myocarditis. Results Native T1 relaxation times were significantly longer in patients with acute myocarditis than in control subjects (1185.3 msec ± 49.3 vs 1089.1 msec ± 44.9, respectively; P < .001). Areas under the curve of native T1 relaxation times (0.94) were higher compared with those of other cardiac MR parameters (late gadolinium enhancement, 0.90; T2 ratio, 0.79; extracellular volume fraction, 0.71; early gadolinium enhancement ratio, 0.63; P = .390, .018, .002, and < .001, respectively). Sensitivity (92%), specificity (91%), and diagnostic accuracy (91%) for native T1 relaxation times (cutoff, 1140 msec) were equivalent compared with those of the established combined Lake Louise criteria (sensitivity, 92%; specificity, 80%; diagnostic accuracy, 85%). Conclusion Diagnostic performance with native T1 mapping was superior to that with T2 ratio and early gadolinium enhancement ratio, and specificity was higher with native T1 mapping than that with Lake Louise criteria. This study underlines the potential of native T1 relaxation times to complement current cardiac MR approaches in patients suspected of having acute myocarditis. © RSNA, 2014 Online supplemental material is available for this article .
    Radiology 06/2014; DOI:10.1148/radiol.14132540 · 6.21 Impact Factor
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    ABSTRACT: Introduction The estrogen antagonist tamoxifen (TAM) increases the thrombotic risk similar to estrogen containing oral contraceptives (OC). In OC users this risk is attributed to alterations of hemostasis resulting in acquired resistance to activated protein C (APC). TAM-induced APC resistance has not been reported yet. Materials and Methods Blood samples were collected prospectively from women with breast cancer before (n = 25) and monthly after start of adjuvant TAM treatment (n = 75). APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. To detect increased in vivo APC generation APC plasma levels were measured using a highly sensitive oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were measured additionally. Results APC sensitivity decreased by 41% (p = 0.001) compared to baseline after one month of TAM application and remained significantly decreased during the study period. Free protein S increased (p = 0.008) while other analyzed procoagulant factors, inhibitors, and activation markers of coagulation decreased or did not change significantly. In five patients the APC concentration increased to non-physiological levels but an overall significant increase of APC was not observed. Conclusions This is the first study showing acquired APC resistance under TAM therapy. Acquired APC resistance might explain the increased thrombotic risk during TAM treatment. Observed changes of hemostasis parameters suggest different determinants of TAM-induced APC resistance than in OC-induced APC resistance. The presence of acquired APC resistance in TAM patients warrants further evaluation if these patients may benefit from antithrombotic prophylaxis in the presence of additional thrombotic risk factors.
    Thrombosis Research 05/2014; DOI:10.1016/j.thromres.2014.02.004 · 2.43 Impact Factor
  • RöFo - Fortschritte auf dem Gebiet der R 04/2014; 186(S 01). DOI:10.1055/s-0034-1373474 · 1.96 Impact Factor
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    ABSTRACT: To investigate the impact of Bruch Membrane pathology on the choroid in Pseudoxanthoma elacticum (PXE) DESIGN: Monocenter cross sectional prospective case series. The study included 61 eyes of 51 patients with PXE and 54 eyes of 54 normal subjects. The diagnosis of PXE was based on skin biopsy and/or genetic analysis. Eyes with PXE were subdivided into 3 groups: Eyes without choroidal neovascularization (CNV) or chorioretinal atrophy (group 1), eyes with active or fibrotic CNV (group 2) and eyes with chorioretinal atrophy only (group 3). Choroidal thickness was measured using enhanced depth imaging optical coherence tomography (EDI-OCT). Compared to controls (331μm±24; mean±95%CI), mean subfoveal choroidal thickness in eyes of PXE patients was significantly reduced within all three groups (group 1: 243μm±29; group 2: 184μm±28; group 3: 104μm±28; p<0.001). Associated structural changes included apparent loss of small choroidal vessels. The difference of PXE compared to control eyes was most obvious close to the optic disc and approximated the level of controls towards the periphery. Within the PXE subgroups eyes without CNV or chorioretinal atrophy (group 1) showed the least reduction of choroidal thickness, while it was most pronounced within group 3. The results indicate that changes of Bruch Membrane can be associated with choroidal alterations, which are most pronounced in presence of advanced disease. A role of Bruch Membrane for choroidal homeostasis may reflect a possible contribution of Bruch Membrane alterations to CNV and geographic atrophy development in age-related macular degeneration.
    American Journal of Ophthalmology 04/2014; DOI:10.1016/j.ajo.2014.04.005 · 4.02 Impact Factor
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    ABSTRACT: Purpose: To further characterize a subgroup of patients exhibiting the fundus autofluorescence (FAF) "diffuse-trickling" phenotype associated with geographic atrophy (GA). Methods: In the context of the Fundus Autofluorescence in Age related Macular Degeneration (FAM) Study, patients with "diffuse-trickling" GA were examined and characterized by FAF and spectral-domain optical coherence tomography imaging (HRA, Spectralis HRA+OCT, Heidelberg Engineering). Age, gender distribution, and medical history were compared to FAM study patients (n=288, 60.1% female) with other GA phenotypes ("non-diffuse-trickling"). In a subset of patients, subfoveal choroidal thickness (SCT) was analyzed. Results: Patients with "diffuse-trickling" (n=61) - compared to patients with "non-diffuse-trickling" GA - had a significantly younger age at first presentation (68.2±11.6 vs.75.4±8.1 years, p<0.001), a shift in the proportion of men from 55% in the age group <65 to 19% in the age group ≥65, and a significantly higher rate of myocardial infarction (MI) in the age group <65 (24% vs. 0%,p=0.011); all but one patient with MI were male. Further evaluation revealed that in the age group <65, 54% of patients with "diffuse-trickling" had been hospitalized due to cardiovascular diseases including hypertensive crisis, angina, and MI. Analysis of choroidal thickness revealed a significantly thinner SCT in "diffuse-trickling" compared to "non-diffuse-trickling" GA (135.2±56.4 vs. 191.4±77.8µm,p<0.001). Conclusions: The results indicate an association of "diffuse-trickling" GA with systemic cardiovascular disorders in the younger study population. Together with the ocular morphological characteristics including a lobular appearance and a thin choroid, a vascular insufficiency at the level of the choroid may play a pathogenetic role in this distinct GA phenotype.
    Investigative ophthalmology & visual science 04/2014; 55(5). DOI:10.1167/iovs.13-13409 · 3.43 Impact Factor
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    ABSTRACT: The German Version of the Manchester Triage System (MTS) has found widespread use in EDs across German-speaking Europe. Studies about the quality criteria validity and reliability of the MTS currently only exist for the English-language version. Most importantly, the content of the German version differs from the English version with respect to presentation diagrams and change indicators, which have a significant impact on the category assigned. This investigation offers a preliminary assessment in terms of validity and inter-rater reliability of the German MTS. Construct validity of assigned MTS level was assessed based on comparisons to hospitalization (general / intensive care), mortality, ED and hospital length of stay, level of prehospital care and number of invasive diagnostics. A sample of 45,469 patients was used. Inter-rater agreement between an expert and triage nurses (reliability) was calculated separately for a subset group of 167 emergency patients. For general hospital admission the area under the curve (AUC) of the receiver operating characteristic was 0.749; for admission to ICU it was 0.871. An examination of MTS-level and number of deceased patients showed that the higher the priority derived from MTS, the higher the number of deaths (p<0.0001 / χ(2) Test). There was a substantial difference in the 30-day survival among the 5 MTS categories (p<0.0001 / log-rank test).The AUC for the predict 30-day mortality was 0.613. Categories orange and red had the highest numbers of heart catheter and endoscopy. Category red and orange were mostly accompanied by an emergency physician, whereas categories blue and green were walk-in patients. Inter-rater agreement between expert triage nurses was almost perfect (κ = 0.954). The German version of the MTS is a reliable and valid instrument for a first assessment of emergency patients in the emergency department.
    PLoS ONE 02/2014; 9(2):e88995. DOI:10.1371/journal.pone.0088995 · 3.53 Impact Factor
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    ABSTRACT: This study investigated the efficacy of 131iodine-labeled lipiodol (131I-lipiodol) as a palliative therapy, evaluated overall survival (OS) across Barcelona Clinic Liver Cancer (BCLC) stages, and determined the main prognostic factors influencing OS in patients with hepatocellular carcinoma (HCC). Patients, methods: We retrospectively analyzed 57 (44 men; mean age, 65.7 years; mean activity per session, 1.6 GBq; mean cumulative activity in patients with >1 sessions, 3.9 GBq) HCC patients who underwent 131I-lipiodol therapy. A majority of patients exhibited Child-Pugh class B (53.6%) disease and a good Eastern Cooperative Oncology Group performance status (0-1; 72%). Multinodular disease was observed in 87.7% patients, bilobar disease in 73%, and portal vein occlusion (PVO) in 54%. Furthermore, 21.1% patients were staged as BCLC B and 59.6 % as BCLC C. All patients were followed until death. Results: The median OS was 6.4 months, which varied significantly with disease stage (median OS for BCLC A, B, C, and D was 29.4, 12.0, 4.6, and 2.7 months, respectively; p = 0.009); Child-Pugh score and class; presence of ascites, PVO, or extrahepatic disease; largest lesion size; favourable treatment response; international normalized ratio, baseline albumin and alpha-fetoprotein levels. Patients with a Child-Pugh A liver disease had a longer OS. Conclusion: Currently, different treatment modalities for HCC include radioembolization, transarterial chemoembolization, and systemic therapy with sorafenib; however, 131I-lipiodol therapy remains a feasible alternative for patients without a favourable response to other therapies, particularly for patients with Child-Pugh A liver cirrhosis.
    Nuklearmedizin 01/2014; 53(3). DOI:10.3413/Nukmed-0610-13-07 · 1.67 Impact Factor
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    ABSTRACT: The objective of this study was to investigate the efficacy of the fixed-dose combination olmesartan/amlodipine 40/10 mg in patients with moderate essential hypertension not controlled on candesartan 32 mg. This was a prospective, single-arm, phase IV study. The primary endpoint was the change in mean daytime systolic blood pressure (BP). A total of 77 of 89 screened patients started candesartan 32 mg, 62 olmesartan 40 mg, and 57 olmesartan 40 mg/amlodipine 10 mg. Mean daytime systolic BP was reduced by 9.8±15.2 mm Hg (P<.001) vs candesartan monotherapy. Office BP reduction was 9.2±18.8/5.0±8.9 mm Hg (P<0.001). Treatment goals (<140/90 mm Hg for office and <135/85 mm Hg for ambulatory BP) were achieved in 58.2% and 78.4% of patients, respectively. There was one drug-related adverse event (edema) and no serious adverse events. Patients of Caucasian ethnicity with moderate essential hypertension uncontrolled on candesartan experienced a further drop in BP using olmesartan and amlodipine.
    Journal of Clinical Hypertension 01/2014; 16(1):41-6. DOI:10.1111/jch.12227 · 2.36 Impact Factor
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    ABSTRACT: TNFα levels are increased in liver cirrhosis even in the absence of infection, most likely owing to a continuous endotoxin influx into the portal blood. Soluble TNFα receptors (sTNFR type I and II) reflect release of the short-lived TNFα, because they are cleaved from the cells after binding of TNFα. The aims were to investigate the circulating levels of soluble TNFR-I and -II in cirrhotic patients receiving TIPS. Forty-nine patients with liver cirrhosis and portal hypertension (12 viral, 37 alcoholic) received TIPS for prevention of re-bleeding (n = 14), therapy-refractory ascites (n = 20), or both (n = 15). Portal and hepatic venous blood was drawn in these patients during the TIPS procedure and during the control catheterization two weeks later. sTNFR-I and sTNFR-II were measured by ELISA, correlated to clinical and biochemical characteristics. Before TIPS insertion, sTNFR-II levels were lower in portal venous blood than in the hepatic venous blood, as well as in portal venous blood after TIPS insertion. No significant differences were measured in sTNFR-I levels. Hepatic venous levels of sTNFR-I above 4.5 ng/mL (p = 0.036) and sTNFR-II above 7 ng/mL (p = 0.05) after TIPS insertion were associated with decreased survival. A multivariate Cox-regression survival analysis identified the hepatic venous levels of sTNFR-I (p = 0.004) two weeks after TIPS, and Child score (p = 0.002) as independent predictors of mortality, while MELD-score was not. Hepatic venous levels of sTNFR-I after TIPS insertion may predict mortality in patients with severe portal hypertension.
    PLoS ONE 12/2013; 8(12):e83341. DOI:10.1371/journal.pone.0083341 · 3.53 Impact Factor
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Publication Stats

8k Citations
1,208.33 Total Impact Points


  • 1988–2015
    • University of Bonn
      • • Department of Neurobiology
      • • Institute of Biomedical Statistics, Computer Science and Epidemiology
      • • Klinik und Poliklinik für Dermatologie und Allergologie
      • • Zentrum für Innere Medizin
      • • Klinik und Poliklinik für Nuklearmedizin
      • • Institute of Human Genetics
      • • Medizinische Klinik und Poliklinik I
      • • Medizinische Klinik und Poliklinik II
      Bonn, North Rhine-Westphalia, Germany
  • 2006–2014
    • Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V.
      Bonn, North Rhine-Westphalia, Germany
    • University Medical Center Schleswig-Holstein
      • Department of Pediatrics
      Kiel, Schleswig-Holstein, Germany
    • Universität des Saarlandes
      Saarbrücken, Saarland, Germany
  • 1994–2014
    • University of Bonn - Medical Center
      • Institute for Clinical Chemistry and Clinical Pharmacology
      Bonn, North Rhine-Westphalia, Germany
  • 2010
    • Clinic for Minimally Invasive Surgery
      Berlín, Berlin, Germany
  • 2008–2010
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
    • Universitätsklinikum Jena
      Jena, Thuringia, Germany
  • 2005–2007
    • University of Münster
      • Department of Psychiatry
      Münster, North Rhine-Westphalia, Germany
    • University of Hamburg
      Hamburg, Hamburg, Germany
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      • Department of Obstetrics and Gynaecology, School of Midwifery
      Erlangen, Bavaria, Germany
  • 2000–2004
    • Philipps University of Marburg
      Marburg, Hesse, Germany
  • 1994–2004
    • University of Cologne
      Köln, North Rhine-Westphalia, Germany
  • 2002
    • Johannes Gutenberg-Universität Mainz
      • I. Department of Medicine
      Mayence, Rheinland-Pfalz, Germany
  • 2001
    • Washington University in St. Louis
      • Department of Obstetrics and Gynecology
      San Luis, Missouri, United States
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
    • Ludwig-Maximilian-University of Munich
      • Department of Internal Medicine I
      München, Bavaria, Germany
  • 1999
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 1998
    • Sigmund-Freud-Institut
      Frankfurt, Hesse, Germany
  • 1997
    • Hebrew University of Jerusalem
      Yerushalayim, Jerusalem, Israel
  • 1996
    • Stanford University
      Palo Alto, California, United States