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468 Publications visible to you, out of a total of 468
Acute renal failure in patients with severe sepsis and septic shock–a significant independent risk factor for mortality: results from the German Prevalence Study
SepNet - German Competence Network Sepsis

Abstract (Expand)

BACKGROUND Sound data about the prevalence of acute renal failure (ARF) among patients with severe sepsis and septic shock are lacking. Further, it is not known whether ARF is an independent risk factor …r for mortality in septic patients or merely an indicator of disease severity. METHODS A prospective cross-sectional one-day prevalence study was carried out in a representative sample of German ICUs, divided into five strata (\textless 200 beds; 201-400 beds; 401-600 beds; \textgreater 600 beds; university hospitals). 3877 patients were screened of whom 415 had severe sepsis and septic shock. RESULTS Fourteen patients (3.4%) had chronic dialysis-dependent RF and were excluded from analysis. Of the remaining 401 patients, 166 (41.4%) had ARF, as defined by a rise in creatinine above twice the upper limit of normal and/or a drop in urine output to \textless 0.5 ml/kg bodyweight. Median APACHE II score was 22 in patients with ARF and 16 in patients without ARF (p\textless 0.0001). Patients with severe sepsis/septic shock had an overall hospital mortality of 55.2%. Hospital mortality in patients with ARF was 67.3% and without ARF 42.8% (p\textless 0.0001). After adjustment for APACHE II score and age, ARF remained a significant independent risk factor for death [odds ratio (OR) 2.11, 95% confidence interval (CI) 1.27-3.52]. Mortality in septic patients was not associated with pre-existing, non-dialysis-dependent chronic kidney disease, whereas in dialysis-dependent patients with sepsis mortality increased to 86%. CONCLUSION In this representative survey in patients with severe sepsis/septic shock, prevalence of ARF is high with 41.4%. ARF represents a significant independent risk factor for mortality in these patients.

Authors: Michael Oppert, Christoph Engel, Frank-Martin Brunkhorst, Holger Bogatsch, Konrad Reinhart, Ulrich Frei, Kai-Uwe Eckardt, Markus Loeffler, Stefan John

Date Published: 15th Oct 2007

Publication Type: Journal article

Human Diseases: disease by infectious agent

Association of the BRCA1 missense variant R1699W with a malignant phyllodes tumor of the breast
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Familial breast carcinomas that are attributable to BRCA1 or BRCA2 mutations have characteristic morphologic and immunhistochemical features. BRCA1-associated carcinomas are poorly differentiated … infiltrating ductal carcinomas frequently exhibiting morphologic features of typical or atypical medullary carcinomas such as prominent lymphocytic infiltrate and pushing margins. We report on a patient carrying the deleterious BRCA1 germline mutation R1699W, who presented with a malignant phyllodes tumor of the breast. The re-investigation of archival material by a reference pathologist of the German Consortium for Hereditary Breast and Ovarian Cancer (GCHBOC) revealed BRCA-associated pronounced pushing margins. In a total of 618 unrelated index patients who are registered in the GCHBOC database, no other phyllodes tumor has been described, while 10 carriers of the R1699W mutant have been identified. We conclude that the histopathologic appearance of the phyllodes tumor indicates an association with the BRCA1 mutation R1699W although it is a rare event in BRCA-positive families.

Authors: Kerstin Rhiem, Uta Flucke, Christoph Engel, Barbara Wappenschmidt, Axel Reinecke-Lüthge, Reinhard Büttner, Rita Katharina Schmutzler

Date Published: 1st Jul 2007

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a consortium of investigators of modifiers of BRCA1/2 study
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and … BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 31I allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.06]. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% CI, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers.

Authors: Fergus J. Couch, Olga Sinilnikova, Robert A. Vierkant, V. Shane Pankratz, Zachary S. Fredericksen, Dominique Stoppa-Lyonnet, Isabelle Coupier, David Hughes, Agnès Hardouin, Pascaline Berthet, Susan Peock, Margaret Cook, Caroline Baynes, Shirley Hodgson, Patrick J. Morrison, Mary E. Porteous, Anna Jakubowska, Jan Lubinski, Jacek Gronwald, Amanda B. Spurdle, Rita Schmutzler, Beatrix Versmold, Christoph Engel, Alfons Meindl, Christian Sutter, Jurgen Horst, Dieter Schaefer, Kenneth Offit, Tomas Kirchhoff, Irene L. Andrulis, Eduard Ilyushik, Gordon Glendon, Peter Devilee, Maaike P. G. Vreeswijk, Hans F. A. Vasen, Ake Borg, Katja Backenhorn, Jeffery P. Struewing, Mark H. Greene, Susan L. Neuhausen, Timothy R. Rebbeck, Katherine Nathanson, Susan Domchek, Theresa Wagner, Judy E. Garber, Csilla Szabo, Michal Zikan, Lenka Foretova, Janet E. Olson, Thomas A. Sellers, Noralane Lindor, Heli Nevanlinna, Johanna Tommiska, Kristiina Aittomaki, Ute Hamann, Muhammad U. Rashid, Diana Torres, Jacques Simard, Francine Durocher, Frederic Guenard, Henry T. Lynch, Claudine Isaacs, Jeffrey Weitzel, Olufunmilayo I. Olopade, Steven Narod, Mary B. Daly, Andrew K. Godwin, Gail Tomlinson, Douglas F. Easton, Georgia Chenevix-Trench, Antonis C. Antoniou

Date Published: 1st Jul 2007

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Evaluation of the invasion front pattern of squamous cell cervical carcinoma by measuring classical and discrete compactness.
ProstataCA

Abstract (Expand)

The invasion front pattern of squamous cell carcinoma (SCC) is a conspicuous histological phenomenon, which is assessed without precise criteria. The current study was performed to introduce the classical … (C(C)) and discrete compactness (C(D)) as new morphometric parameters for quantification of this pattern. A retrospective analysis of 76 surgically treated patients with cervical carcinoma was conducted and the pattern of invasion was qualitatively classified as closed, finger-like or diffuse, respectively, by two pathologists. After digitization of the histological slides with a field of view of 10.4 mm x 8.3mm, tumor areas were labeled and C(C) and C(D) were computed based on the drawings (binary images). Additionally, intraindividual variation of compactness was evaluated for 12 selected tumors. The qualitative pattern assessment by the pathologists was moderately reproducible with an interobserver agreement of 72% and a kappa coefficient of 0.44. The values of C(C) and C(D) referring to the invasion front patterns assigned by both pathologists were significantly different between the three classified groups (p< or =0.01 and p< or =0.0001), so that, both theoretically and in practice, compactness regards the same morphological feature. In due consideration of the analysis of the area under the ROC (receiver operating characteristic) curves and the variation coefficient of different tumor regions, C(D) is more suitable for practical use than C(C). Tumors with a microscopic invasion into the parametria and with lymph-vascular space invasion were found to have a lower value of C(D), which indicates a more diffuse pattern of invasion (p=0.028 and p=0.033). We conclude that the discrete compactness C(D) is a new and reproducible parameter for a computer assisted quantification of the invasion front pattern and, thus, defines a further phenotypic feature of SCC of the uterine cervix.

Authors: J. Einenkel, U. D. Braumann, L. C. Horn, N. Pannicke, J. P. Kuska, A. Schutz, B. Hentschel, M. Hockel

Date Published: 25th May 2007

Publication Type: Not specified

Human Diseases: cervical cancer

Epidemiology of sepsis in Germany: results from a national prospective multicenter study
SepNet - German Competence Network Sepsis

Abstract (Expand)

OBJECTIVE To determine the prevalence and mortality of ICU patients with severe sepsis in Germany, with consideration of hospital size. DESIGN Prospective, observational, cross-sectional 1-day …day point-prevalence study. SETTING 454 ICUs from a representative nationwide sample of 310 hospitals stratified by size. Data were collected via 1-day on-site audits by trained external study physicians. Visits were randomly distributed over 1 year (2003). PATIENTS Inflammatory response of all ICU patients was assessed using the ACCP/SCCM consensus conference criteria. Patients with severe sepsis were followed up after 3 months for hospital mortality and length of ICU stay. MEASUREMENTS AND RESULTS Main outcome measures were prevalence and mortality. A total of 3,877 patients were screened. Prevalence was 12.4% (95% CI, 10.9-13.8%) for sepsis and 11.0% (95% CI, 9.7-12.2%) for severe sepsis including septic shock. The ICU and hospital mortality of patients with severe sepsis was 48.4 and 55.2%, respectively, without significant differences between hospital size. Prevalence and mean length of ICU stay of patients with severe sepsis were significantly higher in larger hospitals and universities (\textless/= 200 beds: 6% and 11.5 days, universities: 19% and 19.2 days, respectively). CONCLUSIONS The expected number of newly diagnosed cases with severe sepsis in Germany amounts to 76-110 per 100,000 adult inhabitants. To allow better comparison between countries, future epidemiological studies should use standardized study methodologies with respect to sepsis definitions, hospital size, and daily and monthly variability.

Authors: Christoph Engel, Frank M. Brunkhorst, Hans-Georg Bone, Reinhard Brunkhorst, Herwig Gerlach, Stefan Grond, Matthias Gruendling, Guenter Huhle, Ulrich Jaschinski, Stefan John, Konstantin Mayer, Michael Oppert, Derk Olthoff, Michael Quintel, Max Ragaller, Rolf Rossaint, Frank Stuber, Norbert Weiler, Tobias Welte, Holger Bogatsch, Christiane Hartog, Markus Loeffler, Konrad Reinhart

Date Published: 23rd Mar 2007

Publication Type: Journal article

Human Diseases: disease by infectious agent

Combined serial section-based 3D reconstruction of cervical carcinoma invasion using H&E/p16INK4a/CD3 alternate staining.
ProstataCA

Abstract (Expand)

BACKGROUND: Malignant growth and invasiveness of cancers is a function of both intratumoral and stromal factors. The accessibility to nutrients, oxygen and growth factors, the stromal composition, and … the interference with the immune system all shape the tumor invasion front. A recent study has shown a prognostic difference with respect to different invasion patterns analyzed on histological specimens of cervical cancers. The present study analyzes the spatial organization of a cervical cancer and the relation of the tumor invasion front and the infiltration with CD3(+) T-cells. METHODS: From a cervical squamous cell carcinoma specimen, 84 serial sections were performed and three interleaving series were stained with hematoxylin/eosin and immunohistochemistry directed against the cervical carcinoma biomarker p16(INK4a) and the T-cell marker CD3. Sections were passed through an image processing chain to obtain a reconstructed and segmented tissue volume. For local tumor invasion front analysis the mean curvature was used, which in turn was related to the respective local minimum tumor to T-cell distance as well to a T-cell originated diffusing substance's concentration at the tumor surface. RESULTS: Spatial models of the tumor tissue and the infiltrating T-cells were computed. The overall discrete compactness of the tumor invasion front was 0.89, corresponding to a pathological assessment of diffuse infiltration. The comparison of the tumor invasion front with the density of T-cell infiltration revealed an increased smoothening in regions with high T-cell infiltration. CONCLUSIONS: We could demonstrate the spatial organization of a cervical cancer and model the interaction between infiltrating T-cells with the tumor invasion front shape. Increased smoothening in regions with high T-cell infiltration suggests that T-cells may have an influence on the shaping of the tumor invasion front, e.g., by attacking tumor cells displaying specific antigens. The applied technique allows visualization of the spatial organization of tissues and could be extended to analyze multiple stains on alternating sections.

Authors: N. Wentzensen, U. D. Braumann, J. Einenkel, L. C. Horn, M. von Knebel Doeberitz, M. Loffler, J. P. Kuska

Date Published: 7th Feb 2007

Publication Type: Not specified

Human Diseases: cervical cancer

The interleukin-10 gene promoter polymorphism -1087AG does not correlate with clinical outcome in non-Hodgkin's lymphoma.
GLA - German Lymphoma Alliance

Abstract (Expand)

The Interleukin 10 (IL-10) gene is highly polymorphic, and the IL-10(-1087AG) (rs1800896) gene variation is the only so far studied intensively in association with certain diseases. Conflicting data … have been published about an association of IL-10(-1087AG) gene variation with lower rates of complete remission and lower overall survival (OS) in patients with diffuse large B-cell lymphoma. To further investigate this in malignant lymphoma, we established the IL-10 genotypes in patients from the NHL-B1/ B2 studies from the German High-Grade Non-Hodgkin's Lymphoma Study Group. In our study, allele frequencies of lymphoma patients are comparable as in healthy controls. No increase of IL-10(-1087G) alleles was found. In addition we did not find any difference in OS or event-free survival between patients with IL-10(-1087AA) and the other genotypes. Comparable results were obtained for the IL-10 loci at -3538 (A/T), -1354 (A/G), -824 (C/T) and -597 (A/C) (rs1800890, rs1800893, rs1800871 and rs1800872).

Authors: D. Kube, T. D. Hua, M. Kloss, B. Kulle, J. Brockmoller, L. Wojnowski, M. Loffler, M. Pfreundschuh, L. Trumper

Date Published: 12th Jan 2007

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma

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