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190 Publications visible to you, out of a total of 190
Prognostic factors for hematotoxicity of chemotherapy in aggressive non-Hodgkin's lymphoma.
GLA - German Lymphoma Alliance

Abstract (Expand)

BACKGROUND: Little is known on the heterogeneity of hematotoxicity in patients receiving multicycle chemotherapy. PATIENTS AND METHODS: We analyzed data of 1399 patients with aggressive lymphoma from … trials using CHOP (combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone)-like therapies. Multivariate modeling was carried out for leukocytopenia, thrombocytopenia and anemia and the models were validated by two large independent datasets from trials with/without usage of the CD20-antibody rituximab. RESULTS: On the basis of these models, we are able to predict the remarkable heterogeneity of hematotoxicity and propose to use risk groups. Regarding leukocytopenia, the low toxicity risk group experienced World Health Organization grade 4 in <10% of the cycles while the high toxicity risk group in almost all cycles. For thrombocytopenia, groups were detectable with almost no grade 3 or 4 toxicity and others where two out of three cycles were affected. In a separate set of models, the first cycle toxicity was the strongest predictor for later hematotoxicity. The risk for leukocytopenia was associated with infections, antibiotic use, hospitalization and treatment-related mortality, indicating the clinical usefulness of the models. For the first time, a Web-based tool is made available to easily predict the hematotoxicity in clinical practice (www.toxcalculator.com). CONCLUSION: This analysis has implications for patient management and prophylaxis.

Authors: M. Ziepert, R. Schmits, L. Trumper, M. Pfreundschuh, M. Loeffler

Date Published: 1st Dec 2007

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma

Large histological serial sections for computational tissue volume reconstruction.
ProstataCA

Abstract (Expand)

OBJECTIVES: A proof of principle study was conducted for microscopic tissue volume reconstructions using a new image processing chain operating on alternately stained large histological serial sections. … METHODS: Digital histological images were obtained from conventional brightfield transmitted light microscopy. A powerful nonparametric nonlinear optical flow-based registration approach was used. In order to apply a simple but computationally feasible sum-of-squared-differences similarity measure even in case of differing histological stainings, a new consistent tissue segmentation procedure was placed upstream. RESULTS: Two reconstructions from uterine cervix carcinoma specimen were accomplished, one alternately stained with p16(INK4a) (surrogate tumor marker) and H&E (routine reference), and another with three different alternate stainings, H&E, p16(INK4a), and CD3 (a T-lymphocyte marker). For both cases, due to our segmentation-based reference-free nonlinear registration procedure, resulting tissue reconstructions exhibit utmost smooth image-to-image transitions without impairing warpings. CONCLUSIONS: Our combination of modern nonparametric nonlinear registration and consistent tissue segmentation has turned out to provide a superior tissue reconstruction quality.

Authors: U. D. Braumann, N. Scherf, J. Einenkel, L. C. Horn, N. Wentzensen, M. Loeffler, J. P. Kuska

Date Published: 17th Oct 2007

Publication Type: Not specified

Human Diseases: cervical cancer

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

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

Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with Pre-diabetic phenotypes: meta-analysis of 57 studies on nondiabetic individuals
Genetical Statistics and Systems Biology

Abstract (Expand)

OBJECTIVE The provariant of the Pro12Ala polymorphism in peroxisome proliferator-activated receptor (PPAR)gamma has been identified as a risk allele for type 2 diabetes. The purpose of the present study …y was to reveal a significant association with pre-diabetic phenotypes in nondiabetic individuals based on a systematic meta-analysis of all available published evidence. RESEARCH DESIGN AND METHODS We performed a classical meta-analysis of data from approximately 32,000 nondiabetic subjects in 57 studies to assess the effect of the Pro12Ala polymorphism on pre-diabetic traits. RESULTS In the global comparison, there were no differences in BMI, glucose, insulin, or homeostasis model assessment of insulin resistance between the Pro/Pro and X/Ala genotype. However, in the Caucasian subgroup, the X/Ala genotype was associated with significantly increased BMI. In the obese subgroup (BMI \textgreater30 kg/m(2)), fasting glucose (P = 0.041) and insulin resistance (by homeostasis model analysis) (P = 0.020) were significantly greater in the Pro/Pro group. In subjects with the homozygous Ala/Ala genotype, fasting insulin was significantly lower compared with the Pro/Pro genotype (P = 0.040, N(Ala/Ala) = 154). CONCLUSIONS Across all studies, the Pro12Ala polymorphism had no significant effect on diabetes-related traits. Only in selected subgroups, such as Caucasians and obese subjects, did we see an association of the Ala allele with greater BMI and greater insulin sensitivity. This demonstrates the importance for appropriate stratification of analyses by environmental or other genetic factors. Meta-analysis of Ala/Ala homozygotes more clearly demonstrated the association with greater insulin sensitivity of carriers of the Ala allele.

Authors: Anke Tönjes, Markus Scholz, Markus Loeffler, Michael Stumvoll

Date Published: 25th Oct 2006

Publication Type: Journal article

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