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190 Publications visible to you, out of a total of 190
PROGRESS - prospective observational study on hospitalized community acquired pneumonia
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Community acquired pneumonia (CAP) is a high incidence disease resulting in about 260,000 hospital admissions per year in Germany, more than myocardial infarction or stroke. Worldwide, CAP …P is the most frequent infectious disease with high lethality ranging from 1.2 % in those 20-29 years old to over 10 % in patients older than 70 years, even in industrial nations. CAP poses numerous medical challenges, which the PROGRESS (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis) network aims to tackle: Operationalization of disease severity throughout the course of disease, outcome prediction for hospitalized patients and prediction of transitions from uncomplicated CAP to severe CAP, and finally, to CAP with sepsis and organ failure as a life-threatening condition. It is a major aim of PROGRESS to understand and predict patient heterogeneity regarding outcome in the hospital and to develop novel treatment concepts. METHODS PROGRESS was designed as a clinical, observational, multi-center study of patients with CAP requiring hospitalization. More than 1600 patients selected for low burden of co-morbidities have been enrolled, aiming at a total of 3000. Course of disease, along with therapy, was closely monitored by daily assessments and long-term follow-up. Daily blood samples allow in depth molecular-genetic characterization of patients. We established a well-organized workflow for sample logistics and a comprehensive data management system to collect and manage data from more than 50 study centers in Germany and Austria. Samples are stored in a central biobank and clinical data are stored in a central data base which also integrates all data from molecular assessments. DISCUSSION With the PROGRESS study, we established a comprehensive data base of high quality clinical and molecular data allowing investigation of pressing research questions regarding CAP. In-depth molecular characterization will contribute to the discovery of disease mechanisms and establishment of diagnostic and predictive biomarkers. A strength of PROGRESS is the focus on younger patients with low burden of co-morbidities, allowing a more direct look at host biology with less confounding. As a resulting limitation, insights from PROGRESS will require validation in representative patient cohorts to assess clinical utility. TRIAL REGISTRATION The PROGRESS study was retrospectively registered on May 24(th), 2016 with ClinicalTrials.gov: NCT02782013.

Authors: Peter Ahnert, Petra Creutz, Markus Scholz, Hartwig Schütte, Christoph Engel, Hamid Hossain, Trinad Chakraborty, Michael Bauer, Michael Kiehntopf, Uwe Völker, Sven Hammerschmidt, Markus Loeffler, Norbert Suttorp

Date Published: 1st Dec 2016

Publication Type: Journal article

Obesity is Associated with White Matter Changes and Cognitions among Healthy Elderly
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Midlife obesity has often been associated with accelerated cognitive decline during aging. Obesity leads to changes in multiple physiological factors that could impact neuronal tissue. Numerous studies … have linked obesity and higher body mass index (BMI) with differences in cognitive functions and brain structure, including total brain volume, regional gray matter volume and white matter (WM) microstructure. However, regarding to WM, the available neuroimaging studies incorporated mainly small sample sizes that yielded less conclusive results. Thus, we investigated the association of obesity, measured using BMI and waist to hip ratio (WHR), with changes in WM microstructure, as well as variance in cognitive test scores in a large cohort of community-dwelling healthy individuals older than 60 years.

Authors: Rui Zhang, L. Lampe, Frauke Beyer, Sebastian Huhn, S. K. Masouleh, T. Luck, S. G. Riedel-Heller, Markus Löffler, M. L. Schroeter

Date Published: 28th Nov 2016

Publication Type: Not specified

Human Diseases: obesity

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial.
SepNet - German Competence Network Sepsis

Abstract (Expand)

Importance: Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock … remains controversial. Objective: To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock. Interventions: Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190). Main Outcomes and Measures: The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]). Results: The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, -1.8%; 95% CI, -10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, -5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, -5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, -4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia. Conclusions and Relevance: Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients. Trial Registration: clinicaltrials.gov Identifier: NCT00670254.

Authors: D. Keh, E. Trips, G. Marx, S. P. Wirtz, E. Abduljawwad, S. Bercker, H. Bogatsch, J. Briegel, C. Engel, H. Gerlach, A. Goldmann, S. O. Kuhn, L. Huter, A. Meier-Hellmann, A. Nierhaus, S. Kluge, J. Lehmke, M. Loeffler, M. Oppert, K. Resener, D. Schadler, T. Schuerholz, P. Simon, N. Weiler, A. Weyland, K. Reinhart, F. M. Brunkhorst

Date Published: 1st Nov 2016

Publication Type: Journal article

Human Diseases: disease by infectious agent

The Cognitive Functioning of Socially Isolated Individuals may Profit from High Mental Work Demands
LIFE Adult

Abstract (Expand)

Objectives: Previous studies have shown that individuals with poor social relationships have an increased risk for dementia. Dementia risk, however, can also be positively influenced by lifestyle … factors. One such very important factor is high mental demands at work, in particular as the work environment affects a very long lifetime period. Thus, our objective was to investigate whether the cognitive functioning of socially isolated individuals may profit from high mental work demands. Methods: Analyses were based on n = 10,000 participants (aged 40 – 80 years) of the population-based German LIFE-Adult-Study. All participants underwent medical examinations and filled out standardized questionnaires. Cognitive functioning was assessed via the Verbal Fluency Test (VFT) and the Trail-Making Test (TMT). Social relationships were assessed via the Lubben Social Network Scale (LSNS-6). The interaction between social isolation and mental demands on cognitive functioning was analyzed via multivariate regression analyses. Results: The difference in cognitive functioning between high and low mental work demand conditions was larger in socially isolated individuals (VFT: 2.7 words, TMT-B: 26 seconds) compared to socially well integrated individuals (VFT: 2.1 words, TMT-B: 9 seconds). Multivariate regression analyses – adjusted for age, gender, and education – indicated that both mental work demands as well as social relationships are significantly associated with the level of cognitive functioning (p < 0.001). Results also suggest interaction effects indicating a stronger impact of mental work demands on cognitive functioning in socially isolated individuals than in well integrated individuals. Conclusion: The findings imply that individuals with poor social relationships may particularly benefit from high mental work demands regarding their risk for dementia. The level of mental demands at work could therefore be an important target for tailored preventative approaches.

Authors: F. S. Then, M. L. Schroeter, V. Witte, C. Engel, M. Loeffler, J. Thiery, A. Villringer, T. Luck, S. G. Riedel-Heller

Date Published: 15th Sep 2016

Publication Type: Journal article

CNS International Prognostic Index: A Risk Model for CNS Relapse in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP.
GLA - German Lymphoma Alliance

Abstract (Expand)

PURPOSE: To develop and validate a risk score for relapse in the CNS in patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: A total of 2,164 patients (18 to 80 years old) with … aggressive B-cell lymphomas (80% DLBCL) treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like chemotherapy, who were enrolled in studies from the German High-Grade Non-Hodgkin Lymphoma Study Group and the MabThera International Trial, were analyzed for occurrence of relapse/progression in the CNS. The resulting risk model was validated in an independent data set of 1,597 patients with DLBCL identified in the British Columbia Cancer Agency Lymphoid Cancer database. RESULTS: The risk model consists of the International Prognostic Index (IPI) factors in addition to involvement of kidneys and/or adrenal glands (CNS-IPI). In a three-risk group model, the low-risk group (46% of all patients analyzed), the intermediate-risk group (41%), and the high-risk group (12%) showed 2-year rates of CNS disease of 0.6% (CI, 0% to 1.2%), 3.4% (CI, 2.2% to 4.4%), and 10.2% (CI, 6.3% to 14.1%), respectively. Patients from the validation British Columbia Cancer Agency data set showed similar rates of CNS disease for low-risk (0.8%; CI, 0.0% to 1.6%), intermediate-risk (3.9%; CI, 2.3% to 5.5%), and high-risk (12.0%; CI, 7.9% to 16.1%) groups. CONCLUSION: The CNS-IPI is a robust, highly reproducible tool that can be used to estimate the risk of CNS relapse/progression in patients with DLBCL treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Close to 90% of patients with DLBCL belong to the low- and intermediate-risk groups and have a CNS relapse risk < 5%; they may be spared any diagnostic and therapeutic intervention. In contrast, those in the high-risk group have a > 10% risk of CNS relapse and should be considered for CNS-directed investigations and prophylactic interventions.

Authors: N. Schmitz, S. Zeynalova, M. Nickelsen, R. Kansara, D. Villa, L. H. Sehn, B. Glass, D. W. Scott, R. D. Gascoyne, J. M. Connors, M. Ziepert, M. Pfreundschuh, M. Loeffler, K. J. Savage

Date Published: 10th Sep 2016

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

THE COGNITIVE FUNCTIONING OF SOCIALLY ISOLATED INDIVIDUALS MAY PROFIT FROM HIGH MENTAL WORK DEMANDS
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Background: Previous studies have shown that individuals with poor social relationships have an increased risk for dementia. Dementia risk, however, can also be positively influenced by lifestyle factors … such as high mental demands at work (in particular as the work environment affects a very long lifetime period). Thus, our objective was to investigate whether the cognitive functioning of socially isolated individuals may profit from high mental work demands. Methods: Analyses were based on n=10,000 participants (aged 40-80 years) of the population-based German LIFE-Adult-Study. All participants underwent medical examinations and filled out standardized questionnaires. Cognitive functioning was assessed via the Verbal Fluency Test (VFT) and the Trail-Making Test (TMT). Social relationships were assessed via the Lubben Social Network Scale (LSNS-6). Results: The difference in cognitive func- tioning between high and low mental work demand conditions was larger in socially isolated individuals (VFT: 2.7 words, TMT-B: 26 seconds) compared to socially well integrated individuals (VFT: 2.1 words, TMT-B: 9 seconds). Multivariate regression analyses – adjusted for age, gender, and education – indicated that both mental work demands as well as social relationships are significantly asso- ciated with the level of cognitive functioning

Authors: F. S. Then, M. L. Schroeter, A. V. Witte, Christoph Engel, Markus Löffler, J. Thiery, A. Villringer, T. Luck, S. G. Riedel-Heller

Date Published: 1st Sep 2016

Publication Type: Not specified

Human Diseases: cognitive disorder

Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial.
SepNet - German Competence Network Sepsis

Abstract (Expand)

IMPORTANCE: High-dose intravenous administration of sodium selenite has been proposed to improve outcome in sepsis by attenuating oxidative stress. Procalcitonin-guided antimicrobial therapy may hasten … the diagnosis of sepsis, but effect on outcome is unclear. OBJECTIVE: To determine whether high-dose intravenous sodium selenite treatment and procalcitonin-guided anti-infectious therapy in patients with severe sepsis affect mortality. DESIGN, SETTING, AND PARTICIPANTS: The Placebo-Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT), a multicenter, randomized, clinical, 2 x 2 factorial trial performed in 33 intensive care units in Germany, was conducted from November 6, 2009, to June 6, 2013, including a 90-day follow-up period. INTERVENTIONS: Patients were randomly assigned to receive an initial intravenous loading dose of sodium selenite, 1000 microg, followed by a continuous intravenous infusion of sodium selenite, 1000 microg, daily until discharge from the intensive care unit, but not longer than 21 days, or placebo. Patients also were randomized to receive anti-infectious therapy guided by a procalcitonin algorithm or without procalcitonin guidance. MAIN OUTCOMES AND MEASURES: The primary end point was 28-day mortality. Secondary outcomes included 90-day all-cause mortality, intervention-free days, antimicrobial costs, antimicrobial-free days, and secondary infections. RESULTS: Of 8174 eligible patients, 1089 patients (13.3%) with severe sepsis or septic shock were included in an intention-to-treat analysis comparing sodium selenite (543 patients [49.9%]) with placebo (546 [50.1%]) and procalcitonin guidance (552 [50.7%]) vs no procalcitonin guidance (537 [49.3%]). The 28-day mortality rate was 28.3% (95% CI, 24.5%-32.3%) in the sodium selenite group and 25.5% (95% CI, 21.8%-29.4%) (P = .30) in the placebo group. There was no significant difference in 28-day mortality between patients assigned to procalcitonin guidance (25.6% [95% CI, 22.0%-29.5%]) vs no procalcitonin guidance (28.2% [95% CI, 24.4%-32.2%]) (P = .34). Procalcitonin guidance did not affect frequency of diagnostic or therapeutic procedures but did result in a 4.5% reduction of antimicrobial exposure. CONCLUSIONS AND RELEVANCE: Neither high-dose intravenous administration of sodium selenite nor anti-infectious therapy guided by a procalcitonin algorithm was associated with an improved outcome in patients with severe sepsis. These findings do not support administration of high-dose sodium selenite in these patients; the application of a procalcitonin-guided algorithm needs further evaluation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00832039.

Authors: F. Bloos, E. Trips, A. Nierhaus, J. Briegel, D. K. Heyland, U. Jaschinski, O. Moerer, A. Weyland, G. Marx, M. Grundling, S. Kluge, I. Kaufmann, K. Ott, M. Quintel, F. Jelschen, P. Meybohm, S. Rademacher, A. Meier-Hellmann, S. Utzolino, U. X. Kaisers, C. Putensen, G. Elke, M. Ragaller, H. Gerlach, K. Ludewig, M. Kiehntopf, H. Bogatsch, C. Engel, F. M. Brunkhorst, M. Loeffler, K. Reinhart

Date Published: 1st Sep 2016

Publication Type: Journal article

Human Diseases: disease by infectious agent

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