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1005 Publications visible to you, out of a total of 1005
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

Association, characterisation and meta-analysis of SNPs linked to general reading ability in a German dyslexia case-control cohort
Genetical Statistics and Systems Biology

Abstract (Expand)

Dyslexia is a severe disorder in the acquisition of reading and writing. Several studies investigated the role of genetics for reading, writing and spelling ability in the general population. However, … many of the identified SNPs were not analysed in case-control cohorts. Here, we investigated SNPs previously linked to reading or spelling ability in the general population in a German case-control cohort. Furthermore, we characterised these SNPs for functional relevance with in silico methods and meta-analysed them with previous studies. A total of 16 SNPs within five genes were included. The total number of risk alleles was higher in cases than in controls. Three SNPs were nominally associated with dyslexia: rs7765678 within DCDC2, and rs2038137 and rs6935076 within KIAA0319. The relevance of rs2038137 and rs6935076 was further supported by the meta-analysis. Functional profiling included analysis of tissue-specific expression, annotations for regulatory elements and effects on gene expression levels (eQTLs). Thereby, we found molecular mechanistical implications for 13 of all 16 included SNPs. SNPs associated in our cohort showed stronger gene-specific eQTL effects than non-associated SNPs. In summary, our results validate SNPs previously linked to reading and spelling in the general population in dyslexics and provide insights into their putative molecular pathomechanisms.

Authors: Bent Müller, Arndt Wilcke, Ivonne Czepezauer, Peter Ahnert, Johannes Boltze, Holger Kirsten

Date Published: 1st Sep 2016

Publication Type: Journal article

Sleep disturbances and upregulation of brain arousal during daytime in depressed versus non-depressed elderly subjects.
LIFE Adult

Abstract (Expand)

OBJECTIVES: Although patients with depression often suffer from sleep disturbances, most of them are not sleepy. Upregulation of brain arousal has been proposed as pathophysiological mechanism explaining … sleep disturbances, inner tension, autonomic hyperarousal and anhedonia in depression. The aim of the current study was to examine the association between night-time sleep disturbances and brain arousal regulation the next day in depressed versus non-depressed subjects. METHODS: Twenty-eight elderly subjects (21 female; age = 70.5 +/- 4.4 years) with depressive syndromes without psychotropic medication, and 28 controls (22 female; age = 70.9 +/- 4.5 years), underwent a 15-min resting electroencephalogram; the Vigilance Algorithm Leipzig (VIGALL 2.1) provided an objective measure of brain arousal regulation. Sleep disturbances were assessed by a validated and self-rated sleep questionnaire. RESULTS: In the depressive group, but not in controls, more sleep disturbances were associated with a higher brain arousal stability score (high score corresponds to upregulation) the next day (sleep onset latency: rs = 0.69, P < .0001; sleep quality: rs = -0.59, P < .001). CONCLUSIONS: The data confirm the hypothesis that in persons with depressive syndromes sleep disturbances are related to upregulation of brain arousal the next day. This finding is in line with the concept that dysregulation of brain arousal is a central pathophysiological aspect in depression.

Authors: C. Ulke, C. Sander, P. Jawinski, N. Mauche, J. Huang, J. Spada, D. Wittekind, R. Mergl, T. Luck, S. Riedel-Heller, T. Hensch, U. Hegerl

Date Published: 25th Aug 2016

Publication Type: Journal article

Human Diseases: mental depression

FTO Obesity Risk Variants Are Linked to Adipocyte IRX3 Expression and BMI of Children - Relevance of FTO Variants to Defend Body Weight in Lean Children?
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Genome-wide association studies have identified variants within the FTO (fat mass and obesity associated) locus as the strongest predictors of obesity amongst all obesity-associated gene …e loci. Recent evidence suggests that variants in FTO directly affect human adipocyte function through targeting IRX3 and IRX5 and thermogenesis regulation. AIM We addressed the relevance of this proposed FTO-IRX pathway in adipose tissue (AT) of children. RESULTS Expression of IRX3 was higher in adipocytes compared to SVF. We found increased adipocyte-specific expression of IRX3 and IRX5 with the presence of the FTO risk haplotype in lean children, whereas it was unaffected by risk variants in obese peers. We further show that IRX3 expression was elevated in isolated adipocytes and AT of lean compared to obese children, particularly in UCP1-negative adipocytes, and inversely correlated with BMI SDS. Independent of BMI, IRX3 expression in adipocytes was significantly related to adipocyte hypertrophy, and subsequent associations with AT inflammation and HOMA-IR in the children. CONCLUSION One interpretation of our observation of FTO risk variants linked to IRX3 expression and adipocyte size restricted to lean children, along with the decreased IRX3 expression in obese compared to lean peers, may reflect a defense mechanism for protecting body-weight, which is pertinent for lean children.

Authors: Kathrin Landgraf, Markus Scholz, Peter Kovacs, Wieland Kiess, Antje Körner

Date Published: 25th Aug 2016

Publication Type: Journal article

Comparing Measures of Association in 2x2 Probability Tables
Genetical Statistics and Systems Biology

Abstract

Not specified

Authors: Dirk Hasenclever, Markus Scholz

Date Published: 23rd Aug 2016

Publication Type: Journal article

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