Institute For Medizinische Informatik

fur, Germany

Institute For Medizinische Informatik

fur, Germany
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Dotsch A.,University of Duisburg - Essen | Eisele L.,Institute For Medizinische Informatik | Rabeling M.,University of Duisburg - Essen | Rump K.,University of Duisburg - Essen | And 11 more authors.
International Journal of Molecular Sciences | Year: 2017

Hypoxia-inducible-factor-2α (HIF-2α) and HIF-2 degrading prolyl-hydroxylases (PHD) are key regulators of adaptive hypoxic responses i.e., in acute respiratory distress syndrome (ARDS). Specifically, functionally active genetic variants of HIF-2α (single nucleotide polymorphism (SNP) [ch2:46441523(hg18)]) and PHD2 (C/T; SNP rs516651 and T/C; SNP rs480902) are associated with improved adaptation to hypoxia i.e., in high-altitude residents. However, little is known about these SNPs’ prevalence in Caucasians and impact on ARDS-outcome. Thus, we tested the hypotheses that in Caucasian ARDS patients SNPs in HIF-2α or PHD2 genes are (1) common, and (2) independent risk factors for 30-day mortality. After ethics-committee approval, 272 ARDS patients were prospectively included, genotyped for PHD2 (Taqman SNP Genotyping Assay) and HIF-2α-polymorphism (restriction digest + agarose-gel visualization), and genotype dependent 30-day mortality was analyzed using Kaplan-Meier-plots and multivariate Cox-regression analyses. Frequencies were 99.62% for homozygous HIF-2α CC-carriers (CG: 0.38%; GG: 0%), 2.3% for homozygous PHD2 SNP rs516651 TT-carriers (CT: 18.9%; CC: 78.8%), and 3.7% for homozygous PHD2 SNP rs480902 TT-carriers (CT: 43.9%; CC: 52.4%). PHD2 rs516651 TT-genotype in ARDS was independently associated with a 3.34 times greater mortality risk (OR 3.34, CI 1.09–10.22; p = 0.034) within 30-days, whereas the other SNPs had no significant impact (p = ns). The homozygous HIF-2α GG-genotype was not present in our Caucasian ARDS cohort; however PHD2 SNPs exist in Caucasians, and PHD2 rs516651 TT-genotype was associated with an increased 30-day mortality suggesting a relevance for adaptive responses in ARDS. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

Shankar A.,University College London | Hall G.W.,Childrens Hospital | Gorde-Grosjean S.,Reims University Hospital Center | Hasenclever D.,Institute For Medizinische Informatik | And 11 more authors.
European Journal of Cancer | Year: 2012

Purpose: To examine whether three cycles of a low-intensity chemotherapy consisting of cyclophosphamide [500 mg/m 2 - day 1], vinblastine [6 mg/m 2 - days 1 and 8] and prednisolone [40 mg/m 2 - days 1-7] (CVP) is safe and therapeutically effective in children and adolescents with early stage nodular lymphocyte predominant Hodgkin lymphoma [nLPHL]. Patients and methods: Fifty-five children and adolescents with early stage nLPHL [median age 13 years, range 4-17 years] diagnosed between June 2005 and October 2010 in the UK and France are the subjects of this report. Staging investigations included conventional cross sectional as well as 18 fluro-deoxyglucose [FDG] PET imaging. Histology was confirmed as nLPHL by an expert pathology panel. Results: Of the 45 patients, who received CVP as first line treatment, 36 [80%, 95% Confidence Interval [CI]: (68; 92)] either achieved a complete remission [CR] or CR unconfirmed [CRu], the remaining nine patients achieved a partial response. All nine subsequently achieved CR with salvage chemotherapy [n = 7] or radiotherapy [n = 2]. Ten patients received CVP at relapse after primary treatment that consisted of surgery alone and all achieved CR. To date, only three patients have relapsed after CVP chemotherapy and all had received CVP as first line treatment at initial diagnosis. The 40-month freedom from treatment failure and overall survival for the entire cohort were 75.4% (SE ± 6%) and 100%, respectively. No significant early toxicity was observed. Conclusions: Our results show that CVP is an effective chemotherapy regimen in children and adolescents with early stage nLPHL that is well tolerated with minimal acute toxicity. © 2011 Elsevier Ltd. All rights reserved.

Adamzik M.,Universitatsklinikum Essen | Frey U.H.,Universitatsklinikum Essen | Mohlenkamp S.,Klinik fur Innere Medizin | Scherag A.,Institute For Medizinische Informatik | And 6 more authors.
Anesthesiology | Year: 2011

Background: Because the aquaporin (AQP) 5 promoter -1364A/C polymorphism is associated with altered AQP5 expression, this association could have an impact on key mechanisms in sepsis, such as cell migration, activity of the rennin-angiotensin- aldosterone system (RAAS), and water transport across biologic membranes. Therefore, we tested the hypothesis that the AQP5 promoter -1364A/C polymorphism is associated with increased 30-day survival in severe sepsis. Methods: In a prospective study, adults with severe sepsis (N = 154) were genotyped for the AQP5 promoter -1364A/C polymorphism. The clinical endpoint was 30-day survival. Kaplan-Meier plots and multivariate proportional hazard analyses were used to evaluate the relationship between genotypes and clinical outcomes. Results: Thirty-day survival was significantly associated with AQP5 -1364A/C genotypes (P = 0.001). Survival rates were 57% for AA genotypes (n = 90) but 83% for combined AC/CC genotypes (56 vs. 8, respectively). Multivariate proportional hazard analysis including sex, age, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment score, body mass index, necessity for continuous hemofiltration/dialysis, concentrations of plasma angiotensin II, serum aldosterone, C-reactive protein, and interleukin 6 as covariates revealed the AQP5 -1364A/C polymorphism as a strong and independent prognostic factor for 30-day survival. In this analysis, homozygous AA subjects were at high risk for death within 30 days (hazard ratio, 3.59; 95% CI, 1.47-8.80; P = 0.005) compared with AC/CC genotypes. Conclusion: The C-allele of the AQP5 -1364A/C polymorphism is associated with increased 30-day survival in patients with severe sepsis. This finding suggests the importance of variations in expression of AQP5 channels in severe sepsis.© 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.

Wolf M.,Medical University of Graz | Clar H.,Medical University of Graz | Friesenbichler J.,Medical University of Graz | Schwantzer G.,Institute For Medizinische Informatik | And 5 more authors.
International Orthopaedics | Year: 2014

Purpose: Prosthetic hip joint infection remains a challenging socio-economic problem. Curative treatment is usually a one- or two-stage revision surgery, but neither of these options has yet emerged as the treatment of choice. The aim of this study was to evaluate which of these methods produced superior outcomes. Methods: A retrospective study was performed including 92 patients with deep infections after implantation of primary total hip arthroplasty (THA) who had undergone either one-stage or two-stage revision surgery at a single centre. Infections were classified according to McPherson and we evaluated the rate of persisting infection or reinfection after surgical intervention. Results: The two-stage revision surgery revealed superior outcomes for the analysed infection categories compared to the one-stage procedure except for the least serious category of infections (i.e. McPherson Stage I/A/1, early postoperative infection, no systemic comorbidities, local status uncompromised). Eradication of prosthetic infection was achieved in 94.5 % (n=52) within the group of two-stage exchange, and 56.8 % (n=21) of patients treated with a one-stage procedure. Outcome of patients following a one-stage or a two-stage exchange was overall significantly different with p<0.001. Further deviations between the described two procedures were noted in the subgroups following the classification described by McPherson. Conclusions: Our results indicate superiority of two-stage revision surgery in case of serious infections. The authors believe that decisions on the surgical approach for the treatment of deep prosthesis infections should be made on the basis of standardized staging systems. © 2014 Springer-Verlag.

Czihal M.,Klinikum der LMU | Paul S.,Klinikum der LMU | Rademacher A.,Klinikum der LMU | Bernau C.,Institute For Medizinische Informatik | Hoffmann U.,Klinikum der LMU
Vasa - Journal of Vascular Diseases | Year: 2012

Background: To determine the impact of the postthrombotic syndrome (PTS) on quality of life after primary upper extremity deep venous thrombosis (UEDVT). Patients and methods: Twenty-five patients with a history of primary UEDVT, treated with anticoagulation alone, and twenty healthy controls were retrospectively identified and prospectively assessed for health-related quality of life (SF- 36 and VEINES-QOL-questionnaire) and upper extremity functional impairment (DASH-score). Presence of PTS was classified according to the modified Villalta-score. Comparisons between patients and controls and between patients with and without PTS were performed using Fisher's exact test (categorical variables) and Mann-Whitney-U-test (continuous variables). Results: According to the modified Villalta-score, 32% of the patients suffered from mild to moderate PTS. None of the patients developed severe PTS. Compared to healthy control subjects, patients with a history of primary UEDVT reported on considerably worse health-related quality of life and significantly stronger upper extremity functional impairment. Within the cohort of patients with UEDVT, subjects with PTS had a significantly reduced quality of life and a more severe functional limitation. Conclusions: Quality of life and functional performance are impaired in patients with a history of conservatively treated primary UEDVT. Impairment is most pronounced in patients with mild to moderate PTS occurring in every third patient. © 2012 Hans Huber Publishers, Hogrefe AG, Bern.

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