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Sökning: WFRF:(Frank Josef)

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51.
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52.
  • Zillich, Lea, et al. (författare)
  • Multi-omics signatures of alcohol use disorder in the dorsal and ventral striatum
  • 2022
  • Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Alcohol Use Disorder (AUD) is a major contributor to global mortality and morbidity. Postmortem human brain tissue enables the investigation of molecular mechanisms of AUD in the neurocircuitry of addiction. We aimed to identify differentially expressed (DE) genes in the ventral and dorsal striatum between individuals with AUD and controls, and to integrate the results with findings from genome- and epigenome-wide association studies (GWAS/EWAS) to identify functionally relevant molecular mechanisms of AUD. DNA-methylation and gene expression (RNA-seq) data was generated from postmortem brain samples of 48 individuals with AUD and 51 controls from the ventral striatum (VS) and the dorsal striatal regions caudate nucleus (CN) and putamen (PUT). We identified DE genes using DESeq2, performed gene-set enrichment analysis (GSEA), and tested enrichment of DE genes in results of GWASs using MAGMA. Weighted correlation network analysis (WGCNA) was performed for DNA-methylation and gene expression data and gene overlap was tested. Differential gene expression was observed in the dorsal (FDR < 0.05), but not the ventral striatum of AUD cases. In the VS, DE genes at FDR < 0.25 were overrepresented in a recent GWAS of problematic alcohol use. The ARHGEF15 gene was upregulated in all three brain regions. GSEA in CN and VS pointed towards cell-structure associated GO-terms and in PUT towards immune pathways. The WGCNA modules most strongly associated with AUD showed strong enrichment for immune response and inflammation pathways. Our integrated analysis of multi-omics data sets provides further evidence for the importance of immune- and inflammation-related processes in AUD.
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53.
  • Zimmermann, Stefan, et al. (författare)
  • Out-of-hospital cardiac arrest and percutaneous coronary intervention for ST-elevation myocardial infarction : Long-term survival and neurological outcome
  • 2013
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 166:1, s. 236-241
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Predictors of long-term outcome after ST-elevation myocardial infarction (STEMI) complicated by out-of-hospital cardiac arrest (OHCA) are incompletely understood, including the influence of successful coronary reperfusion.METHODS:We analysed clinical and procedural data as well as 1-year outcome of 72 consecutive patients who underwent primary coronary intervention (PCI) after witnessed OHCA and STEMI and compared the results with 695 patients with STEMI and PCI, but without OHCA. Neurological recovery after OHCA was assessed using the Cerebral Performance Category (CPC) scale.RESULTS:PCI was successful in 83.3% after OHCA vs. 84.3% in the non-OHCA group (p=0.87). One-year mortality was 34.7% vs. 9.5% (p<0.001). 58.3% of the OHCA-patients showed complete neurological recovery (CPC 1) or moderate neurological disability (CPC 2). Another 6.9% showed severe cerebral disability (CPC 3) or permanent vegetative status (CPC 4). Delay from collapse until start of Advanced Cardiopulmonary Life Support (ACLS) was shorter for survivors with CPC status ≤2 (median 1min, range 0-11min) compared to non-survivors or survivors with CPC status >2 (median 8min, range 0-13min), p<0.0001. Age-adjusted multivariate analysis identified 'unsuccessful PCI', 'vasopressors on admission' and 'start of ACLS after >6min' as independent predictors of negative long-term outcome (death or CPC >2).CONCLUSIONS: Mortality is high in patients with STEMI complicated by OHCA - even though PCI was performed with the same success rate as in patients without OHCA. The majority of survivors had favourable neurological outcomes at 1year, especially if advanced life support had been started within ≤6min and PCI was successful.
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54.
  • Zimmermann, Stefan, et al. (författare)
  • Outcomes of contemporary interventional therapy of ST elevation infarction in patients older than 75 years
  • 2009
  • Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 32:2, s. 87-93
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Data on contemporary real-world outcomes of interventional revascularization in patients > or = 75 y of age with ST elevation infarction (STEMI) are limited.METHODS:We analyzed all 504 consecutive patients who underwent angiography for acute STEMI between 1999 and 2005 at our center, and followed them up over one year. Outcomes in patients > or = 75 y of age were compared with younger patients.RESULTS:Patients > or = 75 y of age (n = 115) were majority females (55% versus 21%, p < 0.001), more cases of diabetes (42% versus 27%, p = 0.004), hypertension (78% versus 65%, p = 0.03) and a history of coronary events (25% versus 15%, p = 0.002). Younger patients were more often smokers (63% versus 30%, p < 0.001). After coronary angiography patients > or = 75 y of age underwent less frequent intervention (PCI; 84% versus 93%, p = 0.01). However, if PCI was performed, technical success rates were similar to younger patients (84% versus 86%). The 30-d mortality was 13% versus 6.4% (p = 0.03), but after successful PCI, the 30-d mortality rate was not significantly higher in old patients (7.4% versus 3.9%, p = 0.23). Bleeding complications were very low in both age groups if the radial access route was chosen. Multivariate predictors of 30-d mortality were cardiogenic shock/survived cardiac arrest, ejection fraction < 30%, conservative treatment or unsuccessful PCI (OR 3.01), renal insufficiency, diabetes, and age. One-y mortality was higher in the elderly (24.3% versus 9.9%, p < 0.001). Among 30-d-survivors, only multivessel disease and age were multivariate predictors of 1-y mortality.CONCLUSION:Patients > or = 75 y of age benefit from PCI in STEMI, and failed or unattempted PCI worsens prognosis in the old as well as in younger patients.
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55.
  • Zimmermann, Stefan, et al. (författare)
  • Short-term prognosis of contemporary interventional therapy of ST-elevation myocardial infarction : does gender matter?
  • 2009
  • Ingår i: Clinical Research in Cardiology. - : Springer Science and Business Media LLC. - 1861-0684 .- 1861-0692. ; 98:11, s. 709-715
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:A higher mortality risk for women with acute ST-elevation myocardial infarction (STEMI) has been a common finding in the past, even after acute percutaneous coronary intervention (PCI). We set out to analyze whether there are gender differences in real-world contemporary treatment and outcomes of STEMI.PATIENTS AND METHODS:A retrospective analysis of all consecutive patients with STEMI and acute coronary angiography with the intention of performing a PCI at our center 6/1999-6/2006 was carried out (n = 566). Data were examined for gender-specific differences regarding patients' characteristics, referral patterns, timing of acute symptoms, angiographic findings, procedural details, and adverse events at 30 days after PCI.RESULTS:Women (n = 161) were on average 8 years older than men (n = 405), had higher co-morbidity, were more often transported to the hospital by ambulance and presented less often to the emergency room on their own (4.2% vs. 12.6% in men, P = 0.02). The pre-hospital delay from symptom onset to admission was significantly longer for women (median 185 vs. 135 min, P < 0.02). There was no gender difference in time from admission to PCI (median 46 min vs. 48 min, P = 0.42). Both genders received PCI with similar frequency (88.8% vs. 92.4%, P = 0.19), with similar success rates (83.2% vs. 85.3%, P = 0.68). Thirty-day overall mortality for women was not significantly higher than for men (8.7% vs. 7.2%, P = 0.6). Re-infarction or stroke within 30 days were rare for both genders without gender-specific differences whereas bleeding necessitating blood replacement was significantly more frequent in women (16.8% vs. 5.9%, P < 0.001). In multivariate analysis, female gender was not independently associated with a higher risk of 30-day mortality (OR 0.964, P = 0.93).CONCLUSIONS:Women underwent PCI therapy for STEMI with the same frequency and the same angiographic success as men. Despite their more advanced age and the higher prevalence of co-morbidities, they did not have a significantly higher 30-day mortality rate than men. Female gender was not an independent risk factor of 30-day mortality. Longer pre-hospital delays before hospital admission in women indicate that awareness of risk from coronary artery disease should be further raised in women.
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56.
  • 2018
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
  • Forskningsöversikt (refereegranskat)
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