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Sökning: WFRF:(Hirsch Hans)

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1.
  • Engert, Andreas, et al. (författare)
  • The European Hematology Association Roadmap for European Hematology Research : a consensus document
  • 2016
  • Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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2.
  • Bächli, Heidi, et al. (författare)
  • Skull base and maxillofacial fractures : two centre study with correlation of clinical findings with a comprehensive craniofacial classification system
  • 2009
  • Ingår i: Journal of Cranio-Maxillofacial Surgery. - : Elsevier BV. - 1010-5182 .- 1878-4119. ; 37:6, s. 305-11
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: A comprehensive classification based on high resolution computed tomography (CT) of the whole craniofacial region was correlated with clinical findings of combined skull base and maxillofacial fractures. MATERIAL AND METHODS: In a study of two clinical centres, 70 patients with such injuries were admitted at the Universities of Basel (n=29) and Uppsala (n=41). Clinical signs (rhinorrhoea, periorbital haematoma and pneumencephalus) and surgical versus conservative treatment were correlated with a cranio-maxillofacial injury severity score (CMF-ISS) calculated from the classification system. Fracture classifications were decided in consensus on the basis of CT and semiautomatic classification software. The classification system defined 3 fracture types (A, B, C), 3 groups (A1, A2, A3), and 3 subgroups (A1.1, A1.2, A1.3) with increasing severity from A1.1 (lowest) to C3.3 (highest). RESULTS: Of 70 patients, 43 were operated upon and 27 conservatively treated. The operated patients had significantly higher severity scores than non-operated. Patients with or without periorbital haematoma do not differ significantly in the severity score. The severity of the CMF-ISS score was significantly associated (two sample T-test P<0.01) with the occurrence of pneumencephalus, rhinorrhoea and treatment approach. CONCLUSION: Based on our present results, this system seems to be clinical useful for operative decisions and interventions.
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3.
  • Cesaro, Simone, et al. (författare)
  • Cidofovir for BK Virus-Associated Hemorrhagic Cystitis: A Retrospective Study
  • 2009
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 49:2, s. 233-240
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation (HSCT), but antiviral treatment for this condition has not been evaluated. Methods. We conducted a retrospective survey on the safety and outcome of cidofovir treatment for patients with BKV-HC in centers affiliated with the European Group for Blood and Marrow Transplantation. Results. From 1 April 2004 to 31 December 2007, 62 patients received a diagnosis of BKV-HC after a median interval of 35 days after HSCT (range, 3-577 days). Fifty-seven patients (92%) received intravenous cidofovir, whereas 5 patients received cidofovir intravesically. Complete response (CR) was recorded in 38 (67%) of 57 patients with HC treated with intravenous cidofovir, whereas partial response (PR) was documented in 7 patients (12%). CR was documented in 3 patients and PR in 1 patient with HC treated with intravesical cidofovir. A reduction of 1-3 logs in BKV load was documented in 8 of the 10 patients achieving CR. Mild-to-moderate toxic effects were recorded in 18 of 57 patients who received intravenous cidofovir administration. In a multivariate analysis, the factors significantly associated with response to cidofovir were the stem cell source (Pp. 01) and the use of total body irradiation (P = .03). After a median follow-up of 287 days, overall survival and total treatment-related mortality rates were 63% and 40% for patients achieving CR, compared with 14% and 72% for patients with PR or no response to cidofovir, respectively (P < .001 and P = .001, respectively). Conclusions. Cidofovir may be a potentially effective therapy for BKV-HC, but evidence supporting its use requires randomized controlled trials.
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4.
  • Ebner, Florian, et al. (författare)
  • The association of partial pressures of oxygen and carbon dioxide with neurological outcome after out-of-hospital cardiac arrest : an explorative International Cardiac Arrest Registry 2.0 study
  • 2020
  • Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 28:1, s. 67-67
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Exposure to extreme arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) following the return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) is common and may affect neurological outcome but results of previous studies are conflicting.METHODS: Exploratory study of the International Cardiac Arrest Registry (INTCAR) 2.0 database, including 2162 OHCA patients with ROSC in 22 intensive care units in North America and Europe. We tested the hypothesis that exposure to extreme PaO2 or PaCO2 values within 24 h after OHCA is associated with poor neurological outcome at discharge. Our primary analyses investigated the association between extreme PaO2 and PaCO2 values, defined as hyperoxemia (PaO2 > 40 kPa), hypoxemia (PaO2 < 8.0 kPa), hypercapnemia (PaCO2 > 6.7 kPa) and hypocapnemia (PaCO2 < 4.0 kPa) and neurological outcome. The secondary analyses tested the association between the exposure combinations of PaO2 > 40 kPa with PaCO2 < 4.0 kPa and PaO2 8.0-40 kPa with PaCO2 > 6.7 kPa and neurological outcome. To define a cut point for the onset of poor neurological outcome, we tested a model with increasing and decreasing PaO2 levels and decreasing PaCO2 levels. Cerebral Performance Category (CPC), dichotomized to good (CPC 1-2) and poor (CPC 3-5) was used as outcome measure.RESULTS: Of 2135 patients eligible for analysis, 700 were exposed to hyperoxemia or hypoxemia and 1128 to hypercapnemia or hypocapnemia. Our primary analyses did not reveal significant associations between exposure to extreme PaO2 or PaCO2 values and neurological outcome (P = 0.13-0.49). Our secondary analyses showed no significant associations between combinations of PaO2 and PaCO2 and neurological outcome (P = 0.11-0.86). There was no PaO2 or PaCO2 level significantly associated with poor neurological outcome. All analyses were adjusted for relevant co-variates.CONCLUSIONS: Exposure to extreme PaO2 or PaCO2 values in the first 24 h after OHCA was common, but not independently associated with neurological outcome at discharge.
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6.
  • Feng, Chi, et al. (författare)
  • Hygric properties of porous building materials (VI) : A round robin campaign
  • 2020
  • Ingår i: Building and Environment. - : Elsevier BV. - 0360-1323. ; 185
  • Tidskriftsartikel (refereegranskat)abstract
    • Hygric properties of porous building materials are important for hygrothermal analysis. Their experimental determination is however not always reliable, shown by the discrepant results from different laboratories on the same materials. In this study, a recent round robin campaign initiated by KU Leuven (Belgium) and participated in by eight institutes from different countries is reported. Ceramic brick was selected as the target material. The bulk density and open porosity from vacuum saturation tests, the capillary absorption coefficient and capillary moisture content from capillary absorption tests, and the vapor permeability from cup tests were measured. Results were analyzed statistically and compared with a previous round robin project, EC HAMSTAD. The reproducibility errors for determining the capillary absorption coefficient were noticeably reduced when compared with the EC HAMSTAD project, and the different laboratories in the present study obtained similar results from vacuum saturation tests and capillary absorption tests without a common protocol. For cup tests, large inter-laboratory discrepancies still exist. However, with a stringent common protocol different laboratories achieved consistent results. For all properties a common protocol did not change the average results of all laboratories.
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7.
  • Groenewold, Nynke A., et al. (författare)
  • Volume of subcortical brain regions in social anxiety disorder : mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group
  • 2023
  • Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28:3, s. 1079-1089
  • Tidskriftsartikel (refereegranskat)abstract
    • There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.
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8.
  • Hahn, Gabriele, et al. (författare)
  • Pharmacokinetics and safety of gadobutrol-enhanced magnetic resonance imaging in pediatric patients
  • 2009
  • Ingår i: Investigative Radiology. - 0020-9996 .- 1536-0210. ; 44:12, s. 776-783
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: This clinical study investigated the pharmacokinetics and safety of gadobutrol, a magnetic resonance (MR) imaging extracellular contrast agent, in pediatric patients aged 2 to 17 years. MATERIALS AND METHODS: In this open-label, multicenter study, patients scheduled for routine contrast-enhanced MR imaging of the brain, spine, liver or kidney, or MR angiography received a single intravenous injection of gadobutrol (0.1 mmol/kg/0.1 mL/kg). Patients were stratified by age groups (2-6, 7-11, and 12-17 years). Blood and urine samples were collected at prespecified time points and analyzed for gadolinium concentrations. Plasma data were evaluated by means of a nonlinear mixed effects model, and urine data were analyzed using descriptive statistics. In addition, the safety of gadobutrol was evaluated. RESULTS: A total of 130 patients (2-6 years, n = 45; 7-11 years, n = 39; 12-17 years, n = 46) were included in the final population pharmacokinetic analysis. Gadobutrol pharmacokinetics in children aged 2 to 17 years were adequately described by an open 2-compartment model with elimination from the central compartment. The median estimates (2.5th percentile, 97.5th percentile) of body weight-normalized total body clearance (L/h/kg) per age group were 0.10 (0.05, 0.17) for all ages, 0.13 (0.09, 0.17) in the 2 to 6 year age group, 0.10 (0.05, 0.17) in the 7 to 11 year age group and 0.09 (0.05, 0.10) in the 12 to 17 year age group. The body weight-normalized median estimates of total volume of distribution (L/kg) were 0.20 (0.12, 0.28) for all ages, 0.24 (0.20, 0.28) in the 2 to 6 year age group, 0.19 (0.14, 0.23) in the 7 to 11 year age group and 0.18 (0.092, 0.23) in the 12 to 17 year age group. Median gadolinium plasma concentrations at 20 minutes postinjection were simulated using the population pharmacokinetic model and ranged from 414 (13 kg subject) to 518 micromol/L (65 kg subject). Body weight was identified as the major covariate influencing the pharmacokinetic parameters of total body clearance and central volume of distribution. Age was not found to be an additional independent parameter. The median amount of renally excreted gadolinium was 77.0% of the administered dose within 6 hours postinjection, indicating that gadobutrol was renally excreted in this pediatric population aged 2 to 17 years. Gadobutrol was well tolerated, with drug-related adverse events of mild intensity reported for 8 (5.8%) of 138 patients. CONCLUSIONS: Observed differences in pharmacokinetics were attributed to body weight, with no additional independent effect of age. Thus, no dose adjustment from the standard dose of gadobutrol in adults based on body weight (0.1 mmol/kg) is necessary in pediatric patients aged 2 to 17 years. Gadobutrol was safe and well tolerated in the pediatric population in this study.
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9.
  • Harhash, Ahmed A., et al. (författare)
  • Incidence of cardiac interventions and associated cardiac arrest outcomes in patients with nonshockable initial rhythms and no ST elevation post resuscitation
  • 2021
  • Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 167, s. 188-197
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Out of Hospital Cardiac arrest (OHCA) survivors with ST elevation (STE) with or without shockable rhythms often benefit from coronary angiography (CAG) and, if indicated, percutaneous coronary intervention (PCI). However, the benefits of CAG and PCI in OHCA survivors with nonshockable rhythms (PEA/asystole) and no STE are debated.Methods: Using the International Cardiac Arrest Registry (INTCAR 2.0), representing 44 centers in the US and Europe, comatose OHCA survivors with known presenting rhythms and post resuscitation ECGs were identified. Survival to hospital discharge, neurological recovery on discharge, and impact of CAG with or without PCI on such outcome were assessed and compared with other groups (shockable rhythms with or without STE).Results: Total of 2113 OHCA survivors were identified and described as; nonshockable/no STE (Nsh-NST) (n = 940, 44.5%), shockable/no STE (Sh-NST) (n = 716, 33.9%), nonshockable/STE (Nsh-ST) (n = 110, 5.2%), and shockable/STE (Sh-ST) (n = 347, 16.4%). Of Nsh-NST, 13.7% (129) were previously healthy before CA and only 17.3% (161) underwent CAG; of those, 30.4% (52) underwent PCI. A total of 18.6% (174) Nsh-NST patients survived to hospital discharge, with 57.5% (100) of such survivors having good neurological recovery (cerebral performance category 1 or 2) on discharge. Coronary angiography was associated with improved odds for survival and neurological recovery among all groups, including those with NSh-NST.Conclusions: Nonshockable initial rhythms with no ST elevation post resuscitation was the most common presentation after OHCA. Although most of these patients did not undergo coronary angiography, among those who did, 1 in 4 patients had a culprit lesion and underwent revascularization. Invasive CAG should be at least considered for all OHCA survivors, including those with nonshockable rhythms and no ST elevation post resuscitation.
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10.
  • Harhash, Ahmed A., et al. (författare)
  • Risk Stratification Among Survivors of Cardiac Arrest Considered for Coronary Angiography
  • 2021
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 77:4, s. 360-371
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe American College of Cardiology Interventional Council published consensus-based recommendations to help identify resuscitated cardiac arrest patients with unfavorable clinical features in whom invasive procedures are unlikely to improve survival.ObjectivesThis study sought to identify how many unfavorable features are required before prognosis is significantly worsened and which features are most impactful in predicting prognosis.MethodsUsing the INTCAR (International Cardiac Arrest Registry), the impact of each proposed “unfavorable feature” on survival to hospital discharge was individually analyzed. Logistic regression was performed to assess the association of such unfavorable features with poor outcomes.ResultsSeven unfavorable features (of 10 total) were captured in 2,508 patients successfully resuscitated after cardiac arrest (ongoing cardiopulmonary resuscitation and noncardiac etiology were exclusion criteria in our registry). Chronic kidney disease was used in lieu of end-stage renal disease. In total, 39% survived to hospital discharge. The odds ratio (OR) of survival to hospital discharge for each unfavorable feature was as follows: age >85 years OR: 0.30 (95% CI: 0.15 to 0.61), time-to-ROSC >30 min OR: 0.30 (95% CI: 0.23 to 0.39), nonshockable rhythm OR: 0.39 (95% CI: 0.29 to 0.54), no bystander cardiopulmonary resuscitation OR: 0.49 (95% CI: 0.38 to 0.64), lactate >7 mmol/l OR: 0.50 (95% CI: 0.40 to 0.63), unwitnessed arrest OR: 0.58 (95% CI: 0.44 to 0.78), pH <7.2 OR: 0.78 (95% CI: 0.63 to 0.98), and chronic kidney disease OR: 0.96 (95% CI: 0.70 to 1.33). The presence of any 3 or more unfavorable features predicted <40% survival. Presence of the 3 strongest risk factors (age >85 years, time-to-ROSC >30 min, and non-ventricular tachycardia/ventricular fibrillation) together or ≥6 unfavorable features predicted a ≤10% chance of survival to discharge.ConclusionsPatients successfully resuscitated from cardiac arrest with 6 or more unfavorable features have a poor long-term prognosis. Delaying or even forgoing invasive procedures in such patients is reasonable.
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