@article{HaarmannVollmuthKollikowskietal.2023,
  author    = {Haarmann, Axel and Vollmuth, Christoph and Kollikowski, Alexander M. and Heuschmann, Peter U. and Pham, Mirko and Stoll, Guido and Neugebauer, Hermann and Schuhmann, Michael K.},
  title     = {Vasoactive soluble endoglin: a novel biomarker indicative of reperfusion after cerebral large-vessel occlusion},
  series = {Cells},
  volume    = {12},
  journal   = {Cells},
  number    = {2},
  issn      = {2073-4409},
  doi       = {10.3390/cells12020288},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304995},
  year      = {2023},
  abstract  = {Now that mechanical thrombectomy has substantially improved outcomes after large-vessel occlusion stroke in up to every second patient, futile reperfusion wherein successful recanalization is not followed by a favorable outcome is moving into focus. Unfortunately, blood-based biomarkers, which identify critical stages of hemodynamically compromised yet reperfused tissue, are lacking. We recently reported that hypoxia induces the expression of endoglin, a TGF-β co-receptor, in human brain endothelium in vitro. Subsequent reoxygenation resulted in shedding. Our cell model suggests that soluble endoglin compromises the brain endothelial barrier function. To evaluate soluble endoglin as a potential biomarker of reperfusion (-injury) we analyzed its concentration in 148 blood samples of patients with acute stroke due to large-vessel occlusion. In line with our in vitro data, systemic soluble endoglin concentrations were significantly higher in patients with successful recanalization, whereas hypoxia alone did not induce local endoglin shedding, as analyzed by intra-arterial samples from hypoxic vasculature. In patients with reperfusion, higher concentrations of soluble endoglin additionally indicated larger infarct volumes at admission. In summary, we give translational evidence that the sequence of hypoxia and subsequent reoxygenation triggers the release of vasoactive soluble endoglin in large-vessel occlusion stroke and can serve as a biomarker for severe ischemia with ensuing recanalization/reperfusion.},
  language  = {en}
}
@article{GabrielJirůHillmannKraftetal.2020,
  author    = {Gabriel, Katharina M. A. and J{\´i}rů-Hillmann, Steffi and Kraft, Peter and Selig, Udo and R{\"u}cker, Victoria and M{\"u}hler, Johannes and D{\"o}tter, Klaus and Keidel, Matthias and Soda, Hassan and Rascher, Alexandra and Schneider, Rolf and Pfau, Mathias and Hoffmann, Roy and Stenzel, Joachim and Benghebrid, Mohamed and Goebel, Tobias and Doerck, Sebastian and Kramer, Daniela and Haeusler, Karl Georg and Volkmann, Jens and Heuschmann, Peter U. and Fluri, Felix},
  title     = {Two years' experience of implementing a comprehensive telemedical stroke network comprising in mainly rural region: the Transregional Network for Stroke Intervention with Telemedicine (TRANSIT-Stroke)},
  series = {BMC Neurology},
  volume    = {20},
  journal   = {BMC Neurology},
  doi       = {10.1186/s12883-020-01676-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229214},
  year      = {2020},
  abstract  = {Background Telemedicine improves the quality of acute stroke care in rural regions with limited access to specialized stroke care. We report the first 2 years' experience of implementing a comprehensive telemedical stroke network comprising all levels of stroke care in a defined region. Methods The TRANSIT-Stroke network covers a mainly rural region in north-western Bavaria (Germany). All hospitals providing acute stroke care in this region participate in TRANSIT-Stroke, including four hospitals with a supra-regional certified stroke unit (SU) care (level III), three of those providing teleconsultation to two hospitals with a regional certified SU (level II) and five hospitals without specialized SU care (level I). For a two-year-period (01/2015 to 12/2016), data of eight of these hospitals were available; 13 evidence-based quality indicators (QIs) related to processes during hospitalisation were evaluated quarterly and compared according to predefined target values between level-I- and level-II/III-hospitals. Results Overall, 7881 patients were included (mean age 74.6 years +/- 12.8; 48.4\% female). In level-II/III-hospitals adherence of all QIs to predefined targets was high ab initio. In level-I-hospitals, three patterns of QI-development were observed: a) high adherence ab initio (31\%), mainly in secondary stroke prevention; b) improvement over time (44\%), predominantly related to stroke specific diagnosis and in-hospital organization; c) no clear time trends (25\%). Overall, 10 out of 13 QIs reached predefined target values of quality of care at the end of the observation period. Conclusion The implementation of the comprehensive TRANSIT-Stroke network resulted in an improvement of quality of care in level-I-hospitals.},
  language  = {en}
}
@article{PruggerHeidrichWellmannetal.2012,
  author    = {Prugger, Christof and Heidrich, Jan and Wellmann, J{\"u}rgen and Dittrich, Ralf and Brand, Stefan-Martin and Telgmann, Ralph and Breithardt, G{\"u}nter and Reinecke, Holger and Scheld, Hans and Kleine-Katth{\"o}fer, Peter and Heuschmann, Peter U. and Keil, Ulrich},
  title     = {Trends in Cardiovascular Risk Factors Among Patients With Coronary Heart Disease : Results From the EUROASPIRE I, II, and III Surveys in the M{\"u}nster Region},
  series = {Deutsches {\"A}rzteblatt International},
  volume    = {109},
  journal   = {Deutsches {\"A}rzteblatt International},
  number    = {17},
  doi       = {10.3238/arztebl.2012.0303},
  pages     = {303-U21},
  year      = {2012},
  abstract  = {Background: Target values for cardiovascular risk factors in patients with coronary heart disease (CHD) are stated in guidelines for the prevention of cardiovascular disease. We studied secular trends in risk factors over a 12-year period among CHD patients in the region of Munster, Germany. Methods: The cross-sectional EUROASPIRE I, II and III surveys were performed in multiple centers across Europe. For all three, the Munster region was the participating German region. In the three periods 1995/96, 1999/2000, and 2006/07, the surveys included (respectively) 392, 402 and 457 <= 70-year-old patients with CHD in Munster who had sustained a coronary event at least 6 months earlier. Results: The prevalence of smoking remained unchanged, with 16.8\% in EUROASPIRE I and II and 18.4\% in EUROASPIRE III (p=0.898). On the other hand, high blood pressure and high cholesterol both became less common across the three EUROASPIRE studies (60.7\% to 69.4\% to 55.3\%, and 94.3\% to 83.4\% to 48.1\%, respectively; p<0.001 for both). Obesity became more common (23.0\% to 30.6\% to 43.1\%, p<0.001), as did treatment with antihypertensive and lipid-lowering drugs (80.4\% to 88.6\% to 94.3\%, and 35.0\% to 67.4\% to 87.0\%, respectively; p<0.001 for both). Conclusion: The observed trends in cardiovascular risk factors under-score the vital need for better preventive strategies in patients with CHD.},
  language  = {en}
}
@article{OezkurMagyarThomasetal.2017,
  author    = {Oezkur, Mehmet and Magyar, Attila and Thomas, Phillip and Stork, Tabea and Schneider, Reinhard and Bening, Constanze and St{\"o}rk, Stefan and Heuschmann, Peter U. and Leyh, Rainer G. and Wagner, Martin},
  title     = {TIMP-2*IGFBP7 (Nephrocheck®) Measurements at Intensive Care Unit Admission After Cardiac Surgery are Predictive for Acute Kidney Injury Within 48 Hours},
  series = {Kidney \& Blood Pressure Research},
  volume    = {42},
  journal   = {Kidney \& Blood Pressure Research},
  doi       = {10.1159/000479298},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157988},
  pages     = {456-467},
  year      = {2017},
  abstract  = {Background/Aims: Acute kidney injury (AKI) is a postoperative complication after cardiac surgery with a high impact on mortality and morbidity. Nephrocheck® [TIMP-2*IGFBP7] determines markers of tubular stress, which occurs prior to tubular damage. It is unknown at which time-point [TIMP-2*IGFBP7] measurement should be performed to ideally predict AKI. We investigated the association of [TIMP-2*IGFBP7] at various time-points with the incidence of AKI in patients undergoing elective cardiac surgery including cardio-pulmonary bypass. Methods: In a prospective cohort study, serial blood and urine samples were collected from 150 patients: pre-operative, at ICU-admission, 24h and 48h post-surgery. AKI was defined as Serum-Creatinine rise >0.3 mg/dl within 48hrs. Urinary [TIMP-2*IGFBP7] was measured at pre-operative, ICU-admission and 24h post-surgery; medical staff was kept blinded to these results. Results: A total of 35 patients (23.5\%) experienced AKI, with a higher incidence in those with high [TIMP-2*IGFBP7] values at ICU admission (57.1\% vs. 10.1\%, p<0.001). In logistic regression [TIMP-2*IGFBP7] at ICU admission was independently associated with the occurrence of AKI (Odds Ratio 11.83; p<0.001, C-statistic= 0.74) after adjustment for EuroSCORE II and CBP-time. Conclusions: Early detection of elevated [TIMP-2*IGFBP7] at ICU admission was strongly predictive for postoperative AKI and appeared to be more precise as compared to subsequent measurements.},
  language  = {en}
}
@article{KolominskyRabasWiedmannWeingaertneretal.2015,
  author    = {Kolominsky-Rabas, Peter L. and Wiedmann, Silke and Weing{\"a}rtner, Michael and Liman, Thomas G. and Endres, Matthias and Schwab, Stefan and Buchfelder, Michael and Heuschmann, Peter U.},
  title     = {Time Trends in Incidence of Pathological and Etiological Stroke Subtypes during 16 Years: The Erlangen Stroke Project},
  series = {Neuroepidemiology},
  volume    = {44},
  journal   = {Neuroepidemiology},
  number    = {1},
  issn      = {0251-5350},
  doi       = {10.1159/000371353},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196503},
  pages     = {24-29},
  year      = {2015},
  abstract  = {Background: Population-based data, which continuously monitors time trends in stroke epidemiology are limited. We investigated the incidence of pathological and etiological stroke subtypes over a 16 year time period. Methods: Data were collected within the Erlangen Stroke Project (ESPro), a prospective, population-based stroke register in Germany covering a total study population of 105,164 inhabitants (2010). Etiology of ischemic stroke was classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Results: Between January 1995 and December 2010, 3,243 patients with first-ever stroke were documented. The median age was 75 and 55\% were females. The total stroke incidence decreased over the 16 year study period in men (Incidence Rate Ratio 1995-1996 vs. 2009-2010 (IRR) 0.78; 95\% CI 0.58-0.90) but not in women. Among stroke subtypes, a decrease in ischemic stroke incidence (IRR 0.73; 95\% CI 0.57-0.93) and of large artery atherosclerotic stroke (IRR 0.27; 95\% CI 0.12-0.59) was found in men and an increase of stroke due to small artery occlusion in women (IRR 2.33; 95\% CI 1.39-3.90). Conclusions: Variations in time trends of pathological and etiological stroke subtypes were found between men and women that might be linked to gender differences in the development of major vascular risk factors in the study population.},
  language  = {en}
}
@article{WiedmannHeuschmannHillmannetal.2014,
  author    = {Wiedmann, Silke and Heuschmann, Peter U. and Hillmann, Steffi and Busse, Otto and Wiethoelter, Horst and Walter, Georg M. and Seidel, Guenter and Misselwitz, Bjoern and Janssen, Alfred and Berger, Klaus and Burmeister, Christoph and Matthias, Christine and Kolominsky-Rabas, Peter and Hermanek, Peter},
  title     = {The Quality of Acute Stroke Care-an Analysis of Evidence-Based Indicators in 260 000 Patients},
  series = {Deutsches {\"A}rzteblatt International},
  volume    = {111},
  journal   = {Deutsches {\"A}rzteblatt International},
  number    = {45},
  issn      = {1866-0452},
  doi       = {10.3238/arztebl.2014.0759},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114747},
  pages     = {759-765},
  year      = {2014},
  abstract  = {Background: Stroke patients should be cared for in accordance with evidence-based guidelines. The extent of implementation of guidelines for the acute care of stroke patients in Germany has been unclear to date. Methods: The regional quality assurance projects that cooperate in the framework of the German Stroke Registers Study Group (Arbeitsgemeinschaft Deutscher Schlaganfall-Register, ADSR) collected data on the care of stroke patients in 627 hospitals in 2012. The quality of the acute hospital care of patients with stroke or transient ischemic attack (TIA) was assessed on the basis of 15 standardized, evidence-based quality indicators and compared across the nine participating regional quality assurance projects. Results: Data were obtained on more than 260 000 patients nationwide. Intravenous thrombolysis was performed in 59.7\% of eligible ischemic stroke patients patients (range among participating projects, 49.7-63.6\%). Dysphagia screening was documented in 86.2\% (range, 74.8-93.1\%). For the following indicators, the defined targets were not reached for all of Germany: antiaggregation within 48 hours, 93.4\% (range, 86.6-96.4\%); anticoagulation for atrial fibrillation, 77.6\% (range, 72.4-80.1\%); standardized dysphagia screening, 86.2\% (range, 74.8-93.1\%); oral and written information of the patients or their relatives, 86.1\% (range, 75.4-91.5\%). The rate of patients examined or treated by a speech therapist was in the target range. Conclusion: The defined targets were reached for most of the quality indicators. Some indicators, however, varied widely across regional quality assurance projects. This implies that the standardization of care for stroke patients in Germany has not yet been fully achieved.},
  language  = {en}
}
@article{GelbrichMorbachDeutschbeinetal.2023,
  author    = {Gelbrich, G{\"o}tz and Morbach, Caroline and Deutschbein, Timo and Fassnacht, Martin and St{\"o}rk, Stefan and Heuschmann, Peter U.},
  title     = {The population comparison index: an intuitive measure to calibrate the extent of impairments in patient cohorts in relation to healthy and diseased populations},
  series = {International Journal of Environmental Research and Public Health},
  volume    = {20},
  journal   = {International Journal of Environmental Research and Public Health},
  number    = {3},
  issn      = {1660-4601},
  doi       = {10.3390/ijerph20032168},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304933},
  year      = {2023},
  abstract  = {We assume that a specific health constraint, e.g., a certain aspect of bodily function or quality of life that is measured by a variable X, is absent (or irrelevant) in a healthy reference population (Ref0), and it is materially present and precisely measured in a diseased reference population (Ref1). We further assume that some amount of this constraint of interest is suspected to be present in a population under study (SP). In order to quantify this issue, we propose the introduction of an intuitive measure, the population comparison index (PCI), that relates the mean value of X in population SP to the mean values of X in populations Ref0 and Ref1. This measure is defined as PCI[X] = (mean[X|SP] - mean[X|Ref0])/(mean[X|Ref1] - mean[X|Ref0]) × 100[\%], where mean[X|.] is the average value of X in the respective group of individuals. For interpretation, PCI[X] ≈ 0 indicates that the values of X in the population SP are similar to those in population Ref0, and hence, the impairment measured by X is not materially present in the individuals in population SP. On the other hand, PCI[X] ≈ 100 means that the individuals in SP exhibit values of X comparable to those occurring in Ref1, i.e., the constraint of interest is equally present in populations SP and Ref1. A value of 0 < PCI[X] < 100 indicates that a certain percentage of the constraint is present in SP, and it is more than in Ref0 but less than in Ref1. A value of PCI[X] > 100 means that population SP is even more affected by the constraint than population Ref1.},
  language  = {en}
}
@article{OezkurMagyarThomasetal.2018,
  author    = {Oezkur, Mehmet and Magyar, Atilla and Thomas, Phillip and Reif, Andreas and St{\"o}rk, Stefan and Heuschmann, Peter U. and Leyh, Rainer G. and Wagner, Martin},
  title     = {The COMT-polymorphism is not associated with the incidence of acute kidney injury after cardiac surgery - a prospective cohort study},
  series = {BMC Nephrology},
  volume    = {19},
  journal   = {BMC Nephrology},
  number    = {34},
  doi       = {10.1186/s12882-018-0820-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175529},
  year      = {2018},
  abstract  = {Background: The Catechol-O-methyltransferase (COMT) represents the key enzyme in catecholamine degradation. Recent studies suggest that the COMT rs4680 polymorphism is associated with the response to endogenous and exogenous catecholamines. There are, however, conflicting data regarding the COMT Met/Met phenotype being associated with an increased risk of acute kidney injury (AKI) after cardiac surgery. The aim of the current study is to prospectively investigate the impact of the COMT rs4680 polymorphism on the incidence of AKI in patients undergoing cardiac surgery. Methods: In this prospective single center cohort study consecutive patients hospitalized for elective cardiac surgery including cardiopulmonary-bypass (CPB) were screened for participation. Demographic clinical data, blood, urine and tissue samples were collected at predefined time points throughout the clinical stay. AKI was defined according to recent recommendations of the Kidney Disease Improving Global Outcome (KDIGO) group. Genetic analysis was performed after patient enrolment was completed. Results: Between April and December 2014, 150 patients were recruited. The COMT genotypes were distributed as follows: Val/Met 48.7\%, Met/Met 29.3\%, Val/Val 21.3\%. No significant differences were found for demography, comorbidities, or operative strategy according to the underlying COMT genotype. AKI occurred in 35 patients (23.5\%) of the total cohort, and no differences were evident between the COMT genotypes (20.5\% Met/Met, 24.7\% Val/Met, 25.0\% Val/Val, p = 0.66). There were also no differences in the post-operative period, including ICU or in-hospital stay. Conclusions: We did not find statistically significant variations in the risk for postoperative AKI, length of ICU or in-hospital stay according to the underlying COMT genotype.},
  language  = {en}
}
@article{HillmannWiedmannFraseretal.2015,
  author    = {Hillmann, Steffi and Wiedmann, Silke and Fraser, Alec and Baeza, Juan and Rudd, Anthony and Norrving, Bo and Asplund, Kjell and Niewada, Maciej and Dennis, Martin and Hermanek, Peter and Wolfe, Charles D. A. and Heuschmann, Peter U.},
  title     = {Temporal changes in the quality of acute stroke care in five national audits across Europe},
  series = {BioMed Research International},
  volume    = {2015},
  journal   = {BioMed Research International},
  number    = {432497},
  doi       = {10.1155/2015/432497},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149059},
  year      = {2015},
  abstract  = {Background. Data on potential variations in delivery of appropriate stroke care over time are scarce. We investigated temporal changes in the quality of acute hospital stroke care across five national audits in Europe over a period of six years. Methods. Data were derived from national stroke audits in Germany, Poland, Scotland, Sweden, and England/Wales/Northern Ireland participating within the European Implementation Score (EIS) collaboration. Temporal changes in predefined quality indicators with comparable information between the audits were investigated. Multivariable logistic regression analyses were performed to estimate adherence to quality indicators over time. Results. Between 2004 and 2009, individual data from 542,112 patients treated in 538 centers participating continuously over the study period were included. In most audits, the proportions of patients who were treated on a SU, were screened for dysphagia, and received thrombolytic treatment increased over time and ranged from 2-fold to almost 4-fold increase in patients receiving thrombolytic therapy in 2009 compared to 2004. Conclusions. A general trend towards a better quality of stroke care defined by standardized quality indicators was observed over time. The association between introducing a specific measure and higher adherence over time might indicate that monitoring of stroke care performance contributes to improving quality of care.},
  language  = {en}
}
@article{WutzlerKrogiasGrauetal.2019,
  author    = {Wutzler, Alexander and Krogias, Christos and Grau, Anna and Veltkamp, Roland and Heuschmann, Peter U. and Haeusler, Karl Georg},
  title     = {Stroke prevention in patients with acute ischemic stroke and atrial fibrillation in Germany - a cross sectional survey},
  series = {BMC Neurology},
  volume    = {19},
  journal   = {BMC Neurology},
  doi       = {10.1186/s12883-019-1249-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201078},
  pages     = {25},
  year      = {2019},
  abstract  = {Background Atrial fibrillation (AF) is present in 15-20\% of patients with acute ischemic stroke. Oral anticoagulation reduces the risk of AF-related recurrent stroke but clinical guideline recommendations are rather vague regarding its use in the acute phase of stroke. We aimed to assess the current clinical practice of medical stroke prevention in AF patients during the acute phase of ischemic stroke. Methods In April 2017, a standardized anonymous questionnaire was sent to clinical leads of all 298 certified stroke units in Germany. Results Overall, 154 stroke unit leads participated (response rate 52\%). Anticoagulation in the acute phase of stroke is considered feasible in more than 90\% of AF patients with ischemic stroke. Clinicians assume that about two thirds of all AF patients (range 20-100\%) are discharged on oral anticoagulation. According to local preferences, acetylsalicylic acid is given orally in the majority of patients with delayed initiation of oral anticoagulation. A non-vitamin K-dependent oral anticoagulant (NOAC) is more often prescribed than a vitamin K-dependent oral anticoagulant (VKA). VKA is more often chosen in patients with previous VKA intake than in VKA naive patients. In the minority of patients, stroke unit leads discuss the prescription of a specific oral anticoagulant with the treating general practitioner. Adherence to medical stroke prevention after hospital discharge is not assessed on a regular basis in any patient by the majority of participating stroke centers. Conclusions Early secondary stroke prevention in AF patients in German stroke units is based on OAC use but prescription modalities vary in clinical practice.},
  language  = {en}
}