@article{KraftDrechslerGunrebenetal.2014, author = {Kraft, Peter and Drechsler, Christiane and Gunreben, Ignaz and Heuschmann, Peter Ulrich and Kleinschnitz, Christoph}, title = {Regulation of Blood Coagulation Factors XI and XII in Patients with Acute and Chronic Cerebrovascular Disease: A Case-Control Study}, series = {Cerebrovascular Diseases}, volume = {38}, journal = {Cerebrovascular Diseases}, number = {5}, issn = {1015-9770}, doi = {10.1159/000368434}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199076}, pages = {337-343}, year = {2014}, abstract = {Background: Animal models have implicated an integral role for coagulation factors XI (FXI) and XII (FXII) in thrombus formation and propagation of ischemic stroke (IS). However, it is unknown if these molecules contribute to IS pathophysiology in humans, and might be of use as biomarkers for IS risk and severity. This study aimed to identify predictors of altered FXI and FXII levels and to determine whether there are differences in the levels of these coagulation factors between acute cerebrovascular events and chronic cerebrovascular disease (CCD). Methods: In this case-control study, 116 patients with acute ischemic stroke (AIS) or transitory ischemic attack (TIA), 117 patients with CCD, and 104 healthy volunteers (HVs) were enrolled between 2010 and 2013 at our University hospital. Blood sampling was undertaken once in the CCD and HV groups and on days 0, 1, and 3 after stroke onset in patients with AIS or TIA. Correlations between serum FXI and FXII levels and demographic and clinical parameters were tested by linear regression and analysis of variance. Results: The mean age of AIS/TIA patients was 70 ± 12. Baseline clinical severity measured with NIHSS and Barthel Index was 4.8 ± 6.0 and 74 ± 30, respectively. More than half of the patients had an AIS (58\%). FXI levels were significantly correlated with different leukocyte subsets (p < 0.05). In contrast, FXII serum levels showed no significant correlation (p > 0.1). Neither FXI nor FXII levels correlated with CRP (p > 0.2). FXII levels were significantly higher in patients with CCD compared with those with AIS/TIA (mean ± SD 106 ± 26\% vs. 97 ± 24\%; univariate analysis: p < 0.05); these differences did not reach significance in multivariate analysis adjusted for sex and age. FXI levels did not differ significantly between study groups. Sex and age were significantly associated with FXI and/or FXII levels in patients with AIS/TIA (p < 0.05). In contrast, no statistical significant influence was found for treatment modality (thrombolysis or not), pre-treatment with platelet inhibitors, and severity of stroke. Conclusions: In this study, there was no differential regulation of FXI and FXII levels between disease subtypes but biomarker levels were associated with patient and clinical characteristics. FXI and FXII levels might be no valid biomarker for predicting stroke risk.}, language = {en} } @article{MagyarWagnerThomasetal.2019, author = {Magyar, Attila and Wagner, Martin and Thomas, Phillip and Malsch, Carolin and Schneider, Reinhard and St{\"o}rk, Stefan and Heuschmann, Peter U and Leyh, Rainer G and Oezkur, Mehmet}, title = {HO-1 concentrations 24 hours after cardiac surgery are associated with the incidence of acute kidney injury: a prospective cohort study}, series = {International Journal of Nephrology and Renovascular Disease}, volume = {12}, journal = {International Journal of Nephrology and Renovascular Disease}, doi = {10.2147/IJNRD.S165308}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177250}, pages = {9-18}, year = {2019}, abstract = {Background: Acute kidney injury (AKI) is a serious complication after cardiac surgery that is associated with increased mortality and morbidity. Heme oxygenase-1 (HO-1) is an enzyme synthesized in renal tubular cells as one of the most intense responses to oxidant stress linked with protective, anti-inflammatory properties. Yet, it is unknown if serum HO-1 induction following cardiac surgical procedure involving cardiopulmonary bypass (CPB) is associated with incidence and severity of AKI. Patients and methods: In the present study, we used data from a prospective cohort study of 150 adult cardiac surgical patients. HO-1 measurements were performed before, immediately after and 24 hours post-CPB. In univariate and multivariate analyses, the association between HO-1 and AKI was investigated. Results: AKI with an incidence of 23.3\% (35 patients) was not associated with an early elevation of HO-1 after CPB in all patients (P=0.88), whereas patients suffering from AKI developed a second burst of HO-1 24 hours after CBP. In patients without AKI, the HO-1 concentrations dropped to baseline values (P=0.031). Furthermore, early HO-1 induction was associated with CPB time (P=0.046), while the ones 24 hours later lost this association (P=0.219). Conclusion: The association of the second HO-1 burst 24 hours after CBP might help to distinguish between the causality of AKI in patients undergoing CBP, thus helping to adapt patient stratification and management.}, language = {en} } @article{WagnerAshbyKurtzetal.2015, author = {Wagner, Martin and Ashby, Damien R. and Kurtz, Caroline and Alam, Ahsan and Busbridge, Mark and Raff, Ulrike and Zimmermann, Josef and Heuschmann, Peter U. and Wanner, Christoph and Schramm, Lothar}, title = {Hepcidin-25 in diabetic chronic kidney disease is predictive for mortality and progression to end stage renal disease}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {4}, doi = {10.1371/journal.pone.0123072}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125514}, pages = {e0123072}, year = {2015}, abstract = {Background Anemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD). It may be explained by reduced erythropoietin (EPO) synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25—the key hormone of iron-metabolism—on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels. Methods 249 diabetic patients with CKD of any stage, excluding end-stage renal disease (ESRD), were enrolled (2003-2005), if they were not on EPO-stimulating agent and iron therapy. Hepcidin-25 levels were measured by radioimmunoassay. The association of hepcidin-25 at baseline with clinical variables was investigated using linear regression models. All-cause mortality and a composite endpoint of CKD progression (ESRD or doubling of serum creatinine) were analyzed by Cox proportional hazards models. Results Patients (age 67 yrs, 53\% male, GFR 51 ml/min, hemoglobin 131 g/L, EPO 13.5 U/L, hepcidin-25 62.0 ng/ml) were followed for a median time of 4.2 yrs. Forty-nine patients died (19.7\%) and forty (16.1\%) patients reached the composite endpoint. Elevated hepcidin levels were independently associated with higher ferritin-levels, lower EPO-levels and impaired kidney function (all p<0.05). Hepcidin was related to mortality, along with its interaction with EPO, older age, greater proteinuria and elevated CRP (all p<0.05). Hepcidin was also predictive for progression of CKD, aside from baseline GFR, proteinuria, low albumin- and hemoglobin-levels and a history of CVD (all p<0.05). Conclusions We found hepcidin-25 to be associated with EPO and impaired kidney function in diabetic CKD. Elevated hepcidin-25 and EPO-levels were independent predictors of mortality, while hepcidin-25 was also predictive for progression of CKD. Both hepcidin-25 and EPO may represent important prognostic factors of clinical outcome and have the potential to further define "high risk" populations in CKD.}, language = {en} } @article{KraftDrechslerGunrebenetal.2014, author = {Kraft, Peter and Drechsler, Christiane and Gunreben, Ignaz and Nieswandt, Bernhard and Stoll, Guido and Heuschmann, Peter Ulrich and Kleinschnitz, Christoph}, title = {Von Willebrand Factor Regulation in Patients with Acute and Chronic Cerebrovascular Disease: A Pilot, Case-Control Study}, series = {PLoS ONE}, volume = {9}, journal = {PLoS ONE}, number = {6}, issn = {1932-6203}, doi = {10.1371/journal.pone.0099851}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119588}, pages = {e99851}, year = {2014}, abstract = {Background and Purpose In animal models, von Willebrand factor (VWF) is involved in thrombus formation and propagation of ischemic stroke. However, the pathophysiological relevance of this molecule in humans, and its potential use as a biomarker for the risk and severity of ischemic stroke remains unclear. This study had two aims: to identify predictors of altered VWF levels and to examine whether VWF levels differ between acute cerebrovascular events and chronic cerebrovascular disease (CCD). Methods A case-control study was undertaken between 2010 and 2013 at our University clinic. In total, 116 patients with acute ischemic stroke (AIS) or transitory ischemic attack (TIA), 117 patients with CCD, and 104 healthy volunteers (HV) were included. Blood was taken at days 0, 1, and 3 in patients with AIS or TIA, and once in CCD patients and HV. VWF serum levels were measured and correlated with demographic and clinical parameters by multivariate linear regression and ANOVA. Results Patients with CCD (158±46\%) had significantly higher VWF levels than HV (113±36\%, P<0.001), but lower levels than AIS/TIA patients (200±95\%, P<0.001). Age, sex, and stroke severity influenced VWF levels (P<0.05). Conclusions VWF levels differed across disease subtypes and patient characteristics. Our study confirms increased VWF levels as a risk factor for cerebrovascular disease and, moreover, suggests that it may represent a potential biomarker for stroke severity, warranting further investigation.}, language = {en} } @article{EliasHeuschmannSchmittetal.2013, author = {Elias, Johannes and Heuschmann, Peter U. and Schmitt, Corinna and Eckhardt, Frithjof and Boehm, Hartmut and Maier, Sebastian and Kolb-M{\"a}urer, Annette and Riedmiller, Hubertus and M{\"u}llges, Wolfgang and Weisser, Christoph and Wunder, Christian and Frosch, Matthias and Vogel, Ulrich}, title = {Prevalence dependent calibration of a predictive model for nasal carriage of methicillin-resistant Staphylococcus aureus}, series = {BMC Infectious Diseases}, journal = {BMC Infectious Diseases}, doi = {10.1186/1471-2334-13-111}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96091}, year = {2013}, abstract = {Background Published models predicting nasal colonization with Methicillin-resistant Staphylococcus aureus among hospital admissions predominantly focus on separation of carriers from non-carriers and are frequently evaluated using measures of discrimination. In contrast, accurate estimation of carriage probability, which may inform decisions regarding treatment and infection control, is rarely assessed. Furthermore, no published models adjust for MRSA prevalence. Methods Using logistic regression, a scoring system (values from 0 to 200) predicting nasal carriage of MRSA was created using a derivation cohort of 3091 individuals admitted to a European tertiary referral center between July 2007 and March 2008. The expected positive predictive value of a rapid diagnostic test (GeneOhm, Becton \& Dickinson Co.) was modeled using non-linear regression according to score. Models were validated on a second cohort from the same hospital consisting of 2043 patients admitted between August 2008 and January 2012. Our suggested correction score for prevalence was proportional to the log-transformed odds ratio between cohorts. Calibration before and after correction, i.e. accurate classification into arbitrary strata, was assessed with the Hosmer-Lemeshow-Test. Results Treating culture as reference, the rapid diagnostic test had positive predictive values of 64.8\% and 54.0\% in derivation and internal validation corhorts with prevalences of 2.3\% and 1.7\%, respectively. In addition to low prevalence, low positive predictive values were due to high proportion (> 66\%) of mecA-negative Staphylococcus aureus among false positive results. Age, nursing home residence, admission through the medical emergency department, and ICD-10-GM admission diagnoses starting with "A" or "J" were associated with MRSA carriage and were thus included in the scoring system, which showed good calibration in predicting probability of carriage and the rapid diagnostic test's expected positive predictive value. Calibration for both probability of carriage and expected positive predictive value in the internal validation cohort was improved by applying the correction score. Conclusions Given a set of patient parameters, the presented models accurately predict a) probability of nasal carriage of MRSA and b) a rapid diagnostic test's expected positive predictive value. While the former can inform decisions regarding empiric antibiotic treatment and infection control, the latter can influence choice of screening method.}, language = {en} } @article{MorbachWagnerGuentneretal.2017, author = {Morbach, Caroline and Wagner, Martin and G{\"u}ntner, Stefan and Malsch, Carolin and Oezkur, Mehmet and Wood, David and Kotseva, Kornelia and Leyh, Rainer and Ertl, Georg and Karmann, Wolfgang and Heuschmann, Peter U and St{\"o}rk, Stefan}, title = {Heart failure in patients with coronary heart disease: Prevalence, characteristics and guideline implementation - Results from the German EuroAspire IV cohort}, series = {BMC Cardiovascular Disorders}, volume = {17}, journal = {BMC Cardiovascular Disorders}, number = {108}, doi = {10.1186/s12872-017-0543-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157738}, year = {2017}, abstract = {Background: Adherence to pharmacotherapeutic treatment guidelines in patients with heart failure (HF) is of major prognostic importance, but thorough implementation of guidelines in routine care remains insufficient. Our aim was to investigate prevalence and characteristics of HF in patients with coronary heart disease (CHD), and to assess the adherence to current HF guidelines in patients with HF stage C, thus identifying potential targets for the optimization of guideline implementation. Methods: Patients from the German sample of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EuroAspire) IV survey with a hospitalization for CHD within the previous six to 36 months providing valid data on echocardiography as well as on signs and symptoms of HF were categorized into stages of HF: A, prevalence of risk factors for developing HF; B, asymptomatic but with structural heart disease; C, symptomatic HF. A Guideline Adherence Indicator (GAI-3) was calculated for patients with reduced (≤40\%) left ventricular ejection fraction (HFrEF) as number of drugs taken per number of drugs indicated; beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, and mineralocorticoid receptor antagonists (MRA) were considered. Results: 509/536 patients entered analysis. HF stage A was prevalent in n = 20 (3.9\%), stage B in n = 264 (51.9\%), and stage C in n = 225 (44.2\%) patients; 94/225 patients were diagnosed with HFrEF (42\%). Stage C patients were older, had a longer duration of CHD, and a higher prevalence of arterial hypertension. Awareness of pre-diagnosed HF was low (19\%). Overall GAI-3 of HFrEF patients was 96.4\% with a trend towards lower GAI-3 in patients with lower LVEF due to less thorough MRA prescription. Conclusions: In our sample of CHD patients, prevalence of HF stage C was high and a sizable subgroup suffered from HFrEF. Overall, pharmacotherapy was fairly well implemented in HFrEF patients, although somewhat worse in patients with more reduced ejection fraction. Two major targets were identified possibly suited to further improve the implementation of HF guidelines: 1) increase patients´ awareness of diagnosis and importance of HF; and 2) disseminate knowledge about the importance of appropriately implementing the use of mineralocorticoid receptor antagonists. Trial registration: This is a cross-sectional analysis of a non-interventional study. Therefore, it was not registered as an interventional trial.}, language = {en} } @article{MontellanoKluterRueckeretal.2022, author = {Montellano, Felipe A. and Kluter, Elisabeth J. and R{\"u}cker, Viktoria and Ungeth{\"u}m, Kathrin and Mackenrodt, Daniel and Wiedmann, Silke and Dege, Tassilo and Quilitzsch, Anika and Morbach, Caroline and Frantz, Stefan and St{\"o}rk, Stefan and Haeusler, Karl Georg and Kleinschnitz, Christoph and Heuschmann, Peter U.}, title = {Cardiac dysfunction and high-sensitive C-reactive protein are associated with troponin T elevation in ischemic stroke: insights from the SICFAIL study}, series = {BMC Neurology}, volume = {22}, journal = {BMC Neurology}, number = {1}, doi = {10.1186/s12883-022-03017-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300119}, year = {2022}, abstract = {Background Troponin elevation is common in ischemic stroke (IS) patients. The pathomechanisms involved are incompletely understood and comprise coronary and non-coronary causes, e.g. autonomic dysfunction. We investigated determinants of troponin elevation in acute IS patients including markers of autonomic dysfunction, assessed by heart rate variability (HRV) time domain variables. Methods Data were collected within the Stroke Induced Cardiac FAILure (SICFAIL) cohort study. IS patients admitted to the Department of Neurology, W{\"u}rzburg University Hospital, underwent baseline investigation including cardiac history, physical examination, echocardiography, and blood sampling. Four HRV time domain variables were calculated in patients undergoing electrocardiographic Holter monitoring. Multivariable logistic regression with corresponding odds ratios (OR) and 95\% confidence intervals (CI) was used to investigate the determinants of high-sensitive troponin T (hs-TnT) levels ≥14 ng/L. Results We report results from 543 IS patients recruited between 01/2014-02/2017. Of those, 203 (37\%) had hs-TnT ≥14 ng/L, which was independently associated with older age (OR per year 1.05; 95\% CI 1.02-1.08), male sex (OR 2.65; 95\% CI 1.54-4.58), decreasing estimated glomerular filtration rate (OR per 10 mL/min/1.73 m2 0.71; 95\% CI 0.61-0.84), systolic dysfunction (OR 2.79; 95\% CI 1.22-6.37), diastolic dysfunction (OR 2.29; 95\% CI 1.29-4.02), atrial fibrillation (OR 2.30; 95\% CI 1.25-4.23), and increasing levels of C-reactive protein (OR 1.48 per log unit; 95\% CI 1.22-1.79). We did not identify an independent association of troponin elevation with the investigated HRV variables. Conclusion Cardiac dysfunction and elevated C-reactive protein, but not a reduced HRV as surrogate of autonomic dysfunction, were associated with increased hs-TnT levels in IS patients independent of established cardiovascular risk factors.}, language = {en} } @article{MuellerScholdenKirchhofMorbachetal.2019, author = {M{\"u}ller-Scholden, Lara and Kirchhof, Jan and Morbach, Caroline and Breunig, Margret and Meijer, Rudy and R{\"u}cker, Viktoria and Tiffe, Theresa and Yurdadogan, Tino and Wagner, Martin and Gelbrich, G{\"o}tz and Bots, Michiel L. and St{\"o}rk, Stefan and Heuschmann, Peter U.}, title = {Segment-specific association of carotid-intima-media thickness with cardiovascular risk factors - findings from the STAAB cohort study}, series = {BMC Cardiovascular Disorders}, volume = {19}, journal = {BMC Cardiovascular Disorders}, number = {84}, doi = {10.1186/s12872-019-1044-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200720}, year = {2019}, abstract = {Background The guideline recommendation to not measure carotid intima-media thickness (CIMT) for cardiovascular risk prediction is based on the assessment of just one single carotid segment. We evaluated whether there is a segment-specific association between different measurement locations of CIMT and cardiovascular risk factors. Methods Subjects from the population-based STAAB cohort study comprising subjects aged 30 to 79 years of the general population from W{\"u}rzburg, Germany, were investigated. CIMT was measured on the far wall of both sides in three different predefined locations: common carotid artery (CCA), bulb, and internal carotid artery (ICA). Diabetes, dyslipidemia, hypertension, smoking, and obesity were considered as risk factors. In multivariable logistic regression analysis, odds ratios of risk factors per location were estimated for the endpoint of individual age- and sex-adjusted 75th percentile of CIMT. Results 2492 subjects were included in the analysis. Segment-specific CIMT was highest in the bulb, followed by CCA, and lowest in the ICA. Dyslipidemia, hypertension, and smoking were associated with CIMT, but not diabetes and obesity. We observed no relevant segment-specific association between the three different locations and risk factors, except for a possible interaction between smoking and ICA. Conclusions As no segment-specific association between cardiovascular risk factors and CIMT became evident, one simple measurement of one location may suffice to assess the cardiovascular risk of an individual.}, language = {en} } @article{TiffeMorbachRueckeretal.2019, author = {Tiffe, Theresa and Morbach, Caroline and R{\"u}cker, Viktoria and Gelbrich, G{\"o}tz and Wagner, Martin and Faller, Hermann and St{\"o}rk, Stefan and Heuschmann, Peter U.}, title = {Impact of patient beliefs on blood pressure control in the general population: findings from the population-based STAAB cohort study}, series = {International Journal of Hypertension}, volume = {2019}, journal = {International Journal of Hypertension}, doi = {10.1155/2019/9385397}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200992}, pages = {9385397}, year = {2019}, abstract = {Background. Effective antihypertensive treatment depends on patient compliance regarding prescribed medications. We assessed the impact of beliefs related towards antihypertensive medication on blood pressure control in a population-based sample treated for hypertension. Methods. We used data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) study investigating 5000 inhabitants aged 30 to 79 years from the general population of W{\"u}rzburg, Germany. The Beliefs about Medicines Questionnaire German Version (BMQ-D) was provided in a subsample without established cardiovascular diseases (CVD) treated for hypertension. We evaluated the association between inadequately controlled hypertension (systolic RR >140/90 mmHg; >140/85 mmHg in diabetics) and reported concerns about and necessity of antihypertensive medication. Results. Data from 293 participants (49.5\% women, median age 64 years [quartiles 56.0; 69.0]) entered the analysis. Despite medication, half of the participants (49.8\%) were above the recommended blood pressure target. Stratified for sex, inadequately controlled hypertension was less frequent in women reporting higher levels of concerns (OR 0.36; 95\%CI 0.17-0.74), whereas no such association was apparent in men. We found no association for specific-necessity in any model. Conclusion. Beliefs regarding the necessity of prescribed medication did not affect hypertension control. An inverse association between concerns about medication and inappropriately controlled hypertension was found for women only. Our findings highlight that medication-related beliefs constitute a serious barrier of successful implementation of treatment guidelines and underline the role of educational interventions taking into account sex-related differences.}, language = {en} } @article{WagnerWannerSchichetal.2017, author = {Wagner, Martin and Wanner, Christoph and Schich, Martin and Kotseva, Kornelia and Wood, David and Hartmann, Katrin and Fette, Georg and R{\"u}cker, Viktoria and Oezkur, Mehmet and St{\"o}rk, Stefan and Heuschmann, Peter U.}, title = {Patient's and physician's awareness of kidney disease in coronary heart disease patients - a cross-sectional analysis of the German subset of the EUROASPIRE IV survey}, series = {BMC Nephrology}, volume = {18}, journal = {BMC Nephrology}, number = {321}, doi = {10.1186/s12882-017-0730-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158387}, year = {2017}, abstract = {Background Chronic kidney disease (CKD) is a common comorbid condition in coronary heart disease (CHD). CKD predisposes the patient to acute kidney injury (AKI) during hospitalization. Data on awareness of kidney dysfunction among CHD patients and their treating physicians are lacking. In the current cross-sectional analysis of the German EUROASPIRE IV sample we aimed to investigate the physician's awareness of kidney disease of patients hospitalized for CHD and also the patient's awareness of CKD in a study visit following hospital discharge. Methods All serum creatinine (SCr) values measured during the hospital stay were used to describe impaired kidney function (eGFR\(_{CKD-EPI}\) < 60 ml/min/1.73m2) at admission, discharge and episodes of AKI (KDIGO definition). Information extracted from hospital discharge letters and correct ICD coding for kidney disease was studied as a surrogate of physician's awareness of kidney disease. All patients were interrogated 0.5 to 3 years after hospital discharge, whether they had ever been told about kidney disease by a physician. Results Of the 536 patients, 32\% had evidence for acute or chronic kidney disease during the index hospital stay. Either condition was mentioned in the discharge letter in 22\%, and 72\% were correctly coded according to ICD-10. At the study visit in the outpatient setting 35\% had impaired kidney function. Of 158 patients with kidney disease, 54 (34\%) were aware of CKD. Determinants of patient's awareness were severity of CKD (OR\(_{eGFR}\) 0.94; 95\%CI 0.92-0.96), obesity (OR 1.97; 1.07-3.64), history of heart failure (OR 1.99; 1.00-3.97), and mentioning of kidney disease in the index event's hospital discharge letter (OR 5.51; 2.35-12.9). Conclusions Although CKD is frequent in CHD, only one third of patients is aware of this condition. Patient's awareness was associated with kidney disease being mentioned in the hospital discharge letter. Future studies should examine how raising physician's awareness for kidney dysfunction may improve patient's awareness of CKD.}, language = {en} }