Publications by authors named "Sebastian Zimmer"

68 Publications

Circulating chaperones in patients with aortic valve stenosis undergoing TAVR: impact of concomitant chronic kidney disease.

Transl Res 2021 Mar 5. Epub 2021 Mar 5.

Heart Centre, Department of Cardiology, University of Bonn, Bonn, Germany. Electronic address:

Chronic kidney disease (CKD) is a frequent comorbidity of aortic valve stenosis (AVS). Circulating chaperones have emerged as both effectors and prognostic markers for various diseases. We investigated the role of circulating chaperones in patients with severe AVS undergoing transcatheter aortic valve replacement (TAVR). In this observational cohort study, 159 consecutive patients undergoing TAVR were included and serum levels of Glucose-regulated protein 78 (GRP78) and heat shock protein 27 (HSP27) were measured by ELISA. The primary end point was defined as 1-year mortality. Patients with lower levels of circulating GRP78 (<1347 ng/mL) had an increased 1-year mortality rate compared to patients with higher levels of GRP78 (25.0% vs 10.3%, P = 0.026). GRP78 was associated with lower 1-year mortality in a univariate analysis (HR 0.354, P = 0.047). After adjusting for age, sex, several comorbidities and biomarkers, GRP78 (HR 0.295, P = 0.024) and CKD (HR 2.809, P = 0.044) remained independent predictors of the primary end point of 1-year mortality in a multivariate analysis. Patients with concomitant CKD had significantly higher levels of HSP27 compared to patients without CKD (1690 pg/mL vs 1076 pg/mL, P = 0.0109). In patients with CKD, elevated HSP27 was identified as a protective marker (1-year mortality: 9.6% vs 31.4%, log-rank P = 0.0166). Using cut-off values for GRP78 and HSP27 we were able to stratify patients with CKD undergoing TAVR into 4 groups with distinct mortality rates (50% vs 22.2% vs 24% vs 7.9%, log-rank P = 0.0170). GRP78 is an overall predictor of mortality after TAVR, while the combination of GRP78 and HSP27 helps to predict mortality in patients with CKD receiving TAVR.
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http://dx.doi.org/10.1016/j.trsl.2021.03.003DOI Listing
March 2021

Long-term clinical outcome and mortality risks after paclitaxel-coated balloon angioplasty in patients with peripheral artery disease: An observational clinical study.

Health Sci Rep 2021 Mar 26;4(1):e236. Epub 2021 Jan 26.

Department of Internal Medicine II-Cardiology, Pulmonology and Angiology University Hospital Bonn Bonn Germany.

Background And Aims: Drug-eluting devices (DEDs) are usually used as a standard therapy for revascularization in femoropopliteal artery disease. Randomized controlled trails have found that DEDs with paclitaxel result in superior patency rates and decreased target lesion revascularization. A meta-analysis by Katsanos et al indicated an increased long-term mortality in patients treated with paclitaxel-coated devices. The aim of this observational clinical study was to assess the long-term clinical outcomes and mortality risk after paclitaxel-coated balloon angioplasty in patients with symptomatic peripheral artery disease.

Methods: We retrospectively evaluated 287 patients with peripheral interventions, including 173 drug-coated balloon (DCB) angioplasties and 114 plain old balloon angioplasties (POBA), performed at our center between 2015 and 2018.

Results: There were no significant differences in mortality rates between patients who received DCB angioplasty and those who received POBA. In the first year, the hazard ratio (HR) for DCB angioplasty was 0.59 (95% confidence interval [CI] 0.31 to 1.12, = .104). After 2 years, this HR was 0.64 (95% CI 0.36-1.17, = .145), while the 3-year and 4-year HR increased to 0.71 and 1.30 (3-year: 95% CI 0.37-1.33, = ,283; 4-year: 95% CI 0.55-3.08, = .546). No paclitaxel dose-response relationship with mortality rate was identified when adjusted for key predictors of mortality.

Conclusions: Analyses of patient level data identified no significant mortality differences between DCB angioplasty and POBA after 4 years of follow-up. Furthermore, there was no dose-response relationship between paclitaxel and mortality. These findings demonstrate that paclitaxel DCB is safe. Further long-term multicenter studies are needed to determine the risk of late mortality.
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http://dx.doi.org/10.1002/hsr2.236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837675PMC
March 2021

QRS duration is a risk indicator of adverse outcomes after MitraClip.

Catheter Cardiovasc Interv 2021 Feb 1. Epub 2021 Feb 1.

Heart Center Bonn, Department of Medicine II, University Hospital Bonn, Bonn, Germany.

Background: While QRS duration is a known marker of left ventricular (LV) function, little is known about its utility for predicting clinical prognosis after transcatheter mitral valve repair (TMVR). We investigated the association between QRS duration and one-year adverse events after TMVR with the MitraClip system.

Methods: From January 2011 through April 2019, we identified consecutive patients who underwent TMVR. Patients who had prior cardiac resynchronization therapy or a ventricular pacing rhythm were excluded. The patients were divided into two groups according to their QRS duration (<120 or ≥ 120 ms). Cox proportional hazard model was applied to determine the association between QRS duration and the composite outcome (all-cause mortality and re-hospitalization due to heart failure) within 1 year.

Results: A total of 348 patients were analyzed. Prolonged QRS duration (≥120 ms) was associated with an increased risk of the composite outcome (adjusted-HR 2.35, 95%CI 1.30-4.24, p = .005). There was a linear relationship between prolonged QRS duration and the increased risk of the composite outcomes. The observed association was consistent both in patients with left ventricular ejection fraction ≤35% and those with >35%. Furthermore, a QRS duration ≥120 ms was associated with lower improvement of LVEF at follow-up (adjusted-β coefficient - 5.31%, 95%CI -8.17 to -2.46, p < .001).

Conclusions: Prolonged QRS duration was associated with an increased risk of mortality and re-hospitalization and less improvement of LVEF following TMVR. QRS duration could be a useful marker to predict adverse outcomes and LV function after TMVR.
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http://dx.doi.org/10.1002/ccd.29505DOI Listing
February 2021

CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in mice upon transverse aortic constriction.

PLoS One 2021 7;16(1):e0243788. Epub 2021 Jan 7.

Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.

The CX3CL1/CX3CR1 axis mediates recruitment and extravasation of CX3CR1-expressing subsets of leukocytes and plays a pivotal role in the inflammation-driven pathology of cardiovascular disease. The cardiac immune response differs depending on the underlying causes. This suggests that for the development of successful immunomodulatory therapy in heart failure due to chronic pressure overload induced left ventricular (LV) hypertrophy, the underlying immune patterns must be examined. Here, the authors demonstrate that Fraktalkine-receptor CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in a mouse model of transverse aortic constriction (TAC). The comparison of C57BL/6 mice with CX3CR1 deficient mice displayed reduced LV hypertrophy and preserved cardiac function in response to pressure overload in mice lacking CX3CR1. Moreover, the normal immune response following TAC induced pressure overload which is dominated by Ly6Clow macrophages changed to an early pro-inflammatory immune response driven by neutrophils, Ly6Chigh macrophages and altered cytokine expression pattern in CX3CR1 deficient mice. In this early inflammatory phase of LV hypertrophy Ly6Chigh monocytes infiltrated the heart in response to a C-C chemokine ligand 2 burst. CX3CR1 expression impacts the immune response in the development of LV hypertrophy and its absence has clear cardioprotective effects. Hence, suppression of CX3CR1 may be an important immunomodulatory therapeutic target to ameliorate pressure-overload induced heart failure.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243788PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790399PMC
January 2021

PASCAL versus MitraClip-XTR edge-to-edge device for the treatment of tricuspid regurgitation: a propensity-matched analysis.

Clin Res Cardiol 2021 Mar 12;110(3):451-459. Epub 2020 Dec 12.

Herzzentrum Bonn, Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Background: Transcatheter tricuspid valve repair (TTVR) is a promising technique for the treatment of tricuspid regurgitation (TR). Data comparing the performance of novel edge-to-edge devices (PASCAL and MitraClip-XTR) are scarce.

Methods: We identified 80 consecutive patients who underwent TTVR using either the PASCAL or MitraClip-XTR system to treat symptomatic TR from July 2018 to June 2020. To adjust for baseline imbalances, we performed a propensity score (PS) 1:1 matching. The primary endpoint was a reduction in TR severity by at least one grade at 30 days.

Results: The PS-matched cohort (n = 44) was at high-surgical risk (EuroSCORE II: 7.5% [interquartile range (IQR) 4.8-12.1%]) with a mean TR grade of 4.3 ± 0.8 and median coaptation gap of 6.2 mm [IQR 3.2-9.1 mm]. The primary endpoint was similarly observed in both groups (PASCAL: 91% vs. MitraClip-XTR: 96%). Multiple device implantation was the most common form (59% vs. 82%, p = 0.19), and the occurrence of SLDA was comparable between the PASCAL and MitraClip-XTR system (5.7% [2 of 35 implanted devices] vs. 4.4% [2 of 45 implanted devices], p = 0.99). No periprocedural death or conversions to surgery occurred, and 30-day mortality (5.0% vs. 5.0%, log-rank p = 0.99) and 3-month mortality (10.0% vs. 5.0%, log-rank p = 0.56) were similar between both groups. During follow-up, functional NYHA class, 6-min walking distance, and health status improved in both groups.

Conclusions: Both TTVR devices, PASCAL and MitraClip-XTR, appeared feasible and comparable for an effective TR reduction. Randomized head-to-head comparisons will help to further define the appropriate scope of application of each system.
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http://dx.doi.org/10.1007/s00392-020-01784-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907034PMC
March 2021

AIM2 Stimulation Impairs Reendothelialization and Promotes the Development of Atherosclerosis in Mice.

Front Cardiovasc Med 2020 11;7:582482. Epub 2020 Nov 11.

Department of Internal Medicine II, Heart Center Bonn, University Hospital Bonn, Bonn, Germany.

Atherosclerosis has been shown to result from chronic inflammation caused by constitutive activation of the pattern recognition receptors (PRR), which are principle effectors of the innate immune system. PRR are present in the endosome or on the cellular membrane and can sense the aberrant release of nucleic acids, which is often a sign of acute or chronic cellular damage. Absent in melanoma 2 (AIM2) is a PRR that is expressed by vascular cells and specializes in detecting cytoplasmic double-stranded DNA (dsDNA). Activation of AIM2 leads eventually to activation of the inflammasome, but the role of AIM2 in vascular disease and atherosclerosis has not been well-studied. Therefore, in this study we took advantage of acute and chronic models of vascular injury to determine the biological role of AIM2 in atherogenesis. We were able to induce significant release of proinflammatory cytokines in mice through the intravenous injection of a synthetic ligand for AIM2, double-stranded poly dA:dT. This cytokine release was shown to impair reendothelialization of the carotid artery and increase the number of circulating endothelial microparticles (EMP) after acute denudation, compared to treatment with vehicle. We saw an increase in the production of reactive oxygen species in the aorta, the number of circulating EMP, and, most interestingly, atherosclerotic plaque formation in apolipoprotein E-deficient (ApoE) mice when they received continual subcutaneous poly dA:dT, in contrast to vehicle-treated animals. Finally, treatment with poly dA:dT did not impair vascular reendothelialization in AIM2 mice compared to vehicle controls in the carotid artery injury model. Overall, our data suggest that AIM2, as a known regulator of the inflammasome, is an active participant in atherogenesis, and highlight the importance of fully understanding the pathological mechanisms involved. It seems to be worth of further exploration as a therapeutic target, and future studies focusing on the effects of AIM2 activation as well as its pharmacological inhibition may reveal promising new therapeutic concepts for the treatment of atherosclerosis.
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http://dx.doi.org/10.3389/fcvm.2020.582482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685997PMC
November 2020

Hospital admissions during Covid-19 lock-down in Germany: Differences in discretionary and unavoidable cardiovascular events.

PLoS One 2020 20;15(11):e0242653. Epub 2020 Nov 20.

Department of Cardiology, Heart Center, University of Bonn, Bonn, Germany.

Background: A decline in hospitalization for cardiovascular events and catheter laboratory activation was reported for the United States and Italy during the initial stage of the Covid-19 pandemic of 2020. We report on the deployment of emergency services for cardiovascular events in a defined region in western Germany during the government-imposed lock-down period.

Methods: We examined 5799 consecutive patients who were treated by emergency services for cardiovascular events during the Covid-19 pandemic (January 1 to April 30, 2020), and compared those to the corresponding time frame in 2019. Examining the emergency physicians' records provided by nine locations in the area, we found a 20% overall decline in cardiovascular admissions.

Results: The greatest reduction could be seen immediately following the government-imposed social restrictions. This reduction was mainly driven by a reduction in discretionary admissions for dizziness/syncope (-53%), heart failure (-38%), exacerbated COPD (-28%) and unstable angina (-23%), while unavoidable admissions for ST-elevation myocardial infarction (STEMI), cardiopulmonary resuscitation (CPR) and stroke were unchanged. There was a greater decline in emergency admissions for patients ≥60 years. There was also a greater reduction in emergency admissions for those living in urban areas compared to suburban areas.

Conclusions: During the Covid-19 pandemic, a significant decline in hospitalization for cardiovascular events was observed during the government-enforced shutdown in a predefined area in western Germany. This reduction in admissions was mainly driven by "discretionary" cardiovascular events (unstable angina, heart failure, exacerbated COPD and dizziness/syncope), but events in which admission was unavoidable (CPR, STEMI and stroke) did not change.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242653PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678984PMC
December 2020

MicroRNA-mediated vascular intercellular communication is altered in chronic kidney disease.

Cardiovasc Res 2020 Nov 2. Epub 2020 Nov 2.

Department of Internal Medicine II, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Aims: Chronic kidney disease (CKD) is an independent risk factor for the development of coronary artery disease (CAD). For both, CKD and CAD, the intercellular transfer of microRNAs (miR) through extracellular vesicles (EVs) is an important factor of disease development. Whether the combination of CAD and CKD affects endothelial function through cellular crosstalk of EV-incorporated miRs is still unknown.

Methods And Results: Out of 172 screened CAD patients, 31 patients with CAD+CKD were identified and matched with 31 CAD patients without CKD. Additionally, 13 controls without CAD and CKD were included. Large EVs from CAD+CKD patients contained significantly lower levels of the vasculo-protective miR-130a-3p and miR-126-3p compared to CAD patients and controls. Flow cytometric analysis of plasma-derived EVs revealed significantly higher numbers of endothelial cell-derived EVs in CAD and CAD+CKD patients compared to controls. EVs from CAD+CKD patients impaired target human coronary artery endothelial cell (HCAEC) proliferation upon incubation in vitro. Consistent with the clinical data, treatment with the uremia toxin indoxyl sulfate (IS) reduced miR-130a-3p levels in HCAEC-derived EVs. EVs from IS-treated donor HCAECs reduced proliferation and reendothelialization in EV-recipient cells and induced an anti-angiogenic gene expression profile. In a mouse-experiment, intravenous treatment with EVs from IS-treated endothelial cells significantly impaired endothelial regeneration. On the molecular level, we found that IS leads to an upregulation of the heterogenous nuclear ribonucleoprotein U (hnRNPU), which retains miR-130a-3p in the cell leading to reduced vesicular miR-130a-3p export and impaired EV-recipient cell proliferation.

Conclusions: Our findings suggest that EV-miR-mediated vascular intercellular communication is altered in patients with CAD and CKD, promoting CKD-induced endothelial dysfunction.

Translational Perspective: In the present study we identify a novel hnRNPU-dependent mechanism of how kidney disease and uremia reduce endothelial proliferation. HnRNPU can therefore be used as a target to influence vesicular microRNA levels to improve endothelial healing.
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http://dx.doi.org/10.1093/cvr/cvaa322DOI Listing
November 2020

Prevention and treatment of pulmonary congestion in patients undergoing venoarterial extracorporeal membrane oxygenation for cardiogenic shock.

Eur Heart J 2020 10;41(38):3753-3761

Intensive Care Unit, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Marchioninistraße 15, 81377 Munich, Germany.

Cardiogenic shock is still a major driver of mortality on intensive care units and complicates ∼10% of acute coronary syndromes with contemporary mortality rates up to 50%. In the meantime, percutaneous circulatory support devices, in particular venoarterial extracorporeal membrane oxygenation (VA-ECMO), have emerged as an established salvage intervention for patients in cardiogenic shock. Venoarterial extracorporeal membrane oxygenation provides temporary circulatory support until other treatments are effective and enables recovery or serves as a bridge to ventricular assist devices, heart transplantation, or decision-making. In this critical care perspective, we provide a concise overview of VA-ECMO utilization in cardiogenic shock, considering rationale, critical care management, as well as weaning aspects. We supplement previous literature by focusing on therapeutic issues related to the vicious circle of retrograde aortic VA-ECMO flow, increased left ventricular (LV) afterload, insufficient LV unloading, and severe pulmonary congestion limiting prognosis in a relevant proportion of patients receiving VA-ECMO treatment. We will outline different modifications in percutaneous mechanical circulatory support to meet this challenge. Besides a strategy of running ECMO at lowest possible flow rates, novel therapeutic options including the combination of VA-ECMO with percutaneous microaxial pumps or implementation of a venoarteriovenous-ECMO configuration based on an additional venous cannula supplying towards pulmonary circulation are most promising among LV unloading and venting strategies. The latter may even combine the advantages of venovenous and venoarterial ECMO therapy, providing potent respiratory and circulatory support at the same time. However, whether VA-ECMO can reduce mortality has to be evaluated in the urgently needed, ongoing prospective randomized studies EURO-SHOCK (NCT03813134), ANCHOR (NCT04184635), and ECLS-SHOCK (NCT03637205). These studies will provide the opportunity to investigate indication, mode, and effect of LV unloading in dedicated sub-analyses. In future, the Heart Teams should aim at conducting a dedicated randomized trial comparing VA-ECMO support with vs. without LV unloading strategies in patients with cardiogenic shock.
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http://dx.doi.org/10.1093/eurheartj/ehaa547DOI Listing
October 2020

The Role of Macrophage-Inducible C-Type Lectin in Different Stages of Chronic Liver Disease.

Front Immunol 2020 7;11:1352. Epub 2020 Jul 7.

Department of Internal Medicine I, University Hospital, Goethe University, Frankfurt, Germany.

The macrophage-inducible C-type lectin (mincle) is part of the innate immune system and acts as a pattern recognition receptor for pathogen-associated molecular patterns (PAMPS) and damage-associated molecular patterns (DAMPs). Ligand binding induces mincle activation which consequently interacts with the signaling adapter Fc receptor, SYK, and NF-kappa-B. There is also evidence that mincle expressed on macrophages promotes intestinal barrier integrity. However, little is known about the role of mincle in hepatic fibrosis, especially in more advanced disease stages. Mincle expression was measured in human liver samples from cirrhotic patients and donors collected at liver transplantation and in patients undergoing bariatric surgery. Human results were confirmed in rodent models of cirrhosis and acute-on-chronic liver failure (ACLF). In these models, the role of mincle was investigated in liver samples as well as in peripheral blood monocytes (PBMC), tissues from the kidney, spleen, small intestine, and heart. Additionally, mincle activation was stimulated in experimental non-alcoholic steatohepatitis (NASH) by treatment with mincle agonist trehalose-6,6-dibehenate (TDB). In human NASH, mincle is upregulated with increased collagen production. In ApoE deficient mice fed high-fat western diet (NASH model), mincle activation significantly increases hepatic collagen production. In human cirrhosis, mincle expression is also significantly upregulated. Furthermore, mincle expression is associated with the stage of chronic liver disease. This could be confirmed in rat models of cirrhosis and ACLF. ACLF was induced by LPS injection in cirrhotic rats. While mincle expression and downstream signaling via FC receptor gamma, SYK, and NF-kappa-B are upregulated in the liver, they are downregulated in PBMCs of these rats. Although mincle expressed on macrophages might be beneficial for intestinal barrier integrity, it seems to contribute to inflammation and fibrosis once the intestinal barrier becomes leaky in advanced stages of chronic liver disease.
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http://dx.doi.org/10.3389/fimmu.2020.01352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358277PMC
April 2021

Severe chronic spontaneous urticaria in children - treatment options according to the guidelines and beyond - a 10 years review.

J Dermatolog Treat 2020 Jun 26:1-4. Epub 2020 Jun 26.

Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

This is a retrospective study of 18 children with chronic spontaneous urticaria (CSU), where standard therapies, including up-dosing of antihistamines and omalizumab, were unable to cure the disease and where alternative strategies with experimental and off-label medication had to be used. Being aware that our questionnaire is validated only for elder children or adults, we utilized the UAS7 to monitor disease control with the help of the parents. The UAS7 score decreased from a mean of 25 to an average of 13 after 8 weeks of therapy in 13 patients. Five patients had no significant reduction of UAS7 by week 8. In two of five patients, where periodic improvement was seen, omalizumab therapy was continued and showed complete response after 1-2 years. In three children, alternative treatments with cyclosporine and dupilumab, approved by the ethics committee, showed symptom improvement from a mean UAS7 of 29 to a mean value of 6. When omalizumab therapy including up-dosing strategies or shortened interval shows no symptom improvement, alternative therapies, sometimes off-label have to be considered in time.
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http://dx.doi.org/10.1080/09546634.2020.1782326DOI Listing
June 2020

Prognostic Value of Non-Contrast CT Markers and Spot Sign for Outcome Prediction in Patients with Intracerebral Hemorrhage under Oral Anticoagulation.

J Clin Med 2020 Apr 10;9(4). Epub 2020 Apr 10.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Introduction: In patients with spontaneous intracerebral hemorrhage (ICH), several non-contrast computed tomography (NCCT) markers and the spot sign (SS) in computed tomography (CT) angiography (CTA) have been established for the prediction of hematoma growth and neurological outcome. However, the prognostic value of these markers in patients under oral anticoagulation (ORAC) is unclear. We hypothesized that outcome prediction by these imaging markers may be significantly different between patients with and without ORAC. Therefore, we aimed to investigate the predictive value of NCCT markers and SS in patients with ICH under ORAC.

Methods: This is a retrospective study of the database for patients with ICH at a German tertiary stroke center. Inclusion criteria were (1) patients with ICH, (2) oral anticoagulation within the therapeutic range, and (3) NCCT and CTA performed on admission within 6 h after onset of symptoms. We defined a binary outcome: modified Rankin Scale (mRS) ≤ 3 = good outcome versus mRS > 3 = poor outcome at discharge. The predictive value of each sign was assessed in uni- and multivariable logistic regression models.

Results: Of 129 patients with ICH under ORAC, 76 (58.9%) presented with hypodensities within the hematoma in admission NCCT, 64 (52.7%) presented with an irregular shape of the hematoma, 60 (46.5%) presented with a swirl sign, 49 (38.0%) presented with a black hole sign, and 46 (35.7%) presented with a heterogeneous density of the hematoma. Moreover, 44 (34.1%) patients had a satellite sign, in 20 (15.5%) patients, an island sign was detected, 18 (14.0%) patients were blend-sign positive, and 14 (10.9%) patients presented with a CTA spot sign. Inter-rater agreement was very high for all included characteristics between the two readers. Multivariable logistic regression analysis identified the presence of black hole sign (odds ratio 10.59; < 0.001), swirl sign (odds ratio 14.06; < 0.001), and satellite sign (odds ratio 6.38; = 0.011) as independent predictors of poor outcome.

Conclusions: The distribution and prognostic value of several NCCT markers and CTA spot sign in ICH patients under ORAC is comparable to those with spontaneous ICH, even though these parameters are partly based on coagulant status. These findings suggest that a similar approach can be used for further research regarding outcome prediction in ICH patients under ORAC and those with spontaneous ICH.
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http://dx.doi.org/10.3390/jcm9041077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230516PMC
April 2020

Endovascular management of femoral access-site and access-related vascular complications following percutaneous coronary interventions (PCI).

PLoS One 2020 19;15(3):e0230535. Epub 2020 Mar 19.

Department of Internal Medicine II-Cardiology, Pulmonology and Angiology, University Hospital Bonn, Bonn, Germany.

Background: Major vascular complications (VCs) of ilio-femoral arterial access after percutaneous coronary interventions are infrequent, but are associated with increased mortality and morbidity. Routine endovascular repair of VCs is becoming the treatment of choice, especially for patients who cannot tolerate vascular surgery due to advanced cardiovascular disease or are in a bailout situation. Here, we review the different types of vascular access site complications associated with percutaneous coronary interventions (PCIs) and assess the safety and efficacy of endovascular treatment.

Methods: Data were retrospectively analysed from patients who experienced VCs after transfemoral PCIs, from December 2014 to May 2018. During this period, out of 2833 patients who underwent femoral coronary interventions, 53 (1.9%) experienced major VCs.

Results: In total, 40/53 (75.5%) cases with major VCs led to unplanned endovascular repair and 13/53 (24.5%) cases required surgical repair. VCs included 17 (32.1%) retroperitoneal bleeding events (BARC-2, 3a,b), 20 (37.7%) intimal dissections, and 16 (30.2%) femoral pseudoaneurysms. Overall, 32 (60.4%) patients received a covered stent, two (3.8%) received a nitinol stent, five (9.4%) patients with dissections were treated with prolonged balloon angioplasty alone, and one patient with femoral pseudoaneurysm underwent thrombin injection with simultaneous balloon occlusion. The mean hospital stay for patients after endovascular treatment was 11.06 ± 5.2 days, while for patients after surgical repair it was 17 ± 8.2 days. Endovascularly treated patients were transfused with red blood cells (13/40 32.5% vs. 2/13 15.4%) significantly more often than patients treated surgically, although surgically treated patients received more red blood cell concentrates per unit than endovascularly treated patients (1 ± 0.47 vs. 2 ± 0.93). During the one-year follow-up, no intermittent claudication was reported, and no patient required secondary endovascular or surgical repair.

Conclusions: For patients who cannot tolerate vascular surgery due to advanced cardiovascular disease or are in a bailout situation, endovascular management of VCs following PCIs seems to be a feasible and safe treatment option, and represents an alternative to surgical repair in life-threatening situations. Endovascular treatment was associated with significantly fewer red blood cell concentrates per patient and fewer days in hospital than surgical treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230535PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082010PMC
June 2020

High-Sensitivity Troponin T Testing: Consequences on Daily Clinical Practice and Effects on Diagnosis of Myocardial Infarction.

J Clin Med 2020 Mar 12;9(3). Epub 2020 Mar 12.

Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, 53127 Bonn, Germany.

It remains unclear how introduction of high-sensitivity troponin T testing, as opposed to conventional troponin testing, has affected the diagnosis of acute myocardial infarction (AMI) and resource utilization in unselected hospitalized patients. In this retrospective analysis, we include all consecutive cases from our center during two corresponding time frames (10/2016-04/2017 and 10/2017-04/2018) for which different troponin tests were performed: conventional troponin I (cTnI) and high-sensitivity troponin T (hs-TnT) assays. Testing was performed in 18,025 cases. The incidence of troponin levels above the 99th percentile was significantly higher in cases tested using hs-TnT. This was not associated with increased utilization of echocardiography, coronary angiography, or percutaneous coronary intervention. Although there were no changes in local standard operating procedures, study site personnel, or national coding guidelines, the number of coded AMI significantly decreased after introduction of hs-TnT. In this single-center retrospective study comprising 18,025 mixed medical and surgical cases with troponin testing, the introduction of hs-TnT was not associated with changes in resource utilization among the general cohort, but instead, led to a decrease in the international classification of diseases (ICD)-10 coded diagnosis of AMI.
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http://dx.doi.org/10.3390/jcm9030775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141275PMC
March 2020

Aortic Valve Stenosis: From Basic Mechanisms to Novel Therapeutic Targets.

Arterioscler Thromb Vasc Biol 2020 04 12;40(4):885-900. Epub 2020 Mar 12.

From the Heart Center Bonn, Department of Medicine II, University Hospital Bonn, Germany (P.R.G., M.R.H., D.C., S.T.N., S.Z., G.N., F.J.).

Aortic valve stenosis is the most prevalent heart valve disease worldwide. Although interventional treatment options have rapidly improved in recent years, symptomatic aortic valve stenosis is still associated with high morbidity and mortality. Calcific aortic valve stenosis is characterized by a progressive fibro-calcific remodeling and thickening of the aortic valve cusps, which subsequently leads to valve obstruction. The underlying pathophysiology is complex and involves endothelial dysfunction, immune cell infiltration, myofibroblastic and osteoblastic differentiation, and, subsequently, calcification. To date, no pharmacotherapy has been established to prevent aortic valve calcification. However, novel promising therapeutic targets have been recently identified. This review summarizes the current knowledge of pathomechanisms involved in aortic valve calcification and points out novel treatment strategies.
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http://dx.doi.org/10.1161/ATVBAHA.119.313067DOI Listing
April 2020

Toll-Like Receptor 7 Stimulation Promotes the Development of Atherosclerosis in Apolipoprotein E-Deficient Mice.

Int Heart J 2020 Mar 4;61(2):364-372. Epub 2020 Mar 4.

Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn.

Atherosclerosis is a chronic inflammatory disease with multiple characteristic facets, including vascular inflammation, endothelial dysfunction, plaque development, impaired blood flow, and cholesterol deposition through dyslipidemia. Toll-like receptors (TLRs) of the innate immune system have been closely linked to the development of atherosclerotic lesions. TLR7 recognizes viral or endogenous single-stranded RNA, which is released during vascular apoptosis and necrosis. The role of TLR7 in vascular disease remains controversial, and therefore, we sought to investigate the effects of TLR7 stimulation in mice.Intravenous injection of a ligand for TLR7 (R848) induced a significant pro-inflammatory cytokine response in mice. This was associated with impaired reendothelialization upon acute denudation of the carotid artery, as measured by Evan's blue staining, and increased numbers of circulating endothelial microparticles (EMPs) and circulating Sca1/Flk1 positive cells as a marker for increased endothelial damage. Chronic subcutaneous stimulation of TLR7 in apolipoprotein E-deficient (ApoE) mice increased aortic production of reactive oxygen species (ROS), the number of circulating EMPs, and most importantly, augmented the formation of atherosclerotic plaque when compared with vehicle-treated animals.Systemic stimulation of TLR7 leads to impaired reendothelialization upon acute vascular injury and is associated with the production of pro-inflammatory cytokines and increased levels of circulating EMPs and Sca1/Flk1 positive cells. Importantly, ApoE mice chronically treated with R848 displayed increased atherosclerotic plaque development and elevated levels of ROS in the aortic tissue. In addition, TLR7-activation-induced apoptosis and impaired migration in human coronary artery endothelial cells and showed significant upregulation of the signaling cascade of IL-1 receptor-associated kinase (IRAK) 2 and IRAK4. Our data highlight the importance of fully understanding the pathomechanisms involved in atherogenesis, and further studies are necessary to identify the ligand-specific effects of TLR7 for possible therapeutic targeting.
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http://dx.doi.org/10.1536/ihj.19-365DOI Listing
March 2020

Prognostic impact of cancer history in patients undergoing transcatheter aortic valve implantation.

Clin Res Cardiol 2020 Oct 18;109(10):1243-1250. Epub 2020 Feb 18.

Department of Medicine II, Heart Center Bonn, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.

Background: The benefit of TAVI in cancer patients is currently unclear.

Objectives: The purpose of this study is to investigate prognostic impact of cancer status (active cancer or previous cancer) in severe aortic stenosis (AS) patients undergoing transcatheter aortic valve implantation (TAVI).

Methods: Consecutive TAVI patients in the Heart Center Bonn were enrolled and we stratified the patients into three groups: current cancer (active cancer), non-current cancer (previous cancer), or no cancer. The primary outcome was all-cause death within a 5-year follow-up. We evaluated mean aortic pressure gradient (mPG) values following TAVI (baseline mPG) and at the final follow-up (follow-up mPG).

Results: In total, 1568 TAVI patients were eligible and 298 patients (19.0%) had active or previous cancer. At the 5-year follow-up, cancer patients had a significantly worse prognosis than non-cancer patients (log rank, P < 0.001). In a multivariable analysis, previous cancer was a significant predictor for 5-year mortality (hazard ratio [HR], 1.56; P < 0.001). Estimated mortality rates at 5-year follow-up rates among active cancer, previous cancer, and non-cancer were 84.0%, 65.8%, and 50.2% (long-rank P < 0.001), respectively. The hazard ratios of active cancer and previous cancer for 5-year mortality were 2.79 (P < 0.001) and 1.38 (P = 0.019) compared to non-cancer patients. We found significantly higher mPG during follow-up than at baseline in cancer patients (follow-up 8.10 vs baseline 7.40 mmHg; Wilcoxon P = 0.012).

Conclusions: Active, and also previous, cancer status are associated with less beneficial long-term prognosis in TAVI patients.
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http://dx.doi.org/10.1007/s00392-020-01615-yDOI Listing
October 2020

Murine sca1/flk1-positive cells are not endothelial progenitor cells, but B2 lymphocytes.

Basic Res Cardiol 2020 01 24;115(2):18. Epub 2020 Jan 24.

Westdeutsches Herz- und Gefäßzentrum, Klinik für Kardiologie und Angiologie, Universitätsklinikum Essen, Essen, Germany.

Circulating sca1/flk1 cells are hypothesized to be endothelial progenitor cells (EPCs) in mice that contribute to atheroprotection by replacing dysfunctional endothelial cells. Decreased numbers of circulating sca1/flk1 cells correlate with increased atherosclerotic lesions and impaired reendothelialization upon electric injury of the common carotid artery. However, legitimate doubts remain about the identity of the putative EPCs and their contribution to endothelial restoration. Hence, our study aimed to establish a phenotype for sca1/flk1 cells to gain a better understanding of their role in atherosclerotic disease. In wild-type mice, sca1/flk1 cells were mobilized into the peripheral circulation by granulocyte-colony stimulating factor (G-CSF) treatment and this movement correlated with improved endothelial regeneration upon carotid artery injury. Multicolor flow cytometry analysis revealed that sca1/flk1 cells predominantly co-expressed surface markers of conventional B cells (B2 cells). In RAG2-deficient mice and upon B2 cell depletion, sca1/flk1 cells were fully depleted. In the absence of monocytes, sca1/flk1 cell levels were unchanged. A PCR array focused on cell surface markers and next-generation sequencing (NGS) of purified sca1/flk1 cells confirmed their phenotype to be predominantly that of B cells. Finally, the depletion of B2 cells, including sca1/flk1 cells, in G-CSF-treated wild-type mice partly abolished the endothelial regenerating effect of G-CSF, indicating an atheroprotective role for sca1/flk1 B2 cells. In summary, we characterized sca1/flk1 cells as a subset of predominantly B2 cells, which are apparently involved in endothelial regeneration.
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http://dx.doi.org/10.1007/s00395-020-0774-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981106PMC
January 2020

Combination of ALA-induced fluorescence-guided resection and intraoperative open photodynamic therapy for recurrent glioblastoma: case series on a promising dual strategy for local tumor control.

J Neurosurg 2020 Jan 24:1-11. Epub 2020 Jan 24.

1Department of Neurosurgery.

Objective: High-grade glioma (HGG) prognosis remains dismal, with inevitable, mostly local recurrence. Regimens for improving local tumor control are therefore needed. Photodynamic therapy (PDT) using porfimer sodium has been investigated but was abandoned due to side effects and lack of survival benefits. Intracellular porphyrins induced by 5-aminolevulinic acid (5-ALA) are approved for fluorescence-guided resections (FGRs), but are also photosensitizers. Activated by light, they generate reactive oxygen species with resultant cytotoxicity. The authors present a combined approach of 5-ALA FGR and PDT.

Methods: After 5-ALA FGR in recurrent HGG, laser diffusors were strategically positioned inside the resection cavity. PDT was applied for 60 minutes (635 nm, 200 mW/cm diffusor, for 1 hour) under continuous irrigation for maintaining optical clarity and ventilation with 100% oxygen. MRI was performed at 24 hours, 14 days, and every 3 months after surgery, including diffusion tensor imaging and apparent diffusion coefficient maps.

Results: Twenty patients were treated. One surgical site infection after treatment was noted at 6 months as the only adverse event. MRI revealed cytotoxic edema along resection margins in 16 (80%) of 20 cases, mostly annular around the cavity, corresponding to prior laser diffusor locations (mean volume 3.3 cm3). Edema appeared selective for infiltrated tissue or nonresected enhancing tumor. At the 14-day follow-up, enhancement developed in former regions of edema, in some cases vanishing after 4-5 months. Median progression-free survival (PFS) was 6 months (95% CI 4.8-7.2 months).

Conclusions: Combined 5-ALA FGR and PDT provides an innovative and safe method of local tumor control resulting in promising PFS. Further prospective studies are warranted to evaluate long-term therapeutic effects.
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http://dx.doi.org/10.3171/2019.11.JNS192443DOI Listing
January 2020

Intravascular Lithotripsy in Calcified Coronary Lesions: A Prospective, Observational, Multicenter Registry.

Circ Cardiovasc Interv 2019 11 11;12(11):e008154. Epub 2019 Nov 11.

Heart Center Trier, Krankenhaus der Barmherzigen Brüder Trier, Germany (J.L., N.W.).

Background: Optimal plaque preparation of calcified coronary lesions is key to prevent stent failure. The purpose of this study was to determine the strategy success and safety of intravascular lithotripsy (IVL) in calcified lesions of an all-comers cohort.

Methods: Patients with calcified coronary lesions were screened in 3 centers. Seventy-one patients were eligible for IVL. Patients were assigned to (group A) primary IVL therapy for patients with calcified de-novo lesions (n=39 lesions), (group B) secondary IVL therapy for patients with calcified lesions in which noncompliant balloon dilatation failed (n=22 lesions), and (group C) tertiary IVL therapy in patients with stent underexpansion after previous stenting (n=17 lesions). Primary end point was strategy success (stent expansion with <20% in-stent residual stenosis) and safety outcomes (procedural complications, in-hospital major adverse cardiovascular event).

Results: Seventy-eight calcified lesions were treated using the Shockwave C balloon. Mean diameter stenosis of calcified lesions was 71.8±13.1% at baseline, decreased to 45.1±17.4% immediately after IVL, and to 17.5±15.2% after stenting. Mean minimal lumen diameter was 1.01±0.49 mm at baseline and increased to 1.90±0.61 after IVL, and to 2.88±0.56 mm after stenting. The primary end point of strategy success was reached in 84.6% (group A), 77.3% (group B), and 64.7% (group C). Device delivery and IVL treatment were possible in all lesions. Four type b dissections were observed without further sequelae. No patient suffered from in-hospital major adverse cardiovascular event. Seven Shockwave balloons ruptured during treatment without any sequelae.

Conclusions: IVL provides a valid strategy for lesion preparation in severely calcified coronary lesions with high success rate, low procedural complications, and low major adverse cardiovascular event rates.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008154DOI Listing
November 2019

Brodalumab for the treatment of moderate-to-severe psoriasis: case series and literature review.

Clin Cosmet Investig Dermatol 2019 10;12:509-517. Epub 2019 Jul 10.

MediCorium , Oberursel, Germany.

Brodalumab, a recombinant fully human monoclonal immunoglobulin IgG2 antibody with high affinity to human interleukin (IL)-17RA, is approved for the treatment of moderate-to-severe plaque psoriasis. In controlled clinical trials, brodalumab 210 mg administered by subcutaneous injection at weeks 0, 1, and 2, then 210 mg every 2 weeks, produced a rapid onset and sustained clinical response. Consistently, >80% of patients achieved PASI-75 and efficacy was maintained for >2 years. The benefits are apparent soon after the start of therapy and are maintained in the long term. Such results, from the reviewed literature, support the findings from 4 'real world' cases in mainstream clinical practice which are reported here. Psoriatic plaques, including on the scalp, nails, soles and palms, were largely resolved, and quality of life improved markedly. Therapeutic success was achieved in patients naïve to biologics (2 cases) and in those responding inadequately to other biologics (2 cases). The high affinity of brodalumab to human IL-17RA blocks the biological activities of the pro-inflammatory cytokines IL-17A, IL-17C, IL-17E, IL-17F, and IL-17A/F heterodimer, resulting in inhibition of the inflammation and clinical symptoms associated with psoriasis. This mechanism of blocking multiple IL-17 family cytokines differs from that of other available biologics which selectively target some parts of the Th-17 axis and may account for the effectiveness of brodalumab in patients poorly responsive to other biologics, a feature which has also been shown where subgroup analysis has been undertaken in clinical trials. The drug is well tolerated during the normal 12-week induction phase and with prolonged treatment (52 to 120 weeks), as it was in the current case series.
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http://dx.doi.org/10.2147/CCID.S211938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628099PMC
July 2019

[Clinical Advances in Aortic Diseases: from Aortic Valve to Bifurcation].

Dtsch Med Wochenschr 2019 06 4;144(11):734-738. Epub 2019 Jun 4.

Klinik für Kardiologie, Pneumologie und Angiologie, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf.

There is growing understanding to recognize the aorta as complex system and treat aortic diseases in an integrated fashion.The indication for interventional aortic valve replacement (TAVR) comprises patients with moderate and high perioperative risk and symptomatic, high grade aortic valve stenosis. In contrast "low risk" patients receive conventional therapy. Ongoing randomised trials analyse the expansion of indication towards low risk patients for interventional approaches. A final rating is owing, but first data support the assumption that both therapeutic options may be equivalent. Moreover, the interventional therapy of low flow, low gradient aortic valve stenosis has been revalued and interventional valve-in-valve therapy has been integrated into clinical routine as invidualised decision of the heart team.Aortic diseases include several entities which require specialised diagnostic and therapeutic tools. Studies to evaluate evidence of follow up options need to be performed in future to enable for surveillance tailored to suit medical need.
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http://dx.doi.org/10.1055/a-0663-6474DOI Listing
June 2019

Fatal Cardioembolic Syndrome Due to Late Device-Related Thrombus After Left Atrial Appendage Occlusion.

JACC Cardiovasc Interv 2019 06 15;12(11):e91-e92. Epub 2019 May 15.

Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Bonn, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.jcin.2019.02.016DOI Listing
June 2019

Impact of Hemodynamic Support on Outcome in Patients Undergoing High-Risk Percutaneous Coronary Intervention.

Am J Cardiol 2019 07 10;124(1):20-30. Epub 2019 Apr 10.

Department of Medicine II, Heart Center, University Hospital Bonn, Bonn, Germany. Electronic address:

The use of left-ventricular (LV) hemodynamic support might facilitate high-risk percutaneous coronary interventions (PCI) in patients with complex coronary artery disease. The impact on outcome is a matter of ongoing debate. We assessed the outcome of high-risk patients who underwent protected PCI in comparison to patients who underwent unprotected high-risk PCI. One hundred and thirty nine patients underwent nonemergent high-risk PCI; 24 (17%) patients underwent protected PCI. To address selection bias, we performed a propensity score matched subanalysis. The primary end point was the occurrence of a major adverse cardiac event during the first year. Patients with protected PCI had a higher logistic EuroSCORE (logES) (protected PCI: 19% vs unprotected PCI: 12%; p = 0.01), a higher SYNTAX score (45 vs 36, p = 0.07), and significantly more often reduced LV function (40% vs 55%; p < 0.001). In protected PCI patients, complete revascularization was more often achieved (87% vs 58%, p = 0.007) without the occurrence of death at 30 days of follow-up (0% vs 4%, p = 0.31). After propensity score matching, patients who underwent protected PCI had a similar 1-year major adverse cardiac event rate compared with patients who underwent unprotected PCI (21% vs 17%, p = 0.67), despite significantly higher procedural complexity for example, more often complex left main bifurcation lesions (71% vs 29%; p = 0.004). In conclusion, 1-year outcome of patients who underwent protected PCI was not different from that in patients with less complex procedures without hemodynamic support, despite more complex coronary anatomy, a higher comorbidity burden, and more often reduced LV function.
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http://dx.doi.org/10.1016/j.amjcard.2019.03.050DOI Listing
July 2019

Effective treatment of disseminated superficial actinic porokeratosis with chemical peels - customary treatment for a rare disease.

J Dermatolog Treat 2020 Nov 12;31(7):744-748. Epub 2019 Aug 12.

Department of Dermatology, University Medicine Mainz, Mainz, Germany.

Disseminated superficial actinic porokeratosis (DSAP) is a rare dermatologic disorder of the epidermis. Often misdiagnosed as chronic UV-damage or actinic keratoses, patients are treated for years with different therapeutic options with little success. Current treatment options include imiquimod, ingenol mebutate, cryosurgery, photodynamic therapy and topical or systemic therapy with retinoids. Since those approaches show only little success or come along with major side effects, therapeutic alternatives are strongly requested. We report a series of five female patients with history of DSAP that were successfully treated with chemical peels. All patients suffered from the disease for 14.4 years on average and all were refractory to at least two therapeutic options, mostly imiquimod and topical tretinoin. Patients were treated with glycolic acid 50% and salicylic acid 25% in a two-layer-technique. After a mean of three cycles every 6 weeks a clear reduction in lesion was assessed by physicians. Patients were highly satisfied with outcome and rare occurrence of side effects as assessed by TSQM questionnaire. Chemical peels are safe and well tolerated treatment options for patients with refractory porokeratosis. As characteristic for chronic diseases, frequent repetition of treatment is needed in order to control disease activity.
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http://dx.doi.org/10.1080/09546634.2019.1610551DOI Listing
November 2020

Graded murine wire-induced aortic valve stenosis model mimics human functional and morphological disease phenotype.

Clin Res Cardiol 2019 Aug 14;108(8):847-856. Epub 2019 Feb 14.

Cardiovascular Research Laboratory, Division of Cardiology, Pulmonary Diseases and Vascular Medicine, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.

Aortic valve stenosis (AS) is the most common valve disease requiring therapeutic intervention. Even though the incidence of AS has been continuously rising and AS is associated with significant morbidity and mortality, to date, no medical treatments have been identified that can modify disease progression. This unmet medical need is likely attributed to an incomplete understanding of the molecular mechanism driving disease development. To investigate the pathophysiology leading to AS, reliable and reproducible animal models that mimic human pathophysiology are needed. We have tested and expanded the protocols of a wire-injury induced AS mouse model. For this model, coronary wires were used to apply shear stress to the aortic valve cusps with increasing intensity. These protocols allowed distinction of mild, moderate and severe wire-injury. Upon moderate or severe injury, AS developed with a significant increase in aortic valve peak blood flow velocity. While moderate injury promoted solitary AS, severe-injury induced mixed aortic valve disease with concomitant mild to moderate aortic regurgitation. The changes in aortic valve function were reflected by dilation and hypertrophy of the left ventricle, as well as a decreased left ventricular ejection fraction. Histological analysis revealed the classic hallmarks of human disease with aortic valve thickening, increased macrophage infiltration, fibrosis and calcification. This new mouse model of AS promotes functional and morphological changes similar to moderate and severe human AS. It can be used to investigate the pathomechanisms contributing to AS development and to test novel therapeutic strategies.
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http://dx.doi.org/10.1007/s00392-019-01413-1DOI Listing
August 2019

The psoriasis patient – an exemplification of interdisciplinarity.

Med Monatsschr Pharm 2017 Jun;40(6):245-6

As quite typical for patients with plaque psoriasis, mainly if they are seriously affected, some of the major problems aside the obvious systemic inflammatory component, are social decline due to loss of work and/or personal problems. With this case presentation we are shedding light on the actual extent of this disease in our society.
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June 2017

Management of psoriasis.

Med Monatsschr Pharm 2017 Jun;40(6):238-44

Therapeutic procedures are dictated by burden and duration of disease, previous therapies and comorbidity. Possible triggers are to be taken into consideration and eliminate whenever possible.
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June 2017

What‘s the appearance of psoriasis.

Med Monatsschr Pharm 2017 Jun;40(6):234-7

Psoriatic disorders are a visual diagnosis. Aside from several subtypes of skin psoriasis, skin appendages such nails are often affected. The burden of disease is defined by the disease activity (extent of affliction of skin) as well as restriction of quality of life. Validated scores are a good tool for the evaluation.
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June 2017