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Zusammenfassung Hintergrund Obwohl allergologische Erkrankungen zu den wichtigen Gesundheitsstörungen laut ärztlicher Approbationsordnung zählen, ist die Allergologie in Deutschland nicht als selbstständiges Fach im Studium der Humanmedizin verankert. Ziel der Arbeit Da sämtliche Universitäts- und Hochschulstandorte mit dieser Herausforderung umgehen müssen, war es Ziel unseres Lehrprojekts, eine exemplarische und mit allen beteiligten Kliniken und Instituten abgestimmte Koordination und Verzahnung der allergologischen Lehre an einem Standort zu etablieren. Insbesondere Comprehensive Allergy Centers (CAC) bieten eine bereits vorhandene Infrastruktur, in der diese Neukonzeption der allergologischen Lehre auf andere Standorte übertragen werden könnte. Material und Methoden Nach umfangreicher Bestandsaufnahme der aktuellen allergologischen Lehre an der Universitätsmedizin Göttingen wurde im interdisziplinären Konsens ein neues Lehrkonzept entwickelt, durch die Bereitstellung zusätzlicher digitaler Lehr- und Lernanteile ergänzt („blended learning“) und schließlich evaluiert. Ergebnisse Die allergologische Lehre im klinischen Studienabschnitt zeigte eine starke Fragmentierung, die ohne Koordination der zwölf beteiligten Kliniken/Institute und ohne Abstimmung der jeweiligen Lerninhalte stattfand. In der etablierten Struktur des interdisziplinären CAC erfolgte eine Neukonzeption, Koordination und Schwerpunktsetzung der studentischen Lehre zur klinischen Allergologie. Die Bereitstellung von neuen interaktiven Lerneinheiten sowie ergänzender Materialien zum Selbststudium wurden von den Studierenden positiv bewertet. Eine vergleichende Evaluation von Studierenden nach Absolvieren der unterschiedlichen Curricula zeigte signifikante Verbesserungen im Erreichen der gewünschten Lernziele.

Although allergic diseases are among the most important health disorders, allergology is not anchored as an independent subject in the clinical part of medical studies in Germany.As all universities and institutes face the same challenge, the aim of our project was to establish exemplary coordination and networking of education in allergology at one location in agreement with all involved departments and institutes. Particularly, Comprehensive Allergy Centers (CAC) offer an established infrastructure via which the revised allergology education program can be transferred to other universities.After an extensive inventory of the current allergological curriculum at the University Medical Center Göttingen, a new teaching concept was developed in interdisciplinary consensus, supplemented by first-time provision of additional digital contents ("blended learning"), and finally evaluated.Initially, we observed a high level of fragmentation in the teaching of allergology in the clinical study sections of human medicine, with no coordination between the 12 clinical departments/institutes involved and no coherent framework for the specific learning content. Within the established structure of the interdisciplinary CAC, we revised, coordinated, and defined key areas for improved student education in clinical allergology. The allocation of new interactive learning elements as well as supplementary materials for self-studies was welcomed by the students and positively evaluated. A survey among students after completing the former vs. current curricula showed significant improvements in achieving the desired educational objectives.HINTERGRUND: Obwohl allergologische Erkrankungen zu den wichtigen Gesundheitsstörungen laut ärztlicher Approbationsordnung zählen, ist die Allergologie in Deutschland nicht als selbstständiges Fach im Studium der Humanmedizin verankert.Da sämtliche Universitäts- und Hochschulstandorte mit dieser Herausforderung umgehen müssen, war es Ziel unseres Lehrprojekts, eine exemplarische und mit allen beteiligten Kliniken und Instituten abgestimmte Koordination und Verzahnung der allergologischen Lehre an einem Standort zu etablieren. Insbesondere Comprehensive Allergy Centers (CAC) bieten eine bereits vorhandene Infrastruktur, in der diese Neukonzeption der allergologischen Lehre auf andere Standorte übertragen werden könnte.Nach umfangreicher Bestandsaufnahme der aktuellen allergologischen Lehre an der Universitätsmedizin Göttingen wurde im interdisziplinären Konsens ein neues Lehrkonzept entwickelt, durch die Bereitstellung zusätzlicher digitaler Lehr- und Lernanteile ergänzt („blended learning“) und schließlich evaluiert.Die allergologische Lehre im klinischen Studienabschnitt zeigte eine starke Fragmentierung, die ohne Koordination der zwölf beteiligten Kliniken/Institute und ohne Abstimmung der jeweiligen Lerninhalte stattfand. In der etablierten Struktur des interdisziplinären CAC erfolgte eine Neukonzeption, Koordination und Schwerpunktsetzung der studentischen Lehre zur klinischen Allergologie. Die Bereitstellung von neuen interaktiven Lerneinheiten sowie ergänzender Materialien zum Selbststudium wurden von den Studierenden positiv bewertet. Eine vergleichende Evaluation von Studierenden nach Absolvieren der unterschiedlichen Curricula zeigte signifikante Verbesserungen im Erreichen der gewünschten Lernziele.

Lymphoma-associated Hemophagocytic lymphohistiocytosis (HLH) represents a severe complication of disease progression, mediated through cytokine release from the lymphoma cells. Cytokine adsorption may contribute as a supportive treatment to stabilize organ function by reduction of cytokine levels. So far, no experiences of cytokine adsorption and simultaneous stem cell transplantation were published. We report the case of a patient with aggressive lymphoma secondary to chronic lymphocytic leukemia with rapidly progressive HLH (Richter’s transformation) upon conditioning chemotherapy prior to allogeneic stem cell transplantation (ASCT). Continuous hemodiafiltration was initiated in the treatment of shock with acute renal failure, lactacidosis and need for high-dose catecholamine therapy, integrating an additional cytokine-adsorbing filter (CytoSorb®) to reduce cytokine levels. This was followed by scheduled allogenic stem cell transplantation. We observed a marked decrease in interleukin-6 plasma levels, associated with a reduced need for vasopressor therapy and organ function stabilization. Hematopoietic engraftment was present at day 14 post-ASCT, leading to disease-free discharge at day 100 post-transplantation. Cytokine adsorption may serve as a safe adjunct to HLH/sepsis treatment during allogeneic stem cell transplantation. Clinical studies are required to make future treatment recommendations.

Endpoints of large-scale trials in chronic heart failure have mostly been defined to evaluate treatments with regard to hospitalizations and mortality. However, patients with heart failure are also affected by very severe reductions in exercise capacity and quality of life. We aimed to evaluate the effects of heart failure treatments on these endpoints using available evidence from randomized trials. Interventions with evidence for improvements in exercise capacity include physical exercise, intravenous iron supplementation in patients with iron deficiency, and - with less certainty - testosterone in highly selected patients. Erythropoiesis-stimulating agents have been reported to improve exercise capacity in anaemic patients with heart failure. Sinus rhythm may have some advantage when compared with atrial fibrillation, particularly in patients undergoing pulmonary vein isolation. Studies assessing treatments for heart failure co-morbidities such as sleep-disordered breathing, diabetes mellitus, chronic kidney disease and depression have reported improvements of exercise capacity and quality of life; however, the available data are limited and not always consistent. The available evidence for positive effects of pharmacologic interventions using angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists on exercise capacity and quality of life is limited. Studies with ivabradine and with sacubitril/valsartan suggest beneficial effects at improving quality of life; however, the evidence base is limited in particular for exercise capacity. The data for heart failure with preserved ejection fraction are even less positive, only sacubitril/valsartan and spironolactone have shown some effectiveness at improving quality of life. In conclusion, the evidence for state-of-the-art heart failure treatments with regard to exercise capacity and quality of life is limited and appears not robust enough to permit recommendations for heart failure. The treatment of co-morbidities may be important for these patient-related outcomes. Additional studies on functional capacity and quality of life in heart failure are required.

Bastian Schrader,1 Anna-Maria Bünker,2,3 Charis Conradi,1 Stephan Lüders,2,4 Bernhard Vaske,5 Michael Koziolek,3 Hermann Haller,6 Albrecht Elsässer,1 Joachim Schrader1,2 1Department of Cardiology in Klinikum Oldenburg, University of Oldenburg, Oldenburg, Germany; 2Institute for Hypertension and Cardiovascular Research (INFO), Cloppenburg, Germany; 3Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany; 4Department of Nephrology, St.-Josefs-Hospital, Cloppenburg, Germany; 5Department of Statistics, Institute for Hypertension and Cardiovascular Research (INFO), Cloppenburg, Germany; 6Clinic for Renal and Hypertensive Diseases, Hannover Medical School, Hanover, GermanyCorrespondence: Bastian Schrader Email bastian.schrader@uni-Oldenburg.deIntroduction: It is well documented that insufficient physical activity (PA) contributes substantially to cardiovascular diseases. The number of physically active people in Germany is still too low.Methods: In ELITE study in Germany, 4602 participants are regularly examined for cardiovascular risk factors (CVRF). The aim is to motivate participants to improve their CVRF through individual recommendations and regular follow-up. Here, the PA data are presented in correlation with CVRF at baseline. A feature of this presentation is that the usual CVRF but also the effects on psychosocial factors were recorded simultaneously.Results: Participants were divided into 3 groups based on their PA: 1. frequent exercise (FE): daily to 2– 3x per week (41.4%), 2. moderate exercise (ME): 1x/week to 2x/month (28.8%), 3. rarely exercise (RE): 1x/month to not at all (29.8%). Age did not differ in the 3 groups. The most common CVRF was arterial hypertension, which decreased significantly with an increase in PA. Diabetes, nicotine, and increased BMI were also significantly less frequent in group 1. Antihypertensives were taken less frequently in this group 1. Less physically active participants were significantly more likely to have 3 or more additional CVRF. While group 1 consumed more fruit (64%) and considerably less pork, in group 2 and 3 only 58.3% and 50.3% respectively included fruit in their diet. FE also had a favorable effect on stress, depression and general well-being, all of which were significantly better in group 1.Conclusion: Results confirm the beneficial influences of exercise on known CVRF and on psychosocial parameters. The prevalence of several CVRF per person at low levels of sport is of particular concern, as these participants would benefit most. During a 5-year follow-up, participants will receive intensive education on the need to increase PA. It remains to be seen how successful the effort will be.Keywords: sport, exercise, cardiovascular risk factors, hypertension, diabetes, hypercholesterolemia, stress, ELITE, nutrition

Background Risk of kidney function decline in immunoglobulin A (IgA) nephropathy (IgAN) is significant and may not be predicted by available clinical and histological tools. To serve this unmet need, we aimed at developing a urinary biomarker-based algorithm that predicts rapid disease progression in IgAN, thus enabling a personalized risk stratification. Methods In this multicentre study, urine samples were collected in 209 patients with biopsy-proven IgAN. Progression was defined by tertiles of the annual change of estimated glomerular filtration rate (eGFR) during follow-up. Urine samples were analysed using capillary electrophoresis coupled mass spectrometry. The area under the receiver operating characteristic curve (AUC) was used to evaluate the risk prediction models. Results Of the 209 patients, 64% were male. Mean age was 42 years, mean eGFR was 63 mL/min/1.73 m2 and median proteinuria was 1.2 g/day. We identified 237 urine peptides showing significant difference in abundance according to the tertile of eGFR change. These included fragments of apolipoprotein C-III, alpha-1 antitrypsin, different collagens, fibrinogen alpha and beta, titin, haemoglobin subunits, sodium/potassium-transporting ATPase subunit gamma, uromodulin, mucin-2, fractalkine, polymeric Ig receptor and insulin. An algorithm based on these protein fragments (IgAN237) showed a significant added value for the prediction of IgAN progression [AUC 0.89; 95% confidence interval (CI) 0.83–0.95], as compared with the clinical parameters (age, gender, proteinuria, eGFR and mean arterial pressure) alone (0.72; 95% CI 0.64–0.81). Conclusions A urinary peptide classifier predicts progressive loss of kidney function in patients with IgAN significantly better than clinical parameters alone., Graphical Abstract Graphical Abstract

Contains fulltext : 286841.pdf (Publisher’s version ) (Closed access) BACKGROUND: Resistant hypertension is associated with increased cardiovascular risk. The endothelin pathway has been implicated in the pathogenesis of hypertension, but it is currently not targeted therapeutically, thereby leaving this relevant pathophysiological pathway unopposed with currently available drugs. The aim of the study was to assess the blood pressure lowering efficacy of the dual endothelin antagonist aprocitentan in patients with resistant hypertension. METHODS: PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 study, which was done in hospitals or research centres in Europe, North America, Asia, and Australia. Patients were eligible for randomisation if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardised background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: part 1 was the 4-week double-blind, randomised, and placebo-controlled part, in which patients received aprocitentan 12·5 mg, aprocitentan 25 mg, or placebo in a 1:1:1 ratio; part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg; and part 3 was a 12-week double-blind, randomised, and placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. The study is registered on ClinicalTrials.gov, NCT03541174. FINDINGS: The PRECISION study was done from June 18, 2018, to April 25, 2022. 1965 individuals were screened and 730 were randomly assigned. Of these 730 patients, 704 (96%) completed part 1 of the study; of these, 613 (87%) completed part 2 and, of these, 577 (94%) completed part 3 of the study. The least square mean (SE) change in office systolic blood pressure at 4 weeks was -15·3 (SE 0·9) mm Hg for aprocitentan 12·5 mg, -15·2 (0·9) mm Hg for aprocitentan 25 mg, and -11·5 (0·9) mm Hg for placebo, for a difference versus placebo of -3·8 (1·3) mm Hg (97·5% CI -6·8 to -0·8, p=0·0042) and -3·7 (1·3) mm Hg (-6·7 to -0·8; p=0·0046), respectively. The respective difference for 24 h ambulatory systolic blood pressure was -4·2 mm Hg (95% CI -6·2 to -2·1) and -5·9 mm Hg (-7·9 to -3·8). After 4 weeks of withdrawal, office systolic blood pressure significantly increased with placebo versus aprocitentan (5·8 mm Hg, 95% CI 3·7 to 7·9, p

OBJECTIVES Football as the most popular sport could improve insufficient physical activity in patients with cardiovascular risk factors. A modified 'healthy' football training format could motivate hypertensive patients to return to sport and improve risk factors. METHODS The 3F study: 'Fit and Fun with Football' a prospective interventional study with 1 year follow-up. Football group: n = 103, structured 'health'-football training (1×/week, 90 min) led by Deutscher Fusball Bund-licensed football coaches. Hypertensive patients at least 45 years who have not exercised for several years were compared with a control group (n = 105). PRIMARY STUDY OBJECTIVE Reduction of office (OBP) and/or 24-h ambulatory blood pressure (BP) monitoring (ABPM) and/or reduction of number or dosage of antihypertensive medication. MAIN RESULTS OBP values decreased significantly in the football group from 142.6/87.9 to 130.8/81.8 mmHg (P

Background Due to rising vascular comorbidities of patients undergoing dialysis, the prevalence of permanent hemodialysis catheters as hemodialysis access is increasing. However, infection is a major complication of these catheters. Therefore, identification of potential predicting risk factors leading to early infection related complications is valuable, in particular the significance the CRP (C-reactive protein)-value is of interest. Methods In this retrospective study 151 permanent hemodialysis catheters implanted in 130 patients were examined. The following data were collected at the time of catheter implantation: CRP-value, history of catheter-related infection, microbiological status, immunosuppression and diabetes mellitus. The primary outcomes were recorded over the 3 months following the implantation: catheter-related infection, days of hospital stay and death. Catheter removal or revision, rehospitalization and use of antibiotics were identified as secondary outcomes. Results We identified a total of 27 (17.9%) infections (systemic infection: 2.26 episodes/ 1000 catheter days, local infection: 0.6 episodes/ 1000 catheter days). The development of an infection was independent of the CRP-value (p = 0.66) as well as the presence of diabetes mellitus (p = 0.64) or immunosuppression (p = 0.71). Univariate analysis revealed that infection was more frequent in patients with MRSA-carriage (p

In addition to the early detection of an acute kidney injury (AKI), several problems or questions have to be addressed. These include the identification of the etiology, the severity (functional or structural), the prognosis (recovery or transition to chronic renal failure), the course of the disease (dialysis or not), and the identification of specific treatment options for AKI. The following article provides an overview of established and new AKI biomarkers as well as an outlook on the potential of future biomarker-associated models of AKI.

Background: The determination of renal function is crucial for the clinical management of patients with cancer. The glomerular filtration rate (GFR) serves as a key parameter, estimated by creatinine clearance determination in 24-h collected urine (CrCl) as well as equation-based approaches (eGFR) relying on serum creatinine (eGFR CKD EPIcrea) or serum cystatin C (eGFR cystatin C). Serum creatinine and serum cystatin C levels differentially depend on muscle and tumor mass, respectively. Although muscle and tumor mass may thus represent confounding factors, comparative studies for eGFR estimate approaches in cancer patients are lacking. Methods: The present study retrospectively analyzed GFR estimates based on equations of creatinine (eGFRcr), cystatin C (eGFRcys) and combined creatinine-cystatin C levels (eGFRcr-cys) in a subset of patients. The associations of LDH with cystatin C or LDH with eGFRcr, eGFRcys and GFRcr-cys were explored. Results: The laboratory values of 123 consecutive patients were included. The median age was 59 (24–87) and 47.2% were female. There was a statistically significant difference in the mean of CKD EPIcrea (85.17 ± 21.63 mL/min/1.73 m2), CKD EPIcys (61.16 ± 26.03 mL/min/1.73 m2) and CKD EPIcrea-cys (70.42 ± 23.89 mL/min/1.73 m2) (p < 0.0001). Spearman’s correlation analysis revealed a significant correlation of elevated plasma LDH >1.5 UNV and cystatin C values (r = 0.270, p < 0.01, n = 123). LDH values >1.5 UNV were associated with significantly lower CKD EPIcys (r = 0.184, p < 0.01) or CKD EPIcrea-cys (r = 0.226, p < 0.05) estimates compared to CKD EPIcrea. Conclusions: The inclusion of cystatin C as a biomarker led to a lower eGFR estimates compared to creatinine alone or in a combination of both cystatin C and creatinine. The level of cystatin C correlated with the level of LDH, suggesting that the use of cystatin C-based calculations of GFR in cancer patients with elevated LDH should be used with caution.

The ELITE study (German acronym for "Nutrition, lifestyle and individual information for prevention of heart attack, stroke and dementia") prospectively collects data on hypertension, cardiovascular risk factors (RF), dietary habits, physical activity, cognitive function, and quality of life in North-West Germany, which will then be improved through targeted individual information. The aim of the study is to improve the health of the participants in the long term and to identify reasons for a lack of implementation of prevention measures.Of 4,602 included subjects, 3,868 could be studied so far at one-year follow-up. Blood pressure (BP) was measured according to the guidelines at admission and blood pressure history, premedication, sports behaviour and BMI were recorded by means of questionnaires and compared with the data collected in the follow-up examination after one year.The participants were evaluated in 4 groups (G): G1 - normotensive patients (n = 1,558), G2 - controlled hypertensive patients (n = 502), G3 - untreated uncontrolled hypertensive patients (n = 1,080), G4 - treated uncontrolled hypertensive patients (n = 728). In G1 blood pressure (RR) remained unchanged from 126.3/77.8 to 127.8/78.5, in G2 there was a significant (p0.001) RR increase from 128.1/77.0 to 134.9/79.8. In G3 and G4 RR decreased significantly (p0.001) from 149.9/90.0 to 143.5/86.9 and from 153.1/87.5 to 146.2 84.1 mmHg, respectively. In G3 and G4, RR decreased in 56.1% and 56.3% of subjects and increased in 18% and 21%, respectively. In contrast, RR increase was found more frequently in G1 and G2 (34.3% and 51%, respectively), and RR decrease less frequently (25.4 and 20.7%, respectively). The main reasons for RR decrease were weight loss, more exercise, and more antihypertensives. Frequently, improved compliance and dietary changes were given as reasons. As expected, the opposite often led to RR increase.56% of the hypertensive participants succeeded in lowering their blood pressure, whereas there was a significant increase in blood pressure, especially in those who were well controlled with antihypertensives. This underlines the need to further motivate normotensive patients to maintain their normotension. The results show that the combination of individual written education and lifestyle interventions are an effective tool for the public health sector to combat hypertension. In our participants, lifestyle interventions have a significant impact on BP change. It should be noted critically that there are still too many patients who have not been reached.

Twenty-four patients with bi-allelic familial hypercholesterolemia commencing chronic lipoprotein apheresis (LA) at a mean age of 8.5 ± 3.1 years were analysed retrospectively and in part prospectively with a mean follow-up of 17.2 ± 5.6 years. Mean age at diagnosis was 6.3 ± 3.4 years. Untreated mean LDL-C concentrations were 752 mg/dl ± 193 mg/dl (19.5 mmol/l ± 5.0 mmol/l). Multimodal lipid lowering therapy including LA resulted in a mean LDL-C concentration of 184 mg/dl (4.8 mmol/l), which represents a 75.5% mean reduction. Proprotein convertase subtilisin/kexin type 9-antibodies contributed in 3 patients to LDL-C lowering with 5 patients remaining to be tested. After commencing chronic LA, 16 patients (67%) remained clinically stable with only subclinical findings of atherosclerotic cardiovascular disease (ASCVD), and neither cardiovascular events, nor need for vascular interventions or surgery. In 19 patients (79%), pathologic findings were detected at the aortic valve (AV), which in the majority were mild. AV replacement was required in 2 patients. Mean Lipoprotein(a) concentration was 42.4 mg/dl, 38% had >50 mg/dl. There was no overt correlation of AV pathologies with other ASCVD complications, or Lipoprotein(a) concentration. Physicochemical elimination of LDL particles by LA appears indispensable for patients with bi-allelic familial hypercholesterolemia and severe hypercholesterolemia to maximize the reduction of LDL-C. In conclusion, in this rare patient group regular assessment of both the AV, as well as all arteries accessible by ultrasound should be performed to adjust the intensity of multimodal lipid lowering therapy with the goal to prevent ASCVD events and aortic surgery.

Multiple sclerosis (MS) is an inflammatory disease mainly affecting the central nervous system. In MS, abnormal immune mechanisms induce acute inflammation, demyelination, axonal loss, and the formation of central nervous system plaques. The long-term treatment involves options to modify the disease progression, whereas the treatment for the acute relapse has its focus in the administration of high-dose intravenous methylprednisolone (up to 1000 mg daily) over a period of three to five days as a first step. If symptoms of the acute relapse persist, it is defined as glucocorticosteroid-unresponsive, and immunomodulation by apheresis is recommended. However, several national and international guidelines have no uniform recommendations on using plasma exchange (PE) nor immunoadsorption (IA) in this case. A systematic review and meta-analysis was conducted, including observational studies or randomized controlled trials that investigated the effect of PE or IA on different courses of MS and neuromyelitis optica (NMO). One thousand, three hundred and eighty-three patients were included in the evaluation. Therapy response in relapsing-remitting MS and clinically isolated syndrome was 76.6% (95%CI 63.7&ndash, 89.8%) in PE- and 80.6% (95%CI 69.3&ndash, 91.8%) in IA-treated patients. Based on the recent literature, PE and IA may be considered as equal treatment possibilities in patients suffering from acute, glucocorticosteroid-unresponsive MS relapses.

Diabetic nephropathy (DN) is the main reason for end-stage renal disease. Microalbuminuria as the non-invasive available diagnosis marker lacks specificity and gives high false positive rates. To identify and validate biomarkers for DN, we used in the present study urine samples from four patient groups: diabetes without nephropathy, diabetes with microalbuminuria, diabetes with macroalbuminuria and proteinuria without diabetes. For the longitudinal validation, we recruited 563 diabetic patients and collected 1363 urine samples with the clinical data during a follow-up of 6 years. Comparative urinary proteomics identified four proteins Apolipoprotein A-I (APOA1), Beta-2-microglobulin (B2M), E-cadherin (CDH1) and Lithostathine-1-alpha (REG1A), which differentiated with high statistical strength (p &lt, 0.05) between DN patients and the other groups. Label-free mass spectrometric quantification of the candidates confirmed the discriminatory value of E-cadherin and Lithostathine-1-alpha (p &lt, 0.05). Immunological validation highlighted E-cadherin as the only marker able to differentiate significantly between the different DN stages with an area under the curve (AUC) of 0.85 (95%-CI: [0.72, 0.97]). The analysis of the samples from the longitudinal study confirmed the prognostic value of E-cadherin, the critical increase in urinary E-cadherin level was measured 20 &plusmn, 12.5 months before the onset of microalbuminuria and correlated significantly (p &lt, 0.05) with the glomerular filtration rate measured by estimated glomerular filtration rate (eGFR).

Zusammenfassung Einleitung Zur Prävention kardiovaskulärer Risikofaktoren (RF) existieren zahlreiche Empfehlungen von Fachgesellschaften, die sich auf die persönliche Lebensweise von Menschen beziehen (z. B. Ernährung/Diät, körperliche Aktivität, Stressabbau etc.). Die Umsetzung dieser Empfehlungen ist bislang mangelhaft. In der ELITE-Studie sollen in der Region Oldenburger Münsterland prospektiv Daten zu RF, Ernährungsverhalten, körperlicher Aktivität und Lebensqualität erhoben und durch individuelle Information verbessert werden. Gründe für fehlende Umsetzung von Präventionsmaßnahmen sollen erkannt werden. Methoden Die Studie wird als interventionelle Kohorten-Untersuchung durchgeführt (DRKS-Nr.: 00 006 813; Ethikvotum Universität Göttingen). Bis zu 5000 Personen (mit oder ohne Vorerkrankungen) sollten eingeschlossen werden. Alle Teilnehmer erhalten einen computergenerierten Report ihres persönlichen Risikoprofils mit hieraus resultierenden ausführlichen Empfehlungen, die sich an den aktuellen Leitlinien orientieren. Ergänzend wird empfohlen, den Hausarzt aufzusuchen, um die Befunde zu besprechen und ggf. diagnostische oder therapeutische Maßnahmen einzuleiten. Im Jahresabstand erfolgen über bis zu 5 Jahre Follow-Up-Untersuchungen. Ergebnisse Bis zum 31.12.2017 wurden 4602 Teilnehmer (mittleres Alter 51,5 (± 15,7) Jahre; 53,7 % weiblich) aufgenommen. Übergewichtig sind 39 % der Teilnehmer, adipös 20,4 %. Häufigster anamnestischer RF ist Bluthochdruck (31,4 %), mittlerer Blutdruck 138,4 ± 16,6/83,0 ± 9,9 mmHg. 2165 (47,0 %) Teilnehmer weisen hypertone Blutdruckwerte auf. Zweithäufigster anamnestischer RF sind Fettstoffwechselstörungen (16,6 %). Schlussfolgerung Die Häufigkeit von Teilnehmern mit mindestens einem anamnestisch angegebenen kardiovaskulären RF ist sehr hoch (49,5 %; 16,6 % mehrere RF). Die Häufigkeit von RF entspricht anderen epidemiologischen Daten in Deutschland, sodass das ELITE-Kollektiv einen guten Vergleich mit anderen Erhebungen zulässt.

Though drug adherence is supposed to be low in hypertensive crisis (HTN‐C), there are no data available from direct adherence assessments. The aim of the present study was to evaluate adherence to prescribed antihypertensives and potential interactions of concomitant drugs and foods with prescribed antihypertensives in patients with HTN‐C by a direct evaluation via biochemical urine analysis. In the present cross‐sectional study, 100 patients with HTN‐C, admitted to the emergency department (ED), were included. A biochemical urine analysis using gas chromatography‐tandem mass spectrometry was performed. Out of 100 patients, 86 received antihypertensives. Urine analyses could be evaluated unambiguously in 62 patients. In 15 of these 62 patients (24%), a nonadherence could be demonstrated, and in 21 patients (34%), a partial nonadherence could be demonstrated. Patients with nonadherence or partial nonadherence showed a longer hypertension history (15[5‐22] vs 10[3‐15] years, P = 0.04) were prescribed more general medication (number 7.1 ± 3.4 vs 3.4 ± 1.8; P

Baroreflex activation therapy (BAT) is approved for the treatment of resistant hypertension. In addition to blood pressure (BP) reduction, pilot studies suggested several organoprotective effects of BAT. Thirty‐two patients with resistant hypertension were prospectively treated with BAT. Besides office BP and 24‐hour ambulatory BP (ABP) measurements, detection of a urinary proteome‐based classifier (CKD273), which has been shown to predict chronic kidney disease (CKD) progression, was carried out at baseline and after 6 months of BAT. Office BP significantly decreased from 170 ± 25/90 ± 18 to 149 ± 29/82 ± 18 mm Hg. Analysis of CKD273 score and eGFR with CKD‐EPI equation at baseline revealed strong correlation (r = 0.568, P

Baroreflex activation therapy (BAT) is a sympathoinhibitory procedure for treatment of therapy-resistant hypertension (rsHTN) and severe heart failure with reduced ejection fraction (HFrEF) that been available for several years. The double-blind, randomized Rheos Pivotal Trial demonstrated a blood pressure lowering effect in patients with rsHTN for the first-generation BAT device. A smaller randomized study in heart failure showed that the Barostim Neo system is safe and can improve heart failure symptoms and decrease neuroendocrine activation. However, for this unilateral system, which is currently in clinical use, no data from large randomized trials exist. Despite existing data for BAT in rsHTN and HFrEF, large randomized trials, showing reduction of blood pressure and cardiovascular events are still lacking. Therefore, BAT's efficacy and safety cannot be conclusively assessed.

Acute decompensated heart failure (ADHF) is one of the biggest challenges in the management of chronic heart failure. Despite several advances in medical and device therapy, high readmission and mortality rates continue to be a burden on healthcare systems worldwide. The aim of the current review is to provide an overview on current as well as future approaches in cardiorenal interactions in patients with ADHF. One of the strongest predictors of adverse outcomes in ADHF is renal dysfunction, referred to as cardiorenal syndromes (CRS) or cardiorenal interactions. Patients with ADHF frequently develop worsening of renal function (WRF) and/or acute kidney injury (AKI). Recent studies brought new information about biomarkers in diagnosing and predicting prognosis of CRS. Among others, dry weight at hospital discharge is considered a surrogate marker of successful treatment in ADHF patients with/without renal dysfunction. The etiology of WRF appears to be an important factor for determining risk related to WRF as well as clinical management. The hypertonic saline used as adjunctive therapy for intravenous loop diuretics and/or induction of aquaresis (e.g., using tolvaptan) may be promising and efficient approaches in the future.

Following the publication of the new US guidelines, especially the new classifications of hypertension and the general reduction in treatment targets were discussed worldwide. Applying the US guidelines to a recent German cohort study would in practice lead to a significant increase in the diagnosis of “hypertension” in untreated patients. The number of under-adjusted patients would also increase sharply, increasing more than those predicted in the US Guidelines. Affected by an intensified antihypertensive therapy would be particularly elderly patients, in which adverse drug reactions but also occur more frequently. It seems doubtful whether the massive increase in the diagnosis “hypertension” can improve the supply situation: the opposite effect of avoiding therapists and patients could occur. Determining the individual risk with suitable, evaluated instruments certainly makes sense to treat more targeted patients. More important than new blood pressure limits is a more accurate classification of blood pressure. Repeated self-measurements and ambulatory blood pressure measurement lead to a better selection of patients benefiting from a therapy.

Die therapieresistente und -refraktare arterielle Hypertonie unterscheiden sich in der Haufigkeit, Pathogenese, Prognose und dem therapeutischen Vorgehen. In beiden Fallen bedarf es eines strukturierten Vorgehens mit Ausschluss einer Pseudoresistenz und daran anschliesend einer sekundaren Hypertonie. Die resistente Hypertonie spricht erfahrungsgemas besser auf eine intensivierte diuretische Therapie an, wohingegen die refraktare Hypertonie mutmaslich einer sympathoinhibitorischen Therapie bedarf. Sind Allgemeinmasnahmen und die medikamentose Step-up-Therapie ausgeschopft, stehen interventionelle Verfahren zur Verfugung.

Heart failure and kidney dysfunction are common comorbidities with overlapping and synergizing mechanisms. Coincidence of both pathologies aggravates disease progression rates, symptoms, and outcomes. The treatment of patients with advanced renal insufficiency is faced with limited evidence for therapies that are standard of care in patients with normal and moderate kidney failure, frequent deterioration of kidney function during therapy, and onset of hyperkalemia, which pose challenges for clinical care, requiring intensified physician-patient contacts. A special challenge is the so-called diuretic resistance, which may require extracorporeal drainage.

Baroreceptor activation therapy (BAT) has been available for several years for treatment of therapy-refractory hypertension (trHTN). This procedure is currently being carried out in a limited number of centers in Germany, also with the aim of offering a high level of expertise through sufficient experience; however, a growing number of patients who are treated with BAT experience problems that treating physicians are confronted with in routine medical practice. In order to address these problems, a consensus conference was held with experts in the field of trHTN in November 2016, which summarizes the current evidence and experience as well as the problem areas in handling BAT patients.

Background Baroreceptor-activating therapy (BAT) has been shown to control resistant hypertension in one sham-controlled and further observational studies. Incremental but significant reincrease of blood pressure (BP) have been described after open-label temporary withdrawal of such therapy. Method Our study in 16 randomized patients investigated the course of automated office, ambulatory, and home BP in a randomized, controlled cross-over design. Results After 4 weeks of blinded and randomized withdrawal in hypertension-controlled long-term carriers of BAT (2.67 ± 1.3 years, 145/104 mmHg), the primary end point of 35 mmHg difference, similar to initial BP drop after BAT initiation, was not reached in any patient. Ambulatory BP rose significantly during BAT off by 10/8 ± 4/3 mmHg (3.13/2.10, P = 0.007/0.002) and automated office BP by 10/4 ± 2/1 (4.17/0.58, P = 0.005/0.03) at 4 weeks after BAT on while mean home BP did not change significantly by 2/2 ± 3/2 mmHg (-5.9/-3.5, P = 0.6/0.5). Conclusion Our data in a limited study population show, that BP rise after temporary BAT withdrawal is significant but does not reach a magnitude comparable with the initial drop after de novo implantation. Such results points to preserved hypertension control after electrical BAT withdrawal and deserves further pathophysiological and clinical clarification.

Arterial baroreflex activation through electrical carotid sinus stimulation has been developed for the treatment of resistant hypertension. Previous studies suggested that the peripheral chemoreflex is tonically active in hypertensive patients and may inhibit baroreflex responses. We hypothesized that peripheral chemoreflex activation attenuates baroreflex efficacy evoked by electrical carotid sinus stimulation. We screened 35 patients with an implanted electrical carotid sinus stimulator. Of those, 11 patients with consistent acute depressor response were selected (7 men/4 women, age: 67±8 years, body mass index: 31.6±5.2 kg/m 2 , 6±2 antihypertensive drug classes). We assessed responses to electrical baroreflex stimulation during normoxia, isocapnic hypoxia (SpO 2 : 79.0±1.5%), and hyperoxia (40% end-tidal O 2 fraction) by measuring heart rate, blood pressure, ventilation, oxygen saturation, end-tidal CO 2 and O 2 fractions, and muscle sympathetic nerve activity. During normoxia, baroreflex activation reduced systolic blood pressure from 164±27 to 151±25 mm Hg (mean±SD, P P =0.002), and muscle sympathetic nerve activity from 42±12 to 36±12 bursts/min ( P =0.004). Hypoxia increased systolic blood pressure 8±12 mm Hg ( P =0.057), heart rate 10±6 bpm ( P P =0.031), and ventilation 10±7 L/min ( P =0.002). However, responses to electrical carotid sinus stimulation did not differ between hypoxic and hyperoxic conditions: systolic blood pressure: −15±7 versus −14±8 mm Hg ( P =0.938), heart rate: −2±3 versus −2±2 bpm ( P =0.701), and muscle sympathetic nerve activity: −6±4 versus −4±3 bursts/min ( P =0.531). We conclude that moderate peripheral chemoreflex activation does not attenuate acute responses to electrical baroreflex activation therapy in patients with resistant hypertension. These patients provided insight into human baroreflex-chemoreflex interactions that could not be gained otherwise.

Corrected Proof Children with Alport syndrome develop renal failure early in life. Since the safety and efficacy of preemptive nephroprotective therapy are uncertain we conducted a randomized, placebo-controlled, double-blind trial in 14 German sites of pediatric patients with ramipril for three to six years plus six months follow-up to determine these parameters. Pretreated children and those whose parents refused randomization became an open-arm control, which were compared to prospective real-world data from untreated children. The co-primary endpoints were safety (adverse drug reactions) and efficacy (time to progression). Out of 66 oligosymptomatic children, 22 were randomized and 44 joined the open-arm comparison. Ramipril therapy showed no safety issues (total of 216.4 patient-years on ramipril; adverse event rate-ratio 1.00; 95% confidence interval 0.66-1.53). Although not significant, our results cautiously showed that ramipril therapy was effective: in the randomized arm, Ramipril decreased the risk of disease progression by almost half (hazard ratio 0.51 (0.12–2.20)), diminished the slope of albuminuria progression and the decline in glomerular filtration. In adjusted analysis, indications of efficacy were supported by prospective data from participants treated open label compared with untreated children, in whom ramipril again seemed to reduce progression by almost half (0.53 (0.22-1.29)). Incorporating these results into the randomized data by Bayesian evidence synthesis resulted in a more precise estimate of the hazard-ratio of 0.52 (0.19-1.39). Thus, our study shows the safety of early initiation of therapy and supports the hope to slow renal failure by many years, emphasizing the value of preemptive therapy. Hence, screening programs for glomerular hematuria in children and young adults could benefit from inclusion of genetic testing for Alport-related gene-variants.

Baroreflex activation therapy (BAT) reduces office blood pressure (BP) in patients with resistant hypertension (HTN). Whereas sustained effects from the BAT Rheos device have already been reported, no long-term data on 24-h ambulatory BP (ABP) are currently available for the unilateral BAT Neo device. Patients treated with the BAT neo device for resistant hypertension were prospectively included into this observational study. Office and ABP measurements were performed before BAT implantation as well as 6, 12 and 24 months after initiation of BAT. A total of 60 patients with resistant HTN (office BP 172 ± 25/90 ± 17 mmHg, 24-h ABP 150 ± 16/80 ± 12 mmHg, median of antihypertensive drugs 7 (IQR 6–8)) were included. After 24 months, there was a significant reduction of − 25 ± 33/− 9 ± 18 mmHg (n = 50, both p

Activation of the sympathetic nervous system increases sodium retention in resistant hypertension. Baroreflex activation therapy (BAT) is an interventional method to reduce sympathetic overactivity in patients with resistant hypertension. This study aimed to assess the effect of BAT on urinary sodium excretion. From 2012 to 2015, consecutive patients with resistant hypertension and blood pressure (BP) above target despite polypharmacy strategies were consecutively included in this observational study. BAT was provided with the individual adaption of programmed parameters over the first months. 24-h urinary sodium excretion (UNa) was estimated at baseline and after 6 months using the Kawasaki formula in patients undergoing BAT. Additionally, the fractional sodium excretion, plasma renin activity, and aldosterone levels were assessed. Forty-two patients completed the 6-month follow-up period. Office systolic and ambulatory 24-h systolic BP at baseline were 169 ± 27 mmHg and 148 ± 16 mmHg despite a median intake of 7(3–9) antihypertensive drugs. After 6 months of BAT, systolic office BP decreased to 150 ± 29 mmHg (p

Context Clinical reasoning is an essential skill, the foundations of which should be acquired during undergraduate medical education. Student performance in clinical reasoning can be assessed using key feature examinations. However, within a paradigm of test-enhanced learning, such examinations may also be used to enhance long-term retention of procedural knowledge relevant to clinical reasoning. Objectives This study tested the hypothesis that repeated testing with key feature questions is more effective than repeated case-based learning in fostering clinical reasoning. Methods In this randomised crossover trial, Year 4 medical students attended 10 weekly computer-based seminars during which patient case histories covering general medical conditions were displayed. The presentation format was switched between groups every week. In the control condition, students studied long case narratives. The intervention condition used the same content but augmented case presentation with a sequence of key feature questions. Using a within-subjects design, student performance on intervention and control items was assessed at 13 weeks (exit examination) and 9 months (retention test) after the first day of term. Results A total of 87 of 124 eligible students provided complete data for the longitudinal analysis (response rate: 70.2%). In the retention test, mean ± standard deviation student scores on intervention items were significantly higher than those on control items (56.0 ± 25.8% versus 48.8 ± 24.7%; p

For the prevention of cardiovascular risk factors (RF) there are numerous recommendations of professional societies, which relate to the personal way of life of individuals (for example nutrition/diet, physical activity, stress reduction etc.). The implementation of these recommendations is so far poor. In the ELITE study, data on RF, nutritional behavior, physical activity and quality of life in the Oldenburger Münsterland region are to be collected prospectively and improved by individual information. Reasons for the lack of implementation of preventive measures should be recognized.The study is conducted as an interventional cohort study (DRKS-No.: 00 006 813, Ethics vote University of Göttingen). Up to 5000 people (with or without pre-existing RF) are aimed to be included. All participants receive a computer-generated report of their personal risk profile with detailed recommendations based on current guidelines. In addition, it is recommended to visit the family doctor to discuss the findings and, if necessary, initiate diagnostic or therapeutic measures. Every year, follow-up examinations take place for up to 5 years.By 31.12.2017 4602 participants (mean age 51.5 (± 15.7) years, 53.7 % female) were admitted. Overweight were 39 % of the participants, obese 20.4 %. Most frequent anamnestic RF is hypertension (31.4 %), mean blood pressure was 138.4 ± 16.6/83.0 ± 9.9 mmHg. 2165 (47.0 %) participants show hypertensive blood pressure values. The second most frequent anamnestic RF are lipid metabolism disorders (16.6 %).The incidence of participants with at least one cardiovascular RF is very high (49.5 %, 16.6 % multiple RF). The incidence of RF is similar to other epidemiological data in Germany, so the ELITE collective allows a good comparison with other surveys.Zur Prävention kardiovaskulärer Risikofaktoren (RF) existieren zahlreiche Empfehlungen von Fachgesellschaften, die sich auf die persönliche Lebensweise von Menschen beziehen (z. B. Ernährung/Diät, körperliche Aktivität, Stressabbau etc.). Die Umsetzung dieser Empfehlungen ist bislang mangelhaft. In der ELITE-Studie sollen in der Region Oldenburger Münsterland prospektiv Daten zu RF, Ernährungsverhalten, körperlicher Aktivität und Lebensqualität erhoben und durch individuelle Information verbessert werden. Gründe für fehlende Umsetzung von Präventionsmaßnahmen sollen erkannt werden.Die Studie wird als interventionelle Kohorten-Untersuchung durchgeführt (DRKS-Nr.: 00 006 813; Ethikvotum Universität Göttingen). Bis zu 5000 Personen (mit oder ohne Vorerkrankungen) sollten eingeschlossen werden. Alle Teilnehmer erhalten einen computergenerierten Report ihres persönlichen Risikoprofils mit hieraus resultierenden ausführlichen Empfehlungen, die sich an den aktuellen Leitlinien orientieren. Ergänzend wird empfohlen, den Hausarzt aufzusuchen, um die Befunde zu besprechen und ggf. diagnostische oder therapeutische Maßnahmen einzuleiten. Im Jahresabstand erfolgen über bis zu 5 Jahre Follow-Up-Untersuchungen.Bis zum 31.12.2017 wurden 4602 Teilnehmer (mittleres Alter 51,5 (± 15,7) Jahre; 53,7 % weiblich) aufgenommen. Übergewichtig sind 39 % der Teilnehmer, adipös 20,4 %. Häufigster anamnestischer RF ist Bluthochdruck (31,4 %), mittlerer Blutdruck 138,4 ± 16,6/83,0 ± 9,9 mmHg. 2165 (47,0 %) Teilnehmer weisen hypertone Blutdruckwerte auf. Zweithäufigster anamnestischer RF sind Fettstoffwechselstörungen (16,6 %).Die Häufigkeit von Teilnehmern mit mindestens einem anamnestisch angegebenen kardiovaskulären RF ist sehr hoch (49,5 %; 16,6 % mehrere RF). Die Häufigkeit von RF entspricht anderen epidemiologischen Daten in Deutschland, sodass das ELITE-Kollektiv einen guten Vergleich mit anderen Erhebungen zulässt.

Background Plasma exchange (PE) and immunoadsorption (IA) are alternative treatments of steroid-refractory relapses of multiple sclerosis (MS) or neuromyelitis optica (NMO). Methods Adverse events and neurological follow-ups in 127 MS- (62 PE, 65 IA) and 13 NMO- (11 PE, 2 IA) patients were retrospectively analyzed. Response was defined by improvements in either expanded disability status scale (EDSS) by at least 1.0 or visual acuity (VA) to 0.5, confirmed after 3 and/or 6 months. Results Hundred and forty patients were included in safety analysis, 102 patients provided sufficient neurological follow-up-data. There were no significant differences between IA and PE in side effects (3.9% vs 3.6%, P = .96) or response-rate (P = .65). Responders showed significant lower age (P = .02) and earlier apheresis-initiation (P = .01). Subgroup-analysis confirmed significant lower age in patients with relapsing-remitting MS (RRMS) /clinical isolated syndrome (CIS). Conclusion IA and PE seem equally safe and effective in steroid-resistant MS- or NMO-relapses. Early apheresis and low patient age are additional prognostic factors.

Following the publication of the new US guidelines, especially the new classifications of hypertension and the general reduction in treatment targets were discussed worldwide. Applying the US guidelines to a recent German cohort study would in practice lead to a significant increase in the diagnosis of "hypertension" in untreated patients. The number of under-adjusted patients would also increase sharply, increasing more than those predicted in the US Guidelines. Affected by an intensified antihypertensive therapy would be particularly elderly patients, in which adverse drug reactions but also occur more frequently. It seems doubtful whether the massive increase in the diagnosis "hypertension" can improve the supply situation: the opposite effect of avoiding therapists and patients could occur. Determining the individual risk with suitable, evaluated instruments certainly makes sense to treat more targeted patients. More important than new blood pressure limits is a more accurate classification of blood pressure. Repeated self-measurements and ambulatory blood pressure measurement lead to a better selection of patients benefiting from a therapy.

Unlike safety data of baroreflex activation therapy device (Rheos), only few data of the currently used second device (Barostim neo) are available and little is reported about common side effects.We prospectively analyzed patients with resistant hypertension treated with Barostim neo. A standardized interview regarding side effects of the therapy was performed in routine follow-up visits after device implantation in 42 patients to determine adverse events staged into three degrees.Within 6 months of baroreflex activation therapy, the office mean arterial blood pressure decreased from 169 ± 27 to 148 ± 29 mmHg systolic (P 0.001), respectively, to 145 ± 24 mmHg after 1 year (P 0.001), whereas the number of prescribed antihypertensive classes decreased from 6.6 ± 1.5 to 5.6 ± 1.8 (P 0.001). Adverse events were combination of the following field depending on the severity (I° mild: local discomfort, clinical observation only, no intervention indicated; II° moderate: medically significant such as occurrence of hypertensive crisis, syncope, arrhythmias; III° severe: life-threatening events or urgent medical intervention indicated). Adverse events I° were present in almost all patients (97.6%), and occurred mainly within first 6 months after device activation. Device-related events were most frequently and could be resolved by optimization of device parameters. Most procedure-related adverse events were directly related to the incision or anesthetic procedure. Adverse events II° occurred in 28.6% patients treated with Barostim neo, whereas patients' elevated individual risks might be potential triggers. Because of individual diversity of blood pressure response and the occurrence of adverse events, no standardization of parameters of implantable pulse generator could be found. By adapting the pulse generator settings individually, most of adverse events I° resolved without sequel.Though there are common side effects, Barostim neo significantly lowers blood pressure in resistant hypertension and provides an adequate safety profile. Regular patient visits are necessary to register side effects.

Baroreflex activation through electrical carotid sinus stimulation has been developed for the treatment of patients with arterial hypertension not sufficiently responding to pharmacological therapy. Previous studies suggested that peripheral chemoreflex afferents located in proximity to carotid baroreceptors are tonically active in hypertensive patients and may inhibit baroreflex responses. Therefore, we hypothesized that peripheral chemoreflex activation attenuates the efficacy of electrical carotid sinus stimulation.

Detection of renal artery stenosis (RAS) using Doppler is difficult to evaluate, particularly under conditions such as bilateral RAS or difficultly accessible renal arteries (RA). The objective of the present study was to assess the utility of splenic arterial compared to renal flow as an additional parameter in the Doppler evaluation of RAS. The difference between the resistive indices (RI) determined in renal and splenic parenchymal arteries (ΔRI(K−S)) was evaluated in 181 hypertensive subjects without any evidence of RAS. Subsequently 47 RA in 24 patients with suspected RAS were angiographically assessed. A ΔRI(K−S) of 0.055 (median) was determined in the population without any evidence of RAS similar to RA with angiographically excluded stenosis (ΔRI(K−S) 0.068). In contrast, in angiographic proven RAS, ΔRI(K−S) was significantly lower (−0.050; P

Die Ergebnisse bisheriger Studien zur Blutdrucktherapie bei akutem Schlaganfall erlauben wenige allgemeingultige Therapieempfehlungen. Es sollte versucht werden, ein konstantes Blutdruckniveau ohne grose Schwankungen zu erreichen. Eine antihypertensive Therapie im Akutstadium des Schlaganfalls sollte nur bei stark erhohten Werten eingeleitet werden. Hohe Blutdruckwerte werden bei Patienten mit ischamischem Schlaganfall toleriert, sofern keine Thrombolyse in Betracht kommt. Sollte diese angestrebt werden, muss der Blutdruck schnell auf einen Zielbereich von zumindest

Loss of the Y-chromosome (LOY) is described as both a normal age-related event and a marker of a neoplastic clone in hematologic diseases. To assess the significance of LOY in myelodysplastic syndromes (MDS), we determined the percentage of LOY in clonal CD34+ peripheral blood cells in comparison to normal CD3+ T-cells of 27 MDS patients using fluorescence in situ hybridization (FISH) analysis. Results were compared with the percentage of LOY in CD34+ and CD3+ cells of 32 elderly men without hematologic diseases and in 25 young blood donors. While LOY could not be detected in CD3+ cells of young men, it was observed in CD3+ cells of elderly men without hematologic diseases (2.5% LOY) as well as in CD3+ cells of elderly MDS patients (5.8% LOY). The percentage of CD34+ cells affected by LOY was significantly higher in MDS patients compared to elderly men without hematologic diseases (43.3% vs. 13.2%, P = 0.005), indicating that LOY has an age-related basis but is also associated with MDS. Furthermore, we aimed to define a threshold between age- and disease-associated LOY in MDS. Statistical analysis revealed that a value of 21.5% LOY in CD34+ peripheral blood cells provided the best threshold to discriminate between these two conditions in MDS. We conclude that LOY is clonal in a substantial number of MDS based on an age-related predisposition.

High central blood pressure, augmentation index and pulse wave velocity are independent cardiovascular risk factors. Little is known of the effect of baroreflex activation therapy on central hemodynamics.In this prospective clinical trial, radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressure and hemodynamic indices (i.e. augmentation pressure, augmentation index, pulse wave velocity, systolic and diastolic pressure time integral, subendocardial viability index) at baseline and 6 months after starting baroreflex activation therapy in 25 patients with resistant hypertension.Apart from peripheral blood pressure reduction, 6 months of baroreflex activation therapy significantly reduced mean central aortic blood pressure from 109.7 ± 20.5 to 97.4 ± 18.8 mm Hg (P 0.01) and aortic pulse pressure from 62.9 ± 18.6 to 55.2 ± 16.0 mm Hg (P 0.01). Aortic augmentation pressure and augmentation index at a heart rate of 75 b.p.m. were significantly reduced by 4.3 ± 7.9 mm Hg (P = 0.01) and 3.5 ± 6.8% (P = 0.02). Additionally, pulse wave velocity decreased from 10.3 ± 2.6 to 8.6 ± 1.3 m/s (P 0.01) 6 months after starting baroreflex activation therapy. Systolic pressure time integral was significantly reduced (P = 0.03), whereas subendocardial viability index remained unchanged.Apart from peripheral blood pressure, baroreflex activation therapy reduces central blood pressure, augmentation index at a heart rate of 75 b.p.m. and pulse wave velocity in patients with resistant hypertension, suggesting strong potential to reduce cardiovascular risk.

Progression of chronic kidney disease remains a principal problem in clinical nephrology and there is a pressing need for novel therapeutics and biomarkers. Aberrant promoter CpG island methylation and subsequent transcriptional silencing of specific genes have emerged as contributors to progression of chronic kidney disease. Here, we report that transcriptional silencing of the Ras-GTP suppressor RASAL1 contributes causally to progression of kidney fibrosis and we identified that circulating methylated RASAL1 promoter DNA fragments in peripheral blood correspond with levels of intrarenal levels of RASAL1 promoter methylation and degree of fibrosis in kidney biopsies, enabling non-invasive longitudinal analysis of intrarenal CpG island methylation. Retrospective analysis of patients with hypertensive nephrosclerosis revealed that circulating methylated RASAL1 promoter DNA fragments in peripheral blood decrease with Dihydralazine treatment in patients with hypertensive nephrosclerosis, and provided evidence that low-dose Dihydralazine delays decline of excretory kidney function, whereas Dihydralazine at standard doses had no protective effect. We demonstrate that the protective effect of Dihydralazine is due to induction of endogenous Tet3/Tdg-mediated DNA-de-methylation activity reversing aberrant promoter CpG island methylation, while HIF1α induction at standard doses counterbalances its protective activity. We conclude that RASAL1 promoter methylation is a therapeutic target and a biomarker of renal fibrosis. Our study suggests that therapeutic use of low-dose Dihydralazine in patients with chronic kidney disease and fibrosis deserves further consideration., Highlights • Aberrant RASAL1 promoter methylation contributes causally to progression of kidney fibrosis. • Degree of intrarenal RASAL1 methylation is reflected by levels of circulating methylated RASAL1 promoter fragments. • Low-dose Hydralazine induces endogenous Tet3-dependent de-methylation and inhibits progression of kidney fibrosis.

Activation of baroreceptors in the carotid modulates the autonomic nervous system. Baroreflex activation therapy (BAT), which activates baroreceptors in the carotid, has become available in the treatment of resistant hypertension. Besides this, a carotid implant modulating baroreceptors as well as pharmacological modulation of carotid bodies were quite recently presented. This review will underscore currently available and promising approaches that activate baroreceptors in the carotid, and thereby contribute to beneficial effects in patients with arterial hypertension, and discusses potential organoprotective BAT effects beyond blood pressure (BP) reduction. A systematic review and meta-analysis was conducted including observational studies or randomized controlled trials that investigated the effect of BAT on BP in resistant hypertension. Nine studies, seven observational and two randomized, with a total of 444 patients, were included in the evaluation. Analysing the longest follow-up visit from the different studies, there was a significant reduction of systolic BP after BAT of -36 mmHg [95% confidence interval (CI) -42 to -30 mmHg]. Separate meta-analysis of the short-term (1-6 months) and long-term effects (≥12 months) revealed a reduction of -21 mmHg (95% CI -26 to -17 mmHg) and -38 mmHg (95% CI -46 to -30 mmHg), respectively. There are promising data both in the experimental and the clinical application for BAT. Though the present meta-analysis suggests beneficial effects of BAT on BP, the results must be interpreted extremely carefully. Considering that evidence from controlled trials is very limited, it is evident that there is a strong need for further investigation.