The German CPU registry: Comparison of smokers and nonsmokers.

BACKGROUND: Chest pain is a major reason for admission to an internal emergency department, and smoking is a well-known risk factor for coronary artery disease (CAD) and acute coronary syndrome (ACS). The aim of this analysis is to illustrate the differences between smokers and nonsmokers presenting to German chest pain units (CPU) in regard to patient characteristics, CAD manifestation, treatment strategy, and prognosis. METHODS: From December 2008 to March 2014, 13,902 patients who had a complete 3­month follow-up were enrolled in the German CPU registry. The analysis comprised 5796 patients with ACS and documented smoking status. RESULTS: Of all the patients in the CPU registry, 35.2% were smokers. Compared with nonsmokers, they were 13.5 years younger (58.2 vs. 71.7 years, p < 0.001), predominantly men (77.1% vs. 65.2%, p < 0.001), and were more frequently diagnosed with single-vessel disease (32.1% vs. 25.2%) as well as ST-elevation myocardial infarction (STEMI; 23.8% vs. 15.5%, p < 0.001). Although the Global Registry of Acute Coronary Events (GRACE) Risk Score for hospital mortality was lower in the group of smokers (106.1 vs. 123.3, p < 0.001), we did not observe any differences in CPU death (0.4% vs. 0.4%, p = 0.69) and CPU major adverse cardiac event (MACE) rates (3.8% vs 2.9%, p = 0.073) between the groups. In the 3­month follow-up, we documented higher mortality rates in the nonsmoker group (1.9% vs. 2.9%, p = 0.035) in correlation with the GRACE Risk Score (80.3 vs. 105.2, p < 0.001). MACE rates were similar during the follow-up (3.1% vs. 4.1%, p = 0.065). CONCLUSION: Observations from the German CPU registry demonstrate that smoking is a strong predictor of acute CAD manifestation early in life, especially STEMI. In spite of a lower GRACE Risk Score and fewer comorbidities, smokers had a rate of hospital mortality similar to the older group of nonsmokers.

European guidelines on lifestyle changes for management of hypertension : Awareness and implementation of recommendations among German and European physicians.

BACKGROUND: In the 2013 European Society of Hypertension (ESH) and European Society of Cardiology (ESC) guidelines for the management of arterial hypertension, six lifestyle changes for treatment are recommended for the first time with class I, level of evidence A. We initiated a survey among physicians to explore their awareness and consideration of lifestyle changes in hypertension management. METHODS: The survey included questions regarding demographics as well as awareness and implementation of the recommended lifestyle changes. It was conducted at two German and two European scientific meetings in 2015. RESULTS: In all, 1064 (37.4% female) physicians participated (806 at the European and 258 at the German meetings). Of the six recommended lifestyle changes, self-reported awareness was highest for regular exercise (85.8%) followed by reduction of weight (66.2%). The least frequently self-reported lifestyle changes were the advice to quit smoking (47.3%) and moderation of alcohol consumption (36.3%). Similar frequencies were observed for the lifestyle changes implemented by physicians in their care of patients. CONCLUSION: A close correlation between awareness of guideline recommendations and their implementation into clinical management was observed. European physicians place a stronger emphasis on regular exercise and weight reduction than on the other recommended lifestyle changes. Moderation of alcohol consumption is the least emphasized lifestyle change.

Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures.

Rapid and reliable detection of disease-associated DNA methylation patterns has major potential to advance molecular diagnostics and underpin research investigations. We describe the development and validation of minimal methylation classifier (MIMIC), combining CpG signature design from genome-wide datasets, multiplex-PCR and detection by single-base extension and MALDI-TOF mass spectrometry, in a novel method to assess multi-locus DNA methylation profiles within routine clinically-applicable assays. We illustrate the application of MIMIC to successfully identify the methylation-dependent diagnostic molecular subgroups of medulloblastoma (the most common malignant childhood brain tumour), using scant/low-quality samples remaining from the most recently completed pan-European medulloblastoma clinical trial, refractory to analysis by conventional genome-wide DNA methylation analysis. Using this approach, we identify critical DNA methylation patterns from previously inaccessible cohorts, and reveal novel survival differences between the medulloblastoma disease subgroups with significant potential for clinical exploitation.

Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides.

Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world's most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2',3',4',3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2',3',4'-Trihydroxychalcone (IC50 = 4.2 µM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15-45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme.

[Cannabis--Position Paper of the German Respiratory Society (DGP)]. / Cannabis--Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V. (DGP).

In this position paper, the adverse health effects of cannabis are reviewed based on the existing scientific literature; in addition possible symptom-relieving effects on some diseases are depicted. In Germany, cannabis is the most widely used illicit drug. Approximately 600,000 adult persons show abusive or addictive cannabis consumption. In 12 to 17 year old adolescents, cannabis use increased from 2011 to 2014 from 2.8 to 6.4%, and the frequency of regular use from 0.2 to 1.5%. Currently, handling of cannabinoids is much debated in politics as well as in general public. Health aspects have to be incorporated into this debate. Besides analysing mental and neurological side effects, this position paper will mainly focus on the influences on the bronchopulmonary and cardiovascular system. There is strong evidence for the induction of chronic bronchitis. Allergic reactions including asthma are known, too. Associations with other diseases like pulmonary emphysema, lung cancer and pneumonia are not sufficiently proven, however cannot be excluded either. In connection with the use of cannabis cardiovascular events such as coronary syndromes, peripheral vascular diseases and cerebral complications have been noted. Often, the evidence is insufficient due to various reasons; most notably, the overlapping effects of tobacco and cannabis use can frequently not be separated adequately. Empirically, early beginning, high-dosed, long-lasting and regular cannabis consumption increase the risk of various psychological and physical impairments and negatively affect age-based development. Concerns therefore relate especially to children and adolescents. There is only little scientific evidence for medical benefits through cannabis as a remedy; systematic research of good quality, in particular prospective, randomised, placebo-controlled double-blinded studies are rare. The medical societies signing this position paper conclude that cannabis consumption is linked to adverse health effects which have to be taken into consideration in the debate about the social attitude towards cannabinoids. The societies agree that many aspects regarding health effects of cannabis are still uncertain and need clarification, preferably through research provided by controlled studies.

Rational design and diversity-oriented synthesis of peptoid-based selective HDAC6 inhibitors.

A mini library of HDAC inhibitors with peptoid-based cap groups was synthesized using an efficient multicomponent approach. Four compounds were identified as potent HDAC6 inhibitors with a selectivity over other HDAC isoforms. The most potent HDAC6 inhibitor revealed remarkable chemosensitizing properties and completely reverted the cisplatin resistance in Cal27 CisR cells.

Smoking ban in public areas is associated with a reduced incidence of hospital admissions due to ST-elevation myocardial infarctions in non-smokers. Results from the Bremen STEMI Registry.

INTRODUCTION: Laws banning tobacco smoking from public areas have been passed in several countries, including the region of Bremen, Germany at the end of 2007. The present study analyses the incidence of hospital admissions due to ST-elevation myocardial infarctions (STEMIs) before and after such a smoking ban was implemented, focusing on differences between smokers and non-smokers. In this respect, data of the Bremen STEMI Registry (BSR) give a complete epidemiological overview of a region in northwest Germany with approximately 800,000 inhabitants since all STEMIs are admitted to one central heart centre. METHODS AND RESULTS: Between January 2006 and December 2010, data from the BSR was analysed focusing on date of admission, age, gender, and prior nicotine consumption. A total of 3545 patients with STEMI were admitted in the Bremen Heart Centre during this time period. Comparing 2006-2007 vs. 2008-2010, hence before and after the smoking ban, a 16% decrease of the number of STEMIs was observed: from a mean of 65 STEMI/month in 2006-2007 to 55/month in 2008-2010 (p < 0.01). The group of smokers showed a constant number of STEMIs: 25/month in 2006-2007 to 26/month in 2008-2010 (+4%, p = 0.8). However, in non-smokers, a significant reduction of STEMIs over time was found: 39/month in 2006-2007 to 29/month in 2008-2010 (-26%, p < 0.01). The decline of STEMIs in non-smokers was consistently observed in all age groups and both sexes. Adjusting for potentially confounding factors like hypertension, obesity, and diabetes mellitus did not explain the observed decline. CONCLUSIONS: In the BSR, a significant decline of hospital admissions due to STEMIs in non-smokers was observed after the smoking ban in public areas came into force. No reduction of STEMI-related admissions was found in smokers. These results may be explained by the protection of non-smokers from passive smoking and the absence of such an effect in smokers by the dominant effect of active smoking.

[European guidelines on cardiovascular disease prevention. What has changed in 2012?]. / Europäische Leitlinien zur Prävention kardiovaskulärer Erkrankungen. Was hat sich 2012 geändert?

The new European Guidelines on Cardiovascular Disease Prevention (version 2012) are supported by nine medical societies. They are newly structured, shorter and more readable. Each subchapter starts with key messages and recommendations are labeled with an evidence level. The subchapter ends with "most important newest information" and "persisting gaps of evidence" for further research. Smoking and passive smoking are to be avoided, even a small amount of regular physical activity is beneficial, the Mediterranean type diet is recommended and a body mass index (BMI) between 22 and 25 is associated with the lowest mortality. A blood pressure target of <140/90 mmHg is appropriate for the vast majority of hypertensive patients. Aspirin is not recommended for primary prevention even not for diabetics without vascular disease. Cardiovascular risk is now categorized into four levels: low (<1%), medium (1% to <5%), high (5% to <10%) and very high risk (≥10%). All patients with cardiovascular disease are in the very high risk group with the corresponding treatment goals, e. g. a low density lipoprotein (LDL) cholesterol goal of <70 mg/dl (<1.8 mmol/l). Treatment adherence and behavioral changes can best be achieved by motivational interviews which demand some time. It is emphasized that the physician has the responsibility for clear recommendations in the discharge summaries after hospitalization and for offering help and feed back in the implementation phase of behavioral changes.

In vitro and mouse in vivo characterization of the potent free fatty acid 1 receptor agonist TUG-469.

Activation of the G protein-coupled free fatty acid receptor 1 (FFA1; formerly known as GPR40) leads to an enhancement of glucose-stimulated insulin secretion from pancreatic ß-cells. TUG-469 has previously been reported as a potent FFA1 agonist. This study was performed to confirm the higher in vitro potency of TUG-469 compared to the reference FFA1 agonist GW9508 and to prove in vivo activity in a pre-diabetic mouse model. The in vitro pharmacology of TUG-469 was studied using Ca(2+)-, cAMP-, and impedance-based assays at recombinant FFA1 and free fatty acid receptor 4, formerly known as GPR120 (FFA4) expressing 1321N1 cells and the rat insulinoma cell line INS-1. Furthermore, we investigated the systemic effect of TUG-469 on glucose tolerance in pre-diabetic New Zealand obese (NZO) mice performing a glucose tolerance test after intraperitoneal administration of 5 mg/kg TUG-469. In comparison to GW9508, TUG-469 showed a 1.7- to 3.0-times higher potency in vitro at 1321N1 cells recombinantly expressing FFA1. Both compounds increased insulin secretion from rat insulinoma INS-1 cells. TUG-469 is > 200-fold selective for FFA1 over FFA4. Finally, a single dose of 5 mg/kg TUG-469 significantly improved glucose tolerance in pre-diabetic NZO mice. TUG-469 turned out as a promising candidate for further drug development of FFA1 agonists for treatment of type 2 diabetes mellitus.

[Primary prevention of coronary artery disease: is there a role for risk scores?]. / Primärprävention der koronaren Herzerkrankung: Was nützen die Risiko-Scores?

Primary prevention of coronary artery disease is becoming increasingly important due to treatment costs. The assessment of overall cardiovascular risk in Germany is usually performed using the PROCAM algorithm or the ESC score. If the 10-year risk of myocardial infarction or cardiovascular death exceeds 20% or 5%, respectively, intensive risk intervention is cost effective and the number needed to treat (NNT) is usually <200. An NNT of <200 can also be achieved by treating a single pronounced risk factor. The CARRISMA system uses lifestyle factors in addition to conventional factors to improve risk stratification and also supports lifestyle modification. During the last two decades average life expectancy has increased by 6 years and possibilities for prevention have improved. Risk stratification for prevention should therefore be offered up to the age of 70, as in the Framingham risk score. Risk scores support evidence-based and cost-effective prevention even in higher age groups.

The effect of optimal medical therapy on 1-year mortality after acute myocardial infarction.

OBJECTIVES: Five drug classes have been shown to improve the prognosis of acute myocardial infarction in clinical trials: aspirin, beta-blockers, statins, renin angiotensin system (RAS) blockers and thienopyridines. We aimed to assess whether the benefits of combining these drugs (termed optimal medical therapy, OMT), will result in a reduction of mortality in clinical practice. DESIGN: Nationwide registry SETTING: Hospitals with a cardiology unit or internal medicine department. PATIENTS: 5353 patients with acute myocardial infarction. At hospital discharge 89% received aspirin, 90% beta-blockers, 84% statins, 81% RAS blockers, 70% a thienopyridine and 46.2% OMT. INTERVENTIONS: Pharmacotherapy MAIN OUTCOME MEASURES: OR with 95% CI for mortality from myocardial infarction were calculated and adjusted for patient risk at baseline. RESULTS: Total mortality was reduced by 74% in patients receiving OMT (adj OR 0.26; 95% CI 0.18 to 0.38) versus patients receiving one or no drug. This was consistent in subgroups defined by STEMI/NSTEMI, diabetes and gender. Mortality was also reduced in patients receiving 2-4 drugs (adj OR 0.49; 95% CI 0.35 to 0.68), diabetic patients being the only subgroup with no significant effect. Analyses on the relative importance of either component revealed that withdrawal of beta-blockers (adj OR 0.63; 95% CI 0.34 to 1.16) and/or a combination of aspirin/clopidogrel (adj OR 0.59; 95% CI 0.20 to 1.17) abolished the risk reduction conferred by OMT. CONCLUSIONS: OMT over 1 year was associated with a significantly lower mortality of patients with acute myocardial infarction in clinical practice. However OMT is provided to less than half of eligible patients leaving room for substantial improvement.

[Revenue for the German federal budget from cigarette smoking by persons younger than 18 years]. / Einnahmen des Bundeshaushalts aus dem Zigarettenkonsum Minderjähriger.

OBJECTIVES: The purpose of this study was to estimate the tax value of tobacco products consumed by persons younger than 18 years in 2007. METHODS: Tax, population, and consumption data were used to compute an estimate of the tax value of tobacco products consumed by minors. RESULTS: Youth smoking generated an estimated 193 Million Euro in federal tax revenue in one year. CONCLUSIONS: The revenues from cigarettes smoked by youth should be used to finance youth-specific prevention programmes.

[Reduction of in-hospital mortality and improved secondary prevention after acute myocardial infarction. First results from the registry of secondary prevention after acute myocardial infarction (SAMI)]. / Rückgang der Krankenhaus-Sterblichkeit und verbesserte Sekundärprävention nach akutem Myokardinfarkt. Erste Ergebnisse des SAMI-Registers.

BACKGROUND AND OBJECTIVE: In hospital mortality of acute myocardial infarction (AMI) has been reduced due to the availability of better therapeutic strategies. But there is still a gap between mortality rates in randomised trials and daily clinical practice. Thus, it was aim of the present registry to document the course and outcome of patients with AMI and to improve patient care by implementing recent guidelines. PATIENTS AND METHODS: In a nationwide registry study in hospitals in Germany with a cardiology unit or an internal medicine department data on consecutive patients were recorded for six to twelve months at admission, discharge and during a follow-up of one year. RESULTS: From 02/2003 until 10/2004 a total of 5,353 patients with acute myocardial infarction (65.7 % male, mean age of 67.6 +/- 17.7 years; 55.1 % of them with ST elevation myocardial infarction (STEMI) were included in the registry. Of the patients with STEMI, 76.6 % underwent acute intervention, 37.1 % had thrombolysis, 69.7 % percutaneous transluminal coronary angioplasty (PTCA). 40.0 % of those with non-Stemi (NSTEMI) had an acute intervention, 6.6 % thrombolysis, 73.5 % PTCA. Recommended secondary prevention consisted of ASS (93.2 %), beta-blockers (93.0 %), CSE-inhibitors (83.5 %), ACE-inhibitors (80.9 %) and clopidogrel (74.0 %). In-hospital mortality was 10.5 % (STEMI) and 7.4 % (NSTEMI). CONCLUSION: The 9 % mortality among patients with acute myocardial infarction treated in the hospitals participating in the SAMI registry is low compared to that in similar collectives. The high number of patients who had thrombofibrinolysis and coronary interventions as well as the early initiation of drug therapy contributed to these results. Medical treatment in the prehospital phase of these patients remains still insufficient and to a substantial extent contributes to the mortality of acute myocardial infarction.

Possible gender-dependent association of vascular endothelial growth factor (VEGF) gene and ALS.

Individuals homozygous for haplotypes -2578-A/-1154-A/-634-G or -2578-A/-1154-G/-634-G in the promoter/5'UTR of the VEGF gene have a 1.8-fold increased risk of ALS in several European populations. We did not observe any significant association with single markers, or haplotype pairs, in a German sample of 580 sporadic ALS patients and 628 controls. However, the promoter SNP-1154 (rs1570360) was associated with affection status in women (p = 0.036), suggesting that the VEGF effect may be dependent on the sex ratio of the sample.

Association study between the D10S1423 microsatellite marker and Alzheimer's disease.

Several studies have reported conflicting results concerning the genetic association between Alzheimer's disease (AD) and the microsatellite marker D10S1423 on chromosome 10p12-14. In an ethnically homogeneous German population of 422 patients with AD and 254 cognitively healthy controls, the 238-bp allele of the D10S1423 marker showed a weak, but after correction for multiple testing no longer significant association with AD (p = 0.015, uncorrected; p = 0.11, corrected). These findings do not support the presence of a relevant susceptibility locus for AD on chromosome 10p12-14.