Towards a COVID-19 symptom triad: The importance of symptom constellations in the SARS-CoV-2 pandemic.

Pandemic scenarios like SARS-Cov-2 require rapid information aggregation. In the age of eHealth and data-driven medicine, publicly available symptom tracking tools offer efficient and scalable means of collecting and analyzing large amounts of data. As a result, information gains can be communicated to front-line providers. We have developed such an application in less than a month and reached more than 500 thousand users within 48 hours. The dataset contains information on basic epidemiological parameters, symptoms, risk factors and details on previous exposure to a COVID-19 patient. Exploratory Data Analysis revealed different symptoms reported by users with confirmed contacts vs. no confirmed contacts. The symptom combination of anosmia, cough and fatigue was the most important feature to differentiate the groups, while single symptoms such as anosmia, cough or fatigue alone were not sufficient. A linear regression model from the literature using the same symptom combination as features was applied on all data. Predictions matched the regional distribution of confirmed cases closely across Germany, while also indicating that the number of cases in northern federal states might be higher than officially reported. In conclusion, we report that symptom combinations anosmia, fatigue and cough are most likely to indicate an acute SARS-CoV-2 infection.

[What entertainment television can do to convey medical knowledge to students and laypeople-raising awareness of rare diseases]. / Was das Unterhaltungsfernsehen zur Vermittlung von medizinischem Wissen an Studierende und Laien beitragen kann ­ Sensibilisierung für seltene Erkrankungen.

People with complex and rare diseases often have a difficult time in our health system. It can take years to reach a diagnosis and there is often no suitable therapy. Rare diseases are anything but rare among patients: around 4 million people are affected in Germany alone. Nevertheless, rare diseases can often only be diagnosed when they are well enough known and the population is made aware of their existence-this applies to both laypeople and medical professionals. The rather unusual form of imparting knowledge via entertainment television can make an important contribution to disseminate medical knowledge and to raise awareness of medical topics. In specific cases, entertainment television can help to diagnose rare diseases or encourage laypeople to take lifesaving measures, which we try to illustrate in this paper.Series and quiz shows reach more viewers than traditional health programs. They have also proven to be exceptionally effective in student teaching. Since the narrative form focuses on cheering and guessing, instead of simply conveying facts, the medical topics become more emotionally anchored memories and easier to recall. Entertainment television thus offers an innovative approach to increase the health literacy of the population-a potential that could be used more intensively in Germany.

Postmortem Examinations for the Etiological Identification of Juvenile Coronary Arteriosclerosis.

The postmortem of suddenly deceased younger adults sometimes reveals that they experienced manifest coronary arteriosclerosis. We looked at 21 cases where stenosis of the coronary arteries was at least 50%. We supplemented our postmortem findings and the results from the postmortem identification of the lipid metabolism parameters with anamnestic details. We also conducted a genetic analysis. The risk factors such as smoking and family history were relatively frequent. In most of our cases, the postmortems showed significantly deviating lipid metabolism parameters. Compared to these findings, the genetic analyses only showed a clearly increased presence of APOE genotypes 3/4, whereas we observed no abnormalities in relation to the LDL receptor. The study results illustrate the multifactor genesis of premature coronary arteriosclerosis. Despite these limitations, the unexpected finding of juvenile coronary arteriosclerosis should entail an effort to establish the individual risk factors involved as this can provide vital information for medically advising other members of the family on their hereditary risks.

New AHA and ACC guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk.

After the publication of the new guidelines of the European Society of Cardiology and the European Atherosclerosis Society for the prevention and treatment of dyslipidemias (Eur Heart J 32:1769-1818, 2011; Eur Heart J 33:1635-1701, 2012), a group of authors has recently published on behalf of the American Heart Association and the American College of Cardiology guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk (Circulation 2013). These new guidelines are supposed to replace the until now widely accepted, at least in the USA, recommendations of the National Cholesterol Education Program Adult Treatment Panel III from the years 2002 (Circulation 106:3143-3421, 2002) and 2004 (Circulation 110:227-39, 2004). Furthermore, they claim to be based mainly on hard evidence derived from the interpretation of results of prospective randomized controlled trials. This Joint Position Statement of the Society for the Prevention of Cardiovascular Diseases e.V. (D.A.CH), the Austrian Atherosclerosis Society and the Working Group on Lipids and Atherosclerosis (AGLA) of the Swiss Society of Cardiology concludes that the use of individualized prevention strategies based on specific indications and LDL cholesterol target concentrations, a strategy whose worth has been widely proven and accepted for more than a decade in Europe, should not be given up.

Improved detection of paroxysmal atrial fibrillation utilizing a software-assisted electrocardiogram approach.

BACKGROUND: Automated complexity-based statistical stroke risk analysis (SRA) of electrocardiogram (ECG) recordings can be used to estimate the risk of paroxysmal atrial fibrillation (pAF). We investigated whether this method could improve the reliability of detection of patients at risk for pAF. METHODS AND RESULTS: Data from 12-lead ECGs, 24-h Holter ECGs, and SRA based on separate 1-hour Holter ECG snips were collected from three groups: 70 patients with a history of pAF but who showed no AF episode in the 12-lead ECG at study entry; 19 patients with chronic AF (at study entry); and 100 young healthy individuals. AF episodes were detected by Holter ECG in 19 of the 70 non-chronic AF patients (27.1% overall, 18.6% in the first hour), and 37 of these 70 patients were classified as at risk for pAF by SRA (representing a sensitivity of 52.9% based on the first hour of analyzed recording). Fifty-four of the 70 patients also showed a sinus rhythm in the first hour. SRA detected pAF risk in 23 of these 54 patients (representing a sensitivity of 42.6%). The Holter data showed at least 1 AF episode and at least 1 hour of sinus rhythm in nine of the patients with pAF. For these patients, SRA classified 77.8% as being at risk in the first hour after the end of the AF episode, and 71.4% and 42.9% as being at risk in the second and third hours, respectively. SRA detected almost all cardiologist-confirmed AF episodes that had been recorded in 1-hour ECG snips (sensitivity, 99.2%; specificity, 99.2%). CONCLUSIONS: This outpatient study confirms previous findings that routine use of SRA could improve AF detection rates and thus may shorten the time between AF onset and initiation of prevention measures for patients at high risk for stroke.

["Why is it always the heart which suffers from myocardial infarction?" The "Marburg hypothesis" of the pathogenesis of atherosclerosis]. / "Warum trifft der Herzinfarkt immer das Herz?" Marburger Hypothese zur Pathogenese der Atherosklerose.

There is no question that cholesterol, especially low-density lipoprotein (LDL) cholesterol, represent a major cardiovascular risk factor. The so-called lipid hypothesis has been proven by almost all epidemiologic studies, animal studies and, most importantly, by interventional studies with lipid-lowering drugs, especially statins. However, despite our better understanding of atherogenesis we cannot explain why atherosclerosis occurs most frequently and severely on coronary arteries rather than on other arteries such as those of the hands or feet. In addition, the "lipid hypothesis" is unable to explain the dramatic change in severity of a far more generalized atherosclerosis in patients suffering from diabetes mellitus.Recently, we studied the effects of fatty acids on endothelial integrity and found a dramatic increase in apoptosis under fatty acid exposition. Since it is well known that the heart depends highly on fatty acid delivery to cover its energy demand, we hypothesize that the heart becomes the victim of its energy demand. With the so-called Marburg hypothesis of atherogenesis we can explain the fact why especially the arteries of the heart show early atherosclerotic lesions, but also the fact why patients with diabetes develop more generalized atherosclerosis. Finding mechanisms to reduce the presence of fatty acids within the arterial wall might prevent plaque destabilization and could be a potential target in our fight against atherosclerosis.

Molecular basis of obesity and the risk for cardiovascular disease.

Atherosclerosis and cardiovascular disease (CVD) are the main causes of death in the Western world, for both men and women. The onset and development of diseases of the cardiovascular and cerebrovascular system are strongly dependent on multiple risk factors that promote pathologic conditions like atherosclerosis, hypertension and thrombosis. Besides genetic factors also environmental influences such as diet composition are known to be closely related to CVD. In this context obesity has been postulated as an independent cardiovascular risk factor. Data from the Framingham Heart Study have consistently shown that increasing degrees of obesity are accompanied by greater rates of CVD. At present, obesity affects 10-35% of the European and US population and increases steadily. As obesity is a serious health problem which promotes metabolic abnormalities (insulin resistance, hyperinsulinemia and dyslipidemia) and dramatically increases the risk for CVD, this review will focus on the epidemiologic and genetic background of obesity. Furthermore, the molecular mechanisms involved in obesity development and their contribution to CVD will be discussed.

Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease.

CONTEXT: Free fatty acids (FFAs) are associated with several cardiovascular risk factors and exert harmful effects on the myocardium. OBJECTIVE: The aim of our study was to elucidate the relationship between FFAs and mortality in subjects who underwent coronary angiography. DESIGN, SETTING, AND PARTICIPANTS: Ludwigshafen Risk and Cardiovascular Health is a prospective cohort study of Caucasians who had undergone coronary angiography at baseline (1997-2000). During a median time of follow-up of 5.38 yr, 513 deaths had occurred among 3315 study participants with measured FFAs. MAIN OUTCOME MEASURE: Hazard ratios for mortality according to FFA levels were measured. RESULTS: At the fourth quartile of FFAs, fully adjusted hazard ratios for death from any cause and cardiovascular causes were 1.58 (P = 0.002) and 1.83 (P = 0.001), respectively. In persons with angiographic coronary artery disease (CAD), stable CAD, and unstable CAD, the predictive value of FFAs was similar to that in the entire cohort, but the association did not attain statistical significance in persons without CAD analyzed separately. FFA levels were not related to the presence of angiographic CAD but were elevated in subjects with unstable CAD, compared with probands with stable CAD. Furthermore, FFAs increased with the severity of heart failure and were positively correlated with N-terminal pro-B-type natriuretic peptide (P < 0.001). CONCLUSIONS: FFA levels independently predict all-cause and cardiovascular mortality in subjects with angiographic CAD. A possible diagnostic use of FFAs warrants further studies, but our results may underline the importance of therapeutic approaches to influence FFA metabolism.

Lipids and lipoproteins in women.

Atherosclerosis and coronary artery disease (CAD) are the main causes of death in the Western world, for both men and women. However, in premenopausal women CAD is less frequent than in men, but in elderly women (e.g., > 75 years) myocardial infarction (MI) occurs even more often than in men. In summary, women suffer from CAD and MI but at a later age than men. Therefore it is important to observe and compare the cardiovascular risk factors in women and men. The typical CAD risk factors such as hyperlipidemia, smoking, arterial hypertension, diabetes mellitus, obesity, physical inactivity, and unhealthy nutrition are increasingly important for both genders. Many of these factors are comparable between men and women, but due to hormonal influences especially the lipoprotein metabolism shows some striking differences between men and women, but interestingly enough also between pre- and postmenopausal women. Therefore this paper will focus especially on the gender-specific differences in lipid metabolism as a potential target which might explain both the gender-specific and also pre- and postmenopausal differences in the occurrence of CAD.

Risk of coronary artery disease associated with polymorphism of the cytochrome P450 epoxygenase CYP2J2.

BACKGROUND: Cytochrome P450 (CYP) 2J2 is expressed in the vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs). The EETs are potent endogenous vasodilators and inhibitors of vascular inflammation. However, it is not known whether genetic polymorphisms of CYP2J2 are associated with increased cardiovascular risks. METHODS AND RESULTS: All 9 exons of the CYP2J2 gene and its proximal promoter were sequenced in 132 patients to identify potential variants. Functional consequence of a single nucleotide polymorphism (SNP) in the promoter of CYP2J2 was further evaluated by use of transcription factor-binding and reporter assays. A total of 17 polymorphisms were identified. One of the most relevant polymorphisms in terms of frequency and functional importance is located at -50 (G-50T) in the proximal promoter of CYP2J2. Screening of 289 patients with coronary artery disease and 255 control subjects revealed 77 individuals with the G-50T SNP (17.3% of coronary artery disease patients, 10.6% of control subjects; P=0.026). The association of the G-50T polymorphism remained significant after adjustment for age, gender, and conventional cardiovascular risk factors (OR, 2.23; 95% CI, 1.04 to 4.79). The G-50T mutation resulted in the loss of binding of the Sp1 transcription factor to the CYP2J2 promoter and resulted in a 48.1+/-2.4% decrease in CYP2J2 promoter activity (P<0.01). Plasma concentrations of stable EET metabolites were significantly lower in individuals with the G-50T SNP. CONCLUSIONS: A functionally relevant polymorphism of the CYP2J2 gene is independently associated with an increased risk of coronary artery disease.

Molecular mechanisms involved in atherosclerosis.

BACKGROUND: Research in atherosclerosis is a good example how helpful different disciplines such as clinicians, epidemiologists and basic science can collaborate. In recent years our knowledge on cellular and subcellular mechanisms involved in initiation and progress of atherosclerosis has expanded due to the shared knowledge of different disciplines and thanks to new technologies in molecular biology. PATHOPHYSIOLOGY OF LDL AND HDL METABOLISM: The understanding of the molecular basis of inborn errors of LDL metabolism - such as familial hypercholesterolemia due to a defect of the LDL receptor - provided us new insights in physiology and pathophysiology of LDL metabolism. Most recently we have learned much about the vasoprotective HDL cholesterol. HDL is the major player in reverse cholesterol transport and some of its receptors such as ABCA1 and SR-BI were identified. This knowledge gives us a deeper understanding of the complex system which performs reverse cholesterol transport from peripheral tissue and the vessel wall back to the liver. PLAQUE FORMATION: Furthermore the process of formation and progression of the atherosclerotic plaque has been the focus of recent research. The stability or instability of plaques is depending on the complex interaction of adhesion molecules, monocytes, macrophages, endothelial cells, cytokines, transmitters and proteinases. Since we are unable to prevent plaque formation completely, the stabilization of plaques is a major goal for the coming years. Despite some success (such as the use of statines and ACE inhibitors) there is still a long way to go.