[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.

Safety of gadobutrol in more than 1,000 pediatric patients: subanalysis of the GARDIAN study, a global multicenter prospective non-interventional study.

BACKGROUND: Gadobutrol is a gadolinium-based contrast agent, uniquely formulated at 1.0 mmol/ml. Although there is extensive safety evidence on the use of gadobutrol in adults, few studies have addressed the safety and tolerability of gadobutrol in pediatric patients. OBJECTIVE: This subanalysis of data from the GARDIAN study evaluated the safety and use of gadobutrol in pediatric patients (age <18 years). MATERIALS AND METHODS: The GARDIAN study was a large phase IV non-interventional prospective multicenter post-authorization safety study performed in Europe, Asia, North America and Africa. A total of 23,708 patients were included who were scheduled to undergo cranial or spinal MRI, liver or kidney MRI, or MR angiography with gadobutrol enhancement. The primary study endpoint was the overall incidence of adverse drug reactions (ADRs) and serious adverse events (SAEs) following gadobutrol administration. RESULTS: The GARDIAN study included 1,142 children (age <18 years) who received gadobutrol at a mean dose of 0.13 (range 0.04-0.50) mmol/kg body weight. Gadobutrol was well tolerated in these children, with low rates of ADRs (0.5%) and no SAEs, consistent with results in adults enrolled in the GARDIAN study. Rates of adverse events and ADRs were unrelated to pediatric age or gadobutrol weight-adjusted dose. There were no symptoms suggestive of nephrogenic systemic fibrosis. Investigators rated the contrast quality of gadobutrol-enhanced images as good or excellent in 97.8% of pediatric patients, similar to the main study population. CONCLUSION: Gadobutrol is very well tolerated and provides excellent contrast quality at the recommended weight-adjusted dose in children (age <18 years), similar to the profile in adults.

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.

Validation of automatic bone age determination in children with congenital adrenal hyperplasia.

BACKGROUND: Determination of bone age is routinely used for following up substitution therapy in congenital adrenal hyperplasia (CAH) but today is a procedure with significant subjectivity. OBJECTIVE: The aim was to test the performance of automatic bone age rating by the BoneXpert software package in all radiographs of children with CAH seen at our clinic from 1975 to 2006. MATERIALS AND METHODS: Eight hundred and ninety-two left-hand radiographs from 100 children aged 0 to 17 years were presented to a human rater and BoneXpert for bone age rating. Images where ratings differed by more than 1.5 years were each rerated by four human raters. RESULTS: Rerating was necessary in 20 images and the rerating result was closer to the BoneXpert result than to the original manual rating in 18/20 (90 %). Bone age rating precision based on the smoothness of longitudinal curves comprising a total of 327 data triplets spanning less than 1.7 years showed BoneXpert to be more precise (P<0.001). CONCLUSION: BoneXpert performs reliable bone age ratings in children with CAH.

Effectiveness of Chest CT in Children: CT Findings in Relation to the Clinical Question.

PURPOSE: To estimate the effectiveness and efficiency of chest CT in children based on the suspected diagnosis in relation to the number of positive, negative, and inconclusive CT results. MATERIALS AND METHODS: In this monocentric retrospective study at a university hospital with a division of pediatric radiology, 2019 chest CT examinations (973 patients; median age: 10.5 years; range: 2 days to 17.9 years) were analyzed with regards to clinical data, including the referring department, primary questions or suspected diagnosis, and CT findings. It was identified if the clinical question was answered, whether the suspected diagnosis was confirmed or ruled out, and if additional findings (clinically significant or minor) were detected. RESULTS: The largest clinical subgroup was the hematooncological subgroup (n = 987), with frequent questions for inflammation/pneumonia (66 % in this subgroup). Overall, CT provided conclusive results in 97.6 % of all scans. In 1380 scans (70 %), the suspected diagnosis was confirmed. In 406/2019 cases (20 %), the CT scan was negative also in terms of an additional finding. In 8 of 9 clinical categories, the proportion of positive results was over 50 %. There were predominantly negative results (110/179; 61 %) in pre-stem cell transplant evaluation. In the subgroup of trauma management, 81/144 exams (57 %) showed positive results, including combined injuries (n = 23). 222/396 (56 %) of all additional findings were estimated to be clinically significant. CONCLUSION: In a specialized center, the effectiveness of pediatric chest CT was excellent when counting the conclusive results. However, to improve efficiency, the clinical evaluation before imaging appears crucial to prevent unnecessary CT examinations. KEY POINTS: · Pediatric chest CT in specialized centers has a high diagnostic value.. · CT identifies relevant changes besides the working hypothesis in clinically complex situations.. · Pre-CT clinical evaluation is crucial, especially in the context of suspected pneumonia.. CITATION FORMAT: · Esser M, Tsiflikas I, Kraus MS et al. Effectiveness of Chest CT in Children: CT Findings in Relation to the Clinical Question. Fortschr Röntgenstr 2022; 194: 281 - 290.

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.

["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.

Emergency medical preparedness during the 2006 World Cup in Frankfurt, Germany.

This paper describes emergency medical preparedness during FIFA (Fédération Internationale de Football Association) World Cup matches in Frankfurt, Germany, in 2006. The methods employed were document analysis and personal observation of games over five days in June-July 2006. The medical authorities in Frankfurt drew on a wide range of scientific literature and experiences to elaborate a National Concept. They paid attention to different models of handling mass catastrophes in shaping the final version of the document. The participation of designated authorities, associations, and volunteer organisations was coordinated sufficiently and the games in Frankfurt proceeded without great incident, even though more than 300,000 people in total attended. The adopted emergency medical procedure was appropriate for a mass gathering event. Official and volunteer organisations collaborated precisely in emergency preparedness. While one uniform concept for all mass gatherings events cannot be developed, case reports and experiences are useful tools.

Differing Pulmonary Structural Abnormalities Detected on Pulmonary MR Imaging in Cystic Fibrosis Patients with Varying Pancreatic Function.

PURPOSE: In cystic fibrosis (CF) the phenotypic expression of complaints varies widely. Genotypes with sufficient pancreatic function (PS) exhibit milder lung disease compared to CF patients with insufficient pancreatic function (PI). The purpose of this study was to evaluate structural lung disease (SLD) in CF patients with differing pancreatic status but similar results on pulmonary function testing using a pulmonary magnetic resonance imaging score (MR-CF score). MATERIALS AND METHODS: In this retrospective study, 20 patients in our single-center CF database were included: 10 with PS (mean age 12.5 years; six male; BMI 17.4 kg/m2; FeV1 102 %) were matched by gender, age and lung function with 10 PI patients. Experienced observers semi-quantitatively assessed SLD for each lung lobe. The established MR-CF score measures the extent and the severity of bronchiectasis and bronchial wall thickening, mucus plugging, centrilobular opacity, consolidation, sacculation, and air trapping. The total score and sub-score values were compared to the pancreatic status. RESULTS: Patients with CF-PS had overall statistically significant lower MR-CF scores (p = 0.024), and therefore milder SLD, compared to CF-PI. The differences were most significant for bronchiectasis (p = 0.0042) and air trapping (p = 0.0304). SLD was more severe in the upper lobes in all patients. However, differences between CF-PS and CF-PI patients were present in both the upper and lower lung areas (p = 0.0247 and p = 0.0196, respectively). CONCLUSION: Our results demonstrated that CF patients with impaired pancreatic function show more severe lung pathology detected by MRI, especially bronchiectasis and air trapping. KEY POINTS: · Pulmonary MRI offers morphological and functional details without using ionizing radiation. · CF patients with pancreatic insufficiency show more severe pulmonary structural impairment. · Bronchiectasis and air trapping are the most common structural lung changes with predominance in the upper lung lobes.. CITATION FORMAT: · Kraus MS, Teufel M, Esser M et al. Differing Pulmonary Structural Abnormalities Detected on Pulmonary MR Imaging in Cystic Fibrosis Patients with Varying Pancreatic Function. Fortschr Röntgenstr 2020; 192: 567 - 575.

Whole-Body MRI in Children and Adolescents - S1 Guideline. / Ganzkörper-Magnetresonanztomografie im Kindes- und Jugendalter ­ S1-Leitlinie.

Whole-body MRI is an imaging method that uses advanced modern MRI equipment to provide high-resolution images of the entire body. The goal of these guidelines is to specify the indications for which whole-body MRI can be recommended in children and adolescents and to describe the necessary technical requirements. CITATION FORMAT: · Schaefer JF, Berthold LD, Hahn G et al. Whole-Body MRI in Children and Adolescents - S1 Guidelines. Fortschr Röntgenstr 2019; 191: 618 - 625.

Whole-Body [18F]-FDG-PET/MRI for Oncology: A Consensus Recommendation.

Combined PET/MR imaging (PET/MRI) was proposed for patient management in 2006 with first commercial versions of integrated whole-body systems becoming available as of 2010. PET/MRI followed the prior evolution of hybrid imaging as attested by the successful adoption of combined PET/CT and SPECT/CT since the early 2000 s. Today, around 150 whole-body PET/MRI systems have become operational worldwide. One of the main application fields of PET/MRI is oncologic imaging. Despite the increasing use of PET/MRI, little governance regarding standardized PET/MRI protocols has been provided to date. Standardization and harmonization of imaging protocols is, however, mandatory for efficient on-site patient management and multi-center studies. This document summarizes consensus recommendations on key aspects of patient referral and preparation, PET/MRI workflow and imaging protocols, as well as reporting strategies for whole-body [18F]-FDG-PET/MRI. These recommendations were created by early adopters and key experts in the field of PET, MRI and PET/MRI. This document is intended to provide guidance for the harmonization and standardization of PET/ MRI today and to support wider clinical adoption of this imaging modality for the benefit of patients. CITATION FORMAT:: Umutlu L, Beyer T, Grueneisen JS et al. Whole-Body [18F]-FDG-PET/MRI for Oncology: A Consensus Recommendation. Nuklearmedizin 2019, 58: 1-9.

Whole-Body [18F]-FDG-PET/MRI for Oncology: A Consensus Recommendation.

Combined PET/MR imaging (PET/MRI) was proposed for patient management in 2006 with first commercial versions of integrated whole-body systems becoming available as of 2010. PET/MRI followed the prior evolution of hybrid imaging as attested by the successful adoption of combined PET/CT and SPECT/CT since the early 2000 s. Today, around 150 whole-body PET/MRI systems have become operational worldwide. One of the main application fields of PET/MRI is oncologic imaging. Despite the increasing use of PET/MRI, little governance regarding standardized PET/MRI protocols has been provided to date. Standardization and harmonization of imaging protocols is, however, mandatory for efficient on-site patient management and multi-center studies. This document summarizes consensus recommendations on key aspects of patient referral and preparation, PET/MRI workflow and imaging protocols, as well as reporting strategies for whole-body [18F]-FDG-PET/MRI. These recommendations were created by early adopters and key experts in the field of PET, MRI and PET/MRI. This document is intended to provide guidance for the harmonization and standardization of PET/MRI today and to support wider clinical adoption of this imaging modality for the benefit of patients. CITATION FORMAT: · Umutlu L, Beyer T, Grueneisen JS et al. Whole-Body [18F]-FDG-PET/MRI for Oncology: A Consensus Recommendation. Fortschr Röntgenstr 2019; 191: 289 - 297.

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.

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.

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.

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.

Genetic variation at chromosome 1p13.3 affects sortilin mRNA expression, cellular LDL-uptake and serum LDL levels which translates to the risk of coronary artery disease.

BACKGROUND: A single nucleotide polymorphism (SNP) rs599839 located at chromosome 1p13.3 has previously been associated with risk of coronary artery disease (CAD) and with serum levels of low-density lipoprotein cholesterol (LDL-C). A functional link explaining the association of SNP rs599839 with LDL-C levels and CAD risk has not yet been elucidated. METHODS: We analyzed the association of rs599839 with LDL-C in 6605 individuals across a wide age spectrum and with CAD in four case-control studies comprising 4287 cases and 7572 controls. Genome-wide expression array data was used to assess the association of SNP rs599839 with gene expression at chromosome 1p13. Finally, we overexpressed sortilin in transfected cells to study LDL-uptake in vitro. RESULTS: Each copy of the G-allele of rs599839 associated with a decrease of serum LDL-C by 0.14 mmol/L (90% confidence interval (CI) 0.09-0.17 mmol/L, p=2.6 x 10(-11)). Moreover, each copy of the G-allele associated with a 9% decrease of CAD risk (90% CI 4-14%) in the presently studied four case-control samples and with a 13% decrease (90% CI 10-17%, p=2.18 x 10(-9)) in a pooled meta-analysis including recent genome-wide association studies on CAD. The same allele was associated with higher mRNA-expression levels of the multiligand receptor sortilin (log transformed mRNA AA vs. GG=8.31 vs. 8.55; p=0.01). Overexpression of SORT1 cDNA resulted in a significant increase in LDL-particle uptake (+23%, p=0.01). CONCLUSIONS: Rs599839 associates with decreased LDL-C and a lower risk of CAD. Effects appear to be mediated by increased sortilin expression and subsequently enhanced LDL-uptake into cells.

Imaging of extralobar pulmonary sequestration in a patient with tetralogy of Fallot with pulmonary atresia, ventricular septal defect and multiple aorto-pulmonary collateral arteries with multidetector computed tomography.

Complex pulmonary vascular blood supply is common in patients with tetralogy of Fallot with pulmonary atresia, major systemic to pulmonary collateral arteries and hypoplastic or deficient central pulmonary arteries. An extralobar lung sequestration, which has not been described previously in these patients, was imaged in a 6-week-old infant with multidetector computed tomography with sub-millimeter resolution. Arterial and venous vessels were analyzed using three-dimensional vascular exploration tools and results were confirmed with cardiac catheterization.