No Incidence of BRAF Mutations in Salivary Gland Carcinomas—Implications for Anti-EGFR Therapies

BRAF is the main effector of KRAS in the RAS-RAF-MAPK axis, a signaling pathway downstream of EGFR. The activation of this cascade is an important pathway in cancer development and is considered a key pathway for therapeutic molecules. Recent studies in metastatic colorectal cancer found that an oncogenic activation of BRAF by a point mutation in exon 15 (V600E) could bypass the EGFR-initiated signaling cascade with the effect that patients bearing the mutant BRAF allele are not likely to benefit from EGFR-targeted therapies. We designed an allele-specific PCR and screened 65 salivary gland carcinoma (SGC) of the main histopathological types for the BRAF V600E mutation. All 65 SGC in this cohort (100%) presented the BRAF wildtype. In a previous study, we found a KRAS wildtype in 98.5% of SGC. These findings imply that SGC rarely acquires mutations that result in a constitutive activation of the signaling cascade downstream of EGFR and this pleads in favor of further therapeutic trials with EGFR-targeting monoclonal antibodies

Frequency of secondary dyslipidemia in obese children

Ulrike Korsten-Reck1, Katrin Kromeyer-Hauschild2, Katrin Korsten1, Manfred W Baumstark1, Hans-H Dickhuth1, Aloys Berg11Department of Rehabilitative and Preventive Sports Medicine, University Medical Center, University of Freiburg, 79106 Freiburg, Germany; 2Institute of Human Genetics and Anthropology, Friedrich-Schiller-University Jena, 07740 Jena, GermanyObjective: This paper reports the frequency, type, and degree of dyslipidemia in obese children before therapeutic intervention. The relationships between lipid values and weight status, as well as lipid values and physical fitness, of these children were also investigated.Design and methods: The initial examination of the Freiburg Intervention Trial for Obese Children (FITOC) measured the values of triglycerides (TG), total cholesterol (C), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in 546 obese children aged 7–12 (body mass index [BMI] > 97th percentile), and compared these values with those of the age- and sex-specific reference group in the Lipid Research Clinics Population Studies Data Book (LRC). Four groups were selected according to the following scheme: A, Normolipidemia; B, Hyper-LDL-cholesterolemia alone; C, Hypo-HDL-C + hypertriglyceridemia; D, Combined hyperlipidemia = Hyper-LDL-C + hypertriglyceridemia. Body mass index, BMI-SDS (corrected BMI), and physical performance in watt/kg body weight were measured.Results: A total of 45.8% of the overweight children showed an abnormal lipid profile. Ten percent of the children had high LDL-C levels (group B), while 15% had increased LDL-C and increased TG (group D) (higher prevalence in boys). In 18.9% we found increased TG, combined with decreased HDL-C values (group C).Conclusion: Obese children are at risk of dyslipoproteinemia and related diseases. Children with the highest BMI-SDS and lowest physical fitness have the lowest HDL-C values and increased TG, indicating a higher risk for the metabolic syndrome.Keywords: atherosclerotic risk, childhood, dyslipidemia, obesit

Perzentile für den Body-mass-Index für das Kindes- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben

Fragestellung: Sowohl die Childhood Group der International Obesity Task Force (IOTF) als auch die European Childhood Obesity Group (ECOG) empfehlen den Body-mass-Index als Beurteilungskriterium für Übergewicht und Adipositas bei Kindern und Jugendlichen. Im Erwachsenenalter erfolgt die Definition von Übergewicht und Adipositas anhand fester Grenzwerte, bei der Beurteilung von Kindern und Jugendlichen müssen die alters- und geschlechtsspezifischen Veränderungen des BMI berücksichtigt werden. Methode: Unter Heranziehung von 17 bereits durchgeführten Untersuchungen aus verschiedenen Regionen Deutschlands wurden BMI-Perzentile für Kinder und Jugendliche erstellt. Die Berechnung der Perzentile basiert auf den Körperhöhen- und Körpergewichtsdaten von 17.147 Jungen und 17.275 Mädchen im Alter von 0–18 Jahren. Ergebnisse und Schlussfolgerung: Die vorgestellten Perzentile sollten als Referenz für deutsche Kinder und Jugendliche angewendet werden. Die Arbeitsgemeinschaft „Adipositas im Kindes- und Jugendalter“ (AGA) hat in ihren Leitlinien die Anwendung der hier vorgestellten 90. und 97. Perzentile zur Definition von Übergewicht und Adipositas empfohlen.Objectives: Both the Childhood Group of the International Obesity Task Force (IOTF) and the European Childhood Obesity Group (ECOG) recommend to use the body mass index (BMI = weight in kilograms/height in meter2) to evaluate overweight and obesity in children and adolescents. Whereas it is customary with adults to use fixed cut off points to define overweight and obesity, in children and adolescents age and sex specific developmental changes in BMI need to be addressed, which are due to physiological alterations of fat mass. Method: Because a national reference population for children and adolescents does not exist in Germany, a BMI reference data set was compiled. Therefore measurements of height and weight from 17 different regional studies including 17147 boys and 17275 girls aged 0 to 18 years were used. Results and conclusions: We recommend the use of the presented percentiles as reference to asses under- and overweight (obesity) in German children and adolescents. In the guidelines of the “Arbeitsgruppe Adipositas im Kindes- und Jugendalter”(AGA) the 90th and 97th BMI percentiles as calculated in this reference population are proposed as cut-off points for the definition of overweight and obesity in German children and adolescents

Protection of overweight children in child restraint systems

According to the German road traffic regulations children up to the age of 12 or a height below 150 cm have to use approved and appropriate child restraint systems (CRS). CRS must be approved according to UN-ECE Regulation No. 44. The regulation classifies CRS in 5 weight categories. The upper weight group is approved for children from 22 to 36 kg. However, studies show that already today many children weigh more than 36 kg although they have not reached a height of 150 cm. Therefore, no ECE R44 approved CRS is available for these overweight children. In conclusion, today's sizes and weights of children are no longer represented by the current version of the ECE R44. The heaviest used dummy (P10) weighs just 32.6 kg and has a height of 137.9 cm. Statistical data of German children show that already 5% of the children at a height of 137.9 cm have a weight above 45.3 kg. Regarding children at a height of 145 cm, the 95th percentile limit is at a weight of 53.3 kg. Based on these data 4 dummies with different heights and weights were defined and produced. Two of them are overweight. Up to now, there is no experience how current child restraint systems perform in a car crash if they are used by children with a weight above 36 kg and a height smaller than 150 cm. In the future, different child restraint systems will be tested with respect to the ECE R44 regulation using these overweight dummies

Abdominal Obesity in German Adolescents Defined by Waist-to-Height Ratio and Its Association to Elevated Blood Pressure: The KiGGS Study

Objective: The aim of this study was to compare the fixed 0.5 cut-off and the age- and sex-specific 90th percentile (P90) for waist-to-height ratio (WHtR) in German adolescents with respect to the prevalence of abdominal obesity and to compare the screening ability of WHtR and BMI to identify hypertensive blood pressure (BP) values. Methods: Between 2003 and 2006, the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) was carried out including 3,492 boys and 3,321 girls aged 11-17 years. Abdominal obesity was assessed by two WHtR cut-points (P90; 0.5). Hypertensive BP was defined as BP exceeding age-, sex- and height-specific 95th percentiles or the adult threshold for hypertension (140/90 mm Hg). Results: Agreement between the WHtR cut-offs was very good (Kappa 0.89 for boys; 0.81 for girls), and the prevalence of abdominal obesity was slightly higher using P90 (boys 12.0%; girls 11.3%) compared to 0.5 (boys 10.7%; girls 8.0%). WHtR and BMI-for-age had equivalent ability to discriminate hypertensive BP (ROC-AUC Conclusion: The fixed 0.5 WHtR cut-off can be used in German adolescents to characterize abdominal obesity. However, WHtR is not suitable as a screening tool for hypertensive BP in adolescents