Interessenkonflikte in Leitlinien

https://ift.tt/2EMYLN3

Preisträger 2015 und 2017 der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

https://ift.tt/2vkyyWS

FORSCHUNG HEUTE – ZUKUNFT MORGEN

https://ift.tt/2Hky3Rn

Das angeborene Immunsystem beim Oropharynxkarzinom

Zusammenfassung

Klinisch und biologisch können Plattenepithelkarzinome des Oropharynx („oropharyngeal squamous cell carcinoma", OPSCC), die mit humanen Papillomaviren (HPV) assoziiert sind, als eine eigene Tumorentität im Kopf-Hals-Bereich betrachtet werden. Bisher hat dies außerhalb klinischer Studien keinen Einfluss auf Therapiekonzepte. Der natürliche Replikationszyklus von HPV findet „räumlich getrennt" von zytotoxischen Immunzellen in der Epidermis statt. Dendritische (Langerhans‑)Zellen finden sich jedoch häufig in dieser oberen Hautschicht. Ihre Fähigkeit Antigene zu prozessieren, zu migrieren und schließlich T‑Zellen zu aktivieren, wird durch die Aktivität der viralen Onkoproteine (E5–E7) inhibiert. Die Repression einer funktionellen HLA-I(Human-Leukocyte-Antigen-I)-Expression auf der Oberfläche von Epithelzellen ist hierbei wichtig. Eine entsprechende Aktivierung von natürlichen Killer(NK)-Zellen („Missing-Self-Erkennung") unterbleibt jedoch, da diese in der Epidermis normalerweise fehlen. Genomweite Untersuchungen zeigen spezifische Signaturen bei HPV-assoziierten OPSCC, die distinkt sind von HPV-negativen Tumoren. Dabei sind Gene des HLA-I-Systems bei HPV-assoziierten OPSCC vermehrt von genetischen Veränderungen betroffen. Eigene Daten deuten darauf hin, dass HPV-assoziierte OPSCC häufiger durch CD56-positive (CD56⁺-)NK-Zellen infiltriert sind, was mit dem Verlust der HLA-I-Oberflächenexpression bei der HPV-assoziierten Karzinogenese zusammenhängen könnte. Bei Patienten mit OPSCC korrelieren CD56⁺-Zellen mit einem günstigeren Verlauf nach konventioneller Therapie. Die vorliegenden Daten zeigen, dass HPV-assoziierte OPSCC für künftige immunmodulatorische Therapiekonzepte geeignet sein könnten und der Immunstatus für die Planung klinischer Studien bedeutsam ist.

https://ift.tt/2vfR6qV

Adipose tissue, but not skeletal muscle, sirtuin 1 expression is decreased in obesity and related to insulin sensitivity

Abstract

Purpose

Sirtuin 1 may regulate glucose and lipid metabolism. We aimed to assess adipose tissue and skeletal muscle sirtuin 1 expression in relation to insulin sensitivity, the expression of proinflammatory and metabolic genes, and to study the regulation of sirtuin 1 expression by hyperinsulinemia and circulating free fatty acids elevation.

Methods

We examined 60 normal-weight, 42 overweight and 15 obese young subjects. The hyperinsulinemic-euglycemic clamp technique was applied throughout to measure insulin sensitivity. In 20 subjects, two 6 h clamps were performed, one of them with concurrent Intralipid/heparin infusion. Biopsies of subcutaneous adipose tissue and skeletal muscle were collected for the measurement of gene and protein expression.

Results

Obese subjects had lower adipose sirtuin 1 in comparison with normal-weight and overweight participants. Muscle sirtuin 1 did not differ between the groups. Adipose tissue sirtuin 1 was related to insulin sensitivity, adipose tissue SLC2A4. The relationship between adipose tissue sirtuin 1 and insulin sensitivity was still present after controlling for BMI, however, it disappeared after controlling for adipose tissue SLC2A4. Muscle sirtuin 1 was not related to insulin sensitivity. Hyperisulinemia decreased adipose tissue and increased muscle sirtuin 1 expression. Intralipid/heparin infusion negated these effects.

Conclusions

Adipose tissue, but not muscle, sirtuin 1 is associated with insulin sensitivity in humans, possibly because of its correlation with adipose tissue SLC2A4 expression. Insulin differentially regulates adipose tissue and skeletal muscle sirtuin 1 expression in the short-term and circulating free fatty acids elevation negates these effects, which may be associated with lipid-induced insulin resistance.

https://ift.tt/2BevPzq

Predicting an adrenal crisis: can we do it?

https://ift.tt/2HVMt7S

Effect of ezetimibe on glycemic control: a systematic review and meta-analysis of randomized controlled trials

Abstract

Purpose

Given the increased risk of incident diabetes and the side effects on glycemic control with statin treatment, statin and ezetimibe combination therapy has been widely used. However, whether the same concern exists in ezetimibe remains uncertain. This meta-analysis aimed to investigate the influence of ezetimibe treatment on glycemic control.

Methods

Articles were searched from PubMed, EMBASE, and Cochrane Library. Randomized controlled trials (RCTs) were included if they compared the effects of ezetimibe with placebo, ezetimibe plus statin with the same statin, or low-dose stain plus ezetimibe with high-dose statin on FBG and glycosylated hemoglobin A1c (HbA1c).

Results

Of the 2440 articles retrieved, 16 RCTs were included. Ezetimibe did not cause side effects on FBG (WMD −0.62, 95% CI: −3.13 to 1.90) and HbA1c (WMD 0.07, 95% CI: −0.07 to 0.20%). No significant changes in FBG (WMD −1.78, 95% CI: −6.33 to 2.77%) and HbA1c (WMD −0.05, 95% CI: −0.14 to 0.05%) were observed in ezetimibe plus low-dose statin treatment compared with high-dose statin. According to subgroup analysis, in comparison with high-dose statin, ezetimibe plus low-dose statin taken for more than 3 months showed a significant decrease in FBG (WMD −7.12, 95% CI: −13.86 to −0.38%) compared with that taken for less than 3 months (WMD 0.90, 95% CI: −2.91 to 4.71%). Nevertheless, this difference was invalid when the study conducted by Dagli et al. was removed.

Conclusions

Compared with high-dose statin therapy, ezetimibe with low-dose statin for more than 3 months may have a beneficial tendency of effects on glycemic control.

https://ift.tt/2DYCArF