Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10 −4 in dataset 1 and r = 0.42, P = 1.2 × 10 −4 in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10 −9 ) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer.obesity | epigenetics | aging | biological age | DNA methylation

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Liver samples from morbidly obese patients (n = 45) with all stages of NAFLD and controls (n = 18) were analyzed by array-based DNA methylation and mRNA expression profiling. NAFLD-specific expression and methylation differences were seen for nine genes coding for key enzymes in intermediate metabolism (including PC, ACLY, and PLCG1) and insulin/insulin-like signaling (including IGF1, IGFBP2, and PRKCE) and replicated by bisulfite pyrosequening (independent n = 39). Transcription factor binding sites at NAFLD-specific CpG sites were >1,000-fold enriched for ZNF274, PGC1A, and SREBP2. Intraindividual comparison of liver biopsies before and after bariatric surgery showed NAFLD-associated methylation changes to be partially reversible. Postbariatric and NAFLD-specific methylation signatures were clearly distinct both in gene ontology and transcription factor binding site analyses, with >400-fold enrichment of NRF1, HSF1, and ESRRA sites. Our findings provide an example of treatment-induced epigenetic organ remodeling in humans.

Obesity is associated with hypothalamic inflammation (HI) in animal models. In the current study, we examined the mediobasal hypothalamus (MBH) of 57 obese human subjects and 54 age- and sex- matched nonobese control subjects by MRI and analyzed the T2 hyperintensity as a measure of HI. Obese subjects exhibited T2 hyperintensity in the left but not the right MBH, which was strongly associated with systemic low-grade inflammation. MRS revealed the number of neurons in the left hypothalamic region to be similar in obese versus control subjects, suggesting functional but not structural impairment due to the inflammatory process. To gain mechanistic insights, we performed nutritional analysis and 16S rDNA microbiome sequencing, which showed that high-fat diet induces reduction of in the gut, which is significantly correlated with MBH T2 hyperintensity. In addition to these environmental factors, we found subjects carrying common polymorphisms in the or the gene to be more susceptible to HI. Finally, in a subgroup analysis, bariatric surgery had no effect on MBH T2 hyperintensity despite inducing significant weight loss and improvement of peripheral insulin sensitivity. In conclusion, obesity in humans is associated with HI and disturbances in the gut-brain axis, which are influenced by both environmental and genetic factors.

Endoscopically assisted vacuum therapy is a well-tolerated and effective therapeutic option for treatment of major esophageal leaks after surgery. Additional surgery was avoided in all cases. However, the occurrence of a delayed aortoesophageal fistula calls for careful further investigation of this new technique.

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IntroductionTo accomplish early enteral feeding in the critically ill patient a new transnasal endoscopic approach to the placement of postpyloric feeding tubes by intensive care physicians was evaluated.MethodsThis was a prospective cohort study in 27 critically ill patients subjected to transnasal endoscopy and intubation of the pylorus. Attending intensive care physicians were trained in the handling of the new endoscope for transnasal gastroenteroscopy for two days. A jejunal feeding tube was advanced via the instrument channel and the correct position assessed by contrast radiography. The primary outcome measure was successful postpyloric placement of the tube. Secondary outcome measures were time needed for the placement, complications such as bleeding and formation of loops, and the score of the placement difficulty graded from 1 (easy) to 4 (difficult). Data are given as mean values and standard deviation.ResultsOut of 34 attempted jejunal tube placements, 28 tubes (82%) were placed correctly in the jejunum. The duration of the procedure was 28 ± 12 minutes. The difficulty of the tube placement was judged as follows: grade 1: 17 patients, grade 2: 8 patients, grade 3: 7 patients, grade 4: 2 patients. In three cases, the tube position was incorrect, and in another three cases, the procedure had to be aborted. In one patient bleeding occurred that required no further treatment.ConclusionsFast and reliable transnasal insertion of postpyloric feeding tubes can be accomplished by trained intensive care physicians at the bedside using the presented procedure. This new technique may facilitate early initiation of enteral feeding in intensive care patients.

Conventional laparoscopy is the gold standard in bariatric surgery. Internationally, robot-assisted surgery is gaining in importance. Up to now there are only few reports from Germany on the use of the system in bariatric surgery. Since January 2017 we have been performing robot-assisted gastric bypass surgery. It remains unclear whether the use of the robotic system has advantages over the well-established laparoscopic technique. Within a period from January to early August 2017 a total of 53 gastric bypass operations were performed. Of these 16 proximal redo Roux-en-Y gastric bypass operations were performed with the DaVinci Si system versus 29 laparoscopic procedures. A retrospective analysis of the perioperative course was carried out. Body weight, body mass index (BMI), Edmonton obesity staging system (EOSS) and American Society of Anesthesiologists (ASA) classification did not show significant differences. There were also no significant differences in terms of estimated blood loss, intraoperative complications, duration of surgery, postoperative inflammatory parameters and weight loss. There was no mortality and no need for revisional surgery in either group. After laparoscopic surgery there was a delayed occurrence of a leak of the gastrojejunostomy followed by readmission and endoscopic negative pressure wound therapy. The results show that the proximal Roux-en-Y gastric bypass can be performed safely and efficiently using the DaVinci surgical system. Significant differences to the conventional laparoscopic procedure were not found. Larger randomized controlled trials are needed to define the role of the DaVinci system in bariatric surgery.

A 50-year-old Caucasian woman was admitted to our hospital with intermittent diarrhoea, emesis and increasingly brown-coloured skin, mainly the in light-exposed areas, after biliopancreatic diversion for obesity treatment. Differential diagnoses such as adrenal insufficiency were ruled out, but biochemical analysis demonstrated unusual high pyridoxine serum levels (vitamin B6). History revealed the intake of 300 mg of vitamin B6 per day over 6 months as described by her general practitioner. All symptoms disappeared after the discontinuation of vitamin B6 supplementation. Importantly, in contrast to many other vitamins and supplements, there is no evidence in the literature of the occurrence of vitamin B6 deficiency after bariatric surgery. Therefore, supplementation of vitamins and supplements in bariatric patients has to be carefully considered according to the existing clinical guidelines, as uncritical oversupplementation of micronutrients might result in intoxication and serious illness as presented here.