Mohamed Elkalaawy

DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Here, we combine epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. We discover extensive DNA methylation changes that are robustly associated with obesity (N = 190 samples, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P < 1 × 10-7). We connect obesity-associated methylation variations to transcriptomic changes at >500 target genes, and identify putative methylation-transcription factor interactions. Through Mendelian Randomisation, we infer causal effects of methylation on obesity and obesity-induced metabolic disturbances at 59 independent loci. Targeted methylation sequencing, CRISPR-activation and gene silencing in adipocytes, further identifies regional methylation variations, underlying regulatory elements and novel cellular metabolic effects. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions.

Internal hernia (IH) after one-anastomosis gastric bypass (OAGB) was thought to have an extremely low incidence. In this video, we report three cases of post-OAGB symptomatic internal herniation. The first case is a 45-year-old female who presented 4 months after her OAGB with crampy abdominal pain and reflux symptoms. An exploratory laparoscopy showed Petersen’s hernia; the hernia was reduced with no ischemia and the defect was closed. The second case is a 40-year-old male who presented 7 months after his surgery with abdominal pain and reflux. An exploratory laparoscopy showed Petersen’s hernia; bowel was reduced and defect was closed through a laparotomy. The third case is a 64-year-old male who presented with refractory biliary reflux after OAGB. An elective diagnostic laparoscopy showed Petersen’s hernia; the hernia was reduced and defect was closed. All patients recovered well with no recurrence of symptoms on follow-up. Internal hernia after OAGB is more common than the reported incidence. The threshold for diagnostic laparoscopy should be lowered for a OAGB patient with symptoms suggestive of IH.

Background: The number of women seeking bariatric surgery in order to improve their fertility is increasing. Current guidelines recommend that pregnancy should be delayed for at least 1 year post-surgery. However, there are limited data regarding pregnancy outcomes post-surgery, particularly for sleeve gastrectomy. Methods: We performed a single-centre, retrospective cohort study of pregnancies in women post-bariatric surgery. Surgical and maternity records were reviewed and maternal and fetal outcomes examined. Results: Ninety-seven pregnancies in 69 women were documented over an 8-year period. Forty-one women had undergone a Roux-en-Y gastric bypass and 28 a sleeve gastrectomy. There were 79 pregnancies with a known outcome; 18 women were lost to follow-up during pregnancy. 32.9% of pregnancies occurred in the first post-operative year. Pregnancies conceived in the first post-operative year were associated with a higher miscarriage rate compared to pregnancies after this time (50% vs 30.4%, P35 kg/m² also associated with an increased miscarriage rate (22.8% vs 50%, P35 kg/m². During pregnancy, two women developed gestational diabetes (1.9%) and there were no cases of gestational hypertension. Three women had a post-partum haemorrhage (2.9%). With regards to fetal outcomes, mean birth weight was 3.11±0.1 kg and mean gestational age at birth 39.5±0.4 weeks. Birth weight was not affected by duration from surgery or pre-conception BMI. There were two cases of severe fetal developmental abnormalities. Intrauterine growth restriction was seen in two pregnancies, both in the same woman. Conclusion: Our data support current recommendations to delay conception until 1 year after surgery, however larger data collections are required to build a robust evidence base and allow guideline development.