Most patients reported improved well-being after RYGB surgery, but the prevalence of symptoms was high and nearly one-third of patients were hospitalized, 4- to 5-fold more than among the comparison group. Predictors of symptoms included young age, female sex, smoking, and experiencing symptoms before RYGB surgery. Development of weight loss procedures with fewer subsequent symptoms should be a high priority.

MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial network fragmentation, disorganised cristae, and increased autophagosomes. There was strong transcriptional evidence of mitochondrial stress signalling, increased protein synthesis, and suppression of signatures of cell death in affected tissue, whereas mitochondrial morphology and gene expression were normal in skin fibroblasts. These findings suggest that specific MFN2 mutations cause tissue-selective mitochondrial dysfunction with increased adipocyte proliferation and survival, confirm a novel form of excess adiposity with paradoxical suppression of leptin expression, and suggest potential targeted therapies.DOI: http://dx.doi.org/10.7554/eLife.23813.001

In observational studies, control of confounding can be done in the design and analysis phases. Using examples from large health care database studies, this article provides the clinicians with an overview of standard methods in the analysis phase, such as stratification, standardization, multivariable regression analysis and propensity score (PS) methods, together with the more advanced high-dimensional propensity score (HD-PS) method. We describe the progression from simple stratification confined to the inclusion of a few potential confounders to complex modeling procedures such as the HD-PS approach by which hundreds of potential confounders are extracted from large health care databases. Stratification and standardization assist in the understanding of the data at a detailed level, while accounting for potential confounders. Incorporating several potential confounders in the analysis typically implies the choice between multivariable analysis and PS methods. Although PS methods have gained remarkable popularity in recent years, there is an ongoing discussion on the advantages and disadvantages of PS methods as compared to those of multivariable analysis. Furthermore, the HD-PS method, despite its generous inclusion of potential confounders, is also associated with potential pitfalls. All methods are dependent on the assumption of no unknown, unmeasured and residual confounding and suffer from the difficulty of identifying true confounders. Even in large health care databases, insufficient or poor data may contribute to these challenges. The trend in data collection is to compile more fine-grained data on lifestyle and severity of diseases, based on self-reporting and modern technologies. This will surely improve our ability to incorporate relevant confounders or their proxies. However, despite a remarkable development of methods that account for confounding and new data opportunities, confounding will remain a serious issue. Considering the advantages and disadvantages of different methods, we emphasize the importance of the clinical input and of the interplay between clinicians and analysts to ensure a proper analysis.

Short-term surgical complications occurred in 3% and long-term complications in one-fourth of RYGB patients. Compared with the general population, the RR for any inpatient admission increased after RYGB.

PurposeHealth care databases may be a valuable source for epidemiological research in obesity, if diagnoses are valid. We examined the validity and completeness of International Classification of Diseases, 10th revision [ICD-10] diagnosis coding for overweight/obesity in Danish hospitals.Patients and methodsWe linked data from the Danish National Patient Registry on patients with a hospital diagnosis code of overweight/obesity (ICD-10 code E66) with computerized height and weight measurements made during hospital contacts in the Central Denmark Region Clinical Information System. We computed the positive predictive value (PPV) of the IDC-10 diagnosis of overweight/obesity, using a documented body mass index (BMI) ≥25 kg/m2 as gold standard. We also examined the completeness of obesity/overweight diagnosis coding among all patients recorded with BMI ≥25 kg/m2.ResultsOf all 19,672 patients registered with a first diagnosis code of overweight/obesity in the National Patient Registry, 17,351 patients (88.2%) had any BMI measurement recorded in the Central Denmark Region Clinical Information System, and 17,240 patients (87.6%) had a BMI ≥25 kg/m2, yielding a PPV of 87.6% (95% CI: 87.2–88.1). The PPV was slightly higher for primary diagnosis codes of overweight/obesity: 94.1% (95% CI: 93.3–94.8) than for secondary diagnosis codes: 86.1% (95% CI: 85.6–86.6). The PPV increased with higher patient age: from 75.3% (95% CI: 73.8–76.9) in those aged 18–29 years to 94.7% (95% CI: 92.6–96.9) in patients aged 80 years and above. Completeness of obesity/overweight diagnosis coding among patients recorded with BMI ≥25 kg/m2 was only 10.9% (95% CI: 10.8–11.0).ConclusionOur findings indicate a high validity of the ICD-10 code E66 for overweight/obesity when recorded; however, completeness of coding was low. Nonetheless, ICD-10 discharge codes may be a suitable source of data on overweight/obesity for epidemiological research.