Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms.

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. VIDEO ABSTRACT.

Impact of autofluorescence-guided surgery of parathyroid glands during total thyroidectomy in experienced surgeons: A randomized clinical trial.

INTRODUCTION: Post-surgical hypoparathyroidism often occurs after total thyroidectomy (TT). The aim of this study is to investigate whether the use of near-infrared autofluorescence (NIRAF) of parathyroid glands (PGs) can aid experienced surgeons in identifying more PGs during surgery, potentially reducing unintended resection, and assessing its impact on post-surgical hypoparathyroidism. MATERIALS AND METHODS: All patients undergoing at least a TT by two experienced surgeons, between 2020 and 2021, were enrolled and randomized into two cohorts: NIRAF group (NG) and CONTROL group (CG). Transient hypoparathyroidism was defined by serum concentration of PTH<12 ng/mL at the 1st post-operative day and permanent by the need of calcium-active vitamin D treatment >6 months from the surgery with still undetectable PTH or <12 ng/m. RESULTS: Among 236 patients (111 in NG, 125 in CG), the number of PGs identified was higher in NG (93.9%, 417/444) compared to CG (81.4%, 407/500) (p < 0.001), with a mean of 3.76 ± 0.44 PGs per patient in NG and 3.25 ± 0.79 in CG. The number of unintendedly resected PGs was 14 in NG and 42 in CG (p < 0.0001). Transient hypoparathyroidism was observed in 18 patients (16.2%) in NG and 40 patients (32.0%) in CG (p = 0.004). Permanent hypoparathyroidism affected 1 patient in NG and 7 patients in CG (p = 0.06). The mean operative time was longer in NG (104.3 ± 32.08 min) compared to CG (85.5 ± 40.62 min) (p < 0.001). CONCLUSIONS: NIRAF enhances the identification of PGs, preventing their inadvertent resection and reducing the overall incidence of post-surgical hypoparathyroidism.

Weight loss before bariatric surgery and its impact on poor versus excellent outcomes at 2 years.

PURPOSE: To identify preoperative factors that influence the outcomes of gastric bypass surgery, in terms of excess weight loss at 24 months. METHODS: This retrospective study included two groups of patients who underwent laparoscopic gastric bypass surgery. Group A (poor outcomes) had ≤ 50%EWL or BMI ≥ 30 kg/m2; group B (excellent outcomes) had ≥ 80%EWL at 24 months. A comparative analysis of demography, anthropometry, comorbidities, and metabolic status was performed. A linear regression model was used to evaluate %EWL association; the number of preoperative and postoperative consultations were also compared. RESULTS: A total of 202 patients completed follow-up; 71 (35.1%) and 78 (38%) had poor and excellent outcomes (%EWL 44.1 ± 9.4% vs. 92 ± 10.9%), respectively. Mean age was 40.4 ± 8.9 years. Patients with poor outcomes had higher weight and BMI, lesser preoperative %EWL, higher dyslipidemia and diabetes rates with longer periods of evolution, and increased HbA1c% levels. In the linear regression analysis, preoperative %EWL and initial and preoperative BMI were statistically significant determinants of %EWL at 24 months Diabetes remission was 46.2% (group A) vs. 66.6% (group B). Group A had higher non-attendance rates after surgery. CONCLUSION: The factors independently associated with greater %EWL at 24 months between groups were higher preoperative %EWL, and lower initial and preoperative BMI.

Effect of the intake of dietary protein on insulin resistance in subjects with obesity: a randomized controlled clinical trial.

PURPOSE: We compared the effect of diets with different amounts and sources of dietary protein on insulin sensitivity (IS) in subjects with obesity and insulin resistance (IR). METHODS: Eighty subjects with obesity (BMI ≥ 30 kg/m2) and IR (Matsuda index < 4.3 and HOMA-IR ≥ 2.5) over 18 years old were randomized to four groups for a one-month period: a normal protein diet (< 20%) with a predominance of animal protein (Animal NP) or vegetable protein (Vegetable NP) and a high-protein diet (25-30%) with a predominance of animal protein (Animal HP) or vegetable protein (Vegetable HP). Baseline and final measurements of body weight, body composition, biochemical parameters, blood pressure (BP), resting energy expenditure and plasma amino acid profiles were performed. RESULTS: Body weight, BMI and waist circumference decreased in all groups. Interestingly, the IS improved more in the Animal HP (Matsuda index; 1.39 vs 2.58, P = 0.003) and in the Vegetable HP groups (Matsuda index; 1.44 vs 3.14, P < 0.0001) after one month. The fat mass, triglyceride levels, C-reactive protein levels and the leptin/adiponectin index decreased; while, the skeletal muscle mass increased in the Animal and Vegetable HP groups. The BP decreased in all groups except the Animal NP group. CONCLUSION: Our study demonstrates that a high-protein hypocaloric diets improves IS by 60-90% after one month in subjects with obesity and IR, regardless of weight loss and the source of protein, either animal or vegetable. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT03627104), August 13, 2018.

Social media, advertising, and internet use among general and bariatric surgeons.

INTRODUCTION: The use of the internet and technology has increased, and its implication with medicine is inevitable. Along with these technologies, social media platforms have changed the interaction between peers, forcing an evolution on medical activities and patient relationship. There is no clear information on how surgeons interact with these platforms within their daily practice. METHODS: A transverse study with a survey obtained from general and bariatric surgeons from Mexico was performed, aimed to gather information about social media platforms use (Facebook, Instagram, Twitter, and LinkedIn). Personal, professional, academic, and marketing activities were analyzed and compared between general and bariatric surgeons. Secondly, the same analysis was performed in younger participants. Other variables were also analyzed, such as type of marketing and monthly budget. RESULTS: We obtained 523 surveys (84.1% general and 15.8% bariatric surgeons), where male gender comprised 86.4%. Almost a third considered social media as an important tool. In 53% of the cases, Facebook was preferred for professional activities; Twitter was the second most used. Bariatric surgeons were younger, used all platforms more frequently, and preferred Facebook for every activity. They also invested more in publicity, and showed wider marketing methods than general surgeons. CONCLUSION: There is an important awareness of internet and social media use among general and bariatric surgeons. Facebook leads the activities for both specialties (personal, professional, academic, and marketing), but bariatric surgeons are significantly more involved; additionally, there are more marketing strategies and investment among them.

Single Dose Steroid Injection After Loss of Signal (LOS) During Thyroid Surgery is Effective to Recover Electric Signal Avoiding Vocal Cord Palsy and the Need of Staged Thyroidectomy: Prospective Evaluation on 702 Patients.

BACKGROUND: Steroids are often used for the management of vocal cord palsy after thyroid surgery. There are no reports in the current literature of their intraoperative use, immediately after a loss of signal during neuromonitoring (LOS). We evaluate the impact of a single dose of 4 mg of dexamethasone on laryngeal nerve function, administrated at the time of a LOS during a nerve-monitored thyroidectomy. METHODS: A prospective not randomized study was performed, dividing patients in two groups, when a LOS was detected. LOS was defined as an electromyographic signal (EMG) inferior to 100 µV when stimulating the inferior laryngeal nerve, according to international guidelines. In group 1 (G1), surgeon waits for signal's recovery up to 20 min. Absence of a detectable signal after 20 min was predictive of vocal cord palsy; if it affected the first side of surgery the procedure was interrupted to avoid the risk of bilateral nerve palsy. In group 2 (G2), 4 mg of dexamethasone were injected within 10 min from a detected LOS, waiting 10 min for its effects. An EMG value > to 200 µV within 20' after steroid administration was predictive of full recovery and normal post-operatory vocal cord function. Vocal cords motility was checked at postoperative day 1 in all patients by an experienced ENT. RESULTS: Between January 2017 and December 2018, 702 patients underwent thyroid surgery under intermittent intraoperative nerve monitoring by two expert surgeons. A LOS was found in 22 patients in G1 and 16 in G2. Four patients in G1 spontaneously recovered electric signal (18.2%), while in G2 a signal was recovered in 14/16 patients (87.5%) (p < 0.001). This immediate effect was monitored by EMG, showing the increase in potentials at 10, 15 and 20 min after injection. ENT evaluation found vocal cord palsy, respectively, in 18/22 and 1/16 patients (G1 vs G2, p < 0.001). One of the patients in G2 who recovered electric signal presented transient palsy, fully recovered at 2 months, while the two patients who had a signal < 200 µV did not present postoperative cord palsy. In G1, 10/18 palsy were definitive. No permanent palsies were presents in G2. CONCLUSION: A single 4 mg iv dexamethasone injection within 10 min form a LOS during thyroid surgery exerts a therapeutic action, measurable by EMG modifications. It avoids vocal nerve palsy and the need of a staged thyroidectomy. It may also protect from permanent cord palsy, but the mechanism is unknown.

Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes.

BACKGROUND: Obesity is a well-recognized risk factor for insulin resistance and type 2 diabetes (T2D), although the precise mechanisms underlying the relationship remain unknown. In this study we identified alterations of DNA methylation influencing T2D pathogenesis, in subcutaneous and visceral adipose tissues, liver, and blood from individuals with obesity. METHODS: The study included individuals with obesity, with and without T2D. From these patients, we obtained samples of liver tissue (n = 16), visceral and subcutaneous adipose tissues (n = 30), and peripheral blood (n = 38). We analyzed DNA methylation using Illumina Infinium Human Methylation arrays, and gene expression profiles using HumanHT-12 Expression BeadChip Arrays. RESULTS: Analysis of DNA methylation profiles revealed several loci with differential methylation between individuals with and without T2D, in all tissues. Aberrant DNA methylation was mainly found in the liver and visceral adipose tissue. Gene ontology analysis of genes with altered DNA methylation revealed enriched terms related to glucose metabolism, lipid metabolism, cell cycle regulation, and response to wounding. An inverse correlation between altered methylation and gene expression in the four tissues was found in a subset of genes, which were related to insulin resistance, adipogenesis, fat storage, and inflammation. CONCLUSIONS: Our present findings provide additional evidence that aberrant DNA methylation may be a relevant mechanism involved in T2D pathogenesis among individuals with obesity.

Type 2 diabetes mellitus outcomes after laparoscopic gastric bypass in patients with BMI <35 kg/m2 using strict remission criteria: early outcomes of a prospective study among Mexicans.

BACKGROUND: Mild obesity (BMI 30-34.9 kg/m2) is highly prevalent worldwide and is associated with type 2 diabetes mellitus. The efficacy of bariatric surgery remains unclear, including among Mexicans. The criteria for diabetes remission are inconsistent, as they are based on different thresholds for glycated hemoglobin, with remission rates ranging from 43 to 73%. METHODS: Mildly obese patients with type 2 diabetes mellitus who underwent laparoscopic gastric bypass were prospectively analyzed. The primary objective was to determine the impact of surgery on their metabolic profiles. Demographic, clinical, and biochemical parameters were measured at baseline and at 3, 6, 9, 12, and 18 months. Diabetes remission rate was defined as an HbA1c <5.7%. Complications within 30 days and weight loss (% total weight loss) were also analyzed. RESULTS: Twenty-three Mexican patients underwent surgery. Of the 19 patients, evaluable at 18 months, nine (47.4%) achieved complete diabetes remission, seven (36.8%) showed partial remission, and three (15.8%) showed improvement. Significant improvements in lipid profile, cardiovascular risk, blood pressure, and every metabolic parameter were observed, beginning at the first month and throughout the study. The final total percentage weight loss was 24.9%. Three patients (13%) experienced complications, but none required reoperation or died. CONCLUSION: Laparoscopic gastric bypass is a safe and effective method to improve the metabolic profile of mildly obese Mexican patients with type 2 diabetes mellitus, inducing high remission rates even when the strictest model is used.

Long-term survival after adrenalectomy for stage I/II adrenocortical carcinoma (ACC): a retrospective comparative cohort study of laparoscopic versus open approach.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the standard treatment for benign adrenal lesions. The laparoscopic approach has also been increasingly accepted for adrenal metastases but remains controversial for adrenocortical carcinoma (ACC). In a retrospective cohort study we compared the outcome of LA versus open adrenalectomy (OA) in the treatment of stage I and II ACC. METHODS: This was a double cohort study comparing the outcome of patients with stage I/II ACC and a tumor size <10 cm submitted to LA or OA at Lille University Hospital referral center from 1985 to 2011. Main outcomes analyzed were: postoperative morbidity, overall survival, and disease-free survival. RESULTS: Among 111 consecutive patients operated on for ACC, 34 met the inclusion criteria. LA and OA were performed in 13 and 21 patients, respectively. Baseline patient characteristics (gender, age, tumor size, hormonal secretion) were similar between groups. There was no difference in postoperative morbidity, but patients in LA group were discharged earlier (p < 0.02). After a similar follow-up (66 ± 52 for LA and 51 ± 43 months for OA), Kaplan-Meier estimates of disease-specific survival and disease-free survival were identical in both groups (p = 0.65, p = 0.96, respectively). CONCLUSIONS: LA was associated with a shorter length of stay and did not compromise the long-term oncological outcome of patients operated on for stage I/II ACC ≤ 10 cm ACC. Our results suggest that LA can be safely proposed to patients with potentially malignant adrenal lesions smaller than 10 cm and without evidence of extra-adrenal extension.

Abdominal cocoon syndrome (sclerosing encapsulated peritonitis) causing small bowel occlusion in a patient with gastric bypass.

A rare condition, sclerosing encapsulating peritonitis, is characterized by a fibrotic membrane forming over the bowels, leading to intestinal obstruction. In this case of a 56-year-old male patient with a history of laparoscopic gastric bypass, a computed tomography scan showed findings indicative of the condition. Extensive adhesiolysis was performed, and biopsies confirmed the presence of fusiform cells (D2-40 positive on immunochemistry) resembling fibroblasts, within dense collagenous peritoneal tissue sheets, typical of sclerosing encapsulating peritonitis. The prevalence of this condition is uncertain, and diagnosis typically requires a peritoneal biopsy due to the nonspecific clinical presentation.

La peritonitis esclerosante encapsulada es una condición rara caracterizada por una membrana fibrótica que se genera sobre las asas intestinales causando cuadros de oclusión intestinal. Se presenta el caso de un paciente varón de 56 años con antecedente de derivación gastroyeyunal por laparoscopia que presenta oclusión intestinal. Se realizó tomografía computada que evidenció sitio de transición previo al sitio de anastomosis. Se realizó de anastomosis extensa y toma de biopsias. Histológicamente se observó engrosamiento de la membrana peritoneal, células fusiformes (D2-40 positivo en inmunohistoquímica) similares a fibroblastos con láminas de colágeno peritoneal denso. La peritonitis esclerosante encapsulada es una patología de prevalencia desconocida. El cuadro clínico es inespecífico y el diagnóstico definitivo es por patología con biopsia peritoneal.

The impact of Aprepitant on Nausea and Vomiting following Laparoscopic Sleeve Gastrectomy: A Blinded Randomized Controlled Trial.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is associated with postoperative nausea and vomiting (PONV). We aimed to compare the effects of aprepitant on the incidence of PONV after LSG. METHODS: In this double-blind, randomized controlled trial, the case group received the standard care regimen for PONV (dexamethasone 10 mg, ondansetron 4 mg, and metoclopramide 10 mg) plus prophylactic oral aprepitant 80 mg 1 h preoperatively. The control group received standard care plus a placebo. Comparative analyses using the Rhodes index were performed at 0, 6, 12, and 24 h postoperatively. RESULTS: A total of 400 patients (201 in the aprepitant group and 199 in the placebo group) underwent LSG. The groups were homogeneous. The aprepitant group experienced less PONV: early, 69 (34.3%) vs. 103 (51.7%), p ≤ 0.001; 6 h, 67 (33.3%) vs. 131 (65.8%), p ≤ 0.001; 12 h, 41 (20.4%) vs. 115 (57.8%), p ≤ 0.001; and 24 h, 22 (10.9%) vs. 67 (33.7%), p ≤ 0.001. Fewer patients in the aprepitant group vomited: early, 3 (1.5%) vs. 5 (2.5%), p = 0.020; 6 h, 6 (3%) vs. 18 (9%), p = 0.020; 12 h, 2 (1%) vs. 17 (8.5%), p = 0.006; and 24 h, 1 (0.5%) vs. 6 (3%), p = 0.040. Patients in the aprepitant group required less additional PONV medication: early, 61 (30.3%) vs. 86 (43.2), p = 0.008; 6 h, 7 (3.5%) vs. 34 (17%), p = 0.001; 12 h, 6 (3%) vs. 31 (15.6%), p ≤ 0.001; and 24 h, 5 (2.5%) vs. 11 (5.5%), p ≤ 0.001. CONCLUSIONS: Prophylactic aprepitant improved PONV between 0 h (early) and 24 h postoperatively in patients undergoing LSG.

Metabolic and Bariatric Surgery in Patients with Obesity Class V (BMI > 60 kg/m2): a Modified Delphi Study.

BACKGROUND: Metabolic and bariatric surgery (MBS) is the preferred method to achieve significant weight loss in patients with Obesity Class V (BMI > 60 kg/m2). However, there is no consensus regarding the best procedure(s) for this population. Additionally, these patients will likely have a higher risk of complications and mortality. The aim of this study was to achieve a consensus among a global panel of expert bariatric surgeons using a modified Delphi methodology. METHODS: A total of 36 recognized opinion-makers and highly experienced metabolic and bariatric surgeons participated in the present Delphi consensus. 81 statements on preoperative management, selection of the procedure, perioperative management, weight loss parameters, follow-up, and metabolic outcomes were voted on in two rounds. A consensus was considered reached when an agreement of ≥ 70% of experts' votes was achieved. RESULTS: A total of 54 out of 81 statements reached consensus. Remarkably, more than 90% of the experts agreed that patients should be notified of the greater risk of complications, the possibility of modifications to the surgical procedure, and the early start of chemical thromboprophylaxis. Regarding the choice of the procedure, SADI-S, RYGB, and OAGB were the top 3 preferred operations. However, no consensus was reached on the limb length in these operations. CONCLUSION: This study represents the first attempt to reach consensus on the choice of procedures as well as perioperative management in patients with obesity class V. Although overall consensus was reached in different areas, more research is needed to better serve this high-risk population.

First National Consensus on the Safe Practice of Medical Tourism for Bariatric Surgery in Mexico.

BACKGROUND: Medical tourism is increasing every year, especially in fields such as bariatric surgery. Global concerns rely on the fact of its safety, mainly because of a lack of standardization, unknown number of cases, and the type of specialists performing such procedures. Mexico continues to be among the top countries receiving patients from abroad, but there is no national consensus, guidelines, or recommendations about the practice in such fields. METHODS: A group of 32 bariatric surgeons with an accumulated experience of 25,196 procedures in the medical tourism modality were gathered to perform a national consensus in bariatric surgery tourism. The Delphi methodology was used for this project, with a total of 52 items applied. A consensus was reached when the experts' position was ≥ 70% for each statement. The items included pre- and postoperative phases, patient selection, follow-up, and ethical and legal considerations. RESULTS: Of the 52 statements, 40 (76.9%) reached a consensus of ≥ 70%; 36 in favor, 5 against, and 11 with indeterminate responses. CONCLUSIONS: Although more than two-thirds of the statements related to high standard practice reached a consensus, weak points in the medical tourism modality were identified. This first consensus serves to establish the basis of safe practices, eventually reach national guidelines, and define the top standards of care when performing bariatric surgery tourism.

Women with Anemia Refractory to Oral Iron Treatment Following Bariatric Surgery: a Short-Term Analysis.

INTRODUCTION: Iron deficiency and anemia are common after bariatric surgery. Women have a higher risk of developing such long-term complications. Though oral supplementation is indicated, intravenous iron therapy is required in some cases. METHODS: This retrospective study included patients who underwent bariatric surgery between 2012 and 2018. Postoperative anemia patients receiving parental iron therapy were assessed during the first 24 months. Their baseline characteristics, surgery type, and laboratory test results were analyzed. A follow-up analysis included a subgroup of women with and without gynecological disorders. Patients with vitamin B12 or folic acid deficiencies were excluded. RESULTS: Six hundred eleven (63.3%) met the inclusion criteria: 525 underwent gastric bypass, of which 79.6% were women. Overall, postoperative anemia was 28.9% (24.5% related to gastric bypass), especially among women (84%). Anemia refractory to oral iron therapy was observed in 12.9% of patients. All the patients requiring iron infusions (n = 54) were women, and half of them (51.8%) reported abnormal uterine bleeding. Postsurgical hemogram values were significantly lower in patients with abnormal uterine bleeding (despite the same number of infusions) than in those without gynecological disorders; 89.2% of these women had preoperative anemia. CONCLUSION: Anemia is frequent in bariatric surgery patients despite supplementation. Women undergoing gastric bypass with a history of gynecological disorders are prone to require more iron infusions. Consulting with the patient about a higher risk is important, and probably knowing the plan or including the opinion of an OBGYN to determine as a team the assessment, treatment, and prognosis.

DNA Methylation Remodeling after Bariatric Surgery Correlates with Clinical Parameters.

The altered functions of adipose tissue are one of the main issues in obesity. Bariatric surgery is associated with improvement of obesity associated comorbidities. Here DNA methylation remodeling in adipose tissue after bariatric surgery is examined. After six months postoperative, DNA methylation shows changes in 1155 CpG sites, 66 of these sites correlate with body mass index. Some sites also show correlation with LDL-C, HDL-C, total cholesterol, and triglycerides. CpG sites are located in genes that have not previously been linked to obesity or metabolic diseases. GNAS complex locus is one of those that presented CpG site with the greatest changes after surgery, and the most significant correlation with BMI and lipid profiles. These results show that epigenetic regulation may be involved in the alteration of adipose tissue functions in obesity.

Development and validation of an interpretable machine learning-based calculator for predicting 5-year weight trajectories after bariatric surgery: a multinational retrospective cohort SOPHIA study.

BACKGROUND: Weight loss trajectories after bariatric surgery vary widely between individuals, and predicting weight loss before the operation remains challenging. We aimed to develop a model using machine learning to provide individual preoperative prediction of 5-year weight loss trajectories after surgery. METHODS: In this multinational retrospective observational study we enrolled adult participants (aged ≥18 years) from ten prospective cohorts (including ABOS [NCT01129297], BAREVAL [NCT02310178], the Swedish Obese Subjects study, and a large cohort from the Dutch Obesity Clinic [Nederlandse Obesitas Kliniek]) and two randomised trials (SleevePass [NCT00793143] and SM-BOSS [NCT00356213]) in Europe, the Americas, and Asia, with a 5 year follow-up after Roux-en-Y gastric bypass, sleeve gastrectomy, or gastric band. Patients with a previous history of bariatric surgery or large delays between scheduled and actual visits were excluded. The training cohort comprised patients from two centres in France (ABOS and BAREVAL). The primary outcome was BMI at 5 years. A model was developed using least absolute shrinkage and selection operator to select variables and the classification and regression trees algorithm to build interpretable regression trees. The performances of the model were assessed through the median absolute deviation (MAD) and root mean squared error (RMSE) of BMI. FINDINGS: 10 231 patients from 12 centres in ten countries were included in the analysis, corresponding to 30 602 patient-years. Among participants in all 12 cohorts, 7701 (75·3%) were female, 2530 (24·7%) were male. Among 434 baseline attributes available in the training cohort, seven variables were selected: height, weight, intervention type, age, diabetes status, diabetes duration, and smoking status. At 5 years, across external testing cohorts the overall mean MAD BMI was 2·8 kg/m2 (95% CI 2·6-3·0) and mean RMSE BMI was 4·7 kg/m2 (4·4-5·0), and the mean difference between predicted and observed BMI was -0·3 kg/m2 (SD 4·7). This model is incorporated in an easy to use and interpretable web-based prediction tool to help inform clinical decision before surgery. INTERPRETATION: We developed a machine learning-based model, which is internationally validated, for predicting individual 5-year weight loss trajectories after three common bariatric interventions. FUNDING: SOPHIA Innovative Medicines Initiative 2 Joint Undertaking, supported by the EU's Horizon 2020 research and innovation programme, the European Federation of Pharmaceutical Industries and Associations, Type 1 Diabetes Exchange, and the Juvenile Diabetes Research Foundation and Obesity Action Coalition; Métropole Européenne de Lille; Agence Nationale de la Recherche; Institut national de recherche en sciences et technologies du numérique through the Artificial Intelligence chair Apprenf; Université de Lille Nord Europe's I-SITE EXPAND as part of the Bandits For Health project; Laboratoire d'excellence European Genomic Institute for Diabetes; Soutien aux Travaux Interdisciplinaires, Multi-établissements et Exploratoires programme by Conseil Régional Hauts-de-France (volet partenarial phase 2, project PERSO-SURG).

Renal origin and size are independent predictors of survival after surgery for adrenal metastasis.

BACKGROUND: The adrenal gland is a frequent site of dissemination for certain types of tumors. Aggressive treatment remains controversial. The benefit of adrenalectomy has been observed, but the ultimate role remains to be elucidated. MATERIALS AND METHODS: We conducted a retrospective study analyzing the records of all patients with adrenal metastases submitted to adrenalectomy (open or laparoscopic) at our institution from 1981 to 2010. Baseline characteristics, operative outcomes, and survival were analyzed; predictive factors were also studied by multivariate analysis. RESULTS: A total of 65 patients were included with a median age of 60 years. Primary tumor sites were renal (35%), pulmonary (23%), melanoma (7%), colon (2%), liver (1%), and others. Mean metastasis size was 7 ± 4.2 cm with a mean interval to metastasis diagnosis of 39 months. Laparoscopic approach was done in 50% of cases. Postoperative morbidity was present in 9%, and 2 early deaths were observed. Median overall survival was 48 months and 45% at 5 years. Univariate and multivariate analyses showed better prognosis for renal metastases (p = 0.007 and 0.009) and those with size <5 cm (p = 0.011 and 0.031). Also in univariate analysis: synchronous (p = 0.02), symptomatic (p = 0.04), and laparoscopically operated (p = 0.033) metastasis showed higher survival rates. Metastasis from pulmonary tumors had the worst prognosis. CONCLUSIONS: Adrenalectomy should be considered in patients with adrenal metastasis from renal carcinoma, as well as in those with small secondary lesions from other type of tumor with a controlled primary disease. The clear benefit of adrenalectomy remains to be documented in pulmonary carcinoma metastasis.

Complications Rate Variability after Bariatric Surgery and the Importance of Standardization of a Reporting System.

BACKGROUND: The rate of early (< 30 days) complications after bariatric surgery has been reported to be 0.4-27.4%. Although the incidence of serious adverse events has decreased with time and experience, controversy regarding how they are reported persists, and the current literature is heterogeneous. METHODS: Data from patients, who underwent primary bariatric surgery (gastric bypass and sleeve gastrectomy) at a single institution between 2012 and 2018, were retrospectively reviewed. Any deviation from a "normal" postoperative course (< 30 days) was identified, and a comparative analysis of early complications according to five models was performed: modified Clavien-Dindo; Longitudinal Assessment of Bariatric Surgery (LABS); Bariatric Surgery Centers of Excellence (BSCOE); American Society for Metabolic and Bariatric Surgery (ASMBS); and Li (major/minor). RESULTS: A total of 788 patients (83.7% gastric bypass), of whom 8.8% deviated from a "normal" postoperative course, were included. After applying the five classifications, the results were as follows: Clavien-Dindo, 8.8%; LABS, 2.3%; BSCOE, 0.4%; ASMBS, 9.9%; and Li, 11.2%. The incidence of major/severe/adverse outcomes were as follows: Clavien-Dindo, 2.4%; LABS, 2.3%; BSCOE, 0.4%; ASMBS, 6.9%; and Li 9.2%. Minor complications were as follows: Clavien-Dindo, 6.5%; ASMBS, 3%; and Li, 2%. There was no mortality. CONCLUSION: Germane heterogeneity was found in reporting of early complications after bariatric surgery. Incidence varied according to classification system applied, and Clavien-Dindo demonstrated accuracy as a reporting model. To avoid bias, standardized reporting should be mandatory, and a more stringent and homogeneous reporting system should be established.

DNA methylation and gene expression analysis in adipose tissue to identify new loci associated with T2D development in obesity.

BACKGROUND: Obesity is accompanied by excess adipose fat storage, which may lead to adipose dysfunction, insulin resistance, and type 2 diabetes (T2D). Currently, the tendency to develop T2D in obesity cannot be explained by genetic variation alone-epigenetic mechanisms, such as DNA methylation, might be involved. Here, we aimed to identify changes in DNA methylation and gene expression in visceral adipose tissue (VAT) that might underlie T2D susceptibility in patients with obesity. METHODS: We investigated DNA methylation and gene expression in VAT biopsies from 19 women with obesity, without (OND = 9) or with T2D (OD = 10). Differences in genome-scale methylation (differentially methylated CpGs [DMCs], false discovery rate < 0.05; and differentially methylated regions [DMRs], p value < 0.05) and gene expression (DEGs, p value <0.05) between groups were assessed. We searched for overlap between altered methylation and expression and the impact of altered DNA methylation on gene expression, using bootstrap Pearson correlation. The relationship of altered DNA methylation to T2D-related traits was also tested. RESULTS: We identified 11 120 DMCs and 96 DMRs distributed across all chromosomes, with the greatest density of epigenomic alterations at the MHC locus. These alterations were found in newly and previously T2D-related genes. Several of these findings were supported by validation and extended multi-ethnic analyses. Of 252 DEGs in the OD group, 68 genes contained DMCs (n = 88), of which 24 demonstrated a significant relationship between gene expression and methylation (p values <0.05). Of these, 16, including ATP11A, LPL and EHD2 also showed a significant correlation with fasting glucose and HbA1c levels. CONCLUSIONS: Our results revealed novel candidate genes related to T2D pathogenesis in obesity. These genes show perturbations in DNA methylation and expression profiles in patients with obesity and diabetes. Methylation profiles were able to discriminate OND from OD individuals; DNA methylation is thus a potential biomarker.