Re-sleeve gastrectomy is a safe and sensible intervention in selected patients: retrospective cohort study.

INTRODUCTION: Sleeve gastrectomy is a good treatment intervention to control the metabolic syndrome in patients with obesity worldwide. However, weight regain is of great concern and would usually necessitate a reintervention. In recent years, re-sleeve gastrectomy (ReSG) has been proposed to treat weight regain in the context of a large residual stomach. Our objective was to analyze the long-term results and safety profile of this intervention in a large case series. METHODS: From September 2010 to March 2021, a retrospective cohort study in a tertiary nonuniversity hospital was performed. Seventy-nine patients received a ReSG by laparoscopy. Preoperative radiologic imaging showed a dilation of the gastric pouch exceeding 250 cc in all cases. RESULTS: A total of 79 patients (87% females) with a mean age of 44.8 years old and a mean BMI of 40.0 kg/m 2 were enrolled in the study. The mean follow-up was 44.8 months. The ReSG indication was insufficient weight loss in 37 patients (46.8%) and weight regain in 39 patients (53.2%). The authors noticed a 10.1% complications rate: gastric stenosis (5.1%), bleeding (2.5%), and incisional site hernia in 2.5%, with no death. There was no gastric fistula detected. The mean BMI decreased to 33.1 kg/m 2 after ReSG (a decrease of 6.9 kg/m 2 ). CONCLUSION: After insufficient weight loss or weight regain following sleeve gastrectomy and in the presence of localized or global gastric tube dilation, ReSG seems to be a good treatment choice and a safe procedure.

Social isolation but not deprivation involved in employment status after bariatric surgery.

An increase in employment rate was observed among individuals who underwent bariatric surgery. This study assessed the relationship between employment rate and weight loss, deprivation, and Bariatric Analysis and Reporting Outcome System (BAROS) scores after bariatric surgery in a deprived area. This retrospective study evaluated the employment rate at a mean period of 2.3±0.1 years after bariatric surgery among 133 individuals. The Evaluation of Deprivation and Inequalities in Health Examination Centers (EPICES score), satisfaction scale, and BAROS (self-esteem, physical activity, social life, work conditions, and sexual activity) questionnaires were used. The mean age of the participants was 45 (range: 19-67) years. Approximately 88% were women. The initial mean body mass index (BMI) was 42.7 kg/m2, and about 88% of the participants underwent sleeve gastrectomy. The mean decrease in BMI was 12 ± 0.5 kg/m2. The mean EPICES score (N<30), BAROS, and satisfaction scale (range: 1-5) scores were 31.9±18, 1.3±1.1, and 4.27±1.19, respectively. After surgery, 19 participants obtained a job. However, three were unemployed. Based on a multivariate analysis, employed and unemployed participants (77 vs 52) before surgery had a lower initial BMI and better BAROS and satisfaction scale scores. After surgery, there was no difference between participants who obtained a new job and those still did not have a job in terms of questionnaire responses. Obtaining a new job was not associated with BMI, sex, or age differences. However, there was a positive correlation between social life score and weight loss. Bariatric surgery increased an individual's chance of finding a job independently of deprivation status. Participants with a pre-operative job had a better perception of satisfaction and BAROS scores. Moreover, social isolation was correlated with unsuccessful weight loss.

Correction to: Early sepsis markers in patients admitted to intensive care unit with moderate­to­severe diabetic ketoacidosis.

An amendment to this paper has been published and can be accessed via the original article.

Early sepsis markers in patients admitted to intensive care unit with moderate-to-severe diabetic ketoacidosis.

BACKGROUND: Bacterial infections are frequent triggers for diabetic ketoacidosis. In this context, delayed antibiotic treatment is associated with increased morbidity and mortality. Unnecessary administration of antimicrobial therapy might however, also negatively impact the prognosis. The usefulness of sepsis markers in diabetic ketoacidosis has not been assessed. Thus, we sought to investigate diagnostic performances of clinical and biological sepsis markers during diabetic ketoacidosis. METHODS: In this monocentric retrospective cohort study, all consecutive episodes of diabetic ketoacidosis (defined as pH ≤ 7.25, glycaemia > 300 mg/dL and presence of ketones) admitted in intensive care unit were included. A proven bacterial infection was defined as bacteriological documentation on any bacterial sample. Clinical (presence of fever: temperature > 38 °C and presence of hypothermia: temperature < 36 °C) and biological markers (whole blood count, neutrophils count, neutrophils-to-lymphocytes count ratio and procalcitonin), recorded at admission, were compared according to the presence or absence of a proven bacterial infection. RESULTS: Between 2011 and 2018, among 134 episodes of diabetic ketoacidosis, 102 were included (91 patients). Twenty out of 102 were infected. At admission, procalcitonin (median: 3.58 ng/mL vs 0.52 ng/mL, p < 0.001) and presence of fever (25% vs 44%, p = 0.007) were different between episodes with and without proven bacterial infection in both univariate and multivariate analysis. Whole blood count, neutrophils count, neutrophils-to-lymphocytes count ratio and presence of hypothermia were not different between both groups. The diagnostic performance analysis for procalcitonin revealed an area under the curve of 0.87 with an optimal cutoff of 1.44 ng/mL leading to a sensitivity of 0.90 and a specificity of 0.76. Combining procalcitonin and presence of fever allowed to distinguish proven bacterial infection episodes from those without proven bacterial infection. Indeed, all patients with procalcitonin level of more than 1.44 ng/mL and fever had proven bacterial infection episodes. The presence of one of these 2 markers was associated with 46% of proven bacterial infection episodes. No afebrile patient with procalcitonin level less than 1.44 ng/mL had a proven bacterial infection. CONCLUSION: At admission, combining procalcitonin and presence of fever may be of value to distinguish ketoacidosis patients with and without proven bacterial infection, admitted in intensive care unit.

Fetal spina bifida in a pregnant woman following omega gastric bypass: Case report and literature review.

INTRODUCTION: Bariatric surgery has been increasingly popular during the last years because of its proven efficacy on obesity and related complications. However, nutrient deficiency is common after surgery, in particular after Roux-en-Y gastric bypass (RYGB) or omega gastric bypass (OGB), due to iatrogenic malabsorption. All vitamins and minerals could be involved, including vitamin B9 which plays an important role in the prevention of neural tube defects during pregnancy. We present a case of a spina bifida in the fetus of a pregnant woman following OGB. CASE PRESENTATION: A twenty-six years old young woman underwent OGB five years after weight loss failure post sleeve gastrectomy. Her initial body mass index (BMI) was 42.7 kg/m2. Two years after OGB, she became pregnant. On her gynecologist's advice, the patient discontinued daily vitamin intake before the end of the first trimester, as obstetrical follow-up had been considered appropriate. Regrettably, second trimester ultrasound showed myelomeningocele and surgical abortion was decided during the 25th week of pregnancy. DISCUSSION: Nutritional status in a pregnant woman is crucial, since it determines the fetal outcome. Biochemical and ultrasound monitoring should be performed regularly, especially in pregnant women with a history of bariatric surgery. CONCLUSION: Vitamins, minerals and trace metals deficiencies after bypass bariatric surgery could be prevented by adequate supplementation administered before and during pregnancy.

Changes in total sperm count after gastric bypass and sleeve gastrectomy: the BARIASPERM prospective study.

BACKGROUND: The massive weight loss induced by bariatric surgery is associated with major benefits, but the effect on semen variables is still uncertain. OBJECTIVES: To explore semen modifications with gastric bypass and sleeve gastrectomy. SETTING: Five French University Hospitals. METHODS: Male candidates for bariatric surgery with no history of infertility were recruited in this controlled prospective study. Sperm characteristics were collected before surgery and then 6 months and up to 12 months after surgery. RESULTS: Forty-six adult men who underwent gastric bypass (n = 20) or sleeve gastrectomy (n = 26) were included. Total sperm count tended to be lower at 6 months and showed a significant decrease at 12 months in both surgery groups, at -69.5 million (-96.8 to -42.2 million; P = 0.0021). Total sperm count at 12 months relative to baseline was -41.4 million (P = .0391) after gastric bypass and -91.1 million (P = .0080) after sleeve gastrectomy. This was counterbalanced by an associated resolution of hypogonadism and decrease of DNA fragmentation in most patients with time after surgery. CONCLUSION: Improvement in some semen variables after bariatric surgery observed in 3 previous studies is in contrast to the lower mean total sperm count found in this study at 1 year. The possible reversibility of this effect in the long term and the impact of surgery on fertility both remain unknown.

Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study.

BACKGROUND: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. METHODS: This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. FINDINGS: 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs. INTERPRETATION: Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year. FUNDING: None.

Esophageal adenocarcinoma in Barrett's esophagus after sleeve gastrectomy: Case report and literature review.

INTRODUCTION: Sleeve gastrectomy (SG) has become one of the most dramatically increasing bariatric procedures worldwide due to its excellent results and impact on the obesity pandemic. Morbid obesity is known to increase the risk of esophageal adenocarcinoma. However, the evolution of gastroesophageal reflux disease (GERD) along with Barrett's esophagus (BE) after SG is of concern since there is little data available. We present a case of esophageal adenocarcinoma after SG with known intestinal metaplasia on preoperative gastroscopy. CASE PRESENTATION: We report a case of a 55 years old female patient who presented lower esophageal adenocarcinoma three years after complicated SG with known preoperative BE without dysplasia detected by gastroscopy. Multidisciplinary decision suggested treatment by endoscopic mucosectomy. The endoscopic control at one year did not highlight tumoral recurrence but still BE without dysplasia. DISCUSSION: Literature review regarding the evolution of BE after SG is poor and the relation between SG and the development of subsequent esophageal cancer isn't clear yet. CONCLUSION: Preoperative endoscopy should be performed in order to detect GERD, BE, and potential carcinomas of the upper gastrointestinal tract before undergoing bariatric surgery. The long-term monitoring after SG is essential.

Role of MDH2 pathogenic variant in pheochromocytoma and paraganglioma patients.

PURPOSE: MDH2 (malate dehydrogenase 2) has recently been proposed as a novel potential pheochromocytoma/paraganglioma (PPGL) susceptibility gene, but its role in the disease has not been addressed. This study aimed to determine the prevalence of MDH2 pathogenic variants among PPGL patients and determine the associated phenotype. METHODS: Eight hundred thirty patients with PPGLs, negative for the main PPGL driver genes, were included in the study. Interpretation of variants of unknown significance (VUS) was performed using an algorithm based on 20 computational predictions, by implementing cell-based enzymatic and immunofluorescence assays, and/or by using a molecular dynamics simulation approach. RESULTS: Five variants with potential involvement in pathogenicity were identified: three missense (p.Arg104Gly, p.Val160Met and p.Ala256Thr), one in-frame deletion (p.Lys314del), and a splice-site variant (c.429+1G>T). All were germline and those with available biochemical data, corresponded to noradrenergic PPGL. CONCLUSION: This study suggests that MDH2 pathogenic variants may play a role in PPGL susceptibility and that they might be responsible for less than 1% of PPGLs in patients without pathogenic variants in other major PPGL driver genes, a prevalence similar to the one recently described for other PPGL genes. However, more epidemiological data are needed to recommend MDH2 testing in patients negative for other major PPGL genes.

Update on multiple endocrine neoplasia Type 1 and 2.

Multiple endocrine neoplasia type 1 is a rare genetic syndrome, characterized by the co-occurrence, in the same individual or in related individuals of the same family, of hyperparathyroidism, duodenopancraetic neuroendocrine tumors, pituitary adenomas, adrenocortical tumors, and neuroendocrine tumors (carcinoids) in the thymus, the bronchi, or the stomach. Multiple endocrine neoplastic type 2 is a rare genetic syndrome, characterized by the familial occurrence of medullary thyroid carcinoma either isolated or associated with pheochromocytoma, primary hyperparathyroidism, or typical features (Marfanoid habitus, mucosal neuromas). Subjects with clinical MEN1 and those who carry a mutation in the MEN1 gene should be offered biochemical and imaging screening in order to detect tumors and evaluate their progression over time. Children with mutation in the RET gene should have prophylactic total thyroidectomy according to the category of aggressiveness of the detected mutation whereas those with clinical MEN2 should be operated on upon diagnosis. In MEN1 patients, special attention should be paid to evaluate the progression duodenopancraetic neuroendocrine tumors because of their malignant potential. Also, thymic neuroendocrine tumors should be detected as soon as possible because they represent the most lethal tumor. In MEN2, calcitonin and carcinoembryonic antigen (CEA) serve as excellent tumor markers for medullary thyroid carcinoma. Their preoperative levels are correlated with tumor size and predict postoperative cure. Moreover, calcitonin or CEA doubling time has important prognostic value. In both MEN syndromes, multidisciplinary approaches are very important in the care of affected patients. Moreover, those patients should be comprehensively informed and enabled to participate in the decision-making procedure. In addition to multidisciplinary approaches, every effort should be made to follow the recommendations and guidelines issued by national (the French Group of Endocrine Tumors) and international groups.

Dynamical Behavior of Somatostatin-14 and Its Cyclic Analogues as Analyzed in Bulk and on Plasmonic Silver Nanoparticles.

Primarily known as the inhibitor of growth hormone release, the role of somatostatin in many other inhibiting activities upon binding to its five G-protein-coupled receptors has been elucidated. Because of the short half-life of somatostatin, a number of synthetic analogues were elaborated for this peptide hormone. Herein, after recalling the main somatostatin therapeutic interests, we present the dynamical behavior of somatostatin-14 and its two currently used synthetic cyclic analogues, octreotide and pasireotide. Physical techniques, such as fluorescence, UV-visible absorption, circular dichroism, Raman spectroscopy, surface-enhanced Raman spectroscopy, and transmission electron microscopy, were jointly used in order to get information on the solution structural features, as well as on the anchoring sites of the three peptides on silver colloids. While somatostatin-14 adopts a rather unordered chain within the submillimolar concentration range, its cyclic analogues were revealed to be ordered, i.e., stabilized either in a type-II' ß-turn (octreotide) or in a face-to-face γ-turn/type-I ß-turn (pasireotide) structure. Nevertheless, a progressive structuring trend was observed in somatostatin-14 upon increasing concentration to the millimolar range. Because of their cationic character, the three peptides have revealed their capability to bind onto negatively charged silver nanoparticles. The high affinity of the peptides toward metallic particles seems to be extremely promising for the elaboration of somatostatin-based functionalized plasmonic nanoparticles that can be used in diagnosis, drug delivery, and therapy.

DNA Methylation Is an Independent Prognostic Marker of Survival in Adrenocortical Cancer.

CONTEXT: Adrenocortical cancer (ACC) is an aggressive tumor with a heterogeneous outcome. Prognostic stratification is difficult even based on tumor stage and Ki67. Recently integrated genomics studies have demonstrated that CpG islands hypermethylation is correlated with poor survival. OBJECTIVE: The goal of this study was to confirm the prognostic value of CpG islands methylation on an independent cohort. DESIGN: Methylation was measured by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). SETTING: MS-MLPA was performed in a training cohort of 50 patients with ACC to identify the best set of probes correlating with disease-free survival (DFS) and overall survival (OS). These outcomes were validated in an independent cohort from 21 ENSAT centers. PATIENTS: The validation cohort included 203 patients (64% women, median age 50 years, 80% localized tumors). MAIN OUTCOME MEASURES: DFS and OS. RESULTS: In the training cohort, mean methylation of 4 genes (PAX5, GSTP1, PYCARD, PAX6) was the strongest methylation marker. In the validation cohort, methylation was a significant prognostic factor of DFS (P < 0.0001) and OS (P < 0.0001). Methylation, Ki67, and ENSAT stage were combined in multivariate models. For DFS, methylation (P = 0.0005) and stage (P < 0.0001) but not Ki67 (P = 0.19) remained highly significant. For OS, methylation (P = 0.0006), stage (P < 0.0001), and Ki67 (P = 0.024) were independent prognostic factors. CONCLUSIONS: Tumor DNA methylation emerges as an independent prognostic factor in ACC. MS-MLPA is readily compatible with clinical routine and should enhance our ability for prognostication and precision medicine.

From bulk to plasmonic nanoparticle surfaces: the behavior of two potent therapeutic peptides, octreotide and pasireotide.

Octreotide and pasireotide are two cyclic somatostatin analogues with an important clinical use in the treatment and diagnosis of neuroendocrine tumors. Herein, by the combined use of several techniques (UV-visible absorption, fluorescence, circular dichroism, ζ-potential, transmission electron microscopy, Raman scattering, surface-enhanced Raman scattering, and quantum mechanical calculations) we have followed the structural dynamics of these analogues in the bulk, as well as their binding sites on plasmonic (gold and silver) colloids. In contrast to the previously derived conclusions, the two peptides seem to possess completely different conformational features. Octreotide, a cyclic octapeptide, is formed by a moderately flexible type-II'ß-turn maintained by a deformable disulfide linkage. Pasireotide, in which the cyclic character is made possible by peptide bonds, manifests a rigid backbone formed by two oppositely placed tight turns of different types, i.e.γ-turn and type-I ß-turn. Owing to their cationic character, both analogues induce aggregation of negatively charged gold and silver colloids. Nevertheless, despite their notable structural differences, both peptides bind onto gold nanoparticles through their unique d-Trp residue. In contrast, their binding to silver colloids seems to be of electrostatic nature, as formed through monodentate or bidentate ionic pairs.