Non-Hereditary Obesity Type Networks and New Drug Targets: An In Silico Approach.

Obesity, a chronic, preventable disease, has significant comorbidities that are associated with a great human and financial cost for society. The aim of the present work is to reconstruct the interactomes of non-hereditary obesity to highlight recent advances of its pathogenesis, and discover potential therapeutic targets. Obesity and biological-clock-related genes and/or gene products were extracted from the biomedical literature databases PubMed, GeneCards and OMIM. Their interactions were investigated using STRING v11.0 (a database of known and predicted physical and indirect associations among genes/proteins), and a high confidence interaction score of >0.7 was set. We also applied virtual screening to discover natural compounds targeting obesity- and circadian-clock-associated proteins. Two updated and comprehensive interactomes, the (a) stress- and (b) inflammation-induced obesidomes involving 85 and 93 gene/gene products of known and/or predicted interactions with an average node degree of 9.41 and 10.8, respectively, were produced. Moreover, 15 of these were common between the two non-hereditary entities, namely, ADIPOQ, ADRB2/3, CCK, CRH, CXCL8, FOS, GCG, GNRH1, IGF1, INS, LEP, MC4R, NPY and POMC, while phelligridin E, a natural product, may function as a potent FOX1-DBD interaction blocker. Molecular networks may contribute to the understanding of the integrated regulation of energy balance/obesity pathogenesis and may associate chronopharmacology schemes with natural products.

Long-term (11 + years) efficacy of sleeve gastrectomy as a stand-alone bariatric procedure: a single-center retrospective observational study.

INTRODUCTION: Sleeve gastrectomy (SG) is currently the most commonly performed bariatric procedure worldwide. The aim of the present study was to evaluate the long-term efficacy of SG as a stand-alone bariatric procedure. METHODS: A single-center retrospective analysis of 104 patients who underwent SG as a stand-alone bariatric procedure between January 2005 and December 2009. Weight loss, weight regain, remission or improvement of comorbidities and the new onset of comorbidities were the main outcomes of the study. RESULTS: The percent excess body weight loss (%EBWL), percent excess body mass weight (BMI) loss (%EBMIL), and percent total body weight loss (%TBWL) were 59 ± 25, 69 ± 29, and 29 ± 12, respectively, after a mean follow-up of 13.4 years. At the last follow-up, nearly two thirds of patients (67.3%) had an %EBWL greater than 50. The percentage of patients who experienced significant weight regain ranged from 47 to 64%, depending on the definition used for weight regain. The rate of improvement or remission of hypertension, type 2 diabetes, dyslipidemia, obstructive sleep apnea, and degenerative joint disease at a mean follow-up of 13.4 years was 40%, 94.7%, 70%, 100%, and 42.9%, respectively. The new onset of gastroesophageal reflux disease (GERD) symptoms in the same period was 43%. CONCLUSION: Our data supports that SG results in long-lasting weight loss in the majority of patients and acceptable rates of remission or improvement of comorbidities. Weight regain and GERD may be issues of particular concern during long-term follow-up after SG.

Ghrelin, glucagon-like peptide-1, and peptide YY secretion in patients with and without weight regain during long-term follow-up after bariatric surgery: a cross-sectional study.

Introduction: Weight loss after bariatric surgery is attributed, at least in part, to the altered gastrointestinal (GI) hormone secretion, which is thought to be responsible for a number of beneficial metabolic effects. Material and methods: We conducted a cross-sectional study. Twelve patients who underwent laparoscopic sleeve gastrectomy (SG) and 20 patients who underwent a variant of biliopancreatic diversion with Roux-en-Y gastric bypass and long limbs (BPD/RYGB-LL) were evaluated ≥ 7 years postoperatively. Ghrelin, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) secretion were compared between patients with successful weight loss maintenance (WM group) and patients with weight regain (WR group). Results: In both types of surgery, standard liquid mixed meal (SLMM) ingestion did not result in significant changes in fasting GI hormone levels. Fasting ghrelin levels did not differ between the WM group and the WR group in both types of surgery. In SG patients, SLMM ingestion elicited greater suppression of ghrelin levels in the WM group (p = 0.032). No difference in GLP-1 secretion was observed between the 2 groups of patients in both types of surgery. When patients were examined, regardless of the type of bariatric surgery they had undergone, postprandial PYY levels were lower in the WM group (p < 0.05), while fasting and postprandial PYY levels were correlated positively with an increase in body mass index (BMI) in the evaluation (Spearman's rho ≥ 0.395, p < 0.03). Conclusions: Our data do not support the hypothesis that long-term weight regain after bariatric surgery is associated with an unfavourable GI hormone secretion pattern.

Kisspeptin and the Genetic Obesity Interactome.

BACKGROUND: Kisspeptin (encoded by the KISS1 gene in humans) is an excitatory neuromodulatory peptide implicated in multiple homeostatic systems, including anti-oxidation, glucose homeostasis, nutrition, locomotion, etc. Therefore, in the current obesity epidemic, kisspeptin is gaining increasing interest as a research objective. AIM: To construct an updated interactome of genetic obesity, including the kisspeptin signal transduction pathway. METHODS: Kisspeptin and obesity-related genes or gene products were extracted from the biomedical literature, and a network of functional associations was created. RESULTS: The generated network contains 101 nodes corresponding to gene/gene products with known and/or predicted interactions. In this interactome, KISS1 and KISS1R are connected directly to the luteinizing hormone receptor (LHCGR), gonadotropin-releasing hormone receptor (GNRH1), and indirectly, through the latter, to proopiomelanocortin (POMC), glucagon, leptin (LEP), and/or pro-protein convertase subtilisin/kexin-type 1 (PCSK1), all of which are critically implicated in obesity disorders. CONCLUSIONS: Our updated obesidome includes kisspeptin and its connections to the genetic obesity signalosome with 12 major hubs: glucagon (GCG), insulin (INS), arginine vasopressin (AVP), G protein subunit beta 1 (GNB1) and proopiomelanocortin (POMC), melanocortin 4 receptor (MC4R), leptin (LEP), gonadotropin-releasing hormone 1 (GNRH1), adrenoceptor beta 2 and 3 (ADRB2-3), glucagon-like peptide 1 receptor (GLP1R), and melanocortin 3 receptor (MC3R) genes were identified as major "hubs" for genetic obesity, providing novel insight into the body's energy homeostasis.

Chronic Systemic Inflammation Measured by Bioimpedance Technology Before and After Sleeve Gastrectomy: A Feasibility Study.

Stress induces obesity, while extreme obesity causes stress, anxiety, and even depression. Yet, knowledge on the underlying mechanism(s) has many gaps. To this end, we designed a feasibility study, focused on 18 bariatric patients recruited by the First Propaideutic Department of Surgery at the Hippokration University Hospital in Athens, Greece. The patients (aged 23-58 y, weight 101-185.4 kg before surgery) were weighted and evaluated by advanced bioimpedance technology 2-3 days before surgery at the Biomedical Research Foundation of the Academy of Athens. We employed Bioimpedance Electrolytic Extracellular Tomography (Tomeex), which characterizes (a) neurodegenerative responsiveness to stress, (b) sensory and autonomic tones by basal extracellular conductance (BEC), and (c) activity of limbic and cortical brain areas. The patients' mean body weight loss after 6 months was 48.8 ± 3.1Kg, while stress levels evaluated by appropriate questionnaires decreased (Spearman coefficient significance level p < 0.05). Anxiety and depressive symptoms decreased by 70%, accompanied by changes in measured sensory and autonomic tones (p = 0.003). Baseline blood markers, such as hsCRP and glucose, predicted lower abdominal inflammation (p = 0.034 and p = 0.058, respectively) 6 months postoperatively. In conclusion, chronic inflammation measures by bioimpedance are a useful non-invasive monitoring tool in bariatric surgery.

Anxiety and Depression Affect Early Postoperative Pain Dimensions after Bariatric Surgery.

Uncontrolled postoperative pain and prolonged immobilization after bariatric surgery have been associated with increased postoperative complications and prolonged hospitalization. The aim of our study was to evaluate the postoperative pain that follows bariatric surgery and identify any psychological factors that may affect the early postoperative perception of pain. The study included 100 patients with obesity (women, n = 61; age 37.4 ± 9.9 years, mean ± standard deviation; Body Mass Index (BMI) 47.6 ± 6.5 kg/m2) who underwent bariatric surgery. Preoperative anxiety and depression were evaluated by the Hospital Anxiety and Depression Scale (HADS), and the quantitative and qualitative dimension of early postoperative pain were evaluated by the McGill Pain Questionnaire Short Form (MPQ-SF). Furthermore, the postoperative analgesia protocol was recorded for each patient. Pain declined gradually during the first 24 h postoperative. Although preoperative anxiety had no correlation with the overall pain of postoperative Day 0, patients with a higher level of preoperative anxiety had significantly more intense and more unpleasant pain at 1 h post operation. In addition, depression influences both the intensity and unpleasantness of pain at different time points (1 h, 4 h and 24 h postoperative). Preoperative pain correlated with educational level, but not with age, BMI, gender, marital status, smoking and surgery type. In conclusion, preoperative anxiety and depression influence the early postoperative pain after bariatric surgery, and their preoperative identification is of major importance to enhance the implementation of fast-track postoperative protocols to prevent complications and prolonged hospitalization.

Vascular complications during transcatheter aortic valve implantation: The role of the vascular surgeon.

INTRODUCTION: This study compares the incidence of vascular complications and other major outcomes between patients undergoing transcatheter aortic valve implantation, with and without a standardized preoperative vascular surgeon consultation. METHODS: This retrospective study evaluated all patients scheduled for transcatheter aortic valve implantation during a five-year period at a Hellenic University Hospital. Two main periods were evaluated: Group A (early period (2014-2015), without a standardized preoperative vascular surgeon consultation) and Group B (late period (2016-2018), with a standardized preoperative vascular surgeon consultation). All vascular complications as well as other major outcomes (early death, stroke, myocardial infarction, and treatment) were recorded. Univariate and multivariate analyses were also conducted. RESULTS: Overall, 382 transcatheter aortic valve implantation procedures were conducted (Group A: n = 115; duration = 19 months; Group B: n = 267; duration = 41 months). Overall, 58 vascular complications were recorded (21 patients in Group A and 37 patients in Group B (18.3% versus 13.9%; P = 0.279)). However, vascular complications that necessitated a vascular surgeon's interference were more frequent during the first period (13% versus 4.9%; P = 0.009). Among patients with a vascular complication, early mortality was higher during the first period (14.3% versus 0%; P = 0.034) although stroke and myocardial infarction rates were similar. Age >80 years (OR = 1.856 [1.134-3.452]; P = 0.03) and preoperative vascular surgeon consultation (OR = 0.345 [0.132-0.756]; P = 0.015) were the only independent predictors for vascular complications. CONCLUSIONS: A standardized preoperative evaluation by a vascular surgeon may decrease the risk for vascular complications that necessitate a repair as well as early mortality among patients undergoing transcatheter aortic valve implantation procedures.

Gastritis might be considered as a technical factor affecting laparoscopic sleeve gastrectomy.

There is a paucity of data regarding gastritis as a technical factor affecting the surgical technique. Antritis and gastritis usually cause stomach wall thickness which can interrupt stapler function or even can cause serosal tear during the dissection. We report a video presentation of laparoscopic sleeve gastrectomy in a morbidly obese patient with antritis. Choosing black cartridge for patients with Helicobacter pylori gastritis might be the optimal technique for division of the antrum in laparoscopic sleeve gastrectomy. Further studies are required to clarify this parameter.

Acid and nonacid gastroesophageal reflux after single anastomosis gastric bypass. An objective assessment using 24-hour multichannel intraluminal impedance-pH metry.

BACKGROUND: Single anastomosis gastric bypass (SaGB) was introduced in 2001 as an alternative to "loop" gastric bypass. It was considered as a procedure that would eliminate alkaline reflux and associated esophagitis. OBJECTIVES: Existing evidence about the postoperative incidence of gastroesophageal reflux (GERD) after SaGB is based on studies using symptom questionnaires. The aim of our study was to evaluate GERD 12 months after SaGB by using 24-hour multichannel intraluminal impedance pH metry (24-h MIIpH). SETTING: Surgical department of a university hospital METHODS: Morbidly obese candidates for SaGB underwent 24-hour MIIpH prior and 12 months after their bariatric procedure. RESULTS: There were 11 patients included in this prospective study. Results of 24-hour MIIpH revealed that DeMeester score (40.48 versus 24.16, P = .339) had an increasing trend 12 months after SaGB. Acid reflux episodes decreased, whereas nonacid reflux episodes increased postoperatively, both in proximal and distal esophagus. Total median bolus clearance time and acid clearance time increased. De novo GERD developed in 2 patients (28.6%) and worsening of already existing GERD developed in all patients with preoperative evidence of GERD. CONCLUSION: The use of symptom questionnaires to assess postoperative GERD after SaGB may not accurately depict the real image. Twenty-four-hour MIIpH in 12 months after SaGB revealed an increase of total number of nonacid reflux episodes and a decrease of total number of acid reflux episodes, with longer duration of each acid reflux episode. Close postoperative follow-up with reflux testing and possibly endoscopy could eliminate the risk of complicated GERD.

Evaluating the Homeostasis Assessment Model Insulin Resistance and the Cardiac Autonomic System in Bariatric Surgery Patients: A Meta-Analysis.

Morbid obesity is a severe chronic disease and subject to surgical methods for losing weight. This intervention is expected to drive to better quality of life and health status. Other important aspects which may be influenced are: HOMA-IR (as insulin resistance marker) and heart rate variability (as cardiac function and autonomic nervous system marker), which are independent and valid predictors of future cardiac, neurological, metabolic health. We pooled 4 studies (646 subjects) resulting to HOMA-IR and nine HRV components-grouped in those undergone to gastric bypass (RYGP) and those operated with vertical sleeve gastrectomy (SG) method. We performed a meta-analysis in patients for HOMA-IR and HRV, using Hedge's g correction of Cohen d for small samples. We concluded that RYGP favors insulin resistance decrease, whereas SG increases the vagal tone, improving cardiac function. The severity of cardiovascular diseases history suggests the selection of the surgery method: SG for the most severe cardiovascular cases and RYGP for those with higher HOMA-IR.

The impact of laparoscopic sleeve gastrectomy on weight loss and obesity-associated comorbidities: the results of 3 years of follow-up.

BACKGROUND: Laparoscopic sleeve gastrectomy is one of the most recent advances in the surgical treatment of morbid obesity. Extended follow-up studies of large cohorts are needed to establish the usefulness of the operation. The objectives of this study are to delineate the role of sleeve gastrectomy in weight loss and in comorbidities among obese patients. METHODS: Patients who underwent laparoscopic sleeve gastrectomy in a single bariatric center were followed up for a 3-year period. Weight loss and status of several comorbidities were assessed at the 1st, 3rd, 6th, 12th, 18th, 24(th), and 36th postoperative month. RESULTS: Overall, after 3 years of follow-up of 88 patients, the mean body mass index (BMI) of the patients was 29.8 kg/m(2) (SD ±6.1), the % total weight loss was 38.1% (SD ±12.9), the % excess weight loss was 69.5% (SD ±17.5), and the % estimated BMI loss was 81.4% (SD ±22.3). These parameters changed significantly over the first year of follow-up (p < 0.001) and subsequently stabilized. The percentages of patients with hypertension (33.3%), hyperlipidemia (26.4%), diabetes mellitus (20.7%), obstructive sleep apnea (20.2%), and gastroesophageal reflux disease (GERD-27%) were significantly reduced (10.5, 9.2, 1.1, 1.1, and 9.2% respectively at 36 months postoperation), while 10 new cases of GERD appeared postoperatively. However, only three of the new GERD cases required medication, and only one of them experienced symptoms that persisted after the 3-year period. CONCLUSION: Three years of close follow-up of patients who had undergone laparoscopic sleeve gastrectomy demonstrated satisfactory weight loss results. Promising results were also obtained regarding various comorbidities of obese patients. Longer follow-up studies for more patients are needed to delineate the exact role of sleeve gastrectomy on postoperative outcomes.

"Normal Values of 24H Multichannel Intraluminal Impedance pH-Metry in a Greek Obese Population Based on Montreal Definition of Gerd".

BACKGROUND: Although several studies reporting normal values of 24h multichannel intraluminal impedance pH (MIIpH) have been published, none of them has ever studied obese individuals. The purpose of this study is to determine overall frequency and duration of reflux episodes (acid and non-acid, supine-upright, post and preprandial) in obese asymptomatic volunteers. METHODS: Obese volunteers were enlisted during their preoperative evaluation for bariatric surgery. Volunteers had no gastroesophageal reflux disease (GERD) symptoms and no evidence of esophageal mucosal injury on endoscopy. Participants underwent a 24h MIIpH. RESULTS: In this prospective observational study, data of 22 obese individuals were analyzed. Mean age was 41.9 years and mean BMI was 47.1 kg/m(2). Mean total reflux episodes was 55.6 and 95th percentile was 99.7. Mean percentage of total time with pH <4 was 2.59 % and 95th percentile was 8.57 %. Mean percentage of bolus exposure was 1.84 % with 95th percentile being 4.47 %. Postprandial acid reflux episodes were statistical significant more frequent in comparison to preprandial acid reflux episodes (19.41 vs. 15, p = 0.008). Mean acid clearance duration was 3.6 times higher than median bolus clearance duration (56.05 and 15.55 s, respectively, p = 0.868). CONCLUSION: Our study is the first to provide normal values of 24h MIIpH of asymptomatic obese. Normal values of 24h MIIpH of obese asymptomatic individuals differ from the reported normal values of non-obese healthy individuals; having more reflux episodes and equal or slightly higher median bolus exposure and acid clearance. Our results imply that new cut-off values should be employed in order to define GERD in obese individuals.

Impact of Laparoscopic Sleeve Gastrectomy on Weight Loss and Associated Comorbidities in Adolescents and Young Adults.

BACKGROUND: Obesity is a common disease affecting young adults and adolescents worldwide. This study aims to delineate the role of laparoscopic sleeve gastrectomy (LSG) in weight loss and associated comorbidities to adolescents and young adults. PATIENTS AND METHODS: This study is a retrospective analysis of a prospective cohort of all young adults 16-22 years old who underwent LSG for morbid obesity and were followed up for 24 months. Demographic data, weight loss, and the status of several comorbidities, such as diabetes mellitus, hypertension, and dyslipidemia, were assessed at postoperative Months 1, 3, 6, 12, 18, and 24. RESULTS: Overall, at baseline and after 24 months of close follow-up of 37 adolescents and young adults who had undergone LSG, the body mass index of the patients was 46.93 ± 6.07 kg/m(2) versus 26.2 ± 3.6 kg/m(2) (P < .001), and the body weight was 143 ± 29 kg versus 78 ± 15 kg (P < .001). From the first follow-up visit after operation to the last one at the 24 months, there was also a significant difference in percentage excess weight loss (22.40 ± 6.58% versus 81 ± 17%; P < .001), body mass index difference (-5.47 ± 1.69 kg/m(2) versus -18.08 ± 4.38 kg/m(2); P < .001), and percentage excess body mass index loss (26.06 ± 7.56% versus 96 ± 21%; P < .001). The percentage of the adolescents and young adults with diabetes mellitus, hypertension, and dyslipidemia were diminished gradually at 6 months postoperatively (P < .001). CONCLUSIONS: LSG represents a safe and attractive treatment strategy for morbidly obese adolescents and young adults with comorbidities. In this study group excellent resolution of excess weight and comorbid conditions is achieved 2 years after LSG.

Staple Line Reinforcement with Stitch in Laparoscopic Sleeve Gastrectomies. Is It Useful or Harmful?

BACKGROUND: Reinforcement of the staple line in laparoscopic sleeve gastrectomy (LSG) is a practice that leads to less morbidity, but equivocal results have been reported in the literature. MATERIALS AND METHODS: This is a prospective randomized study comparing two groups of patients who underwent LSG. In one group LSG was performed with a running absorbable suture placement at the staple line. In the other group the running suture was not placed. General data of the patients, as well as intraoperative and postoperative data, were gathered and statistically analyzed. RESULTS: Overall, 146 patients were subjected to LSG. In 84 patients a running suture was placed, and in 62 patients no suture was placed. No significant differences were found between the two groups in demographic data. No significant differences were found also in the intraoperative data, such as number of trocars, number and type of cartridges, drain placement, and operative time (45±21 versus 40±20 minutes, respectively; P<.05). Intraoperative complications were significantly more in the group with the suture placement (33.3% versus 16.1%, respectively; P<.05). Hematomas developed intraoperatively in more patients after the placement of the running suture (9.5% versus 0.0%, respectively; P<.05). Postoperatively, there was no significant difference in morbidity between the two groups (8.3% versus 9.7%, respectively; P>.05). CONCLUSIONS: After this randomized study, final conclusions about the efficacy of this running suture to the staple line cannot be made. To the contrary, problems seem to exist after such reinforcement of the staple line, such as hematomas. Dealing with possible leaks and hemorrhage of the staple line is also problematic after placement of the running suture.

GERD-Related Questionnaires and Obese Population: Can They Really Reflect the Severity of the Disease and the Impact of GERD on Quality of Patients' Life?

INTRODUCTION: There is a strong association between obesity and gastroesophageal reflux disease (GERD). GERD-related questionnaires have been developed in order to objectify symptoms. However, none of them has been tested in obese population. PURPOSE: The purpose of this study is to evaluate if GERD score and GERD-Health-Related Quality of Life (HRQL) can reflect severity of the disease and screen obese patients for GERD preoperatively. GERD's impact on the quality of life of obese patients is being assessed with the use of EORTC-QLQ C30. PATIENTS-METHODS: Obese patients during their preoperative evaluation were recruited regardless of the presence of GERD symptoms. A targeted GERD symptom history was obtained. Patients completed GERD score, GERD-HRQL, and EORTC-QLQ C30, and then, a 24-h multichannel intraluminal impedance pHmetry (MIIpH) was conducted. RESULTS: Forty-seven consecutive obese patients with mean age 39.91 years and mean BMI 46.94 kg/m(2) were included in the study. GERD score and GERD-HRQL have a positive linear correlation with DeMeester score (p = 0.001 and p < 0.001, respectively). EORTC QLQ-C30 does not correlate with DeMeester score. CONCLUSIONS: GERD-related questionnaires could be used in obese population as preoperative screening tool for GERD. However, our results indicate that the quality of life of obese patients is not affected by the existence of GERD.

Using Ligasure™ or Harmonic Ace® in Laparoscopic Sleeve Gastrectomies? A Prospective Randomized Study.

BACKGROUND: Laparoscopic sleeve gastrectomy is one of the most recent advances of surgery for treating morbid obesity. Many laparoscopic devices have evolved to provide vascular control and tissue dissection. METHODS: This is a prospective randomized study comparing the intraoperative and postoperative complications and operative time of two groups of patients who underwent laparoscopic sleeve gastrectomy. In the first group after randomization, sleeve gastrectomy was performed using Ligasure™ and in the second group Harmonic Ace® was used. RESULTS: In total, 94 patients were enrolled in the study allocated in two groups. In group 1, 43 patients were operated using Ligasure™, and in group 2, 51 patients were operated using Harmonic Ace®. No significant differences were highlighted between these two groups with regards to operative time (45.0 ± 15.0 vs 40.0 ± 20.0 min, p = 0.199), intraoperative complications (32.6 vs 15.7 %, p = 0.054) and postoperative complications (4.7 vs 17.6 %, p = 0.051). CONCLUSIONS: Both Ligasure™ and Harmonic Ace® provide surgeons ergonomy, and no significant differences were shown in operative time and complications. Safety and efficacy in such demanding operations is of critical importance. Choice between these two shears lies with surgeon's preference.

Laparoscopic excision of a lymphangioma of the cystic duct.

Lymphangiomas are benign tumors that originate from malformations of the lymphatic vessels. They are rarely seen in adults and are extremely rare in the cystic duct. Herein, we report the case of a 48-year-old woman who presented with a cystic lymphangioma that originated in the cystic duct and was excised laparoscopically. Preoperative imaging revealed the cystic and benign nature of the lesion. Laparoscopic abdominal exploration and excision of the 10-cm cystic lymphangioma were performed. Four trocar sites were used, and the excision was achieved using clips and electrocautery. The laparoscopic excision of these benign masses is safe and efficacious in experienced hands. This procedure requires preoperative planning and must be individualized.