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1.
Minerva Surg ; 79(1): 15-20, 2024 Feb.
Article in English | MEDLINE | ID: mdl-36946129

ABSTRACT

BACKGROUND: Multiquadrant procedures are technically more demanding than sequential operations. The new single port (SP) system allows to work in every abdominal quadrant maintaining an adequate triangulation without the need for changes in the port positioning. METHODS: In February 2020, two patients underwent a robotic SP partial nephrectomy for malignancy combined with a cholecystectomy and a left inguinal hernia repair respectively. RESULTS: Both procedures were successfully completed with one robotic docking and without the need for conversion. The operative time was 213 minutes for the right partial nephrectomy (126 min) with cholecystectomy (18 min), and 257 minutes for the left partial nephrectomy (161 min) with inguinal hernia repair (35 min). Estimated blood loss was 200 (150-250) mL, while the total warm ischemia time was 15 minutes for the right partial nephrectomy and 53 minutes for the left partial nephrectomy. There were no intraoperative complications or perioperative transfusions. The postoperative course was uneventful, and the postoperative hospital stay was 1 and 2 days. Both resections had free margins and the median tumor size was 2.5 (1.5-3.5) cm. Histopathology analysis revealed chronic cholecystitis and renal cell carcinomas with free margins and a median tumor size of 2.5 (1.5-3.5) cm. After a mean follow-up of 24 months, no surgical-related complications or recurrence were detected. CONCLUSIONS: The robotic SP approach facilitates the completion of combined surgical procedures in multiple abdominal quadrants through a single 25mm incision.


Subject(s)
Carcinoma, Renal Cell , Hernia, Inguinal , Kidney Neoplasms , Robotic Surgical Procedures , Robotics , Humans , Robotic Surgical Procedures/methods , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/pathology
2.
Cells ; 12(20)2023 10 15.
Article in English | MEDLINE | ID: mdl-37887297

ABSTRACT

Glycosphingolipids (GSLs) are products of lipid glycosylation that have been implicated in the development of cardiovascular diseases. In diabetes, the adipocyte microenvironment is characterized by hyperglycemia and inflammation, resulting in high levels of GSLs. Therefore, we sought to assess the GSL content in extracellular vesicles derived from the adipose tissues (adiposomes) of obese-diabetic (OB-T2D) subjects and their impact on endothelial cell function. To this end, endothelial cells were exposed to adiposomes isolated from OB-T2D versus healthy subjects. Cells were assessed for caveolar integrity and related signaling, such as Src-kinase and caveolin-1 (cav-1) phosphorylation, and functional pathways, such as endothelial nitric oxide synthase (eNOS) activity. Compared with adiposomes from healthy subjects, OB-T2D adiposomes had higher levels of GSLs, especially LacCer and GM3; they promoted cav-1 phosphorylation coupled to an obvious loss of endothelial surface caveolae and induced eNOS-uncoupling, peroxynitrite generation, and cav-1 nitrosylation. These effects were abolished by Src kinase inhibition and were not observed in GSL-depleted adiposomes. At the functional levels, OB-T2D adiposomes reduced nitric oxide production, shear response, and albumin intake in endothelial cells and impaired flow-induced dilation in healthy arterioles. In conclusion, OB-T2D adiposomes carried a detrimental GSL cargo that disturbed endothelial caveolae and the associated signaling.


Subject(s)
Diabetes Mellitus, Type 2 , Vascular Diseases , Humans , Caveolae/metabolism , Endothelial Cells/metabolism , Lipid Droplets/metabolism , Signal Transduction , src-Family Kinases/metabolism , Vascular Diseases/metabolism , Diabetes Mellitus, Type 2/metabolism
3.
Children (Basel) ; 10(2)2023 Jan 18.
Article in English | MEDLINE | ID: mdl-36832307

ABSTRACT

INTRODUCTION: Different robotic systems have been used widely in human surgery since 2000, but pediatric patients require some features that are lacking in the most frequently used robotic systems. HYPOTHESIS: The Senhance® robotic system is a safe and an effective device for use in infants and children that has some advantages over other robotic systems. METHODS: All patients between 0 and 18 years of age whose surgery was amenable to laparoscopy were offered enrollment in this IRB-approved study. We assessed the feasibility, ease and safety of using this robotic platform in pediatric patients including: set-up time, operative time, conversions, complications and outcomes. RESULTS: Eight patients, ranging from 4 months to 17 years of age and weighing between 8 and 130 kg underwent a variety of procedures including: cholecystectomy (3), inguinal herniorrhaphy (3), orchidopexy for undescended testes (1) and exploration for a suspected enteric duplication cyst (1). All robotic procedures were successfully performed. The 4-month-old (mo), 8 kg patient underwent an uneventful robotic exploration in an attempt to locate a cyst that was hidden in the mesentery at the junction of the terminal ileum and cecum, but ultimately the patient required an anticipated laparotomy to palpate the cyst definitively and to excise it completely. There was no blood loss and no complications. Robotic manipulation with the reusable 3 mm instruments proved successful in all cases. CONCLUSIONS: Our initial experience with the Senhance® robotic platform suggests that this is a safe and effective device for pediatric surgery that is easy to use, and which warrants continued evaluation. Most importantly, there appears to be no lower age or weight restrictions to its use.

4.
Surg Endosc ; 37(3): 2003-2013, 2023 03.
Article in English | MEDLINE | ID: mdl-36282359

ABSTRACT

BACKGROUND: The utilization of the robot for inguinal hernia repairs has increased in the past years. The new Da Vinci Single Port (SP) system provides the benefits of single-incision procedures and might overcome the technical difficulties of previous single-incision techniques. The aim of this study was to evaluate the safety and feasibility of the SP transabdominal preperitoneal inguinal hernia repair (SP-TAPP) and compare its outcomes to the robotic multiport technique (MP-TAPP). METHODS: A prospective cohort of patients who underwent a robotic SP-TAPP and MP-TAPP between 2012 and 2022 was analyzed. Primary endpoints were same-day discharge, morbidity, and inguinal recurrence rates. Secondary endpoints included conversion, operative time, port-site incisional hernia, and chronic pain. RESULTS: MP-TAPP and SP-TAPP were performed in 378 (81.3%) and 87 (18.7%) patients, respectively. Demographics were similar between groups. There were no conversions or intraoperative complications. Mean operative (MP-TAPP: 93.2 vs. SP-TAPP: 78.1 min, p = 0.003) and recovery time (MP-TAPP: 160.8 vs SP-TAPP: 112.6 min, p < 0.001) were significantly shorter in the SP group. Same-day discharge rate was higher (MP-TAPP: 86.5% vs. SP-TAPP: 97.7%, p = 0.001) after SP-TAPP; 30-day morbidity, readmissions, and chronic pain rates were similar between groups. After a mean follow-up of 30.6 months for MP-TAPP and 13.3 months for SP-TAPP, inguinal hernia recurrence and port-site incisional rates were similar between groups. CONCLUSION: Robotic SP-TAPP is safe and feasible. When compared to MP-TAPP, it showed similar postoperative morbidity, higher same-day discharge rates, and a quicker postoperative recovery. Further studies are needed to confirm the benefits of the SP platform.


Subject(s)
Chronic Pain , Hernia, Inguinal , Laparoscopy , Robotic Surgical Procedures , Robotics , Humans , Laparoscopy/methods , Robotic Surgical Procedures/adverse effects , Robotic Surgical Procedures/methods , Prospective Studies , Hernia, Inguinal/surgery , Chronic Pain/etiology , Chronic Pain/surgery , Herniorrhaphy/methods , Treatment Outcome , Surgical Mesh
5.
Updates Surg ; 75(1): 31-39, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36205829

ABSTRACT

Major bile duct injuries (BDIs) may require complex surgical repairs that are usually performed with a conventional open approach. This study aims to analyze current evidence concerning the safety and the outcomes of the minimally invasive (MI) approach for biliary anastomosis in post-cholecystectomy BDIs. A systematic search of MEDLINE, Embase, and Web-Of-Science indexed studies involving MI (laparoscopic or robotic) biliary anastomosis in patients with iatrogenic BDIs was performed. The quality of the studies was assessed using the MINORS criteria. A total of 13 studies involving 198 patients were included. One hundred and twenty-five patients (63.1%) underwent a laparoscopic biliary anastomosis, while 73 (36.1%) received an analogue robotic procedure. All the included BDIs were types D and E (E1-E5). The mean OT varied between 190 and 330 (mean = 227) minutes. Ten studies reported the mean intraoperative blood loss that ranged between 50 and 252 (mean = 135.9) mL. No conversions occurred in the robotic series, while four patients required conversion to open surgery among the laparoscopic ones. The mean length of postoperative hospital stay was 6.3 days. The reported overall morbidity was similar among the robotic and laparoscopic series. During the follow-up period, no surgery-related mortality occurred. A growing number of referral centers are showing the safety and feasibility of the MI approach for biliary anastomosis in patients with major BDIs. Further prospective comparative studies are needed to draw more definitive conclusions.


Subject(s)
Cholecystectomy, Laparoscopic , Humans , Cholecystectomy, Laparoscopic/adverse effects , Cholecystectomy, Laparoscopic/methods , Bile Ducts/surgery , Bile Ducts/injuries , Gallbladder/surgery , Anastomosis, Surgical , Iatrogenic Disease , Retrospective Studies
6.
Int J Mol Sci ; 23(22)2022 Nov 19.
Article in English | MEDLINE | ID: mdl-36430854

ABSTRACT

Vitamin D (VD) deficiency is a hallmark of obesity and vascular dysfunction. We sought to test the hypothesis that VD deficiency may contribute to obesity-related vascular dysfunction by inducing adipokine hypomethylation and augmented expression. To this end, we collected blood and adipose tissues (ATs) from a cohort of 77 obese participants who were classified as having mild, moderate, or severe VD deficiency. The body composition, vascular reactivity, cardiometabolic profiles, and DNA methylation of 94 inflammation-related adipokines were measured. Our results show that higher degrees of VD deficiency were associated with lower DNA methylation and induced the expression of inflammatory adipokines such as B-cell lymphoma 6 (BCL6), C-X-C Motif Chemokine Ligand 8 (CXCL8), histone deacetylase 5 (HDAC5), interleukin 12A (IL12A), and nuclear factor κB (NFκB) in the ATs. They were also associated with higher BMI and total and visceral fat mass, impaired insulin sensitivity and lipid profiles, AT hypoxia, and higher concentrations of circulating inflammatory markers. Moderate and severe VD deficiency correlated with impaired vasoreactivity of the brachial artery and AT-isolated arterioles, reduced nitric oxide generation, and increased arterial stiffness. In a multivariate regression analysis, the VD deficiency level strongly predicted the adipokine methylation score, systemic inflammation, and microvascular dysfunction. In conclusion, our findings suggest that VD deficiency is a possible contributor to obesity-related adipokine hypomethylation, inflammation, and vascular dysfunction.


Subject(s)
DNA Methylation , Vitamin D Deficiency , Humans , Vitamin D Deficiency/complications , Vitamin D Deficiency/genetics , Vitamin D Deficiency/metabolism , Adipose Tissue/metabolism , Obesity/complications , Obesity/genetics , Obesity/metabolism , Inflammation/metabolism , Adipokines/metabolism , DNA/metabolism
7.
Obes Surg ; 32(12): 3900-3907, 2022 12.
Article in English | MEDLINE | ID: mdl-36194348

ABSTRACT

PURPOSE: Same-day discharge (SDD) after bariatric surgery is gaining popularity. We aimed to analyze the safety of SDD after Roux-en-Y gastric bypass (RYGB) and compare its outcomes to inpatients discharged on postoperative days 1-2. MATERIALS AND METHODS: We performed a retrospective analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database for the period 2015-2020. Patients who underwent primary laparoscopic RYGB and were discharged the same day of the operation (SDD-RYGB) and inpatients discharged on postoperative days 1-2 (In-RYGB) were compared. Primary outcomes of interest were overall morbidity, serious morbidity, readmission, reoperation, intervention, and mortality rates. RESULTS: A total of 167,188 patients were included; 2156 (1.3%) SDD-RYGB and 165,032 (98.7%) In-RYGB. Mean age (SDD-RYGB: 44.5 vs. In-RYGB: 44.6 years), proportion of females (SDD-RYGB: 81.4% vs. In-RYGB: 80.6%), and mean body mass index (SDD-RYGB: 45.8 vs. In-RYGB: 45.9 kg/m2) were similar between groups. Overall morbidity (SDD-RYGB: 11.3% vs. In-RYGB: 10.2%; OR: 1.2, p = 0.08), serious morbidity (SDD-RYGB: 3.1% vs. In-RYGB: 3%; OR: 1.03, p = 0.81), reoperation (SDD-RYGB: 1.4% vs. In-RYGB: 1.2%; OR: 1.16, p = 0.42), readmission (SDD-RYGB: 4.8% vs. In-RYGB: 4.8%; OR: 1.01, p = 0.89), and mortality (SDD-RYGB: 0.04% vs. In-RYGB: 0.09%; OR: 0.53, p = 0.53) were comparable between groups. SDD-RYGB had lower risk of 30-day interventions (SDD-RYGB: 1.1% vs. In-RYGB: 1.6%; OR: 0.64, p = 0.04) compared to In-RYGB. CONCLUSION: Same-day discharge after RYGB seems to be safe and has comparable outcomes to admitted patients. Standardized patient selection criteria and perioperative management protocols are needed to further increase the safety of this practice.


Subject(s)
Bariatric Surgery , Gastric Bypass , Obesity, Morbid , Female , Humans , Gastric Bypass/methods , Patient Discharge , Obesity, Morbid/surgery , Quality Improvement , Retrospective Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Bariatric Surgery/methods , Accreditation
8.
Int J Med Robot ; 18(6): e2453, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35962708

ABSTRACT

BACKGROUND: We aim to analyse the safety and feasibility of the DaVinci Single Port (SP) platform in general surgery. METHODS: A prospective series of robotic SP transabdominal pre-peritoneal inguinal hernia repairs (SP-TAPP) and cholecystectomies (SP-C) (off-label) were analysed. Primary endpoints were safety and feasibility defined by the need for conversion and incidence of perioperative complications. RESULTS: A total of 225 SP procedures were performed; 84 (37.3%) SP-TAPP (70 unilateral, 7 bilateral), and 141 (62.7%) SP-C. There were no conversions or additional ports placed. Mean console time was 17.6, 31.9, and 54 min for SP-C, unilateral, and bilateral SP-TAPP, respectively. There was no mortality, intraoperative or major postoperative complications. Mean LOS was 2.7 h for elective SP-TAPP and 2.3 h for SP-C. CONCLUSION: Robotic SP surgery is safe and feasible for two of the most performed general surgery operations. Further experience might allow expanding the applications of robotic single-incision surgery for other procedures.


Subject(s)
Hernia, Inguinal , Laparoscopy , Robotic Surgical Procedures , Robotics , Humans , Robotic Surgical Procedures/methods , Hernia, Inguinal/surgery , Cholecystectomy , Postoperative Complications , Laparoscopy/methods
9.
Int J Med Robot ; 18(6): e2437, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35754403

ABSTRACT

INTRODUCTION: To date, no anti-reflux operations have been reported with the new da Vinci Single-Port (single port (SP)) robotic platform. We aimed to describe this novel surgical approach and evaluate its safety and feasibility. METHODS: All robotic SP operations were performed under an Institutional Review Board approved protocol. RESULTS: Two patients underwent robotic SP anti-reflux surgery through a single incision of 2.7 cm (one Nissen-fundoplication and one re-Redo Nissen-fundoplication). The mean docking-time was 2.5 (2-3) minutes and mean console-time was 147 (119-155) minutes. No additional ports were needed, and no intraoperative complications occurred. Patients tolerated a soft diet on postoperative day 1 and were discharged on POD-2 and 3. CONCLUSION: Robotic SP anti-reflux surgery appears to be safe and feasible. This platform offers similar advantages to the multiport robotic surgery, while adding lower invasiveness and an improved cosmesis. Further studies are needed to confirm our results and evaluate long-term outcomes of this surgical approach.


Subject(s)
Gastroesophageal Reflux , Laparoscopy , Robotic Surgical Procedures , Robotics , Humans , Robotic Surgical Procedures/methods , Robotics/methods , Fundoplication , Laparoscopy/methods
10.
Langenbecks Arch Surg ; 407(4): 1721-1726, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35583834

ABSTRACT

BACKGROUND: Despite the high success rate associated with Heller myotomy in the treatment of primary achalasia, symptom persistence or relapse occurs in approximately 10-20% of patients. Unfortunately, the ideal treatment after failed myotomy is not well established yet. We present a didactical video with a stepwise technique to perform a robotic revisional procedure after failed Heller myotomy. METHODS: In this report, each surgical step is thoroughly described and visually represented with useful technical tips that might help in improving surgical results of revisional Heller myotomy. RESULTS: In patients with previous surgical myotomy, the robotic platform with its high-definition magnified view and EndoWrist instruments allow for a safe and precise redo surgical myotomy. CONCLUSIONS: Despite its improved surgical capabilities, the role of robotic redo Heller myotomy in the treatment algorithm of patients with recurrent symptoms after failed surgical myotomy should be further explored.


Subject(s)
Esophageal Achalasia , Heller Myotomy , Laparoscopy , Robotic Surgical Procedures , Robotics , Esophageal Achalasia/surgery , Fundoplication/methods , Heller Myotomy/methods , Humans , Laparoscopy/methods , Recurrence , Robotic Surgical Procedures/methods , Treatment Outcome
11.
Front Surg ; 9: 880044, 2022.
Article in English | MEDLINE | ID: mdl-35433802

ABSTRACT

Background: With the rising number of bariatric surgeries performed annually, there has also been an increase in revisional bariatric surgeries (RBS). The aim of this study is to evaluate the safety and postoperative outcomes of RBS performed with a minimally invasive approach. Methods: Retrospective analysis on a prospectively collected database of patients who underwent minimally invasive RBS between 2012 and 2019. Primary endpoints were conversion rate, major morbidity, mortality, and 30-day reoperation rate. Comparative analysis of laparoscopic adjustable gastric banding (LAGB) conversion to sleeve gastrectomy (SG) vs. conversion to Roux-en-Y gastric bypass (RYGB) was performed. Results: A total of 221 patients underwent minimally invasive RBS, 137 (62%) laparoscopically and 84 (38%) robotically. The most common RBS were LAGB to SG (59.3%) and LAGB to RYGB conversions (16.7%). The main indication was weight loss failure (88.7%). Conversion rate, major morbidity, and mortality were 0.9, 3.2, and 0.4%, respectively. Urgent reoperation was required in 3.2% of cases. Total weight loss at 1 and 2-years follow- were 14.3 and 17.3%, respectively. Comparative analysis of LAGB conversion to SG vs. RYGB showed similar major morbidity (SG: 2.3% vs. RYGB 0%, p = 1). Greater total weight loss was achieved in LAGB to RYGB conversions at 1-year (SG: 14.8% vs. RYGB 25.3%, p < 0.001). Conclusions: Minimally invasive RBS can be performed safely in a broad patient population with low conversion and complication rates, and improved weight loss outcomes. LAGB to RYGB conversions are associated with greater weight loss. Further randomized trials are needed to draw more conclusive recommendations.

12.
J Clin Med ; 11(7)2022 Mar 25.
Article in English | MEDLINE | ID: mdl-35407426

ABSTRACT

Bariatric surgery has been demonstrated to be effective in achieving significant weight loss and remission of obesity-related comorbidities. However, a percentage of patients fail to lose enough weight, regain weight, or experience postoperative complications, requiring additional interventions. Revisional bariatric surgeries (RBS) involve the wide spectrum of procedures that aim to treat complications of the index operation or achieve further weight loss. These are technically challenging procedures due to adhesions of the internal organs, reduced working space, and a distorted anatomy. Indications, timing, and type of operation for RBS are not standardized, and there is no consensus on the best surgical approach. Some authors claim a robotic platform could be advantageous in these types of procedures that are performed in reduced, deep operating fields, or those requiring precision and accuracy. This review examines the most current and representative literature on the outcomes of robot-assisted RBS. Included studies demonstrate the safety and feasibility of the robotic approach for RBS. However, long operative times and high costs remain major drawbacks of the device. Finally, if we consider that many centers have not yet completed the learning curve for robot-assisted RBS, the potential for improved outcomes seems promising.

13.
Surg Oncol ; 40: 101704, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34995973

ABSTRACT

BACKGROUND: Minimally invasive resection of gastrointestinal stromal tumors (GIST) results in faster recovery and similar oncological safety when compared to conventional approach [1-3]. The new robotic Single Port platform (Da Vinci SP) could help decreasing invasiveness while overcoming technical limitations of previous single incision surgical approaches [4]. METHODS: A 69-year-old male was treated for a 3 cm non-ulcerated GIST in the anterior wall of the proximal gastric body. RESULTS: A robotic partial gastric resection was performed. The Da Vinci SP platform, which hosts three multi jointed, wristed instruments and a 3D HD articulating scope was used. The camera and instruments were introduced in the abdominal cavity through a 25 mm multichannel port. The lesion was identified in the lesser curvature at the level of the body, approximately 3 cm above the incisura. The gastric wall was resected en-bloc with the tumor using a combination of monopolar hook and bipolar forceps. The lesion was lifted using the third robotic arm and was not manipulated during the dissection. The gastric defect was closed with two running sutures of polydioxanone 3/0. Operative time was 82 minutes. Postoperative course was uneventful, and the patient was discharged home on postoperative day 2 with adequate pain control. Histopathology analysis found a 2.3 × 2 cm low grade GIST. CONCLUSIONS: Robotic SP partial gastrectomy is safe and feasible in patients with gastric GIST. The robotic SP approach might help expanding the indications of previous single incision techniques.


Subject(s)
Gastrectomy/methods , Gastrointestinal Stromal Tumors/surgery , Robotic Surgical Procedures/methods , Stomach Neoplasms/surgery , Aged , Humans , Male
14.
Obes Surg ; 32(4): 962-969, 2022 04.
Article in English | MEDLINE | ID: mdl-35060023

ABSTRACT

BACKGROUND: Same-day discharge after sleeve gastrectomy (SG) is gaining popularity. We aimed to determine risk factors associated with readmission in patients who underwent same-day discharge SG. METHODS: We performed a retrospective analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database for the period 2015-2018. Patients who underwent SG and were discharged the same day of the operation were included in the analysis. Multivariable logistic regression analysis was performed to determine risk factors for readmission. RESULTS: A total of 466,270 SG were performed during the study period; 14,624 (3.1%) patients were discharged the same day and were included in the analysis. Mean age was 43.4 (14.7-80) years and 11,718 (80.1%) were female. Mean preoperative BMI was 43.7 ± 7.4 kg/m2. Mean operative time was 58.3 ± 32.4 min. Thirty-day reoperation, reintervention, and mortality rates were 0.7%, 0.7%, and 0.1%, respectively. Readmission rates were similar in same-day discharge and inpatient SG (2.9% vs. 3%, p = 0.5). Female sex (OR 1.52, 95% CI 1.15-2.00), preoperative gastroesophageal reflux disease (OR 1.33, 95% CI 1.08-1.64), renal insufficiency (OR 3.06, 95% CI 1.01-9.32), and intraoperative drain placement (OR 1.78, 95% CI 1.37-2.31) were independent risk factors for readmission following same-day discharge SG. CONCLUSIONS: Same-day discharge SG appears to be safe and is associated with low readmission rates. However, the identification of preoperative and intraoperative variables associated with higher risk of readmission might help defining safer and more effective same-day discharge protocols.


Subject(s)
Bariatric Surgery , Gastric Bypass , Obesity, Morbid , Accreditation , Adult , Bariatric Surgery/adverse effects , Bariatric Surgery/methods , Female , Gastrectomy/adverse effects , Gastrectomy/methods , Gastric Bypass/methods , Humans , Male , Obesity, Morbid/surgery , Patient Discharge , Patient Readmission , Quality Improvement , Retrospective Studies , Risk Factors , Treatment Outcome
15.
Epigenetics ; 17(1): 93-109, 2022 01.
Article in English | MEDLINE | ID: mdl-33487124

ABSTRACT

Obesity is a major risk factor for cardiovascular disease. Blood-detected epigenetic profiles may serve as non-invasive clinically relevant biomarkers. Therefore, we investigated DNA methylation of genes involved in inflammation in peripheral blood of obese subjects and lean controls and their correlation with cardiometabolic measurements. We obtained blood and adipose tissue (AT) samples from bariatric patients (n = 24) and control adults (n = 24). AT-isolated arterioles were tested for flow-induced dilation (FID) and production of nitric oxide (NO) and reactive oxygen species (ROS). Brachial artery flow-mediated dilation (FMD) was measured via doppler ultrasound. Promoter methylation of 94 genes involved in inflammation and autoimmunity were analysed in whole-blood DNA in relation to vascular function and cardiometabolic risk factors. 77 genes had ahigher methylated fraction in the controls compare obese subjects and 28 proinflammatory genes were significantly hypomethylated in the obese individuals; on top of these genes are CXCL1, CXCL12, CXCL6, IGF2BP2, HDAC4, IL12A, and IL17RA. Fifteen of these genes had significantly higher mRNA in obese subjects compared to controls; on top of these genes are CXCL6, TLR5, IL6ST, EGR1, IL15RA, and HDAC4. Methylation % inversely correlated with BMI, total fat %, visceral fat%, blood pressure, fasting plasma insulin, serum IL6 and C-reactive protein, arteriolar ROS, and alcohol consumption and positive correlations with lean %, HDL, plasma folate and vitamin B12, arteriolar FID and NO production, and brachial FMD. Our results suggest that vascular dysfunction in obese adults may be attributed to asystemic hypomethylation and over expression of the immune-related genes.


Subject(s)
Autoimmunity , DNA Methylation , Inflammation , Obesity, Morbid , Adult , Autoimmunity/genetics , Brachial Artery/physiology , Humans , Inflammation/genetics , Obesity, Morbid/genetics , Obesity, Morbid/metabolism , RNA-Binding Proteins
16.
Biomedicines ; 9(8)2021 Aug 18.
Article in English | MEDLINE | ID: mdl-34440238

ABSTRACT

Obesity is characterized by the accumulation of dysfunctional adipose tissues, which predisposes to cardiometabolic diseases. Our previous in vitro studies demonstrated a role of hypoxia in inducing adipokine hypomethylation in adipocytes. We sought to examine this mechanism in visceral adipose tissues (VATs) from obese individuals and its correlation with cardiometabolic risk factors. We propose an involvement of the hypoxia-inducible factor, HIF1α, and the DNA hydroxymethylase, TET1. Blood samples and VAT biopsies were obtained from obese and non-obese subjects (n = 60 each) having bariatric and elective surgeries, respectively. The analyses of VAT showed lower vascularity, and higher levels of HIF1α and TET1 proteins in the obese subjects than controls. Global hypomethylation and hydroxymethylation were observed in VAT from obese subjects along with promoter hypomethylation of several pro-inflammatory adipokines. TET1 protein was enriched near the promotor of the hypomethylated adipokines. The average levels of adipokine methylation correlated positively with vascularity and arteriolar vasoreactivity and negatively with protein levels of HIF1α and TET1 in corresponding VAT samples, serum and tissue inflammatory markers, and other cardiometabolic risk factors. These findings suggest a role for adipose tissue hypoxia in causing epigenetic alterations, which could explain the increased production of adipocytokines and ultimately, vascular dysfunction in obesity.

17.
J Cardiovasc Dev Dis ; 9(1)2021 Dec 28.
Article in English | MEDLINE | ID: mdl-35050217

ABSTRACT

CD147 is a glycoprotein that stimulates the production of matrix metalloproteinases (MMPs), known contributors to cardiovascular risk. The activity of CD147 protein depends on its glycosylation. However, it is unclear whether CD147 protein expression or glycosylation are influenced by the diabetic milieu characterized by hyperglycemia and abundant glycation-end-products (AGEs). We examined the circulating and visceral adipose tissue (VAT) levels of CD147 and their correlation with vascular function in obese, obese diabetic, and non-obese controls (n = 40, each). The circulating levels of CD147 and the glycosylated CD147 protein in VAT were considerably higher in obese, particularly obese diabetic subjects compared to controls. Obese diabetics had the lowest brachial and arteriolar vasoreactivity and the highest carotid pulse-wave velocity (PWV, a measure of arterial stiffness) among the three groups. CD147 correlated positively with body mass index (BMI), total and visceral fat mass, PWV, and plasma levels of glucose, insulin, MMPs, and AGEs and negatively with brachial artery and VAT-arteriolar vasoreactivity and nitric oxide production. Multivariate regression revealed that BMI, body fat mass, insulin, and glucose levels significantly predicted CD147. Our data suggest that higher levels of CD147 in obese subjects, particularly those with diabetes, are linked to vascular dysfunction and several cardiometabolic risk factors.

18.
Nutrients ; 12(7)2020 Jul 07.
Article in English | MEDLINE | ID: mdl-32645905

ABSTRACT

There is a high prevalence of hyperhomocysteinemia that has been linked to high cardiovascular risk in obese individuals and could be attributed to poor nutritional status of folate and vitamin B12. We sought to examine the association between blood homocysteine (Hcy) folate, and vitamin B12 levels and vascular dysfunction in morbidly obese adults using novel ex vivo flow-induced dilation (FID) measurements of isolated adipose tissue arterioles. Brachial artery flow-mediated dilation (FMD) was also measured. Subcutaneous and visceral adipose tissue biopsies were obtained from morbidly obese individuals and non-obese controls. Resistance arterioles were isolated in which FID, acetylcholine-induced dilation (AChID), and nitric oxide (NO) production were measured in the absence or presence of the NO synthase inhibitor, L-NAME, Hcy, or the superoxide dismutase mimetic, TEMPOL. Our results demonstrated that plasma Hcy concentrations were significantly higher, while folate, vitamin B12, and NO were significantly lower in obese subjects compared to controls. Hcy concentrations correlated positively with BMI, fat %, and insulin levels but not with folate or vitamin B12. Brachial and arteriolar vasodilation were lower in obese subjects, positively correlated with folate and vitamin B12, and inversely correlated with Hcy. Arteriolar NO measurements and sensitivity to L-NAME were lower in obese subjects compared to controls. Finally, Hcy incubation reduced arteriolar FID and NO sensitivity, an effect that was abolished by TEMPOL. In conclusion, these data suggest that high concentrations of plasma Hcy and low concentrations of folate and vitamin B12 could be independent predictors of vascular dysfunction in morbidly obese individuals.


Subject(s)
Folic Acid/blood , Hyperhomocysteinemia/epidemiology , Nitric Oxide/metabolism , Obesity, Morbid/epidemiology , Vascular Diseases/epidemiology , Vitamin B 12/blood , Adult , Alcohol Drinking/epidemiology , Arterioles , Bariatric Surgery/methods , Brachial Artery , Female , Folic Acid Deficiency/epidemiology , Homocysteine/blood , Humans , Male , Nutritional Status , Obesity, Morbid/surgery , Vitamin B 12 Deficiency/epidemiology
19.
Surg Endosc ; 34(6): 2758-2762, 2020 06.
Article in English | MEDLINE | ID: mdl-31953732

ABSTRACT

BACKGROUND: RPD (Robotic pancreatoduodenectomy) was first performed by P. C. Giulianotti in 2001 (Arch Surg 138(7):777-784, 2003). Since then, the complexity and lack of technique standardization has slowed down its widespread utilization. RPD has been increasingly adopted worldwide and in few centres is the preferred apporached approach by certain surgeons. Some large retrospective series are available and data seem to indicate that RPD is safe/feasible, and a valid alternative to the classic open Whipple. Our group has recently described a standardized 17 steps approach to RPD (Giulianotti et al. Surg Endosc 32(10): 4329-4336, 2018). Herin, we present an educational step-by-step surgical video with short technical/operative description to visually exemplify the RPD 17 steps technique. METHODS: The current project has been approved by our local Institutional Review Board (IRB). We edited a step-by-step video guidance of our RPD standardized technique. The data/video images were collected from a retrospective analysis of a prospectively collected database (IRB approved). The narration and the images describe hands-on operative "tips and tricks" to facilitate the learning/teaching/evaluation process. RESULTS: Each of the 17 surgical steps is visually represented and explained to help the in-depth understanding of the relevant surgical anatomy and the specific operative technique. CONCLUSIONS: Educational videos descriptions like the one herein presented are a valid learning/teaching tool to implement standardized surgical approaches. Standardization is a crucial component of the learning curve. This approach can create more objective and reproducible data which might be more reliably assessed/compared across institutions and by different surgeons. Promising results are arising from several centers about RPD. However, RPD as gold standard-approach is still a matter of debate. Randomized-controlled studies (RCT) are required to better validate the precise role of RPD.


Subject(s)
Pancreaticoduodenectomy/education , Robotic Surgical Procedures/education , Surgeons/education , Chicago , Databases, Factual , Humans , Learning Curve , Pancreaticoduodenectomy/methods , Pancreaticoduodenectomy/standards , Practice Guidelines as Topic , Prospective Studies , Retrospective Studies , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/standards
20.
Gastrointest Tumors ; 5(3-4): 68-76, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30976577

ABSTRACT

BACKGROUND: Various technical improvements have decreased the morbidity and mortality after pancreaticoduodenectomy. However, postoperative pancreatic fistula (POPF) is the most feared complication, and the ideal technique for pancreatic reconstruction is undetermined. The aim of this study was to identify the risk factors and incidence of POPF with different types of pancreatic stump management after robot-assisted pancreaticoduodenectomy (RAPD). MATERIALS AND METHODS: This study is a retrospective review of consecutive patients who underwent RAPD at the University of Illinois Hospital and Health Sciences System between September 2007 and January 2016. The cohort was divided based on the type of pancreatic stump management: pancreatic duct occlusion with cyanoacrylate glue (CG), pancreaticojejunostomy (PJ), posterior pancreaticogastrostomy (PPG), and transgastric pancreaticogastrostomy (TPG). RESULTS: The cohort included 69 patients: pancreatic duct occlusion with CG (n = 18), PJ (n = 12), PPG (n = 11), and TPG (n = 28). Pancreatic duct diameter < 3 mm and duct occlusion with CG were identified as risk factors for POPF (p < 0.05). The incidence of POPF was lower when TPG and PJ were performed (p < 0.001). CONCLUSIONS: Reconstruction with PJ and TPG had better results compared to pancreatic duct occlusion with CG and PPG. However, TPG was the technique of choice and showed comparable results to PJ.

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