High Body Mass Index Patients Research Articles

Transcatheter aortic valve implantation in patients with uninterrupted vitamin K antagonists.

Bridging of vitamin K antagonist (VKA) with heparin is usually not promoted during interventional or surgical procedures related to increased risk of bleeding and thrombotic events but this strategy has not been evaluated during transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the rate of major bleeding and vascular complications after TAVI performed in patients with uninterrupted VKA. From January 2016 to October 2017, consecutive patients who underwent TAVI with uninterrupted VKA (International Normalized Ratio [INR]between 1.5 and 3.5) were prospectively included in a monocentric registry. TAVI was performed according to current guidelines and a 50 U/kgbolus of heparin was injected at the beginning of the procedure for all patients. Vascular and bleeding complications were assessed using the Valve Academic Research Consortium 3 (VARC3) and the Bleeding Academic Research Consortium (BARC) definitions at a 30-day follow-up. A total of 88 patients were included with a median age of 84 years (81.8-87.0), 42% being female. The median society of thoracic surgeons score was 5.1 (4.1-7.5), the median CHADS2-VAScwas 5.5 (5-6)and 60.2% had a chronic kidney failure. Median INR at the time of implantation was 2.1 (1.8-2.6). The main VKA indication was atrial fibrillation. Transfemoral access was used in 88.6% of the patients. Major bleeding (BARC ≥ 3b) occurred in five patients (5.7%) and major vascular complications occurred in seven patients (8.0%). At 1month follow-up, major bleeding (BARC ≥ 3) or vascular complications occurred in 10 patients (11.4%). In patients with major bleeding peripheral arterial disease (RR = 10.95; 95% confidence interval (CI) 1.63-73.75; p = 0.014) and carotid access (RR = 8.56; 95% CI 1.19-1.51; p = 0.033) were more common. INR > 2.5 was significantly associated with vascular complications (RR = 7.14; 95% CI 1.29-39.63; p = 0.025). At 30 days, mortality and stroke rates were 2.3% and 4.5%, respectively. TAVI with uninterrupted VKA treatment seems feasible and safe with a low risk of major bleeding and vascular complications in this first single-center experience. Particular caution is advocated in high body mass index patients and to keep INR < 2.5.

High Survivorship of a Modular Titanium Baseplate Independent of Body Mass Index and Malalignment.

Tibial component aseptic loosening remains problematic in primary total knee arthroplasty (TKA). Influential factors include component design, metallurgy, and cement technique. Additionally, reports advocate for longer tibial stem fixation in high body mass index (BMI) patients. We have utilized a single stem length modular titanium baseplate in patients regardless of BMI, bone quality, or malalignment. We report the survivorship of this implant with focus on the impact of elevated BMI and postoperative malalignment. We retrospectively reviewed patients who underwent TKA with a single modular titanium baseplate with a cruciate-shaped keel between 2004 and 2018. In total, 2,949 TKAs with a minimum of 1-year follow-up were included. The mean follow-up was 7 years. The primary outcome was component failure stratified by BMI and postoperative malalignment. High viscosity cement was utilized in all cases. Chi-squared and t-tests were used to compare outcome variables across groups. Eighty-five implants (2.8%) were revised with 46 (1.6%) for aseptic loosening. Failure was not associated with BMI, gender, American Society of Anesthesiologists class, or Charlson Comorbidity Index. There was no difference in failure rate by BMI (P= .26) or by malalignment (outside of 3° from neutral mechanical axis) (P= .67). Age was associated with failure as patients with failed TKAs were younger (61 vs 65, P < .01). This design of a specific modular titanium base plate with a cruciate-shaped keel and grit blast surface demonstrated 99% survivorship regardless of patient BMI or malalignment over 7-year follow-up period. Consistent cement technique with high viscosity cement indicates that component design remains an important variable impacting survivorship in TKA.

Spectral-domain OCT measurements in obesity: A systematic review and meta-analysis.

BackgroundPrevious studies proposed possible applications of spectral-domain optical coherence tomography (SD-OCT) measurements in prognosticating pathologies observed in overweight/obesity, including ocular, vascular, and neurologic consequences. Therefore, we conducted a systematic review and meta-analysis to investigate the changes in the in SD-OCT measurements of the patients with higher body mass index (BMI) compared to normal weight individuals.Materials and methodsWe conducted a systematic search on PubMed, Scopus, and Embase. The search results underwent two-phase title/abstract and full-text screenings. We then analyzed SD-OCT measurements differences in patients with high BMI and controls, and performed meta-regression, sub-group analysis, quality assessment, and publication bias assessment. The measurements included macular thickness, cup to disc ratio, ganglion cell-inner plexiform layer (GC-IPL) and its sub-sectors, RNFL and peripapillary RNFL (pRNFL) and their sub-layers, and choroidal thickness and its sub-sectors.Results19 studies were included in this meta-analysis accounting for 1813 individuals, 989 cases and 824 controls. There was an overall trend towards decreased thickness in high BMI patients, but only two measurements reached statistical significance: temporal retinal nerve fiber layer (RNFL) (Standardized mean difference (SMD): -0.33, 95% confidence interval (CI): -0.53 to -0.14, p<0.01) and the choroidal region 1.0 mm nasal to fovea (SMD: -0.38, 95% CI: -0.60 to -0.16, p<0.01).ConclusionSome ocular layers are thinner in patients with higher BMI than the controls. These SD-OCT measurements might correlate with adverse events related to increased body weight and have prognostic abilities. As SD-OCT is a robust, rapid and non-invasive tool, future guidelines and studies are needed to evaluate the possibility of their integration into care of the patients with obesity.

Open Abdominal Aortic Aneurysm Surgery and Renal Dysfunction; Association of Demographic and Clinical Variables with Proximal Clamp Location

While cross-clamp site is a known risk factor for postoperative acute and chronic renal dysfunction following open abdominal aortic aneurysm surgery (AAA), the additive impact of patient demographic and clinical factors is lacking. In this study, we investigated the impact of body mass index (BMI), surgical duration and aneurysm diameter on the association between proximal cross-clamp location and postoperative renal dysfunction. In this study, we conducted a retrospective analysis of 4,197 patients undergoing open AAA surgery between 2011 and 2018 using data housed in the American College of Surgeons National Safety Quality Improvement Program (ACS-NSQIP) database. The primary outcome was renal dysfunction, which was defined as patients requiring dialysis within 30days or patients with ≥2mg/dL rise in creatinine from baseline. We assessed the incidence of renal dysfunction with regard to clamp location and subsequently used multivariable logistic regression to assess clinical and demographic factors associated with renal dysfunction. We used a regression model to plot the association of BMI, surgical duration, and aneurysm diameter with an adjusted probability of postoperative acute and chronic renal dysfunction for individual cross-clamp locations. Of the 4,197 patients analyzed, 405 patients (9.6%) developed renal dysfunction within 30 days with 287 patients requiring dialysis. Patients with supraceliac clamp location had the highest incidence of renal dysfunction (20.4%). Our data showed a significant association of renal dysfunction with higher BMI patients [OR 1.04 (1.02, 1.07), P=0.001], longer operative times [OR1.01 (1.01, 1.02), P<0.001], clamp location between the superior mesenteric artery (SMA) and renal artery [OR 1.80 (1.17, 2.78), P=0.007] and supraceliac clamp location [OR 2.47 (1.62, 3.76), P<0.001]. The incidence of renal dysfunction increases with suprarenal clamps. Patients with higher BMI, longer operative times, and increasing aneurysm diameter, and a suprarenal clamp have a significantly increased risk of renal dysfunction compared to those who also had a suprarenal clamp but lower BMI, shorter operative times and smaller aneurysm diameter.

Assessment of Clinical, Tissue, and Cell-Level Metrics Identify Four Biologically Distinct Knee Osteoarthritis Patient Phenotypes.

ObjectiveClinical heterogeneity of primary osteoarthritis (OA) is a major challenge in understanding pathogenesis and development of targeted therapeutic strategies. This study aims to (1) identify OA patient subgroups phenotypes and (2) determine predictors of OA severity and cartilage-derived stem/progenitor concentration using clinical-, tissue-, and cell- level metrics.DesignCartilage, synovium (SYN) and infrapatellar fatpad (IPFP) were collected from 90 total knee arthroplasty patients. Clinical metrics (patient demographics, radiograph-based joint space width (JSW), Kellgren and Lawrence score (KL)), tissue metrics (cartilage histopathology grade, glycosaminoglycans (GAGs)) and cell-based metrics (cartilage-, SYN-, and IPFP-derived cell concentration ([Cell], cells/mg), connective tissue progenitor (CTP) prevalence (PCTP, CTPs/million cells plated), CTP concentration, [CTP], CTPs/mg)) were assessed using k-mean clustering and linear regression model.ResultsFour patient subgroups were identified. Clusters 1 and 2 comprised of younger, high body mass index (BMI) patients with healthier cartilage, where Cluster 1 had high CTP in cartilage, SYN, and IPFP, and Cluster 2 had low [CTP] in cartilage, SYN, and IPFP. Clusters 3 and 4 comprised of older, low BMI patients with diseased cartilage where Cluster 3 had low [CTP] in SYN, IPFP but high [CTP] in cartilage, and Cluster 4 had high [CTP] in SYN, IPFP but low [CTP] in cartilage. Age (r = 0.23, P = 0.026), JSW (r = 0.28, P = 0.007), KL (r = 0.26, P = 0.012), GAG/mg cartilage tissue (r = −0.31, P = 0.007), and SYN-derived [Cell] (r = 0.25, P = 0.049) were weak but significant predictors of OA severity. Cartilage-derived [Cell] (r = 0.38, P < 0.001) and PCTP (r = 0.9, P < 0.001) were moderate/strong predictors of cartilage-derived [CTP].ConclusionInitial findings suggests the presence of OA patient subgroups that could define opportunities for more targeted patient-specific approaches to prevention and treatment.

Superficial Thinning of the DIEP Flap: A Safe Option to Achieve an Aesthetic Reconstructed Breast in the Obese Patient.

Abdominal flap-based breast reconstruction is challenging in the overweight and obese population not only because of increased donor-site complications, but also because excessive flap thickness makes inset cumbersome, requiring thinning and remodeling that frequently result in aesthetically poor outcomes. The authors started by studying 10 deep inferior epigastric artery perforator flaps with angiographic computed tomography. Then, they prospectively performed 21 breast reconstructions using a superficial thinning technique reliant on a constant suprafascial vessel as the pedicle for the remaining deep fat and compared the rate of complications with their previous experience using traditional flap thinning techniques. All samples studied showed a suprafascial division of the main perforator. Two constant branches were identified, one coursing over the Scarpa fascia and displaying a robust network of linking vessels with the subcutaneous and subdermal plexuses. That anatomical insight was used to develop a flap-thinning technique tested on 21 consecutive high-body mass index patients. A 7-year retrospective analysis (n = 164) showed no significant correlation between body mass index and incidence of complications except for a long-term upper pole step deformity that was associated with increasing body mass index (p = 0.001). No statistically significant difference in complications was found comparing high-body mass index patients from the retrospective group (n = 72) with the superficial thinning group, but a highly suggestive difference (p = 0.061) was found regarding the avoidance of the step deformity using the superficial thinning technique. The presence of a constant suprafascial perforator branch makes superficial DIEP thinning a safe technique that facilitates inset and improves the reconstructed breast contour of obese patients. Therapeutic, IV.

P27.05 High Body Mass Index (BMI) Is Associated With Better Outcomes in Mexican Patients With Advanced Non–Small Cell Lung Cancer (NSCLC)

Population studies suggest that high body mass index (BMI) correlates with a reduced risk for death from some cancer like melanoma. The aim of our study was to evaluate the influence of high BMI on long-term overall survival (OS) in Mexican patients with advanced NSCLC. We evaluated 146 patients with advanced lung cancer (IIIB and IV) who were treated for locally advanced NSCLC. Demographic and clinical data were collected. BMI was estimated at diagnosis in routine screening evaluation before systemic treatment. They were stratified into two BMI groups ≧30kg/m2 and <30kg/m2 . Overall survival was analyzed by BMI group. Kaplan-Meier survival analysis and the log-rank test were used to calculate OS. Univariate and multivariate analysis to identify variables associated with OS was assessed using Cox regression model Baseline patient characteristics and treatment parameters were similar between high BMI and no high patients. Among the included patients, the median age was 63.39 (range: 29-86 years), 49.2 % patients were females and 50.8 % were males. High BMI was associated with improved overall survival 38 vs 25 months p=0.047. There were no difference in overall survival between patient with overweight (25–29.9 kg/m2) and normal weight (18.5-24.9 kg/m2) counterparts ( 26 vs 25 months, p = 0.67) High BMI patients in this retrospective study had significantly improved survival relative to no high BMI patients. Our data suggest that the protective effect of obesity in locally advanced NSCLC. Additional studies are needed to clarify the mechanisms and possible concomitant factors underlying the obesity in NSCLC as dietary and lifestyle interventions.

Association between high BMI and high homocysteine levels in Chinese patients with bipolar disorder

BackgroundBipolar disorder (BD) has been associated with an increased prevalence of weight gain and abnormally elevated plasma homocysteine (Hcy) levels. However, the relationship between BMI and Hcy in BD patients has not been investigated. This study aimed to explore this relationship in Chinese patients with BD. MethodsPlasma Hcy levels, socio-demographic parameters, clinical and anthropometric data were collected from 195 BD inpatients and 84 healthy controls. The level of plasma Hcy was determined by high-performance liquid chromatography. Body mass index (BMI) was calculated by body weight divided by the square of the height. The participants were divided into a high BMI group and a low BMI group using 24 kg/m2 as a threshold. ResultsThe prevalence of high BMI was slightly elevated in BD patients in comparison to healthy controls. Patients with elevated BMI had significantly higher Hcy levels than patients with low BMI. Hcy level was an independent contributor of the occurrence of high BMI in BD patients. The level of Hcy was positively correlated with BMI in BD patients. In addition, depressive episodes of BD were positively correlated with the prevalence of high BMI and married BD patients were more likely to have high BMI levels. ConclusionsThere is a close relationship between BMI and plasma Hcy levels in patients with BD, suggesting that Hcy may be an important indicator for BD-induced weight gain. This finding provides a new avenue for weight management of BD patients and to help avoid the potential risk of cardiovascular diseases.

Impact of High Body Mass Index on Vascular and Bleeding Complications After Transcatheter Aortic Valve Implantation

Increased body mass index (BMI) is an established cardiovascular risk factor. The impact of high BMI on vascular and bleeding complications in patients undergoing transcatheter aortic valve implantation (TAVI) is not clarified. RISPEVA, a multicenter prospective database of patients undergoing TAVI stratified by BMI was used for this analysis. Patients were classified as normal or high BMI (obese and overweight) according to the World Health Organization criteria. A comparison of 30-day vascular and bleeding outcomes between groups was performed using propensity scores methods. A total of 3776 matched subjects for their baseline characteristics were included. Compared with normal BMI, high BMI patients had significantly 30-day greater risk of the composite of vascular or bleeding complications (11.1% vs 8.8%, OR: 1.28, 95% CI [1.02 to 1.61]; p=0.03). Complications rates were higher in both obese (11.3%) and overweight (10.5%), as compared with normal weight patients (8.8%). By a landmark event analysis, the effect of high versus normal BMI on these complications appeared more pronounced within 7 days after the TAVI procedure. A significant linear association between increased BMI and vascular complications was observed at this time frame (p=0.03). In conclusion, compared with normal BMI, both obese and overweight patients undergoing TAVI, experience increased rates of 30-day vascular and bleeding complications. These findings indicate that high BMI is an independent risk predictor of vascular and bleeding complications after TAVI.

Pharmacologic Considerations for the Obese Patient

Obese patients gain lean and mass in different proportions to total body mass. This results in different volumes of distribution (Vd) for medications according to their lipid solubility compared to that of normal weight patients. High body mass index (BMI) patients are at increased risk of medical comorbidities that may affect drug metabolism and clearance. Anesthesiologists should factor in these differences in order to prevent erroneous medication dosing. This review contains 1 figure, 1 table, and 61 references. Keywords: obesity, induction agents, analgesics, inhaled anesthetics, neuromuscular blocking agents, reversal agents, local anesthetics, pharmacology, pharmacokinetics, pharmacodynamics

Operative and long-term oncologic outcomes of laparoscopic versus open major liver resection in high body mass index patients: A propensity score matching analysis

Laparoscopic liver resection (LLR) in high body mass index (BMI) patients has been reported to be particularly challenging owing to technical difficulties and various comorbidities. We reviewed medical records of patients in high BMI (≥ 25.0 kg/m2) with various liver disease who underwent major liver resection between January 2009 and November 2018 at our center. In total, 521 patients were included in this study and divided into LLR (n = 140) and OLR (n = 381) groups. For group comparisons, 1:1 PSM was used with covariates of baseline characteristics, including tumor characteristics and surgical liver resection procedures. After PSM, there were 120 patients in each groups. LLR group had significantly lower blood loss and shorter postoperative hospital stay (p < 0.001, respectively). Otherwise, the operation time of LLR were significantly longer than that of OLR in obese patients (p < 0.001). Age ≥ 70 years, ≥ 30 BMI, malignancy disease, and use of pringle maneuver were independent predictors for postoperative complication in multivariate analysis. In subgroup analysis with HCC patients, there was no significant difference between the two groups in overall survival hazard ratio (HR), 0.225; 95% confidence interval (CI), 0.049-1.047; p = 0.057) or recurrence-free survival rates (HR. LLR for various liver disease in obese patients results in shorter postoperative hospital stays and lower blood loss compared with OLR. In addition, morbidity and long-term oncological outcomes were comparable between LLR and OLR for obese patient with HCC. Our experience suggests that obesity should not be seen as a contraindication for LLR, which is a safe and feasible option for obese patients.

Lipid and neutrophil accumulation and active inflammasome in high BMI tumor regions of human pancreatic ductal adenocarcinoma.

e16271 Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients (n = 44) with a body-mass index (BMI) &gt; 27 (obese [n = 21]) and BMI &lt; 22 (normal [n = 23]) were incubated with anti-human CD66b antibodies and detected using standard immunofluorescent microscopy techniques. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of adipocytes in all tissue sections and CD66b+ neutrophils in all tissue sections of normal BMI patients and in 81% of high BMI patients. There is a significantly greater density of adipocytes in the tumor environment when compared to adjacent normal areas, suggesting that these cells are acting as a damage signal. We have also shown that there are fewer total cells per area in the tumor region, suggesting a disorganization that may allow more adipose tissue to form in these areas of high BMI patients. Our novel data also shows that high BMI results in a significantly higher neutrophil count in tumor specific tissue when compared to patients with a low BMI. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. Conclusions: Our data uniquely shows that CD66b+ neutrophils tend to accumulate inside PDAC in high BMI patients and this is associated with intra-tumoral active inflammasomes. The higher concentrations of these inflammasomes in higher BMI patients may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.

Endoscopic Sleeve Gastroplasty (ESG) for High-Risk Patients, High Body Mass Index (> 50 kg/m2) Patients, and Contraindication to Abdominal Surgery.

For high-risk classified patients, patients with superobesity and in cases of contraindication to abdominal surgery, traditional bariatric surgery might lead to potential morbidity and mortality. Endoscopic sleeve gastroplasty (ESG) is a novel and effective bariatric therapy for morbidly obese patients. Our research group initially evaluated the safety, feasibility, and efficacy of ESG for high-risk, high body mass index (BMI) patients, and patients contraindicated to abdominal surgeries. Eligible patients characterized as high-risk for bariatric surgery due to high-BMI, severe comorbidities, or impenetrable abdomen were prospectively documented. ESG was performed by using Overstich® (Apollo Endosurgery, Austin, TX, USA). Primary outcomes included technical success, post-procedure adverse events and mortality, and the change of weight and BMI. ESG was successfully performed for all patients (N = 24, mean age was 55.6 (± 9.2) years old, 75% male). Baseline weight and BMI were 157.9 (± 49.1) kg and 49.9 (± 14.4) kg/m2. According to Edmonton Obesity Staging System (EOSS), 8 (33.3%), 14 (58.3%), and 2 (8.3%) patients were respectively classified as EOSS 2, 3, and 4. Mean operation time was 114.7 (± 26.0) min, without intraoperative complication. Weight loss, BMI reduction, %total weight loss (%TWL), and %excess weight loss (%EWL) were 17.5 (± 14.6) kg, 5.6 (± 4.6) kg/m2, 12.2% (± 8.9%), and 29.1% (± 17.9%) at post-ESG 12-month, respectively. One (4.2%) moderate post-procedure adverse event (gastric mucosal bleeding) was observed. ESG can be used as a safe, feasible, and effective option for the therapy of patients with superobesity, high-risk patients, and patients contraindicated to abdominal surgery. Graphical Abstract.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) in urological malignancies: a multi-center retrospective study.

We evaluated the incidence and risk factors for antiresorptive agent-related osteonecrosis of the jaw (ARONJ) in prostate and kidney cancer patients. We retrospectively reviewed the clinical data of 547 patients from 13 hospitals. Prostate and kidney cancer patients with bone metastases who were treated with a bone-modifying agent (BMA) between January 2012 and February 2019 were enrolled. Exclusion criteria were BMA use for hypercalcemia, a lack of clinical data, a follow-up period of less than 28days and a lack of evaluation by dentists before BMA administration. The diagnosis and staging of ARONJ were done by dentists. Two-hundred eighteen patients were finally enrolled in the study, including 168 prostate cancer patients and 50 kidney cancer patients. Of them, 49 (29%) prostate cancer patients and 18 (36%) kidney cancer patients needed tooth extraction prior to BMA initiation. The mean follow-up period after BMA initiation was 552.9 ± 424.7days (mean ± SD). In the cohort, 23% of the patients were diagnosed with ARONJ in the follow-up period. The 1-year cumulative incidences of ARONJ were 9.4% and 15.4% in prostate and kidney cancer patients, respectively. Multivariate analysis indicated that kidney cancer, tooth extraction before BMA and a body mass index (BMI) ≥ 25kg/m2 were significant predictors for ARONJ. ARONJ is not a rare adverse event in urological malignancies. Especially, kidney cancer, high BMI patients and who needed tooth extraction before BMA were high risk for developing ARONJ.

A comparative study of pre- or subpectoral expander position with the fenestrated Acellular dermal matrix anterior coverage, on drainage volume and Seroma Formation after Non-Nipple-Sparing Mastectomy

It has been reported that the use of the acellular dermal matrix (ADM) in expander-based breast reconstruction is related to an increase in seroma-related complications. The aim of this study is to compare the actual drainage volume, time to drain removal, and seroma formation rate in patients with prepectoral expander placement with anterior coverage of a fenestrated ADM to those patients with partial subpectoral expander placement with inferior coverage of a fenestrated ADM. This is a single-surgeon retrospective review of patients who underwent prepectoral expander-based breast reconstruction following non-nipple-sparing mastectomy. Patient demographics, operative data, and complications were analyzed and multivariate linear regression analyses were conducted to evaluate the significance of factors that influences total volume of fluid formation. A total of 89 breasts from 87 patients were included in the study. Twenty-seven breasts had prepectoral expander reconstruction and 62 breasts had partial subpectoral expander reconstruction. Mean total volumes of fluid formation (total drainage volume + additional aspirated volume) were not significantly different (p = 0.190) in the two groups. In the subpectoral group only, high body mass index (BMI) was correlated with the total volume of fluid formation among the independent factors. (p = 0.017) CONCLUSIONS: Although total drainage volume was not significantly different between prepectoral and subpectoral groups, prepectoral positioning of the expander can be a protective factor against seroma formation in high BMI patients. Further definitive studies with larger patient numbers are warranted to corroborate these data and draw definitive conclusions.

Significant lipid and neutrophil accumulation and active inflammasome in high BMI tumor regions of human pancreatic ductal adenocarcinoma.

438 Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients (n = 44) with a body-mass index (BMI) &gt; 27 (obese [n = 21]) and BMI &lt; 22 (normal [n = 23]) were incubated with anti-human CD66b antibodies and detected using standard immunofluorescent microscopy techniques. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of adipocytes in all tissue sections and CD66b+ neutrophils in all tissue sections of normal BMI patients and in 81% of high BMI patients. There is a significantly greater density of adipocytes in the tumor environment when compared to adjacent normal areas, suggesting that these cells are acting as a damage signal. Our novel data also shows that high BMI results in a significantly higher neutrophil count in tumor specific tissue when compared to patients with a low BMI. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. Conclusions: Our data uniquely shows that CD66b+ neutrophils tend to accumulate inside PDAC in high BMI patients and this is associated with intra-tumoral active inflammasomes. The higher concentrations of these inflammasomes in higher BMI patients may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.

An Open Source Patient Simulator for Design and Evaluation of Computer Based Multiple Drug Dosing Control for Anesthetic and Hemodynamic Variables

We are witnessing a notable rise in the translational use of information technology and control systems engineering tools in clinical practice. This paper empowers the computer based drug dosing optimization of general anesthesia management by means of multiple variables for patient state stabilization. The patient simulator platform is designed through an interdisciplinary combination of medical, clinical practice and systems engineering expertise gathered in the last decades by our team. The result is an open source patient simulator in Matlab/Simulink from Mathworks(R). Simulator features include complex synergic and antagonistic interaction aspects between general anesthesia and hemodynamic stabilization variables. The anesthetic system includes the hypnosis, analgesia and neuromuscular blockade states, while the hemodynamic system includes the cardiac output and mean arterial pressure. Nociceptor stimulation is also described and acts as a disturbance together with predefined surgery profiles from a translation into signal form of most commonly encountered events in clinical practice. A broad population set of pharmacokinetic and pharmacodynamic (PKPD) variables are available for the user to describe both intra- and inter-patient variability. This simulator has some unique features, such as: i) additional bolus administration from anesthesiologist, ii) variable time-delays introduced by data window averaging when poor signal quality is detected, iii) drug trapping from heterogeneous tissue diffusion in high body mass index patients. We successfully reproduced the clinical expected effects of various drugs interacting among the anesthetic and hemodynamic states. Our work is uniquely defined in current state of the art and first of its kind for this application of dose management problem in anesthesia. This simulator provides the research community with accessible tools to allow a systematic design, evaluation and comparison of various control algorithms for multi-drug dosing optimization objectives in anesthesia.

Assessing the Effectiveness of a Weight Reduction Program in Hospitalized Obese Patients Undergoing Laparoscopic Surgery.

Investigate the efficacy of a hospitalized weight reduction program before laparoscopic surgery among high body mass index (BMI) patients with endometrial cancer. The patients were housed in a shared room, received exercise guidance, and restricted to a total caloric intake of 1200 kcal. A physiotherapist and a dietitian provided pedometer and nutritional guidance, respectively. The primary outcome was weight reduction. Among the 16 patients included, 12 (75%) had Stage I endometrial cancer and 10 (62.5%) underwent laparoscopic surgery. Weight and BMI at first consultation were 88.4±10.4 kg and 34.8±3.9 kg/m2, respectively. The rate of weight reduction was 6.5%±2.5%; on average, BMI decreased by 2.1±1.0 kg/m2. The duration from initial consultation to surgery was 39.1±11.4 days. Hospitalization duration until weight reduction was 20.8±8.0 days; there were no surgical complications. Our hospitalized weight reduction program may be effective for obese endometrial cancer patients.

Abstract 13057: High Visceral-to-Subcutaneous Fat Ratio is Correlated With Increased Cardiovascular Events in Patients With Low Body Mass Index With Suspected Coronary Artery Disease

Introduction: Although abdominal fat distribution given by the ratio of visceral adipose tissue (VAT) to subcutaneous adipose tissue (SAT) area (V/S ratio) is possibly associated with an increased risk of cardiovascular disease (CVD), few studies have examined the effect of the V/S ratio and physique stratified by body mass index (BMI) on long-term clinical outcomes. Methods: We assessed 945 consecutive patients (mean age, 69 years; 42.5% females) with suspected coronary artery disease who underwent computed tomography (CT) angiography. The patients also underwent plain abdominal CT to measure VAT and SAT areas. The V/S ratio was calculated to assess abdominal fat distribution. The patients were classified into four groups based on the median V/S ratio and median BMI (0.627 and 23.61 kg/m 2 , respectively). We examined the association between the V/S ratio and long-term outcomes in each BMI group. The primary outcome was major adverse cardiac events (MACEs, including all-cause death, acute coronary syndrome, emergent hospitalization due to CVD, and any coronary revascularization). Results: Over a median follow-up of 792 days, although the incidence of any cardiovascular event was not associated with the V/S ratio among patients with high BMI, a higher incidence of MACE, all-cause death, and any coronary revascularization was noted among patients with low BMI in the high V/S ratio group than in the low V/S ratio group. In the Kaplan-Meier analysis, a statistically significantly lower MACE-free survival rate was noted among patients with low BMI in the high V/S ratio group than in the low V/S ratio group, despite no differences among high BMI patients in both the V/S ratio groups (Figure). Conclusion: Only in patients with low BMI, a high V/S ratio was associated with increased risks of MACE. A high V/S ratio may be an important risk factor for CVD, especially in patients with low BMI. In contrast, abdominal fat distribution did not affect CVD prognosis in patients with high BMI.

Conversion of Adjustable Gastric Banding to Roux-en-Y Gastric Bypass in One or Two Steps: What Is the Best Approach? Analysis of a Multicenter Database Concerning 832 Patients.

Roux-en-Y gastric bypass (RYGB) is often the preferred conversion procedure for laparoscopic adjustable gastric banding (LAGB) poor responders. However, there is controversy whether it is better to convert in one or two stages. This study aims to compare the outcomes of one and two-stage conversions of LAGB to RYGB. Retrospective review of a multicenter prospectively collected database. Data on conversion in one and two stages was compared. Eight hundred thirty-two patients underwent LAGB conversion to RYGB in seven specialized bariatric centers. Six hundred seventy-three (81%) were converted in one-stage. Patients in the two-stage group were more likely to have experienced technical complications, such as slippage or erosions (86% vs. 37%, p = 0.0001) and to have had a higher body mass index (BMI) (41.6 vs. 39.9Kg/m2, p = 0.005). There were no differences in postoperative complications and mortality rates between the one-stage and two-stage groups (13.5% vs. 10.8%, and 0.7% vs. 0.0% respectively, p = ns). Mean final BMI and %total weight loss (%TWL) for the one-stage and the two-stage groups were 31.6 vs. 32.4Kg/m2 (p = ns) and 30.4 vs. 26.8 (p = 0.017) after a mean follow-up of 33months. Follow-up at 1, 3, and 5years was 98%, 75%, and 54%, respectively. One-stage conversion of LAGB to RYGB is safe and effective. Two-stage conversion carries low morbidity and mortality in the case of band slippage, erosion, or higher BMI patients. These findings suggest the importance of patient selection when choosing the appropriate conversion approach.