Conditions In Obese Patients Research Articles

Challenges of Spine Surgery in Obese Patients: A Case Report with a Review of the Literature

Introduction: Obese patients face unique challenges across all phases of spine care and surgery, including preoperative, intraoperative, and postoperative periods. Significantly higher risks are associated with spinal surgery in obese patients. This study explores the challenges of managing spinal conditions in obese patients and offers strategies to mitigate these risks. Case report: A 56-year-old female with a BMI of 42 was referred for evaluation of chronic lower back pain and radicular leg pain. Imaging results were lumbar fusion for degenerative disc disease at the L4-5 and L5-S1 levels. During surgery, the patient required a prolonged operating time due to her increased soft tissue, which made visualization more difficult. The surgical team had to use longer instruments to navigate through the deeper tissue layers. Fluoroscopy was employed to ensure accurate placement of the fusion hardware. Postoperatively, the patient developed delayed wound healing, which required close monitoring and wound care interventions. She had significant reduction in back pain and improved mobility at her 6-month follow-up. Conclusion: Obese patients present numerous challenges to spine surgeons, ie. elective and non-elective surgeries, anesthetic issues, operative challenges, post-operative issues, complications, and outcomes. To mitigate associated risks and optimize outcomes, specific precautions can be taken during the preoperative, intraoperative, and postoperative phases.

Neuroprotective effects of GLP-1 receptor agonists in neurodegenerative Disorders: A Large-Scale Propensity-Matched cohort study

BackgroundGLP-1 receptor agonists, traditionally used for treating type 2 diabetes mellitus and obesity, have demonstrated anti-inflammatory properties. However, their potential neuroprotective effects in neurodegenerative disorders remain unclear. ObjectiveTo evaluate the impact of GLP-1 receptor agonists on the risk of developing various neurodegenerative conditions in obese patients. MethodsThis comprehensive retrospective cohort study analyzed data from 5,307,845 obese adult patients across 73 healthcare organizations in 17 countries. Propensity score matching was performed, resulting in 102,935 patients in each cohort. We compared the risk of developing neurodegenerative disorders between obese patients receiving GLP-1 receptor agonist therapy and those who were not. ResultsObese patients treated with GLP-1 receptor agonists showed significantly lower risks of developing Alzheimer’s disease (RR = 0.627, 95 %CI = 0.481–0.817), Lewy body dementia (RR = 0.590, 95 %CI = 0.462–0.753), and vascular dementia (RR = 0.438, 95 %CI = 0.327–0.588). The risk reduction for Parkinson’s disease was not statistically significant overall (RR = 0.784, 95 %CI = 0.580–1.058) but was significant for semaglutide users (RR = 0.574, 95 %CI = 0.369–0.893). Semaglutide consistently showed the most pronounced protective effects across all disorders. Additionally, a significant reduction in all-cause mortality was observed (HR = 0.525, 95 %CI = 0.493–0.558). ConclusionThis study provides evidence that the effects of GLP-1 receptor agonists may extend beyond their known metabolic and cardioprotective benefits to include neuroprotection, associated with a decreased risk of developing various neurodegenerative disorders. These findings suggest the potential for expanding the therapeutic applications of GLP-1 receptor agonists to improve neurocognitive outcomes. Further research is warranted to elucidate the mechanisms underlying these neuroprotective effects and to explore their clinical applications in neurodegenerative disease prevention and treatment.

СЕРДЕЧНО-СОСУДИСТЫЙ РИСК У КОМОРБИДНЫХ ПАЦИЕНТОВ ПОСЛЕ МЕТАБОЛИЧЕСКОЙ КОРРЕКЦИИ

Cardiovascular pathology is the leading cause of mortality in the world as well as obesity and associated metabolic disorders are one of the main risk factors for the development and progression of cardiovascular diseases. For most obese patients changing lifestyle for a long period of time seems difficult especially in case of comorbidity. Metabolic surgery is currently recognized as an effective way to treat morbid obesity, reducing the incidence and risk of serious consequences of obesity-related diseases. The aim of this article was to evaluate the effect of metabolic surgery on cardiovascular events and other associated conditions in obese patients. The article provides up-to-date information on modern surgical interventions (gastric bypass, sleeve gastrectomy, mini-gastric bypass and gastric banding). We represent data on the effectiveness of metabolic surgery in obesity, hypertension and dyslipidemia. The effect of bariatric surgery on the remission of type 2 diabetes mellitus is also discussed.

Feasibility and safety of vNOTES for gynecological procedures in obese patients

IntroductionThis study aimed to determine the feasibility and safety of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) to treat benign and malign gynecological conditions in obese patients. Material and methodsWe analyzed data from 79 obese patients with a body mass index (BMI) > 30 Kg/m2 operated by vNOTES for gynecological conditions between May 2020 and April 2023. The primary outcome was the feasibility of performing the surgery as initially planned. Data were presented for subgroups of patients with obesity class I (BMI 30.1 - 34.9 Kg/m2), class II (BMI 35.0 – 39.9 Kg/m2), and class III (BMI ≥ 40.0 Kg/m2). ResultsPatients presented obesity class I in 39 cases (49.4 %), class II in 27 cases (34.2 %), and class III in 13 cases (16.4 %). Fifty-two patients (65.8 %) underwent vNOTES hysterectomy, 26 patients (32.9 %) underwent procedures limited to the adnexa, and 1 patient (1.3 %) underwent myomectomy. The conversion rate was 0 %, 11.1 %, and 7.7 % in obesity class I, II, and III, respectively. Intraoperative bladder injury was observed in 1 case (1.3 %) and rectal serosal tear in 2 cases (2.5 %). Postoperatively, we observed 3 cases (3.8 %) of wound infection, 2 cases (2.5 %) of cystitis, and 1 case (1.3 %) of deep vein thrombosis. DiscussionThis study demonstrated the feasibility and safety of performing gynecological vNOTES procedures in obese patients. However, obesity could be associated with longer and more complex interventions, especially in obesity class II and III patients.

(538) Penile Enlargement for Patient with Buried Penis: Pubic Dermolipectomy, Scrotoplasty and Mons Pubis Reconstruction

Abstract Introduction Acquired buried penis is a common condition in obese patients. Abnormal excess fat accumulation under the pubic skin leads to the partially or completely disappearance of the penis. This condition is related to voiding difficulties and sexual dysfunction. The goal of surgical treatment is to expose full penile lengthy by excising the adipose pubic tissue and part of excess pubic skin. Objective The aim of this kind of surgery is to make possible to have a normal sexual life to obese patients with buried penis. Methods We performed this technique for buried penis in 25 patients aged from 18 to 72 y (mean 48). Preoperatively, the patient is marked for the procedure in the standing position. Two transversal incisions are made on the pubis and joined laterally on both sides towards anterior iliac spines with the care taken to avoid the formation of "dog ears". The suprapubic fat is removed. Following the inner surface of the Scarpas fascia, the fat is also removed from the penoscrotal angle and from the scrotum as much as possible leaving exposed funiculus and testis on both sides. Suspensory ligament of the penis was incised. Penile skin redistribution leads to a better organ exposure. Postoperative vacuum erectile device was used in order to prevent penile retraction. Results Follow up was at 6 months. Early postoperative complications were hematoma (7pts), penile skin edema (5pts), seroma (5pts), wound infection (5pts), penile shaft retraction (3pts). Majority of pts (22pts) were satisfied good aesthetical and functional outcome. Conclusions Pubic dermolipectomy is a safe procedure with satisfactory results to treat men with buried penis. Surgical exposition of the penile shaft was accomplished in all patients. Disclosure No

Obez hastalarda serum leptin ve triptofan düzeylerinin depresyon ve anksiyete ile ilişkisi var mı?

Objectives: Depression and anxiety are common conditions in obese patients. Leptin plays a role in obesity, the role of tryptophan in obesity has been investigated frequently in current studies. The aim of this study is to evaluate whether serum leptin and triptophan levels are related to depression and anxiety in obesity patients. Methods: This is a descriptive and cross-sectional study in which the data of 88 patients aged 18 years and over, BMI 25 kg/m2 and above, who applied to the Family Medicine outpatient clinic between 01.07.2019 and 31.12.2019, were examined. Sociodemographic data form, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) were completed by all patients included in the study. Results: There was no significant relationship between BMI and leptin, BMI and tryptophan levels. A positive correlation was found between tryptophan and weight, waist circumference and systolic blood pressure (SBP). Tryptophan was also significantly higher in smokers and those with a history of psychiatric treatment. Tryptophan levels in men were found to be significantly higher than in women. Serum tryptophan concentration of the patients was positively correlated with weight, waist circumference and SBP. Tryptophan level was found significantly higher in men than in women. Tryptophan was also significantly higher in smokers and those with a history of psychiatric treatment. There was no significant relationship between BDI, BAI and leptin and tryptophan levels. Conclusion: The significant relationships between serum tryptophan level and weight, waist circumference and SBP may be useful in the management, follow-up and treatment of obese patients.

Inhibition of CXXC5 function reverses obesity-related metabolic diseases.

BackgroundMetabolic diseases, including type 2 diabetes, have long been considered incurable, chronic conditions resulting from a variety of pathological conditions in obese patients. Growing evidence suggests the Wnt/β‐catenin pathway is a major pathway in adipose tissue remodelling, pancreatic β‐cell regeneration and energy expenditure through regulation of key metabolic target genes in various tissues. CXXC5‐type zinc finger protein 5 (CXXC5) is identified negative feedback regulator of the Wnt/β‐catenin pathway that functions via Dishevelled (Dvl) binding.MethodsExpression level of CXXC5 was characterised in clinical samples and diabetes‐induced mice model. Diabetes‐induced mice model was established by using high‐fat diet (HFD). HFD‐fed mice treated with KY19334, a small molecule inhibiting CXXC5‐Dvl protein–protein interaction (PPI), was used to assess the role of CXXC5 in metabolic diseases.ResultsHere, we show that CXXC5 is overexpressed with suppression of Wnt/β‐catenin signalling in visceral adipose tissues of patients with obesity‐related diabetes. Meanwhile, Cxxc5−/− mice fed an HFD exhibited resistance to metabolic dysregulation. KY19334 restores the lowered Wnt/β‐catenin signalling and reverses metabolic abnormalities as observed in HFD‐fed Cxxc5−/− mice. Administration of KY19334 on HFD‐fed mice had a long‐lasting glucose‐controlling effect through remodelling of adipocytes and regeneration of pancreatic β‐cells.ConclusionOverall, the inhibition of CXXC5 function by small molecule‐mediated interference of Dvl binding is a potential therapeutic strategy for the treatment of obesity‐related diabetes.

Microalgae polysaccharides ameliorates obesity in association with modulation of lipid metabolism and gut microbiota in high-fat-diet fed C57BL/6 mice

Microalgae are emerging as a good source of natural nutraceuticals and medicines. This study aims at evaluating the anti-obesity effects of two microalgae polysaccharides (CPS from Chlorella pyrenoidosa and SPS from Spirulina platensis) in high-fat diet (HFD)-induced obese C57BL/6 mice, with β-glucan as a positive control polysaccharide. CPS, SPS and β-glucan were daily administered intragastrically during 10-week HFD feeding, and conferred equally effective protection against overweight, energy imbalance, glucose tolerance impairment, systemic inflammation, dyslipidemia, and fat deposition in the liver and epididymal white adipose tissues. By western blotting analysis of CPT-1, PPARγ and SREBP-1c, those polysaccharides increased lipolysis and decreased lipogenesis in the liver. According to high-throughput sequencing of fecal 16S rRNA, CPS, SPS and β-glucan corrected the HFD-induced gut dysbiosis similarly by increasing beneficial bacteria especially Clostridia, Bacterioidia and Mollicutes and decreasing unfavorable bacteria especially Actinobacteria and Verrucomicrobia and, as revealed by PICRUSt functional analysis, they restored the HFD-induced perturbations in many gut bacterial enzymes and pathways involved in the metabolism of SCFAs, secondary bile acids and trimethylamine, implicating a possible anti-obesity mechanism through gut microbiome-mediated modulation of host lipid metabolism. Microalgae polysaccharides can thus serve as potent alternative food ingredients to improve disease conditions in obese patients.

A Randomized Comparison of Non-Channeled GlidescopeTM Titanium Versus Channeled KingVisionTM Videolaryngoscope for Orotracheal Intubation in Obese Patients with BMI > 35 kg·m-2.

Videolaryngoscopes may improve intubating conditions in obese patients. A total of 110 patients with a body mass index > 35 kg∙m−2 were prospectively randomized to tracheal intubation using non-channeled Glidescope Titanium or channeled King Vision videolaryngoscope. The primary outcome was the time to tracheal intubation. Secondary outcomes included: total success rate, number of attempts, the quality of visualization, peri-procedural and post-proceduralcomplications. Time to the first effective breath was shorter with the King Vision (median; 95% CI)—36; 34–39 s vs. 42; 40–50 in the Glidescope group (p = 0.007). The total success rate was higher in the Glidescope group—100% vs. 89.1% (p = 0.03). There was a higher incidence of moderate and difficult laryngoscopy in the King Vision group. No difference was recorded in first attempt success rates, total number of attempts, use of additional maneuvers, intraoperative trauma, or any significant decrease in SpO2 during intubation. No serious complications were noted and the incidence of postoperative complaints was without difference. Although tracheal intubation with King Vision showed shorter time to the first breath, total success was higher in the Glidescope group, and all but one patients where intubation failed with the KingVision were subsequently intubated with the Glidescope.

Evaluation of NAFLD and fibrosis in obese patients \u2013 a comparison of histological and clinical scoring systems

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a frequent condition in obese patients and regularly progresses to non-alcoholic steatohepatitis (NASH) and subsequent cirrhosis. Histologic evaluation is the gold standard for grading and staging, but invasive biopsies are associated with obvious risks. The aim of this study was to evaluate different non-invasive tools for screening of NAFLD and fibrosis in obese patients.MethodsIn a prospective cohort study liver specimens of 141 patients were taken during bariatric surgery. Serological parameters and clinical data were collected and the following scores calculated: NASH clinical scoring system (NCS), aspartate aminotransferase to platelet ratio index (APRI), FIB-4 as well as NAFLD fibrosis score (NFS). Liver function capacity was measured preoperatively by LiMAx test (enzymatic capacity of cytochrome P450 1A2). Intraoperative liver biopsies were classified using NAFLD activity score (NAS) and steatosis, activity and fibrosis (SAF) score.ResultsAPRI was able to differentiate between not NASH and definite NASH with a sensitivity of 74% and specificity of 67% (AUROC 0.76). LiMAx and NCS also showed significant differences between not NASH and definite NASH. No significant differences were found for NFS and Fib-4. APRI had a high sensitivity (83%) and specificity (76%) in distinguishing fibrosis from no fibrosis (AUROC = 0.81). NCS and Fib-4 also revealed high AUROCs (0.85 and 0.67), whereas LiMAx and NFS did not show statistically significant differences between fibrosis stages. Out of the patients with borderline NASH in the histologic NAS score, 48% were classified as NASH by SAF score.ConclusionsAPRI allows screening of NAFLD as well as fibrosis in obese patients. This score is easy to calculate and affordable, while conveniently only using routine clinical parameters. Using the NAS histologic scoring system bears the risk of underdiagnosing NASH in comparison to SAF score.

Correlation between Obstructive Sleep Apnea and Non-Alcoholic Fatty Liver Disease before and after Metabolic Bariatric Surgery.

Emerging evidence has revealed that obstructive sleep apnea (OSA) is associated with non-alcoholic fatty liver disease (NAFLD). However, the impact of OSA on NAFLD among obese patients undergoing metabolic and bariatric surgery (MBS), especially during follow-up period, remains unclear. To analyze the correlation based on preoperative characteristics and postoperative conditions among bariatric patients with comorbid OSA and NAFLD. Clinical data of patients who underwent MBS in our institution between January 2016 and June 2019 were reviewed retrospectively. Correlation analysis and linear regressions were used to identify how OSA links with NAFLD before and after treatment of MBS. Of 308 patients, 181 were diagnosed with OSA and enrolled in the present study, and 127 completed follow-up visits at 6months. The proportion of NAFLD in the mild-moderate OSA and severe OSA groups was 75.0% and 96.0%, respectively. MBS was effective at improving sleep apnea and nocturnal hypoxia, as well as liver steatosis and fibrosis (P< 0.05). And we also found that there were significant correlations not only between OSA- and NAFLD-related characteristics at baseline but also between their improvements after surgery, eventually leading to similar prognosis of NAFLD for both groups (P< 0.05), no matter what presurgical differences existed. In addition, the results of the univariate and multivariate linear regression analyses supported preoperative liver/spleen Hounsfield units ratio (LSR) by computerized tomography (CT) as an independent predictor of the effect of MBS on liver steatosis. In conclusion, MBS plays a pivotal role in the control of medical conditions in obese patients with OSA and NAFLD. Given the correlation between OSA and NAFLD in the present study, in the case of both the severity at baseline as well as the improvement after surgery, OSA may pose an impact on the prognosis of NAFLD in bariatric patients.

Laparoscopic Hysterectomy versus Abdominal Hysterectomy for Obese Women with Benign Diseases

Background: Obesity is a challenging health problem in gynecologic surgery. Laparoscopic has the potential advantages than abdominal hysterectomy of being quicker, efficient with low estimated blood loss.Aim of the work: To compare the safety and effectiveness of laparoscopic and abdominal hysterectomy for benign conditions in obese patients. Patients and Methods: Sixty patients were submitted to history taking, clinical examination, Lab investigations, abdominal ultrasound and biopsy for suspicious pathology. Patients divided into two equal groups. The first for total laparoscopic hysterectomy and the second for trans-abdominal hysterectomy. Patients were followed for six months after surgery. Data collected include operative time, amount of blood loss, complications and duration of hospital stay. Results: BMI was significantly higher among open when compared to laparoscopic group (43.69±3.86 vs 34.5±4.02 respectively), and low parity and low cesarean deliveries were significantly increased in laparoscopic group. The highest indication of hysterectomy in laparoscopic group was adenomyosis (43.3%) followed by fibroid (30.0%), while in open group, the most common indication was fibroid (53.3%) followed by adenomyosis (26.7%). Operative time showed significant decrease in laparoscopic when compared to open hysterectomy groups (56.23±21.5 vs 78.87±8.22 minutes respectively) and blood loss was significantly decreased among laparoscopic group. Finally, the length of hospital stay was significantly decreased in laparoscopic when compared to open groups (the median was 10 versus 24 hours respectively). Conclusion: Laparoscopic hysterectomy is superior to abdominal hysterectomy in obese females with benign conditions in terms of safety and efficacy.

Outcomes of robotic, laparoscopic, and open hysterectomy for benign conditions in obese patients

Objective:To compare outcomes of robotic-assisted (RAH), total laparoscopic hysterectomy (LH), and total abdominal hysterectomy (TAH) for benign conditions in obese patients.Material and Methods:Retrospective cohort (Class II-2) analysis. All obese patients who underwent RAH, LH or TAH for benign conditions by a single surgeon at the University of Texas Medical Branch between January 2009 and December 2011 were identified and their charts reviewed. The patients’ characteristics, operative data, and post-operative outcomes were collected and statistically analyzed.Results:A total of 208 patients who underwent RAH (n=51), LH (n=24) or TAH (n=133) were analyzed. There were no significant differences among the groups in demographic characteristics, indications for surgery or pathologic findings. RAH and LH were associated with lower estimated blood loss (EBL) (p<0.001) and shorter length of hospital stay (LOS) (p<0.001) compared with TAH. In addition, RAH and LH had lower intraoperative and early postoperative (≤6 weeks) complications compared with TAH (p=0.002). However, the procedure time was longer in RAH and LH (p<0.001). No significant differences were noted among the groups for late post-operative complications (after 6 weeks) or unscheduled post-operative visits.Conclusion:Minimally invasive hysterectomy appears to be safe in obese patients with the advantages of less EBL, fewer intraoperative complications, and shorter LOS.

Obesity in Inflammatory Bowel Disease

Introduction: Although the obesity epidemic is worsening in America, there is a relative paucity of the population level studies reporting the prevalence of obesity among the Inflammatory Bowel Disease (IBD)patients. IBD patients are generally believed to be underweight. Our aim is to examine the obesity trends among the hospitalized IBD patients. Methods: The Nationwide Inpatient Sample database from 2005 to 2014 was examined. Specific ICD -9 Codes for Obesity, IBD were used to compile data. Patient demographic data were also analyzed. Results: The database recorded total of 552887 Inflammatory bowel disease(IBD) admissions during that time period. Among those, 515676(93.27%) were Non-obese IBD and 37211 (6.73%) obese IBD patients. The number of hospital admissions for both Obese and nonobese IBD steadily increased from 2005 to 2014, however, the rate was strikingly high for obese (280% vs 46.22%).The number of admission for obese patients increased from 26.1 to 99.09 per 100,000 admissions compared to 636.55 to 930.39 for Non-Obese Patients.Within the Obese IBD patients, Ulcerative colitis group admissions are increasing at a rapid pace compared the Crohn's (304.95% vs 165.33%), though the majority are Crohn's patients., 62.3% vs 37.7%. The Obese IBD patients tend to be older (mean age of 57.72 vs 51.87) with predominately Caucasian race, However, the AA race is more often associated with Obese IBD than the Non-obese 11.6% vs 10% (OR 1.18, 95% CI 1.14 to 1.22, P < 0.001).Both groups have female preponderance, but more among the Obese IBD patients, 67.2% vs 56.8% (OR:1.57, 95% CI: 1.5 to 1.7, P < 0.001). The number of chronic conditions among the obese patients is higher than non-obese patients (7.5 vs 5.1, with P < 0.001). In spite of the higher prevalence of chronic conditions in Obese patients, mortality among the Nonobese patients is higher (1.6 vs 1.04, OR 1.64, 95% CI 1.4 to 1.8, P< 0.001).Obese IBD patients are more likely to have Metabolic diseases as indicated by higher mean Charleson Deyo Comorbidity score in obese patients, 1.4 vs 0.95. On Logistic Regression, Obesity is associated with Hypertension, Diabetes, Congestive Heart Failure, Myocardial Infarction, Black race, female sex. Conclusion: Even though the obese IBD patients are still not the majority of hospital IBD admissions, but they are the rapidly increasing group. Obese IBD patients tend to be older, more likely to have other comorbid conditions as like general population.Figure: Admission per 100,000.Figure: Obesity trends in Inflammatory bowel disease.FigureTable: Table. Primary diagnosis for patients died among obese and non-obese IBD

Conditions of Oral Health in Gastroplasty Obese Patients: Brief Comments

Background: One intervention that has been effective in treating obesity is bariatric surgery in a procedure in which it controls obesity through restriction and / or malabsorption of ingested foods. Objective: The aim of the present study was to describe the oral condition in obese patients and after bariatric surgery. Methods: A bibliographic survey was performed with 12 articles, searched through the PubMed virtual library. The search criteria were: 1) -present direct or indirect relationship of bariatric surgery with the words cited above. 2) - Regarding the period of publication: between 2011 and 2017. 3) - As to the language: Portuguese and English. Conclusion: According to the main literary findings, there was a strong correlation between obesity and / or bariatric surgery with decreased oral health. Keywords: Oral Health; Obesity; Bariatric surgery

Attitude and knowledge of family medicine practitioners towards the association between periodontal disease and obesity.

To assess the attitude and knowledge of family medicine practitioners (FMPs) towards the association between periodontal disease and obesity. A cross-sectional study was performed and a 13-item survey questionnaire was given to FMPs practicing in 12 different teaching hospitals in Karachi, Pakistan. The questions were aimed at exploring the knowledge of FMP's regarding the association of obesity and periodontal disease and their attitude towards the association of obesity and periodontal disease. Chi-square and Spearman co-efficient were conducted to compare subgroups and correlate factors with the knowledge score of FMPs. A total of 314 questionnaires were completed (response rate = 92%). Median age of participants was 41 years and 57% were females. Almost 61% of FMPs answered all the knowledge questions correctly and 64% reported moderate understanding of the association between periodontal health and obesity. Nearly 73% FMPs inquired from obese patients regarding the periodontal disease and more than half (58%) refer patients to a dentist for evaluation. More than half of FMPs perform periodontal disease screening. Nearly all FMPs considered informing obese patients regarding periodontal disease as one of their roles. FMP's play an important role in the early diagnosis, prevention and treatment of periodontal conditions in obese patients. More than two thirds of FMPs showed good knowledge of the association of obesity and periodontal disease. The attitudes of FMPs towards assessing and referring obese patients at a risk of having periodontal disease were reassuring.

EndoBarrier Gastrointestinal Liner in Type 2 Diabetic Patients Improves Liver Fibrosis as Assessed by Liver Elastography.

Many obese people with type 2 diabetes develop non-alcoholic fatty liver disease, which may progress to liver fibrosis. EndoBarrier gastrointestinal liner is an innovative interventional treatment option for type 2 diabetic patients, which could affect diabetes associated liver disease. The aim of this retrospective study was to analyze the effect of 1-year EndoBarrier therapy on liver fibrosis and steatosis. As an indicator of fibrosis, liver stiffness was assessed by liver elastography at baseline, 2 weeks after EndoBarrier implantation and then every 3 months until explantation. 13/19 patients had elevated liver stiffness at baseline, corresponding to liver fibrosis grade 2 to 4. In these patients, liver stiffness reduced significantly during EndoBarrier therapy from 10.4 kPa (IQR 6.0-14.3) at baseline to 5.3 kPa (IQR 4.3-7.7, p<0.01) by the time of EndoBarrier explantation, corresponding to a normalization of the initially pathologic findings in most patients. Liver steatosis was also assessed by elastographic measurements in terms of the controlled attenuation parameter. In all patients, baseline measurements showed high grade steatosis. Improvements were seen from initially 343 dB/m (IQR 326-384) to 317 dB/m (IQR 269-375, p<0.05) by the time of explantation. However, most patients were still classified high grade steatosis after completion of EndoBarrier treatment. In this observational study, we show that liver fibrosis is a common condition in obese patients suffering from type 2 diabetes, and that EndoBarrier gastrointestinal liner substantially improves liver fibrosis in these patients.

Abstract B44: The role of CD4 T cells in murine model of NASH-promoted HCC

Abstract Non-alcoholic steatohepatitis (NASH), a common condition in obese patients, is an important risk factor for HCC. However, only little information exists about the immunological mechanisms of how NASH promotes hepatocarcinogenesis. Methionine choline deficient (MCD) diet is widely used to induce NASH. In this study we fed Lap-tTA-myc mice, which develop HCC, with MCD diet. MCD diet accelerated tumor development in MYC on mice. A robust decrease of hepatic CD4 but not CD8 T cells was observed in NASH mice, which was exacerbated by MYC transgene expression. As expected higher level of cell death was detected in these hepatic CD4 T cells. Phenotypic analysis demonstrated that these CD4 T cells had a CD44highCD62Llow effector memory phenotype and produced more IFNγ. Selective CD4 T cell depletion further accelerated HCC development suggesting an important role of these cells for tumor development. Next, we studied the cause of CD4 T cells. In co-culture experiments we demonstrated that lipid-laden hepatocytes from mice on MCD diet induced selective CD4 but not CD8 T cells death through a contact-independent mechanism. FFAs were found from hepatocyte culture medium, and linoleic acid recapitulates the selective toxicity to CD4 T cells. Blocking ROS abolished linoleic acid-induced CD4 T cell death. Our results suggest the critical role of CD4 T cell in the disease progression of NASH to HCC, and provide a new link between lipid metabolism dysfunction with impaired anti-tumor surveillance. Citation Format: Chi Ma, Miaojun Han, Masaki Terabe, Jay Berzofsky, Dean Felsher, Tim Greten. The role of CD4 T cells in murine model of NASH-promoted HCC. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B44.

Abstract 3166: The role of CD4 T cells in murine model of NASH-promoted HCC

Abstract Aim: Non-alcoholic steatohepatitis (NASH), a common condition in obese patients, is an important risk factor for hepatocellular carcinoma (HCC). However, only little information exists about the immunological mechanisms of how NASH promotes HCC. This study was designed to better understand the role of adaptive immunity during the process of NASH-promoted hepatocarcinogenesis. Experimental procedure: Methionine choline deficient (MCD) diet is widely used to induce NASH. In this study we fed Lap-tTA-myc mice, which develop HCC, with MCD diet. Choline-deficient and amino acid-defined (CDAA) diet and high fat (HF) diet was also used to induce NASH in B6 mice. GK1.5 antibody was used to deplete CD4 T cells. Gas chromatography-mass spectrometry was performed to identify free fatty acids. Difference immune cell subsets were identified by flow cytometry. Cell death was measured by 7AAD/Annexin V staining. Results: MCD diet accelerated tumor development in MYC-on mice. A robust selective decrease of hepatic CD4 but not CD8 T cells was observed in NASH mice, which was exacerbated by MYC transgene expression. The selective decrease of hepatic CD4 T cells was also observed in B6 mice treated with CDAA or HF diet suggesting it's a general phenomena in NASH. As expected higher level of cell death was detected in hepatic CD4 T cells after NASH. Phenotypic analysis demonstrated that these CD4 T cells had a CD44highCD62Llow effector memory phenotype and produced more IFNγ. Selective CD4 T cell depletion further accelerated HCC development suggesting an important role of these cells for tumor development. Next, we studied the cause of CD4 T cell death. In co-culture experiments we demonstrated that lipid-laden hepatocytes from mice on MCD diet induced selective CD4 but not CD8 T cells death through a contact-independent mechanism. FFAs were found from hepatocyte culture medium to be responsible for T cell cytotoxicity, and linoleic acid recapitulates the selective toxicity to CD4 T cells. Blocking ROS abolished linoleic acid-induced CD4 T cell death. In vivo study showed that N-acetyl cysteine reversed the NASH-induced hepatic CD4 T cell decrease and delayed NASH-promoted tumor development. Conclusion: Our results suggest the critical role of CD4 T cells in the disease progression of NASH to HCC, and provide a new link between lipid metabolism dysfunction with impaired anti-tumor surveillance. Citation Format: Chi Ma, Dean Felsher, Tim Greten. The role of CD4 T cells in murine model of NASH-promoted HCC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3166. doi:10.1158/1538-7445.AM2015-3166

Regulation of inflammation by endogenous danger signals in tissue injury and arthritis

Regulation of inflammation by endogenous danger signals in tissue injury and arthritis