IL28B Alleles Exert an Additive Dose Effect When Applied to HCV-HIV Coinfected Persons Undergoing Peginterferon and Ribavirin Therapy

BACKGROUND: Genetic studies have demonstrated a strong association between single nucleotide polymorphisms (SNPs) at IL28B and response to treatment with peginterferon (PEG) and ribavirin (RBV) in HCV monoinfected persons. We sought to test these associations in a prospective PEG / weight based ribavirin (WBR) treatment trial (ACTG A5178) (National Institution of Health registration number NCT00078403) in persons with HCV-HIV coinfection, and to develop a prediction score. METHODS: We selected subjects enrolled in A5178 who completed at least the first 12 weeks of the trial and had DNA available, and genotyped three SNPs at IL28B (rs12979860, rs12980275, rs8099917). We used multivariate logistic regression analysis to evaluate the association between IL28B SNPs and HCV treatment outcomes and to develop the prediction score. RESULTS: 231 HCV/HIV coinfected subjects were included. We observed a strong association between IL28B genotype and response to therapy among those with genotypes 1 or 4 (odds ratio for complete early virologic responses (cEVR) and sustained virologic response (SVR) was 2.98 [1.7-5.3] and 3.4 [1.7-6.9], respectively, for each additional copy of the C allele of rs12979860). Differences in frequency of the responder allele explained some of the discrepancy in HCV treatment outcomes between blacks and whites. A simple pretreatment prediction score that incorporates the IL28B genotype and baseline HCV viral load has a 93% negative predictive value (NPV) for SVR. CONCLUSIONS: IL28B SNPs have an additive allele dose effect in predicting HCV treatment outcomes in HCV/HIV coinfected persons and can be incorporated into a simple pretreatment prediction score that could minimize the risk of exposure to PEG/RBV therapy for persons with unfavorable scores

Safety and efficacy of lumen-apposing metal stents versus plastic stents to treat walled-off pancreatic necrosis: systematic review and meta-analysis

Background and study aims Lumen-apposing metal stents (LAMS) are increasingly used for drainage of walled-off pancreatic necrosis (WON). Recent studies suggested greater adverse event (AE) rates with LAMS for WON. We conducted a systematic review and meta-analysis to compare the safety and efficacy of LAMS with double-pigtail plastic stents (DPPS) for endoscopic drainage of WON. The primary aim was to evaluate stent-related AEs. Methods In October 2019, we searched the Ovid (Embase, MEDLINE, Cochrane) and Scopus databases for studies assessing a specific LAMS or DPPS for WON drainage conducted under EUS guidance. Safety outcomes were AE rates of bleeding, stent migration, perforation, and stent occlusion. Efficacy outcomes were WON resolution and number of procedures needed to achieve resolution. A subanalysis including non-EUS-guided cases was performed. Results Thirty studies including one randomized controlled trial (total 1,524 patients) were analyzed. LAMS were associated with similar bleeding (2.5 % vs. 4.6 %, P = 0.39) and perforation risk (0.5 % vs. 1.1 %, P = 0.35) compared to DPPS. WON resolution (87.4 % vs. 87.5 %, P = 0.99), number of procedures to achieve resolution (2.09 vs. 1.88, P = 0.72), stent migration (5.9 % vs. 6.8 %, P = 0.79), and stent occlusion (3.8 % vs. 5.2 %, P = 0.78) were similar for both groups. Inclusion of non-EUS-guided cases led to significantly higher DPPS bleeding and perforation rates. Conclusions LAMS and DPPS were associated with similar rates of AEs and WON resolution when limiting analysis to EUS-guided cases. Higher bleeding rates were seen in historical studies of DPPS without EUS guidance. Additional high-quality studies of WON treatment using consistent outcome definitions are needed

Aspiration therapy for the treatment of obesity: 4-year results of a multicenter randomized controlled trial.

BackgroundThe AspireAssist is the first Food and Drug Administration-approved endoluminal device indicated for treatment of class II and III obesity.ObjectivesWe earlier reported 1-year results of the PATHWAY study. Here, we report 4-year outcomes.SettingUnited States-based, 10-center, randomized controlled trial involving 171 participants with the treatment arm receiving Aspiration Therapy (AT) plus Lifestyle Therapy and the control arm receiving Lifestyle Therapy (2:1 randomization).MethodsAT participants were permitted to continue in the study for an additional year up to a maximum of 5 years providing they maintained at least 10% total weight loss (TWL) from baseline at each year end. For AT participants who continued the study, 5 medical monitoring visits were provided at weeks 60, 68, 76, 90, and 104 and thereafter once every 13 weeks up to week 260. Exclusion criteria were a history of eating disorder or evidence of eating disorder on a validated questionnaire. Follow-up weight, quality of life, and co-morbidities were compared with the baseline levels. In addition, rates of serious adverse event, persistent fistula, withdrawal, and A-tube replacement were reported. All analyses were performed using a per-protocol analysis.ResultsOf the 82 AT participants who completed 1 year, 58 continued to this phase of the trial. Mean baseline body mass index of these 58 patients was 41.6 ± 4.5 kg/m2. At the end of first year (at the beginning of the follow-up study), these 58 patients had a body mass index of 34.1 ± 5.4 kg/m2 and had achieved an 18.3 ± 8.0% TWL. On a per protocol basis, patients experienced 14.2%, 15.3%, 16.6%, and 18.7% TWL at 1, 2, 3, and 4 years, respectively (P < .01 for all). Forty of 58 patients (69%) achieved at least 10% TWL at 4 years or at time of study withdrawal. Improvements in quality of life scores and select cardiometabolic parameters were also maintained through 4 years. There were 2 serious adverse events reported in the second through fourth years, both of which resolved with removal or replacement of the A tube. Two persistent fistulas required surgical repair, representing approximately 2% of all tube removals. There were no clinically significant metabolic or electrolytes disorders observed, nor any evidence for development of any eating disorders.ConclusionsThe results of this midterm study have shown that AT is a safe, effective, and durable weight loss alternative for people with class II and III obesity and who are willing to commit to using the therapy and adhere to adjustments in eating behavior

EUS-derived criteria for distinguishing benign from malignant metastatic solid hepatic masses

Background Detection of hepatic metastases during EUS is an important component of tumor staging. Objective To describe our experience with EUS-guided FNA (EUS-FNA) of solid hepatic masses and derive and validate criteria to help distinguish between benign and malignant hepatic masses. Design Retrospective study, survey. Setting Single, tertiary-care referral center. Patients Medical records were reviewed for all patients undergoing EUS-FNA of solid hepatic masses over a 12-year period. Interventions EUS-FNA of solid hepatic masses. Main Outcome Measurements Masses were deemed benign or malignant according to predetermined criteria. EUS images from 200 patients were used to create derivation and validation cohorts of 100 cases each, matched by cytopathologic diagnosis. Ten expert endosonographers blindly rated 15 initial endosonographic features of each of the 100 images in the derivation cohort. These data were used to derive an EUS scoring system that was then validated by using the validation cohort by the expert endosonographer with the highest diagnostic accuracy. Results A total of 332 patients underwent EUS-FNA of a hepatic mass. Interobserver agreement regarding the initial endosonographic features among the expert endosonographers was fair to moderate, with a mean diagnostic accuracy of 73% (standard deviation 5.6). A scoring system incorporating 7 EUS features was developed to distinguish benign from malignant hepatic masses by using the derivation cohort with an area under the receiver operating curve (AUC) of 0.92; when applied to the validation cohort, performance was similar (AUC 0.86). The combined positive predictive value of both cohorts was 88%. Limitations Single center, retrospective, only one expert endosonographer deriving and validating the EUS criteria. Conclusion An EUS scoring system was developed that helps distinguish benign from malignant hepatic masses. Further study is required to determine the impact of these EUS criteria among endosonographers of all experience

Weight regain after Roux-en-Y gastric bypass has a large negative impact on the Bariatric Quality of Life Index

Background: Despite initial successful weight loss, some patients may experience weight regain following Roux-en-Y gastric bypass (RYGB). Objective: To assess the impact of weight regain on bariatric patients’ quality of life (QoL). Methods: This was a prospective cross-sectional study. Fifty-six consecutive RYGB patients were recruited and divided into weight-regain and weight-stable cohorts. QoL was assessed using the Bariatric Quality of Life (BQL) questionnaire. The BQL Index scores of the weight-regain and weight-stable groups were compared using Student’s t-test. Additionally, the BQL Index score of the weight-regain group was compared with that of historical prebariatric patients. Predictors of BQL were assessed using univariate and multivariate linear regression analyses. Results: Of 56 RYGB patients, 41 (73%) had weight regain. On average, patients had body mass index (BMI) of 37 ±7.5 kg/m2 and gained 34 ±26% of maximal weight initially lost. Weight-regain patients had lower BQL Index scores than weight-stable patients (44.8±6 vs 53±7, p<0.001). Patients with weight regain had similar BQL Index scores as the prebariatric patients despite lower BMI (BMI of 39.7±6.8 vs 47.2±7.6, p<0.05; BQL Index of 44.8±6 vs 41.6±10.4, p=0.144, respectively). Years from RYGB, BMI and amount of weight regain were associated with BQL Index on a univariate analysis (β=−0.55,−0.52, −0.7; p<0.0001). Only weight regain was a significant predictor of BQL on a multivariate analysis (β =−0.56; p=0.001). Conclusion: Weight regain had a negative impact on bariatric patients’ QoL. Patients who regained at least 15% of maximal weight lost appeared to have as low QoL as those who had not undergone bariatric surgery despite a lower BMI

Obesity and bariatrics for the endoscopist: new techniques

Obesity and its associated conditions, including type 2 diabetes and cardiovascular disease, have reached epidemic proportions. Gastrointestinal weight loss surgery (GIWLS) shows the most promise in achieving significant and sustained weight loss and diabetes resolution. However, a large mismatch exists between the magnitude of the obesity epidemic and the number of surgical procedures performed to produce a significant shift in the distribution of obesity on a population level. This mismatch is fueled by high surgical costs, morbidity and mortality associated with surgical interventions, and the fact that the greatest public health burden of obesity comes from those around the center of the population body mass index distribution with mild to moderate obesity, rather than those at the distribution tail with severe obesity that GIWLS targets. New endoscopic methods, capitalizing on advances in our understanding of the physiological mechanisms by which GIWLS works, are developing to provide viable alternatives in the treatment of bariatric surgical complications, and for the primary treatment of obesity. These methods may have the added advantage of reduced invasiveness, reversibility, cost-effectiveness, and applicability to a larger segment of the population with moderate obesity