Efficacy of endoscopic resuturing versus pharmacotherapy to treat weight recidivism after endoscopic sleeve gastroplasty.

BACKGROUND AND AIMS: A subset of patients experience weight recidivism after primary endoscopic sleeve gastroplasty (P-ESG). Available options for management of weight regain include initiation of antiobesity medications (AOMs) or redo ESG (R-ESG). The comparative effectiveness of these options is not clear. METHODS: This was a retrospective analysis of a prospectively maintained database of patients undergoing ESG. From 2013 to 2021, 79 patients who were started on AOM or underwent R-ESG for management of weight recidivism after P-ESG were included. The primary outcome of this study was final total body weight loss (TBWL) at the end of follow-up. RESULTS: Fifty-five patients were started on AOM and 24 patients underwent R-ESG. Age, gender distribution, and baseline body mass index did not differ significantly between groups. The proportion of noncompliant patients (defined as patients who missed their first post-ESG follow-up visit) was significantly higher in the AOM group compared with the R-ESG group (67% vs 35%, P = .012). The additional TBWL after R-ESG was significantly (both clinically and statistically) better than after initiation of AOM (9.5% ± 7.2% vs 2.1% ± 8.6%, respectively; P = .001). Final TBWL clearly favored R-ESG over AOM for treatment of weight recidivism (19.9% ± 10.4% vs 13.6% ± 9.2%, P = .028). CONCLUSIONS: R-ESG is an effective treatment to induce weight loss after experiencing weight recidivism. These results highlight an important advantage of ESG as a repeatable minimally invasive procedure.

Simultaneous EUS-guided portosystemic pressure measurement and liver biopsy sampling correlate with clinically meaningful outcomes.

BACKGROUND AND AIMS: The measurement of the portosystemic pressure gradient (PSG) in patients with advanced liver disease is helpful to assess the severity of portal hypertension (PH) and predict adverse clinical outcomes. EUS-guided PSG (EUS-PSG) measurement is a novel tool to assess PSG in all patients with advanced liver disease. We sought to assess the safety, feasibility, and technical success of simultaneous EUS-PSG measurement and EUS-guided liver biopsy sampling using a single-center experience. METHODS: Patients with suspected liver disease or cirrhosis were enrolled prospectively from 2020 to 2021. EUS-PSG was measured by calculating the difference between the mean portal pressure and the mean hepatic vein pressure. PH was defined as PSG >5 mm Hg and clinically significant PH as PSG ≥10 mm Hg. The primary outcomes were procedural technical success rate and correlation of EUS-PSG with fibrosis stage obtained from concurrent EUS-guided liver biopsy sampling and the correlation of EUS-PSG with patients' imaging, clinical, and laboratory findings. The secondary outcome was occurrence of procedural adverse events (AEs). RESULTS: Twenty-four patients were included in the study. PSG measurement and EUS-guided liver biopsy sampling were successful in 23 patients (technical success rate of 96%) and 24 patients (100% success), respectively. Analysis revealed a significant association between both PSG and liver stiffness measured on transient elastography (P = .011) and fibrosis-4 score (P = .026). No significant correlation was found between the fibrosis stage on histology and measured PSG (P = .559). One mild AE of abdominal pain was noted. Additionally, EUS-PSG was predictive of clinically evident PH. CONCLUSIONS: Simultaneous EUS-PSG measurement and EUS-guided liver biopsy sampling were both feasible and safe and correlated with clinically evident PH and noninvasive markers of fibrosis.

Effect of Statin Use on Cancer-related Mortality in Nonalcoholic Fatty Liver Disease: A Prospective United States Cohort Study.

BACKGROUND: Indications for use of statins are common among patients with nonalcoholic fatty liver disease (NAFLD). Epidemiologic studies have suggested a possible association between statins and decreased risk of malignancies. We hypothesized that statin use has a protective effect on cancer mortality in patients with NAFLD. METHODS: Participants with NAFLD in 8 rounds of National Health and Nutrition Examination Survey (NHANES) were included in this study. Mortality data were obtained by linking the NHANES data to National Death Index. NAFLD was defined using the previously validated Hepatic Steatosis Index model. RESULTS: A total of 10,821 participants with NAFLD were included and 23% were statin users (n=2523). Statin use was associated with a 43% lower risk of cancer mortality [hazard ratio (HR)=0.57, 95% confidence interval (CI): 0.43-0.75, P<0.001] in multivariable analysis. Statin use under 1 year did not show a significant effect on cancer mortality (HR=0.72, 95% CI: 0.46-1.12), while statin use for 1 to 5 years decreased cancer mortality by 35% (HR=0.65, 95% CI: 0.42-0.99, P=0.46), and statin use >5 years decreased cancer mortality by 56% (HR=0.44, 95% CI: 0.29-0.66, P<0.001). Statin use was associated with a significant decrease in the risk of cancer mortality in NAFLD patients with both low and high risk of liver fibrosis (HR=0.55, 95% CI: 0.38-0.81; and HR=0.53, 95% CI: 0.31-0.89, respectively). CONCLUSION: Using a large US prospective cohort, we showed statin use is associated with a considerable decrease in cancer-related mortality among patients with NAFLD. These results are important for clinical decision making, as statin indications are prevalent among NAFLD patients, but many do not receive benefit in the event that the statin is discontinued due to liver test abnormalities.

Five-Year Outcomes of Endoscopic Sleeve Gastroplasty for the Treatment of Obesity.

BACKGROUND AND AIMS: The growing burden of obesity as a chronic disease necessitates a multifaceted approach to management. There has been an increase in the number of available endoscopic therapies for weight management with endoscopic sleeve gastroplasty (ESG) proving to be one of the best options. The long-term efficacy of ESG for management of obesity is not known. This study sought to assess the long-term safety and efficacy of ESG for treatment of obesity. METHODS: This was a prospective cohort study. Participants underwent ESG in a single academic center, and were prospectively enrolled. All procedures were performed by the same therapeutic endoscopist. Patients with a body mass index of >30 kg/m2 (or >27 with comorbidities), who underwent ESG from August 2013 to August 2019 for treatment of obesity were enrolled. Patients were followed for up to 5 years after their procedure. The primary outcome was weight loss at 5 years after the procedure (% total body weight loss, TBWL) RESULTS: 216 patients (68% female) with a mean age of 46±13 years, and mean BMI of 39±6 kg/m2 underwent ESG. Out of 216 patients, 203, 96, and 68 patients were eligible for a 1-, 3-, and 5-year follow up, with complete follow-up rates of 70%, 71%, and 82%, respectively. At 5 years, mean TBWL was 15.9% (95% CI, 11.7-20.5, p < .001) and 90 and 61% of patients maintained 5 and 10% TBWL, respectively. There was an overall rate of 1.3% moderate adverse events (AEs), without any severe or fatal AEs. CONCLUSIONS: Our results suggest that ESG is safe and effective for treatment of obesity, with durable long-term results for at least up to 5 years after the procedure. This procedure should be considered as a reliable option for treatment of obesity.

Improvement in insulin resistance and estimated hepatic steatosis and fibrosis after endoscopic sleeve gastroplasty.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and is closely associated with obesity and insulin resistance (IR). Weight loss is the best treatment for NAFLD. Endoscopic sleeve gastroplasty (ESG) is a promising endoscopic procedure for treatment of obesity. Our aim is to evaluate the change in IR and estimated hepatic steatosis and fibrosis after ESG. METHODS: One hundred eighteen patients with obesity and NAFLD underwent ESG and were followed for 2 years. Weight loss was evaluated as % total body weight loss. IR was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). The previously validated hepatic steatosis index and NAFLD fibrosis score were used to estimate hepatic steatosis and risk of fibrosis. RESULTS: Patients' mean body mass index was 40 ± 7 kg/m2 at baseline. Eighty-four percent of patients completed 2 years of follow-up. At 2 years, the mean total body weight loss was 15.5% (95% confidence interval, 13.3%-17.8%). Patients' HOMA-IR improved significantly from 6.7 ± 11 to 3.0 ± 1.6 after only 1 week from ESG (P = .019) with continued improvement up to 2 years (P = .03). Patients' hepatic steatosis index score improved significantly, decreasing by 4 points per year (P for trend, <.001). Patients' NAFLD fibrosis score improved significantly, decreasing by 0.3 point per year (P for trend, .034). Twenty-four patients (20%) improved their risk of hepatic fibrosis from F3-F4 or indeterminate to F0-F2, whereas only 1 patient (1%) experienced an increase in the estimated risk of fibrosis (P = .02). CONCLUSIONS: Our results suggest a significant and sustained improvement in estimated hepatic steatosis and fibrosis after ESG in patients with NAFLD. Importantly, we showed an early and weight-independent improvement in insulin resistance, which lasted for 2 years after the procedure.

Endoscopic ultrasound-guided gallbladder drainage as a rescue therapy for unresectable malignant biliary obstruction: a multicenter experience.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is often unsuccessful in patients with duodenal stenosis or malignant ampullary infiltration. While endoscopic ultrasound-guided biliary drainage (EUS-BD) has been proposed as an alternative, EUS-guided gallbladder drainage (EUS-GBD) is an attractive option when both approaches fail. We aimed to assess the effectiveness and safety of EUS-GBD as rescue therapy for malignant distal bile duct obstruction. METHODS: A multicenter retrospective study was performed on patients with unresectable malignant distal bile duct obstruction who underwent EUS-GBD between 2014 and 2019 after unsuccessful ERCP and EUS-BD. Clinical success was defined as a decrease in serum bilirubin of > 50 % within 2 weeks. RESULTS: 28 patients were included, with a lumen-apposing metal stent used in 26 (93 %) and a self-expandable metal stent in two (7 %). The technical success rate was 100 %. The clinical success rate was 93 %, with an improvement in bilirubin (7.3 [SD 5.4] pre-procedure vs. 2.8 [SD 1.1] post-procedure; P = 0.001). Delayed adverse events included food impaction of the stent (n = 3), with a further two patients developing cholecystitis and bleeding. CONCLUSION: This study demonstrates the feasibility of gallbladder drainage to relieve malignant distal bile duct obstruction in patients with failed ERCP and EUS-BD.

Gastrointestinal Bleeding in Patients With Coronavirus Disease 2019: A Matched Case-Control Study.

INTRODUCTION: Although current literature has addressed gastrointestinal presentations including nausea, vomiting, diarrhea, abnormal liver chemistries, and hyperlipasemia as possible coronavirus disease 2019 (COVID-19) manifestations, the risk and type of gastrointestinal bleeding (GIB) in this population is not well characterized. METHODS: This is a matched case-control (1:2) study with 41 cases of GIB (31 upper and 10 lower) in patients with COVID-19 and 82 matched controls of patients with COVID-19 without GIB. The primary objective was to characterize bleeding etiologies, and our secondary aim was to discuss outcomes and therapeutic approaches. RESULTS: There was no difference in the presenting symptoms of the cases and controls, and no difference in severity of COVID-19 manifestations (P > 0.05) was observed. Ten (32%) patients with upper GIB underwent esophagogastroduodenoscopy and 5 (50%) patients with lower GIBs underwent flexible sigmoidoscopy or colonoscopy. The most common upper and lower GIB etiologies were gastric or duodenal ulcers (80%) and rectal ulcers related to rectal tubes (60%), respectively. Four of the esophagogastroduodenoscopies resulted in therapeutic interventions, and the 3 patients with rectal ulcers were referred to colorectal surgery for rectal packing. Successful hemostasis was achieved in all 7 cases that required interventions. Transfusion requirements between patients who underwent endoscopic therapy and those who were conservatively managed were not significantly different. Anticoagulation and rectal tube usage trended toward being a risk factor for GIB, although it did not reach statistical significance. DISCUSSION: In COVID-19 patients with GIB, compared with matched controls of COVID-19 patients without GIB, there seemed to be no difference in initial presenting symptoms. Of those with upper and lower GIB, the most common etiology was peptic ulcer disease and rectal ulcers from rectal tubes, respectively. Conservative management seems to be a reasonable initial approach in managing these complex cases, but larger studies are needed to guide management.

Effect of Alcohol Consumption on Survival in Nonalcoholic Fatty Liver Disease: A National Prospective Cohort Study.

Nonalcoholic fatty liver disease (NAFLD) comprises more than two thirds of patients with chronic liver disease in the United States. The effect of alcohol consumption on survival in patients with NAFLD is not clear. We gathered data on National Health and Nutrition Examination Survey participants from 1988 to 2010, and linked them to the National Death Index for follow-up of their survival. We diagnosed NAFLD based on a previously validated biochemical model (Hepatic Steatosis Index). We built multivariate Cox proportional hazards models to evaluate the effect of alcohol consumption on survival of patients with NAFLD. After excluding participants with significant alcohol use, viral hepatitis, or increased transferrin saturation, 4,568 participants with NAFLD were included in the analysis. In a Cox model adjusted for age, sex, and smoking history, drinking 0.5-1.5 drinks per day decreased the risk of overall mortality by 41% (hazard ratio [HR] = 0.59, 95% confidence interval [CI] 0.40-0.85, P = 0.005) compared with not drinking. Drinking ≥1.5 drinks per day showed a trend toward harm (HR = 1.16, 95% CI 0.99-1.36, P = 0.119). After further adjustment for race, physical activity, education level, diabetes, and fiber and polyunsaturated fatty acid intake, drinking 0.5-1.5 drinks per day continued to show a significant protective effect (HR = 0.64, 95% CI 0.42-0.97, P = 0.035), and drinking ≥1.5 drinks per day showed a significant harmful effect on mortality (HR = 1.45, 95% CI 1.01-2.10, P = 0.047). Among patients with NAFLD, modest alcohol consumption is associated with a significant decrease in all-cause mortality, whereas drinking ≥1.5 drinks per day is associated with an increase in mortality. These results help to inform the discussion of potential risks and benefits of alcohol use in patients with NAFLD.

Risk of Early Colorectal Cancers Needs to Be Considered in Inflammatory Bowel Disease Care.

BACKGROUND: Current guidelines recommend starting colorectal cancer (CRC) surveillance 8-10 years after inflammatory bowel disease (IBD) onset. Recent studies report that the incidence of CRC within 8-10 years of IBD onset (i.e., early CRC) ranges from 12 to 42%. AIMS: To describe the current prevalence of early CRC in a tertiary care center IBD cohort with CRC and to identify associated risk factors. METHODS: We performed a single-center observational study of IBD patients diagnosed with CRC from 2005 to 2015. We compared characteristics of patients with early CRC (diagnosis of CRC within 8 years of initial IBD onset) to those with CRC diagnosed later in their IBD course. RESULTS: Ninety-three patients met inclusion criteria. Eleven (11.8%) patients developed CRC within 8 years of initial IBD onset. On multivariable logistic regression, age greater than 28 at IBD onset (adjusted OR 12.0; 95% CI 2.30, 62.75) and tobacco use (adjusted OR 8.52; 95% CI 1.38, 52.82) were significant predictors of early CRC. A validation cohort confirmed calibration and discrimination of the model. CONCLUSIONS: One out of every eight IBD patients with CRC developed their malignancy prior to the currently recommended timeframe for the initiation of surveillance colonoscopy. IBD onset at 28 years or older and tobacco use were identified as predictors of early CRC. Early CRC should be considered in discussions of cancer surveillance in this population. Prospective cohort studies are necessary to further analyze the impact of early CRC in IBD.

Sick Populations and Sick Subpopulations: Reducing Disparities in Cardiovascular Disease Between Blacks and Whites in the United States.

BACKGROUND: Cardiovascular disease (CVD) death rates are much higher in blacks than whites in the United States. It is unclear how CVD risk and events are distributed among blacks versus whites and how interventions reduce racial disparities. METHODS: We developed risk models for fatal and for fatal and nonfatal CVD using 8 cohorts in the United States. We used 6154 adults who were 50 to 69 years of age in the National Health and Nutrition Examination Survey 1999 to 2012 to estimate the distributions of risk and events in blacks and whites. We estimated the total and disparity impacts of a range of population-wide, targeted, and risk-based interventions on 10-year CVD risks and event rates. RESULTS: Twenty-five percent (95% confidence interval [CI], 22-28) of black men and 12% (95% CI, 10-14) of black women were at ≥6.67% risk of fatal CVD (almost equivalent to 20% risk of fatal or nonfatal CVD) compared with 10% (95% CI, 8-12) of white men and 3% (95% CI, 2-4) of white women. These high-risk individuals accounted for 55% (95% CI, 49-59) of CVD deaths among black men and 42% (95% CI, 35-46) in black women compared with 30% (95% CI, 24-35) in white men and 18% (95% CI, 13-22) in white women. We estimated that an intervention that treated multiple risk factors in high-risk individuals could reduce black-white difference in CVD death rate from 1659 to 1244 per 100 000 in men and from 1320 to 897 in women. Rates of fatal and nonfatal CVD were generally similar between black and white men. In women, a larger proportion of women were at ≥7.5% risk of CVD (30% versus 19% in whites), and an intervention that targeted multiple risk factors among this group was estimated to reduce black-white differences in CVD rates from 1688 to 1197 per 100 000. CONCLUSIONS: A substantially larger proportion of blacks have a high risk of fatal CVD and bear a large share of CVD deaths. A risk-based intervention that reduces multiple risk factors could substantially reduce overall CVD rates and racial disparities in CVD death rates.

Serum 25-Hydroxyvitamin D Levels and the Risk of Dysplasia and Esophageal Adenocarcinoma in Patients with Barrett's Esophagus.

BACKGROUND: To date, there are no studies reporting an association between vitamin D and Barrett's esophagus (BE), the precursor for esophageal adenocarcinoma (EAC). AIMS: Our aim was to study the association between serum 25-hydroxyvitamin D (25(OH)D) levels and prevalence and incidence of dysplasia/EAC in BE. METHODS: Patients from our BE Registry cohort seen between 2000 and 2012 who had serum 25(OH)D levels measured were included. Age, gender, race, BE length, hiatal hernia size, and histological findings were recorded. Patients without high-grade dysplasia (HGD)/EAC at or within 1 year of index biopsy and who had follow-up endoscopies and 25(OH)D levels were studied for incidence of dysplasia/EAC. RESULTS: Among 429 patients with BE, the mean 25(OH)D level was 72 ± 31.2 nmol/L. Hundred and one (23.6 %) patients had deficiency (<50 nmol/L), 149 (34.7 %) had insufficiency (50-74.9 nmol/L), and 179 (41.7 %) had normal levels of 25(OH)D. There was no association between serum 25(OH)D levels and dysplasia (p = 0.90). In the incidence cohort of 246 patients with median follow-up of 46 months, there were 34 cases of low-grade dysplasia, 12 of HGD, and 5 of EAC. Change in 25(OH)D levels did not impact progression to dysplasia/EAC (every 5 nmol/L increase from baseline, hazard ratio 0.98; p = 0.62). CONCLUSIONS: Serum 25(OH)D levels were low in 58.3 % of our BE cohort. There was no association between 25(OH)D levels and prevalence or incidence of HGD/EAC in patients with BE. Further long-term studies are needed to study the association between vitamin D status and progression of dysplasia in BE.

Metabolic mediators of the effects of body-mass index, overweight, and obesity on coronary heart disease and stroke: a pooled analysis of 97 prospective cohorts with 1·8 million participants.

BACKGROUND: Body-mass index (BMI) and diabetes have increased worldwide, whereas global average blood pressure and cholesterol have decreased or remained unchanged in the past three decades. We quantified how much of the effects of BMI on coronary heart disease and stroke are mediated through blood pressure, cholesterol, and glucose, and how much is independent of these factors. METHODS: We pooled data from 97 prospective cohort studies that collectively enrolled 1·8 million participants between 1948 and 2005, and that included 57,161 coronary heart disease and 31,093 stroke events. For each cohort we excluded participants who were younger than 18 years, had a BMI of lower than 20 kg/m(2), or who had a history of coronary heart disease or stroke. We estimated the hazard ratio (HR) of BMI on coronary heart disease and stroke with and without adjustment for all possible combinations of blood pressure, cholesterol, and glucose. We pooled HRs with a random-effects model and calculated the attenuation of excess risk after adjustment for mediators. FINDINGS: The HR for each 5 kg/m(2) higher BMI was 1·27 (95% CI 1·23-1·31) for coronary heart disease and 1·18 (1·14-1·22) for stroke after adjustment for confounders. Additional adjustment for the three metabolic risk factors reduced the HRs to 1·15 (1·12-1·18) for coronary heart disease and 1·04 (1·01-1·08) for stroke, suggesting that 46% (95% CI 42-50) of the excess risk of BMI for coronary heart disease and 76% (65-91) for stroke is mediated by these factors. Blood pressure was the most important mediator, accounting for 31% (28-35) of the excess risk for coronary heart disease and 65% (56-75) for stroke. The percentage excess risks mediated by these three mediators did not differ significantly between Asian and western cohorts (North America, western Europe, Australia, and New Zealand). Both overweight (BMI ≥25 to <30 kg/m(2)) and obesity (BMI ≥30 kg/m(2)) were associated with a significantly increased risk of coronary heart disease and stroke, compared with normal weight (BMI ≥20 to <25 kg/m(2)), with 50% (44-58) of the excess risk of overweight and 44% (41-48) of the excess risk of obesity for coronary heart disease mediated by the selected three mediators. The percentages for stroke were 98% (69-155) for overweight and 69% (64-77) for obesity. INTERPRETATION: Interventions that reduce high blood pressure, cholesterol, and glucose might address about half of excess risk of coronary heart disease and three-quarters of excess risk of stroke associated with high BMI. Maintenance of optimum bodyweight is needed for the full benefits. FUNDING: US National Institute of Health, UK Medical Research Council, National Institute for Health Research Comprehensive Biomedical Research Centre at Imperial College Healthcare NHS Trust, Lown Scholars in Residence Program on cardiovascular disease prevention, and Harvard Global Health Institute Doctoral Research Grant.

Mediators of the effect of body mass index on coronary heart disease: decomposing direct and indirect effects.

BACKGROUND: The prevalence of overweight and obesity is rising globally and together they constitute a major risk factor for coronary heart disease (CHD). Previous estimates of direct effects of high body mass index (BMI) on CHD did not consider an interaction between BMI and its mediators and did not include inflammatory biomarkers as potential mediators. METHODS: We analyzed data from 9 prospective cohort studies with 58,322 participants and 9,459 CHD events and decomposed the total effects into natural direct and indirect effects using a 2-stage regression model. We examined overweight (BMI = 25 to <30 kg/m) separately. We pooled hazard ratios using random-effects models and calculated the percentages of excess relative risk mediated by blood pressure, cholesterol, glucose, fibrinogen and high-sensitive C-reactive protein. RESULTS: There was no interaction between BMI and its mediators in the multiplicative scale (P < 0.05 for all). Blood pressure was the most important mediator. The percentage of excess relative risk of overweight (versus normal BMI, 20 to <25 kg/m) mediated was 28% for blood pressure, 10% for blood glucose, and 14% for cholesterol. The same percentages for obesity were 37% for blood pressure, 17% for blood glucose, and 6% for cholesterol. The percentage mediated through all three metabolic risk factors together was 47% (95% confidence interval = 33%-63%) for overweight and 52% (38%-68%) for obesity. Fibrinogen mediated 6% to 9% and high-sensitive C-reactive protein mediated 6% to 8% of the excess relative risk for overweight and obese participants. CONCLUSIONS: Metabolic mediators explain about half of the adverse effects of high BMI on CHD. The role of inflammatory and prothrombotic biomarkers is much smaller than that of metabolic factors.