Histology, Size, and Number of Advanced Polyps are Associated With Guideline-Discordant Surveillance Recommendations.

Surveillance guidelines following polypectomy promote cost-effective reductions in future colorectal cancer (CRC) risk, but high nonadherence rates1 can have negative consequences on costs and effectiveness. Professional societies recommend a 3-year interval for patients with advanced colorectal polyps (ACPs), although few studies report provider adherence to surveillance intervals.2 This study evaluated rates and predictors of guideline-discordant recommendations for patients with ACPs.

Predictors of Failed Conscious Sedation in Patients Undergoing an Outpatient Colonoscopy and Implications for the Adenoma Detection Rate.

Guidelines to triage patients to conscious sedation (CS) or monitored anaesthesia care (MAC) for colonoscopy do not exist. We aimed to identify the CS failure rate, predictors of failure, and its impact on the adenoma detection rate (ADR). Strict (based on patient experience) and expanded (based on doses of sedative medications) definitions of CS failure were used. Patient and procedure-related variables were extracted. Multivariable logistic regression identified predictors for CS failure and the ADR. Among 766 patients, 29 (3.8%) and 175 (22.8%) patients failed CS by strict and expanded definitions, respectively. Female gender (OR 3.50; 95% CI: 1.37-8.94) and fellow involvement (OR 4.15; 95% CI: 1.79-9.58) were associated with failed CS by the strict definition. Younger age (OR 1.27, 95% CI: 1.07-1.49), outpatient opiate use (OR 1.71; 95% CI 1.03-2.84), use of an adjunct medication (OR 3.34; 95% CI: 1.94-5.73), and fellow involvement (OR 2.20; 95% CI: 1.31-3.71) were associated with failed CS by the expanded definition. Patients meeting strict failure criteria had a lower ADR (OR 0.30; 95% CI: 0.12-0.77). Several clinical factors may be useful for triaging to MAC. The ADR is lower in patients meeting strict criteria for failed CS.

Training Mentor-Mentee Pairs to Build a Robust Culture for Mentorship and a Pipeline of Clinical and Translational Researchers: The Colorado Mentoring Training Program.

The Colorado Mentoring Training program (CO-Mentor) was developed at the University of Colorado Anschutz Medical Campus in 2010, supported by the Colorado Clinical and Translational Sciences Institute. CO-Mentor represents a different paradigm in mentorship training by focusing equally on the development of mentees, who are valued as essential to institutional capacity for effective mentorship. The training model is unique among Clinical and Translational Science Award sites in that it engages mentors and mentees in an established relationship. Dyads participate in 4 day-long sessions scheduled throughout the academic year. Each session features workshops that combine didactic and experiential components. The latter provide structured opportunities to develop mentorship-related skills, including self-knowledge and goal setting, communication skills (including negotiation), "managing up," and the purposeful development of a mentorship support network. Mentors and mentees in 3 recent cohorts reported significant growth in confidence with respect to all mentorship-related skills assessed using a pre-post evaluation survey (P = .001). Mentors reported the most growth in relation to networking to engage social and professional support to realize goals as well as sharing insights regarding paths to success. Mentees reported the most growth with respect to connecting with potential/future mentors, knowing characteristics to look for in current/future mentors, and managing the work environment (e.g., prioritizing work most fruitful to advancing research/career objectives). CO-Mentor represents a novel approach to enhancing mentorship capacity by investing equally in the development of salient skills among mentees and mentors and in the mentorship relationship as an essential resource for professional development, persistence, and scholarly achievement.

A compartmentalized type I interferon response in the gut during chronic HIV-1 infection is associated with immunopathogenesis.

OBJECTIVE(S): Type I interferon (IFN-I) responses confer both protective and pathogenic effects in persistent virus infections. IFN-I diversity, stage of infection and tissue compartment may account for this dichotomy. The gut is a major site of early HIV-1 replication and microbial translocation, but the nature of the IFN-I response in this compartment remains unclear. DESIGN: Samples were obtained from two IRB-approved cross-sectional studies. The first study included individuals with chronic, untreated HIV-1 infection (n = 24) and age/sex-balanced uninfected controls (n = 14). The second study included antiretroviral-treated, HIV-1-infected individuals (n = 15) and uninfected controls (n = 15). METHODS: The expression of 12 IFNα subtypes, IFNß and antiviral IFN-stimulated genes (ISGs) were quantified in peripheral blood mononuclear cells (PBMCs) and colon biopsies using real-time PCR and next-generation sequencing. In untreated HIV-1-infected individuals, associations between IFN-I responses and gut HIV-1 RNA levels as well as previously established measures of colonic and systemic immunological indices were determined. RESULTS: IFNα1, IFNα2, IFNα4, IFNα5 and IFNα8 were upregulated in PBMCs during untreated chronic HIV-1 infection, but IFNß was undetectable. By contrast, IFNß was upregulated and all IFNα subtypes were downregulated in gut tissue. Gut ISG levels positively correlated with gut HIV-1 RNA and immune activation, microbial translocation and inflammation markers. Gut IFN-I responses were not significantly different between HIV-1-infected individuals on antiretroviral treatment and uninfected controls. CONCLUSION: The IFN-I response is compartmentalized during chronic untreated HIV-1 infection, with IFNß being more predominant in the gut. Gut IFN-I responses are associated with immunopathogenesis, and viral replication is likely a major driver of this response.

Association of Proton Pump Inhibitor Use With Serum Biomarkers of Inflammation, Insulin Resistance, Cardiovascular Risk, and Renal Function.

BACKGROUND AND GOALS: Proton pump inhibitor (PPI) use has been associated with cardiovascular disease, chronic kidney disease, and dementia. Prior studies did not account for key confounders and little is known about the association of PPIs with serum biomarkers of inflammation, insulin resistance, cardiovascular risk, and renal function. Our aims were to investigate differences in these biomarkers between PPI users and nonusers. METHODS: Our data are from the National Health and Nutrition Examination Survey (NHANES), a complex cross-sectional multistage probability sample of the US civilian population. We used data on 5189 eligible adults aged 18 to 85 years. Appropriate survey commands were used and potential confounding variables (including BMI, duration of PPI use, use of other non-PPI medications, and health behaviors) were included in multivariable regression models assessing biomarker outcomes. RESULTS: PPI use was associated with differences in mean (±SE) fasting low-density lipoprotein (LDL) (by 11.7±3.7 mg/dL; P=0.006), and apolipoprotein B (by 7.6±2.6 mg/dL; P=0.01). PPI use was not associated with significant differences in total cholesterol (P=0.13), high-density lipoprotein (P=0.27), triglycerides (P=0.70), c-reactive protein (P=0.52), the homeostatic model assessment-insulin resistance (P=0.48), hemoglobin A1c (P=0.39), or homocysteine (P=0.87). PPI use was associated with a decrease in blood urea nitrogen (by 1.0±0.3 mg/dL; P=0.008) but not creatinine (P=0.38) or uric acid (P=0.34). CONCLUSION: PPI was not associated with clinically significant differences in serum biomarkers of inflammation, insulin resistance, cardiovascular risk, and renal function. Rather, increasing BMI was strongly associated with PPI use and clinically significant differences in these biomarkers.

Brief Report: Inflammatory Colonic Innate Lymphoid Cells Are Increased During Untreated HIV-1 Infection and Associated With Markers of Gut Dysbiosis and Mucosal Immune Activation.

BACKGROUND: HIV-1 infection is associated with intestinal inflammation, changes in the enteric microbiota (dysbiosis), and intestinal epithelial cell damage. NKp44 innate lymphoid cells (ILCs) play an important role in epithelial barrier maintenance through the production of interleukin (IL)-22 but also display functional plasticity and can produce inflammatory cytokines [eg, interferon gamma (IFNγ)] in response to cytokine milieu and stimulatory signals. The objective of this pilot study was to enumerate frequencies of IL-22 and IFNγ-expressing colonic NKp44 ILCs during untreated, chronic HIV-1 infection. SETTING: A cross-sectional study was performed to compare numbers of cytokine-expressing ILCs in colonic biopsies of untreated, chronic HIV-1 infected (n = 22), and uninfected (n = 10) study participants. Associations between cytokine ILC and previously established measures of virological, immunological, and microbiome indices were analyzed. METHODS: Multicolor flow cytometry was used to measure the absolute number of colonic CD3NKp44CD56 ILCs expressing IL-22 or IFNγ after in vitro mitogenic stimulation. RESULTS: Numbers of colonic NKp44 ILCs that expressed IFNγ were significantly higher in HIV-1 infected versus uninfected persons and positively correlated with relative abundances of dysbiotic bacterial species in the Xanthomonadaceae and Prevotellaceae bacterial families and with colonic myeloid dendritic cell and T-cell activation. CONCLUSION: Higher numbers of inflammatory colonic ILCs during untreated chronic HIV-1 infection that associated with dysbiosis and colonic myeloid dendritic cell and T-cell activation suggest that inflammatory ILCs may contribute to gut mucosal inflammation and epithelial barrier breakdown, important features of HIV-1 mucosal pathogenesis.

A low-volume polyethylene glycol solution was associated with an increased suboptimal bowel preparation rate but had similar recommendations for an early repeat colonoscopy, procedure times, and adenoma detection rates.

BACKGROUND/AIMS: Low-volume polyethylene glycol (PEG) bowel preparations are better tolerated by patients than high-volume preparations and may achieve similar preparation quality. However, there is little data comparing their effects on a recommendation for an early repeat colonoscopy (because of a suboptimal preparation), procedure times, adenoma detection rate (ADR), and advanced adenoma detection rate (AADR). METHODS: This is a retrospective cohort study of outpatient colonoscopies performed during a one-year period at a single academic medical center in which low-volume MoviPrep® (n = 1841) or high-volume Colyte® (n = 1337) was used. All preparations were split-dosed. Appropriate covariates were included in regression models assessing suboptimal preparation quality (fair, poor, or inadequate), procedure times, recommendation for an early repeat colonoscopy, ADR, and AADR. RESULTS: MoviPrep® was associated with an increase in having a suboptimal bowel preparation (OR 1.36; 95% CI: 1.06-1.76), but it was not associated with differences in insertion (p = 0.43), withdrawal (p = 0.22), or total procedure times (p = 0.10). The adjusted percentage with a suboptimal preparation was 11.7% for patients using MoviPrep® and 8.8% for patients using Colyte®. MoviPrep® was not associated with a significant difference in overall ADR (OR 0.93; 95% CI: 0.78-1.11), AADR (OR 1.18; 95% CI: 0.87-1.62), or recommendation for early repeat colonoscopy (OR 1.16; 95% CI: 0.72-1.88). CONCLUSIONS: MoviPrep® was associated with a small absolute increase in having a suboptimal preparation, but did not affect recommendations for an early repeat colonoscopy, procedure times, or adenoma detection rates. Mechanisms to reduce financial barriers limiting low-volume preparations should be considered because of their favorable tolerability profile.

Low abundance of colonic butyrate-producing bacteria in HIV infection is associated with microbial translocation and immune activation.

OBJECTIVE: Gut microbial translocation is a major driving force behind chronic immune activation during HIV-1 infection. HIV-1-related intestinal dysbiosis, including increases in mucosa-associated pathobionts, may influence microbial translocation and contribute to mucosal and systemic inflammation. Thus, it is critical to understand the mechanisms by which gut microbes and their metabolic products, such as butyrate, influence immune cell function during HIV-1 infection. DESIGN: A cross-sectional study was performed to compare the relative abundance of butyrate-producing bacterial (BPB) species in colonic biopsies and stool of untreated, chronic HIV-1-infected (n = 18) and HIV-1-uninfected (n = 14) study participants. The effect of exogenously added butyrate on gut T-cell activation and HIV-1 infection was evaluated using an ex-vivo human intestinal cell culture model. METHODS: Species were identified in 16S ribosomal RNA sequence datasets. Ex-vivo isolated lamina propria mononuclear cells were infected with C-C chemokine receptor type 5-tropic HIV-1Bal, cultured with enteric gram-negative bacteria and a range of butyrate doses, and lamina propria T-cell activation and HIV-1 infection levels measured. RESULTS: Relative abundance of total BPB and specifically of Roseburia intestinalis, were lower in colonic mucosa of HIV-1-infected versus HIV-1-uninfected individuals. In HIV-1-infected study participants, R. intestinalis relative abundance inversely correlated with systemic indicators of microbial translocation, immune activation, and vascular inflammation. Exogenous butyrate suppressed enteric gram-negative bacteria-driven lamina propria T-cell activation and HIV-1 infection levels in vitro. CONCLUSION: Reductions in mucosal butyrate from diminished colonic BPB may exacerbate pathobiont-driven gut T-cell activation and HIV replication, thereby contributing to HIV-associated mucosal pathogenesis.

Per-oral video cholangiopancreatoscopy with narrow-band imaging for the evaluation of indeterminate pancreaticobiliary disease.

BACKGROUND AND AIMS: Cholangiopancreatoscopy for evaluating pancreaticobiliary pathology is currently limited by suboptimal optics. The aim of this study was to characterize the operating characteristics of per-oral video cholangiopancreatoscopy with narrow-band imaging (POVCP) findings in indeterminate pancreaticobiliary disease and to describe their association with neoplasia. METHODS: Data from consecutive patients undergoing POVCP for the evaluation of indeterminate pancreaticobiliary disease at a single tertiary care center were analyzed. Two experienced investigators had previously agreed on POVCP findings and terminology that were documented in endoscopy reports. Endoscopic procedural data from POVCPs performed between January 2006 and April 2015 and clinical data were abstracted from the endoscopic database and electronic medical records. Study endpoints included tissue-proven neoplasia or benign disease with ≥1 year of follow-up. RESULTS: A total of 109 patients were identified; 13 were excluded because of the presence of stone disease, known pancreaticobiliary malignancy, or presumed benign disease with ≤1 year of follow-up. Most patients (85%) underwent POVCP for biliary disease and 15% underwent POVCP for a pancreatic cause. Tortuous and dilated vessels (P < .001), infiltrative stricture (P < .001), polypoid mass (P = .003), and the presence of fish-egg lesions (P = .04) were found to be significantly associated with neoplasia. The overall POVCP impression had a high sensitivity (85%) and negative predictive value (89%) in assessing for the presence of neoplasia. CONCLUSIONS: Per-oral video cholangiopancreatoscopy is effective in the evaluation of indeterminate pancreaticobiliary disease. Tortuous and dilated vessels, infiltrative stricture, polypoid mass, and the presence of fish-egg lesions are significantly associated with neoplasia.

Medicare Under Age 65 and Medicaid Patients Have Poorer Bowel Preparations: Implications for Recommendations for an Early Repeat Colonoscopy.

BACKGROUND/AIMS: Colonoscopy is performed on patients across a broad spectrum of demographic characteristics. These characteristics may aggregate by patient insurance provider and influence bowel preparation quality and the prevalence of adenomas. The purpose of this study was to evaluate the association of insurance status and suboptimal bowel preparation, recommendation for an early repeat colonoscopy due to suboptimal bowel preparation, adenoma detection rate (ADR), and advanced ADR (AADR). METHODS: This is a cohort study of outpatient colonoscopies (n = 3113) at a single academic medical center. Patient insurance status was categorized into five groups: 1) Medicare < 65y; 2) Medicare ≥ 65y; 3) Tricare/VA; 4) Medicaid/Colorado Indigent Care Program (CICP); and 5) commercial insurance. We used multivariable logistic or linear regression modeling to estimate the risks for the association between patient insurance and suboptimal bowel preparation, recommendation for an early repeat colonoscopy due to suboptimal bowel preparation, ADR, and AADR. Models were adjusted for appropriate covariates. RESULTS: Medicare patients < 65y (OR 4.91; 95% CI: 3.25-7.43) and Medicaid/CICP patients (OR 4.23; 95% CI: 2.65-7.65) were more likely to have a suboptimal preparation compared to commercial insurance patients. Medicare patients < 65y (OR 5.58; 95% CI: 2.85-10.92) and Medicaid/CICP patients (OR 3.64; CI: 1.60-8.28) were more likely to receive a recommendation for an early repeat colonoscopy compared to commercial insurance patients. Medicare patients < 65y had a significantly higher adjusted ADR (OR 1.50; 95% CI: 1.03-2.18) and adjusted AADR (OR 1.99; 95% CI: 1.15-3.44) compared to commercial insurance patients. CONCLUSIONS: Understanding the reasons for the higher rate of a suboptimal bowel preparation in Medicare < 65y and Medicaid/CICP patients and reducing this rate is critical to improving colonoscopy outcomes and reducing healthcare costs in these populations.

Pancreatic Duct Changes in Patients With Chronic Pancreatitis Treated With Polyethylene and Sof-Flex Material Stents: A Blinded Comparison.

OBJECTIVES: Pancreatic stenting is used to improve painful, obstructive chronic pancreatitis. Data suggest that polyethylene stents (PESs) cause stent-associated changes (SACs). Whether a stent composed of more flexible material (Sof-Flex stent [SFS]) is associated with less SAC is unknown. METHODS: This study is a retrospective study of patients who underwent pancreatic duct stenting of at least 1 PES and 1 SFS on separate examinations and had a follow-up pancreatogram at the time of stent removal. The main outcome measurements were assessed for SAC on follow-up pancreatogram and interpreted by 2 radiologists blinded to the clinical data. RESULTS: Stent-associated changes were noted with 28% (13/47) of SFS and with 25% (13/52) of PES (P = 0.65). For 10F stent subgroups, SACs were seen with 25% (6/24) of the SFS compared with 50% (2/4) in the PES. Thirty percent (7/23) of the 8.5F SFS subgroup had SACs versus 29% (2/7) in the PES group (P = 0.887) for 8.5F + 10F combined comparison. CONCLUSIONS: In patients who have had polyethylene or SFSs of varying sizes, approximately 1 in 4 have SACs. Despite the use of a softer stent material for therapeutic stenting, the rate of SACs in the 8.5F and 10F subgroups seems similar between the 2 materials and design.

Antidepressant Use is Associated with Increased Energy Intake and Similar Levels of Physical Activity.

Antidepressants have been associated with weight gain, but the causes are unclear. The aims of this study were to assess the association of antidepressant use with energy intake, macronutrient diet composition, and physical activity. We used data on medication use, energy intake, diet composition, and physical activity for 3073 eligible adults from the 2005-2006 National Health and Nutrition Examination Survey (NHANES). Potential confounding variables, including depression symptoms, were included in the models assessing energy intake, physical activity, and sedentary behavior. Antidepressant users reported consuming an additional (mean ± S.E.) 215 ± 73 kcal/day compared to non-users (p = 0.01). There were no differences in percent calories from sugar, fat, or alcohol between the two groups. Antidepressant users had similar frequencies of walking or biking, engaging in muscle-strengthening activities, and engaging in moderate or vigorous physical activity. Antidepressant users were more likely to use a computer for ≥2 h/day (OR 1.77; 95% CI: 1.09-2.90), but TV watching was similar between the two groups. These results suggest increased energy intake and sedentary behavior may contribute to weight gain associated with antidepressant use. Focusing on limiting food intake and sedentary behaviors may be important in mitigating the weight gain associated with antidepressant use.

Association of Proton Pump Inhibitor (PPI) Use with Energy Intake, Physical Activity, and Weight Gain.

Studies suggest proton pump inhibitor (PPI) use impacts body weight regulation, though the effect of PPIs on energy intake, energy extraction, and energy expenditure is unknown. We used data on 3073 eligible adults from the National Health and Nutrition Examination Survey (NHANES). Medication use, energy intake, diet composition, and physical activity were extracted from NHANES. Multivariate regression models included confounding variables. Daily energy intake was similar between PPI users and non-users (p = 0.41). Diet composition was similar between the two groups, except that PPI users consumed a slightly greater proportion of calories from fat (34.5% vs. 33.2%; p = 0.02). PPI users rated themselves as being as physically active as their age/gender-matched peers and reported similar frequencies of walking or biking. However, PPI users were less likely to have participated in muscle-strengthening activities (OR: 0.53; 95% CI: 0.30-0.95). PPI users reported similar sedentary behaviors to non-users. Male PPI users had an increase in weight (of 1.52 ± 0.59 kg; p = 0.021) over the previous year compared to non-users, while female PPI users had a non-significant increase in weight. The potential mechanisms for PPI-associated weight gain are unclear as we did not find evidence for significant differences in energy intake or markers of energy expenditure.

Acid suppression medications are associated with suboptimal weight loss after laparoscopic Roux-en-Y gastric bypass in patients older than 40 years.

BACKGROUND: Bariatric surgery, including laparoscopic Roux-en-Y gastric bypass (LRYGB), achieves the greatest long-term weight loss in severe obesity. Approximately 50%-60% of severely obese patients have gastroesophageal reflux disease, and a substantial proportion is taking a proton pump inhibitor (PPI) or histamine-2 blocker (H2 B) at the time of LRYGB. The objective of this study was to explore the association of PPI/H2 B use before LRYGB with suboptimal percent weight loss (PWL) after LRYGB. METHODS: This was a cohort study of 472 consecutive patients who underwent LRYGB at a single center from 2004-2011. Suboptimal PWL was defined as<14% at 2 months,<25% at 6 months, and<30% at 12 months. Because of effect modification by age, stratified analyses (by median age of 40 yr) were performed. All models were adjusted for appropriate covariates, including obesity-associated co-morbidities. RESULTS: For patients aged ≤40 years, PPI/H2 B use leading up to LRYGB was not associated with suboptimal PWL at 2 months (P = .86), 6 months (P = .47), or 12 months (P = .66). However, for patients aged>40 years, PPI/H2 B use leading up to LRYGB was associated with a nonsignificant increase in suboptimal PWL at 2 months (odds ratio [OR] 2.23; P = .08) and significant increases in suboptimal PWL at 6 months (OR 7.23; P = .002) and 12 months (OR 11.1; P = .02). Results were independent of GERD. CONCLUSIONS: Mechanisms for the poorer weight loss in patients aged>40 years who were using a PPI/H2 B just before LRYGB should be explored.

The effect of Medicaid status on weight loss, hospital length of stay, and 30-day readmission after laparoscopic Roux-en-Y gastric bypass surgery.

BACKGROUND: Patients with Medicaid are much less likely to undergo bariatric surgery compared to those with commercial insurance. The aims of this study were to compare outcomes after laparoscopic Roux-en-Y gastric bypass (LRYGB) for patients covered by Medicaid, other (non-Medicaid) government insurance, and commercial insurance. METHODS: This was a retrospective cohort study of all eligible patients who underwent LRYGB between July 2004 and October 2011 at a single university hospital (n = 450). Multivariable regression analysis was used to compare percent weight loss (PWL), absolute weight loss (AWL), hospital length of stay (LOS) ≥3 days, and 30-day readmission rates. Analyses were adjusted for appropriate covariates. RESULTS: There was a nonsignificant increase in PWL in Medicaid patients at 2 months (p = 0.08), 6 months (p = 0.09), and 12 months (p = 0.17) compared to commercial insurance patients. Similarly, there was a nonsignificant increase in AWL in Medicaid patients at 2 months (p = 0.054), 6 months (p = 0.08), and 12 months (p = 0.14) compared to commercial insurance patients. Medicaid patients had similar PWL and AWL compared to those with other government insurance (p ≥ 0.29 at all time points). Medicaid patients were more likely to have a hospital LOS ≥ 3 days (OR 2.03; 95 % confidence interval (CI) 1.09-3.77) and a hospital readmission within 30 days of discharge (odds ratio (OR) 2.84; 95 % CI 1.15-6.96) compared to commercial insurance patients. CONCLUSIONS: These data should be considered as states expand Medicaid and make decisions regarding treatment of severe obesity. Interventions to decrease hospital LOS and the 30-day readmission rate, particularly in Medicaid patients, should be explored.

The effect of PPI use on human gut microbiota and weight loss in patients undergoing laparoscopic Roux-en-Y gastric bypass.

Laparoscopic Roux-en-Y gastric bypass (LRYGB) achieves sustainable weight loss possibly by altering the gut microbiota. The effect of a proton pump inhibitor (PPI) on weight loss and the gut microbiota has not been explored. PPI use and the gut microbiota were assessed before and 6 months after LRYGB in eight patients. Bacterial profiles were generated by 16S ribosomal RNA (rRNA) gene sequencing. Prior to LRYGB, PPI users had a higher percent relative abundance (PRA) of Firmicutes compared to nonusers. PPI users at 6 months post-LRYGB had a higher PRA of Firmicutes [48.6 versus 35.6%, p = nonsignificant (NS)] and a trend toward significantly lower percent excess weight loss (49.3 versus 61.4%, p = 0.067) compared to nonusers. PPI use post-LRYGB may impair weight loss by modifying gut microbiota.