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1.
Gastroenterology ; 149(4): 890-6.e2, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26116806

ABSTRACT

BACKGROUND & AIMS: Complete eradication of Barrett's esophagus (BE) often requires multiple sessions of radiofrequency ablation (RFA). Little is known about the effects of case volume on the safety and efficacy of RFA or about the presence or contour of learning curves for this procedure. METHODS: We collected data from the US RFA Patient Registry (from 148 institutions) for patients who underwent RFA for BE from July 2007 to July 2011. We analyzed the effects of the number of patients treated by individual endoscopists and individual centers on safety and efficacy outcomes of RFA. Outcomes, including stricture, bleeding, hospitalization, and complete eradication of intestinal metaplasia (CEIM), were assessed using logistic regression. The effects of center and investigator experience on numbers of treatment sessions to achieve CEIM were examined using linear regression. RESULTS: After we controlled for potential confounders, we found that as the experience of endoscopists and centers increased with cases, the numbers of treatment sessions required to achieve CEIM decreased. This relationship persisted after adjusting for patient age, sex, race, length of BE, and presence of pretreatment dysplasia (P < .01). Center experience was not significantly associated with overall rates of CEIM or complete eradication of dysplasia. We did not observe any learning curve with regard to risks of stricture, gastrointestinal bleeding, perforation, or hospitalization (P > .05). CONCLUSIONS: Based on analysis of a large multicenter registry, efficiency of the treatment, as measured by number of sessions needed to achieve CEIM, increased with case volume, indicating a learning curve effect. This trend began to disappear after treatment of approximately 30 patients by the center or individual endoscopist. However, there was no significant association between safety or efficacy outcomes and previous case volume.


Subject(s)
Adenocarcinoma/surgery , Barrett Esophagus/surgery , Catheter Ablation , Clinical Competence , Esophageal Neoplasms/surgery , Esophagoscopy , Learning Curve , Adenocarcinoma/diagnosis , Aged , Barrett Esophagus/diagnosis , Catheter Ablation/adverse effects , Esophageal Neoplasms/diagnosis , Esophagoscopy/adverse effects , Female , Hospitals, High-Volume , Hospitals, Low-Volume , Humans , Least-Squares Analysis , Linear Models , Logistic Models , Male , Middle Aged , Multivariate Analysis , Postoperative Complications/etiology , Postoperative Complications/surgery , Prospective Studies , Registries , Remission Induction , Reoperation , Risk Factors , Time Factors , Treatment Outcome , United States
2.
Gastrointest Endosc ; 82(2): 276-84, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25841575

ABSTRACT

BACKGROUND: Little is known about differences in Barrett's esophagus (BE) characteristics by sex and race and/or ethnicity or these differences in response to radiofrequency ablation (RFA). OBJECTIVE: We compared disease-specific characteristics, treatment efficacy, and safety outcomes by sex and race and/or ethnicity in patients treated with RFA for BE. DESIGN: The U.S. RFA patient registry is a multicenter collaboration reporting processes and outcomes of care for patients treated with RFA for BE. PATIENTS: Patients enrolled with BE. INTERVENTIONS: RFA. MAIN OUTCOME MEASUREMENTS: We assessed safety (stricture, bleeding, perforation, hospitalization), efficacy (complete eradication of intestinal metaplasia [CEIM]), complete eradication of dysplasia, and number of treatments to CEIM by sex and race and/or ethnicity. RESULTS: Among 5521 patients (4052 men; 5126 white, 137 Hispanic, 82 African American, 40 Asian, 136 heritage not identified), women were younger (60.0 vs 62.1 years) and had shorter BE segments (3.2 vs 4.4 cm) and less dysplasia (37% vs 57%) than did men. Women were almost twice as likely to stricture (odds ratio 1.7; 95% confidence interval, 1.2-2.3). Although white patients were predominantly male, about half of African Americans and Asians with BE were female. African Americans and Asians had less dysplasia than white patients. Asians and African Americans had more strictures than did white patients. There were no sex or race differences in efficacy. LIMITATIONS: Observational study with non-mandated paradigms, no central laboratory for reinterpretation of pathology. CONCLUSION: In the U.S. RFA patient registry, women had shorter BE segments and less-aggressive histology. The usual tendency toward BE in men was absent in African Americans and Asians. Posttreatment stricture was more common among women and Asians. RFA efficacy did not differ by sex or race.


Subject(s)
Barrett Esophagus/ethnology , Barrett Esophagus/surgery , Catheter Ablation , Population Groups/statistics & numerical data , Precancerous Conditions/ethnology , Precancerous Conditions/surgery , Black or African American/statistics & numerical data , Aged , Asian/statistics & numerical data , Barrett Esophagus/pathology , Catheter Ablation/adverse effects , Esophageal Perforation/ethnology , Esophageal Perforation/etiology , Esophageal Stenosis/ethnology , Esophageal Stenosis/etiology , Female , Gastrointestinal Hemorrhage/ethnology , Gastrointestinal Hemorrhage/etiology , Hispanic or Latino/statistics & numerical data , Hospitalization/statistics & numerical data , Humans , Indians, North American/statistics & numerical data , Male , Middle Aged , Postoperative Hemorrhage/ethnology , Postoperative Hemorrhage/etiology , Precancerous Conditions/pathology , Registries , Sex Factors , Treatment Outcome , United States/epidemiology , White People/statistics & numerical data
3.
Clin Gastroenterol Hepatol ; 12(11): 1840-7.e1, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24815329

ABSTRACT

BACKGROUND & AIMS: After radiofrequency ablation (RFA), patients may experience recurrence of Barrett's esophagus (BE) after complete eradication of intestinal metaplasia (CEIM). Rates and predictors of recurrence after successful eradication have been poorly described. METHODS: We used the US RFA Registry, a nationwide registry of BE patients receiving RFA, to determine rates and factors that predicted recurrence of intestinal metaplasia (IM). We assessed recurrence by Kaplan-Meier analysis for the overall cohort and by worst pretreatment histology. Characteristics associated with recurrence were included in a logistic regression model to identify independent predictors. RESULTS: Among 5521 patients, 3728 had biopsies 12 months or more after initiation of RFA. Of these, 3169 (85%) achieved CEIM, and 1634 (30%) met inclusion criteria. The average follow-up period was 2.4 years after CEIM. IM recurred in 334 (20%) and was nondysplastic or indefinite for dysplasia in 86% (287 of 334); the average length of recurrent BE was 0.6 cm. In Kaplan-Meier analysis, more advanced pretreatment histology was associated with an increased yearly recurrence rate. Compared with patients without recurrence, patients with recurrence were more likely, based on bivariate analysis, to be older, have longer BE segments, be non-Caucasian, have dysplastic BE before treatment, and require more treatment sessions. In multivariate analysis, the likelihood for recurrence was associated with increasing age and BE length, and non-Caucasian race. CONCLUSIONS: BE recurred in 20% of patients followed up for an average of 2.4 years after CEIM. Most recurrences were short segments and were nondysplastic or indefinite for dysplasia. Older age, non-Caucasian race, and increasing length of BE length were all risk factors. These risk factors should be considered when planning post-RFA surveillance intervals.


Subject(s)
Barrett Esophagus/surgery , Catheter Ablation/methods , Adult , Aged , Barrett Esophagus/prevention & control , Female , Humans , Incidence , Middle Aged , Prospective Studies , Recurrence , Risk Factors , Treatment Outcome , United States
4.
Nat Med ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38714898

ABSTRACT

Large variability exists in people's responses to foods. However, the efficacy of personalized dietary advice for health remains understudied. We compared a personalized dietary program (PDP) versus general advice (control) on cardiometabolic health using a randomized clinical trial. The PDP used food characteristics, individual postprandial glucose and triglyceride (TG) responses to foods, microbiomes and health history, to produce personalized food scores in an 18-week app-based program. The control group received standard care dietary advice (US Department of Agriculture Guidelines for Americans, 2020-2025) using online resources, check-ins, video lessons and a leaflet. Primary outcomes were serum low-density lipoprotein cholesterol and TG concentrations at baseline and at 18 weeks. Participants (n = 347), aged 41-70 years and generally representative of the average US population, were randomized to the PDP (n = 177) or control (n = 170). Intention-to-treat analysis (n = 347) between groups showed significant reduction in TGs (mean difference = -0.13 mmol l-1; log-transformed 95% confidence interval = -0.07 to -0.01, P = 0.016). Changes in low-density lipoprotein cholesterol were not significant. There were improvements in secondary outcomes, including body weight, waist circumference, HbA1c, diet quality and microbiome (beta-diversity) (P < 0.05), particularly in highly adherent PDP participants. However, blood pressure, insulin, glucose, C-peptide, apolipoprotein A1 and B, and postprandial TGs did not differ between groups. No serious intervention-related adverse events were reported. Following a personalized diet led to some improvements in cardiometabolic health compared to standard dietary advice. ClinicalTrials.gov registration: NCT05273268 .

5.
Clin Gastroenterol Hepatol ; 11(6): 636-42, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23103824

ABSTRACT

BACKGROUND & AIMS: The goal of radiofrequency ablation (RFA) for patients with Barrett's esophagus (BE) is to eliminate dysplasia and metaplasia. The efficacy and safety of RFA for patients with BE and neoplasia are characterized incompletely. METHODS: We performed a retrospective study of 244 patients treated with RFA for BE with dysplasia or intramucosal carcinoma. Efficacy outcomes were complete eradication of intestinal metaplasia (CEIM), complete eradication of dysplasia, total treatments, and RFA sessions. Safety outcomes included death, perforation, stricture, bleeding, and hospitalization. We identified factors associated with incomplete EIM and stricture formation. RESULTS: CEIM was achieved in 80% of patients, and complete eradication of dysplasia was achieved in 87%; disease progressed in 4 patients. A higher percentage of patients with incomplete EIM were female (40%) than those with CEIM (20%; P = .045); patients with incomplete EIM also had a longer segment of BE (5.5 vs 4.0 cm; P = .03), had incomplete healing between treatment sessions (45% vs 15%; P = 0.004), and underwent more treatment sessions (4 vs 3; P = .007). Incomplete healing was associated independently with incomplete EIM. Twenty-three patients (9.4%) had a treatment-related complication during 777 treatment sessions (3.0%), including strictures (8.2%), postprocedural hemorrhages (1.6%), and hospitalizations (1.6%). Patients who developed strictures were more likely to use nonsteroidal anti-inflammatory drugs than those without strictures (70% vs 45%; P = .04), have undergone antireflux surgery (15% vs 3%; P = .04), or had erosive esophagitis (35% vs 12%; P = .01). CONCLUSIONS: RFA is highly effective and safe for treatment of BE with dysplasia or early stage cancer. Strictures were the most common complications. Incomplete healing between treatment sessions was associated with incomplete EIM. Nonsteroidal anti-inflammatory drug use, prior antireflux surgery, and a history of erosive esophagitis predicted stricture formation.


Subject(s)
Barrett Esophagus/complications , Barrett Esophagus/surgery , Catheter Ablation/adverse effects , Catheter Ablation/methods , Esophageal Neoplasms/complications , Esophageal Neoplasms/surgery , Aged , Aged, 80 and over , Esophageal Stenosis/epidemiology , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
6.
Gastroenterology ; 143(5): 1179-1187.e3, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22885331

ABSTRACT

BACKGROUND & AIMS: Gastrointestinal (GI) diseases account for substantial morbidity, mortality, and cost. Statistical analyses of the most recent data are necessary to guide GI research, education, and clinical practice. We estimate the burden of GI disease in the United States. METHODS: We collected information on the epidemiology of GI diseases (including cancers) and symptoms, along with data on resource utilization, quality of life, impairments to work and activity, morbidity, and mortality. These data were obtained from the National Ambulatory Medical Care Survey; National Health and Wellness Survey; Nationwide Inpatient Sample; Surveillance, Epidemiology, and End Results Program; National Vital Statistics System; Thompson Reuters MarketScan; Medicare; Medicaid; and the Clinical Outcomes Research Initiative's National Endoscopic Database. We estimated endoscopic use and costs and examined trends in endoscopic procedure. RESULTS: Abdominal pain was the most common GI symptom that prompted a clinic visit (15.9 million visits). Gastroesophageal reflux was the most common GI diagnosis (8.9 million visits). Hospitalizations and mortality from Clostridium difficile infection have doubled in the last 10 years. Acute pancreatitis was the most common reason for hospitalization (274,119 discharges). Colorectal cancer accounted for more than half of all GI cancers and was the leading cause of GI-related mortality (52,394 deaths). There were 6.9 million upper, 11.5 million lower, and 228,000 biliary endoscopies performed in 2009. The total cost for outpatient GI endoscopy examinations was $32.4 billion. CONCLUSIONS: GI diseases are a source of substantial morbidity, mortality, and cost in the United States.


Subject(s)
Endoscopy, Digestive System/statistics & numerical data , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/epidemiology , Hospitalization/statistics & numerical data , Quality of Life , Endoscopy, Digestive System/economics , Gastrointestinal Diseases/mortality , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/epidemiology , Health Care Surveys/statistics & numerical data , Health Surveys/statistics & numerical data , Humans , Incidence , Medicaid/statistics & numerical data , Medicare/statistics & numerical data , SEER Program/statistics & numerical data , Survival Rate , United States/epidemiology , Vital Statistics
7.
Am J Gastroenterol ; 108(2): 187-95; quiz 196, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23247578

ABSTRACT

OBJECTIVES: Radiofrequency ablation (RFA) of Barrett's esophagus (BE) is safe and effective in eradicating dysplasia and intestinal metaplasia, and may reduce rates of esophageal adenocarcinoma (EAC). We assessed rates of and risk factors for disease recurrence after successful treatment of BE with RFA. METHODS: We performed a retrospective cohort study of patients who completed RFA for dysplastic BE or intramucosal carcinoma (IMC), achieved complete eradication of dysplasia (CE-D) or intestinal metaplasia (CE-IM), and underwent subsequent endoscopic surveillance at a single center. Rates of disease recurrence and progression were determined. Patients with and without recurrent disease were compared to determine risk factors for recurrence. RESULTS: Two hundred and sixty-two subjects underwent RFA during the study period. Of these, 119 and 112 patients were retained in endoscopic surveillance after CE-D and CE-IM, respectively. Median observation time was 397 days (range: 54-1,668 days). Eight patients (7% of those with CE-IM) had recurrent disease after a median of 235 days (range 55-1,124 days). Progression to IMC (n=1) or EAC (n=2) occurred in three of these eight patients, all of whom had pre-ablation high-grade dysplasia (HGD). Five patients had recurrence of non-dysplastic BE (n=3), low-grade dysplasia (n=1), and HGD (n=1). During 155 patient-years of observation, recurrence occurred in 5.2%/year, and progression occurred in 1.9%/year. No clinical characteristics were associated with disease recurrence. CONCLUSIONS: In patients with BE and dysplasia or early cancer who achieved CE-IM, BE recurred in ≈ 5%/year. Patient characteristics did not predict recurrence. Subjects undergoing RFA for dysplastic BE should be retained in endoscopic surveillance.


Subject(s)
Barrett Esophagus/surgery , Carcinoma/surgery , Catheter Ablation , Esophageal Neoplasms/surgery , Intestines/pathology , Precancerous Conditions/surgery , Adult , Aged , Barrett Esophagus/mortality , Barrett Esophagus/pathology , Carcinoma/mortality , Disease Progression , Endoscopy, Gastrointestinal , Esophageal Neoplasms/mortality , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Metaplasia/diagnosis , Middle Aged , Population Surveillance , Recurrence , Retrospective Studies , Risk Factors , Treatment Outcome
8.
Dig Dis Sci ; 58(7): 1955-9, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23649374

ABSTRACT

BACKGROUND: Acid-sensing ion channels (ASICs) are esophageal nociceptors that are candidates to mediate heartburn in non-erosive reflux disease (NERD). Amiloride, a diuretic, is known to inhibit ASICs. For this reason, we sought a role for ASICs in mediating heartburn by determining whether amiloride could block heartburn in NERD induced by esophageal acid perfusion. METHODS: In a randomized double-blind crossover study, we perfused the esophagus with amiloride or (saline) placebo prior to eliciting acid-induced heartburn in patients with a history of proton pump inhibitor-responsive NERD. Those with NERD and positive modified Bernstein test were randomized to perfusion with amiloride, 1 mmol/l, or placebo for 5 min, followed by repeat acid-perfusion. Heartburn severity and time to onset was measured and the process repeated following crossover to the alternative agent. RESULTS: 14 subjects completed the study. Amiloride did not reduce the frequency (100 vs. 100 %) or severity of acid-induced heartburn (Mean 2.50 ± SEM 0.33 vs. 2.64 ± 0.45), respectively. There was a trend towards longer time to onset of heartburn for amiloride versus placebo (Mean 2.93 ± SEM 0.3 vs. 2.36 ± 0.29 min, respectively), though these differences did not reach statistical significance (p > 0.05). CONCLUSIONS: Amiloride had no significant effect on acid-induced heartburn frequency or severity in NERD, although there was a trend towards prolonged time to onset of symptoms.


Subject(s)
Acid Sensing Ion Channel Blockers/therapeutic use , Amiloride/therapeutic use , Gastroesophageal Reflux/complications , Heartburn/drug therapy , Administration, Topical , Adolescent , Adult , Aged , Cross-Over Studies , Double-Blind Method , Drug Administration Schedule , Female , Heartburn/etiology , Humans , Hydrochloric Acid/administration & dosage , Male , Middle Aged , Severity of Illness Index , Time Factors , Treatment Outcome , Young Adult
9.
Am J Lifestyle Med ; 17(5): 639-648, 2023.
Article in English | MEDLINE | ID: mdl-37711348

ABSTRACT

Dietary fiber are non-digestible carbohydrates that are diverse, have varied functions, and are acquired by consuming plant-based foods. Some forms of fiber are digested by the gut microbiota and produce bioactive metabolites called short chain fatty acids-butyrate, acetate, and propionate. Dietary fiber is able to alter human physiology through multiple mechanisms that can result in health benefits. Unfortunately, nearly 19 out of 20 Americans do not consume the minimum recommended amount of fiber each day. This bears profound relevance to public health because at least six of the ten leading causes of death are potentially preventable or clinically improved through dietary means. Additionally, these same conditions share a common underlying pathophysiology-metabolic dysfunction. This can manifest as abdominal obesity, high blood pressure, insulin resistance, dyslipidemia, or collectively as metabolic syndrome. In this review, we will assess the evidence that consumption of dietary fiber undermines these forms of metabolic dysfunction, examine the mechanism of action for these physiologic effects, and consider the potential for dietary fiber to improve human health on a public health level by simply encouraging our patients to consume more plant-based foods in abundance and diversity.

10.
Gut Microbes ; 15(1): 2240050, 2023.
Article in English | MEDLINE | ID: mdl-37526398

ABSTRACT

Short-chain fatty acids (SCFA) are involved in immune system and inflammatory responses. We comprehensively assessed the host genetic and gut microbial contribution to a panel of eight serum and stool SCFAs in two cohorts (TwinsUK, n = 2507; ZOE PREDICT-1, n = 328), examined their postprandial changes and explored their links with chronic and acute inflammatory responses in healthy individuals and trauma patients. We report low concordance between circulating and fecal SCFAs, significant postprandial changes in most circulating SCFAs, and a heritable genetic component (average h2: serum = 14%(SD = 14%); stool = 12%(SD = 6%)). Furthermore, we find that gut microbiome can accurately predict their fecal levels (AUC>0.71) while presenting weaker associations with serum. Finally, we report different correlation patterns with inflammatory markers depending on the type of inflammatory response (chronic or acute trauma). Our results illustrate the breadth of the physiological relevance of SCFAs on human inflammatory and metabolic responses highlighting the need for a deeper understanding of this important class of molecules.


Subject(s)
Gastrointestinal Microbiome , Humans , Gastrointestinal Microbiome/genetics , Fatty Acids, Volatile/metabolism , Feces , Inflammation
11.
Cell Rep Med ; 4(4): 100993, 2023 04 18.
Article in English | MEDLINE | ID: mdl-37023745

ABSTRACT

Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (ß = -0.72, p = 1 × 10-5) and in response to fiber supplementation (ß = -0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10-4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.


Subject(s)
Bariatric Surgery , Bile Acids and Salts , Humans , Appetite , Bariatric Surgery/adverse effects , Feces , Inflammation
12.
Gastrointest Endosc ; 76(4): 733-9, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22732872

ABSTRACT

BACKGROUND: EMR is commonly performed before radiofrequency ablation (RFA) for nodular dysplastic Barrett's esophagus (BE). OBJECTIVE: To determine the efficacy and safety of EMR before RFA for nodular BE with advanced neoplasia (high-grade dysplasia [HGD] or intramucosal carcinoma [IMC]). DESIGN: Retrospective study. SETTING: University of North Carolina Hospitals, from 2006 to 2011. PATIENTS: 169 patients with BE with advanced neoplasia: 65 patients treated with EMR and RFA for nodular disease and 104 patients treated with RFA alone for nonnodular disease. INTERVENTIONS: EMR, RFA. MAIN OUTCOME MEASUREMENTS: Efficacy (complete eradication of dysplasia, complete eradication of intestinal metaplasia, total treatment sessions, RFA treatment sessions), safety (stricture formation, bleeding, and hospitalization). RESULTS: EMR followed by RFA achieved complete eradication of dysplasia and complete eradication of intestinal metaplasia in 94.0% and 88.0% of patients, respectively, compared with 82.7% and 77.6% of patients, respectively, in the RFA-only group (P = .06 and P = .13, respectively). The complication rates between the 2 groups were similar (7.7% vs 9.6%, P = .79). Strictures occurred in 4.6% of patients in the EMR-before-RFA group. compared with 7.7% of patients in the RFA-only group (P = .53). LIMITATIONS: Retrospective study at a tertiary-care referral center. CONCLUSION: In patients treated with EMR before RFA for nodular BE with HGD or IMC, no differences in efficacy and safety outcomes were observed compared with RFA alone for nonnodular BE with HGD or IMC. EMR followed by RFA is safe and effective for patients with nodular BE and advanced neoplasia.


Subject(s)
Barrett Esophagus/surgery , Catheter Ablation , Esophagoscopy , Esophagus/surgery , Aged , Barrett Esophagus/pathology , Combined Modality Therapy , Esophagus/pathology , Female , Humans , Male , Middle Aged , Mucous Membrane/pathology , Mucous Membrane/surgery , Postoperative Complications/epidemiology , Retrospective Studies , Treatment Outcome
13.
Gut Microbes ; 13(1): 1997559, 2021.
Article in English | MEDLINE | ID: mdl-34787065

ABSTRACT

The endocannabinoid (EC) system has pleiotropic functions in the body. It plays a key role in energy homeostasis and the development of metabolic disorders being a mediator in the relationship between the gut microbiota and host metabolism. In the current study we explore the functional interactions between the endocannabinoid system and the gut microbiome in modulating inflammatory markers. Using data from a 6 week exercise intervention (treatment n = 38 control n = 40) and a cross sectional validation cohort (n = 35), we measured the associations of 2-arachidonoylglycerol (2-AG), anandamide (AEA), N-oleoylethanolamine (OEA) and N-palmitoylethanolamine (PEA) with gut microbiome composition, gut derived metabolites (SCFAs) and inflammatory markers both cross-sectionally and longitudinally. At baseline AEA and OEA were positively associated with alpha diversity (ß(SE) = .32 (.06), P = .002; .44 (.04), P < .001) and with SCFA producing bacteria such as Bifidobacterium (2-AG ß(SE) = .21 (.10), P < .01; PEA ß(SE) = .23 (.08), P < .01), Coprococcus 3 and Faecalibacterium (PEA ß(SE) = .29 (.11), P = .01; .25 (.09), P < .01) and negatively associated with Collinsella (AEA ß(SE) = -.31 (.12), P = .004). Additionally, we found AEA to be positively associated with SCFA Butyrate (ß(SE) = .34 (.15), P = .01). AEA, OEA and PEA all increased significantly with the exercise intervention but remained constant in the control group. Changes in AEA correlated with SCFA butyrate and increases in AEA and PEA correlated with decreases in TNF-ɑ and IL-6 statistically mediating one third of the effect of SCFAs on these cytokines. Our data show that the anti-inflammatory effects of SCFAs are partly mediated by the EC system suggesting that there may be other pathways involved in the modulation of the immune system via the gut microbiome.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Bacteria/metabolism , Endocannabinoids/immunology , Fatty Acids, Volatile/pharmacology , Anti-Inflammatory Agents/metabolism , Bacteria/chemistry , Bacteria/classification , Bacteria/genetics , Cohort Studies , Cross-Sectional Studies , Fatty Acids, Volatile/metabolism , Female , Gastrointestinal Microbiome , Humans , Immune System/drug effects , Immune System/immunology , Interleukin-6/genetics , Interleukin-6/immunology , Longitudinal Studies , Male , Middle Aged
14.
Am J Gastroenterol ; 104(11): 2721-8, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19690527

ABSTRACT

OBJECTIVES: This study used high-resolution impedance manometry (HRIM) to determine pressure topography thresholds of peristaltic integrity predictive of incomplete esophageal bolus clearance. METHODS: A total of 16 normal controls and 8 patients with dysphagia were studied using a solid-state HRIM assembly incorporating 36 manometric sensors and 12 impedance segments. Each of the 10 saline swallows in each study was dichotomously scored as either complete or incomplete bolus clearance by impedance criteria, and peristaltic integrity was evaluated using pressure topography isobaric contours ranging from 10 to 30 mm Hg in 5- mm Hg increments. Each isobaric contour plot was characterized by the location and length of breaks in the isobaric contour. RESULTS: All subjects had normal esophagogastric junction (EGJ) relaxation and none met the pressure topography criteria of hiatus hernia. In all, 70 (29%) of the 240 individual swallows had incomplete bolus clearance. In every case, an intact >or=20 mm Hg isobaric contour was associated with complete bolus clearance. The largest defect in the 20 and 30 mm Hg isobaric contours associated with complete bolus clearance measured 1.7 and 3.0 cm, respectively, in length, whereas the smallest defect predictive of incomplete bolus clearance measured 2.1 and 3.2 cm, respectively. CONCLUSIONS: In individuals with normal EGJ relaxation and morphology, peristaltic contractions with breaks <2 cm in the 20 mm Hg isobaric contour or <3 cm in the 30 mm Hg isobaric contour are associated with complete bolus clearance, and longer breaks predict incomplete bolus clearance.


Subject(s)
Deglutition Disorders/etiology , Esophageal Motility Disorders/complications , Esophageal Motility Disorders/diagnosis , Esophagogastric Junction/physiopathology , Manometry/methods , Adult , Case-Control Studies , Deglutition Disorders/diagnosis , Electric Impedance , Female , Gastrointestinal Transit/physiology , Humans , Male , Manometry/instrumentation , Middle Aged , Predictive Value of Tests , Probability , Reference Values , Reproducibility of Results , Severity of Illness Index , Signal Processing, Computer-Assisted , Transducers, Pressure , Young Adult
15.
Curr Gastroenterol Rep ; 11(3): 182-9, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19463217

ABSTRACT

The past few years were an exciting time in the study of esophageal motor disorders because new technologies emerged to study esophageal motor function and bolus transit. Although conventional manometry was long considered the "gold standard" for defining esophageal motor disorders, many technologic improvements occurred due to advances in transducer technology, computerization, and graphic data presentation. In addition, a relatively new technology, intraluminal impedance, was incorporated into manometric modalities. The most sophisticated systems now include combined high-resolution manometry with high-resolution impedance. Although these techniques provide more detailed information about esophageal function, whether they improve our ability to diagnose and treat patients more effectively is debatable. However, more recent data support that these advances actually improve our ability to diagnose and treat esophageal motor disorders. This article provides an update on these technologies in clinical practice and how they may be helpful in the future.


Subject(s)
Deglutition/physiology , Esophageal Motility Disorders/diagnosis , Image Processing, Computer-Assisted/methods , Manometry/methods , Diagnosis, Differential , Electric Impedance , Endoscopy, Gastrointestinal/methods , Esophageal Motility Disorders/physiopathology , Humans , Severity of Illness Index
16.
Am J Ther ; 15(5): 444-9, 2008.
Article in English | MEDLINE | ID: mdl-18806520

ABSTRACT

BACKGROUND: Gastrointestinal (GI) hemorrhage is responsible for 200-400,000 hospitalizations in the United States annually. Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for > or =30% of admissions due to GI hemorrhage. Misoprostol reduces the number of NSAID-related upper GI events while proton pump inhibitors (PPIs) reduce the incidence of endoscopic ulcers. AIMS: To measure the utilization of GI prophylaxis in patients discharged from hospital on ulcerogenic medicines. PATIENTS AND METHODS: We performed a medical record review of all 480 patients discharged from the medical service over a 3-month period on aspirin or nonaspirin NSAIDs. Use of gastroprotection was recorded, particularly among those patients not previously prescribed a PPI or misoprostol. Patients with a different indication for PPI therapy were excluded. RESULTS: In all, 480 patients were identified, and 142 were excluded. Of the 338 remaining patients, 154 (46%) were prescribed GI prophylaxis. In particular, 240 patients had not been receiving a PPI or misoprostol at the time of admission (gastroprotection naive). Of these, 23.3% received a new prescription for GI prophylaxis at discharge. Use of gastroprotection increased among patients older than 60 years compared with those 60 years and younger (P = 0.008), but there was no difference among patients with higher baseline comorbidity or those receiving multiple agents of interest. CONCLUSIONS: Although hospitalization offers an opportunity to recognize patients at high risk of developing upper GI complications from NSAIDs, utilization of appropriate gastroprotection seemed suboptimal. Educational efforts directed at physicians may help them recognize risk factors for GI hemorrhage and current indications for prophylaxis.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Ulcer Agents/therapeutic use , Gastrointestinal Diseases/prevention & control , Patient Discharge , Age Factors , Aged , Drug Utilization , Female , Gastrointestinal Diseases/chemically induced , Humans , Male , Middle Aged , Misoprostol/therapeutic use , Proton Pump Inhibitors/therapeutic use , Retrospective Studies , Risk Factors
17.
J Gastrointest Surg ; 17(1): 21-8; discussion p.28-9, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22965650

ABSTRACT

BACKGROUND: Ongoing gastroesophageal reflux may impair healing and re-epithelialization after radiofrequency ablation (RFA) of Barrett's esophagus (BE). Because prior fundoplication may improve reflux control, our aim was to assess the relationship between prior fundoplication and the safety/efficacy of RFA. METHODS: We assessed the U.S. RFA Registry, a nationwide registry of BE patients receiving RFA at 148 institutions, to compare the safety and efficacy of ablation between those with prior fundoplication and those with medical management (proton pump inhibition). RESULTS: Among 5,537 patients receiving RFA, 301 (5.4 %) had prior fundoplication. Of fundoplication subjects, 1.0 % developed stricture and 1.0 % were hospitalized after RFA. Rates of stricture, bleeding, and hospitalization were not statistically different (p = ns) between patients with and without prior fundoplication. Complete eradication of intestinal metaplasia and complete eradication of dysplasia were achieved in 71 % and 87 % of fundoplication patients, and 73 % and 87 % of patients without fundoplication, respectively (p = ns for both). Patients with prior fundoplication needed similar numbers of RFA sessions for eradication compared with those without fundoplication. CONCLUSIONS: Radiofrequency ablation, with or without prior fundoplication, is safe and effective in eradicating BE. Prior fundoplication was associated with similar adverse event and efficacy rates when compared with medical management.


Subject(s)
Barrett Esophagus/surgery , Catheter Ablation , Fundoplication , Gastroesophageal Reflux/surgery , Aged , Barrett Esophagus/etiology , Female , Follow-Up Studies , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/drug therapy , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Prospective Studies , Proton Pump Inhibitors/therapeutic use , Registries , Retrospective Studies , Treatment Outcome , United States
18.
Cleve Clin J Med ; 79(4): 273-81, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22473727

ABSTRACT

Although proton pump inhibitors (PPIs) are now the first-line treatment for gastroesophageal reflux disease (GERD), surgery still has several specific indications. We review the current treatment of GERD and discuss how antireflux surgery fits into the overall scheme.


Subject(s)
Gastroesophageal Reflux/surgery , Laryngopharyngeal Reflux/surgery , Proton Pump Inhibitors/therapeutic use , Barrett Esophagus/surgery , Cough/etiology , Esophageal pH Monitoring , Esophagitis, Peptic/surgery , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/drug therapy , Heartburn/etiology , Heartburn/therapy , Humans , Laryngitis/etiology , Laryngopharyngeal Reflux/drug therapy
19.
Gastrointest Endosc Clin N Am ; 21(1): 95-109, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21112500

ABSTRACT

Studies in the last several years have consistently shown radiofrequency ablation (RFA) to be effective, safe, and well tolerated in the treatment of nondysplastic and dysplastic Barrett's esophagus (BE). The results found at academic medical centers have been reproduced in the community setting. RFA provides a safe and cost-effective alternative to surgery or surveillance in the management of high-grade dysplasia (HGD). RFA should be given serious consideration as first-line therapy for HGD. This article reviews the evidence behind RFA to differentiate it from other management strategies in terms of efficacy, durability, safety, tolerability, and cost-effectiveness. The role of RFA in the management of BE is described, including endoscopic resection. Future directions are identified for research that will help to better define the role of RFA in the management of BE.


Subject(s)
Barrett Esophagus/surgery , Catheter Ablation/methods , Esophagus/surgery , Precancerous Conditions/surgery , Barrett Esophagus/pathology , Catheter Ablation/adverse effects , Catheter Ablation/economics , Esophagectomy , Esophagus/pathology , Humans , Precancerous Conditions/pathology
20.
J Gastrointest Surg ; 14(2): 268-76, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19911238

ABSTRACT

OBJECTIVE: The aim of the study was to compare the esophagogastric junction (EGJ) compliance in response to controlled distension in fundoplication (FP) patients and controls using the functional luminal imaging probe (FLIP). BACKGROUND: FP aims to replicate normal EGJ distensibility. FLIP is a new technology that uses impedance planimetry to measure intraluminal cross-sectional area (CSA) during controlled distension. METHODS: Ten controls and ten FP patients were studied with high-resolution esophageal pressure topography (HREPT) and then the FLIP placed across the EGJ. Deglutitive and interdeglutitive EGJ distensibility was assessed with volume-controlled distension. The FLIP measured eight CSAs spaced 4 mm apart within a cylindrical saline-filled bag along with the corresponding intrabag pressure. RESULTS: The EGJ formed an hourglass shape during distensions with the central constriction at the diaphragmatic hiatus. The distensibility of the hiatus was significantly greater during deglutitive relaxation in both subject groups, but FP patients exhibited reduced EGJ distensibility and compliance compared to controls. During the interglutitive period, the corresponding increase in intrabag pressures at larger volumes were also greater in FP patients implying a longer segment of EGJ constriction. The EGJ distensibility characteristics did not correlate with HREPT measures. CONCLUSIONS: FLIP technology was used to compare EGJ distensibility in FP patients and control subjects. The least distensible locus within the EGJ was always at the hiatus. EGJ distensibility was significantly reduced, and the length of constriction increased in FP patients. Future FLIP studies will compare patients with and without post-FP dysphagia and gas bloat, symptoms suggestive of an overly restrictive FP.


Subject(s)
Diagnostic Techniques, Digestive System/instrumentation , Esophagogastric Junction/physiopathology , Fundoplication , Adult , Anatomy, Cross-Sectional , Compliance , Electric Impedance , Female , Humans , Male , Manometry , Middle Aged , Postoperative Period , Young Adult
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