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The incidence of esophageal adenocarcinoma (EA) has drastically increased in the United States since 1970s for unclear reasons. We hypothesized that the widespread usage of antibiotics has increased the procarcinogenic potential of the orodigestive microbiota along the sequence of gastroesophageal reflux (GR), Barrett's esophagus (BE) and EA phenotypes. This case control study included normal controls (NC) and three disease phenotypes GR, BE and EA. Microbiota in the mouth, esophagus, and stomach, and rectum were analyzed using 16S rRNA gene sequencing. Overall, we discovered 44 significant pairwise differences in abundance of microbial taxa between the four phenotypes, with 12 differences in the mouth, 21 in the esophagus, two in the stomach, and nine in the rectum. Along the GR→BE→EA sequence, oral and esophageal microbiota were more diversified, the dominant genus Streptococcus was progressively depleted while six other genera Atopobium, Actinomyces, Veillonella, Ralstonia, Burkholderia and Lautropia progressively enriched. In NC, Streptococcus appeared to control populations of other genera in the foregut via numerous negative and positive connections, while in disease states, the rich network was markedly simplified. Inferred gene functional content showed a progressive enrichment through the stages of EA development in genes encoding antibiotic resistance, ligands of Toll-like and NOD-like receptors, nitrate-nitrite-nitric oxide pathway and acetaldehyde metabolism. The orodigestive microbiota is in a progressive dysbiotic state along the GR-BE-EA sequence. The increasing dysbiosis and antibiotic and procarcinogenic genes in the disease states warrants further study to define their roles in EA pathogenesis.

Background and AimsGastroesophageal reflux disease (GERD) is a prevalent GI disorder which may complicate conditions such as obstructive airways disease (OAD). Our group has identified predictive biomarkers of GERD in particulate exposed 1stresponders with OAD. Additionally, GERD diagnosis and treatment is costly, and invasive. In light of these clinical concerns our aim was to systematically review studies identifying non-invasive, multiOmic and multi-compartmental biomarkers of GERD.MethodsA systematic review of PubMed and EMBASE was performed on February 22, 2022 utilizing keywords focusing on reflux disease and biomarkers. The study was registered with PROSPERO (2022-CRD42022301543). We included: original human studies in English, published after December 31, 2009 focusing on non-invasive biomarkers of GERD. Reflux related conditions included Nonerosive Reflux Disease (NERD) Laryngopharyngeal Disease (LPR), Erosive Esophagitis (EE) and Barretts Esophagus (BE). Predictive measures were synthesized and bias assessed.ResultsPrimary search identified 241 studies. After removing duplicates and applying inclusion/exclusion criteria n=15 articles were identified. Salivary pepsin was the most studied biomarker (n=5) with a significant sensitivity and specificity for GERD and LPR detection. Studies showed that for GERD diagnosis, miR-203 downregulation had the highest area under curve the receiver operator curve(ROCAUC) 0.94(95% CI; 0.90-0.7). An oral microbiome model includingLautropia,StreptococcusandBacteroidetesshowed the greatest discrimination between BE and controls vsLautropiaalone; sensitivity of 96.9%, specificity of 88.2% and ROCAUCof 0.94(0.81-1.00).ConclusionPrior studies identified significant multiOmic, multi-compartmental non-invasive biomarker risks for GERD and its complications such as BE. However, due to study limitations and to further ascertain the reliability and accuracy of these biomarkers more studies are warranted.WHAT YOU NEED TO KNOWBACKGROUNDGastroesophageal reflux disease (GERD) is a prevalent GI disorder which may complicate conditions such as obstructive airways disease (OAD). GERD diagnosis and treatment is costly, and invasive. In light of these clinical concerns our aim was to systematically review studies identifying non-invasive, multiOmic and multi-compartmental biomarkers of GERD.FINDINGSSalivary pepsin was the most studied biomarker with a significant sensitivity and specificity for GERD detection. Studies showed that for GERD diagnosis, miR-203 downregulation had the highest ROCAUC. An oral microbiome model including Lautropia, Streptococcus and Bacteroidetes showed the greatest discrimination between Barrette’s Esophagus and controls vs Lautropia alone.IMPLICATIONS FOR PATIENT CAREPrior studies identified significant multiOmic, multi-compartmental non-invasive biomarker risks for GERD and its complications such as BE. However, due to study limitations and to further ascertain the reliability, accuracy and clinical utility of these biomarkers more studies are warranted.

The COVID-19 pandemic has challenged front-line clinical decision-making, leading to numerous published prognostic tools. However, few models have been prospectively validated and none report implementation in practice. Here, we use 3345 retrospective and 474 prospective hospitalizations to develop and validate a parsimonious model to identify patients with favorable outcomes within 96 h of a prediction, based on real-time lab values, vital signs, and oxygen support variables. In retrospective and prospective validation, the model achieves high average precision (88.6% 95% CI: [88.4–88.7] and 90.8% [90.8–90.8]) and discrimination (95.1% [95.1–95.2] and 86.8% [86.8–86.9]) respectively. We implemented and integrated the model into the EHR, achieving a positive predictive value of 93.3% with 41% sensitivity. Preliminary results suggest clinicians are adopting these scores into their clinical workflows.

In 2021, Delta became the predominant SARS-CoV-2 variant worldwide. While vaccines have effectively prevented COVID-19 hospitalization and death, vaccine breakthrough infections increasingly occurred. The precise role of clinical and genomic determinants in Delta infections is not known, and whether they contributed to increased rates of breakthrough infections compared to unvaccinated controls.We studied SARS-CoV-2 variant distribution, dynamics, and adaptive selection over time in relation to vaccine status, phylogenetic relatedness of viruses, full genome mutation profiles, and associated clinical and demographic parameters.We show a steep and near-complete replacement of circulating variants with Delta between May and August 2021 in metropolitan New York. We observed an increase of the Delta sublineage AY.25 (14% in vaccinated, 7% in unvaccinated), its spike mutation S112L, and AY.44 (8% in vaccinated, 2% in unvaccinated) with its nsp12 mutation F192V in breakthroughs. Delta infections were associated with younger age and lower hospitalization rates than Alpha. Delta breakthrough infections increased significantly with time since vaccination, and, after adjusting for confounders, they rose at similar rates as in unvaccinated individuals.We observed a modest adaptation of Delta genomes in breakthrough infections in New York, suggesting an improved genomic framework to support Delta's epidemic growth in times of waning vaccine protection despite limited impact on vaccine escape.The study was supported by NYU institutional funds. The NYULH Genome Technology Center is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center.

Obesity is a health burden that currently affects over 13% of the global adult population, consisting of over 650 million adults. Obesity is evaluated based on a body mass index (BMI) scale, which is calculated as weight in kilograms divided by the square of height in meters. Adults with a BMI greater than 30kg/m2 are considered to be obese while adults with a BMI greater than 40kg/m2 are considered morbidly obese. Adenosine deaminase (ADA) is a polymorphic enzyme that plays an important role in both immune functions and the regulation of intracellular and extracellular concentrations of adenosine. Three alleles of the ADA gene (ADA1, ADA2, ADA6) are associated with type 1 diabetes mellitus (DM1). ADA2/6 may increase susceptibility to DM1 in females. Given the evidence linking obesity with DM1, we wanted to determine whether a correlation exists between ADA2 allele and obesity. The ADA2 (+22 G->A, rs73598374) SNP changes the amino acid at position 8 from aspartic acid (Asp8)(D) to asparagine (Asn)(N). In this study, we present significant evidence of association between the ADA2 allele and obesity or BMIs greater than 25 in the Latino adult but not in the Caucasian population and therefore, may be a risk for obesity and its complications such as DM1.

Evidence suggests that Helicobacter pylori plays a role in gastric cancer initiation. However, epidemiologic studies on the specific role of other bacteria in the development of gastric cancer are lacking. We conducted a case-control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. We performed shotgun metagenomic sequencing using oral wash samples from 89 case-control pairs and antral mucosal brushing samples from 55 case-control pairs. We examined the associations of relative abundances of bacterial taxa and functional pathways with IM using conditional logistic regression with and without elastic-net penalty. Compared with controls, oral species Peptostreptococcus stomatis, Johnsonella ignava, Neisseria elongata, and Neisseria flavescens were enriched in cases (odds ratios [ORs] = 1.29–1.50, P = 0.004–0.01) while Lactobacillus gasseri, Streptococcus mutans, S. parasanguinis, and S. sanguinis were under-represented (ORs = 0.66–0.76, P = 0.006–0.042) in cases. Species J. ignava and Filifactor alocis in the gastric microbiota were enriched (ORs = 3.27 and 1.43, P = 0.005 and 0.035, respectively), while S. mutans, S. parasanguinis, and S. sanguinis were under-represented (ORs = 0.61–0.75, P = 0.024–0.046), in cases compared with controls. The lipopolysaccharide and ubiquinol biosynthesis pathways were more abundant in IM, while the sugar degradation pathways were under-represented in IM. The findings suggest potential roles of certain oral and gastric microbiota, which are correlated with regulation of pathways associated with inflammation, in the development of gastric precancerous lesions.

Early reports showed high mortality from coronavirus disease 2019 (COVID-19). Mortality rates have recently been lower, raising hope that treatments have improved. However, patients are also now younger, with fewer comorbidities. We explored whether hospital mortality was associated with changing demographics at a 3-hospital academic health system in New York. We examined in-hospital mortality or discharge to hospice from March through August 2020, adjusted for demographic and clinical factors, including comorbidities, admission vital signs, and laboratory results. Among 5,121 hospitalizations, adjusted mortality dropped from 25.6% (95% CI, 23.2-28.1) in March to 7.6% (95% CI, 2.5-17.8) in August. The standardized mortality ratio dropped from 1.26 (95% CI, 1.15-1.39) in March to 0.38 (95% CI, 0.12-0.88) in August, at which time the average probability of death (average marginal effect) was 18.2 percentage points lower than in March. Data from one health system suggest that mortality from COVID-19 is decreasing even after accounting for patient characteristics.

BackgroundReducing costs while increasing or maintaining quality is crucial to delivering high value care.ObjectiveTo assess the impact of a hospital value-based management programme on cost and quality.DesignTime series analysis of non-psychiatric, non-rehabilitation, non-newborn patients discharged between 1 September 2011 and 31 December 2017 from a US urban, academic medical centre.InterventionNYU Langone Health instituted an institution-wide programme in April 2014 to increase value of healthcare, defined as health outcomes achieved per dollar spent. Key features included joint clinical and operational leadership; granular and transparent cost accounting; dedicated project support staff; information technology support; and a departmental shared savings programme.MeasurementsChange in variable direct costs; secondary outcomes included changes in length of stay, readmission and in-hospital mortality.ResultsThe programme chartered 74 projects targeting opportunities in supply chain management (eg, surgical trays), operational efficiency (eg, discharge optimisation), care of outlier patients (eg, those at end of life) and resource utilisation (eg, blood management). The study cohort included 160 434 hospitalisations. Adjusted variable costs decreased 7.7% over the study period. Admissions with medical diagnosis related groups (DRG) declined an average 0.20% per month relative to baseline. Admissions with surgical DRGs had an early increase in costs of 2.7% followed by 0.37% decrease in costs per month. Mean expense per hospitalisation improved from 13% above median for teaching hospitals to 2% above median. Length of stay decreased by 0.25% per month relative to prior trends (95% CI −0.34 to 0.17): approximately half a day by the end of the study period. There were no significant changes in 30-day same-hospital readmission or in-hospital mortality. Estimated institutional savings after intervention costs were approximately $53.9 million.LimitationsObservational analysis.ConclusionA systematic programme to increase healthcare value by lowering the cost of care without compromising quality is achievable and sustainable over several years.

Background: The incidence of kidney stones is increasing in the US population. Oxalate, a major factor for stone formation, is degraded by gut bacteria reducing its intestinal absorption. Intestinal O. formigenes colonization has been associated with a lower risk for recurrent kidney stones in humans. In the current study, we used a clinical trial of the eradication of Helicobacter pylori to assess the effects of an antibiotic course on O. formigenes colonization, urine electrolytes, and the composition of the intestinal microbiome. Methods: Of 69 healthy adult subjects recruited, 19 received antibiotics for H. pylori eradication, while 46 were followed as controls. Serial fecal samples were examined for O. formigenes presence and microbiota characteristics. Urine, collected serially fasting and following a standard meal, was tested for oxalate and electrolyte concentrations. Results: O. formigenes prevalence was 50%. Colonization was significantly and persistently suppressed in antibiotic-exposed subjects but remained stable in controls. Urinary pH increased after antibiotics, but urinary oxalate did not differ between the control and treatment groups. The O. formigenes-positive samples had higher alpha-diversity and significantly differed in Beta-diversity from the O. formigenes-negative samples. Specific taxa varied in abundance in relation to urinary oxalate levels.Conclusions: These studies identified significant antibiotic effects on O. formigenes colonization and urinary electrolytes and showed that overall microbiome structure differed in subjects according to O. formigenes presence. Identifying a consortium of bacterial taxa associated with urinary oxalate may provide clues for the primary prevention of kidney stones in healthy adults.

This study examines the frequency of hospitalization for all non–COVID-19-related conditions in a health system at the epicenter of the COVID-19 pandemic.

Early reports showed high mortality from Covid-19; by contrast, the current outbreaks in the southern and western United States are associated with fewer deaths, raising hope that treatments have improved. However, in Texas for instance, 63% of diagnosed cases are currently under 50, compared to only 52% nationally in March-April. Current demographics in Arizona and Florida are similar. Therefore, whether decreasing Covid-19 mortality rates are a reflection of changing demographics or represent improvements in clinical care is unknown. We assessed outcomes over time in a single health system, accounting for changes in demographics and clinical factors.MethodsWe analyzed biweekly mortality rates for admissions between March 1 and June 20, 2020 in a single health system in New York City. Outcomes were obtained as of July 14, 2020. We included all hospitalizations with laboratory-confirmed Covid-19 disease. Patients with multiple hospitalizations (N=157, 3.3%) were included repeatedly if they continued to have laboratory-confirmed disease. Mortality was defined as in-hospital death or discharge to hospice care. Based on prior literature, we constructed a multivariable logistic regression model to generate expected risk of death, adjusting for age; sex; self-reported race and ethnicity; body mass index; smoking history; presence of hypertension, heart failure, hyperlipidemia, coronary artery disease, diabetes, cancer, chronic kidney disease, or pulmonary disease individually as dummy variables; and admission oxygen saturation, D-dimer, C reactive protein, ferritin, and cycle threshold for RNA detection. All data were obtained from the electronic health record. We then calculated the sum of observed and expected deaths in each two-week period and multiplied each period's observed/expected (O/E) risk by the overall average crude mortality to generate biweekly adjusted rates. We calculated Poisson control limits and indicated points outside the control limits as significantly different, following statistical process control standards. The NYU institutional review board approved the study and granted a waiver of consent.ResultsWe included 4,689 hospitalizations, of which 4,661 (99.4%) had died or been discharged. The median age, and the proportion male or with any comorbidity decreased over time; median real-time PCR cycle threshold increased (indicating relatively less concentration of virus) (Table). For instance, median age decreased from 67 years in the first two weeks to 49 in the last two. Peak hospitalizations were during the fifth and sixth study weeks, which accounted for 40% of the hospitalizations. Median length of stay for patients who died or were discharged to hospice was 8 days (interquartile range, 4-16).Unadjusted mortality dropped each period, from 30.2% in the first two weeks to 3% in the last two weeks, with the last eight weeks being lower than the 95% control limits. Risk adjustment partially attenuated the mortality decline, but adjusted mortality rates in the second-to-last two weeks remained outside the control limits (Figure, Table). The O/E risk of mortality decreased from 1.07 (0.64-1.67) in the first two weeks to 0.39 (0.08-1.12) in the last two weeks.DiscussionIn this 16-week study of Covid-19 mortality at a single health system, we found that changes in demographics and severity of illness at presentation account for some, but not all, of the decrease in unadjusted mortality. Even after risk adjustment for a variety of clinical and demographic factors, mortality was significantly lower towards the end of the study period.Incremental improvements in outcomes are likely a combination of increasing clinical experience, decreasing hospital volume, growing use of new pharmacologic treatments (such as corticosteroids, remdesivir and anti-cytokine treatments), non-pharmacologic treatments (such as proning), earlier intervention, community awareness, and lower viral load exposure from increasing mask wearing and social distancing. It is also possible that earlier periods had a more virulent circulating strain.In summary, data from one health system suggest that Covid-19 remains a serious disease for high risk patients, but that outcomes may be improving.

ObjectiveTo describe outcomes of people admitted to hospital with coronavirus disease 2019 (covid-19) in the United States, and the clinical and laboratory characteristics associated with severity of illness.DesignProspective cohort study.SettingSingle academic medical center in New York City and Long Island.Participants5279 patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection between 1 March 2020 and 8 April 2020. The final date of follow up was 5 May 2020.Main outcome measuresOutcomes were admission to hospital, critical illness (intensive care, mechanical ventilation, discharge to hospice care, or death), and discharge to hospice care or death. Predictors included patient characteristics, medical history, vital signs, and laboratory results. Multivariable logistic regression was conducted to identify risk factors for adverse outcomes, and competing risk survival analysis for mortality.ResultsOf 11 544 people tested for SARS-Cov-2, 5566 (48.2%) were positive. After exclusions, 5279 were included. 2741 of these 5279 (51.9%) were admitted to hospital, of whom 1904 (69.5%) were discharged alive without hospice care and 665 (24.3%) were discharged to hospice care or died. Of 647 (23.6%) patients requiring mechanical ventilation, 391 (60.4%) died and 170 (26.2%) were extubated or discharged. The strongest risk for hospital admission was associated with age, with an odds ratio of >2 for all age groups older than 44 years and 37.9 (95% confidence interval 26.1 to 56.0) for ages 75 years and older. Other risks were heart failure (4.4, 2.6 to 8.0), male sex (2.8, 2.4 to 3.2), chronic kidney disease (2.6, 1.9 to 3.6), and any increase in body mass index (BMI) (eg, for BMI >40: 2.5, 1.8 to 3.4). The strongest risks for critical illness besides age were associated with heart failure (1.9, 1.4 to 2.5), BMI >40 (1.5, 1.0 to 2.2), and male sex (1.5, 1.3 to 1.8). Admission oxygen saturation of 1 (4.8, 2.1 to 10.9), C reactive protein level >200 (5.1, 2.8 to 9.2), and D-dimer level >2500 (3.9, 2.6 to 6.0) were, however, more strongly associated with critical illness than age or comorbidities. Risk of critical illness decreased significantly over the study period. Similar associations were found for mortality alone.ConclusionsAge and comorbidities were found to be strong predictors of hospital admission and to a lesser extent of critical illness and mortality in people with covid-19; however, impairment of oxygen on admission and markers of inflammation were most strongly associated with critical illness and mortality. Outcomes seem to be improving over time, potentially suggesting improvements in care.

BackgroundLittle is known about factors associated with hospitalization and critical illness in Covid-19 positive patients.MethodsWe conducted a cross-sectional analysis of all patients with laboratory-confirmed Covid-19 treated at an academic health system in New York City between March 1, 2020 and April 2, 2020, with follow up through April 7, 2020. Primary outcomes were hospitalization and critical illness (intensive care, mechanical ventilation, hospice and/or death). We conducted multivariable logistic regression to identify risk factors for adverse outcomes, and maximum information gain decision tree classifications to identify key splitters.ResultsAmong 4,103 Covid-19 patients, 1,999 (48.7%) were hospitalized, of whom 981/1,999 (49.1%) have been discharged, and 292/1,999 (14.6%) have died or been discharged to hospice. Of 445 patients requiring mechanical ventilation, 162/445 (36.4%) have died. Strongest hospitalization risks were age ≥75 years (OR 66.8, 95% CI, 44.7-102.6), age 65-74 (OR 10.9, 95% CI, 8.35-14.34), BMI>40 (OR 6.2, 95% CI, 4.2-9.3), and heart failure (OR 4.3 95% CI, 1.9-11.2). Strongest critical illness risks were admission oxygen saturation 2500 (OR 6.9, 95% CI, 3.2-15.2), ferritin >2500 (OR 6.9, 95% CI, 3.2-15.2), and C-reactive protein (CRP) >200 (OR 5.78, 95% CI, 2.6-13.8). In the decision tree for admission, the most important features were age >65 and obesity; for critical illness, the most important was SpO20.5, troponin 64 and CRP>200.ConclusionsAge and comorbidities are powerful predictors of hospitalization; however, admission oxygen impairment and markers of inflammation are most strongly associated with critical illness.

Key Points Question Do outcomes among patients with coronavirus disease 2019 (COVID-19) differ by race/ethnicity, and are observed disparities associated with comorbidity and neighborhood characteristics? Findings This cohort study including 9722 patients found that Black and Hispanic patients were more likely than White patients to test positive for COVID-19. Among patients hospitalized with COVID-19 infection, Black patients were less likely than White patients to have severe illness and to die or be discharged to hospice. Meaning Although Black patients were more likely than White patients to test positive for COVID-19, after hospitalization they had lower mortality, suggesting that neighborhood characteristics may explain the disproportionately higher out-of-hospital COVID-19 mortality among Black individuals., This cohort study of patients testing positive for COVID-19 in a large New York City health system compares rates of hospitalization, critical illness, mortality across racial/ethnic categories., Importance Black and Hispanic populations have higher rates of coronavirus disease 2019 (COVID-19) hospitalization and mortality than White populations but lower in-hospital case-fatality rates. The extent to which neighborhood characteristics and comorbidity explain these disparities is unclear. Outcomes in Asian American populations have not been explored. Objective To compare COVID-19 outcomes based on race and ethnicity and assess the association of any disparities with comorbidity and neighborhood characteristics. Design, Setting, and Participants This retrospective cohort study was conducted within the New York University Langone Health system, which includes over 260 outpatient practices and 4 acute care hospitals. All patients within the system’s integrated health record who were tested for severe acute respiratory syndrome coronavirus 2 between March 1, 2020, and April 8, 2020, were identified and followed up through May 13, 2020. Data were analyzed in June 2020. Among 11 547 patients tested, outcomes were compared by race and ethnicity and examined against differences by age, sex, body mass index, comorbidity, insurance type, and neighborhood socioeconomic status. Exposures Race and ethnicity categorized using self-reported electronic health record data (ie, non-Hispanic White, non-Hispanic Black, Hispanic, Asian, and multiracial/other patients). Main Outcomes and Measures The likelihood of receiving a positive test, hospitalization, and critical illness (defined as a composite of care in the intensive care unit, use of mechanical ventilation, discharge to hospice, or death). Results Among 9722 patients (mean [SD] age, 50.7 [17.5] years; 58.8% women), 4843 (49.8%) were positive for COVID-19; 2623 (54.2%) of those were admitted for hospitalization (1047 [39.9%] White, 375 [14.3%] Black, 715 [27.3%] Hispanic, 180 [6.9%] Asian, 207 [7.9%] multiracial/other). In fully adjusted models, Black patients (odds ratio [OR], 1.3; 95% CI, 1.2-1.6) and Hispanic patients (OR, 1.5; 95% CI, 1.3-1.7) were more likely than White patients to test positive. Among those who tested positive, odds of hospitalization were similar among White, Hispanic, and Black patients, but higher among Asian (OR, 1.6, 95% CI, 1.1-2.3) and multiracial patients (OR, 1.4; 95% CI, 1.0-1.9) compared with White patients. Among those hospitalized, Black patients were less likely than White patients to have severe illness (OR, 0.6; 95% CI, 0.4-0.8) and to die or be discharged to hospice (hazard ratio, 0.7; 95% CI, 0.6-0.9). Conclusions and Relevance In this cohort study of patients in a large health system in New York City, Black and Hispanic patients were more likely, and Asian patients less likely, than White patients to test positive; once hospitalized, Black patients were less likely than White patients to have critical illness or die after adjustment for comorbidity and neighborhood characteristics. This supports the assertion that existing structural determinants pervasive in Black and Hispanic communities may explain the disproportionately higher out-of-hospital deaths due to COVID-19 infections in these populations.

The relationship between gout and cancer remains uncertain. Some investigators have suggested that uric acid has anti-cancer properties (1, 2). In contrast, other studies have suggested that hyperu...

Oxalobacter formigenes (OF) may play a protective role in preventing calcium oxalate stones. This is the first prospective study to evaluate the effect of antibiotics on OF colonization. Intestinal colonization by OF is associated with reduced urinary oxalate excretion. Exposure to antibiotics may be an important factor determining rates of colonization.The effect of antibiotics on OF colonization was compared in two groups: A group receiving antibiotics for gastric infection with Helicobacter pylori (HP) and a group without HP whose members were not receiving antibiotics. OF colonization in stool was detected by oxalate degradation at baseline and after 1 and 6 months.The prevalence at baseline of intestinal colonization with OF was 43.1% among all patients screened. Among the 12 patients who were positive for OF who did not receive antibiotics, 11 (92%) had OF on stool tests at 1 month and 6 months. Of the 19 participants who were positive for OF and who received antibiotics for HP, only 7 (36.8%) continued to be colonized by OF on follow-up stool testing at 1 and 6 months (P=0.003 by Fisher exact test). Amoxicillin and clarithromycin caused 62.5% of subjects to become negative for OF at 1 month; 56.2% remained negative for OF at 6 months.Antibiotics for HP infection effectively reduced colonization with OF, an effect present at 1 and 6 months after treatment. The lasting elimination of OF could be associated with hyperoxaluria and be a factor in recurrent kidney stone disease.

Background & Aims Gastroesophageal reflux causes inflammation and intestinal metaplasia and its downstream sequelum adenocarcinoma in the distal esophagus. The incidence of esophageal adenocarcinoma has increased approximately 6-fold in the United States since the 1970s, accompanied with a significant increase in the prevalence of gastroesophageal reflux disease (GERD). Despite extensive epidemiologic study, the cause for GERD and the unexpected increases remain unexplainable. Microbes are among the environmental factors that may contribute to the etiology of GERD, but very little research has been done on the esophageal microbiome, particularly in its relation to GERD. This is the first comprehensive reported correlation between a change in the esophageal microbiome and esophageal diseases. Methods Biopsy samples of the distal esophagus were collected from 34 patients. Host phenotypes were histologically defined as normal, esophagitis, or Barrett's esophagus (intestinal metaplasia). Microbiomes from the biopsy samples were analyzed by bacterial 16S ribosomal RNA gene survey and classified into types using unsupervised cluster analysis and phenotype-guided analyses. Independence between host phenotypes and microbiome types were analyzed by Fisher exact test. Results Esophageal microbiomes can be classified into 2 types. The type I microbiome was dominated by the genus Streptococcus and concentrated in the phenotypically normal esophagus. Conversely, the type II microbiome contained a greater proportion of gram-negative anaerobes/microaerophiles and primarily correlated with esophagitis (odds ratio, 15.4) and Barrett's esophagus (odds ratio, 16.5). Conclusions In the human distal esophagus, inflammation and intestinal metaplasia are associated with global alteration of the microbiome. These findings raise the issue of a possible role for dysbiosis in the pathogenesis of reflux-related disorders.

Colorectal cancer (CRC), is the second-leading cause of cancer-related deaths in the USA, affecting both men and women. Current projections show little or no change since the publication of a morbidity and mortality study in 2005. The projected number of new cases for 2008 is 154,000, and the projected number of CRC cancer deaths for 2008 is 53,000. The standard diagnostic paradigm is based on histopathology of either biopsy or surgical specimens. This article suggests a new paradigm for colon cancer diagnosis and staging using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS or IMS). IMS may identify potential tumors in normal tissue of cancer patients and predict those cancer patients who are at risk for recurrent cancer.

The laparoscopic adjustable gastric band (LAGB) has been widely used to treat morbid obesity. There is conflicting data on its long-term effect on esophageal function. Our aim was to assess the long-term impact of the LAGB on esophageal motility and pH-metry in patients who had LAGB who had normal and abnormal esophageal function at baseline.Consecutive patients referred for bariatric surgery were prospectively enrolled. A detailed medical history was obtained, and esophageal manometric and 24-h pH evaluations were performed in standard fashion preoperatively and 6 and 12 months postoperatively; patients served as their own controls.Twenty-two patients completed manometric evaluation. Ten patients had normal manometric parameters at baseline; at 6 months, mean lower esophageal sphincter (LES) residual pressure increased significantly from baseline (3.9 +/- 2 vs. 8.9 +/- 4 mmHg, p = 0.014). At 12 months, the mean peristaltic wave duration increased from 3.6 +/- 1 at baseline to 6.8 +/- 2 s, p = 0.025 and wave amplitude decreased during the same period (98.7 +/- 22 vs. 52.3 +/- 24, p = 0.013). LES pressure and percent peristalsis did not differ significantly pre- and post-LAGB. Twelve patients had one or more abnormal manometric findings at baseline; at 12 months, LES pressure in these 12 patients decreased significantly (31.1 +/- 10 vs 23.6 +/- 7, p = 0.011) and wave amplitude was significantly reduced (125.9 +/- 117 vs 103 +/- 107, p = 0.039). LES residual pressure did not change significantly pre- and post-LAGB. Twenty-two individuals were evaluated for impact of Lap-Band on esophageal acid exposure. Sixteen of these patients had normal esophageal pH-metry values at baseline and had no significant changes in 12 months in any pH-metry measurement. Six patients had abnormal pH-metry values at baseline. Among these patients, time with pH4.0 and Johnson/DeMeester score did not change significantly during follow-up. There was a significant decrease in the number of reflux episodes from baseline to 6 months (159 +/- 48 vs. 81 +/- 61, p = 0.016).Abnormal manometric findings are frequently encountered post-LAGB. Increases in LES residual pressure and peristaltic wave duration were the most significant changes. LAGB is not associated with an increase in total esophageal acidification time. Further evaluation of the clinical significance of manometric abnormalities is warranted.

Leptin and ghrelin, hormones involved in human energy homeostasis, are both produced in the stomach.We sought to determine whether the presence of Helicobacter pylori affects gastric and systemic levels of leptin and ghrelin.We consecutively enrolled 256 patients referred for upper endoscopy at a Veterans Affairs outpatient endoscopy center.We obtained fasting serum, fundic and antral biopsies, and gastric juice. Based on histological, biochemical, and serological assays, patients were categorized as H. pylori+ or H. pylori-. Leptin and total ghrelin levels in serum, gastric biopsies, and gastric juice were determined by specific ELISAs.Of the 256 subjects, 120 were H. pylori+ and 96 were H. pylori-; 40 patients of indeterminate status were excluded. Serum and fundic leptin levels correlated with body mass index in the H. pylori+ (r = 0.35; P0.0001 and r = 0.35; P0.0001, respectively) and H. pylori- (r = 0.65; P0.0001 and r = 0.41; P0.0001, respectively) groups, but H. pylori+ subjects had significantly lower serum leptin levels [median 2.2 ng/ml (interquartile range 0.9-4.6) vs. 4.0 ng/ml (1.7-7.2); P = 0.0003]. Serum ghrelin levels were similar in the H. pylori+ and H. pylori- groups [median 1651 pg/ml (interquartile range 845-2247) vs. 1629 pg/ml (992-2886); P = 0.23]. H. pylori status did not significantly affect gastric biopsy leptin and ghrelin levels. Ghrelin levels in gastric juice varied over 4 log(10) (80-776,000 pg/ml) and correlated with gastric juice pH in the H. pylori+ group (r = 0.68; P0.0001).These findings provide evidence that H. pylori status affects leptin and ghrelin homeostasis, presumably via intragastric interactions.

Gastroesophageal reflux disease (GERD) is a frequently encountered disorder. Obesity is an important risk factor for GERD, and there are several pathophysiologic mechanisms linking the two conditions. For obese patients with GERD, much of the treatment effort is focused on weight loss and its consistent benefit to symptoms, while there is a relative lack of evidence regarding outcomes after novel or even standard medical therapy is offered to this population. Physicians are hesitant to recommend operative anti-reflux therapy to obese patients due to the potentially higher risks and decreased efficacy, and these patients instead are often considered for bariatric surgery. Bariatric surgical approaches are broadening, and each technique has emerging evidence regarding its effect on both the risk and outcome of GERD. Furthermore, combined anti-reflux and bariatric options are now being offered to obese patients with GERD. However, currently Roux-en-Y gastric bypass remains the most effective surgical treatment option in this population, due to its consistent benefits in both weight loss and GERD itself. This article aims to review the impact of both conservative and aggressive approaches of obesity treatment on GERD.

BackgroundAccumulating evidence shows that Helicobacter pylori protects against some metabolic and immunological diseases in which the development of these diseases coincide with temporal or permanent dysbiosis. The aim of this study was to assess the effect of H. pylori eradication on the human gut microbiome.MethodsAs part of the currently on-going ESSAY (Eradication Study in Stable Adults/Youths) study, we collected stool samples from 17 H. pylori-positive young adult (18-30 years-old) volunteers. The same cohort was followed up 6, 12 and 18 months-post H. pylori eradication. The impact of H. pylori on the human gut microbiome pre- and post-eradication was investigated using high throughput 16S rRNA gene (V3-V4 region) sequencing using the Illumina Miseq followed by data analysis using Qiime pipeline.ResultsWe compared the composition and diversity of bacterial communities in the fecal microbiome of the H. pylori-positive volunteers, before and after H. pylori eradication therapy. The 16S rRNA gene was sequenced at an average of 150,000-170,000 reads/sample. The microbial diversity were similar pre- and post-H. pylori eradication with no significant differences in richness and evenness of bacterial species. Despite that the general profile of the gut microbiome was similar pre- and post-eradication, some changes in the bacterial communities at the phylum and genus levels were notable, particularly the decrease in relative abundance of Bacterioidetes and corresponding increase in Firmicutes after H. pylori eradication. The significant increase of short-chain fatty acids (SCFA)-producing bacteria genera could also be associated with increased risk of metabolic disorders.ConclusionsOur preliminary stool metagenomics study shows that eradication of H. pylori caused perturbation of the gut microbiome and may indirectly affect the health of human. Clinicians should be aware of the effect of broad spectrum antibiotics used in H. pylori eradication regimen and be cautious in the clinical management of H. pylori infection, particularly in immunocompromised patients.

Background Gastroesophageal reflux disease (GERD) complications may reflect imbalances between protective and injurious factors. Through its effects on cell growth, leptin may influence esophageal mucosal homeostasis. Aims To determine whether leptin receptors are present in the esophagus, and whether serum or gastric leptin levels are associated with esophageal inflammation and metaplasia. Methods From patients referred for upper endoscopy, biopsies were obtained from the stomach and distal esophagus and serum samples were collected. Patients were classified as having normal, inflamed, or Barrett9s esophagus. Quantitative immunohistochemistry was performed on representative sections, and leptin levels in plasma and gastric biopsy samples were determined by specific immunoassay. Results Of 269 individuals enrolled, 105 were H. pylori-negative. Of the 88 patients with complete esophageal biopsies, 44 were normal, 24 were inflamed, and 20 were Barrett9s esophagus. Receptors for leptin were highly expressed on esophageal epithelial cells with similar density and staining pattern in all three conditions, and plasma and antral leptin levels did not differ significantly. Patients with Barrett9s had significantly (p=0.01) higher fundic leptin levels [Median 202 pg/mg (IQR 123-333)] compared to normal [126 pg/mg (78-221)] or inflamed [114 pg/mg (76-195)] esophagus. In multivariate analysis, for every 2-fold increase in fundic leptin, the odds of having Barrett9s was 3.4 times [95% CI 1.5-7.6] higher compared to having a normal esophagus. Conclusions Leptin receptor expression on esophageal epithelial cells provides a pathway for leptin-mediated signal transduction. Variation in gastric leptin production could contribute to differential esophageal healing and metaplasia progression.

The Helicobacter pylori vacA gene encodes a secreted protein (VacA) that alters the function of gastric epithelial cells and T lymphocytes. H. pylori strains containing particular vacA alleles are associated with differential risk of disease. Because the VacA midregion may exist as one of two major types, m1 or m2, serologic responses may potentially be used to differentiate between patients colonized with vacA m1 - or vacA m2 -positive H. pylori strains. In this study, we examined the utility of specific antigens from the m regions of VacA as allele-specific diagnostic antigens. We report that serological responses to P44M1, an H. pylori m1-specific antigen, are observed predominantly in patients colonized with m1 -positive strains, whereas responses to VacA m2 antigens, P48M2 and P55M2, are observed in patients colonized with either m1 - or m2 -positive strains. In an Asian-American population, serologic responses to VacA m region-specific antigens were not able to predict the risk of development of gastric cancer.

Hospital care on weekends has been associated with delays in care, reduced quality, and poor clinical outcomes. The purpose of this study was to evaluate the impact of a weekend hospital intervention on processes of care and clinical outcomes. The multifaceted intervention included expanded weekend diagnostic services, improved weekend discharge processes, and increased physician and care management services on weekends. This was an interrupted time series observational study of adult non-obstetric patients hospitalized at a single academic medical center between January 2011 and January 2014. The study included 18 months prior to and 19 months following the implementation of the intervention. Data were analyzed using segmented regression analysis with adjustment for confounders. The primary outcome was average length of stay. Secondary outcomes included percent of patients discharged on weekends, 30-day readmission rate, and in-hospital mortality rate. The study included 57,163 hospitalizations. Following implementation of the intervention, average length of stay decreased by 13 % (95 % CI 10–15 %) and continued to decrease by 1 % (95 % CI 1–2 %) per month as compared to the underlying time trend. The proportion of weekend discharges increased by 12 % (95 % CI 2–22 %) at the time of the intervention and continued to increase by 2 % (95 % CI 1–3 %) per month thereafter. The intervention had no impact on readmissions or mortality. During the post-implementation period, the hospital was evacuated and closed for 2 months due to damage from Hurricane Sandy, and a new hospital-wide electronic health record was introduced. The contributions of these events to our findings are not known. We observed a lower inpatient census and found differences in patient characteristics, including higher rates of Medicaid insurance and comorbidities, in the post-Hurricane Sandy period as compared to the pre-Sandy period. The intervention was associated with a reduction in length of stay and an increase in weekend discharges. Our longitudinal study also illuminated the challenges of evaluating the effectiveness of a large-scale intervention in a real-world hospital setting.

Objective Existing literature indicates that the mortality rate with each variceal bleeding episode is 30–50%. Over the past 2 decades, there have been significant developments in the management of variceal bleeding. The effect of these developments on the natural history of variceal bleeding is unclear. Therefore, a retrospective, multicenter study was conducted to define the outcomes of variceal bleeding and to describe the patterns of current practice in the management of variceal bleeding. Methods All patients with documented variceal bleeding hospitalized at four large county hospitals from January 1, 1997, to June 30, 2000, were included. Study outcomes were in-hospital, 6-wk, and overall mortality, rate of rebleeding, transfusion requirement, and length of stay. After discharge, patients were followed until death or study closure date, on June 30, 2000. Results A total of 231 subjects were included, and their in-hospital, 6-wk, and overall mortality rates were 14.2%, 17.5%, and 33.5%, respectively. The frequency of rebleeding during follow-up was 29%. Median length of total hospital stay was 8 days (0–34 days). Median number of packed red cell units transfused was 4 U (0–60 U). Upper endoscopy was performed in 95% of patients within 24 h, and endoscopic therapy was done in all but eight patients (ligation 64%, sclerotherapy 33%). Octreotide was administered in 74% of the patients. Portasystemic shunts were performed in 7.5% of the patients for controlling acute variceal bleeding. Conclusions The mortality rate after variceal bleeding in this study was substantially lower than previously reported. This suggests that advances made in the management of variceal bleeding have improved outcomes after variceal bleeding.

Annual fecal occult blood testing (FOBT) is often continued in patients who have had a recent negative colonoscopy, despite recommendations to the contrary. This prospective study aimed to determine the proportion of patients with a positive FOBT who had adenomas and cancers on colonoscopy stratified according to the duration of time since the last negative colonoscopy.A total of 1,119 asymptomatic average-risk patients ≥50 years of age referred for a positive FOBT were prospectively identified and stratified by the duration of time since the last colonoscopy (never,10 years, 5-10 years, or5 years). The proportion of patients in each category with adenomas of any size, adenomas ≥10 mm, advanced neoplasms, and cancers was assessed.The mean age (68.9±9.6 years), sex (95.2% male), and race (48.1% white, 32.1% black, 15.6% Hispanic, and 4.2% other) did not differ between the four groups. Overall, adenomas of any size were detected in 42.8% of patients, adenomas ≥10 mm in 14.7%, advanced neoplasms in 20.7%, and cancers in 7.3%. Advanced neoplasms were detected in 30.4% of patients who have never had a colonoscopy, 27% in those who have had one greater than 10 years prior, 10.0% in 5-10 years prior, and 1.1% in less than 5 years prior.In asymptomatic average-risk patients with a negative colonoscopy within the last 5 years, the prevalence of adenomas is low, and no patient was diagnosed with cancer. These findings support the CDC recommendations to suspend annual FOBT for up to 5 years after a negative colonoscopy.

Background More than half of the world’s adults carry Helicobacter pylori. The eradication of H. pylori may affect the regulation of human metabolic hormones. The aim of this study was to evaluate the effect of H. pylori eradication on meal-associated changes in appetite-controlled insulinotropic and digestive hormones, and to assess post-eradication changes in body mass index as part of a currently on-going multicentre ESSAY (Eradication Study in Stable Adults/Youths) study. Methods We enrolled 29 H. pylori-positive young adult (18–30 year-old) volunteer subjects to evaluate the effect of H. pylori eradication on meal-associated changes on eight gastrointestinal hormones, using a multiplex bead assay. Changes in body mass index and anthropometric measurements were recorded, pre- and post-eradication therapy. Results Pre-prandial active amylin, total peptide YY (PYY) and pancreatic polypeptide (PP) levels were significantly elevated 12 months post-eradication compared with baseline (n = 18; Wilcoxon's signed rank test, p

The care of hepatitis C virus (HCV) in African Americans represents an opportunity to address a major health disparity in medicine. In all facets of HCV infection, African Americans are inexplicably affected, including in the prevalence of the virus, which is higher among them compared with most of the racial and ethnic groups. Ironically, although fibrosis rates may be slow, hepatocellular carcinoma and mortality rates appear to be higher among African Americans. Sustained viral response (SVR) rates have historically significantly trailed behind Caucasians. The reasons for this gap in SVR are related to both viral and host factors. Moreover, low enrollment rates in clinical trials hamper the study of the efficacy of anti-viral therapy. Nevertheless, the gap in SVR between African Americans and Caucasians may be narrowing with the use of direct-acting agents. Gastroenterologists, hepatologists, primary care physicians, and other health-care providers need to address modifiable risk factors that affect the natural history, as well as treatment outcomes, for HCV among African Americans. Efforts need to be made to improve awareness among health-care providers to address the differences in screening and referral patterns for African Americans.

In recent decades, the length of medical training has increased, slowing the entry of new physicians into practice. Experiments with 3-year medical schools, like the one at New York University, attempt to address this delay.

We examined whether colonization of selected oral pathogens is associated with gastric precancerous lesions in a cross-sectional study. A total of 119 participants were included, of which 37 were cases of chronic atrophic gastritis, intestinal metaplasia, or dysplasia. An oral examination was performed to measure periodontal indices. Plaque and saliva samples were tested with real-time quantitative PCR for DNA levels of pathogens related to periodontal disease (Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Actinobacillus actinomycetemcomitans) and dental caries (Streptococcus mutans and S. sobrinus). There were no consistent associations between DNA levels of selected bacterial species and gastric precancerous lesions, although an elevated but non-significant odds ratio (OR) for gastric precancerous lesions was observed in relation to increasing colonization of A. actinomycetemcomitans (OR = 1.36 for one standard deviation increase, 95% Confidence Interval = 0.87-2.12), P. gingivalis (OR = 1.12, 0.67-1.88) and T. denticola (OR = 1.34, 0.83-2.12) measured in plaque. To assess the influence of specific long-term infection, stratified analyses by levels of periodontal indices were conducted. A. actinomycetemcomitans was significantly associated with gastric precancerous lesions (OR = 2.51, 1.13-5.56) among those with ≥ median of percent tooth sites with PD ≥ 3 mm, compared with no association among those below the median (OR = 0.86, 0.43-1.72). A significantly stronger relationship was observed between the cumulative bacterial burden score of periodontal disease-related pathogens and gastric precancerous lesions among those with higher versus lower levels of periodontal disease indices (p-values for interactions: 0.03-0.06). Among individuals with periodontal disease, high levels of colonization of periodontal pathogens are associated with an increased risk of gastric precancerous lesions.

This review is an update to the American College of Gastroenterology (ACG) Committee on Minority Affairs and Cultural Diversity's paper on colorectal cancer (CRC) in African Americans published in 2005. Over the past 10 years, the incidence and mortality rates of CRC in the United States has steadily declined. However, reductions have been strikingly much slower among African Americans who continue to have the highest rate of mortality and lowest survival when compared with all other racial groups. The reasons for the health disparities are multifactorial and encompass physician and patient barriers. Patient factors that contribute to disparities include poor knowledge of benefits of CRC screening, limited access to health care, insurance status along with fear and anxiety. Physician factors include lack of knowledge of screening guidelines along with disparate recommendations for screening. Earlier screening has been recommended as an effective strategy to decrease observed disparities; currently the ACG and American Society of Gastrointestinal Endoscopists recommend CRC screening in African Americans to begin at age 45. Despite the decline in CRC deaths in all racial and ethnic groups, there still exists a significant burden of CRC in African Americans, thus other strategies including educational outreach for health care providers and patients and the utilization of patient navigation systems emphasizing the importance of screening are necessary. These strategies have been piloted in both local communities and Statewide resulting in notable significant decreases in observed disparities.

Although injection drug use (IDU) and blood transfusions prior to 1992 are well-accepted risk factors for hepatitis C virus (HCV) infection, many studies that evaluated tattooing as a risk factor for HCV infection did not control for a history of IDU or transfusion prior to 1992. In this large, multicenter, case-control study, we analyzed demographic and HCV risk factor exposure history data from 3,871 patients, including 1,930 with chronic HCV infection (HCV RNA–positive) and 1,941 HCV-negative (HCV antibody–negative) controls. Crude and fully adjusted odds ratios (ORs) of tattoo exposure by multivariate logistic regression in HCV-infected versus controls were determined. As expected, IDU (65.9% versus 17.8%; P < 0.001), blood transfusion prior to 1992 (22.3% versus 11.1%; P < 0.001), and history of having one or more tattoos (OR, 3.81; 95% CI, 3.23-4.49; P < 0.001) were more common in HCV-infected patients than in control subjects. After excluding all patients with a history of ever injecting drugs and those who had a blood transfusion prior to 1992, a total of 1,886 subjects remained for analysis (465 HCV-positive patients and 1,421 controls). Among these individuals without traditional risk factors, HCV-positive patients remained significantly more likely to have a history of one or more tattoos after adjustment for age, sex, and race/ethnicity (OR, 5.17; 95% CI, 3.75-7.11; P < 0.001). Conclusion: Tattooing is associated with HCV infection, even among those without traditional HCV risk factors such as IDU and blood transfusion prior to 1992. (HEPATOLOGY 2013;57:2117–2123)

Barrett’s esophagus (BE) represents a metaplastic change from squamous epithelium to intestinal epithelium as a result of chronic gastroesophagheal reflux. Since the development of esophageal adenocarcinoma (EAC) is not universal among patients with BE, it is important to understand and to gauge the factors that influence risk of progression to dysplasia and cancer. While heartburn symptoms have been reported to be associated with BE (Eisen et al., 1997; Lagergren et al., 1999a), the severity of gastroesophageal reflux symptoms is not a reliable indicator for the presence of BE (Eloubeidi and Provenzale, 2001). There is a vital need to explore factors other than symptoms that not only may elucidate the pathophysiology of BE development but also that may be predictive of progression to EAC. Significant advances have been made along key areas such as cell cycle abnormalities, growth factors, adiposity, and the gut microbiome. This chapter aims to review some of these elements as well as the prognostic value of biomarkers for progression from BE to EAC. The importance of fulfilling the promise that these biomarkers hold is underscored by the notable increase in the risk of progression to cancer from 0.5% per year in non-dysplastic BE, to 13% in the setting of low-grade dysplasia, and to 40% in high-grade dysplasia (Curvers et al., 2010; Wani et al., 2009).

Esophageal adenocarcinoma is preceded by the development of reflux-related intestinal metaplasia or Barrett esophagus, which is a response to inflammation of the esophageal squamous mucosa, reflux esophagitis. Gastroesophageal reflux impairs the mucosal barrier in the distal esophagus, allowing chronic exposure of the squamous epithelium to the diverse microbial ecosystem or microbiome and inducing chronic inflammation. The esophageal microbiome is altered in both esophagitis and Barrett esophagus, characterized by a significant decrease in gram-positive bacteria and an increase in gram-negative bacteria in esophagitis and Barrett esophagus. Lipopolysaccharides (LPS), a major structure of the outer membrane in gram-negative bacteria, can upregulate gene expression of proinflammatory cytokines via activation of the Toll-like receptor 4 and NF-κB pathway. The potential impact of LPS on reflux esophagitis may be through relaxation of the lower esophageal sphincter via inducible nitric oxide synthase and by delaying gastric emptying via cyclooxygenase-2. Chronic inflammation may play a critical role in the progression from benign to malignant esophageal disease. Therefore, analysis of the pathways leading to chronic inflammation in the esophagus may help to identify biomarkers in patients with Barrett esophagus for neoplastic progression and provide insight into molecular events suitable for therapeutic intervention in prevention of esophageal adenocarcinoma development in patients with reflux esophagitis and Barrett esophagus. Clin Cancer Res; 18(8); 2138–44. ©2012 AACR.

Although recent studies have suggested that tooth loss is positively related to the risk of gastric non-cardia cancer, the underlying oral health conditions potentially responsible for the association remain unknown. We investigated whether clinical and behavioral measures of oral health are associated with the risk of gastric precancerous lesions. We conducted a cross-sectional study of 131 patients undergoing upper gastrointestinal endoscopy. Cases were defined as those with gastric precancerous lesions including intestinal metaplasia or chronic atrophic gastritis on the basis of standard biopsy review. A validated structured questionnaire was administered to obtain information on oral health behaviors. A comprehensive clinical oral health examination was performed on a subset of 91 patients to evaluate for periodontal disease and dental caries experience. A total of 41 (31%) cases of gastric precancerous lesions were identified. Compared with non-cases, cases were significantly more likely to not floss their teeth [odds ratio (OR) = 2.89, 95% confidence interval (CI): 1.09–7.64], adjusting for age, sex, race, body mass index, smoking status, educational attainment and Helicobacter pylori status in serum. Among participants who completed the oral examination, cases (n = 28) were more likely to have a higher percentage of sites with gingival bleeding than non-cases [OR = 2.63, 95% CI: 1.37–5.05 for a standard deviation increase in bleeding sites (equivalent to 19.7%)], independent of potential confounders. Our findings demonstrate that specific oral health conditions and behaviors such as gingival bleeding and tooth flossing are associated with gastric precancerous lesions.