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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.

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.

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.

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.

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.

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.

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.

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.

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.

Our aim was to examine the humoral immune response against Streptococcus gallolyticus subspecies gallolyticus antigens in individuals subjected to a routine colonoscopy in which colon adenomatous polyps were present or not. Serum samples from 133 individuals with adenomatous polyps and serum samples from 53 individuals with a normal colonoscopy were included. Western blot was performed in all subjects using a whole cell antigen from S. gallolyticus ATCC 9809, and rabbit antisera against the whole cell bacteria was prepared as a control. By analyzing the immune profile of the rabbit-immunized sera by Western-blot, at least 22 proteins were identified as immunogenic in S. gallolyticus. When we evaluated sera from human subjects, two proteins of approximately 30 and 22 kDa were most prominent. Based on this 2-protein band pattern, Western-blot profiles from human subjects were compared. The detection of a protein band of 22 kDa was associated with the presence of adenomatous polyps in colon [odds ratios (OR) 7.98, 95% confidence intervals (CI): 3.54-17.93], p < 0.001. When the presence of the 30 kDa protein alone or both the 22 and 30 kDa proteins were analyzed, the OR increased to 22.37 (95% CI: 3.77-131.64), p < 0.001. The specificity was 84.9 for the presence of the 22 kDa protein, and 98.1 for the presence of the 30 kDa protein alone or both 22 and 30 kDa bands. Serum from individuals with adenomatous polyps recognized two proteins from S. gallolyticus. This result confirmed the possible association of S. gallolyticus with adenomatous polyps in the colon.

Background Appetite and energy expenditure are regulated in part by ghrelin and leptin produced in the gastric mucosa, which may be modified by H. pylori colonization. We prospectively evaluated the effect of H. pylori eradication on meal-associated changes in serum ghrelin and leptin levels, and body weight. Methods Veterans referred for upper GI endoscopy were evaluated at baseline and ≥8 weeks after endoscopy, and H. pylori status and body weight were ascertained. During the first visit in all subjects, and during subsequent visits in the initially H. pylori-positive subjects and controls, blood was collected after an overnight fast and 1 h after a standard high protein meal, and levels of eight hormones determined. Results Of 92 enrolled subjects, 38 were H. pylori-negative, 44 H. pylori-positive, and 10 were indeterminate. Among 23 H. pylori-positive subjects who completed evaluation after treatment, 21 were eradicated, and 2 failed eradication. After a median of seven months following eradication, six hormones related to energy homeostasis showed no significant differences, but post-prandial acylated ghrelin levels were nearly six-fold higher than pre-eradication (p = 0.005), and median integrated leptin levels also increased (20%) significantly (p < 0.001). BMI significantly increased (5 ± 2%; p = 0.008) over 18 months in the initially H. pylori-positive individuals, but was not significantly changed in those who were H. pylori-negative or indeterminant at baseline. Conclusions Circulating meal-associated leptin and ghrelin levels and BMI changed significantly after H. pylori eradication, providing direct evidence that H. pylori colonization is involved in ghrelin and leptin regulation, with consequent effects on body morphometry.

To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma (TIF1γ), Smad4 and transforming growth factor-beta (TGFβR) across a spectrum representing colorectal cancer (CRC) development.Tissue microarrays were prepared from archival paraffin embedded tissue, including 51 colorectal carcinomas, 25 tubular adenomas (TA) and 26 HPs, each with matched normal colonic epithelium. Immunohistochemistry was performed using antibodies against TIF1γ, Smad4 and TGFβRII. The levels of expression were scored semi-quantitatively (score 0-3 or loss and retention for Smad4).Overexpression of TIF1γ was detected in 5/26 (19%) HP; however, it was seen in a significantly higher proportion of neoplasms, 15/25 (60%) TAs and 24/51 (47%) CRCs (P0.05). Normal colonic mucosa, HP, and TAs showed strong Smad4 expression, while its expression was absent in 22/51 (43%) CRCs. Overexpression of TGFβRII was more commonly seen in neoplasms, 13/25 (52%) TAs and 29/51 (57%) CRCs compared to 9/26 (35%) HP (P0.05). Furthermore, there was a correlation between TIF1γ overexpression and Smad4 loss in CRC (Kendall tau rank correlation value = 0.35, P0.05). The levels of TIF1γ overexpression were significantly higher in stage III than in stage I and II CRC (P0.05).The findings suggest that over-expression of TIF1γ occurs in early stages of colorectal carcinogenesis, is inversely related with Smad4 loss, and may be a prognostic indicator for poor outcome.

Esophageal adenocarcinoma (EA), the type of cancer linked to heartburn due to gastroesophageal reflux diseases (GERD), has increased six fold in the past 30 years. This cannot currently be explained by the usual environmental or by host genetic factors. EA is the end result of a sequence of GERD-related diseases, preceded by reflux esophagitis (RE) and Barrett’s esophagus (BE). Preliminary studies by Pei and colleagues at NYU on elderly male veterans identified two types of microbiotas in the esophagus. Patients who carry the type II microbiota are >15 fold likely to have esophagitis and BE than those harboring the type I microbiota. In a small scale study, we also found that 3 of 3 cases of EA harbored the type II biota. The findings have opened a new approach to understanding the recent surge in the incidence of EA.Our long-term goal is to identify the cause of GERD sequence. The hypothesis to be tested is that changes in the foregut microbiome are associated with EA and its precursors, RE and BE in GERD sequence. We will conduct a case control study to demonstrate the microbiome disease association in every stage of GERD sequence, as well as analyze the trend in changes in the microbiome along disease progression toward EA, by two specific aims. Aim 1 is to conduct a comprehensive population survey of the foregut microbiome and demonstrate its association with GERD sequence. Furthermore, spatial relationship between the esophageal microbiota and upstream (mouth) and downstream (stomach) foregut microbiotas as well as temporal stability of the microbiome-disease association will also be examined. Aim 2 is to define the distal esophageal metagenome and demonstrate its association with GERD sequence. Detailed analyses will include pathway-disease and gene-disease associations. Archaea, fungi and viruses, if identified, also will be correlated with the diseases. A significant association between the foregut microbiome and GERD sequence, if demonstrated, will be the first step for eventually testing whether an abnormal microbiome is required for the development of the sequence of phenotypic changes toward EA. If EA and its precursors represent a microecological disease, treating the cause of GERD might become possible, for example, by normalizing the microbiota through use of antibiotics, probiotics, or prebiotics. Causative therapy of GERD could prevent its progression and reverse the current trend of increasing incidence of EA.

This paper presents the results oj a jollow-up evaluation conducted to assess the impact oj a community-wide stop smoking contest conducted in Buffalo, lVew York in January 1988. The contest challenged smokers to make a pledge to quit jar 30 days to have a chance to win $1,000 cash, a vacation trip, or other prizes. Finalists were randomly selected and chemically tested to verify abstinence. Telephone jollow-up interviews were conducted on a sample oj 411 contestants six weeks and eight months ajter the quit date. A total oj 2,565 smokers enrolled in the contest. Compared to smokers in the general population, contestants were more likely to be jemale, white, under age 40, and smoke 25 or more cigarettes daily. Over 90 percent oj contestants attempted to stop smoking, 51 percent quit jar the 3D-day contest period, and 32 percent were not smoking ajter eight months.

Although many patients with human immunodeficiency virus (HIV) infection are now living well beyond 50 years of age, there are no data available on colorectal cancer screening in this population. The aim of this study was to determine the utility of screening flexible sigmoidoscopy in patients with HIV.Consecutive patients at average risk for colorectal cancer who were referred for screening flexible sigmoidoscopy were prospectively identified. A detailed medical history was obtained from all patients before flexible sigmoidoscopy, and colonoscopy was recommended for all subjects with positive sigmoidoscopic findings.A total of 2382 patients were enrolled in the study; 165 were HIV positive. The prevalence of neoplastic lesions (adenomas or adenocarcinomas) in the distal colon was significantly higher in HIV-infected patients than in control subjects (25.5% vs 13.1%, P.001), and the odds of HIV-infected patients having a neoplastic lesion was significantly higher even after adjustment for potential confounding variables (odds ratio, 2.34; 95% confidence interval, 1.60-3.44). The prevalence of adenomas of any size (25.5% vs 12.9%, P.001) and advanced neoplasia (7.3% vs 3.8%, P = .03) in the distal colon was significantly higher in HIV-infected patients. Among individuals with positive results on flexible sigmoidoscopy, proximal colonic neoplastic lesions on follow-up colonoscopy were more common in HIV-infected patients after adjustment for age, sex, and race/ethnicity (odds ratio, 1.88; 95% confidence interval, 1.02-3.46).Patients infected with HIV are more likely to have colonic neoplasms on screening flexible sigmoidoscopy than those without HIV, and these individuals should be offered colorectal cancer screening.

Although the association between distal neoplasia on sigmoidoscopy and proximal colonic pathology on follow-up colonoscopy has been well-described, it is not known if these findings are consistent across ethnic groups. The aim of this study was to evaluate ethnic variations in the prevalence of proximal neoplasia on follow-up colonoscopy after a neoplastic lesion is found on sigmoidoscopy.Consecutive asymptomatic patients at average-risk for colorectal cancer who were referred for screening flexible sigmoidoscopy were prospectively enrolled. Colonoscopy was recommended for all patients with a polyp on flexible sigmoidoscopy, regardless of size. Advanced neoplasms were defined as adenomasor = 10 mm in diameter or any adenoma, regardless of size, with villous histology, high-grade dysplasia, or cancer.Among the 2,207 patients who had sigmoidoscopy, 970 were Caucasian, 765 were African American, 395 were Hispanic, and 77 were Asian. The prevalence of neoplasia in the distal colon was 12.6% in Caucasians, 11.2% in African Americans, 15.9% in Hispanics, and 24.7% in Asians (p = 0.002). Of the 290 patients with neoplastic lesions on sigmoidoscopy, follow-up colonoscopy identified neoplasms in the proximal colon in 63.9% of Caucasians, 59.3% of African Americans, 66.7% of Hispanics, and 26.3% of Asians (p = 0.01). Advanced neoplasms in the proximal colon were highest in African Americans (34.9%) and lowest in Asians (10.5%).In our study population, Asians demonstrated a higher prevalence of distal colonic neoplasia and a lower prevalence of proximal colonic neoplasia compared to non-Asians. Future studies should explore ethnic variation in colonic neoplasia prevalence and location since ethnic variation could lead to tailored colorectal cancer screening strategies.

The esophagus, like other luminal organs of the digestive system, provides a potential environment for bacterial colonization, but little is known about the presence of a bacterial biota or its nature. By using broad-range 16S rDNA PCR, biopsies were examined from the normal esophagus of four human adults. The 900 PCR products cloned represented 833 unique sequences belonging to 41 genera, or 95 species-level operational taxonomic units (SLOTU); 59 SLOTU were homologous with culture-defined bacterial species, 34 with 16S rDNA clones, and two were not homologous with any known bacterial 16S rDNA. Members of six phyla, Firmicutes , Bacteroides , Actinobacteria , Proteobacteria , Fusobacteria , and TM7 , were represented. A large majority of clones belong to 13 of the 41 genera (783/900, 87%), or 14 SLOTU (574/900, 64%) that were shared by all four persons. Streptococcus (39%), Prevotella (17%), and Veilonella (14%) were most prevalent. The present study identified ≈56–79% of SLOTU in this bacterial ecosystem. Most SLOTU of esophageal biota are similar or identical to residents of the upstream oral biota, but the major distinction is that a large majority (82%) of the esophageal bacteria are known and cultivable. These findings provide evidence for a complex but conserved bacterial population in the normal distal esophagus.

We hypothesized that laparoscopic adjustable gastric banding (LAGB) reduces weight and modulates ghrelin production, but largely spares gastrointestinal endocrine function. To examine this hypothesis, we determined plasma concentrations of appetite-control, insulinotropic, and digestive hormones in relation to LAGB.Twenty-four patients undergoing LAGB were prospectively enrolled. Body mass index (BMI) was measured and blood samples obtained at baseline and 6 and 12 months post-surgery. Plasma concentrations of leptin, acylated and total ghrelin, pancreatic polypeptide (PP), insulin, glucose-dependent insulinotropic peptide (GIP), active glucagon-like peptide-1 (GLP-1), gastrin, and pepsinogens I and II were measured using enzyme-linked immunoassays.Median percent excess weight loss (%EWL) over 12 months was 45.7% with median BMI decreasing from 43.2 at baseline to 33.8 at 12 months post-surgery (p0.001). Median leptin levels decreased from 19.7 ng/ml at baseline to 6.9 ng/ml at 12 months post-surgery (p0.001). In contrast, plasma levels of acylated and total ghrelin, PP, insulin, GIP, GLP-1, gastrin, and pepsinogen I did not change in relation to surgery (p0.05). Pepsinogen II levels were significantly lower 6 months after LAGB but returned to baseline levels by 12 months.LAGB yielded substantial %EWL and a proportional decrease in plasma leptin. Our results support the hypothesis that LAGB works in part by suppressing the rise in ghrelin that normally accompanies weight loss. Unchanged concentrations of insulinotropic and digestive hormones suggest that gastrointestinal endocrine function is largely maintained in the long term.

BACKGROUND: GERD is a prevalent condition that encompasses bothersome symptoms or mucosal injury. It remains challenging to diagnose the condition in individuals with the most common presentation of non-erosive reflux disease. The current diagnostic tools include symptom assessment, endoscopy, and pH-metry. Few studies have evaluated the utility of combining these factors with histology to diagnose GERD in the general population. This study aimed to assess the diagnostic yield of a model with predefined criteria in diagnosing GERD among those with non-erosive disease. METHODS: Individuals presenting for upper endoscopy were prospectively enrolled, and the presence of upper GI symptoms was assessed via a standardized questionnaire. All subjects underwent EGD with lower esophageal biopsies 2 cm above the squamocolumnar junction. A blinded GI pathologist reviewed all biopsies. Esophageal acid exposure and symptom association were assessed off acid suppression therapy via 48-hour pH-metry. Subjects were categorized as GERD if at least two of the following criteria in this model were present: 1) positive symptoms reported on presentation 2) any endoscopically identified LA grade esophagitis 3) histologic pathology 4) esophageal pH ,4 for more than 4.5% of the time. RESULTS: Among the 292 subjects enrolled 26% were women and 74% were men, while the majority were either Caucasian (43%) or African American (27%). Mean age (59 ± 9 years) did not differ according to gender or race/ethnicity. The prevalence of GERD symptoms was 62% and erosive esophagitis was 20%. Data for all diagnostic criteria was complete for 113 subjects and as expected, the prevalence of positive pH studies (pH+) was highest for those with endoscopic esophagitis compared to those without endoscopic esophagitis (65% vs. 41%, p=0.03). However the sensitivity of EGD alone for pH+ was 29% with a specificity of 87%. Regardless of endoscopic findings, no difference in pH+ studies was found based on symptoms or histology alone. Among the 90 subjects with a normal endoscopy who still met the predefined criteria the prevalence of pH+ was significantly higher compared to those who did not meet the criteria (71% vs. 15%, p,0.001). The positive likelihood ratio for this diagnostic approach among individuals with non-erosive disease was 3. In multivariate logistic regression analysis, the model remained significant for GERD with pH+ after controlling for age, gender, BMI, tobacco and alcohol (OR 11, 95% CI 3.0-39; p,0.001). CONCLUSIONS: Among individuals presenting for general endoscopic evaluation the prevalence of erosive disease is low. A predictive model that includes histology allows for a clinically useful approach in diagnosing GERD in non-erosive disease and can help predict and potentially obviate the need for pH testing. Further assessment should be conducted in diverse populations.

We have characterized the nature and pattern of cell death during regression of the pupillary membrane, a developmentally transient capillary network found in the anterior chamber of the eye. This analysis has revealed that the cellular components of the pupillary membrane include vascular endothelial cells in an intricate network of fine capillaries as well as attendant macrophages. The capillaries are situated on the anterior surface of the lens and held in relative position by a cobweb-like meshwork of extracellular matrix fibres that regress along with the cellular components of this structure. Cell death during regression of the pupillary membrane is characteristic of apoptosis. Specifically, apoptotic bodies containing condensed chromatin can be observed in vascular endothelial cells and genomic DNA isolated from the pupillary membrane shows the nucleosomal fragmentation pattern typical of apoptotic cells. Using a method for labelling fragmented DNA in tissue preparations (TUNEL), we have assessed the overall pattern of apoptotic cell death during pupillary membrane regression. We find that apoptosis occurs either in single cells in healthy vessels or synchronously along the entire length of a capillary segment. Both morphological and TUNEL analysis indicate that capillary regression occurs from junction to junction one segment at a time. We propose a model to explain the pattern of capillary regression observed and conclude from these and previous experiments (Lang and Bishop (1993)Cell 74, 453-462), that during regression of the pupillary membrane, the macrophage elicits target cell death by inducing apoptosis.

Background and Aims: The incidence of colorectal cancer (CRC) can be decreased by appropriate screening. Given limited resources, strategies based on established guidelines may increase screening efficacy particularly by targeting high risk populations. Our aim was to assess physician knowledge of CRC screening guidelines based on family history and ethnicity, and perceived adherence barriers. Methods: Using a stratified sampling strategy of states with high and low incidence of CRC, a random sample of internists (IMs), family medicine physicians (FMPs) and gastroenterologists (GIs) was established from the American Medical Association registry. The study cohort was electronically invited to anonymously complete a web-based 19-item survey (tested for face and content validity) assessing knowledge, and adherence barriers. Responses were evaluated based on established guidelines from the US Multisociety Task Force and American College of Gastroenterology. Results: Among 25,000 invitees, 512 (2%) representing 29 states (55% from high and 45% from low CRC states) completed the survey and served as the study cohort. Reflecting the sampled cohort 38.3% were IMs, 30.1% FMPs, and 28.3% GIs. The majority (76%) had been in practice for >5 years and saw >50 patients per week. Among the participants, 49.6% were in group practice, 27% in academics, 14.6% in solo practice, and 8.8% were hospital based. The overall mean correct score for knowledge of screening guidelines was only 37± 18%. The mean score for GIs (50±19%) was higher compared to IMs (34±15%), and FMPs (31±14%); P=0.003. Private Practitioners scored higher than academicians (49±19% vs. 33±15%; P