bluuebunny/crossref_metadata_2025 huggingface dataset:
1222 Co-Prescription of Ondansetron With Other QT-Prolonging Drugs: Data From a Large Community-Based Hospital System
Authors: Varghese Elsa , Ehrenpreis Eli , Ehrenpreis Jamie
Published: October 2019

INTRODUCTION:

The Food and Drug Administration (FDA) has warned about the co-prescription of ondansetron with other QT-prolonging medications. Electronic medical records (EMR) with built-in warning systems for drug-drug interactions (DDIs) are designed to improve patient safety. However, overriding of warnings are common. Response to warnings for potentially life-threatening DDIs such as QT-prolongation has not been fully investigated. We studied outpatient co-prescription of ondansetron with other QT-prolonging medications in a large community-based health practice.

METHODS:

Data for all outpatient prescriptions for oral ondansetron from January 1 to March 31st, 2016 at NorthShore University HealthSystem was reviewed. A de-identified dataset was developed that included all outpatient prescriptions for oral ondansetron in patients receiving another QT-prolonging drug. Duplicate orders were removed. Interaction warnings, including the severity of the interactions are generated at the time of order placement. Prescriber response to DDI warnings and further analysis of the co-prescribed QT-prolonging drugs was performed. Demographic information was also studied.

RESULTS:

11,935 cases of inpatient and outpatient co-prescriptions of ondansetron with and one or more QT-prolonging drug occurred during the study period. After filtering, there were 884 outpatient ondansetron and QT-prolonging co-prescription orders in 723 patients. All warnings were “severe interactions”. Only 93 (10.5%) prescriptions in outpatients were canceled, while 791 (89.5%) of the prescription orders were overridden. The most common classes of QT-prolonging medications taken by patients with overridden orders for ondansetron were selective serotonin reuptake inhibitors (SSRIs) (33%), macrolide antibiotics (29%), fluoroquinolone antibiotics (13%), and serotonin antagonist reuptake inhibitors (SARIs) (11%) (See Table 1). The most commonly co-prescribed QT prolonging drugs are listed in Table 2. Twelve patients receiving QT-prolonging antiarrhythmic agents had completed orders for ondansetron. 617 (78%) of overridden prescriptions occurred in women.

CONCLUSION:

Warnings for ondansetron co-prescription with other QT-prolonging drugs are usually ignored. Co-prescription of ondansetron with other QT-prolonging drugs is more common in female patients. This is of particular concern because women are more likely to develop serious arrhythmias related to ondansetron-induced QT-prolongation.
1224 Exploring the Possibility of Gastroesophageal Reflux Disease as a Screening Factor for Helicobacter pylori in Patients From Endemic Regions
Authors: Ahmed Ahmed , Rotundo Laura , Silva Alejandro , Feurdean Mirela , Atkin Suzanne
Published: October 2019

INTRODUCTION:

Helicobacter pylori (HP) is a common gastric infection with the highest prevalence in Asia, Africa, Central, and South America as well as in U.S. immigrants from these areas. Current American College of Gastroenterology (ACG) guidelines recommend screening for HP in cases such as patients with active or prior peptic ulcer disease (PUD). However, screening is not recommended for patients who exhibit only symptoms of gastroesophageal reflux disease (GERD) irrespective of regional origin. The goal of this study was to determine if patients from endemic regions with GERD should be screened for HP.

METHODS:

This is a retrospective chart review of all patients who presented to an internal medicine ambulatory care clinic in 2017 with symptoms of GERD and/or PUD for whom orders were placed for HP testing via stool antigen or endoscopic biopsy. GERD symptoms were defined as reflux or heartburn and PUD as any symptom of dyspepsia. Patients were stratified by symptoms: GERD, PUD, or both. Exclusion criteria were as follows: tests ordered but never collected, orders for confirmation of cure for prior infection, multiple tests ordered for the same patient over the study period, tested patients with no symptoms, and patients with symptoms related to a non-H. pylori preexisting disorder. Enrolled patients were further stratified by region of origin.

RESULTS:

122 patients that met the selection criteria were included in this study. 43% (52/122) of all patients were positive for HP. Of those that were positive, 92% (48/52) came from an endemic area (83% from South or Central America) and of these 75% (36/48) had PUD symptoms, 25% (12/48) had GERD only, and 52% (25/48) had both GERD and PUD symptoms. Of HP positive patients from non-endemic areas, all had GERD symptoms (4/4), with 1 having GERD only. Of patients that had GERD symptoms only, 25% (12/48) tested positive for HP and were from endemic areas.

CONCLUSION:

In our study, 25% of patients from endemic regions with solely GERD symptoms tested positive for HP, suggesting that recommendations for screening should include this population. Our data collection was small and skewed towards patients originating from endemic regions of South and Central America, and the results may not be applicable to other endemic regions, such as Asia and Africa. Further studies are needed to establish appropriate screening recommendations that are applicable to other endemic areas, so that the diagnosis of HP is not missed.
1225 Gastric Adenocarcinoma Incidence and Incidence-Based Mortality: A Population-Based Study of 62,863 Cases From the Surveillance, Epidemiology and End Results (SEER) Program Over Last Four Decades
Authors: Afifi Ahmed , Elmehrath Ahmed , Hashim Mahmoud , Abdelwadoud Moaz , Ismail Bahaaeldeen
Published: October 2019

INTRODUCTION:

Gastric cancer (GC) is the third deadliest cancer worldwide therefore tracking its morbidity and mortality trends is necessary to identify the most susceptible population groups, and develop targeted clinical management strategies.

METHODS:

We searched the SEER 9 databases to investigate the incidence and incidence-based mortality (IBM) rates of gastric adenocarcinoma (GAC) from 1973 to 2015 according to patients' gender, age, race, state of residence, and GAC stage. We analyzed the annual percent change (APC) of the incidence and IBM of GAC via Joinpoint® regression software.

RESULTS:

We analyzed 62,863 GAC cases. GAC incidence and IBM rates decreased by 1.66% and 1.53% (P < 0.001) annually, respectively (Table 1). Incidence rates were highest among males, African Americans, and patients aged 65 years or more, whereas the IBM rates were the highest among males, American Indians, Alaska Natives, Asians and Pacific Islanders and patients aged 65 years or older. GAC incidence in stomach cardia increased by 0.66% annually, while GAC incidence in the antrum and lesser curvature decreased by 1.77% and 3.04% annually, respectively. Likewise, GAC IBM in stomach cardia increased by 0.52%, while GAC IBM in antrum and lesser curvature decreased by 1.4% and 2.2% annually, respectively. Geographically, the incidence and IBM rates of GAC decreased in all states over the study period. Notably, Hawaii (HI) had the highest incidence and IBM rates (Table 2). Also, we found that cardia GAC was the most prevalent sub-type in all states except HI, where antrum GAC was the highest.

CONCLUSION:

Despite an overall decrease in GAC incidence and IBM, there is an increase in cardia GAC, which may be secondary to rise in obesity and alcohol consumption along with decrease in H. pylori prevalence. The incidence rate of GAC is higher in HI, Michigan and Connecticut, which is in concordance with the published data from State Cancer Profiles between 2011-2015. We could not evaluate the underlying risk factor for each state due to study's nature; however, the higher incidence rates in HI may be attributed to genetic environmental interactions, as supported by migrant studies. In conclusion, we were able to outline trends in incidence and IBM of GAC in USA over last four decades, which suggest a need for tailoring treatment and preventive strategies to fit each state population.
1228 Cardiac Safety and Clinical Efficacy of High Dose Domperidone for Long-Term Treatment of Gastroparesis
Authors: Woods Kevin , Sarosiek Irene , Espino Karina , Ramirez Marisol , Siddiqui Tariq , McCallum Richard
Published: October 2019

INTRODUCTION:

Domperidone (D), a dopamine 2 receptor antagonist, is an effective anti-emetic that acts at the chemoreceptor trigger zone and only minimally crosses the blood brain barrier while also exerting prokinetic effects on the stomach and proximal small bowel. D is not approved in the USA. Recommended dosing worldwide is 30 mg/day and due to scattered reports of cardio toxicity ECG monitoring is recommended. Our goal was to explore the cardiac safety and clinical efficacy of long-term use of D, titrated as high as 120 mg/day, in patients not responding or unable to tolerate other therapies for gastroparesis (GP).

METHODS:

From our database we identified 19 patients without preexisting cardiac diagnoses, 85% F, mean age 47 (range 27-74), 50% white, 42% Hispanic, who received a high dose D per FDA/IND approved protocol. Baseline GP symptoms were assessed and then monitored for changes during treatment using a physician administered IRB-approved questionnaire which recorded the GP symptoms of nausea, vomiting, early satiety and abdominal pain, which were graded for severity (0-absent to 4-extremely severe) and compared to baseline values. Patients had to be improved symptomatically by ≥50% to be considered responders. Adverse cardiac events were recorded, and follow up ECGs (average 2 repeat ECGs per patient (range 1-7) focused on prolonged QTc intervals (>450 ms in M, >470 ms in F).

RESULTS:

The mean duration of D therapy was 31 months (range 3-96) median time of 17 months. The average dose of D was 80 mg/day (range of 40-120), while 3 (15%) of GP patients recieved 120 mg/day. No patients had serious cardiac adverse events. Two (F) patients had prolonged QTc of 491 ms and 482 ms requiring discontinuation of D and 4 reported heart palpitations or chest pain unrelated to prolonged QTc, and continued the medication. 78% of patients met criteria for treatment response with overall mean symptoms improvement of 71% (range 30-100) compared to pre-D scores. Vomiting was the most improved symptom.

CONCLUSION:

Long-term treatment with high doses of D resulted in significant improvement of GP symptoms in patients previously refractory to other medical therapies. There were no adverse cardiac events reported, and only asymptomatic QTc prolongation was recorded in 11% of patients. These data emphasize both the safety and efficacy of high dose D in the treatment of symptomatic GP.
1229 Resident Education in the Placement and Confirmation of Feeding Tubes
Authors: Oruganti Poornima , Nakshabandi Ahmad , Palmer Lena
Published: October 2019

INTRODUCTION:

Nasogastric feeding tube (FT) placement is often done by trainees without uniform education. Serious complications can occur if FT are improperly inserted. This study assesses trainee education in FT insertion to identify knowledge-gaps and a need for standardized training.

METHODS:

A 16- item, web-based E-questionnaire was distributed to 149 Internal Medicine, Medicine-Pediatrics, Family Medicine, Obstetrics and Gynecology, General Surgery and Neurology residents at a university medical center and a community-based teaching hospital near Chicago, IL. Results were collected and analyzed through the web-based platform. The study was exempted from institutional review.

RESULTS:

One hundred seventeen residents responded (78.5% response rate). Most were Internal Medicine residents (66.1%) in postgraduate year 1 (37.8%). 76.1% of survey respondents received training in residency and 59.8% in medical school. The majority of survey respondents (94.9%) learned by bedside demonstration. The second most common training method was simulator training, but this was reported by only 29.9%. Most survey respondents felt they had adequate training (74.1%); however, only 50% felt very confident in their ability. Most residents reported requirements between 0 and <10 supervised placements before being certified by their institution. Almost a third (32.8%) of respondents were unaware of the requirements for certification, and surprisingly 23.3% reported that none were required. Most indicated that residents or fellows placed the majority of FT at their institutions. Almost all respondents (96.6%) were able to correctly identify abdominal Xray as the gold standard to confirm correct FT placement. Though 47% stated they were responsible for certifying proper positioning of FT, only 62.6% of responders reported they received instruction in Xray interpretation, and only 36.8% were able to correctly answer a question regarding radiographic landmarks of properly-placed tubes.

CONCLUSION:

Our study is the first to survey American medical residents regarding their knowledge, training, and comfort in placing FT. While the data indicate residents generally feel they receive adequate training, only half reported being very confident in this skill, and training in Xray interpretation was inadequate. This suggests a role for standardized training in placement and confirmation of FT to improve patient safety and resident education.
1230 Helicobacter pylori Eradication and Its Association With Metachronous Gastric Cancer Recurrence and Pre-Neoplastic Lesions: A Systematic Review and Meta-Analysis
Authors: Khan Muhammad Y. , Aslam Aysha , Mihali Albana B. , Rawala Muhammad Shabbir , Dirweesh Ahmed , Khan Salman , Siddiqui Ali
Published: October 2019

INTRODUCTION:

Gastric cancer is the 4th leading cause of cancer deaths worldwide displaying global variation in incidence. Helicobacter pylori (H Pylori) is known risk factor for gastric cancer. The magnitude of benefit of H pylori eradication in preventing GC recurrence is unclear. We performed a systematic review (SR) and meta-analysis (MA) of available randomized clinical trials (RCTs) to investigate the impact of H Pylori eradication on GC recurrence and precancerous lesions.

METHODS:

A planned literature search of Medline, PubMed and Google Scholar databases was carried out from inception to 10 February 2019. Ten (RCTs) included for analysis had H Pylori eradication as intervention arm compared to placebo. Statistical analysis was performed using statistical software RevMan, version 5.3. Random effects model and Mantel-Haenszel method for the statistical analysis was used for dichotomous data to calculate the odds ratio (OR). Two sided P values of less than 0.05 was considered statistically significant.

RESULTS:

10 RCTs with total of 7,098 patients were included for final comparison. There were 3548 subjects in H Pylori group and 3550 in the placebo arm. The primary outcome was development of metachronous GC after endoscopic mucosal resection (EMR) in patients with early stage GC. H pylori group showed significant reduction in incidence of metachronous GC compared to placebo OR = 0.47, 95% confidence interval (CI) = 0.33– 0.67, P < 0.0001, I2 = 0%]. Incidence of GC in high risk patients without GC at baseline showed no difference between two groups OR = 0.67, 95% CI = 0.42–1.07, P = 0.09, I2 = 0%). H Pylori eradication group showed statistically significant improvement in AG and IM from baseline compared to placebo group with OR = 2.10, 95% CI = 1.19–3.71, P = 0.01, I2 = 87% and OR = 2.08, 95% CI = 1.28–3.36, P = 0.003, I2 = 30% respectively. RCTs with mean duration of follow up >5 years for GC incidence showed statistically significant reduction in GC incidence in H Pylori eradication group OR = 0.55, 95% CI = 0.40-0.76, P = 0.0003, I2 = 0%.

CONCLUSION:

Our meta-analysis showed the beneficial role of H Pylori eradication in decreasing GC recurrence for patients with early GC post EMR. H Pylori group also showed improvement in AG and IM grades compared to placebo. There was no difference in GC incidence in asymptomatic patients without GC at baseline between the two groups. More studies are needed from the North America, Europe and other non-Asian countries to better understand the differences in geographical regions.
1231 Racial and Ethnic Differences in Mortality in Gastric Cancer and Esophageal Adenocarcinoma in the United States
Authors: Laszkowska Monika , Tramontano Angela , Kim Judith , Camargo M. Constanza , Neugut Alfred , Abrams Julian , Hur Chin
Published: October 2019

INTRODUCTION:

Studies have shown that the incidence of non-cardia gastric cancer (GC) has been declining in recent years, while the rate of cardia GC has been increasing, paralleling the trends of esophageal adenocarcinoma (EAC). Mortality trends in these malignancies have not been well studied, particularly for non-cardia GC. The aim of our study was to examine differences in incidence-based mortality in cardia and non-cardia GC, as well as EAC for comparison, in a representative cohort of the US population.

METHODS:

A total of 19,025 individuals with non-cardia GC, 14,268 with cardia GC, and 18,015 with EAC were identified in the Surveillance, Epidemiology, and End Results database. Age-adjusted incidence-based mortality rates and corresponding annual percent change (APC) were calculated between 2004-2016 to assess trends. Mortality analyses were stratified by race/ethnicity, age, and stage of disease at diagnosis.

RESULTS:

The age-adjusted incidence-based mortality rate (per 100,000 population) for non-cardia GC was 2.50, for cardia GC was 1.85, and for EAC was 2.31. Mortality in non-cardia GC was higher in blacks, Hispanics, and Asians/Pacific Islanders than non-Hispanic whites (P-value < 0.01 for each group). These differences remained statistically significant across all age groups and stages of disease (P-value < 0.01). From 2004-2016, mortality rates have not changed significantly over time for any racial/ethnic group. Interestingly, incidence-based mortality in EAC and cardia GC was higher in non-Hispanic whites than blacks, Hispanics, and Asians/Pacific Islanders (P-value < 0.01 for each group). These differences remained statistically significant across all age groups and stages of disease (P-value < 0.05). From 2004-2016 mortality has been rising in whites for EAC (APC = 3.86, P-value < 0.05) and cardia GC (APC = 3.90, P-value < 0.05), and in Hispanics for cardia GC (APC = 2.23, P-value < 0.05).

CONCLUSION:

Incidence-based mortality is higher in blacks, Hispanics, and Asians/Pacific Islanders in non-cardia GC, and higher in non-Hispanic whites in EAC and cardia GC. These differences persist when adjusting for age and stage of disease at diagnosis. Further research is needed to better understand the underlying causes of these differences in order to improve outcomes.
1233 Disaggregation of Gastric Cancer Risk Between Asian American Subgroups
Authors: Huang Robert , Hwang Joo Ha , Palaniappan Latha
Published: October 2019

INTRODUCTION:

Within the United States (US), 26,000 new cases of gastric cancer (GC) and over 10,000 related deaths occur annually. Within the US, Asians and Pacific Islanders (API) in aggregate are known to be at increased risk for GC. There is limited data regarding GC risk between API subgroups. While screening of the general American population is not cost-effective, improved understanding of GC risk by disaggregated API subgroups may allow for targeted and cost-effective endoscopic screening.

METHODS:

All incident cases of GC diagnosed in the years 2011-2014 were identified from the Surveillance, Epidemiology, and End Results Program registries incorporating California (CA) and Hawaii (HI). From these incidence registries, API subgroup of patients were identified: Korean (CA and HI), Japanese (CA and HI), Chinese (CA and HI), Vietnamese (CA only), Filipino (CA and HI), and Indian (CA only). API subgroup population estimates were obtained from the American Community Survey (ACS). The age-adjusted incidence rates per 100,000 population and 95% confidence intervals (CIs) were generated for each subgroup, and among non-Hispanic whites (NHWs) for reference.

RESULTS:

2,132 incident API GCs, and 3,984 incident NHW GCs were identified. Significant differences in GC incidence exist between API subgroups. In CA, Koreans (23.4 per 100,000, 95% CI 15.8 to 31.0) and Japanese (21.4, CI 16.1 to 26.7) demonstrated high incidence, Chinese (11.0, CI 10.4 to 11.6) and Vietnamese (10.3, CI 7.8 to 12.8) demonstrated intermediate incidence, and Filipinos (4.6, CI 3.4 to 5.8) and Indians (3.7, CI 2.9 to 4.5) demonstrated low incidence (Figure 1). The incidence among NHWs in CA was 6.6 (CI 6.0 to 7.2). In HI, Koreans (16.3, CI 11.4 to 21.2) and Japanese (16.0, CI 12.5 to 19.5) demonstrated high incidence, while Filipino (5.0, CI 3.4 to 6.6) and Chinese (4.8, CI 2.1 to 7.5) demonstrated low incidence (Figure 2). The incidence among NHWs in HI was 4.7 (CI 3.1 to 6.3).

CONCLUSION:

Substantial heterogeneity in risk for GC exist between API subgroups. Koreans and Japanese are at highest risk, with incidence nearly five-fold higher than Filipinos and Indians. This suggests that the higher GC-risk in APIs in aggregate are driven by certain subgroups. This may hold implications for screening for GC. There is a lower incidence of GC in HI compared to CA, even within API subgroups. These differences may represent cohort effects from generational migration, or regional dietary and environmental differences.
1234 Variability in Gastric Cancer Survival by Disaggregated Asian American Subgroups
Authors: Huang Robert , Palaniappan Latha , Hwang Joo Ha
Published: October 2019

INTRODUCTION:

Within the United States (US), 26,000 new cases of gastric cancer (GC) and over 10,000 related deaths occur annually. Asians and Pacific Islanders (API) in the U.S. are known to be at increased risk for GC. Due to differences in H. pylori prevalence, smoking habits, dietary patterns, and other genetic and environmental factors, the behavior of GC may vary between API subgroups. There exists little data regarding survivorship from GC between API subgroups.

METHODS:

All incident cases of GC diagnosed in between 2004-2014 were identified from the Surveillance, Epidemiology, and End Results Program registries. From the incidence registries, the records of Koreans, Japanese, Chinese, Vietnamese, Filipino, and Indians patients were extracted and compared with non-Hispanic white (NHW) patients as a reference. Differences between subgroups in all-cause mortality following diagnosis was evaluated utilizing Kaplan-Meier statistics and the log-rank test. The proportion of GCs diagnosed at a local stage (as defined by National Cancer Institute summary stage) were compared between subgroups. A proportional hazards regression model was used to compare subgroups, and adjust for differences in age and stage of diagnosis.

RESULTS:

There exist substantial differences in all-cause survival between API subgroups (Figure 1, P < 0.001). Koreans demonstrated better overall survival than other subgroups, while NHW demonstrated worst overall survival. Koreans had the highest percentage of GCs diagnosed at local stage (37.8%), while Filipinos had the lowest percentage (18.9%, Figure 2). In univariate proportional hazards regression (Figure 3), all API subgroups except Filipinos demonstrated superior survival compared to NHW. In multivariable regression adjusted for age, gender, and stage of diagnosis, all API subgroups except Filipinos continued to demonstrate superior survival compared to NHW.

CONCLUSION:

API subgroups seem to exhibit better overall survival following GC diagnosis compared to NHWs. Korean Americans appears to have the best overall survival. Part of this difference may be explained by a higher proportion of cancers diagnosed at a Local stage in Koreans. However, even after adjustment for stage of diagnosis API subgroups continued to demonstrate better survival compared to NHWs, suggesting possible underlying biological differences as well.
1238 Tradipitant Complete Responder Analysis in Gastroparesis Patients
Authors: Carlin Jesse L. , Lieberman Verna R. , Dahal Arya , Keefe Madison S. , Xiao Changfu , Birznieks Gunther , Polymeropoulos Mihael H.
Published: October 2019

INTRODUCTION:

A Phase II multicenter, randomized, double-blind, placebo-controlled trial with gastroparesis subjects demonstrating delayed gastric emptying and moderate to severe nausea were randomized to receive oral 85 mg tradipitant bid or placebo (1:1) for four weeks. Of the 152 patients enrolled, 60% of patients had idiopathic and 40% had diabetic gastroparesis.

METHODS:

The primary outcome was change in average nausea score from baseline, measured using the 5-point Gastroparesis Core Symptom Daily Diary (GCSDD). Overall gastroparesis symptoms were evaluated using the Gastroparesis Cardinal Symptom Index (GCSI), and Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM).

RESULTS:

A statistically significant and clinically meaningful improvement in nausea and overall gastroparesis symptoms was observed in patients on tradipitant. Subjects receiving tradipitant had a significant decrease in their average nausea score compared to placebo with LS mean difference (95% CI) of -0.53 (-0.92, -0.13, P = 0.0099) as well as a significant increase in nausea free days (28.8% increase on tradipitant compared to 15.0% increase on placebo, P = 0.0160). A complete nausea response as defined by a nausea severity score ≤1 at week 4 was found to occur in 33% of patients on tradipitant compared to 12% of patients on placebo (P = 0.0013). A clinically meaningful response in overall gastroparesis defined as a 1-point or more improvement on the GCSI total score was observed in 46.6% of patients on tradipitant compared to 23.5% of patients on placebo (P = 0.0053).

CONCLUSION:

Tradipitant treatment resulted in statistically and clinically meaningful improvements in nausea and overall gastroparesis symptoms. Tradipitant was well tolerated with comparable rates of adverse events between tradipitant and placebo groups. These robust efficacy results suggest tradipitant has the potential to become a first line pharmacological treatment for gastroparesis.
1239 Clinical Safety of RHB-105: A Novel Rifabutin Based Triple Therapy for the Treatment of Helicobacter pylori Infection
Authors: Kalfus Ira N. , Bullock Jeff , Almenoff June , Anderson Patricia , Graham David Y.
Published: October 2019

INTRODUCTION:

Increasing H. pylori antimicrobial resistance has resulted in a need for new, improved therapies and recognition by the World Health Organization as a high priority for development of safe and effective treatment options. Rifabutin is an approved antibiotic whose most commonly reported adverse event (AE) is chromaturia. However, daily dosing of 300 mg rifabutin has historically demonstrated some safety concerns including neutropenia, leukopenia and thrombocytopenia. Our research suggests that a lower divided rifabutin dose is effective in H. pylori eradication without concerns of myelotoxicity.

METHODS:

This phase 3 data review is a safety assessment of RHB-105 (all-in-one fixed oral capsule formulation: rifabutin 50 mg, amoxicillin 1000 mg, omeprazole 40 mg) Q8H in treatment naive H. pylori infected patients. In two phase 3 studies, 573 US subjects were randomized to receive RHB-105 (n = 305), placebo (n = 41), or active comparator (n = 227) for 14 days. The first study compared RHB-105 with placebo (77:41 subjects) while the second study compared RHB-105 with active comparator (amoxicillin 1000 mg, omeprazole 40 mg, without rifabutin) 228:227 subjects.

RESULTS:

RHB-105 was well tolerated compared to either placebo or active comparator and the proportion of subjects reporting AEs were generally similar (41.0%, 46.3% vs 34.8%, respectively). AEs occurring in ≥1% of RHB-105 patients vs active comparator were diarrhea (9.5% vs 7.5%), chromaturia (3.0% vs 0.0%), abdominal pain (2.8% vs 1.8%) and vomiting (1.3% vs 0.9%). AEs occurring in ≥1% RHB-105 patients vs placebo were nausea (3.6% vs 2.4%), and chromaturia (3.0% vs 2.4%). Myelotoxicity was not reported in either study. Four SAEs (RHB-105: 2, Placebo: 1, Active comparator: 1) were reported but no deaths were reported. The two SAEs in RHB-105 patients included anemia and diabetic ketoacidosis with neither considered treatment related. Treatment discontinuation due to AE occurred in 4 patients (1.3%) receiving RHB-105, 1 (2.4%) placebo and 1 (0.4%) active comparator. AEs leading to discontinuation of RHB-105 were nausea (occurring in 2 patients), vomiting, and nasal congestion with cold-like symptoms occurring in 1 patient each, respectively.

CONCLUSION:

RHB-105, a low-dose rifabutin based regimen appears to be a generally well-tolerated treatment option for patients with H. pylori infection. As expected, chromaturia was reported more frequently in RHB-105. Importantly myelotoxicity was not reported.
1240 Increased Mucosal Innate Immune Activation in Hereditary Alpha Trytpasemia Subjects Is Predictive of Clinical Response to Tofacitanib Therapy
Authors: Glover Sarah C. , Davis Elizabeth , Shirley James , Konnikova Liza
Published: October 2019

INTRODUCTION:

Hereditary alpha hypertryptasemia (HAT) is a genetic disorder associated with elevated serum tryptase as well as GI symptoms including nausea, vomiting, heartburn, abdominal pain, and diarrhea. HAT subjects are often mis-diagnosed with gastroparesis or IBS. HAT is estimated to impact up 6% of Caucasians in the US (Nat Genet. 2016 Dec;48(12):1564-1569.). Elevated tryptase in HAT is not associated with clonal mast cell (MC) disease, but does cause MC activation. MCs and memory T cells are increased in the HAT small intestine. The mechanism whereby tryptase produces clinical symptoms is unknown. We hypothesize that tryptase expression results in an intestinal epithelial cell (IEC) innate immune activation called pyroptosis. Tofacitanib is a JAK-STAT inhibitor which is believed to reduce innate immune activation. The aim of this pilot study was to evaluate the level of pyroptosis in HAT patients who have no endoscopic or histologic evidence of inflammation and determine its predictive value for clinical response to tofacitanib.

METHODS:

HAT was confirmed by genetic testing in all subjects. All subjects had undergone a colonoscopy and had available small bowel biopsies. Biopsy samples were blindly analyzed for pyroptosis using the Maximus Biological assay kit. Samples with at least 10 villi were analyzed for IEC pyroptosis. Subjects' clinical response to therapy was analyzed, stratified by pre-treatment biopsy pyroptosis levels and type of therapy.

RESULTS:

11 patients (2 M, 9 F) with an average age of 50 were included. All subjects had confirmed duplication or triplication in their TPSAB1 gene. The average tryptase was 18.5 mcg/L (<8.5 mcg/L) and the average number of mast cells per HPF by CD117 exceeded 52.4 per HPF (nml small bowel is < 25/hpf). All subjects reported nausea, vomiting, abdominal pain and diarrhea symptoms. Ileal biopsy pyroptosis reveled a three-fold increase in mucosal innate immune activation, an average of 33 ± 10 positive cells/1000 IECs (normal is up to 10/1000 IEC). Only one HAT subject who was on adalimumab therapy at the time of biopsy had a normal pyroptosis level. Three of the patients in this cohort received treatment with tofacitinib who responded all had elevated pyroptosis levels (22 ± 2.9 positive cells/1000 IECs). Tryptase levels were reduced by 25% to 50% with a dramatic improvement in their GI symptoms.

CONCLUSION:

Mucosal innate immune activation is evident in HAT subjects and can predict response to tofacitinib therapy.
1248 Late Onset Rapid Gastric Emptying: A New Entity to Explain Post-Prandial Symptoms
Authors: Diaz Jesus , Dodoo Christopher , Dwivedi Alok , McCallum Richard
Published: October 2019

INTRODUCTION:

Symptomatic patients with a suspected upper GI dysmotility disorder may have a normal 4 hour gastric emptying (GE) using the standardized radioisotope labeled egg beater meal methodology and do not meet criteria for the diagnosis of either delayed or rapid gastric emptying. We propose conservative thresholds to identify abnormal gastric emptying patterns among such symptomatic patients determined to have normal gastric emptying (NGE) in order to classify a subset as meeting criteria for a new entity, late-onset rapid gastric emptying (LRGE).

METHODS:

We recruited and conducted IRB approved standardized 4-h GE studies on 19 healthy normal subjects (Mean age 49, 68% females, 68% Hispanics) and in 425 patients (Mean age 51, 80% females, 69% Hispanics, and 33% with diabetes) who had symptoms suggesting an upper GI dysmotility disorder and referred for a standardized 4-h GES from 2009 to 2015. Patients had postprandial symptoms ranging from nausea, early satiety, fullness, epigastric pain, stool urgency, and bloating. Their GES was reported as normal based on no rapid gastric emptying at 1 h or delayed GE at 2 or 4 hrs. The 95% upper reference limits for the decrement percentages in gastric retention values from 1-2 h, 2-3 h and 3-4 h were determined using normal distribution in the 19 healthy normal subjects. These thresholds were applied to from the 425 NGE patients referred from 2009-2015. A 95% confidence interval (CI) of LRGE prevalence was determined.

RESULTS:

Approximately 5% of patients who had normal standardized 4-h GES results had an abnormal GE pattern based on the proposed criteria for late-onset rapid gastric emptying. Our data raises awareness to apply the gastric emptying decrement cut offs we have established to identify the diagnosis of LRGE in patients who otherwise would be interpreted as having normal GE and this will enable an explanation and management for their postprandial symptom profile.

CONCLUSION:

Approximately 5% of patients who had normal standardized 4-h GES results had an abnormal GE pattern based on the proposed criteria for late-onset rapid gastric emptying. Our data raises awareness to apply the gastric emptying decrement cut offs we have established to identify the diagnosis of LRGE in patients who otherwise would be interpreted as having normal GE and this will enable an explanation and management for their postprandial symptom profile.
1250 Gastric Intestinal Metaplasia Is a Common Finding Among Veterans Undergoing Endoscopy in South Texas
Authors: Haris Muhammad , Camero Alfredo , Valadez David , Fazeli Cameron , Ladak Farah , Echavarria Juan , Andrews Christine L. , Coss Elizabeth , Govani Shail
Published: October 2019

INTRODUCTION:

Gastric intestinal metaplasia (GIM) is a premalignant change of the mucosa of the stomach. Risk factors for intestinal metaplasia previously identified include chronic infection with Helicobacter pylori (HP), dietary factors, smoking, alcohol consumption, and chronic bile reflux. We aim to study the prevalence of GIM and its risk factors in a Texan Veteran population.

METHODS:

A retrospective chart review was performed among adults undergoing outpatient esophagogastroduodenoscopy (EGD) in 2013 and 2017 at a large Veterans Administration facility in Texas. Patient records were reviewed for demographic information, medication use, smoking and alcohol use, indication for EGD, presence of HP or GIM on gastric biopsies. Studies performed specifically to survey for known GIM were excluded. For patients with presence of GIM, data for type and location on biopsy were recorded. Student's t test was used for quantitative comparisons while the chi-square test or Fisher's exact test was used for qualitative comparisons using R.

RESULTS:

A total of 860 EGDs were reviewed, of which 340 (39.5%) underwent gastric biopsy. Of those undergoing gastric biopsy, 298 (87.7%) were male with a mean age of 58.0 years (±12.5) and 155 (45.6) were Non-Hispanic Caucasian, 92 (27.1) were Hispanic, and 39 (11.5%) were African-American. A total of 38 (11.2%) patients were found to have GIM. Among patients with GIM, 6 (15.8%) were found to have incomplete GIM. There was no significant difference in mean age among patients with GIM, 61.1 (±13.1) versus those without GIM, 57.6 (±12.4), P = 0.11. The rate of GIM among the non-Hispanic Caucasian population was significantly lower than patients of other ethnicities (7.7% vs. 16.9%, P = 0.02). We did not identify a statistically significant difference between GIM rates among those with HP and those without HP (18.4% vs. 10.3%, P = 0.17). PPI use was associated with lower rates of GIM (8.4% vs. 16.0%, P = 0.03).

CONCLUSION:

GIM was identified in 1 out of 9 patients in this Veterans cohort in Texas. As previously reported, GIM rates were higher in the Hispanic, African American and Asian patients. Patients taking PPIs were less like to have GIM. HP infection was not associated with GIM in this cohort. Longitudinal data is needed to better understand the risks of gastric cancer and how to risk stratify patients for ongoing surveillance in this diverse population.
1251 Predictors of Stage III/IV Gastric Cancer in the United States
Authors: Ali Sajjadh M. J. , Catalano Marc F.
Published: October 2019

INTRODUCTION:

The incidence of gastric cancer is declining by 1.5% every year in the United States with an estimated 27,510 new cases and 11,410 deaths in 2019. Five-year relative survival of early gastric cancer (Stage I/II) was 63.2% which declined to 12.3% in advanced stages (Stage III/IV). Most studies have looked at factors associated with overall gastric cancer incidence, but none have compared the factors associated with early and advanced gastric cancer at presentation. We aimed to study the factors that predict advanced cancer stages when compared to early stages.

METHODS:

The SEER 18 database was queried for gastric cancer cases from 2010 to 2016 when American Joint Committee on Cancer Staging 7th edition was used. Cases were classified into early (Stage I/II) and advanced (Stage III/IV), and multinomial logistic regression was used to predict age, racial/ethnic, gender and tumor characteristics that were more likely with advanced cancer.

RESULTS:

Analyses demonstrated that males were more likely to have advanced cancer than females (OR 1.216, CI 1.158-1.277). No significant differences were found when comparing Blacks to Whites (1.091, 0.651-1.828) and non-Hispanic Blacks to non-Hispanic Whites (0.963, 0.572-1.622). Spanish Hispanic Latinos were more likely to have advanced cancer than non-Spanish Hispanic Latinos (1.098, 1.028-1.172). Samoans were more likely (2.213, 1.191-4.111) and Koreans were less likely (0.699, 0.553-0.884) to have advanced cancer than whites. Patients in the age groups of 25-29, 30-34 and 35-39 years were more likely to have advanced cancer than those aged ≥50 years (2.657, 1.754-4.025; 1.586, 1.244-2.022 and 1.823, 1.495-2.223 respectively). Tumor sites such as cardia (1.884, 1.718-2.067), fundus (1.428, 1.253-1.627), and body (1.256, 1.129-1.398) were more likely to have advanced cancer when compared to the lesser curvature.

CONCLUSION:

Certain variables, including age, gender, race/ethnicity and tumor site/grade/histology were more likely to be associated with advanced cancer when compared to early cancer. Younger groups had higher chances of advanced cancer at presentation compared to those aged above 50 years reflecting the probable influences of screening alarm symptoms with endoscopy and the genetic influences of tumor biology. Compared to cancers at the lesser curvature, cancers detected at other sites like cardia, fundus, antrum and pylorus were more likely to be advanced cancers. Studies on larger populations are required to classify and further stratify risk factors.
1252 Isolated Brain Metastasis From Pancreatic Cancer in Lynch Syndrome
Authors: Dalal Kunal , Khrizman Polina , Chaaya Adib
Published: October 2019

INTRODUCTION:

Pancreatic cancer is the 4th leading cause of death in US. The incidence of pancreatic cancer metastasis to brain is rare ranging from 0.1 to 0.3% from various studies. Overall from our knowledge, this is the 26th reported case. This is the first reported case of a patient with a history of Lynch syndrome (LS) who was diagnosed with solitary brain metastasis from pancreatic adenocarcinoma and subsequently treated.

CASE DESCRIPTION/METHODS:

A 69-year-old female with history of LS and sarcoidosis presented complaining of new onset acute expressive aphasia. Patient's oncologic history significant for colon cancer status post (s/p) subtotal colectomy in 2007, pancreatic adenocarcinoma s/p Whipple in 4/2015. The pathology demonstrated isolated tumor cells in two peripancreatic lymph nodes treated with adjuvant gemcitabine. She had surveillance imaging in 9/2017 showing new metastatic disease, PET-avid retroperitoneal lymphadenopathy and cervical lymphadenopathy. Biopsy showed adenocarcinoma of pancreatic origin. She began gemcitabine/abraxane in 10/2017 with complete resolution on interval imaging in 1/2018. She continued chemotherapy with no metastatic disease on surveillance imaging and was well until presenting with aphasia in 2/2019. MRI of the brain revealed 2 cm enhancing left frontal lobe mass with vasogenic edema and 3 mm midline shift. Labwork including Ca 19-9 and CEA were normal. Because of the uncertainty of the origin of the metastatic disease, left frontal craniotomy and tumor resection was performed. Pathology demonstrated IHC positive for CK7, CK19, CA19-9, CDX-2, and negative for TTF-1, CK20, compatible with metastatic pancreatic adenocarcinoma. Subsequently, the patient underwent single fraction 20 Gy of CyberKnife radiosurgery. The patient symptoms improved and surveillance MRI in 6/2019 demonstrated decreased enhancement consistent with response to treatment.

DISCUSSION:

To our knowledge this is the first documented case of isolated brain metastatic from pancreatic adenocarcinoma in a LS patient. This case suggests awareness and brain imaging are necessary when pancreatic cancer patients present for neurological complaints. LS is due to germline mutations, which has a different pathogenesis from usual sporadic pancreatic adenocarcinoma. This may explain the unusual presentation, excellent response to therapy, and prolonged survival. Treatment with surgical resection and stereotactic radiosurgery can be considered.
1253 Rare Case of Superior Mesenteric Arteriovenous Fistula as Complication of Recurrent Pancreatitis
Authors: Kaur Anahat , Bulchandani Sheetal , Saeed Lyla
Published: October 2019

INTRODUCTION:

Superior mesenteric arteriovenous fistula (SMAVF) is a rare entity. Most common cause of SMAVF is post-traumatic, however they may be congenital, iatrogenic or secondary to connective tissue disorders. We report a case of SMAVF in setting of acute on chronic pancreatitis.

CASE DESCRIPTION/METHODS:

62-year-old male with history of pancreas divisum, infrarenal abdominal aortic aneurysm, cholelithiasis and chronic calcific pancreatitis initially presented for elective Endoscopic Retrograde Cholangiopancreatography (ERCP) for obstructing pancreatic ductal stone with stent placement. After the procedure, patient had to be admitted and treated for acute post-ERCP pancreatitis. Patient underwent repeat ERCP in four weeks for stent replacement but had recurrence of pancreatitis after the second procedure. Computerized Tomography (CT) scan of the abdomen done at that time was consistent with pancreatic pseudocyst causing minimal mass effect on Superior Mesenteric Vein (SMV) without vascular thrombosis. Patient was discharged once stable but unfortunately returned to the hospital for a third time within two weeks complaining of nausea, vomiting, severe abdominal pain and diarrhea. CT Angiogram of the abdomen and pelvis was obtained this admission which showed changes consistent with colitis, increasing size of pancreatic pseudocysts with possible necrosis, new SMV thrombosis and SMAVF in region of middle colic artery. This was confirmed on mesenteric angiogram. Patient was started on anticoagulation to treat thrombosis and clinically improved after symptomatic management. The case was discussed at multidisciplinary conference and no acute intervention for SMAVF was recommended. Patient eventually underwent laparoscopic cholecystectomy few months later for cholelithiasis and SMAVF was noted to be stable on repeat CT scan at four-month interval.

DISCUSSION:

SMAVFs are extremely rare. As of 2005, only 40 cases of post-traumatic SMAVF and similar number of iatrogenic cases had been cited in literature. Clinical presentation can be asymptomatic or manifest as abdominal pain, anorexia, diarrhea, gastrointestinal bleed, portal hypertension and congestive heart failure. Splanchnic venous thrombosis, as seen in our patient, develops in 50 percent cases with necrotizing pancreatitis. Such thrombosis can further lead to development of SMAVF which was also noted in this case.
1256 Cystoisospora belli Infection of the Gallbladder: More Common Than You May Think
Authors: Fazio Richard M. , Waintraub Daniel J. , Rahmani Rabin , Hajdu Cristina H. , Park James S.
Published: October 2019

INTRODUCTION:

Cystoisosporiasis is an underrecognized gallbladder infection of immunocompetent hosts due in part to subtle histopathologic findings and low index of suspicion during examination of routine cholecystectomy specimens. This case will highlight the importance of detecting the organism in order to gain understanding of its life cycle and to raise awareness of the potential symptoms for those who become immunosuppressed.

CASE DESCRIPTION/METHODS:

A 65-year-old male with compensated cirrhosis presented with complaints of intermittent right upper quadrant pain for three months. He denied symptoms of diarrhea, jaundice, fever, chills, recent travel and sick contacts. CBC, BMP and liver enzymes were unremarkable. A right upper quadrant ultrasound illustrated multiple gallstones within the gallbladder along with wall thickening measuring up to 4.8 mm. The patient underwent a laparoscopic cholecystectomy with resolution of symptoms. Pathologic evaluation of the resected gallbladder described elongated “banana-shaped” zoites of C. belliwithin parasitopherous vacuoles in the gallbladder columnar mucosa.

DISCUSSION:

Cystoisospora belli (C. belli) is an intracellular protozoan of the intestinal epithelium often associated with gastrointestinal (GI) disease in immunocompromised patients or those who travel to endemic areas. The infection is acquired by fecal-oral route through ingestion of infective oocysts in contaminated water. Symptoms of C. belli include watery diarrhea, abdominal pain, nausea, vomiting and weight loss due to malabsorption, whereas most infected immunocompetent patients remain asymptomatic. C. belli is known to reside within parasitophorous vacuoles in epithelial cells of the small intestine; however, incidence of gallbladder infection is on the rise as there becomes an increased awareness and recognition on the part of the pathologist. Previously, lack of recognition has stemmed from multiple factors including a low index of suspicion in patients without clinical symptoms or those who remain immunocompetent, the underwhelming appearance of infected gallbladders with lack of significant tissue reaction, as well as the sparse distribution of the organisms themselves. The unexpectedly high prevalence in gallbladder specimens has given rise to the idea that the gallbladder may be an anatomic reservoir for this commensal organism in the immunocompetent host. For this reason, C. belli infection should be considered in patients exhibiting typical GI symptoms following immunosuppression.