bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
1258 A Case of Direct Necrosectomy via Sinus Tract Endoscopy in the Retroperitoneum: A Unique Approach to a Difficult Problem
Authors: Bader Geoffrey A. , Zibert Kimberly , Miller Charles B. 
Published: October 2019

INTRODUCTION:
Pancreatic fluid collections are one of the most common complications of acute pancreatitis. While the majority of pancreatic fluid collections are self-limited, acute necrotic collections have a high likelihood of evolving into walled off pancreatic necrosis, with nearly two-thirds of cases requiring intervention. Endoscopic debridement of centrally located walled off pancreatic necrosis via transmural stents and direct necrosectomy is becoming increasingly popular due to its high success rate and low associated morbidity and mortality. Management of lateral walled off pancreatic necrosis has traditionally been managed surgically. New innovations in multidisciplinary, minimally invasive procedures are becoming increasingly utilized, though case reports are rare. We present a case of sinus tract endoscopy via a surgically placed trocar to debride an extensive collection of walled off necrosis in the left retroperitoneal space.

CASE DESCRIPTION/METHODS:
Our patient is a 65-year-old female with a history of alcohol induced, necrotizing pancreatitis with infected walled off necrotic collections extending along the infrarenal spaces bilaterally. She initially underwent computed tomography guided percutaneous catheter placement, which failed to provide source control. Given the large size and technically difficult location of the infrarenal necrosis, a multidisciplinary approach was pursued. In the operating room, the general surgery service placed a 15 mm surgical trocar into the left retroperitoneal space to successfully access the lesion. The therapeutic gastroenterology team then advanced a pediatric colonoscope via the trocar into the retroperitoneal space. Following the previously placed percutaneous drains, and utilizing various sized snares, 3-prong grasper, and Rat tooth forceps, all necrotic tissue was successfully debrided and retrieved. A wire was left in place and used to successfully place a surgical drain. The patient tolerated the procedure well without acute complications. Repeat cross sectional imaging demonstrated significant interval decrease in size of the necrotic collections. The patient recovered without further intervention and was doing well at 6 month follow up.

DISCUSSION:
Sinus tract endoscopy via surgically or CT guided placement of trocars is an efficacious and safe procedure for lateral walled off pancreatic necrosis. Our case illustrates the evolving role for minimally invasive procedures for pancreatic fluid collections inaccessible to transmural approaches.