Gastrointestinal History Research Articles

Association between early and current gastro-intestinal symptoms and co-morbidities in children and adolescents with Angelman syndrome.

Angelman syndrome (AS) is a neurogenetic disorder that causes severe intellectual disability, expressive language deficits, motor impairment, ataxia, sleep problems, epileptic seizures and a happy disposition. People with AS frequently experience gastrointestinal (GI) symptoms. This study used data from the Global Angelman Syndrome Registry to explore the relationship between early and current GI symptoms and co-morbidity in children and adolescents with AS (n=173). Two groups that experienced a high (n=91) and a low (n=82) frequency of GI symptoms were examined in relation to feeding and GI history in infancy, sleep and toileting problems, levels of language and communication and challenging behaviours. Predictors of GI symptoms were then investigated using a series of logistic regressions. This analysis found that constipation and gastroesophageal reflux affected 84% and 64%, of the sample, respectively. The high frequency of GI symptoms were significantly associated with: 'refusal to nurse', 'vomiting', 'arching', 'difficulty gaining weight', gastroesophageal reflux, 'solid food transition', frequency of night-time urinary continence and sleep hyperhidrosis during infancy. GI symptoms were not significantly associated with sleep, toileting, language or challenging behaviours. Significant predictors of high frequency GI symptoms were gastroesophageal reflux and sleep hyperhidrosis. Future research needs to investigate the association between AS and GI co-morbidity in adults with AS.

Translocation of LVAD Pump and Driveline Causing Bowel Perforation

Introduction Left ventricular assist devices (LVADs) have known risks of device infection and gastrointestinal (GI) bleeding. We present the first known case of LVAD pump migration causing colonic perforation. Case Report A 67-year old man with ischemic cardiomyopathy status post HeartMate II LVAD implantation presented to the emergency department with melena. He was found to be in hemorrhagic shock requiring pressor support, with a hemoglobin of 5.2 g/dl. He had a history of chronic driveline infection with Stenotrophomonas maltophilia treated with long-term suppressive doxycycline and an outflow graft kink requiring stenting 7 months prior. His GI history was notable for recurrent GI bleeding secondary to colonic AVMs and polyps requiring multiple cauterizations and clips. His anticoagulation was periodically interrupted and restarted, as the patient had several readmissions for recurrent GI bleeding, until it was ultimately stopped 3 months prior. This admission, an abdominal CT showed erosion of the LVAD driveline into the transverse colon (Panel A). Subsequent colonoscopy identified the driveline within transverse colon lumen (Panel B). In conjunction with both cardiothoracic and abdominal surgery teams, the patient underwent robotic-assisted colonic exploration which revealed both driveline and LVAD pump had migrated into the colon. Patient underwent removal of the LVAD and primary colo-colonic anastomosis with abdominal washout. Laparoscopic omentopexy was performed to cover the intraabdominal LVAD components. His postoperative course was uncomplicated. Summary This case illustrates a rare but serious complication of LVAD and chronic device infection: migration of LVAD pump and driveline causing colonic perforation. Left ventricular assist devices (LVADs) have known risks of device infection and gastrointestinal (GI) bleeding. We present the first known case of LVAD pump migration causing colonic perforation. A 67-year old man with ischemic cardiomyopathy status post HeartMate II LVAD implantation presented to the emergency department with melena. He was found to be in hemorrhagic shock requiring pressor support, with a hemoglobin of 5.2 g/dl. He had a history of chronic driveline infection with Stenotrophomonas maltophilia treated with long-term suppressive doxycycline and an outflow graft kink requiring stenting 7 months prior. His GI history was notable for recurrent GI bleeding secondary to colonic AVMs and polyps requiring multiple cauterizations and clips. His anticoagulation was periodically interrupted and restarted, as the patient had several readmissions for recurrent GI bleeding, until it was ultimately stopped 3 months prior. This admission, an abdominal CT showed erosion of the LVAD driveline into the transverse colon (Panel A). Subsequent colonoscopy identified the driveline within transverse colon lumen (Panel B). In conjunction with both cardiothoracic and abdominal surgery teams, the patient underwent robotic-assisted colonic exploration which revealed both driveline and LVAD pump had migrated into the colon. Patient underwent removal of the LVAD and primary colo-colonic anastomosis with abdominal washout. Laparoscopic omentopexy was performed to cover the intraabdominal LVAD components. His postoperative course was uncomplicated. This case illustrates a rare but serious complication of LVAD and chronic device infection: migration of LVAD pump and driveline causing colonic perforation.

S621 GI Consultation Before TEE: A Necessary Step for Clearance in the Inpatient Setting?

Introduction: Although esophagogastroduodenoscopy (EGD) before transesophageal echocardiogram (TEE) is common in patients with known gastrointestinal (GI) disease, there is a lack of objective evidence to support this practice. The goal of our study is to elucidate whether presence or absence of GI history and/or symptoms significantly affect the clearance for TEE. Methods: This is a retrospective cohort study performed at a tertiary care center. It included all adult patients admitted for whom an inpatient EGD was ordered and performed prior to TEE from 7/1/2008 - 4/1/2021 for the purposes of medical clearance. Data on Gastroenterology consults ordered with the indication for clearance for TEE were collected. Furthermore, indication for TEE, hospital day numbers between GI consult, EGD and TEE performance were recorded. Data was summarized using descriptive statistics and cumulative frequencies. Results: In total, 83 patients were identified. Of these, 16.9% (n=14) had no prior GI history, 31.3% (n=26) had a diagnosis of cirrhosis with or without EV, 2.4% (n=2) had a history of cirrhosis with EV with prior banding, 15.7% (n=13) had a history of dysphagia of unknown etiology, 9.6% (n=8) had a history of esophageal strictures and 24.1% (n=20) were categorized as other (Figure 1A). With regards to GI symptoms, 44.6% (n=37) had no GI symptoms, 33.7% (n=28) had dysphagia, 8.4% (n=7) had GI bleed, and 13.3% (n=11) were categorized as other (Figure 1B). The average time from admit to GI consult was 5.1 days with an average of 2.3 days from GI consult to EGD, and an average of 7.3 days from admit to EGD performance. Meanwhile, the time from admit to TEE was 9.3 days. Conclusion: The findings from this study showed that performing an EGD prior to TEE prolonged hospital stay significantly and EGD is not electively required prior to TEE. EGD did not change the management or need for TEE despite a high-risk population. Only 3 instances were identified in which a TEE was not initially performed due to inability to pass the TEE probe, prompting a GI consult. Subsequently, all 3 EGD’s were completed without complications and no contraindications to TEE were reported. Eliminating the need for EGD prior to TEE would improve hospital costs, decrease inpatient hospital nights, decrease anesthesia exposure and, finally, avoid delaying treatment plans.Figure 1.: A: GI Medical History; Legend: No GI history (16.9 %), Cirrhosis +/- EV (31.3 %), Cirrhosis with EV with prior banding (9.6 %), Dysphagia of unknown etiology (15.7 %), Esophageal strictures (2.4 %), Other (24.1%). B: Reported GI Symptoms; Legend: No GI symptoms (44.6 %), Dysphagia (33.7 %), GI bleeding (melena, hematochezia, hematemesis) (8.4 %), Other (13.3 %).

S2946 A Rare Case of COVID-19 Infection Presenting With Devastating Intestinal Perforation Requiring Emergent Surgical Intervention: A Case Report

Introduction: COVID-19 pandemic is believed to be a systemic disease that affects not only the lungs but also other vital organs however, current available literature mainly focuses on acute respiratory symptoms. Symptoms include fever, myalgia and dyspnea. However gastrointestinal (GI) symptoms were reported in 3-50% of cases, including nausea, vomiting, abdominal pain, and diarrhea. Here we report a case of COVID-19 presenting with intestinal perforation. Case Description/Methods: 52-year-old female with a remote history of Roux-en-Y gastric bypass surgery who was diagnosed with COVID-19 three days prior to admission presented with epigastric pain, nausea, vomiting, and constipation for 2 days. Vital signs were normal. Laboratory workup was remarkable for non-anion gap metabolic acidosis and elevated inflammatory markers. Chest X-Ray showed air under the diaphragm. Abdominal CT scan showed pneumoperitoneum in the right subdiaphragmatic and mid abdomen/pelvis. Surgery was consulted and patient underwent emergent diagnostic laparoscopy and subsequent exploratory laparotomy with findings of large perforation at gastrojejunostomy, Intra-abdominal abscess. Patient underwent revision of gastrojejunostomy, drainage of intra-abdominal abscess with perotinel lavage. Intraabdominal cultures isolated Klebsiella pneumonia, Citrobacter freundii, Prevotella melaninogenica,Enterococcus faecalis and several Candida. Blood cultures isolated Clostridium subterminale bacteremia. Patient was started on IV antibiotics. The patient was discharged to be followed by surgery for resolution of symptoms and drainage removal. Discussion: Gastrointestinal symptoms of COVID-19 disease were reported in accumulated literature. Moreover, COVID-19 virus has been isolated in stool specimens. The question becomes, are those GI manifestations considered part of systemic symptoms of an airborne infection, or COVID-19 itself can potentially be transmitted feco-orally. Pathophysiology is yet unclear, suggested hypothesis includes direct invasion of intestinal cells by the SARS-CoV-2 RNA, as GI cells express ACE2. Another theory is imbalance of autonomic innervation of GI tract given the neuroinvasive tendency of COVID-19. It is not clear whether patients with past GI diseases like inflammatory bowel disease, peptic ulcers, and prior GI surgery are more prone to GI complications. This case highlights GI complications in Covid-19-positive patients especially those with GI history for early diagnosis and prevention of possible complications.Figure 1.: Figure (A): CT shows free air, Figure (B): CT abdomen shows air-fluid level, Figure (C): Abdominal X-ray shows air under the diaphragm.

Gastrointestinal Bleeding and Angiodysplasia in Von Willebrand Disease: Results from the Ongoing French HRQoL Study: Wish-Qol

Von Willebrand Disease (VWD), the most common inherited bleeding disorder, is related to a von Willebrand factor (VWF) defect and/or functional abnormality. VWD is primarily characterized by mucocutaneous bleedings as a result of primary haemostasis defect, excessive haemorrhage after invasive procedures, and, less commonly, by soft tissue haematomas and joint bleedings.Some patients with VWD may be subjected to recurrent overt or occult bleedings in the gastrointestinal (GI) tract associated with angiodysplasia which are challenging complications. Angiodysplasia occurs most commonly in middle-age or elderly patients in the cecum and ascending colon, but sometimes throughout the whole colon and stomach. These affected patients may need to be hospitalized for long periods of time and often require several weeks of therapy leading to high costs and poor quality of life. We report here the first results of GI bleedings impact on the Health-Related Quality of Life (HRQoL) of patients with VWD enrolled in the French WiSH-QoL study.As both VWD and its treatment affect patients' and, possibly, their families' everyday life, the French non-interventional study, WISH-QoL aims to assess HRQoL in VWD patients of any age and to evaluate associated costs related to VWD management.Clinical phenotype such as bleeding score (BS - Tosetto score), biological profile is documented. Patients are treated with the triple-secured plasma-derived VWF concentrate almost devoid of FVIII WILFACTIN. Patients fill in a booklet collecting information on socio-demographic and resources consumption. Clinical characteristics and therapeutic approach are recorded. HRQoL is assessed with the generic SF-36 (for adults) and the chronic-generic DISABKIDS Short Form (for children and adolescents) and the VWD-specific VWD-QoL (for adults, children and adolescents). In addition treatment satisfaction is evaluated. At least 350 patients will be followed during 2 years.Since October 2014, 327 patients have been included.At time of the current analysis, out of 312 patients with evaluable data, special attention is given to the specific clinical subgroup of 36 patients with recurrent bleeding from the gastrointestinal tract.These patients exhibited an age distribution ranging from 3.3 to 83.0 year-old with a 44.5 y.o median. Among them, 3 children were less than 6 years but elderly were more represented with 10 adults more than 65 years. Females were more represented than males 20 (55.5%) vs. 16 (45.5%), respectively.Among them, 5 had type 1 VWD (type 1Vincenza: 3; type 1: 2), 20 had type 2 (2A: 11; 2B: 6; 2M: 1 and 2 unspecified: 2), 10 had type 3 and 1 with a type undetermined (Table1).The median Tosetto bleeding score (BS) reported for 33 patients with GI bleeds was higher +12 ranging from +4 to +28 compared to +5 (-1 to +31) in patients without history of GI bleeds as described in Table1. It was also able to distinguish disease severity by VWD type; Type 3 VWD had the highest bleeding scores.At time of inclusion, 24 of these 36 patients were On-Demand treatment and 12 patients (4.7 - 70.4 years of age) were and are still requiring Long-Term secondary Prophylaxis (LTP) with this VWF because of joint and or gastro-intestinal bleeds. For 12 out of these 36 patients, the endoscopic procedure Argon plasma coagulation (APC) was used. For 5 of these patients, the procedure was associated with a secondary LTP and they were on regular prophylaxis with VWF concentrate at WiSH-QoL study entry.As frequently in VWD management, patients may need to stay on long-term iron therapy. This concomitant treatment has been recorded in 15 (45%) patients' file. Ten (28%) patients have also received anti-ulcer drugs.Thus, this study will provide an important contribution to knowledge in VWD patients with GI episodes that is challenging due to the severity and recurrence of bleeds. These findings may teach us what would be the best treatment such as LTP. With the HRQoL results especially the VWD-specific evaluation of HRQoL and treatment satisfaction, a deeper insight into these patients' real daily life and their specific health care needs will be gathered as well. [Display omitted] DisclosuresBorel-Derlon:LFB: Honoraria. Chatelanaz:LFB: Employment. Doriat-Robin:LFB: Employment. Goudemand:LFB: Honoraria. Von Mackensen:LFB: Honoraria.

Men and Those With a History of Smoking Are Associated With the Development of Postoperative Ileus Following Elective Colorectal Cancer Resection at a Private Academic Hospital in Johannesburg, South Africa: A Retrospective Cohort Study.

Introduction: A scarcity of local published data on colorectal cancer (CRC) postoperative complications, including postoperative ileus (POI), exists. POI is a temporary gastrointestinal (GI) state of absent or reduced gastric motility shown to increase patient morbidity, prolong length-of-stay (LOS), and intensify the healthcare resource burden. The pathogenesis of POI involves a neurogenic and inflammatory phase plus a pharmacological component.Aim and Objectives: This study aimed to determine centre-specific preoperative risk factors associated with the development of ileus post elective therapeutic CRC resection. The objectives were to determine whether patient demographics; functional status; comorbidities; GI history; pharmacotherapy (including neoadjuvant chemotherapy); and lastly neoadjuvant radiation and chemoradiation were associated with the development of POI.Method: Patients who underwent CRC resection between January 2016 and May 2019 were retrospectively identified from an existing database. Urgent—or non-therapeutic surgeries; surgeries with the complication anastomotic leak or GI obstruction; patients under 18 at the time of surgery or surgeries preceded by preoperative parenteral nutrition were excluded. A comparison was done of the incidence of exposure in the study cohort to investigated variables as potential risk factors for the complication POI.Results: A total of 155 patient cases were included, and 56 (36%) of them developed POI. Univariate comparison of patients who developed POI with demographic characteristics of patients who did not suggested that women were at lower risk to develop POI compared to men (p = 0,013; RR 0,56; 95% CI 0,36–0,89). Functional status suggested that all previous smokers were at a higher risk to develop POI compared to lifetime non-smokers (p = 0,0069; RR 1,78; 95% CI 1,17–2,70). Multivariable comparison of ≤ 5 qualifying parameters showed no significance.Conclusion: The high local incidence of POI in this patient population shows that intervention is required to reduce the POI rate and improve postoperative outcomes. This study suggests that for men and all patients with a history of smoking both, CRC resection preoperative recommendations with the intention to prevent POI should include instructions initiating the activation of preventive strategies like the Enhanced Recovery After Surgery (ERAS) programme. More studies are needed to adequately determine local perioperative risk factors for POI.

Gastrointestinal symptomatology, diagnosis, and treatment history in patients with underweight avoidant/restrictive food intake disorder and anorexia nervosa: Impact on weight restoration in a meal‐based behavioral treatment program

Gastrointestinal (GI) concerns are often presumed to complicate nutritional rehabilitation for restrictive eating disorders, yet their relationship to weight restoration outcomes is unclear. This retrospective chart review examined GI history and weight-related discharge outcomes in primarily adult, underweight inpatients with anorexia nervosa (AN, N=107) or avoidant/restrictive food intake disorder (ARFID, N=22) treated in a meal-based, behavioral eating disorder program. Lifetime GI symptomatology, diagnoses, diagnostic tests, and procedures were abstracted from medical records. Generalized linear models examined associations of GI diagnoses, tests, and procedures with discharge BMI and rate of weight gain. Ninety-nine percent of patients reported GI symptomatology and 83% had one or more GI diagnoses; with constipation and GERD most common. GI diagnoses (p <.01) and testing (p <.001) were more common in ARFID than AN. Average inpatient weight gain (1.59 kg/week), and discharge BMI (18.5kg/m2 ), did not differ by group. Slower weight gain in patients with (1.3kg/week), versus without (1.7kg/week), history of tube feeding (p=.02), accounted for a main effect of GI procedures on inpatient rate of gain (p=.01). Despite ubiquitous GI symptomatology, meal-based weight restoration achieved average weekly weight gain above recommended APA guidelines for hospitalized patients with an eating disorder. History of tube feeding was associated with slower mean weight gain, which remained, however, within recommended APA guidelines.

The clinical and molecular characteristics of patients with personal or family history of gastrointestinal malignancies/polyposis and checkpoint kinase 2 (CHEK2) mutations.

44 Background: Checkpoint Kinase 2 (CHEK 2) encodes the protein CHK2, a serine/threonine kinase involved in pathways that conduct DNA repair as well as apoptosis in response to initial DNA damage. Germline mutations in the CHEK2 gene are associated with several malignancies such as colon, breast, stomach, prostate, kidney, thyroid and soft tissue cancers. Here, we describe the clinical and molecular characteristics of patients with personal or family history of gastrointestinal (GI) malignancies/polyposis and CHEK2 gene mutations. Methods: This is an IRB-approved retrospective chart-review study. Between 2016 and 2020, 1011 unique genetic counseling visits were conducted. Germline testing was recommended by a certified genetic counselor if medically necessary. All patients with a germline CHEK2 mutation were identified (N = 16). Patients with a CHEK2 mutation and personal and family history of GI malignancies/polyposis were further explored and their clinical and molecualr characteristics are summarized. Results: The reasons for referral to the Cancer Genetics Counseling Services in patients with pathogenic CHEK2 mutations were personal history of colon cancer (N = 3) and family history of colon cancer (N = 4). One patient with the CHEK2 c.1100delC mutation had a personal history of juvenile polyposis syndrome and a family history of colon cancer. In our cohort, 11 out of 16 (69%) patients had a CHEK2 mutation and personal or family history of GI malignancies/polyposis. The median age was 57 years old (25-80). Six (55%) patients were males. All (100%) patients were Caucasians. Seven (64%) patients had a pathogenic germline CHEK2 mutation and 4 (36%) patients had a variant of unknown significance (VUS). Among patients with pathogenic germline CHEK2 mutations (N = 7), 5 (72%) patients had CHEK2 c.1100delC mutation, 1 (14%) patient had CHEK2 c.190G &gt; A mutation and 1 (14%) patient had CHEK2 c.470T &gt; C mutation. The CHEK2 VUS mutations seen in our cohort were CHEK2 c.539G &gt; A, CHEK2 p.V395L, CHEK2 gain of exons 3-15 and CHEK2 c.1421G &gt; A mutations. Conclusions: All patients in our cohort with CHEK2 mutations were Caucasians. The majority of our patients (69%) had an underlying personal or family history of GI malignancies/polyposis. In patients with personal or family history of GI malignancies/polyposis and CHEK2 mutation, 64% were found to have pathogenic CHEK2 mutations. The most common diagnosed CHEK2 mutation in our cohort was CHEK2 c.1100delC mutation.

2874 Gastrointestinal (GI) and Hepatobiliary Conditions Among Medical Students: A Single Center Study

INTRODUCTION: Medical students go through many stressful situations and suffer from various GI and hepatobiliary conditions. The purpose of the study was to assess the prevalence of GI and hepatobiliary conditions among medical students, the variability among gender and race, and what effect it had on their daily life. METHODS: A survey questionnaire link via surveymonkey.com was emailed to every medical student at Sidney Kimmel Medical College. The survey was completely voluntary and anonymous. RESULTS: 246 students answered the survey and 67 of had a GI and/or hepatobiliary conditions. 42.6% were female and 57.4% were male. 50% were aged between 21-25, 50% between 26-30, and family history of GI and hepatobiliary conditions was positive in 52.2%. Among the different ethnicities, 82.0% identified as Caucasians, 13.4% as Asians, 4.5% as African Americans, and 1.4% as Middle-Eastern. The different GI and hepatobiliary conditions reported were as follows: gastroesophageal reflux disease (GERD) – 40.2%, irritable bowel syndrome (IBS) – 38.8%, ulcerative colitis – 5.9%, lactose intolerance - 4.4%, 2.9% (2 cases) had eosinophilic esophagitis, Crohn’s disease, liver hemangioma, and esophageal spasm, and 1.4% (1 response) had: peptic ulcer disease. Regarding treatment, 45.50% were not taking any medication, 44.1% were taking medication, 7.30% took both medication and psychotherapy, and 2.90% psychiatric ttreatment. The gastrointestinal and hepatobiliary conditions affected their daily life mildly (rated 1-3) in 64.7%, moderately (rated 4-7) in 26.4%, and severely (rated 8-10) in 8.8%. CONCLUSION: A significant number of medical students suffered from gastrointestinal disorders, most had the illness for over 5 years, and greater than half were taking medications. The disorders were more common in males than in females and greater than half had a positive family history. In addition, 35.2% mentioned that the condition had a moderate-to-severe effect on their daily life. GERD was the most common disorder followed by IBS which were both prevalent in almost one-third of the students with a GI condition. Overall, these findings are significant for the effect on the daily life of these medical students and the possible long-term effects on their morbidity and mental health. This study gives further evidence of the importance of stress reduction and renewed focus on student wellness in stressful academic environments.

122 Multidisciplinary Quality Improvement Initiative to Reduce Bowel Complications in Post-Operative Orthopedic Patients

INTRODUCTION: Gastrointestinal (GI) complications in patients undergoing orthopedic surgery are common but underreported. Prolonged immobility and the use of post-operative narcotics can increase the risk of GI complications which include: constipation, ileus, bowel obstruction, stercoral colitis, perforation, and death. In 2017 we observed an increase in GI complications among patients undergoing orthopedic surgery at our orthopedic hospital. This prompted a multidisciplinary quality improvement (QI) initiative to reduce GI complications among patients admitted after joint or spine surgery. METHODS: Following a surge of GI complications at our university-affiliated tertiary referral orthopedic satellite hospital in early 2018 we created a multidisciplinary QI program. The first component was a didactic lecture delivered by a GI attending to the orthopedic trainees, attendings, physician extenders, nurses and staff. The 1 hour lecture discussed an effective GI history, exam and reviewed the symptoms and treatment of common GI conditions affecting post-operative patients. The second component was the development of a post-operative constipation and bowel assessment algorithm focused on early identification, escalation and treatment of GI conditions (Figure 1). The third component was a redesign of the electronic medical record post-operative constipation order sets in order to facilitate implementation of the aforementioned bowel algorithm. This new order set changed laxative orders from “as needed” to standing with an option to be held for diarrhea. These QI initiatives were implemented on a rolling basis from 1/31/2018 to 5/31/2018. Cases of ileus, obstruction and perforation were determined based on coding for admitted orthopedic patients. RESULTS: The proportion of patients admitted with each diagnosis was compared from the first quarter (1/1 to 3/31) of 2018 to 2019 corresponding to 6 months after the implementation of all QI components (Figure 2). We achieved a 71% reduction in overall bowel complications (P &lt; 0.05). The greatest reduction was achieved in post-operative ileus by 81% (P &lt; 0.05). Following the QI initiative there was only 1 perforation corresponding to a 50% reduction. CONCLUSION: We created a multidisciplinary QI program that successfully reduced GI complications in patients hospitalized following orthopedic surgery. The greatest impact was in the reduction of post-operative ileus and serious adverse events such as perforation.

Safety of Apixaban in Patients with CKD Stage V and ESRD with Venous Thromboembolism

IntroductionHistorically, warfarin (Coumadin) was the only choice of anticoagulation in patients with chronic renal disease (CKD) stage V and end stage renal disease on dialysis (ESRD). Although apixaban (Eliquis) is approved for use in patients with CKD for venous thrombosis (VTE), its role in patients with CKD 5 and on dialysis is less defined. The purpose of this retrospective study is to compare the rates of bleeding, particularly gastrointestinal (GI) and intracranial bleeding in patients with CKD stage V or dialysis who are anticoagulated with warfarin or apixaban for indication of VTE.MethodsData for this study was queried from a commercial database (Explorys Inc, Cleveland, OH, USA), an aggregate of electronic health record data from 26 major integrated US healthcare systems representing a sixth of the US population. Cases and controls were identified using Systematized Nomenclature of Medicine (SNOMED) clinical terms or codes. Cases were defined as patients with CKD stage 5 or ESRD and were on apixaban for VTE. Controls were defined as those with CKD stage 5 or ESRD and were on warfarin for VTE. For the primary end point of bleeding, only patients above the age of 15 were selected. Those with previous history of GI or intracranial bleeding, atrial fibrillation, traumatic injury, cancer and cirrhosis were excluded. In the coumadin group, in addition to above, patients who were on for indication of artificial valves, arterial thrombosis and PVD were also excluded. 30 and 90-day rates of GI and intracranial bleeding were recorded for both groups. Logistic regression models were used to adjust of confounding variables (defined a priori as age > 65 or< 65, use of antiplatelet agents, gender, race and presence or absence of hypertension greater than 160/100 mm of hg). Rates or proportions were compared using Chi-squared test using Medcalc software (2018).Logistic regression analysis was done using Statistical Package for Social Sciences (SPSS, version 21, IBM Corp, Armonk, NY). P< 0.05 was considered statistically significant.ResultsA total of 990 cases and 8110 controls were identified. 30 and 90-day pooled GI and intracranial bleeding rates for apixaban users were 40% and 35% respectively. 30 and 90 day pooled GI and intracranial bleeding rates for warfarin users were 58% and 54% respectively. Difference in 30 day bleeding between cases and controls was 18% (95% CI 14.7-21.2; p< 0.0001) and 90 day bleeding was 19% (95% CI 15.7-22.1; p <0.001)Due to the limitations of the study, both major and minor GI bleeds were included. Given this study was retrospective, efficacy data in preventing recurrent VTE could not be assessed.Logistic regression of risk factors associated with risk of bleeding revealed that age over 65 years, presence hypertension> 160/100 mm of Hg, use of antiplatelet agents, African american race, and use of warfarin as opposed to apixaban were all significantly associated with increased risk of both 30 and 90 day bleeding. Please see Table 1 and 2 for further details.DiscussionOur study has shown that pooled rates of GI and intracranial bleeds were lower in the apixaban users even when used in patients with CKD stage V or ESRD patients, showing that apixaban is safe even when used for the indication of VTE prevention in this cohort. The results of this study are in concert with a recently published meta-analysis, which showed similar lower risks of bleeding when used in the advanced CKD cohort when used for the indication of atrial fibrillation. However, more studies are needed to prove its efficacy in this cohort. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Identification of clinical parameters to increase the diagnostic yield of the non-emergent upper gastrointestinal series in pediatric outpatients.

Outpatient, non-emergent upper gastrointestinal (GI) series are frequently requested in children with no surgical history who have nonspecific symptoms such as abdominal pain, failure to thrive and vomiting. The positive yield of an upper GI series in these patients, and, thus, its utility, has not been studied. We evaluated the incidence of positive upper GI findings in children without a history of GI pathology or abdominal surgery in order to identify clinical indications associated with a greater diagnostic yield. Findings of upper GI series performed between October 2015 and October 2017 in three institutions in children younger than 18years of age were retrospectively reviewed. The upper GI series protocol for each institution was also reviewed. Children with a medical or surgical GI history, children with insufficient history in the chart and those with an incomplete upper GI series were excluded from the study. Exam indications, patient demographics and clinical history were obtained from the electronic medical records. Of 1,267 children who underwent outpatient upper GI series, 720 (median age: 2years) had no GI history and were included in the study. The most common indications were non-bilious vomiting (62%), reflux symptoms (28%) and abdominal pain (20%). Upper GI series were normal in 605/720 cases (84%), including 25/26 children with reported bilious emesis. Of the 115 positive studies, 78 (68%) showed only gastroesophageal reflux (GER) (median age: 11months). Of the remaining 37 studies, 19 demonstrated esophageal findings. One case of malrotation without midgut volvulus was identified in a patient who presented with dysphagia and reflux symptoms. Using a multinomial logistic regression model and adjusting for other variables, reflux symptoms and younger patient age were independent predictors of GER on upper GI series (relative risk ratios of 2.2 and 0.9, respectively). Dysphagia and/or foreign body sensation and older patient age were independent predictors of the presence of esophageal findings (relative risk ratios of 3.3 and 1.1, respectively). The yield of routine upper GI series in children with nonspecific symptoms, such as abdominal pain and vomiting, and no surgical history is low. Diagnostic yield was improved in older children and in those complaining of dysphagia and/or foreign body sensation. Routine upper GI series should be avoided in clinically well children with symptoms only of uncomplicated GER and no significant GI history. In children with a history of dysphagia and/or foreign body sensation, an esophagram/barium swallow can suffice.

Clinical and Radiographic Gastrointestinal Abnormalities in McCune-Albright Syndrome.

McCune-Albright syndrome (MAS) is a rare disorder characterized by fibrous dysplasia of bone, café-au-lait macules, and hyperfunctioning endocrinopathies. It arises from somatic gain-of-function mutations in GNAS, which encodes the cAMP-regulating protein Gαs. Somatic GNAS mutations have been reported in intraductal papillary mucinous neoplasms (IPMNs) and various gastrointestinal (GI) tumors. The clinical spectrum and prevalence of MAS-associated GI disease is not well established. Define the spectrum and prevalence of MAS-associated GI pathology in a large cohort of patients with MAS. Cross-sectional study. National Institutes of Health Clinical Center and The Johns Hopkins Hospital. Fifty-four consecutive subjects with MAS (28 males; age range, 7 to 67 years) were screened with magnetic resonance cholangiopancreatography (MRCP). Thirty of 54 subjects (56%) had radiographic GI abnormalities. Twenty-five (46%) of the screened subjects had IPMNs (mean age of 35.1 years). Fourteen of the 25 had IPMNs alone, and 11 had IPMNs and abnormal hepatobiliary imaging. The 30 patients with MAS-associated GI pathology had a higher prevalence of acute pancreatitis, diabetes mellitus, and skeletal disease burden of fibrous dysplasia than patients without GI disease. A broad spectrum of GI pathology is associated with MAS. IPMNs are common and occur at a younger age than in the general population. Patients with MAS should be considered for screening with a focused GI history and baseline MRCP. Further determination of the natural history and malignant potential of IPMNs in MAS is needed.

Increased Small Intestinal Permeability during Severe Acute Exacerbations of COPD

Background: Disturbances of intestinal integrity, manifested by increased gastro-intestinal (GI) permeability, have been found in chronic obstructive pulmonary disease (COPD) patients during physical activity, often associated with intermittent hypoxic periods. Evidence about extrapulmonary organ disturbances, especially of the GI tract, during hospitalised acute exacerbation of COPD (AE-COPD) with hypoxaemic respiratory failure (RF) is lacking. Objective: The aim was to assess changes in GI permeability in patients with AE-COPD and during recovery 4 weeks later. Methods: All patients admitted to our hospital with AE-COPD accompanied by hypoxaemia at admission (PaO₂ <8.7 kPa or O₂ saturation <93%) were screened between October 2013 and February 2014. Patients with a history of GI or renal disease, chronic heart failure, or use of non-steroidal anti-inflammatory drugs in the 48 h before the test were excluded. GI permeability was assessed by evaluating urinary excretion ratios of the orally ingested sugars lactulose/L-rhamnose (L/R ratio), sucrose/L-rhamnose (Su/R ratio) and sucralose/erythritol (S/E ratio). Results: Seventeen patients with severe to very severe COPD completed the study. L/R ratio (×10³) at admission of AE-COPD was significantly higher than in the recovery condition (40.9 [29.4–49.6] vs. 27.3 [19.5–47.7], p = 0.039), indicating increased small intestinal permeability. There were no significant differences in the individual sugar levels in urine nor in the 0- to 5-h urinary S/E and Su/R ratios between the 2 visits. Conclusion: This is the first study showing increased GI permeability during hospitalised AE-COPD accompanied by hypoxaemic RF. Therefore, GI integrity in COPD patients is an attractive target for future research and for the development of interventions to alleviate the consequences of AE-COPD.

AB0254 Gastrointestinal health of ra patients - from top to tail

BackgroundGastrointestinal problems are common but not well studied in RA patients. Symptoms may affect patient health, quality of life and concordance with medication.ObjectivesTo assess the prevalence, severity and nature of...

Hospitalizations for gastrointestinal and cardiovascular events in the CADEUS cohort of traditional or Coxib NSAID users.

To assess hospital admission rates for gastrointestinal (GI) or cardiovascular (CV) events in real-life use of nonsteroidal anti-inflammatory drugs (NSAIDs). CADEUS is a real-life population-based cohort study of 23 535 coxib (celecoxib or rofecoxib) and 22 919 traditional NSAID (tNSAID) users. Each hospitalization reported between index day (NSAID delivery) and questionnaire submission (median = 75 days) was explored using hospital discharge summaries. An expert committee validated blindly serious GI and CV events according to predefined criteria. Coxib users were older and had more GI history than tNSAID users. There were 21 hospitalizations for GI events, 12 in the coxib cohort and nine in the tNSAID cohort (respectively one and three upper GI haemorrhages and no ulcer perforations). Rates of GI events were 0.39 per 1000 patients [95% confidence interval (CI) 0.18, 0.75] for tNSAID users and 0.51 per 1000 patients (95% CI 0.26, 0.89) for coxib users. There were 21 hospitalizations for CV events, 13 in the coxib cohort and eight in the tNSAID cohort. None was fatal. Rates of CV events were, respectively, 0.59 (95% CI 0.24, 1.22), 0.51 (95% CI 0.19, 1.11) and 0.35 (95% CI 0.15, 0.69) per 1000 patients for celecoxib, rofecoxib and tNSAIDs. GI or CV event rates were not different between products even for patients >60 years old. Hospitalization rates for GI bleeding were 10-20 times lower than expected from published randomized clinical trials, probably because of differences in drug usage and concomitant gastroprotection. CV event rates conformed to those expected from general population data. These results emphasize the necessity of developing population healthcare databases to explore such low event rates.

Use of Gastroprotective Drugs in Patients Receiving Low-dose Aspirin

Low-dose aspirin is widely used for prevention of stroke, heart attacks, and death in patients with atherothrombotic disease, but its use is associated with serious gastrointestinal (GI) adverse effects. Gastroprotective drugs (GPDs) have been used to reduce aspirin-related GI complications but are usually underutilized. The aim of this study was therefore to determine the prescription pattern of GPDs with low-dose aspirin therapy. All patients who had attended general and specialist outpatient clinics of Tung Wah Hospital between September 1, 2007 and September 30, 2007 and received low-dose aspirin therapy were included in the study. Data were collected through retrospective chart review and recorded on a standardized data collection form. Univariate analysis was performed using chi2 tests for discrete variables. Factors that might be associated with prescription of GPD with low-dose aspirin were assessed in multiple logistic regression models. Three hundred and three patients were included in this study, and the rate of GPD prescription was 48.5%. Most of the patients received H2-receptor antagonist, and, to a lesser degree, antacid and proton pump inhibitor. Patients with history of GI ulcer/bleeding were much more likely to be co-prescribed GPD than those who had no history of GI disorders (OR, 26.5). Compared with patients who were managed in general outpatient clinic, those managed in specialist clinic were more likely to receive GPD (OR, 3.04). The prescription rate of GPD with aspirin is low. Also, it seems that physicians are unaware of the risk factors related to aspirin-induced GI complications.

Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation

To review the clinical effectiveness and cost-effectiveness of cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drugs (NSAIDs) (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis (OA) and rheumatoid arthritis (RA). Electronic databases were searched up to November 2003. Industry submissions to the National Institute for Health and Clinical Excellence (NICE) in 2003 were also reviewed. Systematic reviews of randomised controlled trials (RCTs) and a model-based economic evaluation were undertaken. Meta-analyses were undertaken for each COX-2 selective NSAID compared with placebo and non-selective NSAIDs. The model was designed to run in two forms: the 'full Assessment Group Model (AGM)', which includes an initial drug switching cycle, and the 'simpler AGM', where there is no initial cycle and no opportunity for the patient to switch NSAID. Compared with non-selective NSAIDs, the COX-2 selective NSAIDs were found to be equally as efficacious as the non-selective NSAIDs (although meloxicam was found to be of inferior or equivalent efficacy) and also to be associated with significantly fewer clinical upper gastrointestinal (UGI) events (although relatively small numbers of clinical gastrointestinal (GI) and myocardial infarction (MI) events were reported across trials). Subgroup analyses of clinical and complicated UGI events and MI events in relation to aspirin use, steroid use, prior GI history and Helicobacter pylori status were based on relatively small numbers and were inconclusive. In the RCTs that included direct COX-2 comparisons, the drugs were equally tolerated and of equal efficacy. Trials were of insufficient size and duration to allow comparison of risk of clinical UGI events, complicated UGI events and MIs. One RCT compared COX-2 (celecoxib) with a non-selective NSAID combined with a gastroprotective agent (diclofenac combined with omeprazole); this included arthritis patients who had recently suffered a GI haemorrhage. Although no significant difference in clinical GI events was reported, the number of events was small and more such studies, where patients genuinely need NSAIDs, are required to confirm these data. A second trial showed that rofecoxib was associated with fewer diarrhoea events than a combination of diclofenac and misoprostol (Arthrotec). Previously published cost-effectiveness analyses indicated a wide of range of possible incremental cost per quality-adjusted life-year (QALY) gained estimates. Using the simpler AGM, with ibuprofen or diclofenac alone as the comparator, all of the COX-2 products are associated with higher costs (i.e. positive incremental costs) and small increases in effectiveness (i.e. positive incremental effectiveness), measured in terms of QALYs. The magnitude of the incremental costs and the incremental effects, and therefore the incremental cost-effectiveness ratios, vary considerably across all COX-2 selective NSAIDs. The base-case incremental cost per QALY results for COX-2 selective NSAIDs compared with diclofenac for the simpler model are: celecoxib (low dose) 68,400 pounds; celecoxib (high dose) 151,000 pounds; etodolac (branded) 42,400 pounds; etodolac (generic) 17,700 pounds; etoricoxib 31,300 pounds; lumiracoxib 70,400 pounds; meloxicam (low dose) 10,300 pounds; meloxicam (high dose) 17,800 pounds; rofecoxib 97,400 pounds; and valdecoxib 35,500 pounds. When the simpler AGM was run using ibuprofen or diclofenac combined with proton pump inhibitor (PPI) as the comparator, the results change substantially, with the COX-2 selective NSAIDs looking generally unattractive from a cost-effectiveness point of view (COX-2 selective NSAIDs were dominated by ibuprofen or diclofenac combined with PPI in most cases). This applies both to 'standard' and 'high-risk' arthritis patients defined in terms of previous GI ulcers. The full AGM produced results broadly in line with the simpler model. The COX-2 selective NSAIDs examined were found to be similar to non-selective NSAIDs for the symptomatic relief of RA and OA and to provide superior GI tolerability (the majority of evidence is in patients with OA). Although COX-2 selective NSAIDs offer protection against serious GI events, the amount of evidence for this protective effect varied considerably across individual drugs. The volume of trial evidence with regard to cardiovascular safety also varied substantially between COX-2 selective NSAIDs. Increased risk of MI compared to non-selective NSAIDs was observed among those drugs with greater volume of evidence in terms of exposure in patient-years. Economic modelling shows a wide range of possible costs per QALY gained in patients with OA and RA. Costs per QALY also varied if individual drugs were used in 'standard' or 'high'-risk patients, the choice of non-selective NSAID comparator and whether that NSAID was combined with a PPI. With reduced costs of PPIs, future primary research needs to compare the effectiveness and cost-effectiveness of COX-2 selective NSAIDs relative to non-selective NSAIDs with a PPI. Direct comparisons of different COX-2 selective NSAIDs, using equivalent doses, that compare GI and MI risk are needed. Pragmatic studies that include a wider range of people, including the older age groups with a greater burden of arthritis, are also necessary to inform clinical practice.

GI Risk Factors and Use of GI Protective Agents Among Patients Receiving Nonsteroidal Antiinflammatory Drugs

Patient characteristics increase the risk of gastrointestinal (GI) complications associated with nonsteroidal antiinflammatory drugs (NSAIDs). Patients at risk may not be prescribed protective therapies that might mitigate their risk of NSAID-associated GI complications. To assess GI risk among Veterans Affairs (VA) patients on NSAID therapy, determine whether therapy conformed to VA guidelines for lessening the risk of GI complications, and identify patient risk factors associated with conformance. Using databases from 3 VA medical centers, we retrospectively identified patients receiving NSAIDs and obtained data regarding age, history of GI bleed over 8 years, GI adverse effects associated with NSAIDs, diagnoses, and medication history over one year. We inferred health status from age-adjusted Charlson comorbidity index values. Each patient's risk of developing GI complications over one year was calculated using these data. Among patients at significant or substantial risk, we assessed conformance to VA guidelines. We used logistic regression to identify risk factors associated with conformance and determine adjusted ORs (AORs) with 95% CIs for each risk factor. There were 19 122 patients receiving NSAIDs. Of 4589 patients at significant risk and 1246 at substantial risk, 1161 (25.3%) and 356 (28.6%), respectively, were prescribed guideline-conformant therapy. Risk factors associated with conformance (p < or = 0.001) among patients at significant risk were rheumatoid arthritis (AOR 1.34; 95% CI 1.13 to 1.58) and GI adverse effects (AOR 1.53; 95% CI 1.42 to 1.64). For substantial risk patients, risk factors associated with conformance (p < or = 0.031) were rheumatoid arthritis (AOR 1.65; 95% CI 1.37 to 1.98), concomitant corticosteroids (AOR 1.21; 95% CI 1.02 to 1.43), GI hospitalization (AOR 2.01; 95% CI 1.57 to 2.59), and GI adverse effects (AOR 1.79; 95% CI 1.47 to 2.18). Many patients at risk for GI adverse events do not receive guideline-conformant therapy. Educational interventions to improve conformance could focus on specific risk factors for GI complications.

Obscure-Overt Gastrointestinal Bleeding

A 65-year-old man was admitted for recurent gastrointestinal (GI) bleeding. The patient, assing dark red blood per rectum, was hospitalized months previously at an outside hospital. He reuired 2 units of packed red blood cells (RBCs), and here was no further evidence of bleeding by the econd day of hospitalization. Upper endoscopy, olonoscopy, and upper GI series with small-bowel ollow-through (SBFT) radiography were unrevealng. The patient was discharged home on oral iron herapy and was to be observed. He was again aditted with the same symptoms. He denied abdomnal pain, GI history other than the recent episode of leeding, any family history of GI bleeding, use of onsteroidal anti-inflammatory drugs (NSAIDs) or spirin, or heavy alcohol use. He had hypertension, or which he takes a thiazide diuretic and an angioensin-converting enzyme inhibitor. On admission, is blood pressure was 100/80 mm Hg, and his heart ate was 116 bpm. His abdomen was soft, nondisended, and nontender, and he had normal bowel ounds. He had no cutaneous lesions. Within 12 ours, the patient was hemodynamically stable after esuscitation with intravenous fluids and 3 units of acked RBCs. There is no evidence of ongoing overt I bleeding.