Gastrointestinal Risk Research Articles

ASSESSMENT OF NUTRIENT INTAKE AND PHYSICAL ACTIVITY PATTERN IN VEGETARIAN GERIATRIC POPULATION, AGED 60-70 YEARS

Several changes have been seen in eating behavior which creates an impact on the palatability, food choice, social features, and psychological factors of the person which lowers the recommended dietary intake/daily requirements. Objectives: The purpose of this study was to examine the association between the nutrient intake and physical activity and also to assess dietary habits along with medical conditions in geriatric population aged 60-70 years. Methods: This purposive analysis included 100 samples of both male (n=55) and female (n= 45) gender. The dietary habits and nutrient intake of all participants were assessed using a food frequency questionnaire (FFQ) and 24-hour dietary recall. The cognitive and physical function was evaluated using The Lawton Instrumental Activities of Daily Living Scale (Lawton IADL Scale), chair test and history of medical conditions were accumulated using online and telephonic mode. Results: The evaluation of nutrient intake was found to have a significant correlation with physical exercise of the active participants (n=77) which included dairy products (p=0.05), green leafy vegetables (p=0.024), other vegetables (p=0.022), root vegetables (p=0.018), fruits (p=0.047) and sugar (p=0.003). In addition, the eating habits were observed to have a notable association with medical history of the subjects, that exhibits gastrointestinal problems, cardiovascular risk, diabetes, thyroid and asthma to be considerably linked with the eating pattern. However, the optimum daily requirement of nutrients (energy, protein, calcium and vitamin C) was determined to be inadequate. Conclusion: Recommended dietary requirements can be beneficial in performing physical exercises to diminish the risk of frailty and the risk of comorbidities by comprehending certain daily physical activities. These findings further reward the advantages of adopting an active lifestyle.

Review Article: Gastrointestinal Bleeding Risk with Direct Oral Anticoagulants.

Although direct oral anticoagulants (DOACs) are associated with an overall favourable safety profile, the risk of gastrointestinal bleeding with DOACs compared with vitamin K antagonists (VKAs) remains controversial. Accordingly, we aimed to provide a focused overview of the risk of gastrointestinal bleeding associated with dabigatran, rivaroxaban, apixaban and edoxaban and its management. We reviewed published studies reporting on DOACs with gastrointestinal bleeding as an outcome, including randomised controlled trials (RCTs), retrospective database studies and large-scale prospective cohort studies. Cumulative evidence confirms no notable difference in major gastrointestinal bleeding risk between DOACs and VKAs. Moreover, gastrointestinal bleeding in DOAC-treated patients seems less severe and requires less intensive management. The main cause of upper gastrointestinal bleeding in DOAC-treated patients appears to be gastroduodenal ulcers, whereas lower gastrointestinal bleedings are mainly due to diverticula followed by angiodysplasia and haemorrhoids. The lack of head-to-head RCTs with DOACs precludes drawing conclusions on the DOAC with the lowest gastrointestinal bleeding risk. Prescribing physicians should be aware of risk factors for DOAC-related gastrointestinal bleeding (e.g. age > 65, heavy alcohol use, uncontrolled hypertension, hepatic or renal dysfunction, active cancer, anaemia) and adopt preventive measures accordingly. Management of DOAC-associated major gastrointestinal bleeding involves temporary discontinuation of the DOAC, investigation of the bleeding source and treatment of bleeding with fluid resuscitation combined with transfusion and endoscopic haemostasis. DOACs as a class do not increase the risk of major gastrointestinal bleeding compared to VKAs, which supports their continued use for different anticoagulant indications.

Risk of upper gastrointestinal bleeding in patients on oral anticoagulant and proton pump inhibitor co-therapy.

BackgroundProton pump inhibitors (PPIs) are known to reduce the risk of upper gastrointestinal bleeding in patients on oral anticoagulants, and patients are increasingly on oral anticoagulants and PPI co-therapy. However, evidence is lacking on the safety and effectiveness of oral anticoagulants when co-administered with PPIs.MethodsAmong patients initiating oral anticoagulants (warfarin and non-vitamin K antagonist oral anticoagulants [NOACs], i.e. rivaroxaban, dabigatran, apixaban, and edoxaban) during 2013–2017, those concomitantly prescribed PPIs were identified (n = 19,851). The primary endpoint was hospitalization for major upper gastrointestinal bleeding, and secondary endpoints were death and ischemic stroke.ResultsDuring a mean 1.4 years of follow-up, the primary endpoint occurred in 512 (2.58%) patients. Overall, NOACs were associated with lower upper gastrointestinal bleeding risk after adjustment for age, sex, comorbidities and concomitant medications (adjusted hazard ratio 0.78, 95% confidence interval 0.65–0.94), compared to warfarin. There was no significant difference in upper gastrointestinal bleeding risk among the individual NOACs. This trend of reduced risk for upper gastrointestinal bleeding in NOACs compared to warfarin was consistent for both regular and reduced doses, throughout bleeding risk groups, and other subgroup analyses. NOACs were also associated with lower risk of death compared to warfarin. The risk for ischemic stroke was not significantly different among the oral anticoagulants in patients with atrial fibrillation.ConclusionIn patients on oral anticoagulant and PPI co-therapy, NOACs were associated with lower risk of upper gastrointestinal bleeding and mortality compared to warfarin, while there was no difference among the oral anticoagulants for stroke prevention. In patients on PPI therapy, NOACs may preferred over warfarin for decreasing risk of upper gastrointestinal bleeding and mortality.

Genome sequencing unveils a regulatory landscape of platelet reactivity

Platelet aggregation at the site of atherosclerotic vascular injury is the underlying pathophysiology of myocardial infarction and stroke. To build upon prior GWAS, here we report on 16 loci identified through a whole genome sequencing (WGS) approach in 3,855 NHLBI Trans-Omics for Precision Medicine (TOPMed) participants deeply phenotyped for platelet aggregation. We identify the RGS18 locus, which encodes a myeloerythroid lineage-specific regulator of G-protein signaling that co-localizes with expression quantitative trait loci (eQTL) signatures for RGS18 expression in platelets. Gene-based approaches implicate the SVEP1 gene, a known contributor of coronary artery disease risk. Sentinel variants at RGS18 and PEAR1 are associated with thrombosis risk and increased gastrointestinal bleeding risk, respectively. Our WGS findings add to previously identified GWAS loci, provide insights regarding the mechanism(s) by which genetics may influence cardiovascular disease risk, and underscore the importance of rare variant and regulatory approaches to identifying loci contributing to complex phenotypes.

Associations between Prediagnostic Circulating Bilirubin Levels and Risk of Gastrointestinal Cancers in the UK Biobank.

Simple SummaryEvidence from experimental studies suggests that bilirubin, a metabolic by-product of hemoglobin breakdown, has anticancer activity and may, therefore, reduce the risk of gastrointestinal (GI) cancers. We conducted a prospective study among 440,948 participants in the UK Biobank and found that higher prediagnostic circulating bilirubin levels were robustly associated with a lower risk of developing esophageal adenocarcinoma, which is compatible with the antioxidant hypothesis of bilirubin. We further observed negative associations between bilirubin and risk of colorectal cancer, which were less robust and could be due to reverse causality, whereby undiagnosed cancer affects bilirubin levels. The observed positive associations between bilirubin and risk of hepatobiliary cancers may indicate underlying liver disease processes. No associations were found for cancers of the mouth, stomach, and pancreas. Bilirubin is a novel biomarker for disease development that is routinely measured in clinical settings. Provided that our findings are replicated in further studies, circulating bilirubin could serve as a future risk stratification marker for certain GI cancers.We investigated associations between serum levels of bilirubin, an endogenous antioxidant, and gastrointestinal cancer risk. In the UK Biobank, prediagnostic serum levels of total bilirubin were measured in blood samples collected from 440,948 participants. In multivariable-adjusted Cox proportional hazard regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between bilirubin levels and gastrointestinal cancer risk (colorectum, esophagus, stomach, mouth, pancreas, and liver). After a median follow-up of 7.1 years (interquartile range: 1.4), 5033 incident gastrointestinal cancer cases were recorded. In multivariable-adjusted models, bilirubin levels were negatively associated with risk of esophageal adenocarcinoma (EAC, HR per 1-SD increment in log-total bilirubin levels 0.72, 95%CI 0.56–0.92, p = 0.01). Weak and less robust negative associations were observed for colorectal cancer (CRC, HR per 1-SD increment in log-total bilirubin levels 0.95, 95%CI 0.88–1.02, p = 0.14). Bilirubin levels were positively associated with risk of hepatocellular carcinoma (HCC, HR per 1-SD increment in log-total bilirubin levels 2.07, 95%CI 1.15–3.73, p = 0.02) and intrahepatic bile duct (IBD) cancer (HR per 1-SD increment 1.67, 95%CI 1.07–2.62, p = 0.03). We found no associations with risks of stomach, oral, and pancreatic cancers. Prediagnostic serum levels of bilirubin were negatively associated with risk of EAC and positively associated with HCC and IBD cancer. Further studies are warranted to replicate our findings for specific GI cancers.

Family History and Risk of Upper Gastrointestinal Cancer in the Linxian General Population.

ObjectiveThe objective of this study was to investigate family history (FH) of upper gastrointestinal (UGI) cancer and risk of esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC), and gastric non-cardia carcinoma (GNCC) in the Linxian General Population Nutrition Intervention Trial (NIT) cohort. Methods: This prospective analysis was conducted using the Linxian NIT cohort data. Subjects with FH of UGI cancer was treated as an exposed group while the remainders were considered as a comparison group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between FH of UGI cancer and risk of UGI cancer incidence and mortality were estimated using Cox proportional hazards models.ResultsThere were 5,680 newly diagnosed UGI cancer cases during the follow-up period, with a total of 4,573 UGI cancer deaths occurred, including 2,603 ESCC, 1,410 GCC, and 560 GNCC deaths. A positive FH of UGI cancer was associated with a significantly increased risk of ESCC and GCC (Incidence: HRESCC = 1.45, 95%CI: 1.35–1.56; HRGCC = 1.27, 95%CI: 1.15–1.40; Mortality: HRESCC = 1.40, 95%CI: 1.30–1.52; HRGCC = 1.27, 95%CI: 1.14–1.42) after adjusting for age at baseline, gender, smoking status, alcohol drinking, education level, and frequency of fresh fruit and vegetable consumption. Subjects with FH in both parents had the highest risk of ESCC and GCC incidence (HRESCC = 1.65, 95%CI: 1.40–1.95; HRGCC = 1.42, 95%CI: 1.12–1.81) and deaths (HRESCC = 1.65, 95%CI: 1.38–1.97; HRGCC = 1.42, 95%CI: 1.09–1.85). Spouse diagnosed with UGI cancer did not increase the risk of any UGI cancers of the subjects. In subgroup analysis, FH of UGI cancer was shown to significantly increase the risk of GCC in non-drinkers (Incidence: HR = 1.31, 95%CI: 1.17–1.47; Mortality: HR = 1.33, 95%CI: 1.17–1.50). No associations were observed for risk of GNCC. Sensitivity analysis by excluding subjects who were followed up less than three years did not materially alter our results.ConclusionOur data point to the role of the FH of UGI cancer to the risk of ESCC and GCC incidence and mortality. The influence of family history on the risk of UGI cancer varies from different types of family members.

Metal(Loids) Bioaccessibility in Road Dust from the Surrounding Villages of an Active Mine

Human activities, in general, cause a significant impact on the environment and human health. The present study aims to characterize the road dust of villages located near an active mine and to assess metal(loids) bioaccessible fractions. From the collected road dust samples (<250 µm fraction), the pseudo total, gastric (G) and gastrointestinal (GI) phase (UBM assay) concentrations, mineralogical composition, enrichment factor (EF), and risk for humans were determined. The obtained results revealed that arsenic represents the highest risk to humans, with mean pseudototal values higher than the maximum reference value range. The enrichment factor pointed to As as having significant to very high enrichment in all of the villages. In addition, Cd presented the maximum EF values in all of the villages, and was thus classified as having a very high enrichment. Particles enriched in As, Ca, Fe, Cu, Al, and Ti were identified by SEM-EDS in weathered agglomerates, and were linked to mine wastes and long-distance transport through both wind and/or traffic. The arsenic bioaccessibility fraction (%BAF) presented low values in the studied samples, possibly because of the low complex solubility of Fe with adsorbed As, limiting the release of arsenic and reducing its bioaccessibility. The concentrations of bioaccessible Cd for the G and GI phases were within the reference range, while for Cu, they were above and for Pb they were lower than the reference value range. The results show that the pseudototal fraction risk is overestimated when compared with BAF%; nevertheless, the total G and GI risks were above the carcinogenic target risk (1 × 10−6) in most of the samples. The carcinogenic risk of the bioaccessible contaminants showed that As represented the higher risk for developing cancer over a lifetime, with ingestion being the main risk route.

Impact of Portal Vein Thrombosis on Endoscopic Variceal Band Ligation in Liver Cirrhosis

Background. Portal vein (PV) thrombosis (PVT) is a common complication of liver cirrhosis and can refer to thrombosis within the PV that can extend to its left or right branches and in some cases to the superior mesenteric vein or the splenic vein (Chawla and Bodh, 2015). For severe PVT patients, there are possibilities of increasing PV resistance and reduction of the blood flow though PV towards liver, which exacerbate liver function damage meanwhile elevating the gastrointestinal variceal bleeding risk. Endoscopic Variceal band ligation (EVL) is often used to prevent esophageal variceal bleeding; postoperative complications such as severe gastrointestinal bleeding and bleeding-related death, fever, retrosternal pain, and esophageal stenosis may appear. There was absence of the research which evaluated the impact of PVT in liver cirrhosis on the complication of endoscopic Variceal band ligation for now. We herein aimed to compare cirrhosis patients with and without PVT of recent complications after EVL. Method. We established the retrospective investigation on 144 consecutive cirrhosis patients (excluding patients with hepatocellular carcinoma and who received portal vein-systemic circulation devascularization or shunt surgery, splenectomy, hepatectomy, liver transplantation, transjugular intrahepatic portal vein stent shunt (TIPS), endoscopic varices Variceal ligation, or sclerotherapy before) who have received first endoscopic esophageal varices band ligation in Gastrointestinal Endoscopy Center of the First Affiliated Hospital, College of Medicine, ZheJiang University, between January 2014 and December 2017. Portal vein Doppler ultrasonography, liver computerized tomography (CT), and angiography or liver-enhanced magnetic resonance imaging (MRI) were applied to evaluate the portal vein thrombosis of each patient before EVL. There were 18 patients confirmed with portal vein thrombosis while the other 126 patients without PVT. The primary end point for this research is the upper gastrointestinal hemorrhage and related death occurred from the date of ligation until leaving hospital, and the secondary end point is the appearance of postoperative fever and retrosternal pain. Results. There are no significant differences of gastrointestinal bleeding, bleeding-related death, fever, or retrosternal pain after EVL and the length of hospital stays between cirrhotic patients with or without PVT ( P = 0.34 , 0.51 , 0.58 , 0.61 , 0.88 ). Conclusion. Liver cirrhosis with portal vein thrombosis did not increase incidence of recent complications of the endoscopic Variceal band ligation.

Phase I study of functionalized hafnium oxide nanoparticles (NBTXR3) activated by radiotherapy in cisplatin-ineligible locally advanced HNSCC patients.

6051 Background: The non-surgical standard of care (SOC) for the treatment of locally advanced head and neck squamous cell carcinoma (LA HNSCC) patients is concurrent chemoradiation with high dose cisplatin or cetuximab in case of contra-indication to cisplatin. However elderly patients, and those with poor performance status, comorbidities, and/or intolerance, may not benefit from these SOC treatments and represent a high unmet need. New approaches are thus needed to improve clinical outcomes without adding toxicity. NBTXR3, a novel radioenhancer, composed of functionalized hafnium oxide nanoparticles, is injected once intratumorally and activated by radiotherapy (RT).NBTXR3 increases the RT energy deposit inside tumor cells and subsequently increases tumor cell death compared to RT alone, while sparing healthy tissues. We present here the results of the dose expansion part of the phase I study evaluating NBTXR3 plus intensity modulated radiation therapy (IMRT) in this population. Methods: Patients with stage III-IVA or T3/T4 (AJCC/UICC TNM staging system 8th ed.) HNSCC of the oropharynx or oral cavity, ineligible to cisplatin or cetuximab and amenable for RT, received a single intratumoral injection of NBTXR3 and IMRT (70 Gy in 35 fractions /7 weeks). A classical 3 + 3 dose escalation design has tested four doses of NBTXR3, equivalent to 5, 10, 15, and 22% of baseline theoretical tumor volume. The RP2D established as 22% of baseline tumor volume is further tested in the dose expansion part. The primary endpoints of the dose expansion part are objective response rate (ORR) and complete response rate (CRR) of the primary tumor, by imaging according to RECIST 1.1. Safety is also evaluated. Results: As of August 13, 2020, 43 patients have been treated in the phase I dose expansion part. The median age was 70.7 years old (range: 50.7- 89.9), 70% of patients had cardiac disorder risk, 44% had gastrointestinal disorder risk and 44% metabolic and nutrition disorder risk. The median tumor volume was 42.8 mL (range: 1.3 - 222.3). At a median time of 7.8 months after NBTXR3 injection, the ORR of the primary lesion was 83.9% and the CRR 67.7% in the evaluable population for efficacy (N = 31). Three patients (7%) experienced at least one serious adverse event (AE) related to the injection procedure and/or NBTXR3 which represented less than 1% of all reported AEs. RT-related toxicity was as expected with IMRT. Three deaths due to AEs related to RT and other causes were reported. The recruitment is ongoing and updated efficacy and safety results will be presented. Conclusions: NBTXR3 intratumoral administration followed by IMRT may represent an option in elderly patients or patients with multiple comorbidities with LA-HNSCC who have limited therapeutic options. NBTXR3 activated by RT showed promising anti-tumor efficacy, supporting further evaluation in a phase III randomized trial. Clinical trial information: NCT01946867.

Performance of PRECISE-DAPT Score for predicting upper gastrointestinal bleedings in patients with stable coronary artery disease on long-term antithrombotic therapy

Abstract Funding Acknowledgements Type of funding sources: None. Background PRECISE-DAPT score has become developed for predicting the risk of bleedings in patients treated with coronary stenting and subsequent 1-year dual antiplatelet therapy. The utility of PRECISE-DAPT score in the setting of all-comer CAD population with different regimes of long-term antithrombotic therapy remains unclear. Upper gastrointestinal bleeding (UGIB) is the predominant hemorrhagic complication in CAD patients; however, the PRECISE-DAPT capacity with respect to this type of bleeding has never been evaluated. Purpose to evaluate the role of PRECISE-DAPT score in the assessment of upper gastrointestinal bleeding risk in patients with stable coronary artery disease (CAD) receiving long-term antithrombotic therapy. Methods Data were obtained from single center prospective Registry of Long-term AnTithrombotic TherApy (REGATTA-1 NCT04347200). The PRECISE-DAPT score was calculated in a total of 434 patients with stable CAD (77,4% males, median age 61 [IQR 55-69] yrs). Most of the patients 93,6 % received DAPT due to recent PCI with a switch to aspirin monotherapy after 6 months. 1,4 % of patients received aspirin only, 22 (5,1%) of patients received oral anticoagulants because of concomitant atrial fibrillation. The primary outcome was any overt UGIB (BARC ≥2). Results In a total of 451 person-years of follow-up (median follow-up was 378 days, IQR 365-421), UGIB occurred 40 patients (incidence at 1 year 8.9 per 100 patients). The median time to first occurrence of UGIB was 55 [IQR 8-115] days. Median PRECISE-DAPT score was 12 points [IQR 6; 20]. The cut-off value for PRECISE-DAPT score to predict UGIB was 16 points (AUC = 0.732, p = 0.0001, 95% CI 0.367-0.827) that correspond to at least moderate bleeding risk according to original score discrimination. Kaplan-Meier bleeding rates were separated by score cut-off (Log-Rank p < 0,001) and the risk difference remains consisted in regression model (OR 2.79 [1.07-7.29]; p = 0.0348). Conclusion(s): PRECISE DAPT score demonstrated good discriminatory capacity (cut-off 16 points) with respect to UGIB in patients with stable CAD receiving long-term antithrombotic therapy.

Cost-utility analysis of imrecoxib compared with diclofenac for patients with osteoarthritis

BackgroundTo estimate the cost -utility of imrecoxib compared with diclofenac, as well as the addition of a proton pump inhibitor to both two treatment strategies, for patients with osteoarthritis, from a Chinese healthcare perspective.MethodsA Markov model was built. Costs of managing osteoarthritis and initial adverse events were collected from a Medical Database which collected information from 170 hospitals. Other parameters were obtained from the literature. Subgroup analyses were conducted for people at high risk of gastrointestinal or cardiovascular adverse events. Deterministic and probabilistic sensitivity analyses were performed.ResultsImrecoxib was highly cost-effective than diclofenac (the ICER was $401.58 and $492.77 in patients at low and high gastrointestinal and cardiovascular risk, respectively). The addition of a proton pump inhibitor was more cost -effective compared with single drug for both treatment strategies. Findings remained robust to sensitivity analyses. 59.04% and 57.16% probability for the co-prescription of imrecoxib and a proton pump inhibitor to be the most cost-effective strategy in all patients considered using the cost-effectiveness threshold of $30,000.ConclusionsThe addition of a proton pump inhibitor to both imrecoxib and diclofenac was advised. Imrecoxib provides a valuable option for patients with osteoarthritis. Uncertainties existed in the model, and the suggestions can be adopted with caution.

Anticancer potential of metformin: focusing on gastrointestinal cancers.

Gastrointestinal cancers are one of the most common types of cancer that have high annual mortality; therefore, identification and introduction of safe drugs in the control and prevention of these cancers are of particular importance. Metformin, a lipophilic biguanide, is the most commonly prescribed agent for type 2 diabetes management. In addition to its great effects on lowering the blood glucose concentrations, the anti-cancer properties of this drug have been reported in many types of cancers such as gastrointestinal cancers. Hence the effects of this agent as a safe drug on the reduction of gastrointestinal cancer risk and suppression of these types of cancers have been studied in different clinical trials. Furthermore, the proposed mechanisms of metformin in preventing the growth of these cancers have been investigated in several studies. In this review, we discuss recent advances in elucidating the molecular mechanisms that are relevant for metformin use in gastrointestinal cancer treatment.

Consumption of artificially sweetened soft drinks and risk of gastrointestinal cancer: a meta-analysis of observational studies.

There remain inconclusive findings from previous observational epidemiological studies on whether consumption of artificially sweetened soft drinks (ASSD) increases the risk of gastrointestinal (GI) cancer. We investigated the associations between the consumption of ASSD and the risk of GI cancer using a meta-analysis. Systematic review and meta-analysis. PubMed and EMBASE were searched using keywords until May 2020 to identify observational epidemiological studies on the association between the consumption of ASSD and the risk of GI cancer. Twenty-one case-control studies and seventeen cohort studies with 12 397 cancer cases and 2 474 452 controls. In the random-effects meta-analysis of all the studies, consumption of ASSD was not significantly associated with the risk of overall GI cancer (OR/relative risk (RR), 1·02; 95 % CI, 0·92, 1·14). There was no significant association between the consumption of ASSD and the risk of overall GI cancer in the subgroup meta-analyses by study design (case-control studies: OR, 0·95; 95 % CI, 0·82, 1·11; cohort studies: RR, 1·14; 95 % CI, 0·97, 1·33). In the subgroup meta-analysis by type of cancer, consumption of ASSD was significantly associated with the increased risk of liver cancer (OR/RR, 1·28; 95 % CI, 1·03, 1·58). The current meta-analysis of observational epidemiological studies suggests that overall, there is no significant association between the consumption of ASSD and the risk of GI cancer.

Gastrointestinal stromal tumors: relationship between preoperative CT features and pathologic risk stratification.

To investigate a relationship between contrast-enhanced computed tomography (CECT) features of gastrointestinal stromal tumors (GISTs) and risk of relapse according to Miettinen stratified risk classifications. After ethical committee approval, a retrospective analysis was conducted on the preoperative CECT of patients with pathologically proven GIST undergoing surgery between June 2009 and December 2019. Chi-square analysis was used to evaluate the correlation between Miettinen stratified risk categories and the following imaging features: tumor size and location, growth pattern, margins, type and degree of contrast enhancement, presence of calcifications, necrosis, signs of ulceration/fistulation, internal hemorrhagic foci, enlarged feeding or draining vessels (EFDV), ascites, peritoneal implants, lymphadenopathy, or metastasis. A total of 54 patients (mean age 65 ± 11, 29 men) were included in the study with a total of 56 GISTs. Necrosis, ulceration/fistulation, hemorrhage, margins, enlarged vessels, type of contrast enhancement, and metastasis turned out to be associated with Miettinen risk categories (p < 0.005). Logistic regression analysis identified the presence of necrosis and EFDV as predictors of pathologic risk of relapse (overall accuracy of 89.3%). Preoperative CECT may be helpful in predicting pathologic risk categories of GISTs, as determined by the Miettinen classification system.

Obesity and incident gastrointestinal cancers: overall body size or central obesity measures, which factor matters?

BMI does not reflect the location or amount of body fat. We aimed to investigate the role of general and central obesity measures in the prediction of incident gastrointestinal cancers. In this analysis of the Golestan Cohort Study, we included 47 586 cancer-free individuals followed for 12.3 years (IQR: 10.5-13.2). We investigated the association of obesity measures including BMI, waist circumference and waist-to-hip ratio (WHR) at enrollment and the incidence of esophageal, gastric, colorectal and pancreatic cancers. Cox proportional hazard models were used to estimate the association between covariates and gastrointestinal cancer risk. We observed no significant associations between obesity measures and incidence of the above-mentioned gastrointestinal cancers in men. In women, BMI, waist circumference and WHR were associated with significant reductions in the risk of esophageal squamous cell carcinoma (ESCC): hazard ratio (HR): 0.67 [95% confidence interval (CI): 0.56-0.81], HR: 0.71 (95% CI: 0.60-0.84) and HR: 0.80 (95% CI: 0.68- 0.94), respectively. In addition, WHR was associated with significantly increased risks for colorectal cancer (HR: 1.39, 95% CI: 1.08-1.78) and gastric cancer (HR: 1.24, 95% CI: 1.01-1.51) in women. In this study, statistically significant associations between obesity measures and incident esophageal, gastric and colorectal cancers were seen in women.

Major gastrointestinal bleeding risk with direct oral anticoagulants: Does type and dose matter? - A systematic review and network meta-analysis.

The relative risk of major gastrointestinal bleeding (GIB) among different direct oral anticoagulants (DOACs) is debatable. Randomized controlled trials (RCTs) comparing DOACs with each other are lacking. We performed network meta-analysis to assess whether the risk of major GIB differs based on type and dose of DOAC. Literature search of PubMed, EMBASE and Cochrane databases from inception to August 2019, limited to English publications, was conducted to identify RCTs comparing DOACs with warfarin or enoxaparin for any indication. Primary outcome of interest was major GIB risk. We used frequentist network meta-analysis through the random-effects model to compare DOACs with each other and DOACs by dose to isolate the impact on major GIB. Twenty-eight RCTs, including 139 587 patients receiving six anticoagulants, were selected. The risk of major GIB for DOACs was equal to warfarin. Comparison of DOACs with each other did not show risk differences. After accounting for dose, rivaroxaban 20 mg, dabigatran 300 mg and edoxaban 60 mg daily had 47, 40 and 22% higher rates of major GIB versus warfarin, respectively. Apixaban 5 mg twice daily had lower major GIB compared to dabigatran 300 mg (OR, 0.63; 95% CI, 0.44-0.88) and rivaroxaban 20 mg (OR, 0.60; 95% CI, 0.43-0.83) daily. Heterogeneity was low, and the model was consistent without publication bias (Egger's test: P = 0.079). All RCTs were high-quality with low risk of bias. DOACs at standard dose, except apixaban, had a higher risk of major GIB compared to warfarin. Apixaban had a lower rate of major GIB compared to dabigatran and rivaroxaban.

Increased occurrence of liver and gastrointestinal diseases and anaemia in women with Turner syndrome - a nationwide cohort study.

Liver and gastrointestinal diseases are frequent in women with Turner syndrome. However, their association with bleeding disorders, anaemia and the impact of hormone replacement therapy is unknown. To investigate the risk of liver and gastrointestinal diseases, haemorrhage and anaemia in women with Turner syndrome compared with the female background population, and the long-term impact of hormone replacement therapy on these conditions. One thousand one hundred and fifty-six women with Turner syndrome diagnosed during 1960-2014 were identified using the Danish Cytogenetic Central Registry and linked with personal-level data from the National Patient Registry and the Medication Statistics Registry. Statistics Denmark randomly identified 115577 age-matched female controls. Negative binomial regression was used to analyse hospital discharge diagnoses. Medical prescriptions, mortality and the effect of hormone replacement therapy were estimated using stratified Cox regression. Liver disease increased 13-fold (IRR 12.9 (95% CI 5.8-28.8)), due to toxic liver disease (IRR 8.0 (95% CI 1.8-35.4)), liver insufficiency (IRR 6.7 (95% CI 1.7-26.9)), fibrosis/cirrhosis (IRR 16.5 (95% CI 2.2-122.1)) and unspecified liver disease (IRR 10.6 (95% CI 4.4-25.3)). Furthermore, presence of abnormal liver enzymes increased 12-fold (IRR 12.4 (95% CI 4.2-36.6)). The risk of gastrointestinal haemorrhage (IRR 3.4 (95% CI 1.8-6.2)), anaemia (IRR 3.2 (95% CI 2.0-5.0)) and coagulation disorders (IRR 2.9 (95% CI 1.1-7.1)) was increased. However these diagnoses were not associated with inflammatory bowel disease. Gastrointestinal mortality was increased three-fold (HR 3.1 (95% CI 1.5-6.2)), partly due to death by liver disease (HR 3.0 (95% CI 1.1-8.2)), gastrointestinal haemorrhage (HR 29.6 (95% CI 3.1-285.1)) and capillary malformations (HR 18.6 (95% CI 4.1-85.0)). There was no effect of hormone replacement therapy on gastrointestinal risk but a trend towards a beneficial impact on liver diseases. The risk of being diagnosed with liver disease was higher than previously reported. The occurrence of gastrointestinal haemorrhage and anaemia was increased in Turner syndrome. There was no effect of hormone replacement therapy on gastrointestinal risk but a trend towards a beneficial impact on liver diseases was detected.

303 - Effect of Remestemcel-L Treatment in Pediatric Steroid Refractory Acute Graft-Versus-Host Disease: A Biomarker Substudy

Introduction: Steroid-refractory acute graft-versus-host dose disease (SR-aGVHD) is a common, potentially fatal complication of hematopoietic stem cell transplantation (HSCT) with no approved therapies for use in children Methods: Whole blood samples for biomarker analyses were collected at baseline, and days 28, 100, 160 and 180. Circulating levels of NK cells, T and B lymphocytes and of activated T cells (CD25+, HLA-DR+), key effectors of aGVHD development and progression, were measured by multicolor flow cytometry. Plasma levels of regenerating islet-derived protein 3α (REG3α) were measured using a multiplexed immunoassay; soluble suppression of tumorigenicity 2 (ST2) levels were measured by ELISA. REG3α and ST2 were used to derive the MAGIC algorithm probability (MAP) score at each time point as an index of gastrointestinal disease burden and risk of 6-month non-relapse mortality (NRM), with a threshold probability of 0.291 cut-off for GVHD low and high risk of NRM. Least-Squares Means (LSM) were calculated for longitudinal biomarker analyses using the restricted maximum likelihood (REML) approach followed by post-hoc pairwise comparisons between days using the Tukey-Kramer HSD significance test. These analyses were exploratory, so no adjustment was made for multiplicity. Results: Biomarker data were collected in 40 subjects. At baseline, the mean age was 8.5 years, aGVHD severity by IBMTR grade C or D, median MAP was 0.369, with a MAP ≥ 0.291 in 60% of subjects, reflecting active gastrointestinal inflammation and high risk for 6-month NRM. In this biomarker cohort day 28 (N=40) overall response was 70% and survival was 78% and 70% through day 100 and 180, respectively. Baseline biomarker profile was consistent with an inflammatory state characteristic of SR-aGVHD, with elevated plasma levels of Reg3α, ST2 and frequencies of activated CD4+ and CD8+ T cells. MAP decreased from ≥0.291 to Conclusions: Clinically meaningful overall response and survival with remestemcel-L-treatment in pediatric SR-aGVHD are associated with changes in soluble and cellular biomarkers consistent with reduced inflammation and risk of mortality. These observed changes in biomarkers provide mechanistic evidence of immunomodulation. Download : Download high-res image (411KB) Download : Download full-size image Disclosures See: Mesoblast, Inc,: Current Employment. Segal: Mesoblast, Inc,: Current Employment. Simmons: Mesoblast, LTD: Current Employment. Kurtzberg: Mesoblast, Inc,: Consultancy, Honoraria.

A New Score for Predicting Acute Gastrointestinal Bleeding in Patients Administered Oral Antiplatelet Drugs.

Antiplatelet drugs may increase the risk of gastrointestinal bleeding. Currently, there is no specific score for predicting the risk of gastrointestinal bleeding caused by oral antiplatelet drugs. In this study, the gastrointestinal bleeding risk score was established and compared with the CRUSADE score in order to reduce the occurrence of clinical gastrointestinal bleeding events. Our study included 4052 patients who received oral antiplatelet drugs. Data were obtained from the patient medical records inpatient system. Cases of acute gastrointestinal bleeding and mortality were recorded. The bleeding score was established by logistic regression, area under the receiver operating characteristic curve, and the Hosmer–Lemeshow test. Finally, 171 patients had acute gastrointestinal bleeding. The mortality rates of patients in the bleeding and nonbleeding groups were 24.6 and 4.7%, respectively. A multivariate analysis revealed that an age of >65 years, anemia, recent major bleeding, a history of gastrointestinal bleeding, combined oral anticoagulants, and dual antiplatelet therapy are risk factors, and combined proton pump inhibitors are protective factors for acute gastrointestinal bleeding. We used these risk factors to establish a score for predicting acute gastrointestinal bleeding, named (ABC)2D score. The area under the curve for (ABC)2D score was 0.857 (p < 0.001), higher than the CRUSADE score of 0.693 (p < 0.001). The Hosmer–Lemeshow p value was 0.324. We developed the (ABC)2D score based on seven risk factors (i.e., age, anemia, recent major bleeding, a history of gastrointestinal bleeding, no-proton pump inhibitors use, combined oral anticoagulants, and dual antiplatelet therapy). (ABC)2D score was superior to the CRUSADE score. This new risk-scoring model may help to identify patients at a significant risk of gastrointestinal bleeding.

Gastrointestinal Infection and Risk of Microscopic Colitis: A Nationwide Case-Control Study in Sweden

Gastrointestinal infections have been linked to changes in the composition and function of gut microbiome and development of inflammatory bowel diseases. We therefore sought to examine the relationship between gastroenteritis and risk of microscopic colitis (MC). We conducted a case-control study of all adult patients with MC diagnosed between 1990 and 2016 in Sweden matched to up to 5 general population controls according to age, sex, calendar year, and county. Cases of MC were identified using Systematized Nomenclature of Medicine codes from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, a cohort of gastrointestinal pathology reports from all 28 pathology centers in Sweden. We used logistic regression modeling to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Through December of 2016, we matched 13,468 MC cases to 64,479 controls. The prevalence of previous diagnosed gastrointestinal infection was 7.5% among patients with MC, which was significantly higher than in controls (3.0%, Pcomparison < .001). After adjustment, gastroenteritis was associated with an increased risk of MC (aOR 2.63; 95% CI 2.42-2.85). Among specific pathogens, Clostridioides difficile (aOR 4.39; 95% CI 3.42-5.63), Norovirus (aOR 2.87; 95% CI 1.66-4.87), and Escherichia species (aOR 3.82; 95% CI 1.22-11.58), but not Salmonella species, were associated with an increased risk of MC. The association between gastrointestinal infections and risk of MC was stronger for collagenous subtype (aOR 3.23; 95% CI 2.81-3.70) as compared with lymphocytic colitis (aOR 2.51; 95% CI 2.28-2.76; Pheterogeneity= .005). The associations remained significant after adjustment for immune-mediated conditions and polypharmacy and when compared with unaffected siblings. In a nationwide study, we found that gastrointestinal infection, particularly Clostridioides difficile, is associated with an increased risk of subsequent MC. This study was approved by the Regional Ethics Committee, Stockholm, Sweden (Protocol no. 2014/1287-31/4).