Gastrointestinal Risk Research Articles

Cohort profile: Nordic Helicobacter Pylori eradication project (NordHePEP)

Purpose This cohort description presents the Nordic Helicobacter Pylori Eradication Project (NordHePEP), a population-based cohort of patients having received eradication treatment for Helicobacter pylori (HP). The cohort is created with the main purpose of examining whether and to what extent HP eradication treatment influences the risk of gastrointestinal cancer. Participants NordHePEP includes all adults (aged ≥18 years) having been prescribed and dispensed HP eradication treatment according to the nationwide complete drug registries in any of the five Nordic countries (Denmark, Finland, Iceland, Norway, or Sweden) between 1994 and 2020 (start and end year varies between countries). We have retrieved and merged individual-level data from multiple national registries, including drug, patient, cancer, population, and death registries. Findings The cohort includes 674,771 patients having received HP eradication treatment. During up to 23 years of follow-up, 59,292 (8.8%) participants were diagnosed with cancer (non-melanoma skin cancer excluded), whereof 15,496 (2.3%) in the gastrointestinal tract. Future plans We will analyse HP eradication treatment in relation to gastrointestinal cancer risk. Standardised incidence ratios will be calculated as the observed cancer incidence in the cohort divided by the expected cancer incidence, derived from the background population of the corresponding age, sex, and calendar year.

Time Trend of Upper Gastrointestinal Cancer Incidence in China from 1990 to 2019 and Analysis Using an Age-Period-Cohort Model.

The aim of this study was to investigate the upper gastrointestinal cancer incidence trend in China from 1990 to 2019 with Joinpoint software and to evaluate the age effect, cohort effect, and period effect using the age–period–cohort model, with the data obtained from the Global Burden of Disease, Injuries, and Risk Factors Study. The crude incidence rate (CR) of upper gastrointestinal cancer in China increased from 41.48/100,000 in 1990 to 62.64/100,000 in 2019, and the average annual percent change (AAPC) was 1.42 (p < 0.05). The age-standardized incidence rate (ASIR) decreased from 50.77/100,000 to 37.42/100,000, and the AAPC was −1.12 (p < 0.05). The net drift was −0.83 (p < 0.05), and the local drifts in the 35–79 age groups of males and all age groups of females were less than 0 (p < 0.05). The age effect showed that the upper gastrointestinal cancer onset risk gradually increased with age, the period effect was fundamentally manifested as a downward trend in onset risk after 2000, and the cohort effect indicated the decreased onset risk of the overall birth cohort after 1926. The ASIR of upper gastrointestinal cancer in China from 1990 to 2019 showed a downward trend, and the onset risk indicated the age, period, and cohort effects.

S1563 ACE Inhibitor Use Is Associated With Angioectasias on Video Capsule Endoscopy (VCE) in Patients With Iron Deficiency Anemia

Introduction: Small bowel bleeding poses a clinical challenge in patients with vascular lesions. Bleeding recurrence after endoscopic therapy is high and medical therapies have limited efficacy. In those with left ventricular assist devices (LVADs), the use of angiotensin converting enzyme inhibitors (ACEi) has been associated with a reduced rate of gastrointestinal bleeding. Conversely, the antiplatelet effects of ACEi have been described thought due to their effects in decreasing platelet aggregation. Our aim was to determine whether ACEi or angiotensin receptor blocker (ARB) therapy had an impact on the rate of positive VCE small bowel findings in those with iron deficiency anemia (IDA). Methods: Data was collected from consecutive inpatient and outpatient VCE examinations performed between January 1, 2009 to March 1, 2018 at a single U.S. tertiary medical center performed for IDA. VCE studies were excluded in those with incomplete small bowel examinations (9) or technical failure (1). Patient demographics, laboratory values, medication use and endoscopic findings were recorded. VCE findings were based on the P0-P2 grading system. The primary outcome of interest was a positive (P2) VCE. Data were analyzed using Wilcoxon rank-sum test for continuous variables and Fischer’s exact test for dichotomous variables. Bivariate logistic regression was performed to identify independent factors predictive of positive VCE. Results: Eighty-two VCE were included in the final analysis. Median age was 67.6 (IQR: 57.1-75.5) years and 38 (46.3%) patients were male. Thirty-seven (45.1%) VCE examinations were positive with the most common finding of angiectasia in 21 (55.3%). Risk factors for positive VCE are listed in Table 1. In univariate analysis, ACEi therapy associated with both positive VCE (P=0.014) and the presence of angiectasia (P=0.021), whereas ARB therapy did not associate with positive VCE. ACEi findings remained significant in bivariate analysis after controlling for cardiac and pulmonary comorbidities. Conclusion: In this single center study the presence of ACEi use was associated with small bowel and/or stomach angiectasias on VCE in univariate analysis and when controlled for cardiac and pulmonary risk factors. Further studies are required to determine the mechanistic impact of ACEi on gastrointestinal bleeding risk such as the reduction in von Willebrand factor or factors that affect platelet aggregation. Table 1. - Univariate predictors of positive video capsule endoscopy in iron deficiency anemia Negative VCE (n = 45) Positive VCE (n =37) P-value Age, years, mean (SD) 63.6 (15.8) 68.6 (9.3) 0.303 Male sex, n (%) 21 (46.7) 17 (46) 1 White race, n (%) 22 (48.9) 20 (54.1) 0.223 Active smoking, n (%) 6 (14) 11 (29.7) 0.105 Outpatient location, n (%) 31 (68.9) 21 (56.8) 0.357 Chronic kidney disease, n (%) 10 (22.2) 13 (35.1) 0.224 Chronic liver disease, n (%) 3 (6.7) 4 (10.8) 0.696 Congestive heart failure, n (%) 10 (22.2) 13 (35.1) 0.224 Diabetes mellitus, n (%) 15 (33.3) 15 (40.5) 0.645 Cardiac valvular disease, n (%) 7 (15.6) 6 (16.2) 1 Coronary artery disease, n (%) 14 (31.1) 14 (37.8) 0.641 Cardiac arrhythmia, n (%) 10 (22.2) 18 (48.7) 0.019 Chronic lung disease, n (%) 10 (22.2) 13 (35.1) 0.224 Left ventricular assist device, n (%) 2 (4.4) 2 (5.4) 1 Blood transfusion in the preceding 4 weeks, n (%) 17 (37.8) 16 (43.2) 0.656 Aspirin, n (%) 20 (44.4) 14 (37.8) 0.654 Thienopyridine, n (%) 3 (6.7) 2 (5.4) 1 Coumadin, n (%) 1 (2.2) 5 (13.5) 0.086 SSRI/SNRI, n (%) 7 (15.6) 9 (24.3) 0.404 ACEi 7 (15.6) 15 (40.5) 0.014 ARB 9 (20) 7 (18.9) 1 Hemoglobin, g/dL1 9.9 (1.7) 9.2 (2.3) 0.216 Platelets, 109/L1 225.4 (67.5) 208.6 (84.9) 0.202 BUN, mg/dL1 21.9 (13.1) 26.7 (22) 0.869 Creatinine, mg/dL1 1.3 (0.5) 1.9 (1.5) 0.197 Ferritin, ng/mL,1 128 (259) 39.6 (28.7) 0.966 Percent saturation, %1 14.8 (15.1) 13.7 (15.4) 0.76

Predominant contribution of the dose received from constituent heavy-ions in the induction of gastrointestinal tumorigenesis after simulated space radiation exposure.

Gastrointestinal (GI) cancer risk among astronauts after encountering galactic cosmic radiation (GCR) is predicted to exceed safe permissible limits in long duration deep-space missions. Current predictions are based on relative biological effectiveness (RBE) values derived from in-vivo studies using single-ion beams, while GCR is essentially a mixed radiation field composed of protons (H), helium (He), and heavy ions. Therefore, a sequentially delivered proton (H) → Helium (He) → Oxygen (O) → Silicon (Si) beam was designed to simulate simplified-mixed-field GCR (Smf-GCR), and Apc1638N/+ mice were total-body irradiated to sham or γ (157Cs) or Smf-GCR followed by assessment of GI-tumorigenesis at 150days post-exposure. Further, GI-tumor data from equivalent doses of heavy-ions (i.e., 0.05Gy of O and Si) in 0.5Gy of Smf-GCR were compared to understand the contributions of heavy-ions in GI-tumorigenesis. The Smf-GCR-induced tumor and carcinoma count were significantly greater than γ-rays, and male preponderance for GI-tumorigenesis was consistent with our earlier findings. Comparison of tumor data from Smf-GCR and equivalent doses of heavy ions revealed an association between higher GI-tumorigenesis where dose received from heavy-ions contributed to > 95% of the total GI-tumorigenic effect observed after Smf-GCR. This study provides the first experimental evidence that cancer risk after GCR exposure could largely depend on doses received from constituent heavy-ions.

Effects of Probiotics Supplementation on Risk and Severity of Infections in Athletes: A Systematic Review.

The aim of this review was to appraise the literature on the effects of probiotics supplementation on gastrointestinal (GI) and upper respiratory tract infection (URTI) risk and prognosis in athletes. The search was conducted using the following electronic databases: MEDLINE (PubMed); Web of Science; Scopus; and SPORTDiscus (EBSCO). According to the PRISMA guidelines, randomized controlled studies performed on healthy athletes with a note dose of probiotics supplementation were considered. From the 2304 articles found, after eliminating reviews and studies on animals and unhealthy subjects and after screening of titles and abstracts, 403 studies were considered eligible. From these, in accordance with the inclusion and exclusion criteria, 16 studies were selected, ten of which concerned endurance athletes. The majority of the studies reported beneficial effects of probiotics in reducing the risk of developing the examined infections or the severity of related symptoms. However, due to the differences in formulations used and populations analyzed in the available studies, further research is needed in this field to achieve stronger and more specific evidence.

Twice- or once-daily dosing of direct oral anticoagulants and gastrointestinal bleeding in patient with atrial fibrillation

AimsDirect oral anticoagulant (DOAC) is widely used for the prevention of embolic stroke in non-valvular atrial fibrillation (NVAF) patients. However, the gastrointestinal bleeding risk in several DOAC regimens was higher than warfarin, especially in once-daily regimens. Methods and resultsWe conducted a single-center prospective registry of patients with NVAF treated with DOACs: the DIRECT registry (N = 2216; follow-up duration 650 [IQR 103–1574] days, UMIN000033283). All patients were divided into 2 groups: the twice-daily (BID) regimen group (dabigatran and apixaban) versus the once-daily (QD) regimen group (rivaroxaban and edoxaban). Out of 2216 patients, we successfully matched 904 patients in the QD group and 904 patients in the BID group using propensity score. The primary endpoint was gastrointestinal bleeding defined as any bleeding in the gastrointestinal tract that was identified through medical records regardless of bleeding site or severity. The BID group showed a significantly lower gastrointestinal bleeding rate than the QD group (3.5/100 person-year vs. 6.2/100 person-year, log-rank P < 0.0001). The secondary endpoints were all death, stroke, major bleeding, and any bleeding. The rate of major bleeding was significantly lower in patients with BID regimen group (log-rank P = 0.040). In contrast, all death, stroke, and any bleeding did not differ between both groups (log-rank P = 0.280, 0.520 and 0.066, respectively). ConclusionsThe BID regimen as compared with the QD regimen was associated with reduced risk of gastrointestinal bleeding.

Tracking gastrointestinal nematode risk on cattle farms through pasture contamination mapping

Gastrointestinal nematode (GIN) parasites in grazing cattle are a major cause of production loss and their control is increasingly difficult due to anthelmintic resistance and climate change. Rotational grazing can support control and decrease reliance on chemical intervention, but is often complex due to the need to track grazing periods and infection levels, and the effect of weather on larval availability. In this paper, a simulation model was developed to predict the availability of infective larvae of the bovine GIN, Ostertagia ostertagi, at the level of individual pastures. The model was applied within a complex rotational grazing system and successfully reproduced observed variation in larval density between fields and over time. Four groups of cattle in their second grazing season (n = 44) were followed throughout the temperate grazing season with regular assessment of GIN faecal egg counts, which were dominated by O. ostertagi, animal weight and recording of field rotations. Each group of cattle was rotationally grazed on six group-specific fields throughout the 2019 grazing season. Maps and calendars were produced to illustrate the change in pasture infectivity (density of L3 on herbage) across the 24 separate grazing fields. Simulations predicted differences in pasture contamination levels in relation to the timing of grazing and the return period. A proportion of L3 was predicted to persist on herbage over winter, declining to similar intensities across fields before the start of the following grazing season, irrespective of contamination levels in the previous year. Model predictions showed good agreement with pasture larval counts. The model also simulated differences in seasonal pasture infectivity under rotational grazing in systems that differed in temperature and rainfall profiles. Further application could support individual farm decisions on evasive grazing and refugia management, and improved regional evaluation of optimal grazing strategies for parasite control. The integration of weather and livestock movement is inherent to the model, and facilitates consideration of climate change adaptation through improved disease control.

Age Modifies Intracranial and Gastrointestinal Bleeding Risk from P2Y12 Inhibitors in Patients Receiving Dialysis.

Individuals aged ≥75 years are the fastest-growing population starting dialysis for end-stage kidney disease (ESKD) due to living longer with coronary artery disease. ESKD alone can increase bleeding risk, but P2Y12 inhibitor (P2Y12-I) antiplatelet medications prescribed for cardiovascular treatment can exacerbate this risk in patients with ESKD. The age-specific rates of bleeding complications in dialysis patients with ESKD on P2Y12-I remain unclear, as does how age modifies the bleeding risk from P2Y12-I use in these patients. In a retrospective cohort study, we collected data on 40,972 patients receiving maintenance hemo- or peritoneal dialysis who were newly prescribed P2Y12-I therapy between 2011 and 2015 from the USRDS registry. We analyzed the effect of age on the time to first bleed and the interactions between age and P2Y12-I type on modifying the effects of a bleed. Twenty percent of the cohort were aged ≥75 years. There were 3096 (8%) gastrointestinal (GI) and 1298 (3%) intracranial (IC) bleeding events during a median follow-up of 1 year. Annual incidence rates for IC bleeds were 2% in those aged <55 years and 3% in those aged ≥75 years. Rates for GI bleeds were 4% in those aged <55 years and 9% in those aged ≥75 years. On clopidogrel, prasugrel, and ticagrelor, for every decade increase in age of the cohort members, the risk of IC bleed increased by 9%, 55%, and 59%, and the risk of GI bleed increased by 21%, 28%, and 39%, respectively. At age ≥75 years, prasugrel was associated with a greater risk of IC bleed than clopidogrel. At age ≥60 years, ticagrelor was associated with a greater risk of GI bleed than clopidogrel. More potent P2Y12-Is (prasugrel and ticagrelor) were associated with a disproportionately higher risk of IC bleed with increasing age compared with that of clopidogrel-prasugrel was much worse than clopidogrel at age ≥75 years. All three drugs were associated with only modest increase in the risk of GI bleed with every decade increase in age-ticagrelor was much worse than clopidogrel at ≥60 years of age. These results highlight the need for head-to-head clinical trials for the use of P2Y12-Is in patients with ESKD to determine age cutoffs where the risk of bleeding outweighs the benefits of thrombosis prevention.

Association of Diet, Body Mass Index, and Lifestyle on the Gastrointestinal Health Risk in a Sample of Adults.

Gastrointestinal functional disorders are characterized by abnormalities in motility with visceral hypersensitivity, representing a global public health problem. We aimed to determine whether eating habits, lifestyle characteristics, and body mass index (BMI) are associated with gastrointestinal health risk. The Gastrointestinal Health (GIH) test of the World Gastroenterology Organization (WGO) and the Roma IV criteria were applied. We obtained information on food consumption habits and aerobic exercise, among other variables. Not exercising regularly, drinking water and eating vegetables less than recommended, having high body weight, and taking symptomatic medication were variables that explained 73% of the probabilities of not having good GIH (R2 = 0.734). According to Rome IV criteria, women had a 50% higher risk than men of having functional bowel disorder (RR 1.6, 95% CI: 1.04, 2.45). Among the men studied, eating few or no vegetables and drinking less than 1 L of water daily was more frequent; however, the women had significantly more intestinal symptoms. In addition, constipation was higher among women than men (p = 0.020). All of the above explains the prognostic value of eating habits and the importance of paying attention to body weight to reduce the risk of gastrointestinal disease.

A new model to predict the risk of major gastrointestinal bleeding in patients on direct oral anticoagulants (dabigatran and rivaroxaban).

The aim of this study was to identify factors associated with gastrointestinal bleeding (GIB) in patients on direct oral anticoagulants (DOACs) and develop a risk score that would provide an effective tool for the clinical assessment of GIB. This was a multicentre retrospective analysis of clinical and follow-up data of patients treated with DOACs. The score was developed through logistic regression. The performance of score was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity and Hosmer-Lemeshow test. The 11 903 patients had a mean age of 65.1years. In multivariate analysis, age ≥65 years, alcohol use, history of peptic ulcer, history of major bleeding, abnormal liver function or renal function, cancer, platelet count <100 × 109 /L, anaemia, and concurrent antiplatelet agent or non-steroidal anti-inflammatory drug treatment were independent risk factors for GIB, and concurrent treatment with gastrointestinal protective agents were a protective factor. The Alfalfa-DOAC-GIB score was constructed using these 12 factors. The AUC of the Alfalfa-DOAC-GIB score was 0.77 (95% CI 0.74-0.81), which was higher than that of the HAS-BLED score (0.69; 95% CI 0.65-0.72) and the New score (0.65; 95% CI 0.61-0.68). Based on 12 factors, we developed a gastrointestinal bleeding risk score. The newly developed Alfalfa-DOAC-GIB score has better predictive value than the HAS-BLED score and the New score, and might be an effective tool to help reduce the occurrence of GIB in patients using DOACs.

Proton Pump Inhibitor Use and Associated Infectious Complications in the PICU: Propensity Score Matching Analysis.

We aimed to evaluate the association between proton pump inhibitor (PPI) exposure and nosocomial infection (NI) during PICU stay. Propensity score matched analysis of a single-center retrospective cohort from January 1, 2017, to December 31, 2018. Tertiary medical and surgical PICU in France. Patients younger than 18 years old, admitted to the PICU with a stay greater than 48 hours. Patients were retrospectively allocated into two groups and compared depending on whether they received a PPI or not. Seven-hundred fifty-four patients were included of which 231 received a PPI (31%). PPIs were mostly used for stress ulcer prophylaxis (174/231; 75%), but upper gastrointestinal bleed risk factors were rarely present (18%). In the unadjusted analyses, the rate of NI was 8% in the PPI exposed group versus 2% in the nonexposed group. After propensity score matching ( n = 184 per group), we failed to identify an association between PPI exposure and greater odds of NI (adjusted odds ratio 2.9 [95% CI, 0.9-9.3]; p = 0.082). However, these data have not excluded the possibility that there is up to nine-fold greater odds of NI. This study highlights the prevalent use of PPIs in the PICU, and the potential association between PPIs and nine-fold greater odds of NI is not excluded.

Gastrointestinal manifestations, risk factors, and management in patients with post-transplant lymphoproliferative disorder: A systematic review.

BACKGROUNDPatients with a history of solid organ transplantation (SOT) or hematopoietic stem cell transplantation (HSCT) are at an increased risk of developing post-transplant lymphoproliferative disorder (PTLD). The gastrointestinal (GI) tract is commonly affected as it has an abundance of B and T cells.AIMTo determine typical GI-manifestations, risk factors for developing PTLD, and management.METHODSMajor databases were searched until November 2021.RESULTSNon-case report studies that described GI manifestations of PTLD, risk factors for developing PTLD, and management of PTLD were included. Nine articles written within the last 20 years were included in the review. All articles found that patients with a history of SOT, regardless of transplanted organ, have a propensity to develop GI-PTLD.CONCLUSIONGI tract manifestations may be nonspecific; therefore, consideration of risk factors is crucial for identifying GI-PTLD. Like other lymphoma variants, PTLD is very aggressive making early diagnosis key to prognosis. Initial treatment is reduction of immunosuppression which is effective in more than 50% of cases; however, additional therapy including rituximab, chemotherapy, and surgery may also be required.

Stress ulcer prophylaxis in critically ill adult patients with sepsis at risk of gastrointestinal bleeding: a retrospective cohort study.

The Surviving Sepsis Campaign Guidelines recommend stress ulcer prophylaxis (SUP) for patients with sepsis who have gastrointestinal (GI) bleeding risks; however, the effect of SUP has not been specially studied in these patients. To determine the effects of SUP versus no prophylaxis on patient-important outcomes in critically ill adult patients with sepsis who have risk factors for GI bleeding. This retrospective cohort study utilised data from the Medical Information Mart for Intensive Care III database. We compared those who received SUP with proton-pump inhibitors or histamine-2 receptor antagonists for ≥3 days with those who received no prophylaxis. Propensity score matching (PSM) was conducted to make comparisons between groups with similar distributions of study variables. The primary outcome was inhospital mortality. A total of 7744 patients were included in the analysis, with 1088 (14.0%) in the non-SUP group and 6656 (86.0%) in the SUP group. A 1:1 PSM created 866 patients in each cohort. No significant differences were noted between the two groups with regard to inhospital mortality (22.3% vs 20.4%; P = 0.379), GI bleeding (4.7% vs 6.4%; P = 0.172), pneumonia (38.9% vs 36.6%; P = 0.346), Clostridium difficile infection (CDI) (6.4% vs 8.9%; P = 0.0.057) or intensive care unit (ICU) length of stay (LOS) (4.2 days vs 4.6 days; P = 0.394). Among critically ill, septic, adult patients at risk for GI bleeding, SUP showed no effect on hospital mortality, the rate of GI bleeding, pneumonia, CDI and ICU LOS.

Penetrating complications of bevacizumab-containing chemotherapy in previously-irradiated recurrent cervical cancer: a Korean multicenter retrospective study of the Gynecologic Oncology Research Investigators coLLaborAtion (GORILLA) group (GORILLA1001) (036)

<b>Objectives:</b> Gynecologic Oncology Group 240 study showed that incorporating bevacizumab in the treatment of recurrent, persistent, or metastatic cervical cancer conferred overall survival (OS) benefit. However, fistula occurred significantly higher in the bevacizumab (+) group than the chemotherapy alone group. Moreover, all fistulas in the bevacizumab (+) group were developed in patients who were previously irradiated. This study aimed to evaluate the incidence and to identify risk factors for penetrating complications, including gastrointestinal (GI) and genitourinary (GU) fistula/perforation, of bevacizumab plus chemotherapy in recurrent cervical cancer patients who underwent pelvic radiation therapy (RT). <b>Methods:</b> Medical records of the patients with recurrent cervical cancer who previously underwent pelvic radiation at five university hospitals in Korea from 2007 to 2020 were retrospectively reviewed. Women who received chemotherapy immediately after RT were excluded. Clinical-pathologic factors were compared between groups of the following two settings: <i>1)</i> fistula/perforation (+) and (-); <i>2)</i> bevacizumab plus chemotherapy and chemotherapy alone. Univariate and multivariate regression analyses were performed to identify risk factors for penetrating complications. OS was also compared between groups of the two comparisons. <b>Results:</b> Of 219 women with recurrent cervical cancer who previously underwent pelvic RT, 144 (65.8%) received bevacizumab-containing chemotherapy, and 75 (34.2%) received chemotherapy alone. Fistula/perforation of any grade occurred in 36 (16.4%): fistulas alone in 27 (11 GI, 8 GU, and 8 both) and perforations in nine patients. Women receiving bevacizumab experienced fistula/perforation more frequently than those who used chemotherapy alone (20.8% [30/144] vs 8.0% [6/75]; p=0.015) (Table 1). Multivariate regression analysis showed that bevacizumab administration was the only independent risk factor for the occurrence of fistula/perforation. Age, diabetes, hypertension, tumor histology (squamous vs non-squamous), cumulative dose of RT, primary treatment (operation vs. RT vs both), use of intensity-modulated RT, and the time interval between RT and bevacizumab failed to show association with fistula/perforation. During median follow-up of 33.7 months (1.2-185.6 months), significant OS difference was shown neither between bevacizumab (+) versus bevacizumab (-) (HR: 1.03; median 119.8 months [95% CI: 97.3-142.3months] vs 115.7 months [96.0-135.4 months]; p=0.928) nor between fistula/perforation (+) versus fistula/perforation (-) (HR: 1.78; median 84.2 months [59.3-109.0 months] vs 129.5 months [114.1-144.9 months]; p=0.065). <b>Conclusions:</b> The study results suggest that incorporating bevacizumab in the chemotherapy regimen to treat recurrent cervical cancer with a previous history of pelvic RT incurs a considerable risk of GI and/or GU penetrating complications, which might damage the survival outcome as well as the quality of life. The risk and benefit of incorporating bevacizumab in the treatment of previously irradiated recurrent cervical cancer patients are needed to be carefully weighed, considering that effective prevention of the penetrating complications is difficult because of the lack of knowledge regarding other risk factors.

Modern anticoagulation with factor Xa inhibitors in oncology: is the gastrointestinal bleeding rate (also) decisive?

The increased risk of thrombosis and bleeding with an active tumor disease is known as the so-called "thrombo-hemorrhagic syndrome", which places high demands on anticoagulation. There are currently 4 randomized, prospective studies on the use of new, non-vitamin K dependent oral anticoagulants (NOAC) for the treatment of venous thromboembolism (VTE) that have occurred in oncology. The FXa inhibitors rivaroxaban, edoxaban and twice apixaban were each used in individual studies versus the standard therapeutic agent dalteparin. Since there is no direct head-to-head comparison of the FXa inhibitors mentioned within a study, the largest study - always compared to dalteparin - was evaluated for each NOAC. The studies were analyzed with regard to their effectiveness, safety, fatal bleeding rates, the risk of gastrointestinal bleeding (GIB) and other differences using descriptive statistics. With dalteparin, the mean VTE recurrence rate was approximately 9% over a 6-month treatment period. All three FXa inhibitors were not inferior to dalteparin in terms of potency. The VTE recurrence rate was - 2.3% lower in edoxaban and apixaban-treated patients and - 5.0% in rivaroxaban-treated patients. In terms of safety, there was an increased rate of severe bleeding (both + 2.4%) for rivaroxaban and edoxaban compared to dalteparin; in particular, the number of GIBs was significantly increased. In contrast, the number of severe bleeding was not increased for apixaban, as was the case for various bleeding types including GIB. In the Apixaban study, the overall rate of severe GIB, which accounted for about 50% of all severe bleeding, and that of clinically relevant non-severe bleeding, were the lowest. The FXa inhibitors are not inferior to the standard therapy with dalteparin in the VTE recurrence rate in oncological patients. The GIB rate appears to be an important predictive factor for the safety of this group of substances, so that tumor location, gastrointestinal risk factors and other individual criteria should be given greater consideration in future therapy decisions for or against an FXa inhibitor.

Vascular and lymphatic regulation of gastrointestinal function and disease risk

The vascular and lymphatic systems in the gut regulate lipid transport while restricting transfer of commensal gut microbiota and directing immune cell trafficking. Increased permeability of the endothelial systems in the intestine associates with passage of antigens and microbiota from the gut into the bloodstream leading to tissue inflammation, the release of pro-inflammatory mediators and ultimately to abnormalities of systemic metabolism. Recent studies show that lipid metabolism maintains homeostasis and function of intestinal blood and lymphatic endothelial cells, BECs and LECs, respectively. This review highlights recent progress in this area, and information related to the contribution of the lipid transporter CD36, abundant in BECs and LECs, to gastrointestinal barrier integrity, inflammation, and to gut regulation of whole body metabolism. The potential role of endothelial lipid delivery in epithelial tissue renewal after injury and consequently in the risk of gastric and intestinal diseases is also discussed.

Association of Plasma Iron Status with Subsequent Risk of Total and Site-Specific Cancer: A Large Case-Cohort Study within JPHC Study.

High ferritin and low hepcidin levels in the plasma were associated with increased liver cancer risk. Evaluating iron metabolism including hepcidin levels may help identify people with high liver cancer risk.

Pharmacotherapy for Spine-Related Pain in Older Adults.

As the population ages, spine-related pain is increasingly common in older adults. While medications play an important role in pain management, their use has limitations in geriatric patients due to reduced liver and renal function, comorbid medical problems, and polypharmacy. This review will assess the evidence basis for medications used for spine-related pain in older adults, with a focus on drug metabolism and adverse drug reactions. A PubMed/OVID search crossing common spine, neck, and back pain terms with key words for older adults and geriatrics was combined with common drug classes and common drug names and limited to clinical trials and age over 65years. The results were then reviewed with identification of commonly used drugs and drug categories: nonsteroidal anti-inflammatories (NSAIDs), acetaminophen, corticosteroids, gabapentin and pregabalin, antispastic and antispasmodic muscle relaxants, tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tramadol, and opioids. Collectively, 138 double-blind, placebo-controlled trials were the focus of the review. The review found a variable contribution of high-quality studies examining the efficacy of medications for spine pain primarily in the geriatric population. There was strong evidence for NSAID use with adjustments for gastrointestinal and renal risk factors. Gabapentin and pregabalin had mixed evidence for neuropathic pain. SNRIs had good evidence for neuropathic pain and a more favorable safety profile than TCAs. Tramadol had some evidence in older patients, but more so in persons aged <65years. Rational therapeutic choices based on geriatric spine pain diagnosis are helpful, such as NSAIDs and acetaminophen for arthritic and myofascial-based pain, gabapentinoids or duloxetine for neuropathic and radicular pain, antispastic agents for myofascial-based pain, and combination therapy for mixed etiologies. Tramadol can be well tolerated in older patients, but has risks of cognitive and classic opioid side effects. Otherwise, opioids are typically avoided in the treatment of spine-related pain in older adults due to their morbidity and mortality risk and are reserved for refractory severe pain. Whenever possible, beneficial geriatric spine pain pharmacotherapy should employ the lowest therapeutic doses with consideration of polypharmacy, potentially decreased renal and hepatic metabolism, and co-morbid medical disorders.

Genetic risk, metabolic syndrome, and gastrointestinal cancer risk: A prospective cohort study.

Gastrointestinal (GI) cancer risk has been associated with metabolic syndrome (MetS), a surrogate indicator for unhealthy lifestyles, and a number of genetic loci, but the combined effect of MetS and genetic variants on GI cancer risk is uncertain. We included 430,036 participants with available MetS and genotype data from UK Biobank. During the follow-up time, 5494 incident GI cancer cases, including esophageal cancer, gastric cancer, and colorectal cancer, were identified. We created a GI polygenic risk score (GI-PRS) for overall GI cancer derived from three site-specific cancer PRSs. Cox proportional hazards regression was used to estimate the associations of MetS and GI-PRS with the risk of GI cancer. MetS was significantly associated with 28% increment in GI cancer risk (hazard ratio [HR]MetS vs. non-MetS : 1.28, 95% confidence interval [CI]: 1.21-1.35, p < 0.0001), whereas a high GI-PRS (top quintile) was associated with 2.28-fold increase in risk (HRhigh vs. low : 2.28, 95% CI: 2.09-2.49, p < 0.0001). Compared with participants without MetS and at low genetic risk (bottom quintile of GI-PRS), those with MetS and at high genetic risk had 2.75-fold increase in GI cancer risk (HR: 2.75, 95% CI: 2.43-3.12, p < 0.0001). Additionally, MetS in comparison with no MetS had 1.49‰, 2.75‰, and 3.37‰ absolute risk increases in 5 years among participants at low, intermediate (quintiles 2-4 of GI-PRS) and high genetic risk, respectively, representing the number of subjects diagnosed as MetS causing a new GI cancer case in 5 years were 669, 364, and 296, respectively. Metabolic and genetic factors may jointly contribute to GI cancer risk and may serve as predictors by quantitative measurements to identify high-risk populations of GI cancer for precise prevention.

Preventive strategies for feeding intolerance among patients with severe traumatic brain injury: A cross-sectional survey

ObjectivesThis study aimed to investigate the application status of preventive measures for feeding intolerance in patients with severe traumatic brain injury (STBI) in China and analysis the differences and their causes. MethodsA cross-sectional survey was conducted. From December 2019 to January 2020, ICU nurses and physicians of 89 hospitals in China were surveyed by using a questionnaire on preventive strategies for feeding intolerance in patients with STBI. The questionnaire included two parts: the general information of participants (10 items) and application of preventive measures for feeding intolerance in STBI patients (18 items). ResultsTotally 996 nurses and physicians completed the questionnaire. Among various methods, gastrointestinal symptoms(85.0%) and injury severity (71.4%) were mostly used to assess gastrointestinal functions and risk of feeding intolerance among STBI patients, respectively. Initiating enteral nutrition (EN) within 24–48 h (61.5%), nasogastric tubes (91.2%), 30°–45° of head-of-bed elevation (89.5%), continuous feeding by pump (72.9%), EN solution temperature of 38–40 °C (65.5%), <500 ml initial volume of EN solution (50.0%), monitoring gastric residual volume with a syringe (93.7%), and assessing gastric residual volume every 4 h (51.5%) were mostly applied for EN delivery among STBI patients. Prokinetic agents (73.3%), enema (73.6%), probiotics (79.0%), antacid agents (84.1%), and non-nutritional preparations as initial EN formula (65.6%) were commonly used for preventing feeding intolerance among STBI patients. ConclusionsThe survey showed that nurses and clinicians in China have a positive attitude towards preventive strategies for feeding intolerance. However, some effective new technologies and methods have not been timely applied in clinical practice. We suggest that managers, researchers, clinicians, nurses, and other health professionals should collaborate to explore effective and standard preventive strategies for feeding intolerance among patients with STBI.