Adverse Gastrointestinal Research Articles

Risk of Serious Adverse Gastrointestinal Events with Potassium Binders in Hospitalized Patients: A National Study.

Concerns about serious adverse gastrointestinal (GI) events with sodium polystyrene sulfonate (SPS) led to development of two new potassium binders, patiromer and sodium zirconium cyclosilicate (SZC), for treatment of hyperkalemia. To compare risk of intestinal ischemia/thrombosis or other serious GI events associated with SPS, patiromer, or SZC in hospitalized patients. Retrospective cohort study. National sample of 3,144,960 veterans hospitalized 2016-2022 in the U.S. Department of Veterans Affairs Healthcare System. Demographics, comorbidities, medications and outcomes were ascertained from the VA Corporate Data Warehouse. Exposures were SPS, patiromer, SZC. Outcomes were 30-day intestinal ischemia/thrombosis, and a composite of intestinal ischemia/thrombosis, peptic ulcer/perforation or bowel resection/ostomy. Potassium binders were used during 39,270 (1.3%) hospitalizations: SPS = 30,040 (1.0%), patiromer = 3,750 (0.1%), and SZC = 5,520 (0.2%). Intestinal ischemia/thrombosis occurred with 106/30,040 (0.4%) SPS, 12/3750 (0.3%) patiromer and 24/5520 (0.4%) SZC, vs. 6998/3,105,650 (0.2%) without potassium binder. Adjusted odds ratios (aOR) were 1.40 [95% CI, 1.16 to 1.69] with SPS, 1.36 [CI, 0.79 to 2.36] with patiromer, and 1.78 [CI, 1.21 to 2.63] with SZC exposures. Composite GI adverse events occurred with 754/30,040 (2.5%) SPS, 96/3750 (2.6%) patiromer, 2.6% SZC, vs. 144/5520 (2.4%) without binder; aOR were 1.00 [CI, 0.94 to 1.08] with SPS, 1.08 [CI, 0.89 to 1.32] with patiromer, and 1.08 [CI, 0.93 to 1.27] with SZC exposures. No statistical difference in intestinal ischemia/thrombosis between each new agent and SPS was seen (p = 0.274 for SPS vs. SZC; p = 0.916 for SPS vs. patiromer). Risk of intestinal ischemia/thrombosis or other serious adverse GI events was low and did not differ across three potassium-binding drugs.

Enteral Feedings Do Not Increase the Risk of NEC in ELBW Infants Undergoing Treatment of Patent Ductus Arteriosus With Acetaminophen.

Acetaminophen (APAP) is an alternative to indomethacin and ibuprofen for treatment of patent ductus arteriosus (PDA). The side effect profile of non-steroidal anti-inflammatory drugs (NSAIDs) presents enteral feeding safety concerns; however, the safety of enteral feeding on APAP is largely unknown. Optimal feeding strategies during pharmacological PDA treatment are unknown, leading to practice variation. This study aims to assess the incidence of adverse gastrointestinal (GI) outcomes in neonates treated with APAP for PDA closure while receiving enteral feedings. Single-center retrospective cohort study of 59 extremely low birth weight (ELBW), premature neonates who received APAP for PDA treatment divided into Low Volume (LV; ≤ 20 mL/kg/day) and High Volume (HV; > 20 mL/kg/day) enteral feeding groups. The primary outcome was the incidence of any suspected or confirmed necrotizing enterocolitis (NEC). Timing of nutrition milestones, parenteral nutrition (PN) days, and adverse outcomes (feeding intolerance, liver dysfunction, death prior to discharge) were evaluated. The incidence of suspected or confirmed NEC was 19.5% in the LV group and 13.3% in the HV group (p = 0.593). The HV group reached full feeds 6 days sooner (18 vs 24 days, p = 0.024) and had fewer PN days (17 vs 23.5 days, p = 0.044) with no difference in adverse outcomes. Provision of > 20 mL/kg/day of enteral feeds during APAP treatment of PDA decreased time to full feeds and PN days compared to trophic feedings (≤ 20 mL/kg/day) with no difference in adverse GI outcomes. Continuing enteral feeding during APAP PDA treatment appears safe while improving achievement of nutritional milestones.

PMAT variant rs3889348 is associated with metformin-induced gastrointestinal among Chinese Type 2 diabetes patients.

Aim: This study examined intronic gene variants for their association with metformin intolerance in a Chinese population, focusing on the plasma monoamine transporter (PMAT) cis-protein expression quantitative trait loci (cis-eQTL) variant rs3889348. Methods: We recruited Type 2 diabetes patients from two hospitals and identified 111 metformin-intolerant patients using a questionnaire, and selected 206 metformin-tolerant patients from 2180 Type 2 diabetes mellitus patients. Genetic testing revealed an association between adverse gastrointestinal (GI) effects and SLC22A1 and PMAT. Results: The single-nucleotide polymorphism rs3889348 is associated with metformin-induced adverse GI effects. Each additional copy of the G allele increases the score by 5.23 (95% CI: 1.82-8.64; p=0.003). Patients taking more transporter inhibitors were more likely to respond to metformin-induced GIintolerance (p=0.042). Conclusion: PMAT cis-eQTL rs3889348 was significantly associated with metformin-induced adverse GI effects.

Clinical outcomes of intravenous iron therapy in patients with heart failure and iron deficiency: Meta-analysis and trial sequential analysis of randomized clinical trials

BackgroundIron deficiency in patients with heart failure (HF) is underdiagnosed and undertreated. The role of intravenous (IV) iron is well-established to improve quality of life measures. Emerging evidence also supports its role in preventing cardiovascular events in patients with HF. MethodologyWe conducted a literature search of multiple electronic databases. Randomized controlled trials that compared IV iron to usual care among patients with HF and reported cardiovascular (CV) outcomes were included. Primary outcome was the composite of first heart failure hospitalization (HFH) or CV death. Secondary outcomes included HFH (first or recurrent), CV death, all-cause mortality, hospitalization for any cause, gastrointestinal (GI) side effects, or any infection. We performed trial sequential and cumulative meta-analyses to evaluate the effect of IV iron on the primary endpoint, and on HFH. ResultsNine trials enrolling 3337 patients were included. Adding IV iron to usual care significantly reduced the risk of first HFH or CV death [risk ratio (RR) 0.84; 95 % confidence interval (CI) 0.75–0.93; I2 = 0 %; number needed to treat (NNT) 18], which was primarily driven by a reduction in the risk of HFH of 25 %. IV iron also reduced the risk of the composite of hospitalization for any cause or death (RR 0.92; 95 % CI 0.85–0.99; I2 = 0 %; NNT 19). There was no significant difference in the risk of CV death, all-cause mortality, adverse GI events, or any infection among patients receiving IV iron compared to usual care. The observed benefits of IV iron were directionally consistent across trials and crossed both the statistical and trial sequential boundaries of benefit. ConclusionIn patients with HF and iron deficiency, the addition of IV iron to usual care reduces the risk of HFH without affecting the risk of CV or all-cause mortality.

Liraglutide in adolescents with simple obesity and gastrointestinal comorbidities: treatment experience

BACKGROUND: Liraglutide was approved for treatment of obesity in children and adolescents since 12 years. Due to gastrointestinal (GI) side effects not all patients reach maximal dose; this can affect the efficacy of obesity treatment.AIM: To study efficacy and tolerability of liraglutide in adolescents with obesity.MATERIALS AND METHODS: We analyzed medical data of adolescents with simple obesity and GI comorbidities before and in 3 months after start of liraglutide (BMI SDS; obesity complications; liraglutide side effects, and maximal doses), duration of therapy, reasons for discontinuation, and BMI SDS in 3–6 months after discontinuation.RESULTS: Liraglutide was administered for 10 adolescents (7 girls, 3 boys) 15.4 (13.5; 16.2) years with BMI SDS 3.3 (2.9; 3.7). Three months of treatment led to significant (p=0.001) decrease of BMI SDS till 2.8 (2.6; 3.5). Maximal dose of liraglutide was 3.0 mg (6 patients), 2.4 mg (2), 1.8 mg (1), and 1.2 mg (1). No correlation between maximal dose and BMI ΔSDS was detected. While dose titration patients complained of nausea (9), diarrhea (3), obstipation (1), and flatulence (1). In majority of cases complains were not dose-dependent. Only in 1 patient nausea and diarrhea that did not allow to increase liraglutide dose above 1.2 mg; additional investigation after discontinuation of therapy revealed GI infection.Therapy was discontinued in 3 months by 2 patients (1 — side effects, 1 — satisfactory result), in 4–5 months by 3 patients (1 — relapse of excessive weight gain, 2 — financial reasons), in 6 months by 1 patient (satisfactory result); 4 continued therapies. In 3–6 months after discontinuation of therapy BMI SDS increased and did not significantly differ from basal.CONCLUSION: Liraglutide is effective for treatment of obesity in adolescents and well tolerated by majority of patients. In case of pronounced adverse events additional GI investigation is recommended. Patients can discontinue treatment not only due to side effects, but also when they achieve their goal, and due to financial reasons.

Blenderized food tube feeding in very young pediatric patients with special healthcare needs.

Up to 85% of children with severe developmental disabilities have feeding disorders and require enteral tube feeding. Many caregivers desire blenderized tube feeding (BTF) instead of commercial formula (CF) for their child, citing a desire for a more physiologic feeding, to reduce gastrointestinal (GI) symptoms and/or promote oral intake. In this retrospective, single-center study, medical records (n = 34) of very young children (aged ≤36 months) with severe developmental disabilities were reviewed. Comparisons of growth parameters, GI symptoms, oral feeding, and GI medication use were made between the initial introduction of BTF and again at the last patient encounter when the children aged out of the program. Of the 34 charts reviewed (16 male and 18 female patients), comparisons between baseline BTF introduction and the last patient encounter indicated reductions in adverse GI symptoms, significant GI medication reduction (P = 0.000), increased oral food intake, and nonsignificant improvements in growth parameters. These positive outcomes were realized whether children received full or partial BTF or type of BTF formulation. Consistent with similar research studies, transitioning very young children with significant special healthcare needs from CF to BTF resulted in improvement in GI symptoms, reduced need for GI medications, supported growth goals, and contributed to improved oral feeding.

Tyramine-induced gastrointestinal dysregulation is attenuated via estradiol associated mechanisms in a zebrafish larval model

Development of targeted therapeutics to alleviate gastrointestinal (GI) inflammation and its debilitating consequences are required. In this context, the trace aminergic system may link together sex, diet and inflammation. Utilising a zebrafish larval model of GI inflammation, the current study aimed to investigate mechanisms by which excess amounts of trace amines (TAs) may influence GI health. In addition, we probed the potential role of 17β-estradiol (E2) and its receptors, given the known female-predominance of many GI disorders. To assess GI functionality and integrity, live imaging techniques (neutral red staining) and post-mortem immunofluorescent staining of tight junction proteins (occludin and ZO-1) were analyzed respectively. In addition, behavioural assays, as an indication of overall wellbeing, as well as whole body H2O2 and prostaglandin E2 assays were performed to inform on oxidative and inflammatory status. Excess β-phenethylamine (PEA), tryptamine (TRP) and ρ-tyramine (TYR) resulted in adverse GI and systemic effects. In this regard, clear beneficial effects of E2 to modulate the effects of PEA, TRP and TYR was evident. Moreover, agmatine displayed potential protective effects on GI epithelium and whole body oxidative status, however, potential to induce systemic inflammation suggests the importance of dosage and administration optimisation. Taken together, TYR seems like the most prominent TA to have damaging GI effects, feasibly exacerbating GI inflammation. In this context, the relative lack of E2 may provide mechanistic insights into the reported female-predominance of GI disorders. Moreover, an effective therapeutic in this context may be required to maintain GI TA load despite fluctuating E2 levels.

Opioid-induced microbial dysbiosis disrupts irinotecan (CPT-11) metabolism and increases gastrointestinal toxicity in a murine model.

Opioids are commonly used for the management of cancer-associated pain and chemotherapy-induced diarrhoea. The chemotherapeutic irinotecan (CPT-11) causes severe gastrointestinal (GI) toxicity due to deconjugation of inactive metabolite SN-38 glucuronide (SN-38G) by bacterial β-glucuronidases to the active 7-ethyl-10-hydroxycamptothecin (SN-38). Opioids are known to cause gut microbial dysbiosis, this study evaluated whether CPT-11 anti-tumour efficacy and GI toxicity are exacerbated by opioid co-administration. Eight-week-old C57BL/6 male mice were co-administration with CPT-11 ± opioid. 16S rRNA sequencing was used for gut microbiome analysis. LC-MS analyses of plasma and intestinal extracts were performed to investigate the pharmacokinetic profile of CPT-11. Histological analysis and quantitative real-time polymerase chain reaction were used to determine the severity of intestinal tissue damage. Human liver microsome In vitro assay was performed to confirm the effects of opioids on CPT-11 metabolism. Gut microbiome analysis showed that morphine treatment induced enrichment of β-glucuronidase-producing bacteria in the intestines of CPT-11-treated mice, resulting in SN-38 accumulation and exacerbation of GI toxicity in the small intestine. Oral administration of both antibiotics and glucuronidase inhibitor protected mice against GI toxicity induced with CPT-11 and morphine co-administration, implicating a microbiome-dependent mechanism. Additionally, morphine and loperamide decreased the plasma concentration of SN-38 and compromised CPT-11 anti-tumour efficacy, this seemed to be microbiome independent. Gut microbiota play a significant role in opioid and chemotherapeutic agent drug-drug interactions. Inhibition of gut microbial glucuronidase may also prevent adverse GI effects of CPT-11 in patients on opioids.

Adverse Gastrointestinal Events With Sodium Polystyrene Sulfonate Use in Patients on Maintenance Hemodialysis: An International Cohort Study

Background: There are concerns regarding the gastrointestinal (GI) safety of sodium polystyrene sulfonate (SPS), a medication commonly used in the management of hyperkalemia. Objective: To compare the risk of GI adverse events among users versus non-users of SPS in patients on maintenance hemodialysis. Design: International prospective cohort study. Setting: Seventeen countries (Dialysis Outcomes and Practice Patterns Study [DOPPS] phase 2-6 from 2002 to 2018). Patients: 50 147 adults on maintenance hemodialysis. Measurements: An adverse GI event defined by a GI hospitalization or GI fatality with SPS prescription compared with no SPS prescription. Methods: Overlap propensity score–weighted Cox models. Results: Sodium polystyrene sulfonate prescription was present in 13.4% of patients and ranged from 0.42% (Turkey) to 20.6% (Sweden) with 12.5% use in Canada. A total of 935 (1.9%) adverse GI events (140 [2.1%] with SPS, 795 [1.9%] with no SPS; absolute risk difference 0.2%) occurred. The weighted hazard ratio (HR) of a GI event was not elevated with SPS use compared with non-use (HR = 0.93, 95% confidence interval = 0.83-1.6). The results were consistent when examining fatal GI events and/or GI hospitalization separately. Limitations: Sodium polystyrene sulfonate dose and duration were unknown. Conclusions: Sodium polystyrene sulfonate use in patients on hemodialysis was not associated with a higher risk of an adverse GI event. Our findings suggest that SPS use is safe in an international cohort of maintenance hemodialysis patients.

Predictors of Adverse Gastrointestinal Events After Stereotactic Body Radiation Therapy for Liver Tumors.

To identify predictors of adverse gastrointestinal (GI) events related to stereotactic body radiation therapy (SBRT) for liver tumors. We retrospectively analyzed 56 patients who underwent SBRT for liver tumors at our institution between 2016 and 2021. The α/β ratio of the GI tract (stomach, duodenum, and large intestine) was assumed to be 3 Gy in the Linear-Quadratic model (LQ model). The dose to the GI tract, that is, the biologically effective dose 3 (BED3) was converted to a 2 Gy equivalent dose (Gy2/3=2 Gy equivalent dose, α/β=3). Using this 2 Gy equivalent dose, predictors of adverse GI events of Grade 2 or higher were investigated. The median observation period was 10 months (0-40 months) and median age was 77 years (range=29-93 years). Forty-three of the 56 patients had hepatocellular carcinoma and the other 13 had metastatic liver tumors. Tumors were irradiated with 30-54 Gy/5-18 fractions of planning target volume D95% prescription (80% isodose). Eight of the 56 patients had Grade 2 or higher adverse GI events. By univariate analysis, GI D1cc, Dmax, V20, V25, V30, and V35 were all significant predictors of Grade 2 or higher adverse GI events. Among these, gastrointestinal V35 was the most significant predictor of Grade 2 or higher adverse GI events. For SBRT of liver tumors, GI V35 was the best predictor of Grade 2 or higher adverse GI events.

Life threatening gastrointestinal tract complications in a patient of rheumatoid arthritis. Is it drug or disease related?

Introduction: Gastrointestinal (GI) complications are very frequent and sometimes fatal in patients with Rheumatoid Arthritis (RA). Gastrointestinal perforation is a rare but serious event, most frequently involving the lower GIT, which has been observed in patients with RA.
 Case Presentation: We present here an Adverse Drug Reaction (ADR) which is small bowel ischemia with perforation in a 61-year-old RA patient, who was taking a tablet of Prednisolone and tablet Hydroxychloroquine.
 Discussion: Several studies indicated that RA patients may be at a higher risk of GI perforation. This could be attributed to the disease pathophysiology or the use of drugs for treatment like Glucocorticoids and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Rheumatologists must be vigilant for GI complications while prescribing anti-rheumatoid drugs.
 Conclusion: GI perforations are rare events in RA patients, but cause significant morbidity and mortality. Increasing age and other comorbid conditions also increase the risk of adverse GI events.

An extract of hops (Humulus lupulus L.) modulates gut peptide hormone secretion and reduces energy intake in healthy-weight men: a randomized, crossover clinical trial

Gastrointestinal enteroendocrine cells express chemosensory bitter taste receptors that may play an important role in regulating energy intake (EI) and gut function. To determine the effect of a bitter hop extract (Humulus lupulus L.) on acute EI, appetite, and hormonal responses. Nineteen healthy-weight men completed a randomized 3-treatment, double-blind, crossover study with a 1-wk washout between treatments. Treatments comprised either placebo or 500mg of hop extract administered in delayed-release capsules (duodenal) at 11:00h or quick-release capsules (gastric) at 11:30h. Ad libitum EI was recorded at the lunch (12:00h) and afternoon snack (14:00h), with blood samples taken and subjective ratings of appetite, gastrointestinal (GI) discomfort, vitality, meal palatability, and mood assessed throughout the day. Total ad libitum EI was reduced following both the gastric (4473kJ; 95% CI: 3811, 5134; P = 0.006) and duodenal (4439kJ; 95% CI: 3777, 5102; P = 0.004) hop treatments compared with the placebo (5383kJ; 95% CI: 4722, 6045). Gastric and duodenal treatments stimulated prelunch ghrelin secretion and postprandial cholecystokinin, glucagon-like peptide 1, and peptide YY responses compared with placebo. In contrast, postprandial insulin, glucose-dependent insulinotropic peptide, and pancreatic polypeptide responses were reduced in gastric and duodenal treatments without affecting glycemia. In addition, gastric and duodenal treatments produced small but significant increases in subjective measures of GI discomfort (e.g., nausea, bloating, abdominal discomfort) with mild to severe adverse GI symptoms reported in the gastric treatment only. However, no significant treatment effects were observed for any subjective measures of appetite or meal palatability. Both gastric and duodenal delivery of a hop extract modulates the release of hormones involved in appetite and glycemic regulation, providing a potential "bitter brake" on EI in healthy-weight men.

Colchicine may become a new cornerstone therapy for coronary artery disease: a meta-analysis of randomized controlled trials.

Colchicine is an ancient anti-inflammatory drug. In recent years, an increasing number of studies have shown that colchicine improves the prognosis of patients with coronary artery disease (CAD), while other studies have reported the opposite. The aim of this study was to evaluate the relative efficacy and safety of colchicine in treating CAD. PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were searched from inception to 20 October 2020 for randomized controlled trials (RCTs) comparing colchicine and placebo in patients with CAD. The primary outcomes were the primary composite outcomes of cardiovascular death, myocardial infarction (MI), ischemic stroke, or ischemia-driven coronary revascularization after colchicine administration. The secondary outcomes were cardiovascular death, death from any cause, noncardiac death, MI, ischemic stroke, coronary revascularization, gastrointestinal (GI) symptoms, and the different effects of colchicine in acute and chronic CAD. We assessed the pooled odds ratio (OR) of all-cause and cardiovascular mortality for CAD in fixed-effects models, the pooled risk ratio (RR) of the primary composite outcomes, MI, ischemic stroke, and ischemia-driven coronary revascularization in fixed-effects models and the pooled RR of GI symptoms in random-effects models. The Cochrane risk of bias tool was used to assess the risk of bias in the included RCTs. Eleven of the 894 identified studies (n = 12,899 patients) were included (6501 subjects in the colchicine group; 6389 subjects in the control group). The colchicine group had significantly lower pooled RRs of the primary composite outcomes (0.73, 95% confidence interval (CI) 0.64-0.84, P < 0.0001), MI (0.77, 95% CI 0.64-0.92, P = 0.004), ischemic stroke (0.47, 95% CI 0.30-0.76, P = 0.002), and ischemia-driven coronary revascularization (0.77, 95% CI 0.66-0.89, P = 0.0007), while the pooled RR of adverse GI events (2.15 95% CI 1.40-3.31, P = 0.0005) was significantly higher. Colchicine had a lower pooled RR of ischemic stroke (0.28, 95% CI 0.12-0.65, P = 0.003) for patients with acute compared with chronic CAD. Colchicine treatment significantly decreased the risk of primary cardiovascular composite outcomes, MI, ischemic stroke, and ischemia-driven coronary revascularization in CAD patients but increased adverse GI events. There was no significant difference in all-cause mortality, cardiovascular mortality, and non-cardiovascular death between the colchicine and control groups. Colchicine performs better in acute CAD patients with ischemic stroke than chronic CAD patients. Colchicine might be a new treatment for patients with CAD.

Maintaining continuity of nutrient intake after weaning. I. Review of pre-weaning strategies.

Weaning is a crucial phase of swine production marked by a multitude of biological and environmental stressors, which have a significant impact on immediate postweaning behavior and feed intake (FI). During this time, the piglet’s gastrointestinal (GI) system is also undergoing extensive epithelial, immune, and nervous system development. In this review, our objective is to describe the different preweaning strategies that can be used to minimize nutrient intake disruption and improve FI in the immediate postweaning period. Reducing nutrient disruption postweaning can be accomplished through the implementation of management and nutritional strategies. Research consistently demonstrates that weaning older, more developmentally mature pigs helps prevent many of the adverse GI effects associated with weaning stress. Providing creep feed to pigs during lactation is another reliable strategy that has been shown to increase immediate postweaning FI by acclimating pigs to solid feed prior to weaning. Likewise, socialization by allowing pigs to mix before weaning improves social skills, minimizing mixing stress, and aggression-related injury immediately postweaning. Supplemental milk replacer has also been shown to elicit a positive response in preweaning growth performance, which may help to reduce preweaning mortality. While socialization and milk replacer are acknowledged to ease the weaning transition, these strategies have not been widely adopted due to labor and application challenges. Additionally, the cost of milk replacer and logistics of retrofitting farrowing houses to accommodate litter socialization have limited adaptation. Further exploration of maternal nutrition strategies, particularly fetal imprinting, is needed to better understand the implications of perinatal learning. Other areas for future research include, combining environmental enrichment with feeding strategies, such as large destructible pellets or play feeders, as well as determining at what time point producers should start socializing pigs before weaning. While more research is needed to develop strategic preweaning management programs, many of the strategies presented in this review provide opportunities for producers to minimize nutrient intake disruption by preventing feed neophobia, reducing stress, and easing the wean pig transition.

Adverse gastrointestinal events with sodium polystyrene sulphonate and calcium polystyrene sulphonate use in dialysis patients: a nationwide registry study.

Sodium polystyrene sulphonate (SPS) and calcium polystyrene sulphonate (CPS) are commonly used cation-exchange resins for the treatment and control of hyperkalaemia. However, their use (particularly SPS) has been limited by reports of adverse gastrointestinal (GI) events. The safety of these compounds in patients undergoing dialysis requires larger investigation. To study the occurrence of adverse GI events (occlusion, perforation, thrombosis/ischaemia) in the periods of SPS or CPS exposition versus the periods without exposition in dialysis patients. Dialysis patients were extracted from the French National Registry and merged with the French hospital discharge database (between 2006 and 2017). For our primary analysis, we used patients who had any claim of SPS use (n = 43 771). Time-varying Cox models, negative binomial regression and pre- versus post-treatment average treatment effects. The mean age was 66 ± 15 years, 37% were female and 92% were undergoing haemodialysis. Over a 1-year follow-up, patients on periods with SPS (on-SPS) did not present an increased risk of adverse GI events versus the periods without SPS (off-SPS): incidence rate (IR)(per 1000person years) = 7.4 (6.4-8.7) versus 9.5 (8.1-11.0); adjusted hazard ratio (HR) (95% CI) = 0.81 (0.60-1.09), P = 0.17. Patients exposed to SPS did not experience a higher rate of adverse GI events in the year after SPS initiation versus the year before SPS initiation; P-value for parallel trend = 0.87. Patients on-CPS also did not show an increased risk of adverse GI events versus off-CPS: IR (per 1000py) = 8.6 (5.1-11.9) versus 7.8 (5.1-11.9); adjusted HR (95% CI) = 0.76 (0.31-1.80), P = 0.52. The rates of adverse GI events in the periods on and off exposure were also similar over a follow-up of 5 years. Our large, nationwide study shows that the incidence of adverse GI events in patients undergoing dialysis was low and that neither the use of SPS nor CPS was associated with increased GI events risk.

To Feed or Not to Feed: A Critical Overview of Enteral Feeding Management and Gastrointestinal Complications in Preterm Neonates with a Patent Ductus Arteriosus.

The management of enteral feeds in preterm infants with a hemodynamically significant patent ductus arteriosus (hs-PDA) is a major challenge for neonatologists due to the fear of gastrointestinal (GI) complications. This review aims to analyze the available evidence on the complex relation between the presence and management of PDA, enteral feeding practices, and GI outcomes in the preterm population. There is limited evidence, based on small and heterogeneous trials, that hs-PDA may affect the splanchnic hemodynamic response to enteral feeds. While the presence of PDA seems a risk factor for adverse GI outcomes, the benefits of feeding withholding during pharmacological PDA treatment are controversial. The lack of robust evidence in support of or against a timely feeding introduction or feeding withholding during pharmacological PDA closure in preterm neonates does not allow to draw any related recommendation. While waiting for further data, the feeding management of this population should be carefully evaluated and possibly individualized on the basis of the infants’ hemodynamic and clinical characteristics. Large, multicentric trials would help to better clarify the physiological mechanisms underlying the development of gut hypoperfusion, and to evaluate the impact of enteral feeds on splanchnic hemodynamics in relation to PDA features and treatment.

The effect of a new mixture of sugar and sugar-alcohols compared to sucrose and glucose on blood glucose increase and the possible adverse reactions: A phase I double-blind, three-way randomized cross-over clinical trial

IntroductionSeveral sweeteners are introduced to replace sucrose in the human diet. However, they had their own limitations and concerns, particularly in terms of their taste and their long-term health consequences. This study examined the effect of a new mixture of sugars and sugar alcohol on the postprandial blood glucose levels and its possible gastrointestinal (GI) adverse reactions in human adults. MethodsIn this double-blind three-way randomized clinical trial, adults (21 with type 2 diabetes and 20 healthy) received 300ml of three beverages containing 50g glucose, sucrose, and lacritose (a mixture of lactose, fructose, sucrose, and erythritol) when they were in the fasted state in a random order. Postprandial serum glucose was checked every 30min up to 2h and the gastrointestinal reactions were collected. ResultsThe mean serum glucose was significantly lower in all time points after ingestion of the lacritose for participants with type 2 diabetes compared to glucose and sucrose (P<0.05). The blood glucose levels were significantly lower in the 30th and 60th min for healthy subjects (P<0.05). Adverse GI reactions were not significant between the test beverages. ConclusionsThe ingestion of a 50g dose of lacritose containing lactose, fructose, sucrose, and erythritol, led to an improved blood glucose levels without any significant adverse effect compared to the same amount of glucose and sucrose. Studying the long-term effects of lacritose on appetite, metabolic markers and adverse reactions is recommended. The trial was registered in Iranian registry of clinical trials: IRCT2015050912571N2.

Gastrointestinal risk of non-steroidal anti-inflammatory drugs and gastroprotective agents used in the treatment of osteoarthritis in elderly patients: A nationwide retrospective cohort study .

Osteoarthritis is highly prevalent in older adults and often treated with nonsteroidal anti-inflammatory drugs (NSAIDs). COX-2-selective NSAIDs have been shown to offer better gastrointestinal (GI) safety benefits than non-selective NSAIDs (ns-NSAIDs). However, most COX-2-selective NSAIDs have not been comprehensively evaluated for use in combination with gastroprotective agents (GPAs). This study compared the risk of adverse GI events in patients treated with COX-2-selective NSAIDs and ns-NSAIDs alone, or in combination with GPAs. We utilized National Health Insurance Claim Data collected from 2012 to 2015. Newly diagnosed patients with osteoarthritis (60 years or older) were included in this study. The study population was divided into two groups: 1) COX-2-selective NSAID treatment and 2) ns-NSAIDs treatment. Patients were followed-up for up to 6 months to determine whether GI events occurred. The Cox proportional hazards model was used to identify differences in risk. Subgroup analyses were conducted for monotherapies and combination treatments with GPAs. The number of subjects prescribed COX-2-selective NSAID and ns-NSAIDs were 20,868 (5.6%) and 353,494 (94.4%), respectively. After adjustment for confounding factors, COX-2-selective NSAID were safer than ns-NSAIDs (adjusted hazard ratio (aHR) = 0.80, 95% confidence interval (CI): 0.77-0.82). Use of GPAs with COX-2-selective NSAID was associated with a lower risk of GI events than use of ns-NSAIDs (aHR = 0.92, 95% CI: 0.87-0.97). Use of COX-2-selective NSAID was associated with a lower risk of GI adverse events than use of ns-NSAIDs as a monotherapy. Furthermore, COX-2-selective NSAID were safer than ns-NSAIDs in combination with GPAs. .

1720 A Case of Sunitinib-Induced Necrotizing Esophagitis

INTRODUCTION: Acute esophageal necrosis (AEN), also known as “black esophagus” or “acute necrotizing esophagitis”, is a rare entity thought to be caused by a known ischemic insult from a low perfusion state. Etiologies include multi-organ dysfunction, hypoperfusion, vasculopathy, sepsis, among others. Sunitinib, a chemotherapeutic agent for renal cell cancer and gastrointestinal stromal tumors, has common gastrointestinal (GI) side effects of diarrhea and vomiting but severe GI side effects are rare. We present a unique case of Sunitinib-induced AEN. CASE DESCRIPTION/METHODS: A 72-year-old man presented to the hospital for a two days history of epigastric abdominal pain, bilious vomiting, and multiple episodes of non-bloody diarrhea. His medical history was significant for metastatic papillary renal cell carcinoma on Sunitinib. On presentation, his blood pressure was 74/52 mm Hg and heart rate 107 beats per minute. He exhibited generalized abdominal tenderness without rebound or guarding. His hemoglobin was 15 g/dL. He was admitted to the ICU for hypovolemic shock thought to be secondary to severe gastroenteritis requiring the use of vasopressors. He later developed ongoing melena and his hemoglobin decreased to 10.8 g/dl requiring urgent Endoscopy. The examination revealed circumferential, black, necrotic mucosa in the lower one-half of the esophagus with a sharp demarcation of healthy mucosa at the level of gastroesophageal junction without any active bleeding. Findings were consistent with AEN. The patient remained hypotensive despite aggressive resuscitation and the use of vasopressors. Unfortunately, the patient died several days later. DISCUSSION: AEN is characterized by the classic endoscopic image of diffuse, circumferential, black-appearing necrotic mucosa. The exact etiology leading to the hypoperfusion state in our case is unclear and could be attributed to Sunitinib. The most common adverse GI reactions to Sunitinib include diarrhea (53%), nausea (44%), and vomiting (24%) which were intractable in the above case. This medication has also been linked to severe GI hemorrhage. Sunitinib inhibits platelet-derived growth factors and vascular endothelial growth factors which play a major role in angiogenesis and apoptosis. We believe that by inhibiting these cellular processes, the patient was predisposed to development of AEN which was potentiated by the patient’s hypovolemic state.

Risk of Hospitalization for Serious Adverse Gastrointestinal Events Associated With Sodium Polystyrene Sulfonate Use in Patients of Advanced Age

Sodium polystyrene sulfonate is commonly prescribed for the treatment of hyperkalemia. Case reports of intestinal injury after administration of sodium polystyrene sulfonate with sorbitol resulted in a US Food and Drug Administration warning and discontinuation of combined 70% sorbitol-sodium polystyrene sulfonate formulations. There are ongoing concerns about the gastrointestinal (GI) safety of sodium polystyrene sulfonate use. To assess the risk of hospitalization for adverse GI events associated with sodium polystyrene sulfonate use in patients of advanced age. Population-based, retrospective matched cohort study of eligible adults of advanced age (≥66 years) dispensed sodium polystyrene sulfonate from April 1, 2003, to September 30, 2015, in Ontario, Canada, with maximum follow-up to March 31, 2016. Initial data analysis was conducted from August 1, 2018, to October 3, 2018; revision analysis was conducted from February 25, 2019, to April 2, 2019. Cox proportional hazards regression models were used to examine the association of sodium polystyrene sulfonate use with a composite of GI adverse events compared with nonuse that was matched via a high-dimensional propensity score. Additional analyses were limited to a subpopulation with baseline laboratory values of estimated glomerular filtration rate and serum potassium level. Dispensed sodium polystyrene sulfonate in an outpatient setting. The primary outcome was a composite of adverse GI events (hospitalization or emergency department visit with intestinal ischemia/thrombosis, GI ulceration/perforation, or resection/ostomy) within 30 days of initial sodium polystyrene sulfonate prescription. From a total of 1 853 866 eligible adults, 27 704 individuals were dispensed sodium polystyrene sulfonate (mean [SD] age, 78.5 [7.7] years; 54.7% male), and 20 020 sodium polystyrene sulfonate users were matched to 20 020 nonusers. Sodium polystyrene sulfonate use compared with nonuse was associated with a higher risk of an adverse GI event over the following 30 days (37 events [0.2%]; incidence rate, 22.97 per 1000 person-years vs 18 events [0.1%]; incidence rate, 11.01 per 1000 person-years) (hazard ratio, 1.94; 95% CI, 1.10-3.41). Results were consistent in additional analyses, including the subpopulation with baseline laboratory values (hazard ratio, 2.91; 95% CI, 1.38-6.12), and intestinal ischemia/thrombosis was the most common type of GI injury. The use of sodium polystyrene sulfonate is associated with a higher risk of hospitalization for serious adverse GI events. These findings require confirmation and suggest caution with the ongoing use of sodium polystyrene sulfonate.