Proton pump inhibitors and gastrointestinal symptoms among patients with COVID-19 infection.

INTRODUCTION: The administration of proton pump inhibitors (PPIs) is anticipated to elevate an individual's susceptibility to enteric infections as a result of altering the gut flora. The influence of PPIs on the clinical manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain. This study aims to investigate the impact of PPI usage on the clinical manifestation of COVID-19, namely its gastrointestinal symptoms. METHODS: This is a cross-sectional cohort study involving COVID-19 patients. Patients were interviewed using a predesigned questionnaire that asked about their demographics, clinical manifestations of COVID-19 infection, and the extent and type of PPIs in use. PPI usage was confirmed by reviewing patients' electronic medical records. The primary outcome was to establish any association between the use of PPI and the symptoms and clinical presentation of COVID-19. RESULTS: Out of a total of 254 participants, 69 (27.2%) were considered PPI users. Patients who were on PPI medications reported a significantly lower rate of myalgia (27.5% vs 51.9%; p = 0.0006) and heartburn (5.7% vs 15.6%; p = 0.03) but had a significantly higher rate of abdominal pain (27.5% vs 13.5%; p = 0.001) and diarrhoea (28.9% vs 14.5%, p = 0.02) when compared to those who were not using PPIs. Patients on PPIs were also shown to have significantly higher odds of developing diarrhoea (OR 2.0, 95% CI: 1.08 to 3.93, p = 0.02) and abdominal pain (OR 2.0, 95% CI: 1.22 to 3.93, p = 0.03), but a lower risk of developing myalgia (OR 0.5, 95% CI: 0.3 to 0.9, p = 0.02) when compared to non-PPI users. CONCLUSION: This study shows that the use of PPIs could impact COVID-19 clinical presentation toward more gastrointestinal manifestations. Further studies investigating the link between other acid suppression medications and COVID-19 manifestations and severity should be carried out.

Gastrointestinal safety evaluation of semaglutide for the treatment of type 2 diabetes mellitus: A meta-analysis.

BACKGROUND: Semaglutide, as an innovative weekly formulation, has attracted much attention. Nevertheless, the predominant occurrence of gastrointestinal adverse events (GIAEs) poses a noteworthy challenge linked to the use of this medication, substantially affecting its clinical applicability and the overall well-being of patients. Therefore, this systematic review aims to comprehensively discuss the GIAEs, providing a basis for clinical therapeutic decisions. METHODS: We systematically searched 4 independent databases for randomized controlled trials investigating the application of semaglutide in managing type 2 diabetes mellitus. The search period spanned from the inception of the databases to December 2023. We conducted a comprehensive meta-analysis, employing Review Manager 5.4.1 software, to systematically analyze and evaluate potential biases. Our primary emphasis was on assessing the gastrointestinal safety profile of semaglutide. RESULTS: The outcomes unveiled a noteworthy rise in the collective occurrence of GIAEs across all dosage groups of semaglutide in comparison with the control group (P < .05). Upon further analysis, it was observed that semaglutide showed a heightened occurrence of GIAEs in contrast to the placebo. However, statistically significant distinction was not observed when compared to the reduction of conventional doses or the transition to other types of glucagon-like peptide-1 receptor agonist. Additionally, an extended treatment duration with semaglutide (>30 weeks) demonstrated an association with a certain degree of decrease in the incidence of gastrointestinal events. Funnel plot assessment for publication bias demonstrated high-quality inclusion of studies with no apparent publication bias. CONCLUSION: The frequency of GIAEs in using semaglutide was observed to be elevated in comparison to the control group. However, it was comparable to other glucagon-like peptide-1 receptor agonist or low-dose treatment regimens. Additionally, an extended treatment duration played a role in decreasing the frequency of GIAEs. These findings provide valuable insights for clinical practice. Nonetheless, further research is crucial to explore supplementary data indicators, informing clinical practices and better serving the interests of patients.

Polystyrene exposure induces lamb gastrointestinal injury, digestive disorders and inflammation, decreasing daily gain, and meat quality.

Microplastics (MPs), recognized as an emerging environmental menace, have been extensively investigated in both marine and terrestrial fauna. This study is comprehensive to investigate how polystyrene (PS) affects ruminant animals. The experimental design comprised 24 individually housed lambs, divided into a CON group (diet without PS) and three PS-exposed (25 µm, 50 µm, 100 µm) groups, each with six lambs, the exposure of PS was 100 mg/day, and the duration of exposure was 60 days. The study yielded noteworthy results: (ⅰ) PS leads to a decrease in average daily gain along with an increase in feed conversion rate. (ⅱ) PS decreases rumen ammonia nitrogen. The rumen microbiota diversity remains consistent. However, the relative abundance of Bacteroidetes and Actinobacteria increased in the PS-exposed groups, while the relative abundance of Coriobacteriales_incertae_Sedis and Prevotellaceae_YAB2003_group decreased. (ⅲ) PS leads to decrease in hemoglobin, thrombocytocrit, and albumin levels in lamb blood, thus triggering oxidative stress accumulation, along with swelling of the kidneys and liver. (ⅳ) PS inflicts severe damage to jejunum, consequently impacting digestion and absorption. (ⅴ) PS reduces meat quality and the nutritional value. In conclusion, PS-exposure inhibited lambs' digestive function, adversely affects blood and organs' health status, reducing average daily gain and negatively influencing meat quality. PS particles of 50-100 µm bring worse damage to lambs. This research aims to fill the knowledge void concerning MPs' influences on ruminant animals, with a specific focus on the meat quality of fattening lambs.

Review article: Contemporary management of gastrointestinal, pancreatic and hepatic toxicities of immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are effective oncologic agents which frequently cause immune-related adverse events (irAEs) which can impact multiple organ systems. Onco-Gastroenterology is a novel and emerging subspecialty within gastroenterology focused on cancer treatment-related complications. Gastroenterologists must be prepared to identify and manage diverse immune-mediated toxicities including enterocolitis, hepatitis, pancreatitis and other ICI-induced toxicities. AIM: To provide a narrative review of the epidemiology, diagnostic evaluation and management of checkpoint inhibitor-induced gastrointestinal and hepatic toxicities. METHODS: We searched Cochrane and PubMed databases for articles published through August 2023. RESULTS: Gastrointestinal and hepatic irAEs include most commonly enterocolitis and hepatitis, but also pancreatitis, oesophagitis, gastritis, motility disorders (gastroparesis) and other rarer toxicities. Guidelines from the National Comprehensive Cancer Network, American Society of Clinical Oncology and European Society for Medical Oncology, in combination with emerging cohort and clinical trial data, offer strategies for management of ICI toxicities. Evaluation of irAEs severity by formal classification and clinical stability, and a thorough workup for alternative etiologies which may clinically mimic irAEs underlie initial management. Treatments include corticosteroids, biologics and other immunosuppressive agents plus supportive care; decisions on dosing, timing and choice of steroid adjuncts and potential for subsequent checkpoint inhibitor dosing are nuanced and toxicity-specific. CONCLUSIONS: Expanding clinical trial and cohort data have clarified the epidemiology and clinical characteristics of gastrointestinal, pancreatic and hepatic toxicities of ICIs. Guidelines, though valuable, remain based principally on retrospective cohort data. Quality prospective, controlled studies may refine algorithms for treatment and potential immunotherapy rechallenge.

Imaging gastrointestinal damage due to acute mercury poisoning using a mitochondria-targeted dual near-infrared fluorescent probe.

Mercury (Hg) is one of the most widespread pollutants that pose serious threats to public health and the environment. People are inevitably exposed to Hg via different routes, such as respiration, dermal contact, drinking or diet. Hg poisoning could cause gingivitis, inflammation, vomiting and diarrhea, respiratory distress or even death. Especially during the developmental stage, there is considerable harm to the brain development of young children, causing serious symptoms such as intellectual disability and motor impairments, and delayed neural development. Therefore, it's of great significance to develop a specific, quick, practical and labor-saving assay for monitoring Hg2+. Herein, a mitochondria-targeted dual (excitation 700 nm and emission 728 nm) near-infrared (NIR) fluorescent probe JZ-1 was synthesized to detect Hg2+, which is a turn-on fluorescent probe designed based on the rhodamine fluorophore thiolactone, with advantages of swift response, great selectivity, and robust anti-interference capability. Cell fluorescence imaging results showed that JZ-1 could selectively target mitochondria in HeLa cells and monitor exogenous Hg2+. More importantly, JZ-1 has been successfully used to monitor gastrointestinal damage of acute mercury poisoning in a drug-induced mouse model, which provided a great method for sensing Hg species in living subjects, as well as for prenatal diagnosis.

Tolerance and Safety of an Anti-Regurgitation Formula Containing Locust Bean Gum, Pre-, and Postbiotics: A Multi-Country Multi-Center Prospective Randomized Controlled Study in Infants with Regurgitation.

This multi-center prospective randomized controlled trial was a tolerance and safety study investigating the thickener locust bean gum (LBG) in infants with regurgitation, to support the re-evaluation of the safety of LBG in infant formula. The primary objective was to demonstrate that after an 8-week intervention, stool consistency was not inferior (i.e., was not looser or more watery) in infants fed an anti-regurgitation (AR) formula containing LBG vs. the stool consistency of infants fed with an unthickened control formula. A total of 103 full-term infants with regurgitation were randomized to the test or control formula. The test formula contained LBG (0.4 g/100 mL), short-chain galacto-oligosaccharides, and long-chain fructo-oligosaccharides (scGOS/lcFOS; 9:1; 0.4 g/100 mL) and postbiotics and the control formula contained scGOS/lcFOS (0.8 g/100 mL), the same amount of postbiotics, and did not contain LBG. The average stool consistency score at the 8th intervention week was the primary outcome parameter. Secondary outcome parameters were stool consistency at other timepoints, stool frequency, Infant Gastrointestinal Symptom Questionnaire (IGSQ) score, growth, (serious) adverse events ([S]AEs), regurgitation severity, and infant well-being. Overall, the infants were 36.9 ± 12.9 [mean ± SD] days old, 62.7% girls in the test, and 50.0% girls in the control group. The primary analysis showed that the test group did not have looser or more watery stools than the control group. IGSQ sum scores decreased comparably in both groups. The frequency of regurgitation was significantly lower in the test group compared to the control group (mixed model repeated measurement, p ≤ 0.028) and parent-reported well-being scores were favorable. Adequate growth was observed in both groups. Both products were well-tolerated and safe and the AR formula with LBG was efficacious in reducing regurgitation frequency. This study provides further evidence for the dietary management of regurgitation by LBG-containing formulae in infants who are not exclusively breastfed, and the reassurance it can bring to parents.

Gastrointestinal dysfunction in the valproic acid induced model of social deficit in rats.

Autism spectrum disorder (ASD) has increased in incidence over the past several decades, and is associated with a range of co-morbidities including gastrointestinal (GI) dysfunctions including gastroesophageal reflux, abdominal pain, bloating, constipation and/or diarrhea. Several animal models have been used that replicate several aspects of ASD but no single model has been able to replicate the entire disease pathophysiology. In humans, prenatal exposure to valproic acid (VPA) has been identified as a significant risk factor and rodent models have shown that in utero VPA exposure leads to behavioral deficits in offspring. The present study aimed to investigate whether in utero exposure to VPA induces GI dysfunction in rats. Timed pregnant Sprague-Dawley rats were injected with a single dose of VPA at embryonic day 12.5. Both male and female offspring subsequently underwent behavioral studies and assessment of GI function in adulthood. In utero VPA treatment induced social deficits in both male and female offspring, decreasing sociability and social novelty. Histological examination showed that VPA treated offspring had decreased thickness of GI muscle and mucosa, while immunohistochemical studies showed a decrease in myenteric neuron number in the fundus. Functional studies showed that both male and female VPA offspring had a delay in gastric emptying compared to vehicle treated offspring. Results of the current study suggest that the rat VPA model of behavioral deficits may be a convenient model by which both mechanistic and functional insights into GI dysfunction may be studied.

Managing Gastrointestinal Symptoms Resulting from Treatment with Trofinetide for Rett Syndrome: Caregiver and Nurse Perspectives.

Rett syndrome (RTT) is a rare genetic neurodevelopmental disorder mainly affecting female individuals. Trofinetide was recently approved as the first treatment for RTT, largely on the basis of results from the phase 3 LAVENDER trial, in which trofinetide showed improvements in core symptoms of RTT compared with placebo. However, gastrointestinal (GI) symptoms such as diarrhea and vomiting were commonly reported side effects, and taste was also a reported issue. The objective of this article is to describe the perspectives of five caregivers of girls in trofinetide clinical trials as well as those of three nurse trial coordinators, with a focus on management of GI symptoms of trofinetide treatment.Audio Abstract available for this article. Audio Abstract: Jane Lane provides an overview and discusses key findings of the article titled "Managing Gastrointestinal Symptoms Resulting from Treatment with Trofinetide for Rett Syndrome: Caregiver and Nurse Perspectives." (MP4 83274 KB).

Sevelamer-Induced Gastrointestinal Disease in 12 Patients with End-Stage Renal Disease: A Case Series.

INTRODUCTION: Isolated case reports and case series have linked the use of sevelamer to severe gastrointestinal (GI) inflammation and perforation among patients with end-stage renal disease. METHODS: In this study, we identified 12 cases of biopsy-proven sevelamer-induced gastrointestinal disease from a large urban community hospital over the course of 5 years. We described baseline characteristics, sites and types of injury, histological findings, timing and dosing of sevelamer initiation compared with symptom onset, and in a smaller subset, endoscopic resolution post drug cessation. We also reviewed preexisting conditions to identify trends in populations at risk. RESULTS: Several of the patients reviewed had preexisting conditions of decreased motility and/or impaired mucosal integrity. The presentation of disease was broad and included both upper-GI and lower-GI pathologies and in varying severity. DISCUSSION: There is a broad phenotypic range of sevelamer-induced gastrointestinal disease. As this becomes a more frequently recognized pathology, clinicians should be aware of how it may present and which populations may be more susceptible.

Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH-AEG-SEPD-SEOM-GETECCU.

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2% to 40%, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.

Insights into Prospects of Novel NSAID Prodrugs in the Management of Gastrointestinal Toxicity: A Perspective Review.

Non-steroidal anti-inflammatory drugs (NSAIDs) have a long history in the healthcare system due to their therapeutic potential. These NSAIDs cause ulcerogenicity, stomach pains, gastrointestinal hemorrhage, mucosa bleeding, and pancreatitis when used moderately and consistently. With researchers, managing the aforementioned adverse effects therapeutically is getting increasingly difficult. One method for creating NSAID moieties with low penetration as well as ulcerogenic properties is the prodrug technique. During the oral consumption of NSAID-prodrugs, ulcerations, intestinal hemorrhage, and mucosa hemorrhage have significantly decreased. Considering this background, this review focussed on NSAID prodrugs as well as their justifications, the pathogenesis of NSAIDs inducing gastrointestinal toxicity, and the role of different antioxidants and spacer groups. Prodrug moieties have more advantages over parent medicines concerning both solubility and lipophilicity. In general, NSAID-class prodrugs can successfully treat both acute and long-term inflammation and aches without causing ulcerotoxicity and related gastrointestinal side effects, which reduces their burden from the pharmacoeconomic perspective.

Prediction of gastrointestinal symptoms trajectories using omega-3 and inflammatory biomarkers in early-stage breast cancer patients receiving chemotherapy.

PURPOSE: Gastrointestinal (GI) symptoms are common among breast cancer patients undergoing chemotherapy, negatively impacting treatment outcomes and quality of life. Evidence points to inflammatory processes as the underlying cause of chemotherapy-associated GI symptoms. Relatedly, omega-3 (n-3) has been linked to anti-inflammatory processes. The primary objective of this study was to examine the associations between baseline n-3, baseline inflammatory markers and GI symptom progression in early-stage breast cancer patients receiving chemotherapy. METHODS: In this secondary analysis of a prospective cohort study, we analyzed baseline levels of inflammatory biomarkers (measured using a Luminex bead-immunoassay) and plasma levels of DHA, EPA, and FFA (measured using enzyme-linked immunosorbent assay). GI symptoms were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire in Cancer Patients (EORTC QLQ-C30) symptom scale scores at baseline (T1) and at least 6 weeks after, during chemotherapy (T2). Inferential statistics were used to analyze associations between the variables of interest. RESULTS: The analysis included 31 female breast cancer patients (mean age ± SD = 50.5 ± 8.8; 89.6% receiving anthracycline-based chemotherapy). Higher levels of docosahexaenoic acid (DHA) and interleukin-8 (IL-8) predicted increases in appetite loss. Similarly, higher IL-8 predicted worsened nausea and vomiting. CONCLUSION: Baseline IL-8 and DHA predicted GI symptom progression in early-stage breast cancer patients undergoing chemotherapy. Future studies are required to evaluate how therapeutic intervention targeting these biomarkers may mitigate gastrointestinal symptoms in cancer patients.

Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH-AEG-SEPD-SEOM-GETECCU.

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2 % to 40 %, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.

Magnitude and Determinants of Long-term Use of Proton Pump Inhibitors Among Portuguese Older Adults in Primary Health Care.

PURPOSE: Proton Pump Inhibitors (PPIs) have been associated with several adverse effects of particular concern in older populations. Their use for a period longer than 8 weeks is not recommended for older adults. Strategies to discontinue PPIs have been offered; however, their use remains high. This study aims to characterize PPI use in Portuguese older people and to identify the factors associated with potentially inappropriate use. METHODS: A cross-sectional study was conducted on 1200 randomly selected older adults (≥65 years of age), users of primary health care facilities in the Regional Health Administration (Administração Regional de Saúde of Centro [ARSC]) of Portugal between April 2021 and August 2022. Data concerning their characteristics and PPI use were provided by the Shared Services of the Health Ministry (Serviços Partilhados do Ministério da Saúde) and collected retrospectively. Associations between independent variables and PPI use were investigated by logistic regression analysis. FINDINGS: Of the older adults, 37.92% were receiving PPIs and 78.68% of them were taking them for a longer period than recommended; 49.79% were taking PPIs without having any digestive system-related disease. Multivariate analysis showed that the prolonged use of PPIs was not associated with any specific pattern, although inappropriate PPI use is high among Portuguese older adults. IMPLICATIONS: Long-term PPI use in older adults is widespread and does not fit any particular patient profile; therefore, cross-cutting educational interventions should be designed independently of the patient's pathologic condition or treatment.

Regular use of low-dose of opioids after gastrointestinal surgery may lead to postoperative gastrointestinal tract dysfunction in children: a Chinese national regional health center experience sharing.

BACKGROUND: The need for pain management is increasing in pediatrics, but the side effects of overuse or abuse of analgesics can be harmful to children's health and even life-threatening in severe cases. METHODS: Patients who underwent resection of Meckel's diverticulum at the Children's Hospital of Chongqing Medical University from July 1, 2019, to July 1, 2022, were included in this study. Opioids were administered through patient-controlled analgesia (PCA). Based on the preoperative choices made by the legal guardians, patients were stratified into two groups: PCA Group (PCAG) and Non-PCA Group (NPCAG). Data pertaining to the clinical characteristics and prognoses of these patients were subsequently collected and analyzed to assess the impact of opioid administration. RESULTS: In the study, a total of 126 patients were enrolled, with 72 allocated to the Patient-Controlled Analgesia Group (PCAG) and 54 to the Non-Patient-Controlled Analgesia Group (NPCAG). When compared to the NPCAG, the PCAG exhibited a longer duration of postoperative fasting (median 72 vs. 62 h, p = 0.044) and increased utilization of laxatives (12[16.7%] vs. 2[3.7%], p = 0.022). However, the PCAG also experienced higher incidences of intestinal stasis and abnormal intestinal dilation (13[18.1%] vs. 3[5.6%], p = 0.037). No statistically significant differences were observed in pain assessments at the conclusion of the surgical procedure (0 vs. 1[1.9%], p = 0.429) or within the first 24 h postoperatively (16[22.2%] vs. 18[33.3%], p = 0.164). Additionally, NPCAG patients did not necessitate increased administration of rescue analgesics (2[2.8%] vs. 4[7.4%], p = 0.432). CONCLUSIONS: The administration of opioids did not demonstrably ameliorate postoperative pain but was associated with a heightened incidence of postoperative gastrointestinal tract dysfunction. The retrospective nature of the current research should be considered and should be clarified further.

Immune-related adverse events with severe pain and ureteral expansion as the main manifestations: a case report of tislelizumab-induced ureteritis/cystitis and review of the literature.

Immune checkpoint inhibitor (ICI) is an up-to-date therapy for cancer with a promising efficacy, but it may cause unique immune-related adverse events (irAEs). Although irAEs could affect any organ, irAEs-induced whole urinary tract expansion was rarely reported. Herein, we reported a 27-year-old male patient with thymic carcinoma who received the treatment of tislelizumab, paclitaxel albumin and carboplatin. He was hospitalized for severe bellyache and lumbago after 6 courses of treatment. Antibiotic and antispasmodic treatment did not relieve his symptoms. The imaging examinations reported whole urinary tract expansion and cystitis. Therefore, we proposed that the patient's pain was caused by tislelizumab-induced ureteritis/cystitis. After the discontinuation of tislelizumab and the administration of methylprednisolone, his symptoms were markedly alleviated. Herein, we reported a rare case of ICI-induced ureteritis/cystitis in the treatment of thymic cancer and reviewed other cases of immunotherapy-related cystitis and tislelizumab-related adverse events, which will provide a reference for the diagnosis and treatment of ICI-related irAEs.

Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss.

This database study examines the association between glucagon-like peptide 1 agonists (eg, semaglutide, liraglutide) used for weight loss and reports of gastrointestinal adverse events.