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ObjectivesVedolizumab (VDZ) and ustekinumab (UST) are second-line treatments in pediatric patients with ulcerative colitis (UC) refractory to antitumor necrosis factor (anti-TNF) therapy. Pediatric studies comparing the effectiveness of these medications are lacking. Using a registry from ImproveCareNow (ICN), a global research network in pediatric inflammatory bowel disease, we compared the effectiveness of UST and VDZ in anti-TNF refractory UC.MethodsWe performed a propensity-score weighted regression analysis to compare corticosteroid-free clinical remission (CFCR) at 6 months from starting second-line therapy. Sensitivity analyses tested the robustness of our findings to different ways of handling missing outcome data. Secondary analyses evaluated alternative proxies of response and infection risk.ResultsOur cohort included 262 patients on VDZ and 74 patients on UST. At baseline, the two groups differed on their mean pediatric UC activity index (PUCAI) (p = 0.03) but were otherwise similar. At Month 6, 28.3% of patients on VDZ and 25.8% of those on UST achieved CFCR (p = 0.76). Our primary model showed no difference in CFCR (odds ratio: 0.81; 95% confidence interval [CI]: 0.41-1.59) (p = 0.54). The time to biologic discontinuation was similar in both groups (hazard ratio: 1.26; 95% CI: 0.76-2.08) (p = 0.36), with the reference group being VDZ, and we found no differences in clinical response, growth parameters, hospitalizations, surgeries, infections, or malignancy risk. Sensitivity analyses supported these findings of similar effectiveness.ConclusionsUST and VDZ are similarly effective for inducing clinical remission in anti-TNF refractory UC in pediatric patients. Providers should consider safety, tolerability, cost, and comorbidities when deciding between these therapies.

PURPOSE: Biosimilar tumor necrosis factor inhibitors (b-TNFi) reduce healthcare costs and maintain equal efficacy when compared to their originator counterparts (o-TNFi). Current practice is to start patients on a slower standard infusion rate during the initial transition from an o-TNFi to a b-TNFi. There is a knowledge gap around switching from rapid originator infusion to rapid biosimilar infusion in the pediatric inflammatory bowel disease (IBD) population. SUMMARY: We present a case series of 8 pediatric patients with IBD who were switched from a rapid-infusion o-TNFi to a rapid-infusion b-TNFi from 2016 through 2022. Our primary interest was safety, which we evaluated based on the occurrence of infusion reactions or need for new premedications within the first 6 months of starting a b-TNFi. We also examined effectiveness through the incidence of IBD-related hospitalizations, TNFi failure, and need for co-medication or dose escalation over the same period. In our cohort, 4 patients had Crohns disease and 4 had ulcerative colitis. All patients were switched to a biosimilar for nonmedical reasons. During the follow-up period, no patients had infusion reactions necessitating new premedications, serious adverse events, or medication nonresponse. CONCLUSION: Patients who directly transitioned from a rapid-infusion o-TNFi to a rapid-infusion b-TNFi did not experience serious adverse events. Given the fiscal and patient experience advantages of rapid-rate infusions, larger studies are needed to consider a change in practice.

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we perform single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC.

Protein display systems are powerful techniques used to identify protein molecules that bind with high affinity to target proteins of interest. The initial challenge in implementing a display system is the construction of a high-diversity naïve library. Here, we describe the methods to generate a designed ankyrin repeat protein (DARPin) display library using degenerate oligonucleotides. Specifically described is the construction of a single DARPin repeat module by overlap extension PCR, concatenation of the module by restriction enzyme digestion and ligation, and incorporation of the concatenated modules into a full-length DARPin sequence in a bacterial cloning or display vector containing the hydrophilic N- and C-terminal capping domains. Protocols for PCR amplification of DARPin sequences to estimate diversity of naïve and enriched libraries via next-generation sequencing are included, as is a simple Linux-based program for analysis of naïve and enriched sequences. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Generation of a single DARPin repeat by overlap extension PCR Basic Protocol 2: Concatenation of DARPin repeats Basic Protocol 3: Ligation of internal repeats into cloning/display vector containing N- and C-terminal capping repeats Basic Protocol 4: Estimation of library size and diversity by next-generation sequencing (NGS) Basic Protocol 5: NGS analysis of naïve and enriched libraries.

Ulcerative colitis is a gastrointestinal problem with increasing prevalence. In this study, the effect of hesperidin (commonly found in citrus white peel) on colitis was investigated. For this purpose, 28 Wistar albino female rats, 3-- 4 months old and weighing between 250--350 g, were used in the study. Rats were randomly divided into four groups: control (n=7), colitis (n=7), protective effect (n=7), and treatment (n=7) groups. Colitis was induced in rats with acetic acid (except control), and hesperidin was then administered at 150 mg/kg for 1 week before and after colitis. At the end of the study, IFN-γ and IL-6 values in blood, TAS, TOS, and OSI in tissue were evaluated. Intestinal tissues were assessed visually by haematoxylin and eosin staining. Our results showed that the levels of IFN-γ and IL-6 were highest in the colitis group and lowest in the treatment group, with statistical significance. The most histopathological damage was seen in the colitis group, while less prevalent in the treatment and control groups. The results of the study show that hesperidin had limited protective and therapeutic effects on experimental colitis mouse models. [ABSTRACT FROM AUTHOR]

Background/Aims: The effect of proton pump inhibitors (PPIs) on the lower gastrointestinal (GI) tract is uncertain, with potential to worsen damage. This study aimed to find the best method for protecting the entire GI tract from mucosal damage. Methods: A retrospective cohort study at Samsung Medical Center (2002-2019) included 195,817 patients prescribed GI mucosa-damaging agents. The primary goal was to assess the effectiveness of GI protective agents in preventing significant hemoglobin drops (>2 g/dL), indicating overall GI mucosal damage. Self-controlled case series and landmark analysis were used to address biases in real-world data. Results: The incidence rate ratios for rebamipide, PPI, and histamine-2 receptor antagonist (H2RA) were 0.34, 0.33, and 0.52, respectively. Rebamipide showed a significantly lower incidence rate than H2RA and was comparable to PPIs. Landmark analysis revealed significant reductions in hemoglobin drop risk with rebamipide and H2RA, but not with PPI. Conclusions: Rebamipide, like PPIs, was highly effective in preventing blood hemoglobin level decreases, as shown in real-world data. Rebamipide could be a comprehensive strategy for protecting the entire GI tract, especially when considering PPIs' potential side effects on the lower GI tract. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancers are still the leading cause of death worldwide. This is related, among other things, to the non-specific symptoms, especially in the initial stages, and also to the limited possibilities for treatment. Therefore, research is still being conducted to improve the detection of this type of cancer and increase the effectiveness of therapy. The potential application of natural compounds in cancer management deserves special attention. In the group of such products, there are polyphenolic compounds that reveal, e.g., anti-oxidative, anti-carcinogenic, anti-inflammatory, anti-diabetic, and neuroprotective properties. One of these polyphenols is rosmarinic acid, commonly found in plants such as the Boraginaceae and Nepetoideae subfamilies of the Lamiaceae (mint) family. A number of studies have considered the positive effects of rosmarinic acid in the treatment of many cancers, including gastrointestinal ones such as oral, stomach, pancreas, colon, and liver cancers. The main aim of this paper was to summarize the mechanisms of action of rosmarinic acid in gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Background: Thiopurine co‐therapy with anti‐tumour necrosis factor‐alpha (anti‐TNFα) agents is associated with higher anti‐TNFα drug levels and reduced immunogenicity in inflammatory bowel disease (IBD). Aims: We aimed to evaluate the association between 6‐thioguanine nucleotide (6‐TGN) and anti‐TNFα levels and the optimal 6‐TGN threshold level associated with higher anti‐TNFα levels in combination therapy. Methods: We performed a retrospective cross‐sectional multicentre study of patients with IBD on combination anti‐TNFα and thiopurine maintenance therapy between January 2015 and August 2021. Primary outcomes were infliximab and adalimumab levels. Secondary outcomes were antibodies to infliximab (ATI) or adalimumab (ATA). Univariable and multivariable linear regression were performed to identify variables associated with anti‐TNFα levels. Receiver operator characteristic curves were used to define the optimal 6‐TGN cut‐off levels associated with therapeutic anti‐TNFα levels. Results: The study included 743 paired 6‐TGN and anti‐TNFα levels (640 infliximab and 103 adalimumab). 6‐TGN levels were associated with infliximab levels, but not adalimumab levels, on univariable and multivariable regression. The optimal 6‐TGN cut‐off associated with therapeutic infliximab levels (≥5 mcg/mL) was 261 pmol/8 × 108 red blood cell (RBC) (area under the curve (AUC) = 0.57) for standard infliximab dosing and 227.5 pmol/8 × 108 RBC (AUC = 0.58) for escalated dosing. For therapeutic adalimumab levels (≥7.5 mcg/mL), the 6‐TGN cut‐off was 218.5 pmol/8 × 108 RBC (AUC = 0.59) for standard adalimumab dosing and 237.5 pmol/8 × 108 RBC (AUC = 0.63) for escalated dosing. Conclusion: 6‐TGN levels were weakly associated with infliximab but not adalimumab levels in combination therapy. 6‐TGN levels in the lower end of the therapeutic range (230–260 pmol/8 × 108 RBC) may be adequate to maintain higher infliximab levels, particularly with escalated infliximab dosing. [ABSTRACT FROM AUTHOR]

Background/Objectives: Potentially inappropriate prescribing (PIP) is a common health problem in older adults and is associated with negative health outcomes such as the occurrence of adverse drug events. Several studies have been conducted in different countries and settings to assess the prevalence of PIP, including in Home Care Services. However, data on the prevalence of PIP in home-care services in Saudi Arabia are limited. This study aimed to evaluate PIP use among older patients receiving home healthcare services in Saudi Arabia and to identify the predictors and commonly implicated medications.; Methods: A cross-sectional study was conducted over an 8-month period between January and August 2023. Data were collected from the medical records of patients older than 65 years who were currently receiving home health care services at King Faisal Hospital in Taif City, Saudi Arabia. PIPs were identified using the 2019 updated Beers Criteria.; Results: A total of 375 patients were included. Out of these, 285 PIPs were identified, of which 219 patients (58.4%) received at least one PIP. The most common therapeutic class associated with the PIPs was gastrointestinal medications (66.3%). Patient age and number of medications were significant predictors of PIP.; Conclusions: Our study found a high prevalence of PIP among elderly patients receiving home health care in Taif, Saudi Arabia. This study highlights the need for improved patient data automation and implementation of the Beers criteria to prevent PIPs in the future. [ABSTRACT FROM AUTHOR]

Self-medication without a medical or dental prescription is an action that leads to a significant problems associated with the overuse of medication in Brazil. The inappropriate use of antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) leads to problems related to microbial agent resistance and gastrointestinal complications. The purpose of this study was to elucidate the patterns of antibiotic and NSAIDs consumption among the adult population of Brazil. The questionnaire was answered by 400 people residing in Brazil who had access to the link in the year 2023. The findings showed that approximately 89.5% of the volunteers had used NSAIDs, and 32.2% had used antibiotics whether or not these medications had been prescribed by doctors or dentists. It was noted that a large proportion of the adverse effects reported by the volunteers involved symptoms related to gastrointestinal complaints. There was a high prevalence of NSAIDs consumption in the studied population, which is consistent with the high frequency of risk of adverse reactions caused by these drugs, particularly in the gastrointestinal tract. In relation to antibiotics, it was observed that the non-prescription consumption of these medications by the population was considered high, reaching one-third of the total number of volunteers who consumed such medications. [ABSTRACT FROM AUTHOR]

BackgroundUlcerative colitis (UC) and Crohn's disease are 2 types of inflammatory bowel disease (IBD), a group of chronic digestive disorders caused by aberrant immune responses to intestinal microbes. Although changes in the composition of immune cell subsets in the context of IBD have been previously described, the interactions and communication among cells are less well understood. Moreover, the precise mechanisms of action underlying many biologic therapies, including the anti-α4β7 integrin antagonist vedolizumab, remain incompletely understood. Our study aimed to explore possible additional mechanisms through which vedolizumab acts.MethodsWe performed cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) on peripheral blood and colon immune cells derived from patients with ulcerative colitis treated with the anti-α4β7 integrin antagonist vedolizumab. We applied a previously published computational approach, NicheNet, to predict immune cell-cell interactions, revealing putative ligand-receptor pairs and key transcriptional changes downstream of these cell-cell communications (CCC).ResultsWe observed decreased proportions of T helper 17 (TH17) cells in UC patients who responded to vedolizumab and therefore focused the study on identifying cell-cell communications and signals of TH17 cells with other immune cells. For example, we observed that colon TH17 cells from vedolizumab nonresponders were predicted to have a greater degree of interactions with classical monocytes compared with responders, whereas colon TH17 cells from vedolizumab responders exhibited more interactions with myeloid dendritic cells compared with nonresponders.ConclusionsOverall, our results indicate that efforts to elucidate cell-cell communications among immune and nonimmune cell types may increase the mechanistic understanding of current and investigational therapies for IBD.

Objectives: To assess the effectiveness of remimazolam against normal saline (placebo) as a sedative agent for endoscopy in a multicenter, randomized, double‐blind, investigator‐initiated phase III controlled trial. Methods: We included 48 Japanese patients undergoing upper gastrointestinal endoscopy. For the procedure, an initial remimazolam dose of 3 mg and additional doses of 1 mg were administered, as determined in the phase II clinical study. The primary study end‐point was the successful sedation rate during gastrointestinal endoscopy, determined as a Modified Observer's Assessment of Alertness/Sedation score ≤4 before the start of endoscopy, the completion of gastrointestinal endoscopy, and two or fewer additional doses per 6 min. Results: The successful endoscopy sedation rates were 91.9% and 9.1% in the remimazolam and placebo groups, respectively (P < 0.01). The time from the end of endoscopy to arousal was 0.0 (0.0–0.0) min for both groups. The number of additional doses required to achieve sedation was lower in the remimazolam group than that in the placebo group (P < 0.01). Conclusions: Remimazolam demonstrated a significantly higher sedation effect during upper gastrointestinal endoscopy in Japanese patients with safe and fast recovery compared with placebo. [ABSTRACT FROM AUTHOR]

The gut is an intricate and diverse organ system for investigating visceral pattern generation. The gut made an early evolutionary breakthrough. There is evidence that the molecular mechanisms governing the development of gastrointestinal patterns are species-specific. Some have suggested using marine drugs to treat gastrointestinal disorders. The study, which used an integrated network pharmacology approach, aimed to find out how well fucoidan worked and what Fucus vesiculosus might be doing to help prevent digestive problems. Researchers gathered information on how potential bioactive components of brown seaweed and their associated targets interact with the disease gene targets of gastrointestinal disorders. We studied the signaling pathways linked to F. vesiculosus in the context of gut health treatments using a KEGG (Kyoto Encyclopedia of Genes and Genomes pathway) and GO (Gene ontology) enrichment analysis. We built and studied the protein–protein interaction (PPI) and compound-target networks using Cytoscape. PPI network analysis yielded a total of 44 important targets, including BCL2, ESR1, and STAT3. The KEGG enrichment analysis revealed a strong correlation between the signaling pathways used in the treatment and the prevention of gastrointestinal disorders. We docked significant genes with TNF, STAT3, BCL2, and ALB. Fucoxanthin and fucoidan possess beneficial properties for improving gut health by treating gastric-intestinal issues. This study showed that by controlling several targets and many pathways with multiple components, F. vesiculosus exhibited preventive effects against gastrointestinal disorders. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced diarrhea (CID) is a potentially serious side effect that often occurs during anticancer therapy and is caused by the toxic effects of chemotherapeutic drugs on the gastrointestinal tract, resulting in increased frequency of bowel movements and fluid contents. Among these agents, irinotecan (CPT-11) is most commonly associated with CID. Hesperidin (HPD), a flavonoid glycoside found predominantly in citrus fruits, has anti-oxidation properties and anti-inflammation properties that may benefit CID management. Nevertheless, its potential mechanism is still uncertain. In this study, we firstly evaluated the pharmacodynamics of HPD for the treatment of CID in a mouse model, then used network pharmacology and molecular docking methods to excavate the mechanism of HPD in relieving CID, and finally further proved the predicted mechanism through molecular biology experiments. The results demonstrate that HPD significantly alleviated diarrhea, weight loss, colonic pathological damage, oxidative stress, and inflammation in CID mice. In addition, 74 potential targets for HPD intervention in CID were verified by network pharmacology, with the top 10 key targets being AKT1, CASP3, ALB, EGFR, HSP90AA1, MMP9, ESR1, ANXA5, PPARG, and IGF1. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the PI3K–Akt pathway, FoxO pathway, MAPK pathway, TNF pathway, and Ras pathway were most relevant to the HPD potential treatment of CID genes. The molecular docking results showed that HPD had good binding to seven apoptosis-related targets, including AKT1, ANXA5, CASP3, HSP90AA1, IGF1, MMP9, and PPARG. Moreover, we verified apoptosis by TdT-mediated dUTP nick-end labeling (TUNEL) staining and immunohistochemistry, and the hypothesis about the proteins above was further verified by Western blotting in vivo experiments. Overall, this study elucidates the potential and underlying mechanisms of HPD in alleviating CID. [ABSTRACT FROM AUTHOR]

The enteric nervous system (ENS) interacts bidirectionally with the local immune system, responding to inflammation within the gastrointestinal (GI) tract. In a previous study using the same samples, several gene targets were identified as being differentially expressed in the inflamed colonic tissue of pigs challenged with dextran sodium sulphate (DSS). Additionally, animals in the basal DSS group, exhibited reduced growth and increased fecal and pathology scores, while the relative abundance of beneficial taxa was reduced and harmful bacteria increased. While changes in the innate immune response and barrier function are widely cited regarding inflammatory bowel disease (IBD), the effects of inflammation on the local structures of the enteric nervous system (ENS) are less well understood. Hence, the objectives of this study were to: (1) evaluate the expression of a range of functionally diverse neuroactive receptors, transporters and neurotrophic factors in RNA derived from the colonic tissue from the same pigs; (2) examine associations with these neuroactive components and inflammatory, barrier function and matrix remodeling targets. Mature pigs were split into two experimental groups: (1) basal diet (n = 10); (2) basal diet + DSS (n = 11). The pigs were orally challenged with DSS once daily for four days and sacrificed humanely. Colonic tissue was collected for gene expression analysis. Most of the targets evaluated in this study were present at low levels or in some cases were undetectable by QPCR, including the dopamine receptor DRD5 and the serotonin receptor HTR3A. The dopamine receptors (DRD1, DRD3, DRD4), serotonin receptor (HTR4), and other selected neuroactive receptors (GRM7, GABRA2) were down-regulated in the DSS-challenged animals relative to the basal group (p < 0.05). Most notably, DRD2, was up-regulated four-fold, suggesting an active process involving this receptor (p < 0.05). Relationships with (previously published) gene expression data from the same samples suggest that DRD1 and DRD2 are influenced by different pathways and may also be interlinked with matrix remodeling and, more specifically, genes relevant to the epithelial to mesenchymal transition (CDH1, CDH2, IL6, IL13, IL10, MMP1, MMP2) an important fibrotic process in the pathogenesis of IBD. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of death worldwide. Around one-third of the total global cancer incidence and mortality are related to gastrointestinal (GI) cancers. Over the past few years, rapid developments have been made in patient-derived organoid (PDO) models for gastrointestinal cancers. By closely mimicking the molecular properties of their parent tumors in vitro, PDOs have emerged as powerful tools in personalized medicine and drug discovery. Here, we review the current literature on the application of PDOs of common gastrointestinal cancers in the optimization of drug treatment strategies in the clinic and their rising importance in pre-clinical drug development. We discuss the advantages and limitations of gastrointestinal cancer PDOs and outline the microfluidics-based strategies that improve the throughput of PDO models in order to extract the maximal benefits in the personalized medicine and drug discovery process. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of intestinal microecological agents in enhancing gastrointestinal function in perioperative period of Hirschsprung disease. Methods: 30 cases with surgically managed Hirschsprung in The Affiliated Hospital of Guizhou Medical University, China between March 2020 and March 2022, were randomized into control and study groups comprising 15 patients each. Both groups underwent laparoscopic-assisted megacolon-modified Swenson radical surgery. Control group received preoperative oral cefaclor suspension for three days, while the study group received Bacillus subtilis diphtheriae granules in addition to preoperative oral cefaclor suspension for four days prior to surgery, and continued from day 10 to day 24 after surgery. Symptoms, efficacy, safety, intestinal microecology, gastrointestinal function, inflammation, and nutrition were assessed upon admission, and 10 days after surgery. Postoperative complications were compared. Results: Bacterial counts in both groups increased significantly on Day 10 after surgery compared to the counts at admission (p < 0.05). The study group exhibited significantly higher counts compared to the control group (p < 0.05). The bacilli-to-cocci ratio in the study group did not change significantly (p > 0.05). Nutritional status was significantly higher in the study group compared to control group 10 days after surgery (p < 0.05). Furthermore, the incidence of small bowel colitis was lower in the study group compared to control group. There was no significant difference in the incidence of complications in both groups (p > 0.05). Conclusion: Perioperative use of intestinal microecological agents effectively corrects dysbiosis, improves gastrointestinal function, regulates nutritional indices, and reduces postoperative complications in patients with Hirschsprung disease. Future studies involving a larger number of participants from different ethnic extractions would be required to improve the quality of results obtained from this investigation. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aimed to evaluate the frequency of multidrug-resistant (MDR) bacteria in biliary samples, MDR-bacteria risk factors, and the relationship between MDR-bacteria positivity and some clinical outcomes. Materials and Methods: The study was conducted between May 2018 and May 2023, including patients over the age of 18 who had positive culture results in biliary samples. The frequency of MDR-bacteria in biliary samples was evaluated. Risk factors for MDR bacteria were assessed using univariate and multivariate analyses. MDR and non-MDR groups were compared inappropriate empirical antibiotic treatment, total antibiotic treatment duration, length of stay, and in-hospital mortality. Results: 342 microorganisms were isolated from 202 patients. Escherichia coli was the most commonly (37.2%) isolated Gram-negative microorganism, and Enterococcus spp. was the most commonly (70.2%) isolated Gram-positive microorganism. The incidence of MDR microorganisms was 42.3%. Gastrointestinal malignancy (OR: 1.96; 95% CI, 1.03-3.71) and previous antibiotic use (OR: 2.26; 95% CI, 1.09-4.68) were independent risk factors for MDR-bacteria. In the MDR group, inappropriate empirical antibiotic treatment (56.6% vs. 41%, p = 0.091), total antibiotic treatment duration (13 vs. 8 days, p = 0.054), length of stay (24 vs. 15 days, p = 0.001), and in-hospital mortality (27.3% vs. 22.3%, p = 0.416) were higher compared to the non-MDR group. Conclusion: MDR-bacteria positivity is associated with inappropriate antibiotic treatment, prolonged hospitalization, and increased mortality. Screening, antibiotic prophylaxis, and empirical treatment approaches should be carefully performed in patients with malignancy and recent antibiotic use, which are significant risk factors for MDR-bacteria. [ABSTRACT FROM AUTHOR]

Background: Non‐steroidal anti‐inflammatory drugs (NSAIDs) are commonly recommended for perioperative opioid‐sparing multimodal analgesic treatments. Concerns regarding the potential for serious adverse events (SAEs) associated with perioperative NSAID treatment are especially relevant following gastrointestinal surgery. We assessed the risks of SAEs with perioperative NSAID treatment in patients undergoing gastrointestinal surgery. Methods: We conducted a systematic review of randomised clinical trials assessing the harmful effects of NSAIDs versus placebo, usual care or no intervention in patients undergoing gastrointestinal surgery. The primary outcome was an incidence of SAEs. We systematically searched for eligible trials in five major databases up to January 2024. We performed risk of bias assessments to account for systematic errors, trial sequential analysis (TSA) to account for the risks of random errors, performed meta‐analyses using R and used the Grading of Recommendations Assessment, Development and Evaluation framework to describe the certainty of evidence. Results: We included 22 trials enrolling 1622 patients for our primary analyses. Most trials were at high risk of bias. Meta‐analyses (risk ratio 0.78; 95% confidence interval [CI] 0.51–1.19; I2 = 4%; p =.24; very low certainty of evidence) and TSA indicated a lack of information on the effects of NSAIDs compared to placebo on the risks of SAEs. Post‐hoc beta‐binomial regression sensitivity analyses including trials with zero events showed a reduction in SAEs with NSAIDs versus placebo (odds ratio 0.73; CI 0.54–0.99; p =.042). Conclusion: In adult patients undergoing gastrointestinal surgery, there was insufficient information to draw firm conclusions on the effects of NSAIDs on SAEs. The certainty of the evidence was very low. [ABSTRACT FROM AUTHOR]

Upper gastrointestinal bleeding (UGIB) is a significant concern in children, contributing to 6–20% of cases in pediatric intensive care units. This study evaluates the roles of Helicobacter pylori (H. pylori) infection and non-steroidal anti-inflammatory drug (NSAID) usage in the etiology of UGIB in children, with a particular focus on trends observed during the COVID-19 pandemic. We conducted a retrospective analysis of 103 pediatric patients who underwent esophagogastroduodenoscopy (EGD) for UGIB between January 2015 and December 2023. Of these, 88 patients were included in the final analysis, where the source of bleeding was successfully identified. Hematemesis was the most common presentation, and the source of bleeding was identified in 85.43% of cases. The prevalence of H. pylori infection remained stable across the pre-pandemic (39.7%) and post-pandemic (36.7%) periods. However, NSAID usage increased nearly threefold during the pandemic, with 36.7% of post-pandemic UGIB cases associated with NSAID use, compared to 12.1% pre-pandemic. These findings underscore the significant roles of H. pylori and NSAID use in pediatric UGIB, with a notable increase in NSAID-related cases during the pandemic. [ABSTRACT FROM AUTHOR]

Objective: In this retrospective study, we assessed the efficacy of oral lactase in infants with lactose intolerance in terms of sex, birth weight, and interference by other medications. Methods: The study was conducted on patients aged 0–6 months who had been diagnosed with lactose intolerance on admission to the Department of Social Pediatrics at Dokuz Eylul University. Demographic data, the onset of symptoms, and medications used were recorded. Results: We found that 86.7% of the infants responded to lactase, with no significant differences based on sex, birth weight, or age at symptom presentation. We observed, however, that the efficacy of treatment did improve over time, thereby deriving benefits from intestinal development and adaptation. Interestingly, the response to lactase was reduced in infants receiving concomitant simethicone for colic symptoms, suggesting a potential drug interaction, while probiotics had no impact on treatment outcomes. Conclusions: We advise against using additional medications with oral lactase, pointing out a possible interaction with simethicone that might decrease the effectiveness of treatment. [ABSTRACT FROM AUTHOR]

Background: Huangkui Lianchang Decoction (HLD) is a traditional Chinese herbal formula for treating ulcerative colitis (UC). However, its mechanism of action remains poorly understood. The Study aims to validate the therapeutic effect of HLD on UC and its mechanism by integrating network pharmacology, bioinformatics, and experimental validation. Methods: UC targets were collected by databases and GSE19101. The active ingredients in HLD were detected by ultra-performance liquid chromatography-tandem mass spectrometry. PubChem collected targets of active ingredients. Protein–protein interaction (PPI) networks were established with UC-related targets. Gene Ontology and Kyoto Encyclopedia (KEGG) of Genes and Genomes enrichment were analyzed for the mechanism of HLD treatment of UC and validated by the signaling pathways of HLD. Effects of HLD on UC were verified using dextran sulfate sodium (DDS)-induced UC mice experiments. Results: A total of 1883 UC-related targets were obtained from the GSE10191 dataset, 1589 from the database, and 1313 matching HLD-related targets, for a total of 94 key targets. Combined with PPI, GO, and KEGG network analyses, the signaling pathways were enriched to obtain IL-17, Toll-like receptor, NF-κB, and tumor necrosis factor signaling pathways. In animal experiments, HLD improved the inflammatory response of UC and reduced UC-induced pro-inflammatory factors such as Tumor Necrosis Factor Alpha (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6). HLD suppressed proteins TLR4, MyD88, and NF-κB expression. Conclusions: This study systematically dissected the molecular mechanism of HLD for the treatment of UC using a network pharmacology approach. Further animal verification experiments revealed that HLD inhibited inflammatory responses and improved intestinal barrier function through the TLR4/MyD88/NF-κB pathway. [ABSTRACT FROM AUTHOR]

The study focused on evaluating the functional properties of four lactic acid bacteria (LAB) strains - Lactobacillus fermentum 30, Lactobacillus cellobiosus 36, Lacticaseibacillus paracasei 36/1, and Lacticaseibacillus paracasei 30/1 - and their associations, aiming to assess acid resistance, bile tolerance, enzyme stability, and adhesion capabilities using in vitro methods. The survival rates of these LAB strains and their associations were investigated under simulated gastric juice (SGJ) and simulated intestinal juice (SIJ). In SGJ, the association L. fermentum 30 + L. cellobiosus 36 showed higher survival rates compared to individual strains, with approximately 75% viability after 2 hours incubation. Similarly, the association L. paracasei 30/1 + L. paracasei 36/1 exhibited enhanced survival in SGJ, maintaining about 80% viability. In SIJ, both associations demonstrated improved survival compared to individual strains, with L. fermentum 30 + L. cellobiosus 36 and L. paracasei 30/1 + L. paracasei 36/1 maintaining approximately 70% and 75% viability, respectively. The adhesion capabilities of these LAB strains and associations were evaluated using human erythrocytes. All strains displayed high adhesive activity, particularly notable in L. paracasei 36/1 + L. paracasei 30/1, which demonstrated a significantly higher adhesion index compared to other strains. These findings highlight the robust survival and adhesive properties of the LAB strains and their associations under simulated gastrointestinal conditions. Further research is warranted to explore their potential applications in promoting gut health and combating gastrointestinal disorders. [ABSTRACT FROM AUTHOR]

The role of infectious agents in gastrointestinal diseases is becoming greater, because normally the human intestines have many bacteria with an increased concentration in the lower parts of the gastrointestinal tract. The most common among the colonizing microorganisms are the so-called problematic gram-negative bacteria. In recent years, the role of one microbe in the progression of gastrointestinal diseases - Klebsiella pneumoniae - has been increasing. This bacterium is often isolated from patients with autoimmune and oncological problems such as Crohn's disease, ulcerative colitis and colorectal carcinoma. The aim of the present review is to show the role of Klebsiella pneumoniae as a potential pathogen in intestinal carriage. [ABSTRACT FROM AUTHOR]

Purpose: Adalimumab has evolved to one of the more affordable first-line biologics for the treatment of inflammatory bowel disease (IBD), since its patent expired. However, poor adherence to adalimumab is a concern and may limit its effectiveness. It is plausible that good adherence improves treatment outcomes in IBD patients, but evidence is scarce. The aim of this study was to assess whether high refill-adherence (medication possession ratio (MPR) ≥ 80%) to adalimumab is associated with less active disease in IBD patients. Methods: In this retrospective study, the MPR was used to assess refill-adherence of IBD patients using adalimumab. Disease activity was defined as a composite endpoint determined by endoscopy findings, laboratory results, validated questionnaires and clinical assessment by a gastroenterologist. Logistic regression was used to determine the association between high refill-adherence (MPR ≥ 80%) and disease activity. Results: IBD was in remission in 72 of the 113 included patients and 41 had active disease at the time of the most recent prescription. Out of the patients who were in remission, 86.1% were adherent vs. 75.6% in patients with active disease. High refill-adherence was significantly associated with lower odds of active disease after adjustment for confounders: adjusted odds ratio 0.297, 95% confidence interval 0.099–0.892. Conclusion: High refill-adherence to adalimumab therapy was associated with less active disease in IBD patients. Our results confirm the relevance of good adherence to adalimumab for achieving optimal treatment results, which may limit the need for switching to more expensive biologics. [ABSTRACT FROM AUTHOR]

Although previous studies have focused on hepatobiliary and gastrointestinal adverse drug reactions (ADRs) associated with COVID‐19 vaccines, literature on such ADRs with other vaccines is limited, particularly on a global scale. Therefore, we aimed to investigate the global burden of vaccine‐associated hepatobiliary and gastrointestinal ADRs and identify the vaccines implicated in these occurrences. This study utilized data from the World Health Organization (WHO) international pharmacovigilance database to extract reports of vaccine‐associated hepatobiliary and gastrointestinal ADRs from 1967 to 2023 (total reports = 131 255 418). Through global reporting counts, reported odds ratios (ROR) with 95% confidence interval (CI), and information components (IC) with IC0.25, the study examined the association between 16 vaccines and the incidence of hepatobiliary and gastrointestinal ADRs across 156 countries. Of the 6 842 303 reports in the vaccine‐associated ADRs, 10 786 reports of liver injury, 927 870 reports of gastrointestinal symptoms, 2978 reports of pancreas and bile duct injury, and 96 reports of intra‐abdominal hemorrhage between 1967 and 2023 were identified. Most hepatobiliary and gastrointestinal ADRs surged after 2020, with the majority of reports attributed to COVID‐19 messenger RNA (mRNA) vaccines. Hepatitis A vaccines exhibited the highest association with liver injury (ROR [95% CI]: 10.30 [9.65–10.99]; IC [IC0.25]: 3.33 [3.22]), followed by hepatitis B, typhoid, and rotavirus. Specifically, ischemic hepatitis had a significant association with both Ad5‐vectored and mRNA COVID‐19 vaccines. Gastrointestinal symptoms were associated with all vaccines except for tuberculosis vaccines, particularly with rotavirus (11.62 [11.45–11.80]; 3.05 [3.03]) and typhoid (11.02 [10.66–11.39]; 3.00 [2.96]). Pancreas and bile duct injury were associated with COVID‐19 mRNA (1.99 [1.89–2.09]; 0.90 [0.83]), MMR (measles, mumps, and rubella), and papillomavirus vaccines. For intra‐abdominal hemorrhage, inactivated whole‐virus COVID‐19 vaccines (3.93 [1.86–8.27]; 1.71 [0.41]) had the highest association, followed by COVID‐19 mRNA (1.81 [1.42–2.29]; 0.77 [0.39]). Most of these ADRs had a short time to onset, within 1 day, and low mortality rate. Through a global scale database, the majority of ADRs occurred within 1 day, emphasizing the importance of healthcare workers' vigilant monitoring and timely management. [ABSTRACT FROM AUTHOR]

Research has been conducted to explore the link between oral diseases and numerous exogenous aspects that cause it to enhance bad breath. Oral diseases that cause bad breath consist of oral infections, poor oral hygiene, several foodstuffs, and basic medical conditions. Some of the prevalent oral diseases are periodontitis and gingivitis because they create bad breath resulting from overgrowth of microorganisms in the oral cavity. Apart from the infection in the mouth, halitosis is also triggered by extra oral such as respiratory and gastrointestinal ailments and drugs; all these factors lead to the development of volatile Sulphur compounds as well as other odorizing molecules, which are subsequently spread through the blood and exhaled through the lungs. In addition to situations mentioned above, extra oral factors, for example, respiratory and GI conditions and particular medicines, can cause the production of VSCs as well as additional odorous compounds. The bloodstream serves as a vehicle for these substances, and then the lungs expel them. In general, the connection between oral illness and external factors that contribute to foul breath is intricate. A comprehensive approach to managing bad breath may involve addressing both oral and extra oral factors and addressing any underlying medical conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: Enteric viruses are the main cause of gastrointestinal disease in dogs. Canine astrovirus (CaAstV) is an enteric virus that causes severe dehydration, diarrhea and vomiting, among other gastrointestinal symptoms. The present study is based on the design, standardization, and execution of a rapid and sensitive qPCR protocol using SYBR Green for the identification of CaAstV in dogs with gastroenteritis in Ecuador as a causative agent of gastrointestinal disease in co-infection with other viruses, such as canine parvovirus. The assay was shown to be repeatable, specific and sensitive based on the tests performed. The method was tested on 221 samples from dogs with gastroenteritis, of which 52.8% showed positivity for CaAstV. Sequencing of a segment of the ORF1b gene of the virus genome was performed to validate the presence of the virus, leading to the identification of two possible lineages of the virus circulating in Ecuador. This is the first report of CaAstV in the country. The present trial demonstrates the need for the application of molecular methods for the diagnosis and monitoring of emerging viruses in animals that could be influencing canine mortality due to gastrointestinal disease. Enteric viruses are responsible for a significant number of gastrointestinal illnesses in dogs globally. One of the main enteric viruses is the canine astrovirus (CaAstV), which causes diarrhea in dogs of various ages. It is linked to symptoms such as diarrhea, vomiting, depression and a significant mortality rate due to gastrointestinal disorders. It is a single-stranded positive RNA virus, with three open reading frames, ORF1a, ORF1b and ORF2, where the last one codes for the virus capsid protein and is the most variable and antigenic region of the virus. The aim of this work is to develop and standardize a quick detection method to enable the diagnosis of this etiological agent in dogs with gastroenteritis in Ecuador in order to provide prompt and suitable treatment. The assay was specific for amplification of the genome of CaAstV, as no amplification was shown for other canine enteric viruses (CPV-2, CCoV and CDV), sensitive by being able to detect up to one copy of viral genetic material, and repeatable with inter- and intra-assay coefficients of variation of less than 10% between assays. The standard curve showed an efficiency of 103.9%. For the validation of this method, 221 fecal samples from dogs affected with gastroenteritis of various ages from different provinces of Ecuador were used. From the RT-qPCR protocol, 119 samples were found positive for CaAstV, equivalent to 53.8% of the samples processed. CaAstV was detected in dogs where both the highest virus prevalence in the tested strains and the highest viral loads were seen in the younger canine groups up to 48 weeks; in addition, different strains of the virus were identified based on a sequenced fragment of ORF1b, demonstrating the first report of the presence of CaAstV circulating in the domestic canine population affected by gastroenteritis in Ecuador, which could be associated with the etiology and severity of enteric disease. [ABSTRACT FROM AUTHOR]

BackgroundPegozafermin is a long-acting glycopegylated (pegylated with the use of site-specific glycosyltransferases) fibroblast growth factor 21 (FGF21) analogue in development for the treatment of nonalcoholic steatohepatitis (NASH) and severe hypertriglyceridemia. The efficacy and safety of pegozafermin in patients with biopsy-proven noncirrhotic NASH are not well established.MethodsIn this phase 2b, multicenter, double-blind, 24-week, randomized, placebo-controlled trial, we randomly assigned patients with biopsy-confirmed NASH and stage F2 or F3 (moderate or severe) fibrosis to receive subcutaneous pegozafermin at a dose of 15 mg or 30 mg weekly or 44 mg once every 2 weeks or placebo weekly or every 2 weeks. The two primary end points were an improvement in fibrosis (defined as reduction by ≥1 stage, on a scale from 0 to 4, with higher stages indicating greater severity), with no worsening of NASH, at 24 weeks and NASH resolution without worsening of fibrosis at 24 weeks. Safety was also assessed.ResultsAmong the 222 patients who underwent randomization, 219 received pegozafermin or placebo. The percentage of patients who met the criteria for fibrosis improvement was 7% in the pooled placebo group, 22% in the 15-mg pegozafermin group (difference vs. placebo, 14 percentage points; 95% confidence interval [CI], -9 to 38), 26% in the 30-mg pegozafermin group (difference, 19 percentage points; 95% CI, 5 to 32; P = 0.009), and 27% in the 44-mg pegozafermin group (difference, 20 percentage points; 95% CI, 5 to 35; P = 0.008). The percentage of patients who met the criteria for NASH resolution was 2% in the placebo group, 37% in the 15-mg pegozafermin group (difference vs. placebo, 35 percentage points; 95% CI, 10 to 59), 23% in the 30-mg pegozafermin group (difference, 21 percentage points; 95% CI, 9 to 33), and 26% in the 44-mg pegozafermin group (difference, 24 percentage points; 95% CI, 10 to 37). The most common adverse events associated with pegozafermin therapy were nausea and diarrhea.ConclusionsIn this phase 2b trial, treatment with pegozafermin led to improvements in fibrosis. These results support the advancement of pegozafermin into phase 3 development. (Funded by 89bio; ENLIVEN ClinicalTrials.gov number, NCT04929483.).

Background: The incidence of diabetic gastrointestinal diseases is increasing year by year. This study aimed to investigate the causal relationship between antidiabetic medications and gastrointestinal disorders, with the goal of reducing the incidence of diabetes-related gastrointestinal diseases and exploring the potential repurposing of antidiabetic drugs. Methods: We employed a two-sample Mendelian randomization (TSMR) design to investigate the causal association between antidiabetic medications and gastrointestinal disorders, including gastroesophageal reflux disease (GERD), gastric ulcer (GU), chronic gastritis, acute gastritis, Helicobacter pylori infection, gastric cancer (GC), functional dyspepsia (FD), irritable bowel syndrome (IBS), ulcerative colitis (UC), Crohn's disease (CD), diverticulosis, and colorectal cancer (CRC). To identify potential inhibitors of antidiabetic drug targets, we collected single-nucleotide polymorphisms (SNPs) associated with metformin, GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, insulin, and its analogs, thiazolidinediones, sulfonylureas, and alpha-glucosidase inhibitors from published genome-wide association study statistics. We then conducted a drug-target Mendelian randomization (MR) analysis using inverse variance weighting (IVW) as the primary analytical method to assess the impact of these inhibitors on gastrointestinal disorders. Additionally, diabetes was selected as a positive control. Results: Sulfonylureas were found to significantly reduce the risk of CD (IVW: OR [95% CI] = 0.986 [0.978, 0.995], p = 1.99 × 10− 3), GERD (IVW: OR [95% CI] = 0.649 [0.452, 0.932], p = 1.90 × 10− 2), and chronic gastritis (IVW: OR [95% CI] = 0.991 [0.982, 0.999], p = 4.50 × 10− 2). However, they were associated with an increased risk of GU development (IVW: OR [95%CI] = 2 0.761 [1.259, 6.057], p = 1 0.12 × 10− 2). Conclusions: The results indicated that sulfonylureas had a positive effect on the prevention of CD, GERD, and chronic gastritis but a negative effect on the development of gastric ulcers. However, our research found no causal evidence for the impact of metformin, GLP-1 agonists, SGLT2 inhibitors, DPP 4 inhibitors, insulin and its analogs, thiazolidinediones, or alpha-glucosidase inhibitors on gastrointestinal diseases. [ABSTRACT FROM AUTHOR]

Background: The pharmacist plays an essential role in identifying and managing drug-related problems. The aim of this research was to assess the costs avoided by clinical pharmacist interventions to resolve drug-related problems. Research design and methods: Clinical pharmacists identified drug-related problems and interventions to address them in consecutive outpatients visiting internal medicine clinics at major teaching and public hospitals in Jordan from September 2012 to December 2013. The costs avoided by each intervention to address drug-related problems were collected from the literature. The collected data were used to calculate the overall cost saved and avoided by the interventions implemented to address the identified drug-related problems, adopting a Jordanian healthcare system perspective. Results: A total of 2747 patients were enrolled in the study. Diagnostic interventions, such as the need for additional diagnostic testing, were employed in 95.07% of the 13935 intervention to address the drug-related problem "Miscellaneous" which was the most frequent drug-related problems. Other common drug-related problems categories included inappropriate knowledge (n = 6972), inappropriate adherence (4447), efficacy-related drug-related problem (3395) and unnecessary drug therapy (1082). The total cost avoided over the research period was JOD 1418720 per month and total cost saved over the study period was JOD 17250.204. Drug-related problems were associated the number of prescription medications (odds ratio = 1.105; 95% confidence interval = 1.069–1.142), prescribed gastrointestinal drugs (3.485; 2.86–4.247), prescribed antimicrobials (3.326; 1.084–10.205), and prescribed musculoskeletal drugs (1.385; 1.011–1.852). Conclusions: The study revealed that pharmacists have provided cognitive input to rationalize and optimize the medication use and prevent errors, that led to the reported projected avoided and saved expenditures via various interventions to address drug-related problems. This highlights the added economic impact to the clinical impact of drug-related problems on patients and the healthcare system. The high prevalence and cost of drug-related problems offer strong rationale for pharmacists to provide more vigilant intervention to improve patient outcomes while maintaining cost effectiveness. [ABSTRACT FROM AUTHOR]

Background Stress during a pandemic increases the risk of alcohol consumption, which may require pharmacological management. Methods An observational single-center retrospective study was conducted from 1 January 2018 to 31 December 2021, and divided into 2-year periods (2018–2019 and 2020–2021). This study focused on calls to one of the emergency departments (EDs) of seven hospitals in the Bari (Italy) metropolitan area for patients requiring emergency services (ESs) who were either admitted or not admitted, due to their refusal. Results A 30% reduction in emergency calls for alcohol-related issues and a 41.17% reduction in calls for patients who refused to be admitted to the ED were observed during the pandemic. During the pandemic, an inverse association was found between pharmacological treatment and number of calls coded green (non-critical) and yellow (fairly critical) in patients admitted to EDs. An inverse association was also found for calls coded green in patients not admitted to EDs and pharmacological treatment. Metadoxine was administered in almost all alcohol-related emergencies, primarily in conjunction with drugs acting on the gastrointestinal tract, irrespective of age, the period considered, and whether patients were admitted or not admitted to the ED. Conclusions ES is the first and only out-of-hospital service encountered by numerous patients with alcohol-use disorders who refuse to be admitted to the ED. These patients should be directed by ES personnel to a multidisciplinary program to receive treatment for drinking, improve their quality of life, and reduce sanitation costs. [ABSTRACT FROM AUTHOR]

Summary: There is a significant concern associated with the delivery of chemotherapeutics to the colon due to limited drug absorption in the gastrointestinal tract. Starch has received great interest as a delivery agent owing to its cost efficacy and high availability. In this study, native resistant starch and acid‐modified resistant starch from Vigna unguiculata were used to produce microcapsules containing camptothecin as an oral‐colon‐specific drug delivery agent. Functional characteristics such as solubility, swelling power, amylose content, emulsifying, foaming together with water and oil absorption capacity of native resistant starch and acid‐modified resistant starch were established. The prepared microcapsules were characterised and subjected to simulated digestion with the obtained residue evaluated for cytotoxicity using the MTT assay. It was observed that acid‐modified resistant starch had the best functional properties (water absorption capacity: 2.76 g g−1, oil absorption capacity: 3.13 g g−1, amylose: 35%, foaming capacity: 17.73%, and emulsifying activity: 33.33%) as compared to its native resistant starch (water absorption capacity: 2.03 g g−1, oil absorption capacity: 2.81 g g−1, amylose: 32%, foaming capacity: 4% and emulsifying activity: 23.56%). The microcapsules had a particle size of 0.25–0.35 μm, moisture content between 1.12% and 3.41% and a high encapsulation efficiency of 96.40 and 98.96% for native resistant starch and acid‐modified resistant starch capsules respectively. Results for MTT assay showed cancerous cells to be inhibited by microcapsules with noncancerous cells less affected. [ABSTRACT FROM AUTHOR]

Information on the conditions under which drugs are transferred from the stomach through the upper small intestine after a high-calorie, high-fat meal is very limited. To simulate the drug presence after disintegration and arrival in the antral region, paracetamol solution and Sporanox® amorphous solid dispersion pellets at two dose levels were administered to the antrum of 8 healthy adults 30 min after administration of a high-calorie, high-fat meal on a crossover basis. The overall median buffer capacity of antral contents was estimated to be 18.0 and 24.0 mmol/ml/ΔpH when titrating with NaOH and HCl, respectively. The corresponding values for the contents of upper the small intestine were 14.0 and 16.8 mmol/ml/ΔpH, respectively. The drug transfer process from the antrum through the upper small intestine occurred with apparent first-order kinetics. The best estimate for the antral emptying half-life was 39min and 45min for paracetamol and itraconazole, respectively, the apparent volume of contents of the upper small intestine was more than double compared with previously reported values in the fasted state, the half-life of drug elimination from the upper small intestine was similar to recent estimates for highly permeable drugs in the fasted state, and the apparent volume of antral contents during the first couple of hours post drug administration was 303mL. Information collected in this study could increase the reliability of in silico and/or in vitro modelling approaches applied in clinical drug development. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: This study aimed to evaluate racial disparities in medication use and associated factors among pregnant women receiving prenatal care at Brazilian Unified Health System primary care health units in the northeast region. Patients and Methods: A total of 1058 pregnant women in the NISAMI Cohort were interviewed between June 2012 and February 2014. Medicines used during pregnancy were classified according to the Anatomical Therapeutic Chemical (ATC) classification system and ANVISA pregnancy risk categories. Prevalence ratios (crude and adjusted) and 95% confidence intervals (CIs) were estimated using Poisson regression with robust error variance. All analyses were stratified by race (Asian, black, brown/mixed, Brazilian indigenous, and white). Results: Approximately 84% of the pregnant women used at least one medication, with a lower proportion among white women. The most reported medications were antianemic preparations (71.08%; 95% CI 68.27– 73.72%), analgesics (21.74%; 95% CI 19.36– 24.32%), and drugs for functional gastrointestinal disorders (18.81%; 95% CI 16.57– 21.28%). Approximately 29% of women took potentially risky medications during pregnancy, with a higher prevalence among Asian and white women. Factors associated with medication use during pregnancy include a greater number of prenatal consultations, higher education levels, health problems, and smoking. In addition, maternal age above 25 years, smoking status, and two or more previous pregnancies were associated with potentially risky medication use during pregnancy. Conclusion: A high prevalence of medication use during pregnancy was found; however, this prevalence was lower among white women. Nonetheless, black and brown women used antianemic preparations less frequently. This finding suggests that race is a factor of inequity in prenatal care, demanding public policies to mitigate it. [ABSTRACT FROM AUTHOR]

Introduction: We examined the gut microbiota of travellers returning from tropical areas with and without traveller's diarrhoea (TD) and its association with faecal lipocalin-2 (LCN2) levels. Methods: Participants were recruited at the Hospital Clinic of Barcelona, Spain, and a single stool sample was collected from each individual to perform the diagnostic of the etiological agent causing gastrointestinal symptoms as well as to measure levels of faecal LCN2 as a biomarker of gut inflammation. We also characterised the composition of the gut microbiota by sequencing the region V3-V4 from the 16S rRNA gene, and assessed its relation with the clinical presentation of TD and LCN2 levels using a combination of conventional statistical tests and unsupervised machine learning approaches. Results: Among 61 participants, 45 had TD, with 40% having identifiable etiological agents. Surprisingly, LCN2 levels were similar across groups, suggesting gut inflammation occurs without clinical TD symptoms. Differential abundance (DA) testing highlighted a microbial profile tied to high LCN2 levels, marked by increased Proteobacteria and Escherichia-Shigella, and decreased Firmicutes, notably Oscillospiraceae. UMAP analysis confirmed this profile's association, revealing distinct clusters based on LCN2 levels. The study underscores the discriminatory power of UMAP in capturing meaningful microbial patterns related to clinical variables. No relevant differences in the gut microbiota composition were found between travellers with or without TD. Discussion: The findings suggest a correlation between gut microbiome and LCN2 levels during travel, emphasising the need for further research to discern the nature of this relationship. [ABSTRACT FROM AUTHOR]

Background and Aim: The quality of clinical practice guidelines (CPGs) for the management of antithrombotic agents in patients undergoing gastrointestinal (GI) endoscopy has not been systematically appraised. The goal of this study was to evaluate the methodological quality of CPGs for the management of antithrombotic agents in periendoscopic period published within last 6 years. Methods: A systematic search of PubMed and Embase databases was performed to identify eligible CPGs published between January 1, 2016, and April 14, 2022, addressing the management of antithrombotic agents in the periendoscopic period. The quality of the CPG was independently assessed by six reviewers using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Domain scores were considered of sufficient quality when > 60% and of good quality when > 80%. Results: The search yielded 343 citations, of which seven CPGs published by the gastroenterology associations in Asia (n = 3), Europe (n = 2), and North America (n = 2) were included for the critical appraisal. The overall median score for the AGREE II domains was 93% (interquartile range [IQR] 11%) for scope and purpose, 79% (IQR 61%) for stakeholder involvement, 79% (IQR 36%) for rigor of development, 100% (IQR 14%) for clarity of presentation, 32% (IQR 36%) for applicability, 93% (IQR 29%) for editorial independence, and 86% (IQR 29%) for overall assessment. Conclusions: The findings show that the overall methodological quality of the CPGs for the management of antithrombotic agents in the periendoscopic period varies across the domains. There is significant scope for improvement in the methodological rigor and applicability of CPGs. [ABSTRACT FROM AUTHOR]

BACKGROUND: The notion that gas-bloat syndrome (GBS) after magnetic sphincter augmentation (MSA) is less detrimental has not been substantiated by data. This study aimed to identify the incidence, natural history, risk factors, and impact on outcomes of GBS after MSA. STUDY DESIGN: Records of patients who underwent MSA at our institution were reviewed. GBS was defined as a score of 4 or more on the gas bloat-specific item within the GERD health-related quality-of-life (GERD-HRQL) questionnaire. Preoperative clinical and objective testing data were compared between those with and without GBS at 1 year using univariate followed by multivariable analysis. GBS evolution over time and its impact on outcomes were assessed in those with 1- and 2-year follow-up. RESULTS: A total of 489 patients underwent MSA. At a mean (SD) follow-up of 12.8 (2.1) months, patient satisfaction was 88.8%, 91.2% discontinued antisecretory medications, and 74.2% achieved DeMeester score normalization. At 1 year, 13.3% of patients developed GBS, and had worse GERD-HRQL scores and antisecretory medication use and satisfaction (p < 0.0001). DeMeester score normalization was comparable (p = 0.856). Independent predictors of GBS were bloating (odds ratio [OR] 1.8, p = 0.043), GERD-HRQL score greater than 30 (OR 3, p = 0.0010), and MSA size 14 or less beads (OR 2.5, p = 0.004). In a subgroup of 239 patients with 2-year follow-up, 70.4% of patients with GBS at 1 year had resolution by 2 years. The GERD-HRQL total score improved when GBS resolved from 11 (7 to 19) to 7 (4 to 10), p = 0.016. Patients with persistent GBS at 2 years had worse 2-year GERD-HRQL total scores (20 [5 to 31] vs 5 [3 to 12], p = 0.019). CONCLUSIONS: GBS affects 13.3% of patients at 1 year after MSA and substantially diminishes outcomes. However, GBS resolves spontaneously with quality-of-life improvement. Patients with preoperative bloating, high GERD-HRQL scores, or small MSA devices are at greatest risk of this complication. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant cancer treatment side effect that can influence both quality of life and treatment course. Melissa Officinalis (MO), due to its high content of flavonoids, has antioxidant, anti-inflammatory, and neuroprotective properties. Materials and Methods: The cancer patients diagnosed with CIPN attended a referral center in Sari (Iran). The hydroalcoholic extract of MO leaves was extracted by the maceration method. The control group received a placebo along with gabapentin as the standard treatment, and the intervention group received 500 mg Melissa officinalis 2 times daily for 3 months plus gabapentin. Patients were evaluated at the baseline and 3 months later, according to Common Terminology Criteria for Adverse Effects (CTCAE) and EORTC QLQ-C30 (Integrated System for Quality of Life Assessment). Results: A total of 40 patients were considered as group D (intervention group), and 35 patients completed the study. Out of 40 subjects in the placebo group (P), 3 patients could not tolerate the drug due to gastrointestinal disturbances. The final values of CTCAE showed a statistically significant difference (p=0.010). Indicators related to the quality of life in both groups showed a significant improvement. In the intervention group, the pain perception and diarrhea experience were significantly reduced. Conclusion: Quality of life indicators were improved by prescribing gabapentin with and without Melissa officinalis. The addition of Melissa officinalis to the chemotherapy regimen may improve diarrhea and pain perception. [ABSTRACT FROM AUTHOR]

Curcumin (CCM) is a polyphenol compound extracted from the turmeric rhizome. It has various biological activities, including antibacterial, anti-inflammatory, anti-cancer, and antioxidant. Due to its diverse activities, it is often used by researchers to study the therapeutic effects on various diseases. However, its poor solubility leads to poor bioavailability, and it is necessary to increase the water solubility with the help of carriers to improve the therapeutic effect. Gastrointestinal disease is a major global health problem that continues to affect human health. In this review, we have summarized the possible mechanism and therapeutic effect of CCM in various gastrointestinal diseases, and the improvement in the curative effect of CCM with nanopreparation. Finally, we concluded that there have been many clinical trials of CCM in combination with other drugs for the treatment of gastrointestinal disease, but so far, few have used CCM nanomaterials for treatment. Although in vitro and preclinical experiments have shown that nanopreparations can improve the efficacy of CCM, there are still insufficient studies on the safety of carriers. [ABSTRACT FROM AUTHOR]

Background: Sodium polystyrene sulfonate (SPS) is a nonselective sodium-potassium exchange resin commonly used along with intravenous (IV) insulin, albuterol, furosemide, and/or calcium for the treatment of acute hyperkalemia. Sodium zirconium cyclosilicate (SZC) is a newer non-absorbed exchange resin that preferentially increases fecal potassium excretion from the gastrointestinal tract. Limited data exists on the efficacy of SZC for the treatment of acute hyperkalemia. Objectives: To assess the achievement of normokalemia (serum potassium level [K+] 3.5-5.2 mmol/L) within 24 hours after administration of SZC or SPS in combination with insulin regular IV push. Methods: A multicenter, retrospective chart review (2020-2021) using electronic medical records at an academic health system. The study population included adult patients receiving one or more doses of SZC or SPS in combination with IV insulin for acute hyperkalemia (K+ >5.2 mmol/L). Patients receiving dialysis were excluded. Serum chemistries were assessed at baseline and an additional 2 values within 24 hours to determine normokalemia and hypokalemia at each follow-up. Results : Of 141 patients included, 51 received SZC and 90 received SPS. Normokalemia at the first follow-up was achieved in 51.0% of patients receiving SZC and 46.7% of patients receiving SPS (P =.622) and was sustained in 35.3%versus 44.4% (P =.289) of patients within 24 hours. Mean serum potassium differences from baseline to first follow-up were similar between SZC and SPS groups (0.9 mmol/L vs 1.0 mmol/L). Hypokalemia within 24 hours of administration occurred in 4 patients—1 in SZC, 3 in SPS. Conclusion: Both SZC and SPS yielded similar rates of normokalemia achievement with IV insulin for the treatment of acute hyperkalemia. Further prospective studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

The burgeoning population of livestock within protected areas exacerbates the transmission risk of parasitic diseases among vulnerable wild ungulates. This study, conducted in the Bani Wildlife Sanctuary nestled in the western Himalayas, focused on the peak periods of livestock grazing (June-October) in 2021 and 2022 to assess the prevalence of gastrointestinal parasites in domestic sheep and goats. A comprehensive examination involved the collection of 230 faecal samples (125 from goats and 105 from sheep) from various locations within the sanctuary, followed by analysis using established sedimentation and floatation techniques. Our findings revealed the presence of 10 distinct parasite taxa, encompassing one coccidian cyst, one cestode, two trematodes, and six nematodes. Comparative analysis with documented parasites infecting wild ungulates underscores the considerable potential for cross-transmission via the faecal-oral route. Notably, the prevalence of gastrointestinal parasite taxa stood at 83.72% in goats and 74.35% in sheep, indicating their heightened susceptibility and potential contribution to pasture infectivity, surpassing that of wild ungulates. These findings suggest a significantly elevated risk of gastrointestinal parasitic transmission from domestic animals to their wild counterparts. Consistent with comparable studies, evidence suggests a correlation between parasite infection in livestock and sympatric wild ungulates, suggesting the perpetuation of these infections within the shared ecosystem. To mitigate this risk, we advocate for the regulation of anthelmintic treatment for domestic livestock and the implementation of grazing zonation strategies to curtail parasite transmission. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Clinical Nursing in Practice is the property of Journal of Clinical Nursing in Practice (Editorial Board, Shanghai Jiao Tong University Press) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)