Intestinal Research Articles

Gastrointestinal Conditions Affect Chronic Pain and Quality of Life in Women

Pain is a chronic condition in many women; drugs used for its treatment are often accompanied by detrimental effects on many organs, including the gut. Once inflamed, the gut can affect pain processes. The aim of this study was to evaluate the general health of women suffering chronic pain, with particular attention to gastrointestinal (GI) conditions. The possibility to improve pain and quality of life through personalized nutritional advice was also tested. Forty women suffering from chronic pain were contacted for the administration of questionnaires to define their pain features and gastrointestinal conditions. Their psychological, clinical and reproductive states were also recorded. Pain scores were correlated with GI, psychological and clinical scores. Diet suggestions were given, and evaluation was repeated after 4 weeks. Thirty-eight women were included in the study: 32 suffered chronic widespread pain and had 6 pelvic pain. Pain had been present in all women for years; more than 80% of women reported various types of disorders related to the gut. Pain scores were worse in the women intolerant to milk and dairy products. The GI score was positively correlated with the pain score. The Dietary Inflammatory Index was very high in all subjects. Personalized nutritional advice followed by 26 subjects for 4 weeks resulted in a significant improvement of pain and quality of life parameters. We describe women with chronic pain as being particularly affected by GI alterations. The change in feeding habits had a beneficial effect on pain and other quality of life parameters.

Probiotic Milk and Oat Beverages with Increased Protein Content: Survival of Probiotic Bacteria Under Simulated In Vitro Digestion Conditions

Background: The increasing prevalence of plant-based dietary preferences, driven by lactose intolerance, allergies, and adherence to vegan diets, has necessitated the exploration of alternative food matrices for probiotic delivery. Objectives: This study aimed to evaluate the effects of whey protein isolate, pea protein isolate, and soy protein isolate on the viability of L. casei and L. johnsonii during simulated in vitro gastrointestinal digestion. Furthermore, the study investigated the impact of two distinct matrices—cow’s milk and an oat-based beverage—on the survival of these probiotic strains. Fermented products were prepared using cow’s milk and an oat-based beverage as matrices, with simulated digestion performed following a seven-day storage period at 5 °C. The in vitro digestion model encompassed oral, gastric, and small intestinal phases, with probiotic viability assessed using the plate-deep method at each stage. Methods: Before digestion, L. casei exhibited higher populations than L. johnsonii in both matrices. Including 3% soy and pea protein, isolates promoted the growth of L. casei in both fermented milk and oat beverages. However, a marked reduction in probiotic viability was observed during the gastric phase, with L. casei counts decreasing by 6.4–7.8 log cfu g−1 in fermented milk and 3.1–4 log cfu g−1 in oat beverages, while L. johnsonii demonstrated similar reductions. Conclusion: These findings underscore the protective role of dairy components on probiotic viability, while the oat-based matrix exhibited a reduced capacity for sustaining probiotic populations throughout digestion. Future research should focus on optimizing plant-based matrices to enhance probiotic stability during gastrointestinal transit.

Uncovering the Potential Somatic Angiotensin-Converting Enzyme (sACE) Inhibitory Capacity of Peptides from Acheta domesticus: Insights from In Vitro Gastrointestinal Digestion

Entomophagy is being proposed as a sustainable and nutritious alternative protein source. Additionally, insect consumption is also associated with some health benefits mediated by bioactive compounds produced during gastrointestinal (GI) digestion. The antihypertensive property resulting from the inhibition of the somatic angiotensin-converting enzyme (sACE) by small peptides is one of the most common bioactivities related to insect consumption. This study aimed to investigate the potential sACE-inhibitory capacity of six peptides (AVQPCF, CAIAW, IIIGW, QIVW, PIVCF, and DVW), previously identified by the in silico GI digestion of Acheta domesticus proteins, validate their formation after in vitro GI digestion of A. domesticus by LC-MS/MS, and assess the bioactivity of the bioaccessible digesta. The results showed that the IC50 values of AVQPCF, PIVCF, and CAIAW on sACE were 3.69 ± 0.25, 4.63 ± 0.16, and 6.55 ± 0.52 μM, respectively. The obtained digesta demonstrated a sACE-inhibitory capacity of 77.1 ± 11.8 µg protein/mL extract (IC50). This is the first report of the sACE-inhibitory capacity attributed to whole A. domesticus subjected to GI digestion without any pre-treatment or protein concentration. This evidence highlights the potential antihypertensive effect of both the digesta and the identified peptides.

Death and survival of gut CD4 T cells following HIV-1 infection ex vivo

Abstract The gastrointestinal (GI) tract is ground zero for the massive and sustained CD4 T cell depletion during acute HIV-1 infection. To date, the molecular mechanisms governing this fundamental pathogenic process remain unclear. HIV-1 infection in the GI tract is associated with chronic inflammation due to a disrupted epithelial barrier that results in microbial translocation. Here, we utilized the Lamina Propria Aggregate Culture model to demonstrate that the profound induction of Granzyme B (GZB) by bacteria in primary gut CD4 T cells ex vivo significantly contributes to HIV-1-mediated CD4 T cell death. Counterintuitively, a substantial fraction of gut GZB+ CD4 T cells harboring high levels of HIV-1 infection survive via a pathway linked to CD120b/TNFR2. Our findings underscore novel mechanisms governing the death and survival of gut CD4 T cells during HIV-1 infection that could inform strategies to counter HIV-1 pathogenesis and persistence in this critical tissue compartment.

Integrated multi-omics analysis of the microbial profile characteristics associated with pulmonary arterial hypertension in congenital heart disease.

Dysregulation of immune and inflammatory cells around blood vessels and metabolic dysfunction are key mechanisms in the development of pulmonary arterial hypertension (PAH). The homeostasis of the human microbiome plays a crucial role in regulating immune responses and the progression of diseases. For pulmonary arterial hypertension associated with congenital heart disease involving body-lung shunt (PAH-CHD), the potential impact of the microbiome on the "gut-lung axis" remains underexplored. This study recruited 15 healthy individuals and 15 patients with pulmonary arterial hypertension due to congenital heart disease from Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, and Kunming Children's Hospital. We performed differential analyses of metabolites and microbiota from both the gut and lower respiratory tract for these two groups. The goal was to investigate the "gut-lung axis" microbiome and metabolome profiles in children with PAH-CHD and to analyze the interrelationships between these profiles. Ultimately, we aim to propose the potential value of these profiles in aiding diagnosis. The results indicated that the gut and pulmonary microbiota of children with PAH-CHD are characterized by an increased abundance of beneficial symbionts, which are closely linked to changes in the metabolome. Metabolite functional enrichment analysis revealed energy metabolism reprogramming in the PAH-CHD group, with active metabolic pathways associated with bile acid secretion and carnitine homeostasis. Moreover, the differential expression of metabolites was correlated with right heart function and growth development.IMPORTANCEPrevious studies have primarily focused on the relationship between the gut microbiome and PAH. However, the impact of microbial homeostasis on the progression of PAH-CHD from the perspective of the gut-lung axis has not been adequately elucidated. Our study utilizes an integrated multi-omics approach to report on the differential characteristics of gut and lung microbiota between children with PAH-CHD and reference subjects. We found that microbiota influence the pathological changes and disease manifestations of PAH-CHD through their metabolic activity. Additionally, alterations in metabolites impact the microbial ecological structure. Our findings suggest that modulating the microbiome composition may have positive implications for maintaining and regulating the immune environment and pathological progression of PAH-CHD.

In vitro validation of colon delivery of vitamin B2 through a food grade multi-unit particle system.

Colon target delivery of active ingredients is frequently applied in pharmaceutical products. However, in functional food and beverage applications, dietary supplements, and medical nutrition, formats targeting colonic delivery to improve human health are rare. Nevertheless, there is emerging evidence for beneficial effects of colonic delivered nutrients on gut microbiota and host health which increases the demand for sustainable food grade materials that are regulatory approved for application. In this paper, we describe a double layer coated multi-unit particle system (MUPS) with a diameter of approximately 730 microns consisting of food grade materials: shellac as outer layer, alginate as inner layer, cellulose as a core and riboflavin as active ingredient. The suitability of the MUPS for colonic delivery was tested in three well-established in vitro digestion and fermentation models: the USP Apparatus 3 and the TNO Intestinal Models 1 and 2 (TIM-1 and TIM-2). All systems confirmed the integrity of the MUPS under simulated upper gastrointestinal tract conditions with approximately 90% of the active ingredient being released under simulated ileal-colonic conditions. The TIM-2 model also showed the effects of riboflavin loaded MUPS on the microbiome composition with an increase in the production of short-chain fatty acids, acetate and butyrate. The results of these experiments provide a reliable basis for validation of this vitamin-loaded food grade MUPS in future human clinical trials. In addition, following the recent announcement of the European Commission to restrict intentionally added microplastics to products, the materials used in the described formulation offer an environmentally friendly alternative to often applied methyl acrylate based coatings.

The Association of High Burden Premature Ventricular Contractions with Esophageal/Upper GI Diseases

Six patients in our clinical program who were diagnosed with high burden (>10%) premature ventricular contractions (PVCs) and concomitant significant upper GI disease with no other significant cardiac history demonstrated a significant reduction in the burden of PVCs following surgical or procedural interventions of the upper GI tract (68.34% reduction, p = 0.024). Furthermore, in all cases, the origin of the PVCs was from the base of the right ventricular outflow tract (RVOT). This is the first report in the literature that we are aware of that makes the unique association that we propose a dual mechanism of action of the upper GI and vagally mediated PVCs and through direct, anatomical extrinsic triggering of the right ventricular outflow tract (RVOT) of the heart. These are very preliminary findings that warrant larger clinical and mechanistic studies that if confirmed, may define a new physiologic subset of PVCs for which we propose a new term, “E-PVCs”.

Gastrointestinal manifestations of Rett syndrome: An updated analysis using the Gastrointestinal Health Questionnaire.

We conducted a nationwide survey using a validated Gastrointestinal Health Questionnaire (GHQ) for Rett syndrome (RTT) to provide an updated and accurate baseline assessment of the prevalence of common gastrointestinal (GI) issues in RTT, based on parental reporting. Parents and caregivers of females with RTT or normally developing, unaffected, age-matched controls completed the GHQ survey. The prevalence of GI symptoms and personality and mood symptoms due to stomach or intestinal problems, as well as GI medication usage and surgical interventions, were assessed in females with RTT and unaffected controls. The relation between GI symptoms and medication usage, surgical status, age, and genetic mutation were analyzed. Parents of 118 females with RTT and 27 unaffected females completed the GHQ. GI symptoms were common in females with RTT, including constipation (81%), gas and bloating (70%), issues with eating, chewing and swallowing (73%), and irritability because of stomach or intestinal problems (53%). Females with RTT commonly used proton pump inhibitors (52%) and laxatives (64%). Medication usage was associated with significantly higher GHQ symptom scores. Parents of individuals with RTT reported a significantly higher prevalence of GI symptoms affecting their daughters in all symptom categories compared with unaffected females. GI problems are common in RTT and pose a significant medical burden to caregivers. The GHQ is a useful tool to assess GI issues in individuals with RTT. Improved recognition of these issues may allow for improved treatment and enhanced quality of life for girls and women affected by RTT.

Gastrointestinal infections and ethnicity in the UK: a systematic review and narrative synthesis

Abstract Background Gastrointestinal (GI) infections exert a significant public health burden on healthcare services in the United Kingdom (UK). The literature suggests an association between ethnicity and health; however, we do not know the extent of inequalities in GI infection/disease in the UK. This systematic review aimed to identify studies that ascertain differences in the incidence or prevalence of GI infections between UK ethnic groups and explore possible explanations for heterogeneity observed within the literature. Methods MEDLINE, CINAHL Plus, Web of Science (Science Social Science Citation Index), and grey literature were searched from 1980 to 21st June 2023 for studies reporting an association between ethnicity and GI infections in UK population samples. Two reviewers independently screened the studies and conducted quality appraisals; data extraction was undertaken by one reviewer and verified by another reviewer. A narrative synthesis was undertaken and a harvest plot supported the textual synthesis to investigate potential sources of heterogeneity in effect estimates by GI pathogen and ethnic group. Results The searches identified 10028 studies, of which 16 met the inclusion criteria. 15 out of 47 effect estimates from a total of 16 studies found that GI infection risk was greater in Black and Ethnic Minority Groups, mainly of Asian ethnicity, compared to the majority White population. 13 studies reported a higher risk in ethnic minorities of Asian ethnicity, while one study described a higher risk in the Non-White ethnic group. One single study on STEC reported a higher risk of GI infection in the White population compared to the Non-White population, while another single study on norovirus found no significant difference by ethnic group. Conclusions This systematic review demonstrates that ethnic minority groups in the UK have a higher risk of GI infections than the general or White population. Key messages • There is a clear need to elucidate further the high incidence of GI infections in UK Indian, Pakistani, and Bangladeshi communities. • Tackling ethnic inequalities requires a concerted approach and translating evidence into policy.

Metastatic Melanoma to the Small Bowel and Colon: A Systematic Review of the Global Experience and Institutional Cohort Analysis Detailing a Rare Clinical Entity.

Cutaneous melanoma is among the most common solid tumors to metastasize to the gastrointestinal (GI) tract. Literature summarizing the clinical experience and features of this unique pathology is lacking. A systematic review of the available literature reporting clinically salient features of melanoma metastases to the small and large intestines was conducted. Additionally, we surveyed our institutional experience of surgically treated melanoma metastasis to the small bowel and colon. A descriptive analysis was performed. Kaplan-Meier curves with log-rank tests were used to analyze time-to-event intervals. Univariable and multivariable Cox logistic regression models were generated to identify predictors of survival. Over 100 studies including 1153 patients were included. GI metastases predominantly affected males, were in the small bowel/jejunum, equally presented as solitary and multiple lesions, and were generally not the first site of distant metastatic disease. The median time from primary lesion diagnosis to GI metastasis was 48 months. Analysis of our institutional cohort suggested that survival in patients receiving complete GI-specific surgical resection and immune checkpoint inhibitors (ICIs) was prolonged compared to palliative resection and without ICI therapy. Positive prognostic factors for survival following GI metastasis included fewer GI metastatic lesions, complete resection, and longer duration between primary tumor diagnosis and GI metastasis. GI metastases are a sign of advanced metastatic melanoma. Clinical suspicion of metastatic involvement in patients with a history of melanoma who develop any abdominal symptoms or anemia should remain high. Receipt of complete surgical resection and ICIs may prolong survival in disseminated melanoma.

Survodutide, a glucagon receptor/GLP-1 receptor (GCGR/GLP-1R) dual agonist, improves cardiometabolic parameters in adults with obesity: analysis of a placebo-controlled, randomised phase 2 trial

Abstract Background Obesity increases the risk of cardiovascular (CV) disease and contributes to CV risk factors, such as hypertension (HTN) and dyslipidaemia. Survodutide is a GCGR/GLP-1R dual agonist in clinical development for obesity. In a phase 2 clinical trial in individuals with obesity without diabetes, survodutide elicited up to 18.7% mean reduction in body weight after 46 weeks (primary endpoint) according to actual treatment.1 Purpose We explored the effect of survodutide on cardiometabolic parameters in this trial cohort. Methods 387 people aged ≥18 to <75 years with body mass index (BMI) ≥27 kg/m2 without diabetes were randomised 1:1:1:1:1 to once-weekly subcutaneous survodutide (0.6, 2.4, 3.6, 4.8 mg) or placebo (PBO) for 46 weeks (wk), comprising an initial 20-wk escalation period when the dose could be adjusted for gastrointestinal (GI) tolerability, followed by a 26-wk maintenance period. We evaluated changes from baseline (BL) to wk 46 in waist circumference; lipid parameters (triglyceride [TG], high-density lipoprotein [HDL], very low-density lipoprotein [VLDL], low-density lipoprotein [LDL], total cholesterol [TC], and non-HDL cholesterol [non-HDL-C]); and blood pressure (BP) by presence/absence of HTN before and at screening. Data were analysed descriptively for all participants receiving ≥1 dose of study drug with data for ≥1 efficacy endpoint, i.e. full analysis set (FAS), according to doses received during the maintenance period (actual treatment) and according to doses assigned at randomization (planned treatment) using on-treatment data. Results In the FAS (n=384), BL demographic and clinical characteristics were similar across treatment groups: overall mean age 49.1 years, BMI 37.1 kg/m2, 262 (68.2%) female, 301 (78.4%) White, 40 (10.4%) Asian, and 37 (9.6%) Black. Before and at screening, 133 (34.6%) participants had hypertension and 108 (28.1%) had dyslipidaemia. Waist circumference was reduced in all survodutide doses vs PBO; the largest mean reduction was 16.6 cm (4.8 mg group; actual treatment). Survodutide was associated with reductions of up to 10.2 mmHg in SBP and 4.8 mmHg in DBP from BL to wk 46 by actual treatment; similar reductions were observed for planned treatment, and reductions were comparable with/without HTN before and at screening (Figure 1). A marked decrease in mean TG was observed in all survodutide groups by planned treatment (Figure 2). Mean HDL was relatively unchanged over the period. Small decreases occurred in mean VLDL (all survodutide doses) and mean LDL (2.4 and 3.6 mg doses). Mean TC and non-HDL-C decreased in 0.6, 2.4, and 3.6 mg groups. Conclusion In people living with obesity, the GCGR/GLP-1R dual agonist survodutide was associated with clinically meaningful reductions in waist circumference, BP (with/out HTN before and at screening), and TG.

Hypofractionated radiotherapy with simultaneous integrated boost for localized prostate cancer patients: effects on immune system and prediction of toxicity

BackgroundThe other side of radiotherapy (RT), in addition to the cytotoxic effect, is the ability to modulate the immune system in terms of activation or suppression, also depending on the dose and fractionation delivered. This immune RT effect can be detected both locally in the irradiated tumor site and in the peripheral blood. The aim of this study was to assess the consequence of pelvic irradiation on peripheral immune cells and cytokine secretions in localized prostate cancer (PC) patients undergoing pelvic irradiation with a simultaneous moderately hypofractionated prostate/prostate bed boost by Volumetric Modulated Arc Therapy (VMAT). Furthermore, we analyzed whether there was a correlation between these peripheral immune parameters and acute and late genitourinary (GU) and gastrointestinal (GI) toxicity.MethodsThirty-eight PC patients were treated with pelvis irradiation (dose per fraction 1.8 Gy) and simultaneous hypofractionated (median dose per fraction: 2.7 Gy) prostate/prostate bed boost. A longitudinal analysis was performed for 12 months on peripheral blood to assess changes in 9 different lymphocyte subpopulations by flow cytometry and 10 circulating cytokines by Multiplex Luminex assay and ELISA.ResultsOur analysis revealed that basal IFN-γ serum values were significantly lower in the definitive (curative intent for patients with prostate) patient group respect to the post-operative one. All the lymphocyte subsets and IFN-α, IFN-β and Il-2 peripheral concentrations displayed significant variations between the different time points considered. The immune cell population that suffers the greatest RT toxicity in the blood was B lymphocyte. We found an interesting correlation between basal TGF-β1 and late GU toxicity. In particular, TGF-β1 concentrations before RT were significantly higher in patients that experienced grade 2-3 of late GU toxicity, respect to grade 0-1. Exploring possible correlations between some clinical/biological findings and radiation planning parameters, we found no statistical significance.ConclusionsOur study analyzed, in the context of hypofractionated radiotherapy in prostate cancer, different parameters of the peripheral immune system. We have highlighted longitudinally the peripheral behavior of the different lymphocyte subpopulations and of a group of 10 cytokines during the first year after RT. One of the analyzed cytokines, such as TGF-β1, has proven to be promising predictive factor of severe late GU toxicity.

Patterns of overeating in middle-aged Chinese from Hong Kong

Abstract Background Obesity is one of the most important risk factors for non-communicable diseases worldwide. Overweightness may be attributable to a wide spectrum of overeating behaviours. However, the various types of overeating behaviors are under-studied in Asia, particularly in non-adolescent age groups. This study aims to estimate the prevalence and factors associated with various overeating patterns among middle-aged Chinese adults. Methods A random telephone survey was conducted in 2023 on Hong Kong Chinese adults between 35 and 59 years or age (n = 785). An instrument composed of modified Positive-Negative Emotional Eating (EE) Scale, Night Eating Questionnaire-Chinese (NEQ), Binge Eating Disorder Screener (BED-7), Depression Anxiety and Stress Scales (DASS-21), demographic factors, BMI and number of reported gastrointestinal (GI) conditions was used. Multiple regression analyses were conducted to test the association of demographic factors, BMI, GI conditions as well as dysphoric mood with overeating behaviors. Results Hong Kong Chinese middle-aged adults reported the following past-month prevalence of overeating behaviors: positive EE (26.1%), general overeating (12.4%), negative EE (9.2%), binge eating (6.0%) and night eating behavior (1.8%). Nightshift work, mental stress, being single and younger age were common risk factors for the various overeating patterns among middle-aged men. Anxiety, high/low educational levels and younger age were common risk factors among middle-aged women. Obesity was associated with binge eating and positive EE in men (OR: 1.7-4.0) and associated with negative EE and general overeating (OR:2.3-2.7) in women. Conclusions This study noted that binge eating, night eating, positive/negative EE, and GOB were distinct eating patterns requiring different clinical approaches. The significant association between various overeating behaviors with BMI, indicates that these individuals should be prioritized to receive healthy eating interventions. Key messages • Adult overeating is not a singular behavior but represents an array of different eating patterns with different risk factors. • Like their Western counterparts, overeating behaviors in Chinese adults are often linked to dysphoric mood, therefore treatment of obesity may require psychological counseling.

Prospective screening and proposed treatment algorithm for immune checkpoint inhibitor induced myositis in neoadjuvant-treated rectal cancer patients: data from the phase II CHINOREC trial

Abstract Background Myositis is an infrequent (<1%) but potentially life-threatening (case fatality rate 40-50%) immune-related adverse event (irAEs) of immune checkpoint inhibitors (ICI), such as ipilimumab (IPI) and nivolumab (NIVO). The true incidence is likely to be underestimated and may not be representative for curative neoadjuvant treatment approaches in gastrointestinal (GI) cancers, especially in combination with chemoradiotherapy (CRT). Currently, the summary of product characteristics (SmPC) does not suggest any pre-emptive screening or surveillance. Methods The CHINOREC study is an ongoing prospective, randomized, open-label, multicenter, phase II investigator-initiated trial (IIT). Patients with intermediate to locally advanced rectal cancer (LARC) receive either neoadjuvant CRT alone or in combination with a single dose of IPI and 3 cycles of NIVO, following surgical resection. Patients are monitored at baseline and throughout the whole study period for myotoxicity biomarkers, including cardiac troponin T (cTnT) and cardiac troponin I (cTnI). Findings From 06/2020 to 11/2023, 80 patients have been enrolled of whom 50 patients were randomized to the CRT+IPI/NIVO arm. Six patients (12%) developed biopsy-verified myositis. Myositis treatment was promptly implemented using a pragmatic step-up approach. Patients received glucocorticoids (GC) with concomitant intravenous immunoglobulin (IVIG). If myotoxicity biomarkers did not improve, patients received infliximab (INFLIXI) and/or plasma exchange (PLEX). Although all patients had strikingly elevated cTnT (median peak 284 ng/L, 95% CI 39-3097), cTnI levels remained largely normal, correlating with a negative cardiac magnetic resonance (CMR). All patients underwent successful tumor surgery without any major surgical complication. As of today, all patients' creatine kinase (CK) and myoglobin (MB) levels have normalized and they are tumor free without any major sequela. Interpretation Longitudinal biomarker screening (cTnT/cTnI) for ICI-induced myotoxicities is pivotal in curative neoadjuvant-treated cancer patients to initiate an early counter treatment in a holistic step-up approach, without compromising oncological principles.

Drug-drug interactions of empagliflozin and dapagliflozin

Abstract Introduction The sodium glucose co-transporter2-inhibitors dapagliflozin (Dapa) and empagliflozin (Empa), initially developed as antihyperglycemic agents, are increasingly also prescribed for non-diabetic patients with heart failure (HF). Glucuronidation by uridine-diphosphate glucuronosyltransferase (UGT)1A9 is the main mechanism of metabolism of Dapa, whereas Empa is eliminated mainly by excretion. Both Dapa and Empa are substrates of P-glycoprotein. The risk for drug-drug interactions (DDI) of Empa and Dapa is assumed to be low. Aim of this study was to summarize reports of DDI of Empa and Dapa from the literature. Methods Search-terms in PubMed were "drug-drug interaction" and AND "sodium glucose co-transporter2-inhibitors" OR "SGLT2" OR "dapagliflozin" OR "empagliflozin". The drugs were classified according the Anatomical Therapeutic Chemical (ATC) system. Included were randomized trials, pharmacovigilance studies, case series, case reports, studies in healthy subjects and in vivo data. The funding of the study and the disclosures of the authors were registered. Results In 45 reports DDI of Empa and Dapa with 29 drugs were described (Table). According to the ATC system, these were drugs for the alimentary tract and metabolism (n=5), blood and blood forming organs (n=2), cardiovascular system (n=11), genitourinary system and sex hormones (n=2), antiinfectives (n=2), antineoplastic and immunomodulating agents (n=3), musculo-skeletal system (n=2) and nervous system (n=2). The reports comprised studies in healthy subjects (n=28), case reports (n=7), case series (n=6), pharmacovigilance studies (n=2), a subgroup analysis of a randomized trial (n=1) and in vivo data (n=1). Most of the reports found no clinically relevant DDI (n=32). Dapa and Empa both had a synergistic diuretic effect with bumetanide, and led to severe infections when combined with the interleukin-17-inhibitors secukinumab or ixekizumab. Empa administered with intravenous iron was reported to increase cell-iron availability, with lithium to reduce lithium exposure and with valproate to increase valproate exposure. Dapa administered with sacubitril-valsartan was reported to lead to severe hypotension, with linezolid to pancytopenia, with donafenib to an increased exposure to donafenib, with rifampicin to a reduction and mefenamic acid to an increase in Dapa exposure. Of the 45 reports, 33 were funded by a pharmaceutical company marketing Dapa or Empa and 33 had authors with conflicts of interest with pharmaceutical companies marketing Dapa or Empa. Conclusions Most data about DDI of Empa and Dapa derive from studies in healthy subjects and from the marketing companies. The clinical relevance DDI of Empa and Dapa in polymorbid patients with polymedication is largely unknown. There is an urgent need for independent studies on DDI of these drugs in diabetic and non-diabetic patients with HF.Table

Metabolomic analysis to predict the onset and severity of necrotizing enterocolitis

BackgroundNecrotizing enterocolitis (NEC) is the most devastating gastrointestinal (GI) emergency in preterm neonates. Untargeted metabolomics may allow the identification of biomarkers involved in NEC pathophysiology.MethodsWe conducted a prospective study including preterm infants born at < 34 gestational weeks (GWs) whose urine was longitudinally collected at birth (< 48 h, T0) and at 14 (T1) and 28 days (T2). Neonates were followed for their development of NEC, spontaneous intestinal perforation (SIP), or other GI conditions and compared to those of matched healthy controls. Urine samples were investigated by untargeted metabolomic analysis based on mass-spectrometry.ResultsThirty-five patients with NEC, 5 patients with SIP, 14 patients with other GI diseases and 113 controls were enrolled and selected for metabolomic analysis on the basis of their clinical characteristics and available samples. Considering urine samples at T0, the one-class classification approach was able to correctly classify 16/20 subjects (80%) who developed NEC, 3/3 (100%) who developed SIP and 5/7 subjects (71.4%) with other GI pathologies as not belonging to the control group. Neonates with surgical NEC had higher N-acetylaspartic acid, butyrylcarnitine and propionylcarnitine levels than did those with medical NEC. Considering the time evolution of the urinary metabolome, the NEC and control groups showed differences independently of the time point.ConclusionsThe urinary metabolome is closely associated with the underlying GI disease from birth. Urinary metabolic features characterize NEC patients from healthy controls until 28 days of life. The early urinary metabolome has the potential to predict surgical NEC. Future studies are needed to validate our results.

Gastrointestinal morphology is an effective functional dietary proxy that predicts small mammal community structure.

The availability and quality of food resources can alter the intensity of competition and predation pressure within communities. Understanding species capacity to respond to global change-driven shifts in resource distribution is therefore crucial for biodiversity conservation. Small mammal communities are often structured by competition for food resources, but understanding and monitoring these processes are currently hindered by lack of functional dietary trait information in these hard-to-sample systems. In this study, we collected a comprehensive suite of gastrointestinal (GI) measurements from 26 small mammal species (including some never reported), compared them with more traditional craniodental traits in predicting dietary guild, and used them in a novel way to understand how diet structures 22 small mammal communities across the Appalachian Mountains of eastern North America. As predicted, we found GI traits to be effective dietary trait proxies; they were equally or more accurate than craniodental proportions in predicting the dietary guild of individual species. Furthermore, at the community level, we found that both the mean and functional dispersion of GI length were positively correlated with latitude and measures of temperature seasonality. Our results indicate that small mammal communities in more seasonal environments are filtered to include species with longer GI tracts (on average) as well as those that can partition food resources more finely, as expected based on the lower productivity of these regions. Conversely, communities in less seasonal environments display functional redundancy from the addition of species with short to intermediate GI lengths. Proportions of the GI tract represent novel dietary traits that can illuminate community assembly processes across regional environmental gradients and in the face of changing timing and availability of resources.

Gastrointestinal germinal center B cell depletion and reduction in IgA+ plasma cells in HIV-1 infection.

Gastrointestinal (GI) B cells and plasma cells (PCs) are critical to mucosal homeostasis and the host response to HIV-1 infection. Here, high-resolution mapping of human B cells and PCs sampled from the colon and ileum during both viremic and suppressed HIV-1 infection identified a reduction in germinal center (GC) B cells and follicular dendritic cells (FDCs) during HIV-1 viremia. Immunoglobulin A-positive (IgA+) PCs are the major cellular output of intestinal GCs and were significantly reduced during viremic HIV-1 infection. PC-associated transcriptional perturbations, including type I interferon signaling, persisted in antiretroviral therapy (ART)-treated individuals, suggesting ongoing disruption of the intestinal immune milieu during ART. GI humoral immune perturbations were associated with changes in the intestinal microbiome composition and systemic inflammation. These findings highlight a key immune defect in the GI mucosa due to HIV-1 viremia.

Artificial Intelligence-Assisted Daily Quality Control System for the Histologic Diagnosis of Gastrointestinal Endoscopic Biopsies: A 1-Year Experience.

Seegene Medical Foundation, one of the major clinical laboratories in South Korea, developed SeeDP, an artificial intelligence (AI)-based postanalytic daily quality control (QC) system that reassesses all gastrointestinal (GI) endoscopic biopsy (EB) slides for incorrect diagnoses. To review the operational records and clinical impact of SeeDP since its launch in March 2022. Operational records of SeeDP were retrieved for the period of March 1, 2022, to February 28, 2023. Among cases scanned during 40 working days (March 10, 2022, to May 4, 2022), all discordant cases encountered by 2 pathologists were reviewed. Cases of SeeDP-assisted revised diagnoses were collected and compared with cases recognized using conventional methods. Occasional scanner failures and various types of aberrant errors compromised QC coverage, resulting in the scanning of only 67.7% (572 254 of 844 906) of all EB slides submitted and 0.8% of the scanned slides being further excluded from the AI analysis. The AI predictions differed from the pathologists' diagnoses in 42 760 of the 557 672 gastrointestinal EB slides (7.7%) successfully assessed by the AI models; however, a detailed review of discordant slides revealed that true misdiagnosis accounted for only 5.5% (25 of 454) of the disagreements. Compared with conventional error recognition methods, SeeDP detected more misdiagnoses (7 versus 14) within a significantly shorter time (average, 3.6 versus 38.7 days; P < .001), including 1 signet ring cell carcinoma initially diagnosed as gastritis. AI-based daily QC systems are plausible solutions to guarantee high-quality pathologic diagnosis by enabling rapid detection and correction of misdiagnosis.

Prevalence of an empty colon in patients with acute and chronic small intestinal mechanical obstruction: A retrospective radiographic study in 100 dogs and cats

Small intestinal mechanical obstruction (SIMO) is a common clinical condition, with radiographic studies typically focusing on the small intestine. However, the colon's appearance in SIMO has not been extensively studied. This retrospective study aimed to determine the prevalence of an empty colon on radiographs of dogs and cats with confirmed SIMO. Pre-surgical abdominal radiographs of 100 patients (68 dogs and 32 cats) with surgically confirmed mechanical ileus and a control group of 30 dogs and 20 cats with non-obstructive gastrointestinal (GI) disease and one without GI disease, respectively, were evaluated. The colon was assessed for content (none/collapsed, gas, faeces) and segmental distribution (ascending, transverse, descending colon) and correlated to the duration of clinical signs (acute, chronic). A colon was classified as empty when ≥2/3 was collapsed and/or gas-filled. The overall prevalence of an empty colon in cases of mechanical ileus was 61% (p=0.028), with 49/68 in dogs (72.1%) and 12/32 in cats (37.5%), p=0.001 between dogs and cats. Clinical signs duration did not influence the prevalence 28/61 (45.9%) acute, 33/61 (54.1%) chronic, p=0.522. However, acute cases had more empty colon segments (2/3 segments: 6/28, 21.4%; 3/3 segments: 22/28, 78.6%) than chronic cases (2/3 segments: 23/33, 69.7%; 3/3 segments: 10/33, 30.3%; p≤0.001). In the control groups, the prevalence of an empty colon was 64% (p=0.048) with and 38%, p=0.048) without GI disease, with no statistical difference between dogs and cats. An empty colon can be a supporting radiographic finding in diagnosing patients with GI disease, including SIMO, in addition to other established characteristic features. Dogs are more likely to have an empty colon in the presence of mechanical ileus.