Gastrointestinal Tract Tissues Research Articles

Elimination of Intestinal Hypoxia in Complex Treatment of Intestinal Failure (Case Report)

INTRODUCTION: Currently, various approaches to the treatment of intestinal failure (IF) are considered. In search for pathogenetically justified therapy, it is possible to use oxygenated saline enteral solution (OSES). АIM: To demonstrate, by gas analysis of the introduced oxygenated saline enteral solution and the excreted intestinal fluid, the possibility of gas exchange in the intestine with increased oxygen extraction under hypoxic conditions. An 8-year-old child with burdened premorbid history and severe community–acquired bilateral pleuropneumonia kept on mechanical ventilation, had signs of IF (disorder in passage, absence of independent defecation for more than two days). During treatment and observation of the child, enteral feeding was attempted with pharmacological stimulation with prokinetics, and introduction of laxative sorbent with prebiotic effect (lactulose). Because of non-effectiveness of these measures, it was decided to perform intestinal lavage with OSES introduced through the nasogastral tube. In 30 minites after start of OSES introduction, the gastrointestinal tract motility notably enhanced, in 1.5 hour from the beginning of the procedure, fractional passage of a significant amount of thick fecal masses was noted, after which intestinate — liquid stool stained yellow with bile, was obtained. During the procedure, a comparative analysis of the gas composition of the introduced OSES and excreted intestinate was done. In the excreted solution, 97-fold decrease of рО2 from 659 to 6.8 mm Hg, and 3.6-fold increase in CO2 tension from 23 to 85.7 mm Hg, were noted. CONCLUSION: Oxygenation of the enteral environment by barbotage of a saline enteral solution introduced through a tube is an effective component of intensive therapy for intestinal failure syndrome, taking into account the ability of the gastrointestinal tract tissues to actively participate in gas exchange: extract oxygen and release carbon dioxide.

Extramedullary Intracranial Plasmacytomas: A Systematic Review of Literature.

Extramedullary plasmacytoma (EMP) is an uncommon disorder characterized by the development of abnormal plasma cell tumors outside the bone marrow. These tumors are typically observed in various locations, including the upper respiratory tract, gastrointestinal tract, and other soft tissues. Among the less explored manifestations of EMP is intracranial EMP, which remains poorly understood due to the limited literature available on the subject. The objective was to comprehend the population characteristics, localization, type, treatment, and outcomes of intracranial EMP. A systematic review of the literature for EMPs was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The strategy "extramedullary plasmacytoma AND multiple myeloma" was used for the search. The search terms were queried using PubMed, Embase, Scopus, Cochrane, and Web of Science databases. We included only those studies that presented clinical studies with patients diagnosed with intracranial plasmacytomas. In this study, a total of 84 patients from 25 studies were analyzed. The average age of diagnosis was 57.25 years, with a slightly higher proportion of females (57%) compared to male patients (43%). The most common locations of intracranial plasmacytomas were the clivus (29.7%), frontal lobe (18.9%), parietal lobe (8.1%), occipital lobe (6.7%), temporal lobe (6.7%), and sphenoid (4%). Chordoma and meningioma were the most common differential diagnoses encountered during clinical investigations. Treatment modalities included radiotherapy (RT), chemotherapy (QT), surgical resection (SR), and conservative approaches. The most frequent treatment combinations were SR + RT (19%) and RT only (17.8%). Mortality was reported in 48% of the cases, with complete resolution observed in 10 cases and partial resolution in 3 cases. The average follow-up duration was 37.5 months. The clivus is the most frequently reported site of extramedullary intracranial plasmacytoma (EMIP) occurrence, representing 29.7% of cases. Chordomas were commonly observed alongside EMIPs and emerged as the primary differential diagnosis. RT was the predominant treatment modality, with SR considered when feasible. RT alone demonstrated the highest effectiveness in managing EMIPs (30%), while QT as a sole intervention showed lower efficacy. However, a combination of dexamethasone, lenalidomide, and targeted RT displayed promising results, offering improved tumor response and increased safety.

Examining the Difficulties in Identifying and Handling Cardiac Amyloidosis; Acquiring Important Knowledge and Robust Treatment Methods.

Systemic amyloidosis is a rare protein misfolding and deposition condition that causes slow organ failure. Each of the more than 15 exclusive sorts of systemic amyloidosis, which encourage amyloid production and tissue deposition, is introduced by a unique precursor protein. Amyloidosis can affect various organs, including the heart, kidneys, liver, nerves, gastrointestinal tract, lungs, muscles, skin, and soft tissues. It can either be acquired or hereditary. Insidious and doubtful signs often cause a put-off in diagnosis. In the closing decade, noteworthy progressions have been made in the identity, prediction, and handling of amyloidosis. Shotgun proteomics based on mass spectrometry has revolutionized amyloid typing and enabled the identification of novel amyloid forms. It is critical to correctly identify the precursor protein implicated in amyloidosis because the kind of protein influences the proper treatment strategy. Cardiac amyloidosis is a disorder characterized by the systemic accumulation of amyloid protein in the myocardium's extracellular space, which causes a variety of symptoms. The buildup of amyloid aggregates precipitates myocardial thickening and stiffening, culminating in diastolic dysfunction and, in due course, heart failure. We examine every kind of systemic amyloidosis in this text to offer practitioners beneficial equipment for diagnosing and treating those unusual diseases. This review presents a comprehensive analysis of cardiac amyloidosis and consolidates current methods for screening, diagnosis, evaluation, and treatment alternatives.

Efficacy and safety of laparoscopic surgery vs open surgery in gastrointestinal tumor resection: a systematic review

Gastrointestinal stromal tumors (GISTs) arise from mesenchymal tissues of gastrointestinal GI tract. This tumor comes in the category of rare tumor as it makes up only 1 to 3% of tumors in the gastrointestinal (GI) tract. It is important to note that it is most prevalent type of tumor originating from mesenchymal cells, accounting for 80% of cases within this category. Despite other treatments, surgical resection is cornerstone of treatment for non-metastatic GISTs. In recent decades, surgical procedures to remove GISTs has witnessed a paradigm shift towards minimally invasive techniques, e.g. laparoscopic surgery (LAP). Open surgery is also being frequently used but it is generally recommended based on other factors such as tumor location in GI tract or whether it is localized or has spread in other organs or tissues. LAP is more advanced form of surgery and it is recommended because of reduced postoperative pain, shorter hospital stays, lower rate of hospitalization and post-operative complications compared to open surgery. In this paper, we aim to discuss surgical interventions for GISTs, with clear aim to compare LAP with Open Surgery OS.

Role of incretins and glucagon receptor agonists in metabolic dysfunction-associated steatotic liver disease: Opportunities and challenges.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver disease worldwide, paralleling the rising pandemic of obesity and type 2 diabetes. Due to the growing global health burden and complex pathogenesis of MASLD, a multifaceted and innovative therapeutic approach is needed. Incretin receptor agonists, which were initially developed for diabetes management, have emerged as promising candidates for MASLD treatment. This review describes the pathophysiological mechanisms and action sites of three major classes of incretin/glucagon receptor agonists: glucagon-like peptide-1 receptor agonists, glucose-dependent insulinotropic polypeptide receptor agonists, and glucagon receptor agonists. Incretins and glucagon directly or indirectly impact various organs, including the liver, brain, pancreas, gastrointestinal tract, and adipose tissue. Thus, these agents significantly improve glycemic control and weight management and mitigate MASLD pathogenesis. Importantly, this study provides a summary of clinical trials analyzing the effectiveness and safety of incretin receptor agonists in MASLD management and provides an in-depth analysis highlighting their beneficial effects on improving liver function, hepatic steatosis, and intrahepatic inflammation. There are emerging challenges associated with the use of these medications in the real world, particularly adverse events, drug-drug interactions, and barriers to access, which are discussed in detail. Additionally, this review highlights the evolving role of incretin receptor agonists in MASLD management and suggests future research directions.

Mechanisms of Action in FLASH Radiotherapy: A Comprehensive Review of Physicochemical and Biological Processes on Cancerous and Normal Cells.

The advent of FLASH radiotherapy (FLASH-RT) has brought forth a paradigm shift in cancer treatment, showcasing remarkable normal cell sparing effects with ultra-high dose rates (>40 Gy/s). This review delves into the multifaceted mechanisms underpinning the efficacy of FLASH effect, examining both physicochemical and biological hypotheses in cell biophysics. The physicochemical process encompasses oxygen depletion, reactive oxygen species, and free radical recombination. In parallel, the biological process explores the FLASH effect on the immune system and on blood vessels in treatment sites such as the brain, lung, gastrointestinal tract, skin, and subcutaneous tissue. This review investigated the selective targeting of cancer cells and the modulation of the tumor microenvironment through FLASH-RT. Examining these mechanisms, we explore the implications and challenges of integrating FLASH-RT into cancer treatment. The potential to spare normal cells, boost the immune response, and modify the tumor vasculature offers new therapeutic strategies. Despite progress in understanding FLASH-RT, this review highlights knowledge gaps, emphasizing the need for further research to optimize its clinical applications. The synthesis of physicochemical and biological insights serves as a comprehensive resource for cell biology, molecular biology, and biophysics researchers and clinicians navigating the evolution of FLASH-RT in cancer therapy.

A measles-vectored vaccine candidate expressing prefusion-stabilized SARS-CoV-2 spike protein brought to phase I/II clinical trials: protection of African green monkeys from COVID-19 disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and is responsible for the largest human pandemic in 100 years. Thirty-four vaccines are currently approved for use worldwide, and approximately 67% of the world population has received a complete primary series of one, yet countries are dealing with new waves of infections, variant viruses continue to emerge, and breakthrough infections are frequent secondary to waning immunity. Here, we evaluate a measles virus (MV)-vectored vaccine expressing a stabilized prefusion SARS-CoV-2 spike (S) protein (MV-ATU3-S2PΔF2A; V591) with demonstrated immunogenicity in mouse models (see companion article [J. Brunet, Z. Choucha, M. Gransagne, H. Tabbal, M.-W. Ku et al., J Virol 98:e01693-23, 2024, https://doi.org/10.1128/jvi.01693-23]) in an established African green monkey model of disease. Animals were vaccinated with V591 or the control vaccine (an equivalent MV-vectored vaccine with an irrelevant antigen) intramuscularly using a prime/boost schedule, followed by challenge with an early pandemic isolate of SARS-CoV-2 at 56 days post-vaccination. Pre-challenge, only V591-vaccinated animals developed S-specific antibodies that had virus-neutralizing activity as well as S-specific T cells. Following the challenge, V591-vaccinated animals had lower infectious virus and viral (v) RNA loads in mucosal secretions and stopped shedding virus in these secretions earlier. vRNA loads were lower in these animals in respiratory and gastrointestinal tract tissues at necropsy. This correlated with a lower disease burden in the lungs as quantified by PET/CT at early and late time points post-challenge and by pathological analysis at necropsy.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the largest human pandemic in 100 years. Even though vaccines are currently available, countries are dealing with new waves of infections, variant viruses continue to emerge, breakthrough infections are frequent, and vaccine hesitancy persists. This study uses a safe and effective measles vaccine as a platform for vaccination against SARS-CoV-2. The candidate vaccine was used to vaccinate African green monkeys (AGMs). All vaccinated AGMs developed robust antigen-specific immune responses. After challenge, these AGMs produced less virus in mucosal secretions, for a shorter period, and had a reduced disease burden in the lungs compared to control animals. At necropsy, lower levels of viral RNA were detected in tissue samples from vaccinated animals, and the lungs of these animals lacked the histologic hallmarks of SARS-CoV-2 disease observed exclusively in the control AGMs.

Diabetes Mellitus and Bacterial Infections: A Review of Main Infections in DM Patients

Millions of single-celled microscopic organism called bacteria reside within the human body. Numerous infectious diseases in humans are caused by some of these pathogen bacteria. One of the major risk factors for bacterial infections is diabetes mellitus. Bacterial infections and diabetes may have a reciprocal relationship in which some illnesses exacerbate insulin resistance. Diabetes may occur as a result of bacteria in the digestive system. Any organ in a human body can become infected by bacteria. The respiratory tract, gastrointestinal tract, urinary tract, skin, and soft tissues are the most frequently infected areas with diabetes. Uncontrolled hyperglycemia increases the risk of bacterial infections by impairing innate and adaptive immune responses. Furthermore, skin ulceration can result from long-term diabetic consequences such peripheral vascular disease and neuropathy (sensorimotor and autonomic). These conditions can also lead to secondary bacterial infections.

Distinguishing between Crohn’s disease and ulcerative colitis using deep learning models with interpretability

Crohn’s disease and ulcerative colitis are two chronic diseases that cause inflammation in the tissues of the entire gastrointestinal tract and are described by the term inflammatory bowel disease. Gastroenterologists find it difficult to evaluate endoscopic images to recognise the characteristics of the two chronic diseases. Therefore, this work aims to build a dataset with images of Crohn’s disease and ulcerative colitis (collected from the public datasets LIMUC, HyperKvasir and CrohnIPI) and train deep learning models (five CNNs and six ViTs) to develop a tool capable of helping doctors to distinguish the type of inflammatory bowel disease. In addition, as these architectures will be too heavy to work in a hospital context, in this work, we are looking to use knowledge distillation to create lighter and simpler architectures with the same precision as the pre-trained architectures used in this study. During this process, it is important to evaluate and interpret the pre-trained architectures before the distillation process, and the architectures resulting from knowledge distillation to ensure that we can maintain performance and that the information learnt by both architectures are similar. It is concluded that is possible to reduce 25x the number of parameters while maintaining good performance and reducing the inference time by 5.32 s. Allied with this, through the interpretability of the models was concluded that both before and after the knowledge distillation are possible to identify ulcers, bleeding situations, and lesions caused by the inflammation of the disease.

Changes in the Metabolism of Fucose-Containing Biopolymers in Rat Gastrointestinal Tissues under Immobilization Stress

The features of fucoglycoprotein metabolism in blood serum and tissues of gastrointestinal tract of rats in the dynamics of experimental stress on 21, 35, 60, 90 days of observation were considered. In blood serum and in homogenates of liver, stomach and small intestine of immobilized rats multidirectional changes in the level of fucose and fucosidase activity were observed. They are manifested by a decrease in the amount of total fucose in blood serum and liver of rats against the background of low activity of the enzyme degrading fucoglycoproteins. The same changes were detected in the tissues of the gastric and small intestine (except on day 35 of the experiment, when the growth of fucose and fucosidase was visualized), which may indicate a change in metabolism toward anabolism. These changes correlate with an increase in the concentration of corticosterone in the blood serum of the rats.

Plastic, It's What's for Dinner: A Preliminary Comparison of Ingested Particles in Bottlenose Dolphins and Their Prey.

Microplastic ingestion was reported for common bottlenose dolphins (Tursiops truncatus) inhabiting Sarasota Bay, FL, USA, a community that also has prevalent exposure to plasticizers (i.e., phthalates) at concentrations higher than human reference populations. Exposure sources are currently unknown, but plastic-contaminated prey could be a vector. To explore the potential for trophic exposure, prey fish muscle and gastrointestinal tract (GIT) tissues and contents were screened for suspected microplastics, and particle properties (e.g., color, shape, surface texture) were compared with those observed in gastric samples from free-ranging dolphins. Twenty-nine fish across four species (hardhead catfish, Ariopsis felis; pigfish, Orthopristis chrysoptera; pinfish, Lagodon rhomboides; and Gulf toadfish, Opsanus beta) were collected from Sarasota Bay during September 2022. Overall, 97% of fish (n = 28) had suspected microplastics, and GIT abundance was higher than muscle. Fish and dolphin samples contained fibers and films; however, foams were common in dolphin samples and not observed in fish. Suspected tire wear particles (TWPs) were not in dolphin samples, but 23.1% and 32.0% of fish muscle and GIT samples, respectively, contained at least one suspected TWP. While some similarities in particles were shared between dolphins and fish, small sample sizes and incongruent findings for foams and TWPs suggest further investigation is warranted to understand trophic transfer potential.

Pre-treatment Evaluation of Patients Eligible for Whole Brain Radiation Therapy: The Risk of Hippocampal Metastases in a Retrospective Study of 248 Cases at a Single Institution.

Whole brain radiation therapy (WBRT) is effective for multiple brain metastases (BMs) but may impair neurocognitive function (NCF). The incidence of hippocampal metastasis (HM) is low, and the factors associated with the occurrence of HM remain unclear. This study aimed to assess the occurrence of limbic system metastasis (LSM), including HM, and to analyze the risk of HM. We retrospectively analyzed 248 patients who underwent three-dimensional conformal radiation therapy for BMs between May 2008 and October 2015. Gadolinium-enhanced brain MRI or CT scans were used for diagnosis. Statistical analysis involved assessing clinical factors, including age, gender, primary tumor, number of BMs, and maximum metastasis diameter, in relation to the presence of HMs using logistic regression and receiver operating characteristic (ROC) curve analysis. The median age at treatment was 62 years (range: 11-83 years). Primary lesion sites included the lung (n = 150; 60.5%), breast (n = 45; 18.1%), gastrointestinal tract (n = 18; 7.3%), and bone and soft tissue (n = 2; 0.8%). Histological cancer types included adenocarcinoma (n = 113; 45.6%), squamous cell carcinoma (n = 26; 10.5%), small cell carcinoma (n = 28; 11.3%), invasive ductal carcinoma (n = 35; 14.1%), sarcoma (n = 3; 1.2%), and others (n = 43; 17.3%). MRI or CT scans of the 248 patients were analyzed, indicating a total count of 2,163 brain metastases (median: five metastases per patient). HMs were identified in 18 (7.3%) patients. The most common location for LSMswas the cingulum/cingulate gyrus in 26 (10.5%) patients. In univariate and multivariate analyses, patients with 15 or fewer BMs had a significantly lower incidence of HMs (odds ratio (OR), 0.018 (95% confidence interval (CI), 0.030-0.24)) (p < 0.0001). A maximal tumor size of less than 2cm significantly increased the incidence of HMs (OR, 13.8 (95%CI, 1.80-105.3)) (p = 0.0003). The presence of cingulum/cingulate gyrus metastases also demonstrated a significant increase in the incidence of HMs (OR, 9.42 (95%CI, 3.30-26.84)) (p < 0.0001). The present study has uncovered a novel association between a high number of metastases in the cingulate gyrus and the development of HMs. Patients with BMs eligible for WBRT with metastases in the cingulate gyrus may be at risk of developing HM.

GPR35 acts a dual role and therapeutic target in inflammation.

GPR35 is a G protein-coupled receptor with notable involvement in modulating inflammatory responses. Although the precise role of GPR35 in inflammation is not yet fully understood, studies have suggested that it may have both pro- and anti-inflammatory effects depending on the specific cellular environment. Some studies have shown that GPR35 activation can stimulate the production of pro-inflammatory cytokines and facilitate the movement of immune cells towards inflammatory tissues or infected areas. Conversely, other investigations have suggested that GPR35 may possess anti-inflammatory properties in the gastrointestinal tract, liver and certain other tissues by curbing the generation of inflammatory mediators and endorsing the differentiation of regulatory T cells. The intricate role of GPR35 in inflammation underscores the requirement for more in-depth research to thoroughly comprehend its functional mechanisms and its potential significance as a therapeutic target for inflammatory diseases. The purpose of this review is to concurrently investigate the pro-inflammatory and anti-inflammatory roles of GPR35, thus illuminating both facets of this complex issue.

Development of a Generic Fetal Physiologically Based Pharmacokinetic Model and Prediction of Human Maternal and Fetal Organ Concentrations of Cefuroxime.

Physiologically based pharmacokinetic (PBPK) models for pregnant women have recently been successfully used to predict maternal and umbilical cord pharmacokinetics (PK). Because there is very limited opportunity for conducting clinical and PK investigations for fetal drug exposure, PBPK models may provide further insights. The objectives of this study were to extend a whole-body pregnancy PBPK model by multiple compartments representing fetal organs, and to predict the PK of cefuroxime in the maternal and fetal plasma, the amniotic fluid, and several fetal organs. To this end, a previously developed pregnancy PBPK model for cefuroxime was updated using the open-source software Open Systems Pharmacology (PK-Sim®/MoBi®). Multiple compartments were implemented to represent fetal organs including brain, heart, liver, lungs, kidneys, the gastrointestinal tract (GI), muscles, and fat tissue, as well as another compartment lumping organs and tissues not explicitly represented. This novel PBPK model successfully predicted cefuroxime concentrations in maternal blood, umbilical cord, amniotic fluid, and several fetal organs including heart, liver, and lungs. Further model validation with additional clinical PK data is needed to build confidence in the model. Being developed with an open-source software, the presented generic model can be freely re-used and tailored to address specific questions at hand, e.g., to assist the design of clinical studies in the context of drug research or to predict fetal organ concentrations of chemicals in the context of fetal health risk assessment.

Anti-Gephyrin Antibodies: A Novel Specificity in Patients With Systemic Sclerosis and Lower Bowel Dysfunction.

Autoantibodies are clinically useful in phenotyping patients with systemic sclerosis (SSc). Gastrointestinal (GI) function is regulated by the enteric nervous system (ENS) and commonly impaired in SSc, suggesting that the SSc autoimmune response may target ENS antigens. We sought to identify novel anti-ENS autoantibodies with an aim to clinically phenotype SSc GI dysfunction. Serum from a patient with SSc with GI dysfunction but without defined SSc-associated autoantibodies was used for autoantibody discovery. Immunoprecipitations performed with murine myenteric plexus lysates were on-bead digested, and autoantigens were identified by mass spectrometry. Prevalence was determined, and clinical features associated with novel autoantibodies were evaluated in a SSc cohort using regression analyses. The expression of gephyrin in human GI tract tissue was examined by immunohistochemistry. We identified gephyrin as a novel SSc autoantigen. Anti-gephyrin antibodies were present in 9% of patients with SSc (16/188) and absent in healthy controls (0/46). Anti-gephyrin antibody-positive patients had higher constipation scores (1.00 vs 0.50, P = 0.02) and were more likely to have severe constipation and severe distention/bloating (46% vs 15%, P = 0.005; 54% vs 25%, P = 0.023, respectively). Anti-gephyrin antibody levels were significantly higher among patients with severe constipation (0.04 vs 0.00; P = 0.001) and severe distention and bloating (0.03 vs 0.004; P = 0.010). Severe constipation was associated with anti-gephyrin antibodies even in the adjusted model. Importantly, gephyrin was expressed in the ENS, which regulates gut motility. Gephyrin is a novel ENS autoantigen that is expressed in human myenteric ganglia. Anti-gephyrin autoantibodies are associated with the presence and severity of constipation in patients with SSc.

Current status and clinical applications of tissue engineering of the gastrointestinal tract: a systematized narrative review

BackgroundSince the advent of regenerative medicine, tissue engineering of the gastrointestinal tract (GIT) has been extensively studied in laboratory animals and humans. Various biologic scaffolds and cell sources have been trialed to repair or reconstruct different GIT defects. Achievements in this field have led to novel approaches in curing GIT diseases and circumventing the morbidity-related complications associated with current therapy.ObjectiveThis review aims to describe recent advances in GIT tissue engineering, with an emphasis on technologies with potential for clinical use.MethodsA literature search was conducted in Ovid MEDLINE® ALL for relevant studies (2000–September 2023) using the keywords “tissue-engineering”, “scaffolds”, “organoids”, “cell-therapy”, “esophagus”, “stomach”, “small intestine”, “colon”, “rectum”, and “anus”. Articles were included if they were in vivo animal studies or clinical studies written in English that investigated tissue engineering for treating GIT defects.ResultsA total of 836 articles were identified in the initial search. Following duplicate removal, abstract, and full-text screening, 48 articles were included in the final review. Many studies on esophageal defects thus far have described the success of covering partial-thickness defects with autologous cell sheets and closing full-thickness defects with decellularized scaffolds in both animals and humans. A limited number of reports have also demonstrated the de novo organogenesis of the esophagus to repair short-segment circumferential esophageal defects with autologous pluripotent cells and scaffolds. In the stomach, multiple animal studies have reported on the feasibility of gastric epithelium regeneration using multipotent cells and/or scaffolds to correct partial- and full-thickness defects. One study observed the regeneration of whole-layer stomach defects using the organoids-on-polymer approach. Similarly, in the intestine, pluripotent cells and scaffolds were shown to effectively repair both partial- and full-thickness defects. Animal experiments have produced tissue-engineered small intestines (TESI) with the organoids-on-polymer approach. Furthermore, in the rectum and anus, mesenchymal stem cell therapies with or without bioscaffolds have shown promise for treating full-thickness defects, as demonstrated in multiple human trials.ConclusionTissue-engineering approaches for repairing various types of GI defects in the esophagus, stomach, intestines, rectum, and anus have been extensively explored in animal models, with promising outcomes. Moreover, successful human trials have demonstrated the feasibility of reconstructing esophageal, rectal, and anal defects using these innovative approaches. Technologies such as mesenchymal stem cells, decellularization, organoids, and cell sheets are the most promising and closer to clinical translation. Collaboration between gastrointestinal surgery and regenerative medicine is expected to bring about novel therapeutic modalities in the future.

Abstract 17 — Overall Infection Risks of Tofacitinib in Patient with Rheumatoid Arthritis: A Meta-Analysis of Randomized Clinical Trials

Background There is an ongoing controversy surrounding whether tofacitinib increases the risk of infections in patients with rheumatoid arthritis (RA). To address this issue, we conducted a meta-analysis using data from randomized clinical trials (RCTs) to assess the overall risk of infection in these patients. Methods We conducted a comprehensive systematic search in EMBASE, MEDLINE, and CENTRAL from their inception until December 2022 to identify relevant RCTs reporting the occurrence of infections in patients with RA who were treated with the standard clinical therapeutic dosage of tofacitinib (5mg twice daily orally). The primary outcomes of the included studies in this review focused on the incidence of total infections, serious infections, non-serious infections, and opportunistic infections (including herpes zoster and tuberculosis). Additionally, we examined secondary outcomes related to the incidence of various sites of infections, including the upper respiratory tract, lower respiratory tract, gastrointestinal tract, hepatobiliary system, urinary tract, skin and soft tissue, blood, dental and oral soft tissue, genital, reproductive tract, bone and joint, and central nervous system infections. Due to the expected anticipation of clinical and methodological heterogeneity across studies, the effect estimate was pooled with a random-effects model, to obtain the RRs and 95% CIs, using Mantel-Haenszel statistical method. Results Twelve eligible RCTs, involving a total of 6,056 patients, were included in the analysis. In comparison to the control group (placebo and other active treatments), tofacitinib exhibited a significant increase in the risk of total infections (RR, 1.21; 95% CI, 1.07-1.37; I2, 28%), serious infections (RR, 1.23; 95% CI, 1.02-1.48; I2, 0%), non-serious infections (RR, 1.20; 95% CI, 1.05-1.36; I2, 29%), and opportunistic infections (RR, 1.66; 95% CI, 1.40-1.97; I2, 0%). Secondary outcomes analyses revealed a significant increase in the risk of lower respiratory infections with tofacitinib (RR, 1.27; 95% CI, 1.10–1.47; I2, 0%). Conclusion Compared with placebo and other active treatments, tofacitinib significantly increased the overall risk of infections (total infections, serious infections, non-serious infections, and opportunistic infections). These findings can help clinicians assess the risk of infections in RA patients treated with tofacitinib.

Impact of Sustained Fructose Consumption on Gastrointestinal Function and Health in Wistar Rats: Glycoxidative Stress, Impaired Protein Digestion, and Shifted Fecal Microbiota.

The gastrointestinal tract (GIT) is the target of assorted pathological conditions, and dietary components are known to affect its functionality and health. In previous in vitro studies, we observed that reducing sugars induced protein glycoxidation and impaired protein digestibility. To gain further insights into the pathophysiological effects of dietary sugars, Wistar rats were provided with a 30% (w/v) fructose water solution for 10 weeks. Upon slaughter, in vivo protein digestibility was assessed, and the entire GIT (digests and tissues) was analyzed for markers of oxidative stress and untargeted metabolomics. Additionally, the impact of sustained fructose intake on colonic microbiota was also evaluated. High fructose intake for 10 weeks decreased protein digestibility and promoted changes in the physiological digestion of proteins, enhancing intestinal digestion rather than stomach digestion. Moreover, at colonic stages, the oxidative stress was harmfully increased, and both the microbiota and the intraluminal colonic metabolome were modified.

Screening of reliable reference genes for the normalization of RT-qPCR in chicken gastrointestinal tract

The application of reverse transcription quantitative real-time PCR technology for the production of gene tissue expression profiles is a widely employed approach in molecular biology research. It is imperative to ascertain internal reference genes that exhibit stable expression across diverse tissues to ensure the precision of tissue gene expression profiles. While there have been studies documenting the most suitable reference genes for various tissues in chickens, there is a dearth of research on the identification of reference genes in the gastrointestinal (GI) tract of chickens. This study utilized 4 different algorithms (Delta CT, BestKeeper, NormFinder, and Genorm) to assess the stability of 19 internal reference genes in various GI tract tissues, including individual GI tract tissues, the anterior and posterior GI tract, and the entire GI tissue. The RefFinder software was employed to comprehensively rank these genes. The research findings successfully identified the most appropriate internal reference genes for each type of GI tissue. Furthermore, TBP, DNAJC24, Polr2b, RPL13, andAp2m exhibited stable expression in the entire and posterior GI tract, whereas HMBS, TBP, Ap2m, GUSB, DNAJC24, and RPL13 demonstrated stable expression in the anterior GI tract. However, the internal reference genes commonly utilized, namely β-Actin, 18s RNA, and ALB, exhibit poor stability and are not advised for future investigations concerning gene expression in the GI region. Consequently, MUC2 and CDX1, 2 genes that specifically express in the gut, were chosen for examination to ascertain the stability of the aforementioned internal reference genes in this particular study. In summary, this study presents a relatively stable set of internal reference genes that can be employed to enhance the precision of quantifying mRNA expression levels in functional genes within the chicken GI tract.

Migration of foreign bodies of firearms origin

Objective. To analyse the results of diagnosis and treatment of wounded with gunshot combat trauma, in which foreign body migration was recorded, and to determine their optimal algorithm.&#x0D; Materials and methods. The data of anamnesis, objective clinical and general clinical and laboratory studies, as well as the results of instrumental diagnostics (radiological, endoscopic, ultrasound examinations) of 67 wounded with blind gunshot wounds of various localisations were analysed. Thoracic, laparoscopic and arthroscopic surgical interventions were performed on a video endoscopic stand, and surgical magnetic instruments were used to diagnose and remove ferromagnetic foreign bodies.&#x0D; Results. The main directions of foreign body migration are the respiratory tract, gastrointestinal tract, vascular bed, cavities (pleural, abdominal, joints) and soft tissues in case of suppuration. Foreign body fixation occurs in the place of narrowing of an artery or vein, distal parts of the respiratory tract, gentle parts of the pleural or abdominal cavity, in organs with structural features (heart, intestine, joint).&#x0D; Conclusions. Although the migration of foreign bodies of gunshot origin is rare, it requires appropriate attention and response.&#x0D; In case of gunshot penetrating wounds of cavities (thoracic, abdominal, large joints), to which foreign bodies may migrate, preference should be given to minimally invasive endoscopic methods of their removal using modern magnetic instruments.