Chronic Gastrointestinal Disease Research Articles

Evaluation of stem cell therapies in companion animal disease models: A concise review (2015-2023).

Companion animals in veterinary medicine develop multiple naturally occurring diseases analogous to human conditions. We previously reported a comprehensive review on the feasibility, safety, and biologic activity of using novel stem cell therapies to treat a variety of inflammatory conditions in dogs and cats (2008-2015) [1]. The purpose of this review is to provide an updated summary of current studies in companion animal disease models that have evaluated stem cell therapeutics that are relevant to human disease. Here we have reviewed the literature from 2015 to 2023 for publications on stem cell therapies that have been evaluated in companion animals, including dogs, cats, and horses. The review excluded case reports or studies performed in experimentally induced models of disease, studies involving cancer, or studies in purpose-bred laboratory species such as rodents. We identified 45 manuscripts meeting these criteria, an increase from 19 that were described in the previous review [1]. The majority of studies were performed in dogs (n=28), with additional studies in horses (n=9) and cats (n=8). Disease models included those related to musculoskeletal disease (osteoarthritis, tendon/ligament injury), neurologic disease (canine cognitive dysfunction, intervertebral disc disease, spinal cord injury) gingival/dental disease (gingivostomatitis), dermatologic disease (atopic dermatitis), chronic multi-drug resistant infections, ophthalmic disease (keratoconjunctivitis sicca, eosinophilic keratitis, immune mediated keratitis), cardiopulmonary disease (asthma, degenerative valve disease, dilated cardiomyopathy), gastrointestinal disease (inflammatory bowel disease, chronic enteropathy) and renal disease (chronic kidney disease). The majority of studies reported beneficial responses to stem cell treatment, with the exception of those related to more chronic processes such as spinal cord injury and chronic kidney disease. However, it should also be noted that 22 studies were open-label, baseline-controlled trials and only 12 studies were randomized and controlled, making overall study interpretation difficult. As noted in the previous review, improved regulatory oversight and consistency in manufacturing of stem cell therapies is needed. Enhanced understanding of the temporal course of disease processes using advanced -omics approaches may further inform mechanisms of action and help define appropriate timing of interventions. Future directions of stem cell-based therapies could include use of stem-cell derived extracellular vesicles, or cell conditioning approaches to direct cells to specific pathways that are tailored to individual disease processes and stages of illness.

Effect of a gamified mobile-based self-management application on disease activity index, quality of life, and mental health in adults with inflammatory bowel disease: A protocol of a randomized controlled trial study.

Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal tract disease subdivided into Crohn's disease (CD) and ulcerative colitis (UC). There is currently no cure for IBD, and individuals with IBD frequently experience a lower health-related quality of life (HRQOL) than the general population. Gamification has become an increasingly popular topic in recent years. Adapting game design concepts to nongaming contexts represents a novel and potential approach to changing user engagement. This study will be conducted with the aim of evaluating the effect of a gamified mobile-based self-management application on disease activity index, quality of life, and mental health in adults with IBD. A multicenter, parallel, two-arm, exploratory randomized controlled trial with a 6-month follow-up per patient will be designed to compare the impact of the gamified mobile-based tele-management system on primary and secondary health outcomes and outpatient visits in 210 patients with all types of IBD which are divided equally into a control group with standard care and an intervention group which will use the developed mobile application named MY IBD BUDDY. All patients will attend study visits at baseline, 12 and 24 weeks, and routine IBD clinic visits or telephone consultations based on randomization group assignment. Disease activity or disease activity index, mental health (anxiety and depression) symptoms, quality of life, self-efficacy, and IBD-specific knowledge will be measured at baseline with two follow-ups at 12 and 24 weeks. In sum, the outcomes of our trial will demonstrate the impact of the gamified mobile-based self-management system on disease activity, quality of life, and anxiety and depression by means of interactive care and patient empowerment. IRCT: IRCT20200613047757N1. Registered November 16, 2021. Prospectively registered and visible at OSF (https://doi.org/10.17605/OSF.IO/AWFY9).

Analysis and prediction of nutritional outcome of patients with pediatric inflammatory bowel disease from Bahrain

BackgroundInflammatory bowel disease (IBD) is a chronic gastrointestinal disease that causes anorexia, malabsorption, and increased energy requirements. Childhood IBD can significantly impact nutritional status and future health.ObjectiveThis study aimed to analyze the nutritional status of patients with pediatric IBD at presentation and during follow-up and to identify predictors of nutritional outcome.MethodsThis retrospective cohort study reviewed the medical records of children diagnosed with IBD in the Pediatric Department, Salmaniya Medical Complex, Bahrain, 1984 − 2023. Demographic data, clinical characteristics, and anthropometric data were collected. World Health Organization growth standards were used to interpret nutritional status.ResultsOf the 165 patients, 99 (60%) had anthropometric data at presentation, and 130 (78.8%) had follow-up data. Most patients were males (64.6%) and had Crohn’s disease (CD) (56.2%), while 43.8% had ulcerative colitis (UC). The median age at presentation was 10.9 years and the mean follow-up duration was 12.6 years. At presentation, 53.5% of the patients were malnourished, that decreased to 46.9% on follow-up. Thinness was reduced from 27.3% at presentation to 12.1% at follow-up (p = 0.003). There was an increased tendency to normal weight on follow-up (59.6%) compared to time of presentation (46.5%), p = 0.035. Overweightness showed a non-significant increase from 26.3% at presentation to 28.3% at follow-up (p = 0.791). Children with IBD were more likely to become obese when they grow up to adulthood (2.3% versus 20.5%, respectively, p < 0.001). Weight-for-age, and height-for-age at presentation were higher among CD compared to UC, but body mass index (BMI) at follow-up was higher among UC patients (p < 0.05). Thinness at follow up was associated with very early-onset disease (p = 0.02), lower weight and BMI at presentation (p < 0.001 each), younger age at follow-up (p = 0.002), pediatric age group (p = 0.023), lower hematocrit (p = 0.017), and higher C-reactive protein (p = 0.007). Overweight at follow up was associated with increased weight and BMI at presentation (p < 0.001 each), longer disease duration (p = 0.005), older age (p = 0.002), and azathioprine intake (p = 0.026). Considering follow-up duration, univariate analysis exhibited that Bahraini nationality, post-diagnosis disease duration, age at follow-up, occurrence of diarrhea, height, and BMI at presentation were factors that decreased liability to abnormal nutritional status, while CD, history of weight loss, perianal disease, and skin rash, and intake of prednisolone expressed increased liability of abnormal nutritional status (p < 0.05).ConclusionPediatric IBD is associated with a high incidence of malnutrition. Thinness is more prominent at presentation, while overweight is higher on follow-up. Multiple risk factors aggravating abnormal nutritional status were highlighted. Accordingly, nutritional counseling should be prioritized in a multidisciplinary approach.

Diagnostic Value of Faecal Calprotectin in Children with Chronic Gastrointestinal Disorders at Yaounde General Hospital

&amp;lt;i&amp;gt;Introduction&amp;lt;/i&amp;gt;: Chronic gastrointestinal disorders are common in children. Numerous faecal biomarkers, such as faecal calprotectin, are used in the aetiological diagnosis of these digestive disorders. The study aimed to investigate the diagnostic value of faecal calprotectin in paediatric chronic gastrointestinal disease compared with that obtained in healthy children. &amp;lt;i&amp;gt;Methodology&amp;lt;/i&amp;gt;: This was a comparative, analytical cross-sectional study from October 2022 through June 2023 at Yaoundé General Hospital. Participants were children aged between four and eighteen with chronic digestive disorders. Using a pre-established questionnaire, we collected the socio-demographic and clinical characteristics of each participant. The participants&amp;apos; faecal calprotectin was tested at the laboratory of the Yaoundé University Hospital Center by Enzyme-Linked Immunosorbent Assay (ELISA). Associations between variables were investigated by linear regression and calculation of the odds ratio (OR). The significance threshold was 5%. &amp;lt;i&amp;gt;Results&amp;lt;/i&amp;gt;: Sixty stool samples were analysed for faecal calprotectin from 30 patients and 30 healthy participants. The mean age of the population was 9.47 (± 3.35) years for patients and 10.67 (± 3.70) years for healthy participants, with a sex ratio of 1.14 for patients and 0.87 for healthy participants. The threshold value for faecal calprotectin was 2.75 µg/g, with a sensitivity of 60%, a specificity of 63%, a positive predictive value of 61.20% and a negative predictive value of 62.06%. There were no significant differences in faecal calprotectin concentrations between children with chronic gastrointestinal disorders (peptic ulcer disease: p=0.10; functional gastrointestinal disorder associated with peptic ulcer disease: p= 0.710; functional gastrointestinal disorder: p= 0.143) and healthy children. &amp;lt;i&amp;gt;Conclusion&amp;lt;/i&amp;gt;: The diagnostic value of faecal calprotectin as a biomarker in the diagnosis of chronic gastrointestinal disease was not observed in this study. However, the biological parameters assessed were measured only once, and given that their concentrations may vary over time, we recommend a subsequent longitudinal study.

The effect of feeding on serum concentrations of cobalamin, folate, trypsin-like immunoreactivity, and pancreatic lipase immunoreactivity in dogs with signs of chronic gastrointestinal disease.

It is unknown if serum concentrations of cobalamin, folate, canine pancreatic lipase immunoreactivity (cPLI), and canine trypsin-like immunoreactivity (cTLI) obtained postprandially are equivalent to measurements obtained after withholding food in dogs with suspected gastrointestinal disease. Measurements of serum concentrations of cobalamin, folate, cPLI, and cTLI postprandially will be equivalent to measurements after 12 hours of withholding food in dogs with signs of chronic gastrointestinal disease. Changes observed will not alter clinical interpretation. 51 client-owned dogs with signs of gastrointestinal disease. Prospective single arm clinical trial. Serum concentrations of cobalamin, folate, cPLI and cTLI 2, 4, and 8 hours postprandially were compared by equivalence testing to values after withholding food for 12 hours (baseline). Mean serum cobalamin concentrations 2 hours (498.1 ± 213.1 ng/L; P = 0.024) and 4 hours (501.9 ± 207.4 ng/L; P = 0.008) postprandial were equivalent to baseline (517.3 ± 211.5 ng/L). Mean serum cTLI 2 hours (31.3 ± 14 μg/L; P < 0.001) and 4 hours (29.6 ± 13.1 μg/L; P = 0.027) postprandial were equivalent to baseline (31.1 ± 15 μg/L). Mean serum folate concentration 2 hours postprandial (15 ± 7.7 μg/L) was equivalent to baseline (13.7 ± 8.3 μg/L; P < 0.001). Equivalence could not be assessed for cPLI due to results below the lower limit of quantification. Feeding altered the clinical interpretation in 27% (cobalamin), 35% (folate), 20% (cTLI), and 12% (cPLI) of dogs. The clinical interpretation for a substantial number of samples changed after feeding, therefore withholding food before sample collection is prudent.

Objective and Subjective Dysphagia Assessment in Inflammatory Bowel Diseases.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease that is seperated into two types: ulcerative colitis (UC) and Crohn's disease (CD). Although dysphagia is a well-studied and important topic in head and neck cancers and neurological disorders, research on the relationship between IBD and swallowing problems is not yet elucidated. The aim of this study was to compare swallowing function in the UC and CD using objective and patient-reported evaluation modalities. This was a prospective cross-sectional research with 86 patients (50 UC and 36 CD) treated at the gastroenterology department. The assessment includes flexible fiberoptic endoscopic examination (FEES). The penetration-aspiration scale, the functional oral intake scale (FOIS), the functional outcome swallowing scale (FOSS), the Eating Assessment Tool-10 test (EAT-10), the Yale Pharyngeal Residue Severity Scale for vallecula (Yale PRSS-Vallecula) and pyriform sinus (Yale PRSS-PS) were all used to determine extent of dysphagia. The CD group had higher EAT-10 scores than UC group (p=0.014). In terms of PAS scores, there was no significant difference between the two groups in all three food types (water, yogurt, and crackers) (p> 0.05). There was not a statistically significant variance between the groups in terms of vallecular residue. (p> 0.05) according to the Yale PRSS-vallecula. Based on the Yale PRSS-PS; the CD group had significantly more residue than the UC group with yoghurt and cracker (p=0.014 and 0.030, respectively). FOSS and FOIS scores did not vary significantly between the two groups (p>0.05). Crohn's disease impairs subjective and pharyngeal swallowing functions more than ulcerative colitis. It is obvious that swallowing should be assessed in patients with inflammatory bowel disease.

Selenium Yeast Alleviates Dextran Sulfate Sodium-Induced Chronic Colitis in Mice by Reducing Proinflammatory Cytokines and Regulating the Gut Microbiota and Their Metabolites.

Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal inflammatory disease. Selenium has been reported to have therapeutic potential in IBD. Selenium yeast is a common selenium supplement that is convenient to access. This study explored the effect of selenium yeast on dextran sulfate sodium- (DSS-)induced chronic colitis in mice. Mice were randomly divided into four groups: the control group, selenium yeast group, chronic colitis group, and chronic colitis+selenium yeast group (n=6). Mice were killed on the 26th day. The disease activity index (DAI) score and histological damage score were calculated. Cytokines, serum selenium, colonic tissue selenium, gut microbiota and their metabolites short-chain fatty acids (SCFAs) were evaluated. Selenium yeast lowered IL-1β, IL-6, TNF-α, IL-17A, IL-22 and IFN-γ (P<0.05). In addition, selenium yeast significantly elevated Turicibacter, Bifidobacterium, Allobaculum, Prevotella, Halomonas, Adlercreutzia (P<0.05), and butyric acid (P<0.05). Selenium yeast could improve DSS-induced chronic colitis in mice by regulating cytokines, gut microbiota and their metabolites.

The ERK-cPLA2-ACSL4 axis mediating M2 macrophages ferroptosis impedes mucosal healing in ulcerative colitis

Ulcerative colitis (UC) is a chronic gastrointestinal disease that can be managed with 5-aminosalicylic acid (5-ASA), the standard treatment for UC. However, the effectiveness of 5-ASA is not always optimal. Our study revealed that despite 5-ASA treatment, cells continued to experience excessive ferroptosis, which may hinder mucosal healing in UC and limit the success of this treatment approach in achieving disease remission. We found that combining 5-ASA with the ferroptosis inhibitor Fer-1 led to a significant inhibition of ferroptosis in macrophages present in the colon tissue, along with an increase in the proportion of M2 macrophages, suggesting that targeting ferroptosis in M2 macrophages could be a potential therapeutic strategy for alleviating UC. Our study also demonstrated that M2 macrophages are more susceptible to ferroptosis compared to M1 macrophages, and this susceptibility is associated with the activated arachidonic acid (AA) metabolism pathway mediated by ERK-cPLA2-ACSL4. Additionally, we found that the expression of cPLA2 gene pla2g4a was increased in the colon of UC patients compared to healthy controls. Furthermore, targeted metabolomics analysis revealed that the combination treatment group, as opposed to the 5-ASA treatment group, exhibited the ability to modulate AA metabolism. Overall, our findings emphasize the importance of addressing macrophage ferroptosis in order to enhance macrophage anti-inflammation, improve mucosal healing, and achieve better therapeutic outcomes for patients with UC.

Interventions to alleviate anxiety and pain during venipuncture in children with chronic gastrointestinal and/or liver disease: A single-center prospective observational study.

The goal of this longitudinal study was to reduce anxiety and pain in children with chronic conditions from the gastrointestinal tract during venipuncture. These children undergo regular venipuncture as part of their medical management and the procedure is often accompanied with anxiety and pain. In addition, children as well as their parents and health care professionals (HCPs) often suffer "compassionate pain" because of emotional interference. In a realistic clinical setting, different psychological and medical interventions were examined: (1) Psychoeducational brochures and (2) four different medical-technical interventions during venipuncture. In a large hospital in Germany, 169 children, their parents, and HCPs were asked to rate anxiety and pain during venipuncture before and after the intervention. Children showed a clear preference for some of the medical-technical interventions. Using Linear Mixed Models anxiety and pain rated by the children themselves showed no significant reduction. However, parents and HCPs reported a significant reduction. Age, gender, and status of liver transplantation were associated with a reduction in anxiety and pain in most of the analyses. Both psychoeducational brochures and medical-technical interventions had a positive impact on anxiety and pain. However, effectivity for the medical-technical interventions was lower than in previous studies utilizing individual interventions. Reasons for this difference as well as possibilities to improve the intervention are discussed. In addition, this study provides practical day-to-day information about the implementation of interventions for the work in pediatric units such as when and how to provide psychoeducational materials.

Mycobacterium avium ssp. paratuberculosis and Crohn's Disease-Diagnostic Microbiological Investigations Can Inform New Therapeutic Approaches.

Mycobacterium avium ssp. paratuberculosis (MAP) is the cause of Johne's disease (JD), which is a chronic infectious gastrointestinal disease of ruminants and is often fatal. In humans, MAP has been associated with Crohn's disease (CD) for over a century, without conclusive evidence of pathogenicity. Numerous researchers have contributed to the subject, but there is still a need for evidence of the causation of CD by MAP. An infectious aetiology in CD that is attributable to MAP can only be proven by bacteriological investigations. There is an urgency in resolving this question due to the rising global incidence rates of CD. Recent papers have indicated the "therapeutic ceiling" may be close in the development of new biologics. Clinical trial outcomes have demonstrated mild or inconsistent improvements in therapeutic interventions over the last decades when compared with placebo. The necessity to revisit therapeutic options for CD is becoming more urgent and a renewed focus on causation is essential for progress in identifying new treatment options. This manuscript discusses newer interventions, such as vaccination, FMT, dietary remediation and gut microbiome regulation, that will become more relevant as existing therapeutic options expire. Revisiting the MAP theory as a potential infectious cause of CD, rather than the prevailing concept of an "aberrant immune response" will require expanding the current therapeutic programme to include potential new alternatives, and combinations of existing treatments. To advance research on MAP in humans, it is essential for microbiologists and medical scientists to microscopically detect CWDM and to biologically amplify the growth by directed culture.

Development of a Culinary Medicine Curriculum to Support Nutrition Knowledge for Gastroenterology Fellows and Faculty.

Gastroenterologists encounter many nutrition-related disorders in their practice, yet the nutritional needs of patients with chronic gastrointestinal (GI) and liver disease are largely unaddressed by treating physicians, due to suboptimal nutrition education. To address this gap, we developed and piloted a culinary medicine course for a GI fellowship training program. The objective of this study is to describe the development, implementation, and acceptability of the course. A registered dietitian, a chef instructor, and a gastroenterology clinical professor trained in culinary medicine developed the four-class tailored curriculum and delivered the classes remotely. Each class had a theme related to commonly encountered GI disorders and included hands-on meal preparation, a nutrition lecture, and a patient case study discussion. Post-course feedback surveys were disseminated. Twenty-three GI physicians enrolled in the course and the attendance rates in classes 1-4 were 83%, 65%, 61%, and 48%, respectively. Among 15 completed feedback surveys, 80% reported that the class contents were either moderately or extremely useful and all endorsed the curriculum for other gastroenterologists. Future studies of culinary medicine programs tailored to medical specialties should identify strategies to maintain engagement and assess the impact on nutrition knowledge, competencies, and translation of these new skills to clinical practice.

P248 Feasibility, accuracy and reproducibility of the ultrasound measurement of psoas muscle compared to bioelectrical impedance analysis for the evaluation of skeletal muscle mass in patients with IBD

Abstract Background Sarcopenia is characterized by the loss of muscle mass and it is a strong predictor of disability and poor outcomes in several chronic gastrointestinal diseases such as inflammatory bowel diseases (IBD). Therefore, it is useful to evaluate muscle mass in patients with chronic gastrointestinal diseases at risk for sarcopenia. Radiological evaluation of muscle mass is obtained with computed tomography (CT), magnetic resonance (MRI) and bioelectrical impedance (BIA). We aimed at assessing the feasibility, reproducibility and diagnostic accuracy of ultrasound (US) measurement of psoas muscle thickness adjusted for body mass index (BMI) compared to skeletal muscle mass (SMM) evaluated with BIA normalized to height2 in the quantification of muscle mass among patients with IBD. Methods We enrolled a total of 86 consecutive patients with IBD (males 68.6%, mean age 50.4 ± 17.6, 7.4% with Crohn’s disease) who underwent US evaluation of psoas muscle thickness and BIA during the same day. US measurement (Philips Epiq, Bothell, USA) was performed by two sonographers, blind to each other. BIA was performed with the Seca mBCA 525 (Hamburg, Germany). A cut-off of 6.68 and 8.97 of SMM normalized to height2 was considered as normal value for women and men respectively. Sensitivity, specificity, positive and negative predictive values(PPV and NPV), positive and negative likelihood ratios (LR+ andLR−) were calculated, all with the respective 95% confidence inter-vals (95% CI). The reproducibility between the US operators was evaluated by intra-class correlation coefficient(ICC) for the quantitative variables of psoas muscle. The study was approved by our local ethics committee and partially funded by the Italian Ministry of Health. Results US psoas muscle thickness measurement was feasible in all the 86 enrolled patients. There was a significant correlation between US measurement and BIA with a Pearson r coefficient of 0.54 (p= &amp;lt;0.0001). Among men a cut off of 108.18 cmxkg/m*2 showed a sensitivity of 93.5% and a specificity of 53,6% in the detection of low SMM at BIA (Figure 1). Among women a cut off of 66.9 cmxkg/m*2 showed a sensitivity of 78.5% and a specificity of 69.2% in the detection of low SMM at BIA (Figure 2). Reproducibility among the operators had an ICC of 0.95 (CI 0.93-0.96). Conclusion Sarcopenia is a prognostic factor of poor outcomes in IBD, therefore it is important to identify patients at risk for it. Nowadays, assessment of muscle mass and eventually sarcopenia relies on radiological techniques (CT/MRI and BIA). At this purpose we propose a simple, non-ionizing, fast and reproducible US technique that compared to BIA showed a high sensitivity and thus can be used in clinical ractice to screen for muscle mass reduction in IBD patients.

Evaluation of Voice in Inflammatory Bowel Diseases

Introduction: Inflammatory bowel diseases, which are among the most common chronic gastrointestinal diseases, can also affect the voice for different reasons. The aim of this study was to investigate acoustic, perceptual, and subjective voice evaluation parameters in inflammatory bowel diseases (IBD). Methods: This prospective case-control study included a total of 80 participants: 28 patients with ulcerative colitis (UC), 22 patients with Crohn’s disease (CD), and 30 healthy controls. Following the endoscopic examination, the fundamental frequency (F0), shimmer (dB), jitter (%), and harmonic/noise ratio (HNR) were measured. GRBAS (grade, roughness, breathiness, asthenia, strain) scale was used for perceptual evaluation, and Voice Handicap Index-10 (VHI-10) Turkish version was used for subjective assessment. Results: The F0 value was within normal limits in both disease groups in male and female participants and in the control group. Jitter and shimmer values were statistically higher in the UC and CD groups than in the control group. HNR did not differ between CD and control; however, it was statistically lower in the UC group when compared to both the control and CD groups. The total GRBAS score did not differ between the UC and CD groups; however, it was greater in IBD patients compared to the control group. However, these differences were within normative parameters. Although total VHI-10 score did not differ between UC and CD groups, both had a higher voice handicap than the control group. Conclusion: IBD might have an effect on the voice and voice quality. This disease group was discovered to have perceptual and subjective voice problems additionally.

The role of primary care physicians in early diagnosis and treatment of chronic gastrointestinal diseases

Gastrointestinal diseases encompass conditions affecting the gastrointestinal tract, including the esophagus, stomach, and small and large intestines. These conditions are prevalent in general practice, with common diseases such as irritable bowel syndrome, inflammatory bowel disease, and celiac disease. Primary care physicians encounter a broad spectrum of clinical problems, necessitating a wide range of knowledge for accurate diagnosis and prescription of medications.It is crucial to recognize the role of primary care physicians in the diagnosis and management of gastrointestinal diseases, given their frequent presentation in primary care settings. This review aims to provide an overview of the role of primary care physicians in the diagnosis and management of various chronic gastrointestinal diseases.Scientific websites and databases were utilized to search for relevant articles. Various keywords were employed in different combinations to retrieve all possible articles related to the current subject. The findings incorporated in this review consist of original articles, review articles, and systematic reviews written in the English language that address our objectives.The selected articles underwent a thorough review based on inclusion criteria. The articles included in this review were published between 2010 and 2022. Despite the availability of original research and reviews, there is insufficient information on the role of primary care physicians in the diagnosis and treatment of chronic gastrointestinal diseases. Physicians may lack knowledge regarding the proper management and diagnosis of these conditions; however, their roles can be enhanced through increased education and awareness

Evaluation of Nitazoxanide versus Metronidazole in Pediatric Giardia lamblia-Induced Diarrhea: A Comparative Efficacy Analysis

Background: The choice between shorter-duration Nitazoxanide and longer-duration Metronidazole regimens for treating Giardia lamblia-induced diarrhea in children requires careful consideration of efficacy, safety, and treatment adherence. Objective: The objective of this study is to compare the efficacy of a 3-day treatment regimen with Nitazoxanide to a 5-day treatment regimen with Metronidazole in children with diarrhea caused by Giardia lamblia. Study Design: Randomized controlled trial (RCT). Settings: Department of Paediatric, Shahida Islam Medical College, Lodhran Pakistan. Duration: From 1st September, 2022 to February 2023. Methods: Pediatric patients aged 1 to 12 years diagnosed with diarrhea attributed to Giardia lamblia infection. Exclusion criteria were children suffering from chronic gastrointestinal diseases, immunodeficiency disorders, or those who had undergone anti-parasitic medication in the last month. Subjects were randomised to one of two treatment groups in a random manner: Nitazoxanide Group: The patients were administered a 3-day regimen of Nitazoxanide at a dosage of 15 mg/kg/day, split into two separate doses. Metronidazole Group: Patients were administered a 5-day regimen of Metronidazole at a dosage of 30 mg/kg/day, which was divided into three equal doses. The primary outcome measure was the resolution of diarrhea, assessed by the absence of loose or watery stools for at least 24 hours. Statistical analysis was performed using SPSS to compare outcomes between the two treatment groups. Results: The mean age of patients in the Nitazoxanide group was 6.7 ± 2.3 years, while in the Metronidazole group, it was slightly lower at 6.3±2.1 years. In terms of gender distribution, there were 40 males (53.3%) and 35 females (46.7%) in the Nitazoxanide group, whereas in the Metronidazole group, there were 35 males (46.7%) and 40 females (53.3%). In the Nitazoxanide group, 90% of patients achieved resolution, with 68 patients. In contrast, 85% of patients in the Metronidazole group had resolved diarrhea, totaling 64 patients. Conclusion: In conclusion, our study found comparable efficacy between nitazoxanide and metronidazole for treating Giardia lamblia-induced diarrhea with 95% parasite clearance in nitazoxanide and 90% in metronidazole. However, nitazoxanide exhibits superior parasite clearance, suggesting its potential as a promising alternative in pediatric clinical practice.

The Role of Microcin B17-Producing Escherichia Coli, Isolated from Patients with Inflammatory Bowel Disease on Rat Intestine

Background: Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal disease, Crohn’s disease (CD) and ulcerative colitis (UC) are two distinct kinds of IBD. Recent researches have linked between Escherichia coli which produce the toxin microcin B17 (E. coli/+mB17) and the development of inflammatory bowel disease (IBD). Objective: This study aimed to demonstrate the relationship between these E. coli isolates and the emergence of IBD in an experimental animal models. Materials and Methods: Twenty female rats, five-weeks-old were divided in to four groups; first group, were orally given E. coli/+mB17 isolated from crohn’s patients stool, the second group rats were orally given E. coli/+mB17 isolated from patients stool with ulcerative colitis, in the third group were orally given E. coli non-producing microcin B17 (E. coli/-mB17) isolated from patients stool with IBD, and the last group received normal saline orally, as control. After fifteen weeks of administration, Blood was drawn for serological tests which include interlukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) and the rats sacrificed for evaluation of histological changes in their intestine. Results: All groups that were administrated bacteria, whether they were toxin producer or not, showed a decrease in their weights with a reduction of appetite. Serological changes observed included an increase in IL-10 level and an increase in TNF-α level in their sera. Regarding the histological examination, there were noticeable histological changes in the large intestines of all rats given bacterial suspension but not in small intestine. Conclusion: All E.coli isolates which were isolated from IBD patients stool (whether it was microcin B17 producing or not) were able to induce inflammatory responses and histological changes in the intestines of rats . Accordingly, other virulence factors (in addition to Microcin B17) may play role in the pathogenesis of IBD.

Exploring the clinical significance of miR-148 expression variations in distinct subtypes of irritable bowel syndrome.

Irritable bowel syndrome (IBS) belongs to chronic functional gastrointestinal diseases featured by abdominal pain and changes in bowel habits. This study aimed to investigate the clinical significance of serum miR-148 expression in different subtypes of IBS. We enrolled 86 IBS patients and 55 healthy controls. miR-148 expression levels were assessed in IBS patients classified into IBS-constipation (IBS-C), IBS-diarrhea (IBS-D), and IBS-mixed stool pattern (IBS-M) subtypes. Receiver-operating characteristic (ROC) curves were employed to evaluate the diagnostic potential of miR-148 in distinguishing among IBS subtypes. Additionally, we analyzed the correlation between miR-148 expression and clinical characteristics, including IBS symptom severity. miR-148 expression was highest in IBS-D (diarrhea) group, followed by IBS-M and IBS-C. With the exception of the IBS-C group, miR-148 expression was elevated in IBS patients compared to controls. ROC curve analysis demonstrated that serum miR-148 exhibited higher diagnostic accuracy for discriminating IBS-C and IBS-D than IBS-M. Correlation analysis revealed a positive relationship between serum miR-148 relative expression and IBS symptom severity system scores. Univariate logistic analysis indicated a positive association between miR-148 expression and IBS-D and a negative correlation with IBS-C. miR-148 expression exhibits differential patterns among IBS subtypes and holds a potential to distinguish IBS-C and IBS-D. Furthermore, miR-148 expression correlates with the severity of IBS symptoms.

Sinapic Acid Attenuates Chronic DSS-Induced Intestinal Fibrosis in C57BL/6J Mice by Modulating NLRP3 Inflammasome Activation and the Autophagy Pathway.

Ulcerative colitis (UC) is a chronic gastrointestinal disease that results from repeated inflammation and serious complications. Sinapic acid (SA) is a hydroxycinnamic acid present in a variety of plants that has antioxidant, anti-inflammatory, anticancer, and other protective effects. This study investigated the antifibrotic effect of SA on chronic colitis induced by dextran sulfate sodium salt (DSS) in mice. We observed that SA could significantly reduce clinical symptoms (such as improved body weight loss, increased colon length, and decreased disease activity index score) and pathological changes in mice with chronic colitis. SA supplementation has been demonstrated to repair intestinal mucosal barrier function and maintain epithelial homeostasis by inhibiting activation of the NLRP3 inflammasome and decreasing the expression of IL-6, TNF-α, IL-17A, IL-18, and IL-1β. Furthermore, SA could induce the expression of antioxidant enzymes (Cat, Sod1, Sod2, Mgst1) by activating the Nrf2/keap1 pathway, thus improving antioxidant capacity. Additionally, SA could increase the protein expression of downstream LC3-II/LC3-I and Beclin1 and induce autophagy by regulating the AMPK-Akt/mTOR signaling pathway, thereby reducing the production of intestinal fibrosis-associated proteins Collagen-I and α-SMA. These findings suggest that SA can enhance intestinal antioxidant enzymes, reduce oxidative stress, expedite intestinal epithelial repair, and promote autophagy, thereby ameliorating DSS-induced colitis and intestinal fibrosis.

Upadacitinib: Mechanism of action, clinical, and translational science.

Upadacitinib is a selective Janus kinase (JAK) inhibitor which is approved by the US Food and Drug Administration, the European Medicines Agency, as well as other agencies around the world for the treatment of several chronic inflammatory diseases, including rheumatic, dermatologic, and gastrointestinal diseases. Through inhibition of JAK, upadacitinib inhibits phosphorylation of downstream effector proteins, which consequently inhibits cytokine signaling for key pathways involved in inflammatory diseases. Upadacitinib more potently inhibits JAK1 than other JAK isoforms. The pharmacokinetics, pharmacodynamics, efficacy, and safety of upadacitinib were characterized in many clinical trials, which demonstrated the superiority of upadacitinib treatment over placebo or an active comparator in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis. The safety profile of upadacitinib supported a favorable benefit-risk profile across all the approved indications. In this article, we review the mechanism of action of upadacitinib and describe how the JAK-STAT (Janus kinase-signal transducers and activators of transcription) pathway is involved in the pathogenesis of several chronic and progressive immune-mediated inflammatory diseases. In addition, this review also provides an overview of key clinical trials that were conducted as well as relevant data which supported the clinical development of upadacitinib and informed the recommended dose(s) in each of the approved indications.

Barriers to Timely Diagnosis of Eosinophilic Gastrointestinal Diseases

Although eosinophilic gastrointestinal diseases, including eosinophilic esophagitis, have been described over the past 2 to 3 decades, barriers to diagnosis and treatment are common and compounded by issues related to social determinants of health, race, ethnicity, and access to care. These barriers contribute to delays in diagnosis, resulting in persistent inflammation in the gastrointestinal tract, which can have significant consequences, including fibrostenotic complications in adults, failure to thrive in children, and decreased quality of life in all affected patients. In this commentary, we summarize gaps in knowledge regarding the epidemiology of eosinophilic gastrointestinal diseases, highlight barriers to diagnosis, discuss potential approaches based on best practices in other atopic and chronic gastrointestinal diseases, and provide recommendations for reducing barriers to timely diagnosis of eosinophilic gastrointestinal diseases in underserved populations.