Stress has been identified as a prominent contributor to the development and advancement of bowel cancer, however its specific involvement is intricate and diverse. This abstract tries to offer a concise summary of the correlation between stress and bowel cancer, consolidating significant discoveries from several research fields. The investigation commences by studying the molecular pathways by which chronic stress impacts the development of colon cancer. Chronic stress causes disruption in the functioning of neuroendocrine, immunological, and inflammatory pathways, leading to the development of a microenvironment within the gastrointestinal system that promotes the growth of tumours. Furthermore, changes in the composition of gut microbiota, variations in epigenetics, and alterations in immune function caused by stress also have a role in increasing the risk and advancing the advancement of cancer. Psychological aspects, including how one perceives stress, the tactics they use to cope with it, and the level of psychosocial support they receive, are crucial in determining a person's susceptibility to bowel cancer and impacting the effectiveness of treatment. Stress management therapies, such as cognitive-behavioral therapy and mindfulness-based stress reduction, have demonstrated potential in enhancing patient well-being and promoting adherence to treatment. Moreover, epidemiological studies and clinical trials offer vital knowledge regarding the correlation between stress and the risk, prognosis, and treatment results of bowel cancer. Although the evidence is inconclusive, it is essential to continue researching the intricate relationship between stress and bowel cancer. This will help us understand the connection better and create specific strategies to reduce its impact on patient outcomes.

Obturator herniæ are a quite rare type of abdominal hernia, accounting for less then 1% of all abdominal wall hernias and for 0.2-1.6% of patient with a small bowel obstruction. The obturator canal is the only portion of the obturator foramen that is not obliterated by the membrane of the same name and hosts the obturator neurovascular bundle; it is, for this reason, a locus minoris resistentiae, through which obturator hernias are formed, generally in elderly, multiparous women. Despite the fact that Computed Tomography offers the possibility of a quick, correct preoperative diagnosis, often signs and symptoms of obturator herniæ are quite unspecific; considering that, at the same time, patients with an obturator hernia are generally elderly, with concurrent conditions, this might cause delays in the diagnosis and treatment and produces the high postoperative mortality rates that obturator herniæ yield

The interplay between Diffuse Idiopathic Skeletal Hyperostosis (DISH) and the gut microbiota represents a compelling area of research, offering insights into the relationship between spinal degenerative diseases and the gut's microbial inhabitants. This comprehensive review seeks to unravel the complex connection, shedding light on its implications for human health and potential therapeutic avenues. A crucial section dives into the world of gut microbiota (GM), exploring its impact on human health, featuring its defining characteristics, and highlighting its role in metabolism, immunomodulation, host interaction, and how its composition changes over time. The subsequent portion delves into the relationship between microbiome composition and pathological bone development, including the link between Intervertebral Disc Degeneration (IDD) and gut inflammation, emphasizing how gut inflammation and GM dysbiosis play pivotal roles. Further dissecting the interconnections, various axes of influence, including the gut-spine axis, gut-bone axis, gut-joint axis, gut-disc axis (specific to DISH), gut-ligament axis, and gut-muscle axis, are discussed. Of particular interest is the section on the impact of GM on DISH-derived pain, addressing a critical aspect of the condition's manifestation. The review discusses the potential of GM modulation as a treatment for DISH, providing hope for therapeutic advancements. Additionally, it highlights the positive impact of lifestyle interventions, such as dietary modifications, sleep optimization, and exercise regimens, in mitigating GM dysbiosis and potentially improving DISH outcomes. Lastly, the intriguing prospect of fecal microbiome transplant and its implications for DISH management is examined, opening new avenues for research and therapeutic interventions. In conclusion, this comprehensive review underscores the intricate interplay between DISH and the gut microbiota, offering a fresh perspective on the impact of GM on spinal degenerative diseases. It emphasizes the potential for innovative treatments, such as GM modulation and lifestyle interventions, and presents fecal microbiome transplant as an exciting area for future exploration.

Background Although the management of the majority of patients with IBS is dealt with by General Practitioners, randomized clinical trials and treatment guidelines are developed mostly in academic settings. Probiotics are one of the most investigated treatment modality for this condition. Scarce information is available as regards GPs attitude in this regard. Methods A literature search was performed to identify papers specifically dealing with probiotic treatment of IBS in the general practice setting. Moreover, the preliminary results of a survey on this topic conducted by the authors among general practitioners in a province in northern Italy are reported. Results Five papers specifically addressing probiotic treatment of IBS in general practice were found. The response rate varied from 4 to 100%. The prescription rate of probiotics by GPs in IBS varied from <10 to 46%, regardless of the patients’ bowel habits. Physicians’ satisfaction with this treatment varied from 20 to 93%. The variability of these results probably depends on factors such as differences in the interpretation of the available data on probiotics use in IBS and traditional/ cultural differences. Moreover, compliance with patient satisfaction, may play a role. Conclusions The reported data on the treatment of IBS with probiotics in general practice is scarce and inhomogeneous, thus it does not allow firm conclusions. It is suggested that the involvement in research on the use of probiotics in IBS of physicians working in general practice would be useful in order to pursue more reliable and useful results, since the majority of the IBS population is followed in general practice and may differ from the one represented in academic clinical trials.

The gut-brain axis (GBA) represents a complex, bidirectional communication network that intri-cately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut micro-biota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, and analyzing 182 relevant articles, this research highlights how neuromodulation can positively impact the management of functional gastrointestinal disorders (FGIDs), chronic pain, inflammation, and a range of GI disorders like Crohn's disease and ulcerative colitis. Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate in-flammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

Background: Patients with Inflammatory Bowel Disease (IBD) believe that diet is a key factor in the pathogenesis of their disease and in worsening their symptoms; they often follow restrictive diets that can lead to malnutrition, anxiety, and stress. Recent studies have found an association between eating disorders and IBD, particularly anorexia nervosa and ARFID (Avoidant Restrictive Food Intake Disorder). None of these studies report the association with orthorexia nervosa, that is the obsession with healthy and natural foods. Aim: to assess the risk of orthorexia nervosa in patients with IBD. Methods: 158 consecutive subjects were recruited, including 113 patients diagnosed with IBD and 45 controls. The Donini standardized questionnaire ORTO-15 was administered to assess the risk of orthorexia; clinical and demographic data were also collected. Results: patients with IBD have a prevalence of orthorexia of 77%, significantly higher than the 47% observed in the control group. In patients with IBD, the risk of orthorexia is associated with lower BMI and history of previous surgery. Conclusion: Many patients with IBD develop orthorexia nervosa that impacts the patient's psychological and social sphere, exposes them to a high risk of nutritional deficiencies, and affects quality of life. Further high quality studies are warranted to evaluate the clinical impact of orthorexia and its correlation with clinical features and frank eating disorders.

Chitinase 3-like 1 （also known as CHI3L1 or YKL-40）is a mammalian chitinase that has no enzymatic activity, but has the ability to bind to chitin, the polymer of N-acetylglucosamine (GlcNAc). Chitin is a component of fungi, crustaceans, arthropods including insects and mites, and parasites, but is completely absent from mammals, including humans and mice. In general, chitin-containing organisms produce CHI3L1 to protect the body from exogenous pathogen as well as hostile environments, and it was thought that it has a similar effect in mammals. However, recent studies have revealed that CHI3L1 plays a pro-inflammatory role by inducing anti-apoptotic activity in epithelial cells and macrophages. Under chronic inflammatory conditions such as inflammatory bowel disease and chronic obstructive pulmonary disease, many groups already confirmed that the expression of CHI3L1 is significantly induced on the apical side of epithelial cells, and activates many downstream pathways involved in inflammation and carcinogenesis. In this review article, we will summarize the expression of CHI3L1 under the chronic inflammatory conditions in various disorders and would like to discuss the potential roles of CHI3L1 in those disorders on various cell types.

Abstract Background: Massive resection of the small intestine leading to short bowel syndrome (SBS) deprives organism of many immunocompetent cells concentrated in gut associated lymphoid tissue- the largest immune organ in humans. We have aimed to access the influence of bowel resection on adaptive immunity in children, basing on peripheral lymphocyte subsets and serum immunoglobulins. Methods: 15 children, who underwent bowel resection in the first month of life and required further home parenteral nutrition were enrolled into the study.. Based on flow cytometry the following subsets of lymphocytes were evaluated: T, B, NK, CD4+, C8+and activated T cells. Results: Significantly statistical differences were found for the rates of lymphocytes B, T, CD8 + and NK cells. Absolute count of NK cells was lower in SBS group than in the control group. Absolute counts of lymphocytes, lymphocytes B, T, CD4+ and percentages of lymphocytes CD4+, and activated T cells inversely correlated with the time after resection. Conclusions: Children with SBS do not present with clinical signs of immunodeficiency as well as deficits in peripheral lymphocyte subsets and serum immunoglobulins. The tendency of the lymphocyte subpopulations to decrease over time after resection points out the necessity for longer follow- up.

Small bowel non-Meckelian diverticulosis is a rare condition with only few published cases despite being described over 200 years ago. In the midst of the COVID-19 pandemic, studies suggested that a lot of patients may experience gastrointestinal manifestations. Intestinal symptoms could worsen the inflammation and infection associated with small bowel diverticulitis. Here, we present two cases: one with inflammation and rupture in a COVID-19 patient and the other as an asymptomatic detection. Furthermore, we provide a mini-review of the literature to emphasize the importance of considering this entity in the differential diagnosis of an acute abdomen.

Objective: Infliximab (IFX) concentrations are a predictive factor (PF) of pharmacokinetic (PK) origin in the treatment of Crohn’s disease (CD). We evaluated clearance, another PF of PK origin, either alone or in combination with concentrations. Methods: PF of PK origin were evaluated from two cohorts, the first received standard dosing (n=37), and the second was designed to proactively target therapeutic IFX concentrations (n=108). Concentrations were measured using homogenous mobility shift assay. Clearance was estimated using nonlinear mixed effects methods with Bayesian priors. C-reactive protein based clinical remission (<3mg/L in the absence of symptoms) was used for the disease control outcome. Longitudinal changes in disease control due to factors including time, IFX concentration, and clearance were analyzed using repeated event analysis. Change in objective function value (∆OFV) was calculated to compare concentration and clearance. Results: Lower baseline clearance and proactive dosing associated with enhanced disease control during induction (p<0.01). Higher IFX concentrations and lower Clearance measured at the second, third and fourth infusion yielded improved disease control during maintenance (p<0.032). During maintenance, the association with disease control was better with clearance than with concentrations (∆OFV= -19.2; p<0.001), and the combination of both further minimized OFV (p<0.001) with markedly improved clinical yield in the presence of both PF of PK origin. Conclusion: PF of PK origin and lower clearance during induction and maintenance yielded enhanced disease control in pediatric CD treated with IFX. The combination of IFX concentration and clearance are better predictors of therapeutic outcome compared to either one alone.

Repeated exposure to environmental ozone causes a chronic state of oxidative stress. This state is present in chronic degenerative diseases and induces a loss of control of the inflammatory response. The dysfunction of redox system and failures in control the inflammatory responses are involved in a vicious circle that maintains and increases the degenerative process. Intestine also responds to secondary reactive species formed by exposure to ozone doses, generating noxious stimuli that increase degenerative damage. This review aims to elucidate how environmental pollution, mainly by ozone, induces a state of chronic oxidative stress with the loss of regulation of the inflammatory response, both in the intestine and in the brain, where the functionality of both structures is altered and plays a determining role in some neurodegenerative and chronic degenerative diseases. For this purpose, we searched for information on sites like the Cochrane Library Database, PubMed, Scopus, and Medscape. Reviewing the data published, we can conclude that environmental pollutants are a severe health problem. Ozone pollution has different pathways of action, both molecular and systemic, and participates in neurodegenerative diseases such as Parkinson's and Alzheimer's disease as well in bowel diseases as Inflammatory Bowel Disease, Crohn's Disease and Irritable Bowel Syndrome.

Prevention of obstetric trauma from damage to the pelvic floor is not always possible and sacral nerve stimulation (SNS) may be necessary later in life. Sacral nerve stimulation has been a promising innovation in the management of moderate to severe faecal incontinence and following sphincter repair failure. Although the indication spectrum for SNS is expanding, the success of neuromodulation for constipation is limited. Adverse events of SNS requiring re-intervention are not common but a long-term successful outcome may depend on interventions for maintenance of the device.

Inflammatory bowel diseases (IBD) represent a growing public health concern due to increasing incidence worldwide. The current notion on the pathogenesis of IBD is that genetically susceptible individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental triggers. Among the environmental factors associated to IBD, diet plays an important role in modulating the gut microbiome, influencing epigenetic changes and, therefore, could be applied as a therapeutic tool to improve the disease course. Nevertheless, the current dietary recommendations for disease prevention and management are scarce and of weak evidence. This review summarizes the current knowledge on the complex interactions among diet, microbiome and epigenetics in IBD. Whereas over-abundance of calories and some macronutrients increases gut inflammation, several micronutrients have the potential to modulate it. Immunonutrition has emerged as a new concept putting forward the importance of vitamins such as vitamins A, C, E, D, folic acid and beta-carotene and trace elements such as zinc, selenium, manganese and iron. However, when assessed in clinical trials, specific micronutrients exerted a limited benefit. Beyond nutrients, anti-inflammatory dietary patterns as a complex intervention approach have become popular over the recent years. Hence, exclusive enteral nutrition in pediatric Crohn’s disease is the only nutritional intervention currently recommended as a first-line therapy. Other nutritional interventions or specific diets including the Specific Carbohydrate Diet, the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet and most recently the Mediterranean diet have shown strong anti-inflammatory properties and provide a promise for improving disease symptoms. Definitely, more work is required to evaluate the role of individual food compounds and complex nutritional interventions with potential to decrease inflammation as means for prevention and management of IBD.

Emerging evidence suggests that the human vermiform appendix is not a vestigial organ, but rather an immunological organ of biological relevance. It is hypothesised that the appendix acts as a bacterial ‘safe house’ for commensal gut bacteria and facilitates re-inoculation of the colon after disruption through the release of biofilms. To date, no studies have attempted to explore this potential mechanistic function of the appendix. We conducted a pre-post intervention study in adults (n=59) exploring reestablishment of the gut microbiota in those with and without an appendix after colonic disruption via bowel preparation and colonoscopy. Gut microbiota composition was measured one week before and one month after bowel preparation and colonoscopy using 16S rRNA sequencing. We observed between group differences in gut microbiota composition between those with (n=45) and without (n=13) an appendix at baseline. These differences were no longer evident one-month post-procedure, suggesting that this procedure may have ‘reset’ any potential appendix-related differences between groups. Both groups experienced reductions in gut microbiota richness and shifts in beta diversity post-procedure, with greater changes in those without an appendix, and there were five bacterial genera whose re-establishment post-procedure appeared to be moderated by appendicectomy status. This small experimental study provides preliminary evidence of a potential differential reestablishment of the gut microbiota after disruption in those with and without an appendix, warranting further investigation into the potential role of the appendix as a microbial safe house.

Short bowel syndrome (SBS) in adults is defined as having less than 180 to 200 cm of remaining small bowel [1–4]. Many literature sources do not provide precise epidemiological data, challenges in estimating the prevalence of SBS include its multifactorial etiology and varying definitions [1–7]. The most common pathologies leading to SBS include Crohn disease, mesenteric ischemia, radiation enteritis, post-surgical adhesions, and post-operative complications [1,2,4–6]. In advanced SBS, parenteral nutrition may be required to ensure that all vital nutrients are delivered directly through the venous system, bypassing the gastrointestinal tract [1,8–10]. In this article, we present a clinical case of a patient who underwent parenteral nutrition for four months due to SBS. The surgical team performed reconstructive re-anastomosis of both the small and large bowel, leading to the discontinuation of parenteral nutrition and the resumption of a regular diet.

The long-term impact of treatment of dogs with steroid-responsive enteropathy (SRE) on the fe-cal microbiome and metabolome has not been investigated. Therefore, this study aimed to evaluate the fecal microbiome and metabolome of dogs with SRE before, during, and following treatment with standard immunosuppressive therapy and an elimination diet. We retrospec-tively selected samples from 9 dogs with SRE enrolled in a previous clinical trial, which received treatment for 8 weeks, and had achieved remission as indicated by the post-treatment clinical scores. Long-term (1 year) samples were obtained from a subset (5/9) of dogs. Samples from 13 healthy dogs were included as controls (HC). We evaluated the microbiome using 16S rRNA sequencing and qPCR. To evaluate the recovery of gut function, we measured fecal metabolites using an untargeted approach. While improvement was observed for some bacterial taxa after 8 weeks of treatment, several bacterial taxa remained significantly different from HC. Seven-ty-five metabolites were altered in dogs with SRE, including increased fecal amino acids and vitamins, suggesting malabsorption as a component of SRE. One year after treatment, however, all bacterial species evaluated by qPCR and 16S rRNA gene sequencing, and all but thirteen me-tabolites were no longer different from healthy controls.

The gut microbiome is important in the homeostasis of gut health and has pivotal roles in digestion, immune regulation, and metabolic processes. The gut microbiome has been implicated in range of diseases and there is a rapidly growing understanding of this ecosystem’s importance in inflammatory bowel disease. We have yet to identify a single microbe that causes either ulcerative colitis or pouchitis, however, perturbations in the gut microbiome are associated with disease states. Importantly, we can manipulate the gut microbiome using dietary interventions, medications, and faecal microbiota transplantation. This review will summarise our knowledge of gut microbiome therapies in ulcerative colitis and pouchitis.

Our aim was to evaluate efficacy and safety of 30mL CaO alone or plus Asc in bowel preparation before colonoscopy. Two hundred and forty six patients were allocated randomly to ingest 2L PEG with 30mL CaO, 1L PEG with 30mL CaO plus 5g Asc, or 3L PEG. We used Boston Bowel Preparation Scale (BBPS) to evaluate bowel preparation efficacy. We also determined other outcomes such as procedure time, polyp or adenoma detection rate and adverse events (AEs). Of 282 patients recruited, 36 were excluded. Groups were matched for baseline characteristics except weight (P = 0.020) and body mass index (BMI) (P = 0.003). Patient’s satisfaction were higher in 2L PEG-CaO (P = 0.016) and 1L PEG-CaO-Asc groups (P = 0·017). Patients’ compliance was 67.5%, 71.4% and 80.5% in 3L PEG, 2L PEG-CaO and 1L PEG-CaO-Asc groups (P = 0.014). Adequate bowel preparation rate was 75%, 78.57% and 53.66% in 3L PEG, 2L PEG-CaO and 1L PEG-CaO-Asc groups (P = 0.021). There were no differences in terms of remaining outcomes. Despite an increase in patients’ satisfaction and compliance, 1L PEG-CaO-Asc significantly decreased adequate bowel preparation rate. However, 2L PEG-CaO improved the patients' satisfaction and compliance and increased adequate bowel preparation rate.

Symptoms attributed to the gastrointestinal manifestations of multi-system disorders play an important role in the long-term management of these conditions. Gastrointestinal complications of a variety of connective tissue disorders have been studied and there is an increased interest in the incidence and prevalence of these symptoms. Descriptions of the occurrence of gastrointestinal complications in Marfan syndrome have appeared infrequently in the medical literature. In this review article we focus on both structural and functional gastrointestinal pathology that may occur in patients with Marfan syndrome.

Objectives: To study sociodemographic and clinical variables including psychiatric comorbidities in patients with irritable bowel syndrome. Methods: A total of 150 patients were screened to select 100 patients for the study who were attending a medical gastroenterology clinic in a tertiary care centre in north India. Diagnosis of IBS was made using Rome IV criteria and severity of symptoms were assessed by the Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS). Clinical evaluation was done for screening of psychiatric comorbidities and diagnosis was made as per DSM 5. Depression, Anxiety and Stress Scale - 21 Items (DASS-21) and Somatic Symptom Scale–8 (SSS-8) were used to assess depression, anxiety, stress and somatic symptoms. Result: The mean age of cases was 35.6 years and majority were i.e., 38.0% in 18-29 years. Males were 62.0% and females were 38.0%. 61.0% of the cases were diagnosed with Moderate IBS. Evaluation on DASS-21 revealed 53.0% were in moderate category in depression, 43.0% were having moderate anxiety and 36.0% were having moderate stress. 48% cases were in high category in somatic symptom scale. Psychiatric comorbidities were present in 29.0% of cases. Depressive disorders were most common psychiatric comorbidity. Conclusion: Patients with IBS presenting to tertiary care centre in Northern India were mostly young males living in semi-urban area, belonging to hindu region, married and had a nuclear family. Patients with IBS commonly have associated psychiatric disorders; anxiety disorders and depression are most common.

Codium fragile, a green algae, exhibit biological properties. In this study, we examined the effect of Codium fragile extract (CFE) on dextran sulfate sodium (DSS)-induced colitis. As the administration of CFE increased, the proliferation of Akkermansia muciniphila, which is key player in metabolic and gastrointestinal disorders, increased. After CFE administration for 10 weeks, acetic acid was revealed as the major metabolite in mouse cecum and β-glucuronidase activity in mouse feces is decreased. Further, CFE significantly alleviates the acute intestinal injury induced by DSS administration, including DAI scores and colon length. MPO activity in the colon was significantly reduced in the CFE-fed group, which indicated that CFE could inhibit neutrophils infiltration and inflammation in mice. In conclusion, a protective effect of CFE against DSS colitis suggests its clinical use for IBD patients.

Spondyloptosis is a condition where there is complete dislocation of L5 over sacrum. It is a form of spinal dislocation in which one spinal segment is lodged in the anterior or posterior space of another or advanced spondylolisthesis [1]. Treatment is usually spinal fusion depending on the level of lesion [2]. This clinical case is of a 15 year old male with a history of fall from auto-rickshaw followed by a blunt trauma from a heavy iron rod falling over his abdomen. There was no history of loss of consciousness, but the patient had an excruciating pain over back immediately after the incident. Patient is now paraplegic with loss of sensation below L5 along with loss bladder and bowel control since the time of injury. The T1 weighted MRI of spine revealed grade 5 anterior lysthesis of L5 over S1 level with complete spinal cord transaction. The patient was operated to restore the vertebral alignment with pedicle screws and rods. After 3 months, patient is now treated for neuro-musculoskeletal , genitourinary and genitointestinal function with biofeedback, pelvic floor exercises and timed voiding [3]. When a patient has issues with urine retention, Valsalva manoeuvres, Crede's method, suprapubic tapping, and anal stretching are employed to help them void more effortlessly [4].

Probiotics have been widely used in gastroenteritis due to acute and chronic illnesses. However, evidence supporting the effectiveness of probiotics in different health conditions are inconclusive and conflicting. The aim of the study was to review existing literature on the effects of probiotics in gastroenteritis among adults. Only original articles on clinical trials that demonstrated the effects of probiotics in adults with gastroenteritis were used for this analysis. Multiple databases such as PubMed, Google Scholar, MEDLINE and Scopus databases were searched for the data. The study followed standard procedures for data extraction using PRISMA flow chart. A quality appraisal of the selected studies was conducted using CADIMA. Finally, a meta-analysis was conducted. Thirty-five articles met the selection criteria; of them, probiotics were found effective in the treatment and/or prevention of chronic inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease in 17 (49%), and the treatment of pouchitis in 4 (11.4%), antibiotic-induced diarrhea in 3 (8.6%), Helicobacter pylori infection in 2 (5.7%) and diverticulitis in 1 (2.9%), while the remaining 7 (20%) were ineffective and 1 study results were inconclusive. Meta-analysis, on the contrary, didn’t demonstrate any significant protective effects of probiotics. Having a τ² value of zero and I² of 6%, the studies were homogeneous and had minimum variances. Further studies are suggested to evaluate the beneficial effects of probiotics in IBDs and other chronic bowel diseases.

The pathophysiology of irritable bowel syndrome in children involves multiple factors. Thus, treatment options are variable, targeting diet and the child’s and parents’ behav-ior, involving pharmacological and psychological interventions or neuromodulation. Parents are increasingly interested in complementary and alternative therapies for children with irritable bowel syndrome, especially when other treatments have been tried without relieving the child’s symptoms. This paper looks into current evidence for the benefits and side effects of herbal remedies and spices in pediatric patients with IBS. The benefits of peppermint oil, STW5, Psyllium fiber, Curcuma, ginger, and other herbal medicines are discussed based on findings in the current literature.

Inflammatory Bowel Disease (IBD) presents distinct challenges during pregnancy due to its influence on maternal health and pregnancy outcomes. This literature review aims to dissect the existing scientific evidence on pregnancy in women with IBD and provide evidence-based recommendations for clinical management. A comprehensive search was conducted across scientific databases, selecting clinical studies, systematic reviews, and other pertinent resources. Numerous studies have underscored an increased risk of complications during pregnancy for women with IBD, including preterm birth, low birth weight, neonates small for gestational age, and congenital malformations. Nevertheless, it's evident that proactive disease management before and throughout pregnancy can mitigate these risks. Continuation of IBD treatment during pregnancy and breastfeeding is deemed safe with agents like thiopurines, anti-TNF, vedolizumab, or ustekinumab. However, there's a call for caution when combining treatments due to the heightened risk of severe infections in the first year of life. For small molecules, their use is advised against in both scenarios. Effective disease management, minimizing disease activity, and interdisciplinary care are pivotal in attending to women with IBD. The emphasis is placed on the continual assessment of maternal and infant outcomes and an expressed need for further research to enhance the understanding of the ties between IBD and adverse pregnancy outcomes.

Crohn's disease (CD) is a chronic, immune-mediated inflammatory bowel disease characterized by transmural damage of various parts of the gastrointestinal tract. The aim of the study is to present our experience in pre-surgical diagnosis, selection of surgical tactics and volume of intervention in different variants of gastrointestinal tract lesions and disease activity. We undertook cross-sectional, retrospective-prospective study of 64 children who underwent surgery due to complicated CD. We analyzed CD activity via PCDAI, medications used, inflam-mation localization, and changes in mass-growth parameters at pre-surgery stage. Three patients from the group of 44 children with two-stage surgical treatment later showed inefficacy of GEBD in post-operative period. The disease progression was revealed and, therefore, subtotal colectomy was required. Three children had secondary adhesion of surgical wounds by means of active immunosuppressive therapy at preoperative period, and five patients developed suture sinuses at post-operative period. Early adhesive intestinal obstruction was revealed in 3 (4.7%) cases, and they required re-surgery. Personalized approach to the surgical treatment of children with complicated CD has shown its efficacy due to the small percentage of postoperative complications with re-surgery. There was significant improvement in mass-growth parameters, recovery of albumin levels, and anemia decrease in 96.9% of cases in the long-term postoperative period (6 months or more). Two children (3.1%) had the narrowing of anastomotic zone lumen, thus, without any obstruction. These cases were associated with violations in drug treatment

Introduction: Ehlers-Danlos syndromes (EDS) constitute a rare entity of genetic disorders, affecting the collagen of all types all. Herein, we describe a case of vascular type of EDS, with coexisting segmental absence of intestinal musculature, while performing simultaneously a narrative review of the existing literature. Case Presentation: A 23-year-old male patient with a history of multiple abdominal operations due to recurrent bowel perforations and the presence of high-output enterocutaneous fistula was admitted to our surgical department for further evaluation and treatment. After detailed diagnostic testing, the diagnosis of vascular type of EDS (vEDS) was made and a conservative therapeutic approach was adopted. In addition, a comprehensive review of the international literature was carried out by applying the appropriate search terms. Results: The diagnosis of vEDS was molecularly confirmed by means of genetic testing. The patient was treated conservatively, with parenteral nutrition and supportive methods. Thirty-four cases of bowel perforation in vEDS have been reported so far. Interestingly, this case is the second one ever to report with co-existence of vEDS with Segmental Absence of Intestinal Musculature. Conclusions: Establishing the diagnosis of vEDS promptly is of vital significance in order to ensure that patients receive appropriate treatment. Due to initial non-specific clinical presentation, EDS should always be included in the differential diagnoses of young patients with unexplained perforations of the gastrointestinal tract.

Migraine is a primary headache disorder with a prevalence of 11.6% globally and 27% in Saudi Arabia. Irritable bowel syndrome has a prevalence of 9.2% worldwide. The prevalence of IBS has not been established nationally. However, provincial studies for both migraine and IBS have been conducted across the nation. There is a significant link between migraines and IBS globally. This identifies an association that needs to be investigated in a nationwide manner. This study aims to observe the association and the relationship between migraine and irritable bowel syndrome in Saudi Arabia. A cross-sectional study was conducted between March 2021 to June 2021 among the general population of Saudi Arabia, whose ages are 15 years old or greater. The data collection tools included MS-Q for migraine symptoms, MIGSEV scale for severity of migraine, and The IBS module of the Rome IV Diagnostic Questionnaire (R4DQ) for IBS symptoms and its subtype. With a total of 2802 participants, the majority of the study sample were males, who constituted 52.5%. Among the study's sample, the prevalence of migraine consisted of 27.4%, and the prevalence of IBS was 16.4%. The odds of having IBS in migraineurs were much higher than in those without migraines (OR 4.127; 95% CI 3.325-5.121), and the association was statistically significant (P&lt;0.001). In conclusion, there is a strong association between migraine and irritable bowel syndrome in Saudi Arabia.

Ulcerative colitis (UC) is one of the two disorders known as inflammatory bowel diseases (IBD) along with Crohn’s disease (CD), with complex pathogenesis, requiring costly invasive investigations. Objective: to examine the most recent biomarkers proposed for UC diagnosis; to establish the strategy used to make the differential diagnosis between UC and CD relying on these biomarkers, also adding the benefit of finding new non-invasive tools in managing this condition. The search was performed in a single database (Web of Science) using the specific keywords „ulcerative colitis”, „biomarkers” and „diagnosis” for the last five years. Study eligibility criteria: clinical trials on adults and pediatric patients with ulcerative colitis compared with Crohn’s disease. Results: We selected 57 studies, randomized controlled trials (RCTs) and clinical case series (CCS), summarizing the latest most specific biomarkers in diagnosis of UC. Limitations: we considered RCTs and CCS from one database, limited to the search topics. Our findings indicate a important number of potential biomarkers with diagnostic value, which bring the advantage of a non-invasive method to approach this challenging disorder.

Ulcerative colitis has a significant impact on the quality of life for the patients, and can substantially increase the risk of colon cancer in patients suffering long-term. Conventional treatments provide only modest relief paired with a high risk of side effects, while complementary and alternative medicines can offer safe and effective options. Over the past decade, we have shown that American ginseng has anti-oxidant and anti-inflammatory properties that can suppress mouse colitis and prevent colitis associated colon cancer. With the goal of isolating a single active compound, we further fractionated the hexane fraction, and found the most abundant molecule in this fraction was the polyacetylene, Panaxynol. After isolating and characterizing Panaxynol, we tested the efficacy of Panaxynol in the treatment and prevention of colitis in mice and studied the mechanism of action. We demonstrate here that Panaxynol effectively treats colitis in a Dextran Sulfate Sodium mouse model by targeting macrophages for DNA damage and apoptosis. Positive outcomes from this study could take American ginseng one-step further towards becoming a conventional drug for the treatment of colitis, and possibility exploring other autoimmune diseases associated with macrophage dysfunction.

Objective. Acute bowel ischemia is a life-threatening abdominal emergency. In many patients percutaneous endovascular repair of visceral arteries in an antegrade direction, across occluding plaques is challenging and sometimes not possible. Case Report. We present the case of technically successful percutaneous retrograde recanalization of occluded superior mesenteric artery in ctitically-ill 82-year-old patient. The superior mesenteric artery was recanalized via the branches of the celiac trunk; the guidewires were navigated to the target artery through the gastroduodenal and pancreatoduodenal arteries. Conclusion. Retrograde percutaneous recanalization of the superior mesenteric artery is technically feasible, even in hemodynamically unstable patients.

The first 1000 days of life is a critical period that contributes significantly to the programming of an individual's future health. Among the many changes that occur during this period, there is growing evidence that the establishment of a healthy gut microbiota early in life plays an important role in the prevention of both short- and long-term health problems. Numerous publications suggest that the quality of gut microbiota colonization depends on several dietary factors, including breastfeeding. In this respect, a relationship between breastfeeding and the risk of inflammatory bowel disease (IBD) has been suggested. IBD are chronic intestinal diseases in which perinatal factors may be partly responsible for its onset. We propose to review the existence of links between breastfeeding and IBD, based on experimental and clinical studies. Overall, despite encouraging experimental data in rodents, the association between breastfeeding and the development of IBD remains controversial in humans, partly due to considerable heterogeneity between clinical studies. The duration of exclusive breastfeeding is probably decisive for its lasting effect on IBD. Thus, specific improvements in our knowledge could support dietary interventions targeting the gut microbiome, such as the early use of prebiotics, probiotics or postbiotics in order to prevent the disease.

Inflammatory Bowel Disease (IBD) is a chronic and progressive inflammatory disorder affecting the gastrointestinal tract (GT) caused by a wide range of genetic, microbial, and environmental factors. IBD is characterized by chronic inflammation, decreased gut microbial diversity and dysbiosis, with a lower amount of beneficial bacteria and a concomitant increase of pathogenic species. It is well known that dysbiosis is closely related to the induction of inflammation and oxidative stress, this last caused by an imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity that leads to cellular ROS accumulation. ROS are responsible for the intestinal epithelium oxidative damage and the increased intestinal permeability found in IBD patients and their reduction could represent a potential therapeutic strategy to limit the IBD progression and alleviate its symptom. Recent evidence highlighted that dietary polyphenols, natural antioxidants, are able to maintain redox equilibrium in the GT preventing gut dysbiosis, intestinal epithelium damage and radical inflammatory responses. Here, we suggest that the relatively new foodomics approaches, together with new technologies for promoting the antioxidative properties of dietary polyphenols, including novel delivery systems, chemical modifications and combination strategies, may provide critical insight to determine the clinical value of polyphenols for IBD therapy and a comprehensive perspective for implementing natural antioxidants as potential IBD candidate treatment.

Our research aimed to explore how resolving periodontal inflammation impacts cytokine expression in the colon of aged Wistar rats. Animal studies have been used to investigate the two-way relationship between periodontitis and Inflammatory Bowel Disease (IBD), where chronic inflammation in either the mouth or intestines can negatively affect the other. We allocated sixteen male Wistar rats, aged between 8-11 months, into four groups: (1) Ligature-induced periodontitis (LIP) without the resolution of periodontal inflammation (RPI) (LIP; n=4), (2) LIP + RPI (n=4), (3) LIP + DSS-induced colitis (DIC) without RPI (n=4), and LIP+DIC+RPI (n=5). We performed histopathological and immunological analyses on the periodontal and intestinal tissues and analysed cytokine expressions using a Rat Cytokine 23-Plex Immunoassay. Our findings showed that animals with and without DIC who underwent RPI showed significantly lower levels of IL-2, IL-4, IL-5, IL-10, IL-13, IL-17, IL-18, and TNF-α in the intestine compared to those without treatment. The RPI effectively reduced the number of inflammatory cells in the lamina propria and restored the epithelial barrier in the intestine in animals with DIC. The resolution of periodontal inflammation significantly reduced the levels of pro-inflammatory cytokines and chemokines in the intestine of aged rats with and without DSS-induced colitis.

Background: Children with anorectal malformation (ARM) require long-term follow-up, especially for fecal continence and main predictors of longer-term success are the type of ARM, associated anomalies and sacral integrity. Three-Dimensional High Resolution Anorectal Manometry (3D-HRAM) provides an image of the pressure profile of anal sphincter complex. Aim of study was to evaluate the anal sphincter function in ARM patients with 3D HRAM correlating this analysis to clinical outcome and to associated malformations. Methods: Forty ARM patients, were submitted to 3D HRAM: manometric, anatomical and clinical score were correlated to response to bowel management (BM). Results: A positive correlation between all scores and type of ARM was found: in high ARM and in patients with spinal anomalies (regardless to ARM type) lower scores were reported and even after BM they do not achieve good continence. Conclusions: 3D-HRAM provides information on the functional anatomy of the sphincter complex. Our study shows good correlation between the manometric results and clinical outcome, confirming spinal malformations and ARM type as most important prognostic risk factors for poor outcome. Specific sphincteric defects can be explored with manometry, allowing for tailored bowel management strategies.

Mechanical bowel obstruction is a common symptom for admission to emergency services, diagnosed annually in more than 300,000 patients in the States, from whom 51% will undergo emergency laparotomy. This condition is associated with serious morbidity and mortality, but it also causes a high financial burden due to long hospital stay. The EUPEMEN project aims to incorporate the expertise and clinical experience of national clinical specialists into development of perioperative rehabilitation protocols. Providing special recommendations for all aspects of patient perioperative care and the participation of diverse specialists, the EUPEMEN protocol for bowel obstruction, as presented in the current paper, aims to provide faster postoperative recovery and reduce length of hospital stay, postoperative morbidity and mortality rate.

Background: Crohn’s and Ulcerative Colitis Questionnaire-32 (CUCQ-32) is a validated questionnaire to measure the quality of life (QoL) in inflammatory bowel disease (IBD). However, it does not have stoma specific questions and can be lengthy. This study aimed to validate a subset of the CUCQ-32 that would be suitable for patients with a stoma. Methods: Baseline data were collected from a cohort of patients with acute ulcerative colitis who were participating in the CONSTRUCT multi-centre clinical trial. A subset of the CUCQ-32 questions was selected by stepwise regression. Further validation was examined using data from the UK IBD biological therapies audit. Construct validity was carried out using the EuroQol 5 dimensions (EQ5D) questionnaire, Simple Clinical Colitis Activity Index (SCCAI) and the Harvey-Bradshaw Index (HBI). Literature review and an expert focus group identified supplementary questions to cover patients with a stoma. Test-retest analysis was done during the patients’ second follow up visits. Results: Using the data from 124 patients, a short version questionnaire (CUCQ-12) was developed. Further validation using data from 484 patients with IBD as part of the UK IBD biological therapies audit. Using the data from 61 patients with a stoma, we identified 5 stoma specific questions for the CUCQ-12+. The CUCQ-12+ demonstrated excellent internal consistency (Cronbach’s α= 0.86); established effective reproducibility (intra-class correlation coefficient= 0.74); correlated well with the EQ5D (r= - 0.48), HBI (r= 0.45) and SCCAI (r= 0.43); and represented good responsiveness statistics (>0.5). Conclusions: CUCQ-12+ is a valid and reliable QoL measure that can be used for all patients with IBD in clinical practice including patients with a stoma.

Crohn’s disease is an inflammatory bowel disease whose prevalence is increasing worldwide. Among medical strategies, the dietary therapy with exclusive enteral nutrition is recommended as first line option, at least for children, because it induces clinical remission and mucosal healing. Modulen®, a polymeric TGF-β2 enriched formula, has a good palatability and is widely used. For the first time in the literature, this review outlines and discusses the clinical outcomes obtained with this therapy, as well as the potential mechanisms of action of its compounds. It can be explained by its TGF-β2 content but also by its protein and lipid composition. Further well-designed studies are required to improve our knowledge and to optimize therapeutic strategies.

This case study examined changes in body composition, resting metabolic rate (RMR), aerobic capacity, and daily physical activity in a patient who had ulcerative colitis who underwent ileal pouch‒anal anastomosis (IPAA) surgery. Body composition, RMR, and VO2 peak were assessed prior to, 4, 8, and 16 weeks after IPAA surgery. Daily physical activity data was extracted from a wrist-worn activity tracker preoperatively and 16 months postoperatively. At baseline, total body mass was 95.3 kg; body fat, 11.6 %; lean body mass, 81.1 kg; RMR, 2,416 kcal/d; and V̇O2peak, 42.7 mL/kg/min. All values decreased from baseline at 4 weeks postoperatively, body mass was 85.2 kg (-10.5%); body fat, 10.9% (-6.0%); lean body mass, 73.1 kg (-9.9%); RMR 2,210 kcal/d (-8.5%) and V̇O2peak, 25.5 mL/kg/min (-40.3%). At 16 weeks postoperatively, most parameters were near their baseline levels (within 1%-7%); exceptions were V̇O2peak, which was 20.4% below baseline, and RMR, which increased to nearly 20% above baseline. After the patient had an IPAA surgery, his total and lean body masses, RMR, and aerobic capacity were markedly decreased. Daily physical activity decreased postoperatively and likely contributed to the decreased aerobic capacity, which may take longer to recover compared to body composition and RMR parameters.

Chronic non-bacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is a rare autoinflammatory bone disease primarily affecting children and adolescents. This review presents a comprehensive analysis of the intricate relationship between CNO and inflammatory bowel disease (IBD), shedding light on shared pathophysiological mechanisms and clinical management. A thorough literature review was conducted, encompassing 24 case reports involving 40 patients. The demographic distribution of patients revealed a near-equal gender ratio, with a median age of diagnosis at 12 years. The diagnosis patterns showed a higher proportion of CNO as the initial diagnosis, while Crohn's disease was more prevalent than ulcerative colitis. The time interval between the clinical presentations varied, ranging from simultaneous detection to a substantial 15-year gap. Treatment modalities included non-steroidal anti-inflammatory drugs (NSAIDs), steroids, aminosalicylates, and biologic agents, such as infliximab, often overlapping in their use, suggesting shared pathophysiological pathways. Both conditions displayed systemic manifestations, and patients often responded well to immunosuppressive medications. The pathophysiology of CNO involves genetic predisposition, cytokine dysregulation, and osteoclast activation. Dysregulated innate immunity results in immune cell infiltration into bones, causing sterile bone lesions. Notably, emerging evidence hints at a potential link between the microbiome and CNO. In contrast, IBD results from imbalanced mucosal immune responses to the intestinal microbiota. Polymorphisms in the promotor region of IL-10, common cytokines, immune cells, and genetic markers indicate shared immunological and genetic factors between CNO and IBD. Both conditions also involve extraintestinal symptoms. This analysis underscores the need for clinical awareness of the co-occurrence of CNO and IBD, especially among pediatric patients. A deepened understanding of the connections between these seemingly distinct diseases could lead to more effective management and improved patient outcomes.

Immune-mediated bowel diseases (IMBD), including Ulcerative colitis and Crohn's disease, represent a significant global health burden with their complex etiology and increasing prevalence. The connection between intestinal parasites and the gut microbiome in immune-mediated bowel disease is a complex and evolving field of research. Several studies have demonstrated that intestinal parasites can modulate the composition and function of the gut microbiome. Parasitic infections can result in alterations in the gut microbial community, including changes in microbial diversity, abundance, and metabolic activity. These changes can influence the immune response and contribute to the development of IMBDs. In contrast, the gut microbiome serves a pivotal function in maintaining intestinal homeostasis and immune regulation. Dysbiosis, characterized by changes in the gut microbial composition, has been associated with the pathogenesis of IMBDs. Imbalances in the gut microbiota can result in increased gut permeability, chronic inflammation, and aberrant immune responses, all of which are hallmarks of IMBDs. The bidirectional interaction between intestinal parasites and the gut microbiome further complicates the understanding of immune-mediated bowel diseases. Certain parasites, such as hookworms and Necator americanus, have been found to downregulate immune responses and may have therapeutic potential in treating celiac disease. On the other hand, infections with parasites like Strongyloides stercoralis and Blastocystis have been shown to mimic the symptoms of IBD, highlighting the intricate relationship between parasites and the pathogenesis of these diseases. Additional investigation is required to comprehensively elucidate the mechanisms that underlie the association between intestinal parasites and the gut microbiome in immune-mediated bowel disease. This knowledge could potentially lead to the development of targeted therapeutic strategies that aim to restore gut microbiota homeostasis and alleviate the symptoms of these debilitating conditions. By understanding and harnessing the complex interplay between parasites, the gut microbiome, and the host immune system, researchers may uncover novel approaches for the management and treatment of immune-mediated bowel diseases.

The irritable bowel syndrome (IBS) is functional gastrointestinal tract disease, include abnormal defecation and abdominal pain. The Rome IV criteria define fecal incontinence as "recurrent and uncontrolled stool leakage that lasts more than 3 months." Fecal incontinence is common in patients with IBS and can have a significant negative impact on daily life and reduce the patient's quality of life. Diet and lifestyle guidance are needed to prevent fecal incontinence. Fecal incontinence can be reduced by ingesting dietary fiber, which can improve stool properties, and avoiding foods with stool-softening properties. Additionally, defecation habit guidance is important for preventing fecal incontinence. If rectal sensation is normal, it is recommended to go to the bathroom as soon as there is a desire to defecate. In elderly people, if there is stool in the rectum due to decreased rectal sensation and it continues to accumulate in the rectum without triggering the urge to defecate, overflowing leaky fecal incontinence may occur. For such patients, defecation habit training teaching them to defecate even if they do not have the desire to defecate may be effective. Education and advice on defecation reduces fecal incontinence and is beneficial to caregivers.

Inflammatory bowel disease (IBD) is a chronic disease mediated by the immune system and characterized by the inflammation of the gastrointestinal tract. This study is to understand how the use of parenteral nutrition (PN) can affect the adult population diagnosed with IBD. We conducted a systematic review, meta-analysis and a meta-regression. On the different databases, (MEDLINE, Scopus, Cochrane, LILACS, CINAHL, WOS) we found 119 registers, the accuracy was 16% (19 registers); After a Full-text review, only 15 research studies were selected for qualitative synthesis and 10 for Meta-analysis and Meta-regression. The variables used were Crohn’s Disease Activity Index (CDAI), albumin, body weight (BW) and post-operative complications (COM). PN has shown to have efficacy for the treatment of IBD and is compatible with other medicines. The CDAI and albumin improve although the effect of PN are greater after a while. However, the effect on the albumin could be less than the observed value in the meta-analysis, due to a possible publication bias. The BW does not change after intervention. COM utilizing PN has been observed, although the proportion is low.

Inflammatory bowel disease (IBD) is a chronic disease mediated by the immune system and characterized by the inflammation of the gastrointestinal tract. One of the possible treatments for this pathology is a change in the type of diet, the enteral nutrition (EN) is one of them. This study is to understand how the use of EN can affect the adult population diagnosed with IBD. We conducted a systematic review, meta-analysis and a meta-regression. On the different databases, (MEDLINE, Scopus, Cochrane, LILACS, Cinhal, WOS) we found 363 registers, the accuracy was 12% (44 registers); After a Full-text review, only 30 research studies were selected for qualitative synthesis and 11 for Meta-analysis and Meta-regression. The variables used were Crohn’s Disease Activity Index (CDAI), C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR). EN has shown to have efficacy for the treatment of Crohn’s Disease and is compatible with other medicines. As for the CDAI or the rates of remission, there were no differences between enteral and parenteral nutrition. Polymeric formulas, have shown better results with respect to the CRP. The long-term treatment could dilute the good CDAI results that are obtained at the start of the EN treatment.

Inflammatory Bowel Disease (IBD) is characterized by chronic remitting and relapsing inflammation of the lower gastrointestinal tract. The etiology underlying IBD remains unknown but is thought to involve a hypersensitive immune response to environmental antigen, including the microbiota. Diagnosis and monitoring of disease is heavily reliant on endoscopy, which is invasive and does not provide information regarding specific mediators. This review describes recent developments in imaging of IBD with a focus on PET and SPECT imaging of inflammatory mediators, and how this may be applied to the microbiota.

The acute phase protein Serum Amyloid A (SAA) is synthesised by the liver in response to inflammatory stimuli. Previous studies have revealed that SAA may be a better predictive marker for the course of inflammatory bowel disease (IBD) compared to C-reactive protein (CRP). Hence, this retrospective monocentric study evaluated whether SAA correlates with biomarkers like faecal calprotectin (FC), CRP, the Neutrophil to Lymphocyte ratio (NLR) and clinical disease activity of IBD patients. Serum samples from the IBD outpatient clinic of the University Hospital Heidelberg were analysed for their SAA concentrations if a FC concentration measurement was available from 14 days before or after collection of the serum sample. 306 serum samples from 265 patients (166 with Crohn’s disease, 91 with ulcerative colitis, 8 with IBD unclassified) met the inclusion criteria. There was a significant positive correlation between SAA and FC, CRP, the NLR and the Simple Clinical Colitis Activity Index. The cut-off for SAA serum concentration at 4.55 mg/l achieved a sensitivity of 57.5% and a specificity of 69.7% for the detection of active inflammation in IBD. SAA may be used as an additional biomarker in the disease monitoring strategy of IBD patients, especially in patients with low CRP concentrations.

The management of blunt abdominopelvic trauma with combined hemoperitoneum and pelvic fractures is challenging for trauma surgeons. Although angioembolization can achieve hemostasis in most visceral organ injuries and pelvic fractures after blunt abdominal trauma, it cannot effectively control hemorrhage in patients with blunt bowel mesenteric injury (BBMI). This study aimed to determine the risk factors associated with hemodynamically unstable patients with BBMI and to test the hypothesis that pelvic fracture is an independent risk factor for patients with unstable BBMI and concomitant pelvic fracture to guide the therapeutic sequence for difficult-to-manage patients. This retrospective study reviewed the data of hospitalized patients with trauma between 2009 and 2021 and included 158 adult patients with surgically proven BBMI. The patients were divided on the basis of the presence of a shock episode before emergency laparotomy. The shock group included 44.3% of all patients in the study (n = 70). Clinical injury severity and prognosis for patients in the shock group were poorer than those for patients in the non-shock group, and more invasive treatments and transfusions were performed for patients in the shock group than for those in the non-shock group. Pelvic fractures were more frequently associated in the shock group than in the non-shock group (21.4% vs. 5.7%; p = 0.003). In multivariate analysis, the presence of intracerebral hemorrhage (odds ratio [OR] = 10.87, 95% confidence intervals [CIs]: 1.70–69.75) and rib fracture (OR = 5.94, 95% CIs = 1.06–33.45) were identified as independent predictors of shock, whereas the effect of pelvic fracture did not achieve statistical significance (OR = 2.94, 95% CIs = 0.66–13.13) after adjusting for confounding factors. For patients with BBMI, outcomes need to be improved during early diagnosis and treatments should be expeditiously performed on the basis of the rapid identification of unstable hemodynamic status. In unstable patients with concomitant pelvic fractures, we support the current management algorithm that recommends performing laparotomy first.

Background: Phylogroup B2 Escherichia coli have been associated with Ulcerative Colitis (UC). In this study, we aimed to compare colonization with the UC-associated E. coli p19A in different mice strains, to investigate the role of alpha hemolysin in a UC mouse model. Methods: In this study, Sigirr -/- and C57BL/6 mice were chosen, and UC was induced by adding Dextran Sulfate Sodium (DSS) to the drinking water. The mice were pre-treated with ciprofloxacin. p19A expressing luminescence and GFP, alpha-hemolysin knock out p19A-∆hlyI II, and non-pathogenic lab E. coli DH10B were cultured in LB broth, and orally gavaged into the mice. Colonization with p19A WT was visualized using an in-vivo imaging system. Results: p19A WT colonized the colon, ileum, Peyer’s patches, liver, and spleen of infected C57BL/6 and Sigirr -/- mice. A total of 99% of the p19A WT infected C57BL/6 mice and 29% of the p19A WT infected Sigirr -/- mice survived to the 4th post infection day. Conclusion: UC-associated E. coli p19A WT colonized the intestines of DSS-treated mice and caused extra-intestinal infection. Hemolysin is an important factor in this pathogenesis, since isogenic hemolysin mutants did not cause the same inflammation.

Inflammatory bowel disease (IBD) is a CC chemokine receptor 6 (CCR6) - associated immune mediated disorder which has attracted an extensive superfluity of experimental analyses. IBD has come to the fore of varied scrutinizing owing to its complexity by nature for comprising of two synergistic sub phenotypes; Crohn’s disease (CD) and Ulcerative colitis (UC). Both these disease entities cause potent immune dysregulation followed by intense tissue damage within the gut mucosal system, initiating symptoms which are severely debilitating. Multiple causative factors are said to be responsible for IBD but direct immune dysfunction is kindled by overplay of innate and adaptive immune responses produced against a pathogenic microbial attack through the weakened or leaky gut epithelial barrier. Once immune homeostasis is not achieved by tolerating agents, the self-assertive adaptive immunity mobilize its various T and B cell cohorts initializing their allied immune mechanisms by vigorously deploying them towards the site of infection. CCR6 and its unique solitary ligand CC-chemokine ligand 20 (CCL20) are small protein molecules which are abundantly expressed by T and B lymphocytes and act as chemotactic immune-modulatory envoys that help in the deployment of the effector lymphocyte arm of the immune system, producing two directly opposing outcomes in IBD. This dichotomous immunity consists of either immune tolerance or inflammation which then develops into a chronic state, remaining catatonic to inherent immunity or targeted clinical therapy. In this review, we have chronologically identified a plethora of experimental studies radiating into 14 different compartments highlighted in the visual depiction which have employed both mouse models and clinical subjects spanning a period of nearly two decades. In doing so, we expect the research community would further benefit by tracing through the history, thereby understanding the CCR6 –CCL20 axis in IBD and identifying the gaps in literature which can be fortuitously filled in the future.

The brain reciprocally communicates with the rest of the body via neural, endocrine, immune, and other systems. This is crucial for coordinating the complex behavioral and physiological responses needed to cope with the many challenges of life. The Anterior Cingulate Cortex (ACC) is a key brain structure involved in assessing rewards and threats, as well as activating appropriate responses. This is a dynamic process that depends on evolving needs and challenges. Important challenges include illness or injury. These typically involve inflammation and pain, which evoke neuroinflammatory processes in the brain to drive sickness behaviours. In the short term, sickness behaviours are considered adaptive, as they promote convalescence (e.g. low mood; lethargy, fatigue, social withdrawal), and enhanced threat appraisal (e.g. anxiety) to combat increased risk/vulnerability associated with sickness. Chronic inflammation, however, appears to remodel the system to inappropriately activate threat-coping responses, resulting in depressive and/or anxious phenotypes. These mood disorders are particularly pronounced in diseases and disorders associated with gut dysfunction, which feature chronic inflammation and altered ACC function. We propose that chronic inflammation remodels ACC physiology such that it errantly predicts heightened danger based on a mental model (a.k.a ‘schema’) of the world. This evokes chronic activation of threat-coping systems, including endocrine signaling (e.g. adrenaline), and anxiety. Inflammation can be driven by brain systems involving ACC, leading to a feedback-cycle that self-reinforces pathological states. This theory accounts for a wealth of clinical and preclinical data that implicate the ACC in disorders of mood and gastrointestinal function, and reveals a key player in the gut-brain axis that may represent a novel therapeutic target.

Berberis vulgaris L. (Berberidaceae) is a shrub that has been widely used in European folk medicine as an anti-inflammatory and antimicrobial agent. The purpose of our study was to elucidate the mechanisms of antiproliferative action of the plant’s methanolic root extract (BVR) against colon cancer cells. Cytotoxicity and pro-apoptotic activity were determined in human colon adenocarcinoma cell lines (LS180 and HT-29) and control colon epithelial CCD841 CoN cells. According to the MTT assay, after 48 h of cell exposure, the IC50 values were as follows: 4.3; 46.1 and 50.2 µg/mL for LS180, HT-29, and CCD841 CoN cells, respectively, showing the greater sensitivity of cancer cells to BVR. The Cell Death Detection ELISAPLUS kit demonstrated that BVR induced programmed cell death only against HT-29 cells. RT-qPCR with relative quantification method showed significant changes in the expression of genes related to apoptosis in both colon cancer cell lines. The genes BCL2L1 (126.84-366.66%), BCL2L2 (277.08-330.12%), CASP3 (180.36-261.36%) and CASP9 (158.08-213.46%) had significantly elevated expression, while BCL2 (23.08-52.06%) had reduced expression. Furthermore, in a panel of antioxidant tests, BVR showed positive effects (63.93±0.01, 122.92±0.01, and 220.29±0.02 mg Trolox equivalents (TE)/g in the DPPH•, ABTS•+ and ORAC assays, respectively). In the lipoxygenase (LOX) inhibition test, BVR revealed 62,60±0.87% of enzyme inhibition. The chemical composition of BVR was determined using UHPLC-UV-CAD-MS/MS analysis and confirmed the presence of several known alkaloids, including berberine, as well as other alkaloids and two derivatives of hydroxycinnamic acid (ferulic and sinapic acid hexosides). This is the first such extensive assessment of the biological activity of BVR. The results are very promising and encourage for the use of BVR as a comprehensive chemopreventive agent (anti-inflammatory, antioxidant, and pro-apoptotic) in colorectal cancer.

Evidence regarding the role of oral antibiotics (oA) alone or combined with mechanical bowel preparation (MoABP) for elective colorectal surgery remains controversial. A prospective database of 8,359 colorectal resections gathered over a 32-month period in 78 Italian surgical units (the iCral 2 and 3 studies), reporting patient-, disease-, and procedure-related variables together with 60-day adverse events, was re-analyzed to identify a subgroup of 1,013 cases (12.1%) that received either oA or MoABP. This dataset was analyzed using a 1:1 propensity score-matching model including 20 covariates. Two well-balanced groups of 243 patients each were obtained: group A (oA), and group B (MoABP). The primary endpoints were anastomotic leakage (AL) and surgical site infections (SSIs) rates. Group A vs. group B showed a significantly higher AL risk [14 (5.8%) vs 6 (2.5%) events; OR 3.77; 95%CI 1.22-11.67; p = .021], while no significant difference was recorded between the two groups regarding SSIs. These results strongly support the use of MoABP for elective colorectal resections.

Introduction: The serological support to early diagnosis and differential diagnosis of inflammatory bowel diseases (IBD) is actually very limited. In this study we evaluated the performance of a promising multiparametric method including either well established and newly developed biomarkers. Methods: This multicenter retrospective observational study finally enrolled 156 patients with IBD, 100 affected by Crohn’s disease (CD) and 56 by ulcerative colitis (UC) recruited at the Gastroenterology Units of Udine (Italy), Rijeka (Croatia) and Belgrade (Serbia). Twently age-sex matched blood donors (BD) were included as controls. Autoantibody profiles were determined using a mosaic cell and tissue-based indirect immunofluorescence (IIF) method simultaneously investigating: anti-saccharomyces cerevisiae antibodies (ASCA), anti-atypical perinuclear neutrophilic antibodies (P-ANCA), anti-pancreatic antigens antibodies (PAB) and anti-goblet cells antibodies (GAB). Results: PAB (anti-CUZD1 and/or anti-GP2 antibodies) were present in 24 CD patients versus none of UC patients or BD (24% sensitivity, 100% specificity). As regards CD patients, combined positivity of PAB and ASCA (sensitivity 84%, specificity 71.4%) performed better than ASCA alone. Colon involvement (87.5% vs. 60.5%; p=0.014), deep mucosal lesions (58.3% vs. 25.0%; p=0.002) and need for biologic therapies (79.2% vs. 46.1%; p=0.005) were significantly more prevalent in PAB-positive than in PAB-negative CD patients. Multivariate analysis identified PAB positivity (OR=3.67; 95%CI=1.29-10.46) and anti-CUZD1 in particular (OR=3.54; 95%CI=1.08-11.63) as significant risk factors for deep mucosal lesions development in CD. Conclusion: A multiparametric diagnostic approach appears very useful to better characterize IBD patients. PAB, isolated or combined with other autoantibodies, may support both differential diagnosis and selection of CD patients at risk for more severe disease.

Inflammatory bowel disease (IBD) comprises systemic inflammatory conditions primarily affecting the gastrointestinal tract, including Crohn's disease and ulcerative colitis. This research aims to analyze the clinical symptoms and pathogenesis of Dextran sodium sulfate (DSS)-induced canine IBD model, and evaluate the restorative effect of ginsenoside from a pathogenesis perspective. We established the DSS-induced canine IBD model and studied the pathological mechanisms. Additionally, we examined the therapeutic effect of ginsenosides by assessing the Canine Inflammatory Bowel Disease Activity Index (CIBDAI), C-reactive protein (CRP) levels, colonic tissue morphology, protein expression, and mucosal bacterial community analysis. Our findings revealed a total ginsenoside content of 22.7% in the ginsenoside extract. Animal experiments demonstrated that dogs with IBD exhibited decreased mental state, significantly increased CIBDAI and CRP levels, disrupted colonic epithelial tissue structure, decreased expression of mucin, tight junctions, and adherens junctions, as well as reduced diversity of the colonic mucosal bacterial community. Furthermore, correlation analysis highlighted a total of 38 bacterial strains correlated with physiological indices. Significantly, ginsenoside treatment could improve these symptoms and reverse the relative abundance of some bacterial communities. In conclusion, Alterations in the properties of the colonic mucus layer or the reduction of MUC2, its core component, in dogs with IBD can lead to bacterial penetration of the mucus layer and subsequent contact with intestinal epithelial cells, resulting in inflammation. Remarkably, ginsenoside intervention showcased the capacity to positively influence the relative abundance of bacteria and impact the colonic mucus layer properties, thereby offering promising prospects for IBD management and recovery.

Abstract: Background: The vaccination status of patients with inflammatory bowel disease (IBD) should be investigated before starting any treatment, and patients eventually vaccinated against vaccine preventable diseases (VPDs). Vaccination rates in patients with IBD are known to be suboptimal. The aim of this study was to investigate the vaccination coverage, attitude towards vaccinations and its possible determinants among a national cohort of IBD patients. Methods: An anonymous web-based questionnaire was sent by the Italian IBD patients’ association (AMICI) in February 2021. Previous vaccination status and patients’ attitude towards vaccinations were rec-orded. The factors influencing their attitudes were examined using crude and adjusted odds ratios (AdjORs) with 95% confidence intervals (CIs). Results: Among 4039 patients invited, 1252 patients (including 729 women, median age 47.7 [37–58]) completed the questionnaire, a response rate of 25.3%. Patients declared being vaccinated against: 74.1% tetanus, 67.7% flu (last season), 43.3% MMR, 37.1% HBV, 29.1% pneumococcus, 20% meningitis, 16% HAV, 15.3% VZV, 7.6% HPV. Two hundred and fifty-nine (20.7%) did not remember every previous vaccination. One thousand one hundred and twelve (88.8%) expressed a positive attitude towards vaccination, 91 (7.3%) were indifferent, 49 (3.9%) reported being opposed to vaccinations. The belief of possible return of VPDs with decline of vaccination coverage rates was the factor most strongly related to a positive at-titude towards vaccinations (AdjOR 5.67, 95% CI 3.45-9.30, p-value <0.001). Conclusions: A low vaccination rate against some VPDs was found among a national cohort of patients with IBD, despite a generally positive attitude towards vaccinations.

Several observational studies have indicated the potential associations between calcium, vitamin D(Vit-D) and irritable bowel syndrome (IBS). However, the causal relationship deduced from these studies is subjected to residual confounding factors and reverse causation. Therefore, we aim to explore the bidirectional causal effects between serum calcium, Vit-D, PTH and IBS at the genetic level by a two-sample Mendelian randomization (MR) analysis. Sensitivity analyses were performed to evaluate the robustness. The estimates were presented as odds ratio (OR) with their 95% confidence intervals (CIs). The results of the inverse-variance-weighted method did not re-veal any causal relationship shared between genetically predisposed calcium (OR = 0.92, 95% CI: 0.80-1.06, P = 0.25) and Vit-D (OR = 0.99, 95% CI: 0.83-1.19, P = 0.94) level and the risk of IBS. The bidirectional analysis demonstrated that genetic predisposition to IBS was associated with a de-creased level of PTH (beta: -0.19, 95%CI: -0.34 to -0.04, P = 0.01). In conclusion, the present study indicates no causal relationship between the serum calcium and Vit-D concentrations and the risk of IBS. The potential mechanisms by which IBS affects serum PTH need to be further investigated.

Ulcerative colitis (UC) is a common chronic disease of the large intestine. Current anti-inflammatory drugs prescribed to treat this disease have limited utility due to significant side-effects. Thus, immunotherapies for UC treatment are still sought. In the DSS mouse model of UC, we recently demonstrated that systemic administration of the Bin1 monoclonal antibody 99D (Bin1 mAb) developed in our laboratory was sufficient to reinforce intestinal barrier function and preserve an intact colonic mucosa, compared to control subjects which displayed severe mucosal lesions, high-level neutrophil and lymphocyte infiltration of mucosal and submucosal areas, and loss of crypts. Here we report effects of Bin1 mAb on colonic neurons and the gut microbiome that correlate with the benefits of treatment. In the DSS model, we found that induction of UC was associated with disintegration of enteric neurons and elevated levels of glial cells, which translocated to the muscularis at distinct sites. Further, we characterized an altered gut microbiome in DSS treated mice associated with pathogenic proinflammatory characters. Both of these features of UC induction were normalized by Bin1 mAb treatment. With regard to microbiome changes, we observed in particular that Firmicutes were eliminated by UC induction and that Bin1 mAb treatment restored this phylum including the genus Lactobacillus and Akkermansia as beneficial microorganisms. Overall, our findings suggest that the intestinal barrier function restored by Bin1 immunotherapy in the DSS model of UC is associated with a preservation of enteric neurons and an improvement in the gut microbiome, contributing overall to a healthy intestinal tract.

Inflammatory bowel diseases, comprising Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing and remitting immune-mediated inflammatory diseases affecting the gastrointestinal tract. Ustekinumab (UST) is a monoclonal antibody blocking the p40 subunit of the anti-interleukin (IL) 12/23. Pivotal trials (CERTIFI and UNITI-IM for CD, UNIFI for UC) established the efficacy of UST for the induction and maintenance of remission in both CD and UC, with the most favorable results in naïve patients to biologics. In recent years, a wealth of ‘real-world’ data has emerged supporting positive clinical, endoscopic, and histological outcomes in patients treated with UST, as well as reassuring safety data. More recently, the results of the first head-to-head trials of UST and tumor necrosis factor (TNF) antagonists have been reported. Moreover, a number of studies exploring the role of UST in specific clinical settings, such as perianal CD, postoperative complications and recurrence, extraintestinal manifestations, chronic antibiotic-refractory pouchitis, and pregnancy, have been reported. This review explores results reported to date on UST, including those from pivotal trials, real-world data, and emerging studies regarding therapeutic drug monitoring and immunogenicity. The safety profile of UST was also reviewed.

Objective: Mechanical bowel preparation is essential for the visualisation of the colon during colonoscopy, and previous studies have identified changes in gut microbiota composition after bowel preparation and colonoscopy. Considering the gut microbiota is increasingly implicated in mood, we aimed to explore the potential impact of this intervention on mood and the microbiota-gut-brain axis. Methods: We conducted a pre-post intervention study, with timepoints of one week before and one month after bowel preparation and colonoscopy, in community-dwelling adults referred for colonoscopy. Our primary outcome was change in average Hospital Anxiety and Depression Scale depression sub-scores using generalised estimating equations. We also examined changes in average anxiety, stress, and quality of life scores, and faecal microbiota composition and potential function using 16S rRNA sequencing. We further explored associations between changes in depressive symptoms and the gut microbiota and conducted post-hoc analyses to explore potential effect modifiers. Key Results: 59 participants were included in the analyses. Depressive symptoms decreased one-month post-procedure compared to baseline (adjusted β=−0.64; 95%CI: −1.18, −0.11). Irritable bowel syndrome (IBS) appeared to moderate this relationship (1.78; 0.292, 3.26); depressive symptoms increased in those with, and decreased in those without, IBS. Changes in gut microbiome composition included reduced alpha diversity, modest effects on beta-diversity, and increases in genera associated with potential health benefits, one-month post-procedure compared to baseline. Increases in the CLR-transformed abundance of Ruminococcaceae UCG-009 were associated with improvements in depressive symptoms. Conclusions: There is preliminary evidence of a potential mental health effect of bowel preparation and colonoscopy, which may be associated with changes to the gut microbiota. There may also be a differential mental health impact of this procedure for those with and without IBS. Considering the limitations of our study, further research is required to confirm these findings and their clinical relevance.

Aim: To analyze a single center's experience with Short Bowel Syndrome/ Chronic Intestinal Failure (SBS/CIF) in adult patients treated with Home Parenteral Nutrition (HPN). Materials and methods: In the last thirty years, 13 patients with SBS/CIF were included in an HPN program. Results: Between 1992 and 2023, 13 patients were included in an HPN program. The primary underlying pathology was acute mesenteric ischemia. The median age of the starting HPN was 44 years old. Most are submitted to several surgeries of extensive intestinal resection with posterior intestinal reconstruction. Five of the 13 patients have died while on HPN for a median of 42 months. The causes of death HPN-related were catheter sepsis, endocarditis with cardiac failure, or hepatic failure. One patient died due to underlying pathology: pelvic abscesses and bleeding related to radiotherapy. Eight patients remain alive with a median time of HPN of 173 months. During the HPN support, the most frequent complications were venous catheter infection and venous territory thrombosis. None of the eight patients alive have hepatic failure. Two patients recently started teduglutide, with good tolerance, and need reduction of HPN support. All these eight patients have a satisfactory quality of life (parenteral support needs range between five to two nutrition bags per week). Conclusion: HPN remains the gold standard of SBS/CIF treatment, although Teduglutide may reduce HPN needs and HPN complications and provide a better quality of life. An HPN multidisciplinary healthcare group support is essential to ensure these patients' survival and quality of life. Keywords Short bowel Syndrome, Chronic Intestinal failure, Home Parenteral Nutrition, Teduglutide, Complications of Parenteral Support.

Intestinal commensal microbes, called the gut microbiota, play a critical role in host immune homeostasis through active microbial metabolites and innate and adaptive immune responses. Dysbiosis or imbalance of the gut microbiota composition is associated with inflammatory bowel disease (IBD) which includes Crohn’s disease and ulcerative colitis. The incidence and prevalence rates of IBD have been increasing worldwide. It is well recognized that butyrate, a microbial metabolite of diet fibers, is a major energy source for colonocytes and plays a crucial role in regulating immune function and maintaining epithelial barrier function and intestinal homeostasis. Emerging evidence suggests that butyrate might be a potential therapeutic agent to treat IBD. In this review, we discuss about gut microbial metabolites, particularly butyrate, the synthesis and metabolism of butyrate, mechanisms of butyrate in immune and epithelial barrier function. Furthermore, we review the current research on various therapeutic implications of butyrate in IBD.

Iron deficiency (ID) is by far the most common nutritional disorder in developing and developed countries. When left untreated, ID leads to anemia. Although the usual recommended treatment for iron deficiency anemia (IDA) is oral iron therapy with countless products, such therapy necessitates administration for &gt;3-6 months with questionable patient compliance since most oral iron products have an unpleasant metallic aftertaste and cause intestinal side effects. In addition, in certain gastrointestinal conditions, such as inflammatory bowel diseases or untreated gluten-sensitive enteropathy, oral iron therapy is contraindicated or unsuccessful. Intravenous iron is considered safe in adults, where adverse events are mild and easily managed. The experience with parenteral iron in children is much more limited and many pediatricians appear reluctant to use it because of uncorroborated fears of serious anaphylactic reactions. In the current article, we thoroughly review the available pediatric literature on the use of all commercially available parenteral iron products except ferumoxytol, which was recently removed from the market. We conclude that parenteral iron appears to be safe in children, it works faster than oral iron and the newer third-generation products allow replacement of the total iron deficit at a single setting.

Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to exert major effects on the immune system, both in vivo and in vitro. This interaction is clearly linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on carefully studied animal models. Microbial-immune system crosstalk has been linked to short chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multi-organ inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.

As an uncommon cause of spinal cord infarction, anterior spinal cord syndrome can manifest with motor paralysis, loss of pain, and temperature sensation distal to the site of the lesion. The main pathogenesis of this syndrome is the disruption of blood flow in the anterior spinal artery. Mortality and morbidity differ with the etiology of the syndrome. So knowing the etiology of blood flow disruption is essential for patient management. This review article highlights the important clinical manifestation of Anterior spinal artery syndrome. Also describes etiology, pathogenesis, diagnosis, prognosis, possible management, and complications.

After an incubation period of weeks to months up to 14% of cats infected with feline coronavirus (FCoV) develop feline infectious peritonitis (FIP): a potentially lethal pyogranulomatous perivasculitis. The aim of this study was to find out if stopping FCoV faecal shedding with antivirals prevents FIP. Guardians of cats from which FCoV had been eliminated at least 6 months earlier were contacted to find out the outcome of their cats: 27 households were identified containing 147 cats; 13 cats were treated for FIP and 109 others shed FCoV. A 4-7 day course of oral GS-441524 antiviral stopped faecal virus shedding. Follow-up was from 6 months to 3.5 years: 11 of 147 cats died, but none developed FIP. No FIP-recovered cat relapsed. Cats from 8 households recovered from chronic FCoV enteropathy. A previous field study of 820 FCoV-exposed cats was used as a retrospective control group: 37 of 820 cats developed FIP: the difference was statistically significant (p = 0.0038). Conclusions: early treatment of FCoV-infected cats with oral antivirals prevented FIP. Nevertheless, should FCoV be re-introduced into a household then FIP can result. Further work is required to establish the role of FCoV in cats with inflammatory bowel disease.

Work from the last years indicate that the extracellular matrix (ECM) plays a direct role in vari-ous cellular processes including proliferation, migration and differentiation. Besides homeostat-ic processes, its regulatory function in inflammation becomes more and more evident. In in-flammation like inflammatory bowel disease, the ECM composition is constantly remodeled which can result in a structuring of fistulizing disease course. Thus, tracking early ECM changes might bear the potential to predict the disease course. In this review, we will provide an over-view of relevant diagnostic methods focusing on ECM changes.

The enteric nervous system is affected by inflammatory bowel diseases (IBD). Gut microbiota ferment dietary fibers and produce short-chain fatty acids, such as Butyrate, which bind to G protein-coupled receptors, such as GPR41, and contribute to maintaining intestinal health. This work aimed to study the GPR41 in myenteric neurons and analyze the effect of Butyrate in mice submitted to experimental ulcerative colitis. The 2, 4, 6 trinitrobenzene sulfonic acid (TNBS) was injected intrarectally in C57BL/6 mice (Colitis). Sham group received ethanol (vehicle). One group was treated with 100mg/kg of Sodium Butyrate (Butyrate), and the other groups received saline. Animals were euthanized 7 days after colitis induction. Analyzes demonstrated colocalization of GPR41 with neurons immunoreactive (-ir) to nNOS and ChAT-ir, and absence of colocalization of the GPR41 with GFAP-ir glia. Quantitative results demonstrated losses of nNOS-ir, ChAT-ir, and GPR41-ir neurons in Colitis group, and Butyrate treatment attenuated neuronal loss. The number of GFAP-ir glia increased in Colitis group, whereas Butyrate reduced the number of these cells. In addition, morphological alterations observed in Colitis group were attenuated in Butyrate group. The presence of GPR41 in myenteric neurons was identified and the treatment with Butyrate attenuated the damage caused by experimental ulcerative colitis.

Endoplasmic reticulum (ER) stress triggers a series of signaling and transcriptional events termed the unfolded protein response (UPR). Severe ER stress is associated with the development of fibrosis in different organs including lung, liver, kidney, heart, and intestine. ER stress is an essential response of epithelial and immune cells in the pathogenesis of inflammatory bowel disease (IBD) including Crohn’s disease. Intestinal epithelial cells are susceptible to ER stress-mediated damage due to secretion of a large amount of proteins that are involved in mucosal defense. In other cells, ER stress is linked to myofibroblast activation, extracellular matrix production, macrophage polarization, and immune cell differentiation. This review focuses on the role of UPR in the pathogenesis in IBD from an immunologic perspective. The roles of macrophage and mesenchymal cells in the UPR from in vitro and in vivo animal models are discussed. The links between ER stress and other signaling pathways such as senescence and autophagy are introduced. Recent advances in the understanding of the epigenetic regulation of UPR signaling are also updated here. The future directions of development of the UPR research and therapeutic strategies to manipulate ER stress levels are also reviewed.

Inflammatory bowel disease (IBD), including Crohn’s Disease (CD) and Ulcerative Colitis (UC) are chronic multifactorial disorders which affect the gastrointestinal tract with variable extent. Despite extensive research, their etiology and exact pathogenesis are still unknown. Cell-free DNAs (cfDNAs) are defined as any DNA fragments which are free from origin cell and able to circulate into bloodstream with or without microvescicles. CfDNAs are now being increasingly studied in different human diseases, like cancer or inflammatory diseases. However, to date it is unclear how IBD etiology is linked to cfDNAs in plasma. Extrachromosomal circular DNA (eccDNA) are non-plasmidic, nuclear, circular and closed DNA molecules found in all eukaryotes tested. CfDNAs appear to play an important role in autoimmune diseases, inflammatory processes, and cancer; recently, interest has also grown in IBD, and their role in the pathogenesis of IBD has been suggested. We now suggest that eccDNAs also plays a role in IBD. In this review we have comprehensively collected available knowledge in literature regarding cfDNA, eccDNA, and structures involving them such as neutrophil extracellular traps and exosomes, and their role in IBD. Finally, we focused on old and novel potential molecular therapies and drug delivery systems, such as nanoparticles, for IBD treatment.

Functional gastro-intestinal disorders (FGID) including irritable bowel syndrome (IBS) are frequently handled by self-management with over the counter (OTC) products such as hyoscine butylbromide (HBB), alone or in combination with paracetamol, and natural products such as peppermint oil. To obtain real-world information, we have performed an anonymous pharmacy-based patient survey among 1686 users of HBB, HBB + paracetamol and peppermint oil. Based on the distinct but overlapping indications for the three OTC products, multiple logistic regression was applied to compare them in users reporting gastrointestinal cramps and pain, bloating, flatulence, or IBS as cardinal symptom. All three treatments reduced symptoms and associated impairments of work/daily chores, leisure activities, and sleep by approximately 50%. Based on the four cardinal symptoms and the four dependent continuous variables of interest (change of intensity of symptoms and of the three impairment domains) a total of 16 logistic regression models were applied. HBB, HBB + paracetamol, and peppermint oil had similar reported overall effectiveness in those models. Gender, age, baseline symptom severity and impairment in one of three domains had small and inconsistent effects on perceived treatment success. We provide evidence that HBB, HBB + paracetamol, and peppermint oil have comparable effectiveness in their approved indications under real-world conditions in an OTC setting.

Malassezia are lipid-dependent basidiomycetous yeast of the normal skin microbiome, although Malassezia DNA has been recently detected in other body sites and has been associated with cer-tain chronic human diseases. This new perspective raises many questions. Are these yeasts truly present in the investigated body site or were they contaminated by other body sites, adjacent or not? Does this DNA contamination come from living or dead yeast? If these yeasts are alive, do they belong to the resident mycobiota or are they transient colonizers which are not permanently established within these niches? And, finally, are these yeasts associated with certain chronic diseases or not? In an attempt to shed light on this knowledge gap, we critically re-viewed the 31 published studies focusing on the association of Malassezia spp. with chronic human diseases, including psoriasis, atopic dermatitis (AD), chronic rhinosinusitis (CRS), asthma, cystic fibrosis (CF), HIV infection, inflammatory bowel disease (IBD), colorectal cancer (CRC), and neurodegenerative diseases.

Different nutraceuticals are often considered by parents of infants and children with abdominal pain and disorders of the gut-brain interaction. Herb extracts and natural compounds have long been used in traditional medicine, but clinical pediatric trials are very limited. This narrative review based on relevant studies identified through Pubmed-Medline literature search updated to October 2023, focused on the effect of nutraceuticals in infantile colic, functional abdominal pain and irritable bowel syndrome in children and adolescents. Significant reduction of colic episodes and crying time was reported in two studies on fennel (seeds oil or tea), in three studies on different multiple herbal extracts (all including fennel), in one study on Mentha piperita, and in at least two double-blind randomized controlled studies on Lactobacillus reuteri DSM 17938 and Bifidobacterium lactis BB-12 (108 CFU/day for at least 21 days) in breast-fed infants. Compared to placebo, in children with functional abdominal pain or irritable bowel syndrome a significant reduction of pain was reported in two studies supplementing peppermint oil capsules or psyllium fibers, in one study on corn fiber cookies or partial hydrolysed guar gum or a specific multiple herbal extract (STW-5) or vitamin D supplementation. To date, there is a moderate certainty of evidence with a weak grade of recommendation for Lactobacillus reuteri DSM 17938 (108 CFU/day) for reducing pain intensity in children with functional abdominal pain and for Lactobacillus rhamnosus GG (1-3 x109 CFU twice daily) for reducing pain frequency and intensity in children with IBS. Further large and well-designed pediatric studies are needed to prove efficacy and safety of different herbal extracts and prolonged use of studied products in infants and children with pain disorders of the gut-brain interaction.

Inflammatory diseases are common pathological processes caused by various acute and chronic factors and some of them are autoimmune diseases. Exosomes are fundamental extracellular vesicles secreted by almost all cells, which contain a series of constituents, i.e. cytoskeletal and cytosolic proteins (actin, tubulin, histones), nucleic acids (mRNA, miRNA, DNA), lipids (diacylglycerophosphates, cholesterol, sphingomyelin, ceramide), and other bioactive components (cytokines, signal transduction proteins, enzymes, antigen presentation and membrane transport/fusion molecules, adhesion molecules). This review would be a synopsis of the actual knowledge on the contribution of exosomes from different cell sources as possible therapeutic agents against inflammation, focusing on several inflammatory diseases, neurological diseases, rheumatoid arthritis and osteoarthritis, intestinal bowel disease, asthma, liver and kidney injuries. Current knowledge indicates that the role of exosomes in therapy of inflammation and in inflammatory diseases could be distinctive. Main limitations to their clinical translation are still production, isolation, and storage. Additionally, there is an urgent need to personalize the treatments in terms of selection of exosomes, their dosages and routes of administration, and a deeper knowledge about their biodistribution, type and incidence of adverse events and long-term effects of exosomes. In conclusion, exosomes can very promising next generation therapeutic option, superior to synthetic nanocarriers and cell therapy, and can represent a new strategy of effective, safe, versatile and selective delivery systems in the future.

Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn’s disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we will discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diseases in humans. It is characterized by visceral pain and/or discomfort, hypersensitivity and abnormal motor responses along with change in gut habits. Although the etio-pathogenesis of IBS is only partially understood, a main role has been attributed to psychosocial stress of different origin. Animals models such as neonatal maternal separation, water avoidance stress and wrap restraint stress have been developed as psychosocial stressors in the attempt to reproduce the IBS symptomatology and identify the cellular mechanisms responsible for the disease. The study of these models has led to the production of drugs potentially useful for IBS treatment. This review intends to give an overview on the results obtained with the animal models; to emphasize the role of the enteric nervous system in IBS appearance and evolution and as a possible target of drug therapies.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies mainly originated from hormones secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout MEN-1 gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signaling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally, act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the roles and the potential therapeutic implications of gene mutations and NOTCH signaling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential roles across all NEN subtypes is required.

Inflammatory bowel diseases, which consist of chronic inflammatory conditions of the colon and the small intestine, are considered a global disease of our modern society. Recently, the interest toward the use of herbal therapies for the management of inflammatory bowel diseases has increased because of their effectiveness and favorable safety profile, compared to conventional drugs. Boswellia serrata Roxb. and Curcuma longa L. are amongst the most promising herbal drugs, however, their clinical use in inflammatory bowel diseases is limited and little is known on their mechanism of action. The aim of this work was to investigate the effects of two phytochemically characterized extracts of B. serrata and C. longa in an in vitro model of intestinal inflammation. Their impact on cytokine release and reactive oxygen species production, as well as the maintenance of the intestinal barrier function and on intestinal mucosa immune cells infiltration, has been evaluated. The extracts showed a good protective effect on the intestinal epithelium at 1 µg/ml, with TEER values increasing by approximately 1.5 fold, compared to LPS-stimulated cells. C. longa showed an anti-inflammatory mechanism of action, reducing IL-8, TNF-α and IL-6 production by approximately 30%, 25% and 40%, respectively, compared to the inflammatory stimuli. B. serrata action was linked to its antioxidant effect, with ROS production being reduced by 25%, compared to H₂O₂-stimulated Caco-2 cells. C. longa and B. serrata resulted to be promising agents for the management of inflammatory bowel diseases by modulating in vitro parameters which have been identified in the clinical conditions.

The aggregate aftermath of persistent inflammation in patients with inflammatory bowel disease (IBD) places them at increased risk for the advancement to colitis-associated colorectal cancer (CACRC). CACRC is preceded by IBD, the highly heterogenous, pharmacologically incurable, pertinacious, reverting/worsening, and immune-mediated inflammatory pathologies of the colon and rectum. The molecular and immunological basis of CACRC is highly correlated with the length/duration and stringency/severity of colon inflammation predisposed by the exogenous/free hemoglobin alpha chain (HbαC) the byproduct of infiltrating immune cells, extravasated erythrocytes, and macrophage erythrophagocytosis. The exogenous free HbαC prompts oxygen-free radical-arbitrated DNA damage (DNAD) through increased cellular reactive oxygen species (ROS) exacerbated by decreased tissue antioxidant defenses. Mitigation of Fenton reaction via pharmaceutical therapy would attenuate the ROS, promote apoptosis, DNAD repair, and subsequent prevent the incidence of CACRC. Three pharmaceutical options that attenuate hemoglobin toxicity include haptoglobin, deferoxamine, and flavonoids (vitamins C/E). Haptoglobin’s clearance rare from plasma is inversely correlated with its size; the smaller the size, the faster the clearance. Thus, the administration of Hp1-1 may prove to be beneficial. Furthermore, deferoxamine’s hydrophilic structure limits its ability to cross cell membranes. Thus, it may be beneficial if administered intracellularly to avoid the higher plasma concentrations and longer incubation periods associated with extracellular administration. Finally, the effectiveness of flavonoids and natural herb antioxidants is associated with high reactivity of hydroxyl substituents. Multiple analyses are currently underway to assess the clinical context of CACRC and outline the molecular basis of HbαC-induced ROS pathogenesis by exposing colonocytes and/or colonoids to HbαC. These cells are then treated with haptoglobin, deferoxamine (DFO), and flavonoids in order to separate free HbαC and measure their impact on hydroxyl radical formation therapies. The molecular pathogenesis of sporadic colorectal cancer (SCRC) i.e., “inflammation-dysplasia-carcinoma” progression sequence is well described, but the immunopathogenesis of CACRC herein reviewed is broadly still in prodromal stage/phase to be validated and understood. Therefore this timely review outlines the molecular and immunological basis of disease pathogenesis and the pharmaceutical intervention as a protective measure for CACRC.

The literature on the causation of multiple sclerosis (MS), both genetic and environmental, extends over hundreds of years, with no firm conclusions on the exact role of autoimmunity and lifestyle. The epidemiology of MS was the basis for this review, but with a new, extensive examination of genes pertaining to each disorder, and disease of first, and second, degree relatives of those with MS. The author’s motivation was to discover some relationship between MS, and notable familial conditions, as the heredity of MS is concluded to be 30%, and the disorders had a chronic and/or idiopathic nature. This investigation hoped to further understand the randomness of MS- who acquires it, and what symptoms develop- after the author’s decades of observing several incidences of multiple members developing MS in a single family. Online databases for the human genome were used to link genes to MS, and symptoms, including excessive depression, fatigue and suicide rates, in coordination with linking genes for specific familial conditions including seizures, stroke, mental illness, bowel disorders, and thyroid conditions. Interesting associations were found, notably a cluster of Th2 cytokines, known to cure the animal model of MS, important receptors for neurotransmitters and hormones, a gene specific to Epstein Barr Virus, and potential genes for mitochondrial dysfunction. The results surprised the author, showing polygenic regions of chromosome 2 and 5, especially a cluster at loci 5q31-q33, may be dysregulated. The conclusion agrees with past hypotheses MS results not from a single gene, but from various genes, including those expressed in glial cells. The individual theories to the causation of MS, starting with Charcot may be explained by multiple pathways converging into a single disease outcome. In coordination with a sunlight factor, chromosome 2 appears to mediate the immune system, and inflammation, through ultraviolet radiation producing vitamin D3 in the skin, but additionally through peptides formed in the melanocyte stimulating and concentrating hormone class. The impact of stress in MS could be primary, given the loci of several stress-related and stress-modulated genes on these chromosomes, and calls for more appreciation of, and greater care for, the MS patients’ state of mind.