Extraintestinal Complications Research Articles

The Fatal Role of Enterohaemorrhagic Escherichia coli Shiga Toxin-associated Extracellular Vesicles in Host Cells.

Enterohemorrhagic Escherichia coli (EHEC) is a specific subset of Shiga toxin-producing Escherichia coli (STEC) strains that are characterized by their ability to cause bloody diarrhea (hemorrhagic colitis) and potentially life-threatening, extraintestinal complications such as hemolytic uremic syndrome (HUS), which is associated with acute renal failure., contributing to severe clinical outcomes. The Shiga toxins (Stxs), produced by EHEC, are primary virulence factors. These potent cytotoxins are composed of one enzymatically active A subunit (StxA) and five receptor-binding B subunits (StxB). Although the toxins are primarily associated with cytotoxic effects, they also elicit other pathogenic consequences due to their induction of a number of biological processes, including apoptosis through ER-stress, pro-inflammatory responses, autophagy, and post-translational modification (PTM). Moreover, several studies have reported the association between Stxs and extracellular vesicles (EVs), including microvesicles and exosomes, demonstrating that Stx-containing EVs secreted by intoxicated macrophages are taken up by recipient cells, such as toxin-sensitive renal proximal tubular epithelial cells. This mechanism likely contributes to the spreading of Stxs within the host, and may exacerbate gastrointestinal illnesses and kidney dysfunction. In this review, we summarize recent findings relating to the host responses, in different types of cells in vitro and in animal models, mediated by Stxs-containing exosomes. Due to their unique properties, EVs have been explored as therapeutic agents, drug delivery systems, and diagnostic tools. Thus, potential therapeutic applications of EVs in EHEC Stxs-mediated pathogenesis are also briefly reviewed.

CLINICAL FEATURES OF CROHN'S DISEASE AND ULCERATIVE COLITIS

The retrospective study was conducted in the Department of Gastroenterology, THQ Hospital, from March 2020 to March 2021 to assess CD and UC's clinical characteristics and demographic features in a relatively diverse group of patients. The study included patients diagnosed with IBD. The questionnaire was used to gather data regarding clinical and demographic features, disease duration, and family history of IBD, surgical interventions, extra-intestinal manifestations, and clinical and socio-economic variables relevant to CD and UC patients. 500 patients were included in the study, of which 135 (28%) had CD and 365 (73%) had UC. UC patients predominantly had bloody diarrhea and/or hematochezia, while CD patients had abdominal pain. 50% of CD patients required surgical intervention, compared to only 9.8% of UC patients. Evaluation of chemotherapy showed that 66.6% of CD patients and 37.8% of UC patients received steroid therapy. 22 (6%) UC patients and 7 (5.1%) CD patients had a family history of IBD (P=.819). The most frequent extra-intestinal complication in UC patients was PSC; it was acute arthropathy in CD patients. It is concluded that the peak age of disease onset in UC and CD patients is similar to other Asian countries. There was non-significant male predominance for UC and CD. Diagnosis of CD is delayed compared to UC, which may be due to negligence towards disease symptoms.

From Eberthella typhi to Salmonella Typhi: The Fascinating Journey of the Virulence and Pathogenicity of Salmonella Typhi.

Salmonella Typhi (S. Typhi), the invasive typhoidal serovar of Salmonella enterica that causes typhoid fever in humans, is a severe threat to global health. It is one of the major causes of high morbidity and mortality in developing countries. According to recent WHO estimates, approximately 11-21 million typhoid fever illnesses occur annually worldwide, accounting for 0.12-0.16 million deaths. Salmonella infection can spread to healthy individuals by the consumption of contaminated food and water. Typhoid fever in humans sometimes is accompanied by several other critical extraintestinal complications related to the central nervous system, cardiovascular system, pulmonary system, and hepatobiliary system. Salmonella Pathogenicity Island-1 and Salmonella Pathogenicity Island-2 are the two genomic segments containing genes encoding virulent factors that regulate its invasion and systemic pathogenesis. This Review aims to shed light on a comparative analysis of the virulence and pathogenesis of the typhoidal and nontyphoidal serovars of S. enterica.

Maximizing iron uptake in inflammatory bowel disease: An updated systematic review and meta-analysis of intravenous vs oral iron therapy

Background and Aims: Anemia is the most common extraintestinal complication of inflammatory bowel diseases (IBD). Iron deficiency anemia (IDA) can be treated with oral or intravenous (IV) iron supplementation. The aim of this study is to compare the efficacy and tolerability of oral and IV iron supplementation for treating anemia in adult IBD patients. Methods: A systematic review and meta-analysis of randomized controlled trials were conducted. Databases including PubMed, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials were searched until December 2022. Trials that included individuals with IBD and compared IV to oral iron for treating IDA were eligible. Two reviewers independently extracted data, and another two reviewers independently graded each trial's risk of bias. The fixed-effect model was used to obtain pooled odds ratio (OR) estimates and their 95% confidence intervals (CI). Results: Five trials, including 910 IBD patients, were eligible for analysis. The meta-analysis showed that IV iron was more effective than oral iron for raising hemoglobin levels to 2.0 g/dL (OR: 1.44, 95% CI: 1.09 - 1.91, P = 0.01). The IV iron groups had decreased rates of treatment withdrawal prompted by adverse side effects or intolerance (OR: 0.26, 95% CI: 0.13 - 0.51, P < 0.0001). There was no evidence of heterogeneity across all studies. Conclusion: IV iron appears to be more efficient and well-tolerated than oral iron for treating anemia associated with IBD. The findings suggest that IV iron may be a preferred treatment option for IBD patients with IDA.

A Retrospective Study of Complications of Enteral Feeding in Critically Ill Children on Noninvasive Ventilation.

The utilization of noninvasive ventilation (NIV) in pediatric intensive care units (PICUs), to support children with respiratory failure and avoid endotracheal intubation, has increased. Current guidelines recommend initiating enteral nutrition (EN) within the first 24-48 h post admission. This practice remains variable among PICUs due to perceptions of a lack of safety data and the potential increase in respiratory and gastric complications. The objective of this retrospective study was to evaluate the association between EN and development of extraintestinal complications in children 0-18 years of age on NIV for acute respiratory failure. Of 332 patients supported with NIV, 249 (75%) were enterally fed within the first 48 h of admission. Respiratory complications occurred in 132 (40%) of the total cohort and predominantly in non-enterally fed patients (60/83, 72% vs. 72/249, 29%; p < 0.01), and they occurred earlier during ICU admission (0 vs. 2 days; p < 0.01). The majority of complications were changes in the fraction of inspired oxygen (220/290, 76%). In the multivariate evaluation, children on bilevel positive airway pressure (BiPAP) (23/132, 17% vs. 96/200, 48%; odds ratio [OR] = 5.3; p < 0.01), receiving a higher fraction of inspired oxygen (FiO2) (0.42 vs. 0.35; OR = 6; p = 0.03), and with lower oxygen saturation (SpO2) (91% vs. 97%; OR = 0.8; p < 0.01) were more likely to develop a complication. Time to discharge from the intensive care unit (ICU) was longer for patients with complications (11 vs. 3 days; OR = 1.12; p < 0.01). The large majority of patients requiring NIV can be enterally fed without an increase in respiratory complications after an initial period of ICU stabilization.

Splenic Lesions as a Soft Pointer Towards the Diagnosis of Enteric Fever: A Case Series.

To the Editors: Enteric fever is a major public health problem in developing countries.1 The highest incidence is in children between 5 and 9 years-of-age.2 Splenic abscess (SA) is a rare extra-intestinal complication of salmonellosis with a reported incidence of 0.29%–2%.3,4 Salmonella SA is rare but carries a high risk of morbidity and mortality if unrecognized and untreated.5 This case series presents 3 cases of enteric fever complicated with splenic lesions. Case 1: A 5-year-old female patient presented with fever, pain in the abdomen, vomiting and loose stools for 10 days. On examination, she had a tender abdomen with hepatomegaly. She was started on ceftriaxone due to suspicion of enteric fever. Ultrasonography (USG) of the whole abdomen on admission day was normal. Widal serology on day 11 of illness was positive (1:320 for Titre of H antibody and Titre of O antibody). Blood culture grew nalidixic acid-resistant Salmonella typhi (Table 1). Because she continued to remain febrile, azithromycin was added on day 7 of the hospital stay, and a repeat USG was performed on day 10 of the stay, showing SA (1.4 × 2.1 × 2.3 cm) at the lower pole. USG-guided needle aspiration was performed, and antibiotics continued. She became afebrile over the next few days, was started on oral cefixime and discharged. TABLE 1. - Baseline Characteristics, Clinical, Lab and Management Details of Cases Patient Characteristics Case 1 Case 2 Case 3 Age at presentation (years) 5 12 4 Symptoms (duration in days) Fever Yes (10) Yes (21) Yes (10) Pain abdomen Yes (8) Yes (18) Yes (3) Vomiting Yes (8) No Yes (3) Loose stools Yes (8) No No Per abdomen examination Tenderness Yes Yes Yes Hepatomegaly (liver span) Yes (11 cm) Yes (12 cm) Yes (12 cm) Splenomegaly No Palpable spleen tip No Investigations at admission Haemoglobin (gm/dL) 9.3 11 11.5 TLC (per mm3) 7,800 8,260 5800 DLC (N%/ L %/ M %) 74/20/3 76/14/4 56/33/10 Platelet count (per mm3) 39,000 3,69,000 1,54,00 CRP (mg/dL) 97 36 43 Widal test (titres) Positive (1:320) Negative Positive (1:320) Antibiotics (days) Ceftriaxone (14) f/b cefixime (7) Azithromycin (14) Ceftriaxone (14) f/b cefixime (7) Ceftriaxone (14) f/b cefixime (7) Follow up USG 1 × 1.06 × 1 cm abscess, 1-month postdischarge. Resolution of splenic abscess, 2-month postdischarge Resolution of splenic abscess Resolution of splenic granuloma Typhoid vaccine status Unvaccinated Unvaccinated Unvaccinated CRP, C-reactive protein; DLC, Differential leukocyte count; f/b indicates followed by; TLC, Total leukocyte count; USG, ultrasonography. Case 2: A 12-year-old male presented with 3 weeks of high-grade fever and left abdominal pain. Examination revealed tenderness and palpable spleen tip. Ceftriaxone was initiated empirically. Widal serology was negative, and the blood culture was sterile. Other investigations to evaluate for the etiology of fever, including tuberculosis, were negative. USG abdomen revealed 3 SA, the largest 2.5 × 2.2 cm in splenic parenchyma. Ultrasound-guided aspiration of the largest abscess was performed. Pus culture grew Salmonella paratyphi A. Ceftriaxone was continued as per the sensitivity report. Subsequently, he became afebrile and was started on cefixime and discharged. Case 3: A 4-year-old female presented with fever for 10 days, pain in the abdomen, and vomiting for 3 days. She was started on intravenous ceftriaxone empirically, keeping a possibility of enteric fever. Due to persistent abdominal pain, USG of the abdomen was performed, which revealed multiple hypo-echoic foci in the spleen suggestive of splenic granuloma. Blood investigations revealed a positive Widal test (1:320 dilution titers for Titre of H antibody and Titre of O antibody) and blood culture grew Salmonella typhi. She became afebrile by day 4 of the hospital stay. She was given 7 days of intravenous ceftriaxone, followed by 7 days of cefixime. USG whole abdomen repeated 1-week post-discharge, showed no splenic granuloma. Salmonella SA is rare but carries a high risk of morbidity and mortality if unrecognized and untreated.5 Diagnosis is often delayed in children due to its rarity and nonspecific symptoms. USG abdomen is usually the first investigation performed in suspected cases, and sensitivity can be as high as 90% in the hands of an experienced operator. Percutaneous needle aspiration and antibiotics for 2–3 weeks may be sufficient in many cases, though the actual duration of antibiotics required is not known. The splenic abscess could be a pointer toward the diagnosis of enteric fever in high-burden settings like India. Though radiologic clearing can require 2–3 months, patients usually become asymptomatic after 2–3 weeks of adequate antibiotics and drainage.

Bilateral gonarthrosis as the onset of Crohn’s disease in children: a clinical presentation

Crohn’s disease is an immune-mediated disease characterized by nonspecific granulomatous transmural inflammation with segmental damage to any part of the gastrointestinal tract with the formation of extraintestinal and systemic complications. The disease is complex, multifactorial, which lasts throughout life and affects the physical and psychological development of the individual. According to modern ideas, the occurrence of Crohn’s disease is influenced by external environmental factors against the background of genetic predisposition. According to the literature, in most cases, patients with Crohn’s disease complain of abdominal pain, diarrhea, unexplained anemia, fever, weight loss, or growth retardation. The classic triad of abdominal pain, diarrhea and weight loss occurs in only 25 % cases. Extraintestinal manifestations such as skin lesions, vasculitis, joint syndrome, aphthous stomatitis or para-anal lesions (anal itching, macerations, fissures, paraproctitis, fistulas) may be the first symptoms in 6–23 % of cases. The diagnosis of Crohn’s disease in children is made on the basis of anamnestic and clinical data, the results of using special research methods, including endoscopic, radiological, ultrasound, histological, spiral computer tomography, magnetic resonance imaging, as well as immunological and genetic markers. Achieving and maintaining remission can minimize psychological problems and improve patients’ quality of life. A clinical case of Crohn’s disease is presented, which was diagnosed in a 14-year-old child who was treated for juvenile idiopathic oligoarthritis since the age of two and had frequent bacterial and inflammatory diseases. The difficulties of diagnostic search are reflected, which are caused by various symptoms and early onset. Treatment and clinical monitoring were carried out in accordance with the international recommendations of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) 2021. The authors emphasize the need for dynamic clinical monitoring of the patient’s condition, as well as a personalized approach to treatment.

Extra-intestinal complications of Ascaris lumbricoides infections in India: A systematic review and meta-analysis.

The aberrant migration of Ascaris lumbricoides may cause extra-intestinal ascariasis (EIA) involving hepato-biliary-pancreatic (HBP) or other extra-gastro-intestinal (EGI) organs. We performed a systematic review and meta-analysis to study the risk factors and clinical presentations of EIA, and differences in HBP and EGI ascariasis. Medline, Web of Science and Embase were searched for cases of EIA in the English language from India. From 1204 articles, 86 studies (105 cases) were included. The majority of the cases involved the HBP system (78%). Among HBP ascariasis, the most commonly involved site was the bile duct (53.6%). Females had 11.3 times higher odds (95% CI 2.852 to 44.856; p=0.001) of HBP ascariasis, while the pediatric population had lower odds (OR=0.323). Previous gallbladder disease was significantly associated with HBP ascariasis in adults (p=0.046), while a significantly higher number of cases of EGI ascariasis were observed among pediatric patients (p=0.003). Ocular symptoms occurred exclusively in the pediatric population (p=0.017). Overall, death was reported in 3.8% of patients (n=4). This review emphasizes the importance of the complications of EIA. It encourages future research into issues such as the reasons of higher gall bladder ascariasis in females and the implications of Ascaris-related complications following biliary tract interventions. It also suggests considering Ascaris as a differential diagnosis for airway obstuction in intubated critically ill patients.

Hepato-Nephroprotective Actions of Salvia officinalis Decoction Extract Against Extraintestinal Alterations Induced with Acetic Acid-Colitis Model in Rats.

Inflammatory bowel disease is associated with multiple extraintestinal disorders, including hepato-nephrological disruptions. The aim of this study was to evaluate the hepato-nephroprotective effect of Salvia officinalis leaf decoction extract (SLDE) on acetic acid (AA)-induced colitis accompanied with liver and kidney injuries. Wistar albinos rats were pretreated with SLDE (50, 100, and 200 mg kg-1, b.w., p.o.) during 10 days and intoxicated for 24 h by acute rectal administration of AA (3%, v/v, 5 mL kg-1, b.w.). Our results showed that S. officinalis treatment protected against AA-induced liver and kidney injuries by plasma transaminase activities and preservation of the hepatic and renal tissue structures. The level of high-density lipoprotein-cholesterol was also reverted back to near normalcy by treatment. Lipid peroxidation was decreased significantly by officinal sage supplementation. Treatment with SLDE increased enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) and nonenzymatic (-SH groups and reduced glutathione) antioxidants in liver and kidney tissues. Also, SLDE treatment significantly protected against inflammation markers and reversed all intracellular mediator perturbations. This study suggests that the S. officinalis has a beneficial effect in controlling kidney and liver injuries by reducing lipid peroxidation and increasing antioxidant enzyme activities and nonenzymatic contents, which reduce the risk of developing extraintestinal complications.

Cross talk between bacterial and human gene networks enriched using ncRNAs in IBD disease

Inflammatory bowel disease (IBD) is a long-term inflammatory immune-mediated gut illness with several extra-intestinal complications. The aims of this study were to identify a novel network-based meta-analysis approach on the basis of the combinations of the differentially expressed genes (DEGs) from microarray data, to enrich the functional modules from human protein–protein interaction (PPI) and gene ontology (GO) data, and to profile the ncRNAs on the genes involved in IBD. The gene expression profiles of GSE126124, GSE87473, GSE75214, and GSE95095 are obtained from the Gene Expression Omnibus (GEO) database based on the study criteria between 2017 and 2022. The DEGs were screened by the R software. DEGs were then used to examine gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The ncRNAs including the miRNAs and ceRNAs were predicted on the PPIs visualized using Cytoscape. Enrichment analysis of genes with differential expression (n = 342) using KEGG and GO showed that the signaling pathways related with staphylococcus aureus and pertussis bacterial infections may stimulate the immune system and exacerbate IBD via the interaction with human proteins including Fibrinogen gamma chain (FGG), Keratin 10 (KRT10), and Toll like receptor 4 (TLR4). By building a ceRNA network, lncRNA XIST and NEAT1 were determined by affecting common miRNAs, hsa-miR-6875-5p, hsa-miR-1908-5p, hsa-miR-186-5p, hsa-miR-6763-5p, hsa-miR-4436a, and hsa-miR-520a-5p. Additionally, the chromosome regions including NM_001039703 and NM_006267, which produce the most potent circRNAs play a significant role in the ceRNA network of IBD. Also, we predicted the siRNAs that would be most effective against the bacterial genes in staphylococcus aureus and pertussis infections. These findings suggested that three genes (FGG, KRT10, and TLR4), six miRNAs (hsa-miR-6875-5p, hsa-miR-1908-5p, hsa-miR-186-5p, hsa-miR-4436a, hsa-miR-520a-5p, and hsa-miR-6763-5p), two lncRNAs (XIST and NEAT1), and chromosomal regions including NM_001039703 and NM_006267 with the production of the most effective circRNAs are involved in the ncRNA-associated ceRNA network of IBD. These ncRNA profiles are related to the described gene functions and may play therapeutic targets in controlling inflammatory bowel disease.

Anemic Syndrome and Molecular Mechanisms and Regulation of Iron Absorption in Gastroenterological Diseases

In this review, we tried to combine and systematize the accumulated information on the problem of anemic syndrome in the pathologies of the gastrointestinal tract. Anemic syndrome is the most frequent extraintestinal complication in patients with gastrointestinal tract pathology, which can significantly impair the quality of life. Depending on the combination of pathogenitic mechanisms, the iron deficiency, anemia of chronic diseases, B12-deficiency, and folate deficiency anemia are distinguished. Other types of anemia are less common. It is necessary to conduct a comprehensive laboratory examination to reveal the leading factor in the development of anemia and select adequate therapy. Anemia is one of the most common complications in patients with inflammatory bowel disease. In clinical practice, the intravenous iron is frequently administered. However, this therapy can lead to excess iron and cause exacerbation of the disease. Understanding the pathogenesis of anemia is important for the selection of therapy and minimizing the risk of complications. Parenteral forms of iron and vitamin preparations are more preferable for this category of patients due to their higher bioavailability, low safety profile, and minimal negative effect on the gastrointestinal tract. Erythropoietin preparations and inhibitors of proinflammatory cytokines are used mainly for the correction of anemia of chronic diseases. The latter showed themselves well in the treatment of patients with anemic syndrome on the background of severe inflammatory bowel diseases. Various clinical trials are being conducted to introduce new drugs to correct anemia. However, today, there is practically no experience of their application. Further study of patients with gastroenterological pathology complicated by anemia is required to form a final conclusion on the effectiveness and appropriateness of the intravenous iron administration in these categories of patients.

The Prevalence of Anemia in Chronic Inflammatory Bowel Disease during COVID-19: Experience of the Gastroenterology Department of the Moulay Ismail Meknes Military Hospital: About 70 Cases

Inflammatory bowel diseases (IBD) include Crohn's disease and ulcerative colitis. IBD represents a pathology that evolves through relapses interspersed with remission. Anemia is the most common extra-intestinal complication in inflammatory bowel disease (IBD). Depending on the hemoglobin level, the anemia is mild, moderate or severe. It can affect quality of life and increase the hospitalization rate of patients. The reported prevalence of anemia in patients with IBD ranges from 6% to 74%. Although the causes of anemia in IBD are multifactorial, iron deficiency anemia remains the most common. Management is based on treating the disease and correcting the anemia with injectable iron. The aim of the work is to take stock of the prevalence and treatment of chronic anemia during IBD, as well as the impact of the covid19 period on the monitoring of this chronic pathology in our structure.

Anemic Syndrome and Molecular Mechanisms and Regulation of Iron Absorption in Gastroenterological Diseases

Anemic syndrome is the most often extraintestinal complication in patients with diseases of the digestive tract (DT), which can significantly impair the quality of life. In the literature review, we tried to combine and systematize the accumulated information on the problem of anemic syndrome in DT diseases. Iron-deficiency anemia, chronic disease anemia, B12-deficiency and folio-deficiency anemia are determined depending on the combination of pathogenetic mechanisms. Other variants of anemia are rare. It is necessary to carry out a complex laboratory examination to establish the leading factor in the development of anemia and determine the adequate therapy. Anemia of inflammatory disease is one of the frequent complications in patients with DT diseases. For the correction of such anemia in clinical practice, iron preparations are used parenterally. However, such therapy can lead to an excess of iron and worsen the course of the underlying disease. The understanding the anemia pathogenesis is important for prescribing therapy and minimizing the risk of complications. Parenteral forms of iron and vitamin preparations should be prioritized for this category of patients due to their higher bioavailability, low safety profile and minimal negative impact on DT. Erythropoietin preparations and inhibitors of proinflammatory cytokines are mainly used to correct anemia of chronic inflammation. Pro-inflammatory cytokines are effective for patients with anemic syndrome and severe inflammatory bowel processes. According to the literature data, various clinical studies aimed at the introduction of new drugs that correct anemia are being conducted. The review presents modern methods of diagnosis and treatment of anemia in order to better understand this disease. A further study of patients with gastroenterological diseases, the course of which is complicated by anemia, is necessary to form a final conclusion about the disease, the effectiveness and feasibility of prescribing parenteral forms of iron preparations.

Recent Advancements in Technologies to Detect Enterohaemorrhagic Escherichia coli Shiga Toxins.

Shiga toxin (Stxs)-producing enterohaemorrhagic Escherichia coli (EHEC) and Shigella dysenteriae serotype 1 are major causative agents of severe bloody diarrhea (known as hemorrhagic colitis) and hemolytic uremic syndrome (HUS) associated with extraintestinal complications such as acute renal failure and neurologic impairment in infected patients under 9 years of age. Extreme nephrotoxicity of Stxs in HUS patients is associated with severe outcomes, highlighting the need to develop technologies to detect low levels of the toxin in environmental or food samples. Currently, the conventional polymerase chain reaction (PCR) or immunoassay is the most broadly used assay to detect the toxin. However, these assays are laborious, time-consuming, and costly. More recently, numerous studies have described novel, highly sensitive, and portable methods for detecting Stxs from EHEC. To contextualize newly emerging Stxs detection methods, we briefly explain the basic principles of these methods, including lateral flow assays, optical detection, and electrical detection. We subsequently describe existing and newly emerging rapid detection technologies to identify and measure Stxs.

Intestinal and Extra-intestinal Complications of Typhoid Fever: an Update

Intestinal and Extra-intestinal Complications of Typhoid Fever: an Update

P677 Combination of vedolizumab and exclusive enteral nutrition in patients with moderate to severe Crohn’s Disease

Abstract Background Crohn’s disease (CD) is an incurable chronic inflammatory condition of the gut. It causes severe gastrointestinal and extraintestinal complications and is associated with high morbidity, poor quality of life and increased health expenditure. Although increasing randomized controlled tests (RCT) studies demonstrated the premise of efficacy of biologics including vedolizumab in adult patients with active CD, there’re still 60% of patients hard to achieve clinical and endoscopic remission in real-world studies. Here, we investigated the efficacy of combination strategy of vedolizumab and exclusive enteral nutrition (EEN) in moderate to severe active CD treatment. Methods Twenty-eight patients with moderately to severely active CD patients treated with vedolizumab in IBD medical center of Renmin Hospital of Wuhan University in Hubei Province were retrospectively enrolled in this cohort. All patients received EEN for 16 weeks with concomitant vedolizumab standard induction. The clinical response, clinical remission, and fecal calprotectin (FC) normalization was evaluated in short- (week 16) and moderate-term (week 32 and 48). Endoscopic response and mucosal healing were assessed at week 16 and 48 (Figure 1). Figure 1: Study design Results Following vedolizumab intravenous induction and 16-weeks EEN treatment, patients achieved 71.4% (20/28) of clinical remission, 73.1% (19/26) of endoscopic response and 71.4% (20/28) FC normalization at week 16. For moderate-term assessment at week 32, sustainable efficacy of current treatment induced 19/24 (79.2%) of clinical response, 15/24 (62.5%) of clinical remission and 16/24 (66.7%) of FC normalization. Clinical response (15/22, 68.2%) and mucosa healing (14/22, 63.6%) were also observed in over 60% of patients at week 48 since treatment induction (Figure 2,3). Figure 2. Clinical and biochemical endpoints Figure 3. Endoscopic endpoint Conclusion Combination of Vedolizumab and 16-weeks EEN increased clinical and endoscopic outcomes in short and moderate term for patients with moderate to severe Crohn’s Disease.

P256 Urinary lithogenic profile and gut and urinary microbiota in patients with inflammatory bowel diseases

Abstract Background Nephrolithiasis (NL) is a common extra-intestinal complication of inflammatory bowel disease (IBD) with recognizable morbidity and mortality. However, its pathogenesis and risk factors are not completely elucidated yet. Because of intestinal malabsorption, enteric hyperoxaluria is a crucial pathogenic mechanism responsible for developing urinary stones in IBD patients. In recent decades, growing evidence has highlighted the association between gut microbiota and NL, with a particular emphasis on the role of some oxalate-degrading bacteria, such as Oxalobacter formigenes, representing the mainstay of the so-called “gut-kidney axis.” More recent studies also hypothesize the involvement of urinary microbiota, but no data on IBD patients are available. Thus, we conducted a pilot study to analyse the urinary lithogenic profile in IBD patients and its relationship with gut and urinary microbiota. Methods Consecutive patients with IBD were prospectively enrolled. The presence of ileoanal pouch, ileostomy, colostomy, or short-bowel syndrome were exclusion criteria. Demographic and clinical data, including previous episodes of NL, were collected. Disease activity was evaluated using Harvey-Bradshaw and Mayo scores for Crohn’s disease (CD) and ulcerative colitis (UC). All patients underwent abdominal ultrasound for NL detection, and blood tests of kidney function (creatinine, blood urea nitrogen, creatinine clearance, electrolytes) were also measured, together with 24h-urine collection for lithogenic profile analysis, including calcium oxalate relative saturation ratio (RSRCaOx). In a subgroup of patients, urinary and faecal microbiota were also analysed through 16S rRNA sequencing. Results 36 patients (20 CD and 16 UC) were enrolled. NL was more frequent in CD than in UC (25% vs. 6.25%). 24-h oxaluria was significantly increased in patients with previous or present NL (p=0.02), and RSRCaOx was significantly higher in CD than in UC (p=0.02) (Figure 1). Gut microbiota analysis revealed a higher relative abundance of Bacteroidetes and a lower abundance of Firmicutes in patients with an elevated RSRCaOx, defined for values more than the median (Figure 2). No statistically significant differences were observed in urinary microbiota composition in relation to high or low levels of RSRCaOx. Conclusion NL is more common in IBD patients with higher oxaluria levels, confirming oxalate excretion's crucial role in NL pathogenesis. Furthermore, our study reports an association between urinary stone development and Firmicutes/Bacteroidetes imbalance in the gut microbiota, suggesting possible further studies to identify patients at higher risk of NL.

Disturbance of intestinal permeability and its role in the development of cardiovascular complications in persons with inflammatory bowel diseases

Inflammatory bowel diseases (IBD) are one of the most complex and significant problems of modern gastroenterology. The steady increase in morbidity, complex pathogenetic mechanisms of development, the presence of severe extra-intestinal manifestations and complications make this problem socially significant. The article presents modern views on some aspects of the pathogenesis of IBD. Currently, the key links in the development and progression of IBD, as well as the development of associated cardiovascular diseases are the state of the intestinal microbiota and the level of endotoxemia. The role of trimethylamine N-oxide as a factor in the early development of atherosclerosis in patients with IBD was determined.

Exploration of the shared pathways and common biomarker PAN3 in ankylosing spondylitis and ulcerative colitis using integrated bioinformatics analysis.

Ulcerative colitis (UC) is a chronic autoimmune-related disease that causes inflammation of the intestine. Ankylosing spondylitis (AS) is a common extraintestinal complication of UC involving the sacroiliac joint. However, the pathogenesis of AS secondary to UC has not been studied. This study aimed to investigate the shared pathways and potential common biomarkers of UC and AS. Microarray data downloaded from the Gene Expression Omnibus (GEO) database were used to screen differentially expressed genes (DEGs) in the UC and AS datasets. Weighted gene co-expression network analysis (WGCNA) was performed to identify co-expression modules related to UC and AS. Shared genes were then further analyzed for functional pathway enrichment. Next, the optimal common biomarker was selected using SVM-RFF and further validated using two independent GEO datasets. Finally, immune infiltration analysis was used to investigate the correlation of immune cell infiltration with common biomarkers in UC and AS. A total of 4428 and 2438 DEGs in UC and AS, respectively, were screened. Four modules were identified as significant for UC and AS using WGCNA. A total of 25 genes overlapped with the strongest positive and negative modules of UC and AS. KEGG analysis showed these genes may be involved in the mitogen-activated protein kinase (MAPK) signaling pathway. GO analysis indicated that these genes were significantly enriched for RNA localization. PAN3 was selected as the optimal common biomarker for UC and AS. Immune infiltration analysis showed that the expression of PAN3 was correlated with changes in immune cells. This study first explored the common pathways and genetic diagnostic markers involved in UC and AS using bioinformatic analysis. Results suggest that the MAPK signaling pathway may be associated with both pathogeneses and that PAN3 may be a potential diagnostic marker for patients with UC complicated by AS.

First molecular characterization of Escherichia coli O157:H7 isolates from clinical samples in Paraguay using whole-genome sequencing

Escherichia coli O157:H7 is a foodborne pathogen implicated in numerous outbreaks worldwide that has the ability to cause extra-intestinal complications in humans. The Enteropathogens Division of the Central Public Health Laboratory (CPHL) in Paraguay is working to improve the genomic characterization of Shiga toxin-producing E. coli (STEC) to enhance laboratory-based surveillance and investigation of foodborne disease outbreaks. Whole genome sequencing (WGS) is proposed worldwide to be used in the routine laboratory as a high-resolution tool that allows to have all the results in a single workflow. This study aimed to carry out for the first time, the genomic characterization by WGS of nine STEC O157:H7 strains isolated from human samples in Paraguay. We were able to identify virulence and resistance mechanisms, MLST subtype, and even establish the phylogenetic relationships between isolates. Furthermore, we detected the presence of strains belonging to hypervirulent clade 8 in most of the isolates studied.