Extraintestinal Complications Research Articles

P0711 The Effect of Extraintestinal Manifestations Presence on Treatment Persistence in IBD Treatment

Abstract Background Inflammatory Bowel Disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a chronic, relapsing inflammatory disorder of the gastrointestinal tract. A significant portion of patients also experience extra-intestinal manifestations (EIMs) that involve various organ systems beyond the intestines. EIMs are often present at the onset of disease or may develop later during the course of IBD, and their severity can vary, influencing overall disease prognosis and quality of life. Effective management of IBD requires a holistic approach that not only addresses the intestinal inflammation but also anticipates and treats these extra-intestinal complications. In this study we aimed to investigate the role of EIM presence on anti-TNF treatment persistence in IBD therapy. Methods This was a single center, retrospective cohort analysis of patients with IBD either received adalimumab or infliximab as a first line biologic treatment. A total of 673 patients were included to this analysis. Demographic information such as gender, age, Montreal classification, EIM presence, smoking and prior medications were noted from patients electronic medical records. Weighted Kaplan-Meier and Cox models were used to assess the outcomes. Results Out of 673 patients, 426 patients had Crohn’s disease, 240 patients had ulcerative colitis and 7 patients had indeterminate colitis. Overall, 379 pateints received adalimumab and 294 patients received infliximab as first line biologic treatment for IBD. While 272 patients had EIM, 349 patients did not have EIM accompanying their IBD. EIM presence was not concluded in 52 patients from their medical charts. Smoking and family history were not different between patiemnts with and without EIM. However, female patients had statistically more EIM (51.3% vs. 38.1%, p<0.05) and patients with Crohn’s disease had statistically more EIM (49.4% vs 34.5%, p<0.05). Anti-TNF drug persistence was significantly higher in patients with EIM when compared to patients with no EIM (Figure 1). This difference was independent of the type of anti-TNF medication used. However, in patients with ulcerative colitis the difference became more significant, while in Crohn’s disease patients although there is trend, the difference was not significant. The concomitant use of immunomodulator drugs did not make any impact. Conclusion In IBD patients, anti-TNF medication persistence was observed to be significantly longer in those with EIM. This difference was significantly greater in ulcerative colitis patients compared to Crohn’s patients. This difference was independent of the concomitant medication use.

P1229 Updated Epidemiology of Osteoporosis in the Inflammatory Bowel Disease Population and Associated Risk Factors: Insights from a Retrospective Cohort Analysis

Abstract Background Osteoporosis is a prominent extra-intestinal complication in patients with inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD). The prevalence of osteopenia and osteoporosis among patients with IBD varies widely, ranging from 22%-77% and 17%-41%, respectively, depending on population characteristics, geographic location, and study design [1]. Despite these variations, the burden of osteoporosis in IBD is unequivocal, impacting quality of life and increasing the risk of fractures. Methods We conducted a retrospective cohort study using the TriNetX database to assess the incidence of osteoporosis in patients with IBD between 2013 and 2023. Data were stratified by age, sex, and race. A comparative analysis of osteoporosis risk in IBD versus non-IBD populations was performed, along with an exploration of risk factors specific to UC and CD cohorts. Propensity score matching was employed to adjust for confounders, including age, sex, race, BMI, smoking, primary sclerosing cholangitis (PSC), steroid use, autoimmune diseases, IBD medications, and surgical history. Risk was quantified as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results A total of 120,396 patients with IBD (mean age 43.8 ± 19.4, female sex 53.073%, White race 79.01%) were analyzed. The five-year incidence of osteoporosis was significantly higher in the IBD cohort (aOR: 1.43, 95% CI: 1.38-1.48) compared to the non-IBD cohort. Among IBD subtypes, CD patients exhibited a higher risk (aOR: 1.53, 95% CI: 1.46-1.60) compared to UC patients (aOR: 1.38, 95% CI: 1.32-1.44) [Figure 1]. Osteoporosis incidence was notably higher in females (IBD: 9.78%, UC: 10.48%, CD: 9.38%) than in males (IBD: 3.55%, UC: 3.67%, CD: 3.87%) and increased significantly with age, reaching 21.67% in patients over 80 years old. Racial disparities were evident, with the highest incidence observed among White patients (7.35%). Significant risk factors for osteoporosis in IBD included long-term corticosteroid use (aOR: 2.29, 95% CI: 2.25-2.32), malnutrition (aOR: 1.56, 95% CI: 1.53-1.59), use of TNF-alpha inhibitors (aOR: 1.40, 95% CI: 1.36-1.43), PSC (aOR: 2.30, 95% CI: 2.08-2.54), intestinal surgery (aOR: 1.21, 95% CI: 1.18-1.23), hemoglobin levels of <10 g/dL (aOR: 1.20, 95% CI: 1.19-1.21), albumin levels of <2.5 g/dL (aOR: 1.07, 95% CI: 1.05-1.08), and mood disorders (aOR: 1.16, 95% CI: 1.15-1.17) [Figure 2]. Conclusion Osteoporosis is a significant concern for patients with IBD, with females, older adults, and CD patients being most at risk. Early and targeted interventions are crucial to reducing bone loss and improving long-term outcomes in this vulnerable population.

Abnormal Esophageal Scintigraphy Associates With a Distinct Clinical Phenotype in Patients With Systemic Sclerosis.

In systemic sclerosis (SSc), absent contractility (AC) rather than ineffective esophageal motility on manometry is associated with a severe esophageal and extraintestinal phenotype. We sought to determine whether slow esophageal transit on scintigraphy associates with a comparable clinical phenotype to that of AC on manometry, as scintigraphy may serve as a noninvasive approach to risk-stratify patients with SSc. Clinical, demographic, and serologic features were compared between patients with and without delayed esophageal transit on scintigraphy. University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract (GIT) 2.0 scores measured GI symptoms, Medsger scores measured physician-assessed SSc disease severity, and the Composite Autonomic Symptom Score 31 survey evaluated dysautonomia symptoms. Of 131 patients, 79 (60%) had delayed esophageal transit by scintigraphy. Patients with delayed esophageal transit were more likely to have diffuse SSc (24 [32%] vs 11 [22%]; P = 0.024), severe lung involvement (22 [41%] vs 7 [19%]; P = 0.034), severe Raynaud (36 [47%] vs 15 [31%]; P = 0.063), and a higher median (interquartile range [IQR]) diarrhea GIT score (0.5 [IQR 0-1] vs 0 [IQR 0-1]; P = 0.050). Lower diffusing capacity of the lungs for carbon monoxide values correlated with a higher esophageal transit time (ρ = -0.32; P = 0.014). After adjusting for disease duration, delayed esophageal transit was significantly associated with severe Medsger lung scores, severe Raynaud phenomenon, and higher modified Rodnan skin scores. Patients with delayed esophageal transit by scintigraphy have a more severe SSc phenotype, similar to patients with AC, on esophageal manometry. Further studies should validate esophageal scintigraphy as a tool to identify patients with SSc with AC who may develop specific GI and extraintestinal complications.

A Case of Crohn's disease with Granulomatous Interstitial Nephritis as an Extraintestinal Complication from the Time of the Diagnosis

Granulomatous interstitial nephritis (GIN) has been reported in <0.5% of patients with inflammatory bowel disease, and most cases of GIN are drug-induced. A 13-year-old boy was referred for the evaluation of abdominal pain, diarrhea, and weight loss. The patient was diagnosed with non-drug-induced GIN and Crohn's disease based on total colonoscopy and a biopsy of the colon and kidney. Both tissues contained macrophages and increased epithelial expression of IκBζ, a protein involved in the NF-κB pathway. There may be more patients with GIN complicated by Crohn's disease than expected, and macrophages may be involved in the pathogenesis.

A Cross-Sectional Evaluation of Disability in Inflammatory Bowel Disease Using IBD Disk in a Tertiary Center from Romania.

Background/Objectives: The management of inflammatory bowel disease (IBD) includes, besides the control of symptoms, the prevention of organ damage and the improvement of the overall disability. Methods: A single-centered, cross-sectional, non-interventional and population-based study was conducted between October 2023 and August 2024 in the Department of Internal Medicine 2 and Gastroenterology of Bucharest Emergency University Hospital to assess the disease disability and quality of life impact using IBD-disk and correlation with different parameters. Results: We included 112 patients; their mean age was 52.35 ± 16.67 years, with a disease duration of 114.9 ± 97.93 months. The majority of patients were represented by men (51.79%). We observed a strong correlation between the CDAI score and overall disability compared to the Mayo score for UC (p = 0.0068). Also, patients with CD and stenotic patterns, as well as the presence of extraintestinal complications, have associated high disability scores. Low hemoglobin levels are associated with high disability (p = 0.0164), while biological treatment is associated with low disability (p = 0.0481). Conclusions: IBD-disk can be used as a valuable tool to assess disability in patients with IBD, also in terms of the activity of the disease, but mostly in terms of the psychological burden of the disease.

Clinical and diagnostic features of Crohn's disease in young children.

Aim: To highlight the distinctive features of CD in young children, based on personal clinical experience in observation and treatment, with the objective of improving the accuracy of diagnosis and the effectiveness of treatment. Materials and Methods: The study involves the results of treatment 11 young children with CD. The diagnosis was based on the combination of the following data: clinical manifestations of the disease and its course, as well as the results of laboratory, instrumental, and step biopsy with morphological studies. Results: In young patients with CD, combined lesions of the small and large intestines predominate, manifesting as gastrointestinal disorders against the background of a severe general condition, intoxication, and extraintestinal complications. Young children with CD often show signs of asthenic syndrome, developmental delay, and high inflammatory activity. All the children in the study showed low serum iron levels, dysproteinemia, and high calprotectin levels. Conclusions: 1. CD in young children has such clinical features as combined lesions of the small and large intestines (45.45% of cases), high activity of the disease. frequent extraintestinal manifestations of the disease, and developmental delay. All young children with CD upon admission to the hospital were in severe condition, exhibiting signs of intoxication, diarrhea, and blood in their stools. 2. Laboratory findings are characterized by serum iron deficiency, dysproteinemia, and high levels of calprotectin. 3. Knowledge of the clinical and diagnostic features of CD is essential for specialists to provide appropriate medical care.

Evaluation of Molecular Assays for Diagnosis of Amoebic Liver Abscess in India with Bayesian Latent Class Analysis.

Amoebic liver abscess (ALA) is the most common extra-intestinal complication of Entamoeba histolytica, accounting for 50,000 deaths annually, and is endemic in South Asia. Diagnosis based on microscopic examination is insensitive, and serological assays are not discerning of current infections in endemic settings with high exposure. For a rapid and confirmatory laboratory diagnosis of ALA, the performance of a polymerase chain reaction (PCR), quantitative real time PCR (qPCR), digital droplet PCR (ddPCR), and a loop-mediated isothermal amplification (LAMP) assay that detects E. histolytica DNA in liver abscess pus, and a lectin antigen detection ELISA were evaluated against clinical diagnosis (based on predefined criteria) as the gold standard. Owing to the lack of a laboratory gold standard, a Bayesian latent class analysis approach was also used to determine sensitivity and specificity of these assays. In the latent class analysis, qPCR and ddPCR showed the highest sensitivity (98% and 98.1%) and specificity (both 96.6%), and although clinical diagnosis had a comparable sensitivity to qPCR and ddPCR (95.2%), poorer specificity (64.3%) was seen. Kappa agreement analysis showed that qPCR and ddPCR had a perfect agreement of 1 followed by an agreement of 0.76 (95% CI: 0.64-0.88) with PCR. Considering the performance characteristics and relative ease of setting up qPCR as well as the wide availability of qPCR equipment needed, this would be the most optimal assay for rapid, confirmatory, molecular diagnosis of ALA in the tertiary care laboratory setting in India, whereas further optimization of LAMP or antibody-based detection is required for use at smaller or secondary hospitals.

S3939 Unveiling the Uncommon: Pyoderma Gangrenosum as an Extraintestinal Complication of Ulcerative Colitis

S3939 Unveiling the Uncommon: Pyoderma Gangrenosum as an Extraintestinal Complication of Ulcerative Colitis

Distinct clinical trajectories of gastrointestinal progression among patients with systemic sclerosis.

Systemic sclerosis (SSc) is heterogeneous in its clinical presentation. Common manifestations cluster together, defining unique subgroups. This investigation aims to characterize gastrointestinal (GI) phenotypes and determine whether they can be distinguished by temporal progression. We examine a well-established SSc patient cohort with a modified Medsger GI severity score measured over time to determine heterogeneity in disease progression. Growth mixture models estimate each patient's phenotype and disease severity trajectory over time. We compare the characteristics of estimated phenotypes using non-parametric statistics and linear and logistic regression to compare patient characteristics between phenotypes while adjusting for disease duration. We examined 2696 SSc patients with at least two Medsger GI scores, identifying four unique phenotypes. The most common phenotype (n = 2325) ("Stable") had an average score of 1 that was consistent over time. Two phenotypes were progressive ["Early Progressive" (n = 142) and "Late Progressive" (n = 115)] with an initial average score of 1. The Early Progressive group increased initially and stabilized, and the Late Progressive group worsened slowly over time. A fourth phenotype ["Early Severe GI"; (n = 114)] had an initial average Medsger GI score just below 3 with high mortality and improving GI severity over time. Clinically distinct GI phenotypes exist among patients with SSc. These phenotypes are not only distinguished by GI and extra-intestinal SSc clinical complications, but they are also temporally distinct. Distinct autoantibody profiles are associated strongly with more severe GI disease.

Role of Extracellular Vesicles in Crohn's Patients on Adalimumab Who Received COVID-19 Vaccination.

Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) affecting the gastrointestinal tract that can also cause extra-intestinal complications. Following exposure to the mRNA vaccine BNT162b2 (Pfizer-BioNTech) encoding the SARS-CoV-2 Spike (S) protein, some patients experienced a lack of response to the biological drug Adalimumab and a recrudescence of the disease. In CD patients in progression, resistant to considered biological therapy, an abnormal increase in intestinal permeability was observed, more often with a modulated expression of different proteins such as Aquaporin 8 (AQP8) and in tight junctions (e.g., ZO-1, Claudin1, Claudin2, Occludin), especially during disease flares. The aim of this study is to investigate how the SARS-CoV-2 vaccine could interfere with IBD therapy and contribute to disease exacerbation. We investigated the role of the SARS-CoV-2 Spike protein, transported by extracellular vesicles (EVs), and the impact of various EVs components, namely, exosomes (EXOs) and microvesicles (MVs), in modulating the expression of molecules involved in the exacerbation of CD, which remains unknown.

Disseminated Salmonella Typhi Infection Presenting with Slurred Speech and Encephalopathy: An Unusual Presentation

Abstract: Salmonella enterica serovar Typhi causes systemic infections and typhoid fever in humans, mainly affecting infants and children. It presents mostly with fever, malaise, anorexia, abdominal pain, constipation, and/or diarrhoea. Complications of the disease include intestinal perforation and haemorrhage. However, sometimes extra-intestinal complications are also reported, which rarely include encephalopathy. This report presents a case of a 28-year-old male who presented with somnolence and later developed slurred speech. A week before his current admission, he was admitted with abdominal pain and underwent a laparoscopic appendectomy, and was discharged uneventfully. Now after eight days he presented with somnolence. His neurological examination was otherwise unremarkable. Imaging studies helped to rule out ischaemic stroke. A detailed system-wise examination revealed mild right upper quadrant tenderness and hepatosplenomegaly on abdominal examination. Imaging revealed hepatosplenomegaly with gallbladder wall oedema and mesenteric lymphadenopathy. Blood culture was reviewed, revealing extensively drug-resistant (XDR) Salmonella Typhi. A diagnosis of XDR Salmonella bacteraemia leading to encephalopathy was made. The patient responded well to antibiotic therapy guided by the culture and sensitivity. Keywords: Salmonella, Complicated typhoid, XDR typhoid, Food hygiene, Speech disturbance, Ischaemic stroke.

Celiac Disease, Gluten-Free Diet and Metabolic Dysfunction-Associated Steatotic Liver Disease.

Celiac disease (CD) is a chronic autoimmune disorder triggered by the ingestion of gluten-containing food by genetically predisposed individuals. Hence, treatment of CD consists of permanent avoidance of wheat, rye, barley, and other gluten-containing foods. Lifelong adherence to a gluten-free diet (GFD) improves the symptoms of CD, but recent evidence suggests it is also associated with a higher risk for hepatic steatosis and the coexistence or emergence of other cardiometabolic risk factors. Moreover, a higher risk for liver steatosis is also reported by some authors as a potential extraintestinal complication of the CD itself. Recent nomenclature changes designate the association between hepatic steatosis and at least one of five cardiometabolic risk factors as metabolic dysfunction-associated steatotic liver disease (MASLD). An extended network of potentially causative factors underlying the association between MAFLD and CD, before and after dietary therapy is implemented, was recently described. The individualized treatment of these patients is less supported by evidence, with most of the current recommendations relying on empiric clinical judgment. This review focuses on the causative associations between CD and hepatic injury, either as an extraintestinal manifestation of CD or a side effect of GFD, also referring to potential therapeutic strategies for these individuals.

Portal vein thrombosis as extraintestinal complications of Crohn’s disease: a case report and review of literature

IntroductionThrombotic events are more than twice as common in inflammatory bowel disease patients as in the general population. We report an interesting and rare case of portal vein thrombosis as a venous thromboembolic event in the context of extraintestinal manifestations of Crohn’s disease. We also conducted a literature review on portal vein thrombosis associated with inflammatory bowel disease, with the following concepts: inflammatory bowel diseases, ulcerative colitis, Crohn’s disease, portal vein, and thrombosis.Case presentationA 24-year-old Syrian female with active chronic Crohn’s disease was diagnosed 11 years ago and classified as A1L3B1P according to the Montreal classification. She had no prior surgical history. Her previous medications included azathioprine and prednisolone. Her Crohn’s disease activity index was 390 points. Gastroduodenoscopy revealed grade I esophageal varices, a complication of portal hypertension. Meanwhile, a colonoscopy revealed several deep ulcers in the sigmoid, rectum, and descending colon. An investigation of portal vein hypertension revealed portal vein thrombosis. We used corticosteroids to induce remission, followed by tapering; additionally she received ustekinumab to induce and maintain remission. She began on low-molecular-weight heparin for 1 week, warfarin for 3 months, and then apixaban, a novel oral anticoagulant, after excluding antiphospholipid syndrome. Primary prophylaxis for esophageal varices was not required. After 1 year, she achieved clinical, biochemical, and endoscopic remission. Despite 1 year of treatment, a computed tomography scan revealed no improvement in portal vein recanalization.ConclusionPortal vein thrombosis is a rare and poorly defined complication of inflammatory bowel disease. It is usually exacerbated by inflammatory bowel disease. The symptoms are nonspecific and may mimic a flare-up of inflammatory bowel disease, making the diagnosis difficult. Portal vein Doppler ultrasound for hospital-admitted inflammatory bowel disease patients may contribute to the diagnosis and management of this complication.

Myeloid Ptpn2 Deficiency in Mice Causes Functional Iron Deficiency

Background: Anemia is the most prevalent extraintestinal complication of inflammatory bowel disease (IBD) and is associated with the manifestation of Crohn’s disease. Anemia significantly reduces the quality of life, increases hospitalization visits, and increases medical care expenses of IBD patients. Iron deficiency is the leading cause of anemia in IBD; however, the physiological mechanisms involved are still poorly understood. Macrophages significantly contribute to iron homeostasis by mechanisms including iron recycling by phagocytosing senescent erythrocytes and damaged cells, and nurturing erythropoiesis in the bone marrow. In this study, we investigated the role of the IBD candidate gene, protein tyrosine phosphatase non-receptor type 2 ( PTPN2), in regulating macrophage iron homeostasis. Methods: Myeloid cell-specific knockout mice ( Ptpn2LysMCre) and control littermates ( Ptpn2fl/fl) were analyzed for serum iron content and liver and spleen non-heme iron. Duodenal epithelial cell (DEC) proteins were assayed by Western blotting. Localization of the brush border ferrous iron transporter, DMT1, and the coupled ferrous iron absorption driver, NHE3, in duodenal tissue was determined by immunohistochemistry (IHC). Gene expression profiles of macrophages were analyzed by Nanostring. Results: Ptpn2LysMCre mice had reduced serum iron ( p&lt;0.0001; n=12) and reduced spleen non-heme iron (p=0.0017; n=6), whereas liver non-heme iron was unaltered (n=6), indicating iron deficiency in select tissues. DMT1 (n=8) and NHE3 (n=5) protein expression in DECs was unaltered and IHC confirmed the unaltered localization of DMT1 and NHE3 (n=6) in the duodenal epithelium of Ptpn2LysMCre mice, suggesting the reduction in serum iron was not due to an impairment in intestinal non-heme iron uptake. Nanostring analyses revealed that the gene expression of the iron transporter Dmt1, iron exporter Fpn, and iron importer Tfr1 were significantly downregulated (p&lt;0.05; n=5) in macrophages from Ptpn2LysMCre mice, indicating an iron sequestering phenotype. Conclusions: Loss of myeloid Ptpn2 in mice causes functional iron deficiency. These findings indicate a major role of myeloid PTPN2 in regulating systemic iron homeostasis. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

C-reactive Protein: An Inflammatory Biomarker and a Predictor of Neurodegenerative Disease in Patients With Inflammatory Bowel Disease?

Inflammatory bowel disease (IBD) refers to two chronic conditions of the digestive tract: ulcerative colitis (UC) and Crohn's disease (CD), representing a progressive inflammatory process that mainly occurs in the gut, with frequent extra-intestinal manifestations. Even if remission is periodically obtained for some patients, the histological activity and digestive symptoms may continue, maintaining a persistent systemic inflammation that could induce further extra-intestinal complications and contribute to the development of neurodegenerative disease. C-reactive protein (CRP) is an acute-phase reactant that is widely accepted as a dominant serum biomarker in IBD. CRP consequently activates the complement cascade, supports the release of pro-inflammatory cytokines, and the clearance of microbial pathogens. All these processes facilitate further processes, including atherosclerosis and hypercoagulability, alteration of the intestinal microbiota, and the increased permeability of the intestinal barrier for neurotoxic substances produced by gut microorganisms, due to the presence of a high level of lipopolysaccharides. For IBD, the connection between intestinal inflammation and central nervous system inflammation could be explained through the activity of the vagus nerve, a carrier of cytokines, CRP, and toxic materials to the brain, potentially inducing vascular lesions and damage of the glial vascular unit, with further risk for degeneration within the central nervous system. CRP is a key marker for IBD pathogenesis and is able to dissociate into its monomeric form, mCRP, on contact with activated cell and tissue components via the systemic circulation. We hypothesize that the chronic inflammatory process within IBD could initiate neuroinflammation and neurodegeneration, and therefore, further investigation of the significance of chronically raised plasma of CRP and mCRP in patients with IBD is warranted, as it may represent a critical predictive factor associated with a later neurodegenerative risk. Any future initiative aimed at pharmacologic modulation of CRP (e.g., blocking CRP-mCRP dissociation), could represent a new therapeutic approach protecting against intestinal inflammation and concomitantly reducing the risk of neuroinflammation, neurodegeneration, and cognitive decline.

Quiescent ulcerative colitis and Crohn’s disease have potential effect on cognitive function

BackgroundUlcerative colitis (UC) and Crohn’s disease (CD) imply chronic intestinal inflammation with both local and systemic manifestations. Cognition is a lifelong process of learning and memory processing, which has been identified to be affected by chronic systemic illnesses.AimTo evaluate the cognitive functions in inflammatory bowel disease (IBD) patients in remissionPatients and methodsInclusion criteria are as follows: 70 IBD patients in remission and a group of 50 healthy control. Mini-mental state examination (MMSE) was used for assessment of global cognitive function and Trail Making Test (TMT) for assessment of executive functions. TMT consists of part A which measures attention and performance speed and part B which measures mental flexibility. Both tests have been previously validated on Arabic-speaking populations.ResultsThe study included 70 patients (50 UC and 20 CD), who have been in remission for 21 ± 9 months. Of the included cases, about 51 were already on steroids ± azathioprine, and 19 patients were on biologics. Males represented 60% (n = 42) while females 40% (n = 28), and their mean age was 34 ± 8 years. Both cases and controls were matched for age and sex. The mean score of MMSE among IBD cases was significantly worse than controls (28.5 ± 3 versus 30, P < 0.001). Also, the duration of TMT parts A and B was significantly longer in cases than controls. The cases group scored 32 ± 19.5 s in TMT part A, versus 23 s by the controls. In TMT B, the recorded scores were 255 ± 48, versus 234 s in cases and control groups respectively (P < 0.001). In the cases group, 6 patients (8%) had below normal MMSE score of less than 24, with mild (3 patients, mean score was 21) to moderate cognitive impairment (3 patients, mean score was 15). The presence of extraintestinal manifestation was the only disease-related factor that was associated with cognitive impairment. Of the patient-related factor: older age, being divorced, and living in rural areas were associated with poorer cognitive functions.ConclusionIBD patients potentially suffer from cognitive impairment. In our study, factors as extraintestinal complications, older age, marital status, and residence in rural areas could be contributing factors to this impairment.

Myositis as a de-novo extraintestinal manifestation of ulcerative colitis in a pediatric patient developing post-colectomy: a case report

This report presents the case of a 13-year-old female with a history of ulcerative colitis who underwent ileostomy closure after total colectomy. Postoperatively, she developed right leg paresis and extensive swelling of the lower extremities. Imaging investigations revealed myositis with avascular necrosis in the distal femoral condyles. These findings were consistent with myositis as an extraintestinal complication of ulcerative colitis.

CROHN'S DISEASE AND GASTROINTESTINAL REPERCUSSIONS: A DETAILED STUDY OF COMORBIDITIES AND CLINICAL IMPLICATIONS

Crohn's disease is a chronic inflammatory condition that affects the gastrointestinal tract, characterized by transmural and segmental inflammation that can involve any part of the digestive system, from the mouth to the anus. This pathology presents a wide range of clinical manifestations, including abdominal pain, diarrhea, rectal bleeding, fistulas, strictures and even extraintestinal complications. The complexity of Crohn's disease lies not only in its varied clinical presentation, but also in its comorbidities and clinical implications, which can significantly affect patients' quality of life and require multifaceted therapeutic approaches. Objective: To identify and synthesize the evidence available in the scientific literature over the last 10 years on the comorbidities and clinical implications of Crohn's Disease, in order to provide a comprehensive and updated view of this aspect of gastrointestinal pathology. Methodology: The systematic review was carried out in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, Scielo and Web of Science databases were used to identify relevant studies published in the last 10 years. The descriptors used were "Crohn's disease", "gastrointestinal manifestations", "comorbidities", "clinical implications" and "systematic review". The inclusion criteria involved studies that specifically investigated the comorbidities and clinical implications of Crohn's Disease, with results available in English, Spanish or Portuguese. Exclusion criteria included duplicate studies, case reports and studies with small samples or less robust methods. Results: Analysis of the selected studies revealed a wide variety of comorbidities associated with Crohn's disease, including arthritis, dermatitis, uveitis, osteoporosis and liver disorders. Furthermore, the significant clinical implications of Crohn's disease were highlighted, such as increased risk of hospitalizations, need for intestinal surgeries and impact on patients' quality of life. Conclusion: Crohn's disease presents a clinical complexity that goes beyond intestinal manifestations, with a series of comorbidities and clinical implications that require an integrated and multidisciplinary approach in its management. This review highlights the importance of understanding these aspects to improve the care and quality of life of patients with this chronic gastrointestinal condition.

Hot Topics on Nutrition in IBD

Inflammatory bowel diseases (IBD) affect primarily the bowel, but they are multisystemic diseases with a wide range of extraintestinal manifestations and complications. Nutritional imbalance occurs frequently in patients with IBD. The spectrum of malnutrition goes from undernutrition (low protein-caloric intake, disease-related malnutrition, micronutrient deficiencies) to overnutrition and obesity. The nutritional status of patients with IBD is increasingly recognized as a key aspect of the treatment and must be addressed in all patients. The screening and correction of the deficiencies should be individualized. Except for enteral nutrition in pediatric Crohn’s disease, no clinical evidence supports specific diets. Nevertheless, the role of personalized nutritional interventions as an adjunct therapy is well established. Compelling new data points to a key role of diet in gut inflammation directly or through modulation of intestinal microbiota. It will be of utmost importance to have well-designed longitudinal studies on dietary interventions alone or combined with current therapies. This review summarizes topics such as the spectrum of malnutrition, the evidence behind the concept of diet as an IBD cause, and the role of diet in IBD therapy.

Investigating shared genetic architecture between inflammatory bowel diseases and primary biliary cholangitis

Inflammatory bowel disease (IBD) is commonly associated with extraintestinal complications, including autoimmune liver disease. The co-occurrence of IBD and primary biliary cholangitis (PBC) has been increasingly observed, but the underlying relationship between these conditions remains unclear. Using summary statistics from genome-wide association studies (GWAS), we investigated the causal effects between PBC and IBD, including Crohn's disease (CD) and ulcerative colitis (UC). We also analyzed the shared genetic architecture between IBD and PBC using data from GWAS, bulk-tissue RNA sequencing, and single cell RNA sequencing, and explored potential functional genes. There was a strong positive genetic correlation between PBC and IBD (linkage disequilibrium score regression: rg= 0.2249, p= 3.38×10-5). Cross-trait analysis yielded 10 shared-risk single nucleotide polymorphisms (SNPs), as well as nine novel SNPs, which were associated with both traits. Using Mendelian randomization, a stable causal effect was established of PBC on IBD. Genetically predicted PBC was found to have a risk effect on IBD (1.105; 95% CI: 1.058-1.15; p= 1.16×10-10), but not vice versa. Shared tissue-specific heritability enrichment was identified for PBC and IBD (including CD and UC) in lung, spleen, and whole-blood samples. Furthermore, shared enrichment was observed of specific cell types (T cells, B cells, and natural killer cells) and their subtypes. Nine functional genes were identified based on summary statistics-based Mendelian randomization. This study detected shared genetic architecture between IBD and PBC and demonstrated a stable causal relationship of genetically predicted PBC on the risk of IBD. These findings shed light on the biological basis of comorbidity between IBD and PBC, and have important implications for intervention and treatment targets of these two diseases simultaneously. The discovery of novel shared single nucleotide polymorphisms (SNPs) and functional genes provides insights into the common targets between inflammatory bowel disease (IBD) and primary biliary cholangitis (PBC), serving as a basis for new drug development and contributing to the study of disease pathogenesis. Additionally, the established significant causality and genetic correlation underscore the importance of clinical intervention in preventing the comorbidity of IBD and PBC. The enrichment of SNP heritability in specific tissues and cell types reveals the role of immune factors in the potential disease mechanisms shared between IBD and PBC. This stimulates further research on potential interventions and could lead to the development of new targets for immune-based therapies.