Role of Calprotectin, IL-6, and CRP in Distinguishing Between Inflammatory Bowel Disease and Diarrhea Predominant Irritable Bowel Syndrome.

Background: The early establishment of prophylaxis and immediate administration of anticoagulant therapy upon the diagnosis of venous thromboembolism should be the treatment objectives in these patients. Objective: The study aimed to determine the optimal cut-off point of Calprotectin, IL-6 (interleukin-6), CRP (C reactive protein) to differentiate UC, IBS-D. Methods: A cross-sectional descriptive study of 335 individuals ≥15 years old was performed, including 31 healthy controls, 215 with IBS-D, 71 diagnosed with UC, and 18 diagnosed with CD. Receiver Operating Characteristics (ROC), sensitivity, specificity, and area under curve (AUC) were computed. Results: The results showed that the median value of calprotectin (IQR) in healthy participants was 20.0 (6.0 - 34.0) µg/g; 17,7 (8,7-38,9) µg/g in IBS-D group; 1710.0 (588 - 4260,0) µg/g in UC group; and 560.5 (177.8 - 1210.0) µg/g in CD group. Calprotectin concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The median value of CRP (range IQR) was 1,3 (0,9 - 2,3) mg/L in IBS-D group; 7.0 (2.4 -16.6) mg/L in UC group; and 10.1 (2.2 - 42.5) mg/L in CD group. CRP concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The median value of IL-6 (range IQR) was 2.3 (1.6 - 5.7) pg/mL in IBS-D group; 16.8 (9.4 - 47.0) pg/mL in UC group; and 9.4 (7.9 - 11.0) pg/mL in CD group. Calprotectin concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The optimal cut-off point of calprotectin that differentiated IBS-D from IBD was 110.5 µg/g, with sensitivity and specificity of 93.3% and 91.4%, respectively; of IL-6 was 7.2 pg/mL with sensitivity and specificity of 92.0% and 78.0%, respectively; of CRP of 2.4 mg/L had specific sensitivities of 83.3% and 86.0%, respectively. Conclusion: The Calprotectin immunoassay has the best value in discriminating between IBD and IBS-D.

Methods of determining optimal cut-point of diagnostic biomarkers with application of clinical data in ROC analysis: an update review.

INTRODUCTION: An important application of ROC analysis is the determination of the optimal cut-point for biomarkers in diagnostic studies. This comprehensive review provides a framework of cut-point election for biomarkers in diagnostic medicine. METHODS: Several methods were proposed for the selection of optional cut-points. The validity and precision of the proposed methods were discussed and the clinical application of the methods was illustrated with a practical example of clinical diagnostic data of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and malondialdehyde (MDA) for prediction of inflammatory bowel disease (IBD) patients using the NCSS software. RESULTS: Our results in the clinical data suggested that for CRP and MDA, the calculated cut-points of the Youden index, Euclidean index, Product and Union index methods were consistent in predicting IBD patients, while for ESR, only the Euclidean and Product methods yielded similar estimates. However, the diagnostic odds ratio (DOR) method provided more extreme values for the optimal cut-point for all biomarkers analyzed. CONCLUSION: Overall, the four methods including the Youden index, Euclidean index, Product, and IU can produce quite similar optimal cut-points for binormal pairs with the same variance. The cut-point determined with the Youden index may not agree with the other three methods in the case of skewed distributions while DOR does not produce valid informative cut-points. Therefore, more extensive Monte Carlo simulation studies are needed to investigate the conditions of test result distributions that may lead to inconsistent findings in clinical diagnostics.

Development of the Nursing Assessment Tool for the Patient With Inflammatory Bowel Disease.

This study aims to develop and validate a nursing assessment tool for patients with inflammatory bowel disease. In this cross-sectional descriptive study using a quantitative approach, nurses were invited to participate. The Delphi technique was used to obtain a consensus among expert nurses. Descriptive analysis was used for each item on the nursing assessment tool. Overall, 345 nurses were identified; 32 were eligible as experts and 13 validated the consultation. Of the 13 expert nurses, most were female (11, 84.62%), their mean age was 46.36 ± 10.59 years, eight (61.54%) graduated from public institutions, and eight (61.54%) had a master's degree. The initial version had 106 items, which was reduced to 95 items. The content of four domains (identification, health-disease profile, psychobiological needs, and physical examination) was validated in two rounds about the content with more than 80% of agreement. Two domains (sociodemographic data and health conditions, and personal cares) were validated in the first round with more than 80% of agreement. All domains were validated for their appearance during the first round with more than 80% of agreement. The Nursing Assessment Tool for Patients with Inflammatory Bowel Disease (IBD) had a considerable level of agreement regarding content and appearance validation in all dimensions.

Illness Perceptions as a Predictor of Symptom Cluster Trajectories in Patients With Inflammatory Bowel Disease: A Latent Growth Mixture Model.

The aims of this study were to (a) identify the trajectory of symptom clusters in patients with inflammatory bowel disease up to 28 weeks after initiation of infliximab therapy and (b) examine the illness perceptions associated with symptom cluster trajectories. This was a prospective study where participants completed the symptom cluster scale at baseline, 14 weeks, and 28 weeks. A latent growth mixture modeling was used to identify trajectories of symptom clusters that were predicted, using baseline covariates (Brief Illness Perception Questionnaire). A total of 206 patients were included and identified as three latent classes: moderate symptom cluster-stable decline group (C1), high symptom cluster-rapid decline group (C2), and stable symptom cluster-stable trend group (C3). C1 was predicted by cognitive illness perceptions (odds ratio [95% confidence interval]: 1.134 [1.071, 1.200], p < .001). C2 was also predicted by cognitive and emotional illness perceptions (odds ratio [95% confidence interval]: 1.169 [1.095, 1.248], p < .001; odds ratio [95% confidence interval]: 1.174 [1.038, 1.328], p = .011). Patients with inflammatory bowel disease, initiating infliximab therapy, had different symptom cluster trajectories. Illness perceptions were associated with symptom cluster classes, which underline the complexity of symptoms. Paying attention to these factors and providing necessary knowledge and psychological supporting care after infliximab therapy would effectively improve patients' symptom burden.

Recent trends in the epidemiology and clinical outcomes of inflammatory bowel disease in South Korea, 2010-2018.

BACKGROUND: Inflammatory bowel disease (IBD) was previously regarded as a Western disease; however, its incidence is increasing in the East. The epidemiology of IBD in Asia differs significantly from the patterns in the West. AIM: To comprehensively investigate the epidemiology of IBD in South Korea, including its incidence, prevalence, medication trends, and outcomes. METHODS: We analyzed claims data from the Health Insurance Review and Assessment Service and Rare and Intractable Diseases (RIDs), operated by the National Health Insurance Service of South Korea. Patients with IBD were identified based on the International Classification of Diseases, Tenth Revision, and RID diagnostic codes for Crohn's disease (CD) and ulcerative colitis (UC) from 2010 to 2018. RESULTS: In total, 14498 and 31409 patients were newly diagnosed with CD and UC, respectively, between 2010 and 2018. The annual average incidence of CD was 3.11 cases per 105 person-years, and that of UC was 6.74 cases per 105 person-years. Since 2014, the incidence rate of CD has been stable, while that of UC has steadily increased, shifting the peak age group from 50-year-olds in 2010 to 20-year-olds in 2018. The CD and UC prevalence increased consistently over the study period; the use of 5-aminosalicylates and corticosteroids gradually decreased, while that of immunomodulators and biologics steadily increased in both CD and UC. The clinical outcomes of IBD, such as hospitalization and surgery, decreased during the study period. CONCLUSION: The CD incidence has been stable since 2014, but that of UC has increased with a shift to a younger age at peak incidence between 2010 and 2018. IBD clinical outcomes improved over time, with increased use of immunomodulators and biologics.

Inflammatory Bowel Disease in Adults - Experience and Challenges in Gastroenterology Practices in Calabar, South-South Nigeria.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that is reported to be rare in Africans. The objective of this study is to share the experience of our Gastroenterology practice in Calabar, Cross River State on IBD. METHODS: This is a ten-year review of the records of patients visiting the Gastroenterology clinic of the University of Calabar Teaching Hospital and two private gastroenterology clinics in Calabar Municipality. The diagnosis of IBD was made based on clinical, laboratory, endoscopic, and histological data obtained. RESULTS: Eight patients presented with features consistent with IBD. Six had ulcerative colitis while 2 had Crohn's disease. Seven patients had moderate disease with the main clinical features being recurrent mucoid bloody diarrhoea. All the patients had treatments with either sulphasalazine or mesalazine as well as azathioprine, steroids and antibiotics with variable response. One patient had strictures requiring a colostomy, while another developed colorectal cancer as complications of IBD. CONCLUSION: Although IBD is uncommon in Nigeria, a high index of suspicion is important, especially in patients presenting with the recurrent passage of mucoid bloody stools. Hence, the role of colonoscopy and histology are invaluable in establishing the diagnosis.

FONDEMENT: La maladie inflammatoire de l'intestin (MII) est un trouble inflammatoire chronique du tractus gastro-intestinal qui est rapporté comme étant rare chez les Africains. L'objectif de cette étude est de partager l'expérience de notre pratique en gastroentérologie à Calabar, dans l'État de Cross River, sur la MII. MÉTHODES: Il s'agit d'une revue de dix ans des dossiers des patients fréquentant la clinique de gastro-entérologie de l'Hôpital universitaire de Calabar et de deux cliniques privées de gastroentérologie dans la municipalité de Calabar. Le diagnostic de MII a été posé sur la base de données cliniques, biologiques, endoscopiques et histologiques obtenues. RÉSULTATS: Huit patients présentaient des caractéristiques compatibles avec la MII. Six présentaient une colite ulcéreuse tandis que 2 présentaient une maladie de Crohn. Sept patients avaient une maladie modérée avec comme principale caractéristique clinique des diarrhées muqueuses sanglantes récurrentes. Tous les patients ont été traités soit avec de la sulfasalazine soit avec de la mésalazine ainsi que de l'azathioprine, des stéroïdes et des antibiotiques avec une réponse variable. Un patient avait des sténoses nécessitant une colostomie, tandis qu'un autre développait un cancer colorectal comme complications de la MII. CONCLUSION: Bien que la MII soit rare au Nigeria, un indice de suspicion élevé est important, surtout chez les patients présentant un passage récurrent de selles muqueuses sanglantes. Ainsi, le rôle de la coloscopie et de l'histologie est inestimable pour établir le diagnostic. MOTS-CLÉS: Adultes, Maladie de Crohn, Maladie inflammatoire de l'intestin, Colite ulcéreuse.

A Prospective Observational Study Analyzing the Diagnostic Value of Hepcidin-25 for Anemia in Patients with Inflammatory Bowel Diseases.

Iron deficiency (IDA) and chronic disease (ACD) anemia are complications of inflammatory bowel diseases (IBDs). Therapeutic modalities in remission and active IBD depend on the type of anemia. This study evaluated the link between hepcidin-25, proinflammatory cytokines, and platelet activation markers as biomarkers of anemia and inflammation in active IBD and remission. This prospective observational study included 62 patients with IBD (49 with ulcerative colitis and 13 with Crohn's) and anemia. Patients were divided into Group I (no or minimal endoscopic signs of disease activity and IDA), Group II (moderate and major endoscopic signs of disease activity and mild ACD), and Control group (10 patients with IBD in remission, without anemia). We assessed the difference among groups in the levels of CRP, hemoglobin (Hgb), serum iron, ferritin, hepcidin-25, interleukins, TNF-α, IFN-γ, soluble CD40 ligand, and sP-selectin. Hepcidin-25 levels were significantly higher in Group II versus Group I (11.93 vs. 4.48 ng/mL, p < 0.001). Ferritin and CRP values showed similar patterns in IBD patients: significantly higher levels were observed in Group II (47.5 ng/mL and 13.68 mg/L) than in Group I (11.0 ng/mL and 3.39 mg/L) (p < 0.001). In Group II, hepcidin-25 was positively correlated with ferritin (ρ = 0.725, p < 0.001) and CRP (ρ = 0.502, p = 0.003). Ferritin was an independent variable influencing hepcidin-25 concentration in IBD patients, regardless of disease activity and severity of anemia. IBD hepcidin-25 best correlates with ferritin, and both parameters reflected inflammation extent and IBD activity.

Freiburg personality inventory in inflammatory bowel disease: diagnosis and psychotherapeutic needs / Inventario de personalidad de Freiburg en la enfermedad inflamatoria intestinal: diagnóstico y necesidades psicoterapéuticas

A pesar de los descubrimientos recientes, los pacientes con enfermedad inflamatoria intestinal (EII) aún enfrentan desafíos para lograr la remisión. Los objetivos del estudio fueron identificar las características de los pacientes con el Inventario de Personalidad de Freiburg y la intensidad de la enfermedad colónica, comorbilidades que podrían estar relacionadas con la personalidad de los sujetos. Los datos se recopilaron en el período 2019-2020 de 46 pacientes y utilizaron métodos no paramétricos. En comparación con el grupo de control, las escalas de Inhibición, Problemas de salud y Emocionalidad tenían puntuaciones brutas significativamente más altas. Las escalas de Orientación Social, Franqueza y Extraversión tuvieron puntajes brutos significativamente más bajos. El estado de salud fue un factor médico que influyó en la escala de Quejas Somáticas, los pacientes que tenían lesiones o comorbilidades tenían puntuaciones brutas significativamente más altas. Los pacientes que tenían comorbilidades además de la EII tenían puntuaciones brutas considerablemente más altas en la escala de Excitabilidad. Se requieren intervenciones psicoterapéuticas de cambio en la percepción de la vida para abordar la descripción del sufrimiento subjetivo relacionado con molestias físicas (escala de quejas somáticas), una fuerte orientación hacia el rendimiento (escala de tensión), cambios de humor, ansiedad y pesimismo (escala de emocionalidad). Otra intervención es la reconsideración y (re)priorización de valores, como la familia, las relaciones íntimas, los amigos, la salud, el crecimiento, el desarrollo, el trabajo equilibrado, todos los cuales pueden promover una sensación de bienestar y equilibrio.(AU)

Despite recent discoveries, patients with inflammatory bowel disease (IBD) still face challenges with attainment of remission. The objectives of the study were to identify the characteristics of patients with the Freiburg Personality Inventory and the intensity of the intestinal disease, comorbidities that could be related to the personality of the subjects. Data were collected in the period 2019–2020 from 46 patients and used nonparametric methods. Compared to the normative sample, the Inhibitedness, Health Concerns, and Emotionality scales had significantly higher raw scores. The Social Orientation, Frankness, and Extraversionscales had significantly lower raw scores. Health status was a medical factor that influenced the Somatic Complaintsscale, patients who had lesions or comorbidities had significantly higher raw scores. Patients who had comorbidities in addition to IBD had considerably higher raw scores on the Excitability scale. Psychotherapeutic change interventions regarding life perception are required to tackle the description of subjective suffering related to physical inconveniences (Somatic Complaintsscale), a strong orientation toward performance (Strainscale), mood swings, anxiety, and pessimism (Emotionality scale). Another intervention is reconsidering values and (re) prioritization, such as family, intimate relationships, friends, health, growth, development, balanced work, all of which can promote a feeling of well-being and balance.(AU)

Infantile inflammatory bowel disease in three Syrian infants: a case series.

BACKGROUND: Inflammatory bowel diseases, consisting of Crohn's disease and ulcerative colitis, are chronic bowel relapsing inflammatory disorders. Inflammatory bowel diseases begin rarely in infants. Approximately 25% of patients with inflammatory bowel diseases present before the age of 20 years. Very early-onset inflammatory bowel disease occurs before the age of 6 years; infantile inflammatory bowel diseases occurs before the age of 2 years, and is extremely rare in infants under 1 year of age. CASE PRESENTATION: Herein, we report a case series of 7-month-, 11-month-, and 12-month-old Syrian infants that presented with diarrhea, hematochezia, and pale appearance and were finally diagnosed with infantile inflammatory bowel disease and treated. CONCLUSIONS: Early diagnosis and ruling out infantile inflammatory bowel diseases despite its rarity are recommended. Over and above that, new drugs such as vedolizumab, golimumab, and less invasive treatment methods should also be taken into consideration for better response and adequate remission with improved quality of life.

Diagnosis change in pediatric inflammatory bowel disease.

OBJECTIVES: This study aims to characterize pediatric inflammatory bowel disease (IBD) patients who change diagnosis and describe the characteristics of that change. METHODS: A retrospective study was conducted on pediatric IBD patients from the ImproveCareNow (ICN) multicenter international cohort from 2007 to January 2019. Primary outcome was change in diagnosis after the first four visits. Other variables included demographics, diagnostics, disease characteristics, and timing. RESULTS: 6.1% of 18,055 patients aged 1-20 years changed diagnosis. Median time between the baseline visit and first diagnosis change was 0.9 years. Change in diagnosis occurred in 257/12,178 (2.1%) patients with Crohn's disease (CD), 347/4758 (7.3%) patients with ulcerative colitis (UC), and 495/1119 (44.2%) patients with IBD-Unclassified (IBD-U). In multivariable analysis, initial diagnosis of IBD-U and longer follow-up times were associated with greater odds of a diagnosis change. CONCLUSION: IBD-U initial diagnosis and longer follow-up were associated with increased diagnosis change risk. The most common change was reclassification to CD. Disease activity, moderate malnutrition, and presence of EIMs were not associated with change in diagnosis.

Gastrointestinal Ostomies in Children: A Primer for the Pediatrician.

Despite the advancement of medical therapies in the care of the preterm neonate, in the management of short bowel syndrome and the control of pediatric inflammatory bowel disease, the need to create fecal ostomies remains a common, advantageous treatment option for many medically complex children.

Inflammatory Bowel Diseases and Non-Alcoholic Fatty Liver Disease: Piecing a Complex Puzzle Together.

Inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis, are systemic and multifaceted disorders which affect other organs in addition to the gastrointestinal tract in up to 50% of cases. Extraintestinal manifestations may present before or after IBD diagnosis and negatively impact the intestinal disease course and patients' quality of life, often requiring additional diagnostic evaluations or specific treatments. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Current evidence shows an increased prevalence of NAFLD (and its more advanced stages, such as liver fibrosis and steatohepatitis) in IBD patients compared to the general population. Many different IBD-specific etiopathogenetic mechanisms have been hypothesized, including chronic inflammation, malabsorption, previous surgical interventions, changes in fecal microbiota, and drugs. However, the pathophysiological link between these two diseases is still poorly understood. In this review, we aim to provide a comprehensive overview of the potential mechanisms which have been investigated so far and highlight open issues still to be addressed for future studies.

GC-MS with Headspace Extraction for Non-Invasive Diagnostics of IBD Dynamics in a Model of DSS-Induced Colitis in Rats.

Inflammatory bowel diseases are extremely common throughout the world. However, in most cases, it is asymptomatic at the initial stage. Therefore, it is important to develop non-invasive diagnostic methods that allow identification of the IBD risks in a timely manner. It is well known that gastrointestinal microbiota secrete volatile compounds (VOCs) and their composition may change in IBD. We propose a non-invasive method to identify the dynamics of IBD development in the acute and remission stage at the level of VOCs in model of dextran sulfate sodium (DSS) with chemically induced colitis measured by headspace GC/MS (HS GC/MS). Methods: VOCs profile was identified using a headspace GC/MS (HS GC/MS). GC/MS data were processed using MetaboAnalyst 5.0 and GraphPad Prism 8.0.1 software. The disease activity index (DAI) and histological method were used to assess intestinal inflammation. The peak of intestinal inflammation activity was reached on day 7, according to the disease activity index. Histological examination data showed changes in the intestine due to different stages of inflammation. As the acute inflammation stage was reached, the metabolomic profile also underwent changes, especially at the short-fatty acids level. A higher relative amounts of acetic acid (p value < 0.025) and lower relative amounts of propanoic acid (p value < 0.0005), butanoic acid (p value < 0.005) and phenol 4-methyl- (p value = 0.053) were observed in DSS7 group on day 7 compared to the control group. In remission stage, disease activity indexes decreased, and the histological picture also improved. But metabolome changes continued despite the withdrawal of the DSS examination. A lower relative amounts of propanoic acid (p value < 0.025), butanoic acid (p value < 0.0005), pentanoic acid (p value < 0.0005), and a significant de-crease of hexanoic acid (p value < 0.0005) relative amounts were observed in the DSS14 group compared to the control group on day 14. A model of DSS-induced colitis in rats was successfully implemented for metabolomic assessment of different stages of inflammation. We demonstrated that the ratios of volatile compounds change in response to DSS before the appearance of standard signs of inflammation, determined by DAI and histological examination. Changes in the volatile metabolome persisted even after visual intestine repair and it confirms the high sensitivity of the microbiota to the damaging effects of DSS. The use of HS GC/MS may be an important addition to existing methods for assessing inflammation at early stages.

An Evaluation of the Usefulness of Selected Screening Methods in Assessing the Risk of Malnutrition in Patients with Inflammatory Bowel Disease.

The aim of this study was to assess the prevalence of malnutrition risk in patients with IBD using different scales to evaluate their usefulness as first-step screening tools for the diagnosis of malnutrition using the GLIM criteria in patients with inflammatory bowel disease. This study included 82 patients with IBD. The Mini Nutritional Assessment, Malnutrition Universal Screening Tool, Saskatchewan IBD-Nutrition Risk and Malnutrition Screening Tool were used to assess malnutrition risk in the study group. In order to diagnose malnutrition, the GLIM criteria were used. According to the GLIM recommendations, malnutrition was diagnosed in 60 patients with IBD (73.17%). Depending on the applied screening tools, the prevalence of moderate and/or high-risk malnutrition in patients with IBD ranged from 20.25% to 43.59%. The highest level of accuracy (ACC) was noted for the MST and MUST questionnaires (92.50% and 90%, respectively), followed by the SASKIBD-NR test (89.97%) and the MNA questionnaire (83.33%). The results of our study indicate a high prevalence of malnutrition in patients with IBD. Thus, there is a need to conduct routine assessments of malnutrition risk using validated scales. The MUST scale seems promising in the assessment of malnutrition risk in patients with IBD as a first step in the assessment of malnutrition using the GLIM criteria.

Epstein-Barr virus associated colitis in kidney transplant patients: a case series.

BACKGROUND: Gastrointestinal complications are common in kidney transplant (KT) patients and can be a consequence of the chronic use of immunosuppression. The differential diagnosis of colitis in KT patients includes intolerance to immunosuppressive agents, namely mycophenolate mofetil, de novo inflammatory bowel disease (IBD) and opportunistic infections. Epstein-Barr virus (EBV) infection may cause post-transplant colitis or trigger de novo IBD, although is seldom thought as the causative pathogen. OBJECTIVES: To describe clinical characteristics, endoscopic and histological findings, treatment and outcome of three patients that developed EBV associated colitis following kidney transplantation. METHODS: We retrospectively analyzed three patients with EBV associated colitis; clinical data including transplantation, gastrointestinal symptoms, endoscopy findings, and follow-up data was obtained. RESULTS: We present a case series of three patients with EBV colitis following KT, with an average age at clinical presentation of 59 years and elapsed time since the KT ranging from five to 22 years. Clinical manifestations included bloody diarrhoea, abdominal pain, weight loss and/or fever. Cytomegalovirus colitis, mycophenolate mofetil-related colitis, lymphoproliferative disease and graft versus host disease were excluded. One patient had a prior diagnosis of IBD. Two of the three patients had an unfavourable outcome with death despite reduction and/or switching of immunosuppressants, optimal medical treatment (including antiviral and intravenous immunoglobulin therapies) and salvage surgical therapy. CONCLUSION: A multidisciplinary approach is necessary to allow an expeditious diagnosis of a rare entity such as EBV associated colitis in KT. Long-term surveillance of these patients and the development of effective and safe therapies is essential.

Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach.

Background: Understanding the molecular pathogenesis of inflammatory bowel disease (IBD) has led to the discovery of new therapeutic targets that are more specific and effective. Our aim was to explore the molecular pathways and genes involved in IBD pathogenesis and to identify new therapeutic targets and novel biomarkers that can aid in the diagnosis of the disease. Methods: To obtain the largest possible number of samples and analyze them comprehensively, we used a mega-analysis approach. This involved reprocessing raw data from multiple studies and analyzing them using bioinformatic and machine learning techniques. Results: We analyzed a total of 697 intestinal biopsies of Ulcerative Colitis (n = 386), Crohn's disease (n = 183) and non-IBD controls (n = 128). A machine learning analysis detected 34 genes whose collective expression effectively distinguishes inflamed biopsies of IBD patients from non-IBD control samples. Most of these genes were upregulated in IBD. Notably, among these genes, three novel lncRNAs have emerged as potential contributors to IBD development: ENSG00000285744, ENSG00000287626, and MIR4435-2HG. Furthermore, by examining the expression of 29 genes, among the 34, in blood samples from IBD patients, we detected a significant upregulation of 12 genes (p-value < 0.01), underscoring their potential utility as non-invasive diagnostic biomarkers. Finally, by utilizing the CMap library, we discovered potential compounds that should be explored in future studies for their therapeutic efficacy in IBD treatment. Conclusion: Our findings contribute to the understanding of IBD pathogenesis, suggest novel biomarkers for IBD diagnosis and offer new prospects for therapeutic intervention.

Long noncoding RNAs and circular RNAs as potential diagnostic biomarkers of inflammatory bowel diseases: a systematic review and meta-analysis.

Introduction: Inflammatory bowel disease (IBD) poses a growing global burden, necessitating the discovery of reliable biomarkers for early diagnosis. The clinical significance of dysregulated expression of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in diagnosing IBD has not been well established. Thus, our study aimed to investigate the diagnostic value of lncRNAs and circRNAs for IBD based on currently available studies. Methods: A comprehensive search was carried out in diverse electronic databases, such as PubMed, Embase, Scopus, Science Direct and Wiley Online Library to retrieve articles published until October 30, 2023. Stata 17.0 software was employed to determine pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), and area under the curve (AUC). Heterogeneity, subgroup analysis, and meta-regression were explored, and publication bias was assessed using Deeks' funnel plot. Fagan's nomogram and likelihood ratio scattergram were employed to evaluate the clinical validity. Result: A total of 11 articles encompassing 21 studies which involved 1239 IBD patients and 985 healthy controls were investigated. The findings revealed lncRNAs exhibit high level of pooled sensitivity 0.94 (95% CI: 0.87-0.97) and specificity 0.99 (95% CI: 0.89-1.00), along with PLR, NLR, DOR, and AUC values of 64.25 (95% CI: 7.39-558.66), 0.06 (95% CI: 0.03-0.13), 1055.25 (95% CI: 70.61-15770.77), and 0.99 (95% CI: 0.97-0.99), respectively. Conversely, CircRNAs showed moderate accuracy in IBD diagnosis, with sensitivity of 0.68 (95% CI: 0.61-0.73), specificity of 0.73 (95% CI: 0.65-0.79), PLR of 2.47 (95% CI: 1.94-3.16), NLR of 0.45 (95% CI: 0.38-0.53), DOR of 5.54 (95% CI: 3.88-7.93), and AUC value of 0.75 (95% CI: 0.71-0.79). Moreover, findings from subgroup analysis depicted heightened diagnostic efficacy when employing lncRNA H19 and a large sample size (≥100), with notable efficacy in diagnosing both ulcerative colitis (UC) and Crohn's disease (CD). Conclusion: LncRNAs exhibit high diagnostic accuracy in distinguishing patients with IBD from healthy controls signifying their possible use as potential biomarkers, while circRNAs showed moderate diagnostic accuracy. Nevertheless, to validate our findings and confirm the clinical utility of lncRNAs and circRNAs in IBD diagnosis, a large pool of prospective and multi-center studies should be undertaken. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023491840.

Associations between immune biomarkers and symptoms of anxiety, depression, and insomnia in paediatric inflammatory bowel disease: A preliminary longitudinal analysis.

Innate immunity may influence the onset of affective symptoms and alter sleep patterns in chronic inflammatory conditions. Here, we tested the prospective associations between baseline serum C-reactive protein (CRP), albumin, and CRP/albumin ratio (CAR, i.e., an emerging biomarker of disease activity), and self-reported symptoms of anxiety, depression, and insomnia at 1-year follow up in paediatric inflammatory bowel disease (n = 17). After controlling for baseline values, CAR (ρ = 0.591, p = 0.026) predicted anxiety symptoms, while albumin predicted both anxiety (ρ = -0.687, p = 0.007) and insomnia symptoms (ρ = -0.648, p = 0.012). Current findings preliminarily suggest that inflammation may influence anxiety and sleep disturbance in paediatric IBD.

Clinical features of inflammatory bowel disease unclassified: a case-control study.

BACKGROUND: Approximately 10-15% of inflammatory bowel disease (IBD) patients with overlapping features of ulcerative colitis (UC) and Crohn's disease (CD) are termed as inflammatory bowel disease unclassified (IBDU). This study aimed to describe the clinical features of IBDU and evaluate the potential associated factors of reclassification. METHODS: The clinical data of 37 IBDU patients were retrospectively analyzed from November 2012 to November 2020. 74 UC and 74 CD patients were randomly selected and age- and sex-matched with the 37 IBDU patients. Clinical characteristics were compared between the three patient groups. Potential factors associated with the IBDU reclassification were evaluated. RESULTS: 60% of IBDU patients displayed rectal-sparing disease, and 70% of them displayed segmental disease. In comparison to UC and CD, the IBDU group demonstrated higher rates of gastrointestinal bleeding (32.4%), intestinal perforation (13.5%), spontaneous blood on endoscopy (51.4%), and progression (56.8%). The inflammation proceeded relatively slowly, manifesting as chronic alterations like pseudopolyps (78.4%) and haustra blunt or disappearance (56.8%). 60% of IBDU patients exhibited crypt abscess, and 16.7% of them exhibited fissuring ulcers or transmural lymphoid inflammation. The proportions of IBDU patients receiving immunosuppressants, surgery, and infliximab were basically the same as those of CD patients. During the 79 (66, 91) months of follow-up, 24.3% of IBDU patients were reclassified as UC, while 21.6% were reclassified as CD. The presence of intestinal hemorrhaging was associated with CD reclassification, while hypoalbuminemia was associated with UC reclassification. CONCLUSIONS: IBDU may evolve into UC or CD during follow-up, and hemorrhage was associated with CD reclassification. Different from the other two groups, IBDU exhibited a more acute onset and a gradual progression. When an IBD patient presents with transmural inflammation or crypt abscess but lacks transmural lymphoid aggregates or fissuring ulcers, the diagnosis of IBDU should be considered.

Home-based fecal calprotectin utilization in a general pediatric gastroenterology clinic.

OBJECTIVE: Remote investigation and monitoring have gained importance in ambulatory practice. A home-based fecal calprotectin (FC) test has been developed where the sample is processed and analyzed at home through a smartphone application. We aimed to assess the use of standard ELISA (sFC) versus home-based (hFC) FC testing in a general pediatric gastroenterology clinic. METHODS: Ambulatory pediatric patients with hFC or sFC performed between August 2019 and November 2020 were included. Data regarding demographics, clinical characteristics, medication use, investigations, and final diagnosis, categorized as inflammatory bowel disease (IBD), functional gastrointestinal (GI) disorders, organic non-IBD (ONI) GI disorders, non-GI disorders, and undetermined after 6 months of investigation, were recorded. RESULTS: A total of 453 FC tests from 453 unique patients were included. Of those, 249 (55%) were hFC. FC levels (median) were higher in children with IBD compared to non-IBD diagnosis (sFC 795 vs. 57 µg/g, hFC 595 vs. 47 µg/g, p < 0.001), and in ONI compared to functional GI disorders (sFC 85 vs. 54 µg/g, p = 0.003, hFC 57 vs. 40 µg/g, p < 0.001). No significant difference was observed between different ONI GI disorders or subtypes of functional disorders. Age did not significantly influence levels. CONCLUSIONS: Overall, hFC and sFC provide similar results in the general pediatric GI ambulatory setting. FC is a sensitive but not disease-specific marker to identify patients with IBD. Values appear to be higher in ONI GI disorders over functional disorders, although cut-off values have yet to be determined.