Pediatric Inflammatory Bowel Disease Patients Research Articles

Diagnostic utility, disease activity, and disease phenotype correlation of serum ASCA, pANCA, and PR3-ANCA in pediatric inflammatory bowel disease

ObjectiveThis study aimed to evaluate the diagnostic utility, disease activity, and phenotypic association of serum anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), PR3-ANCA, and MPO-ANCA in pediatric patients with inflammatory bowel disease (IBD). MethodsPediatric patients diagnosed with IBD were recruited and classified as Crohn's disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBD-U) through full investigation. The Paris classification was used to evaluate disease phenotypes of pediatric CD and UC. ResultsIn all, 229 pediatric patients with IBD (CD 147, UC 53, IBD-U 29) were included. The ASCA IgG seropositivity significantly differed among the three groups (CD 75.4%, UC 17.5%, and IBD-U 60.0%; p < 0.001). PR3-ANCA positive rates were the highest in UC (24.0%), followed by IBD-U (17.6%), and none in CD (p = 0.002); pANCA-positive rates were higher in IBD-U (33.6%), followed by UC (28.0%) than in CD (1.4%) (p < 0.001). Regarding disease phenotype, perianal disease revealed higher serum ASCA IgG titers (median 36.7 U/mL in P1 vs. 25.2 U/mL in P0, p = 0.019). Serum ASCA IgG and IgA cutoff values to distinguish CD were 32.7 (U/mL) and 11.9 (U/mL), respectively, with a specificity of 80.0%. ConclusionSerological biomarkers of ASCA IgG and IgA were effective for differentiating CD in pediatric IBD patients, and serum pANCA and PR3-ANCA, but not MPO-ANCA, were effective in distinguishing UC and IBD-U. Furthermore, measuring serological titers of ASCA IgG and IgA may help differentiate CD and evaluate the disease activity and phenotype of pediatric IBD in practice.

Clinical Outcome of Neutropenic Colitis in Neutropenic Colitis in Pediatric Patients with Pediatric Patients with Leukemia in a Third Level Leukemia in a Third Level Hospital in Mexico Hospital in Mexico

Abstract Objectives To know the incidence and number of To know the incidence and number of patients with complications of patients with complications of neutropenic colitis. neutropenic colitis. Study type and design Descriptive, cross-sectional and retrospective study during the period retrospective study during the period from June 2018 to May 2021. from June 2018 to May 2021. Material and methods In a third level hospital where the In a third level hospital where the population is adults and pediatric in population is adults and pediatric in Mexico city, data were obtained of Mexico city, data were obtained of clinical records of pediatric patients clinical records of pediatric patients with hematological cancer aged 1 to 17 with hematological cancer aged 1 to 17 years of both genders with clinical years of both genders with clinical data of neutropenic colitis. data of neutropenic colitis. For the calculation of the sample, the For the calculation of the sample, the Epi Info program was used with the Epi Info program was used with the formula for descriptive studies and 59 formula for descriptive studies and 59 files are required. Results Total patients 75, male 56%, patients with ALL 87%, the majority of patients had fever and pain 91%, we found ultrasound positive with colitis en 93%, the majority of patients had treatment with cytarabine and methotrexate 60%, the initial treatment for neutropenic colitis was cefepime/metronidazole in 40%, the average days of treatment was 12 days, complications was found in 31%, and the recovery of patients was 100%. Conclusion Patients who are managed with antimetabolites Patients who are managed with antimetabolites have a 10 times greater risk of presenting have a 10 times greater risk of presenting sepsis. sepsis. The main etiological agents continue to be gram The main etiological agents continue to be gram negative microorganisms. negative microorganisms. Despite severe neutropenia, no increase in Despite severe neutropenia, no increase in sepsis was observed. sepsis was observed. It is important to take into account the It is important to take into account the chemotherapy scheme to detect early patients chemotherapy scheme to detect early patients who may be at risk of presenting a complication. who may be at risk of presenting a complication. 13% presented septic shock, however, there 13% presented septic shock, however, there were no reported deaths.

Frequency of hepatitis C virus infection in patients with pediatric inflammatory bowel disease: a cross-sectional study

BackgroundPatients with pediatric inflammatory bowel disease (PIBD) are believed to be at higher risk of hepatitis C virus (HCV) infection not only due to using of immunosuppressive drugs but also because of repeated blood transfusion and endoscopic and other invasive procedures used for diagnoses and effective controlling of the disease, so this study aimed to assess the frequency of HCV infection, in patients with PIBD at the New Children’s Hospital, Cairo University, and identify the potential risk factors.MethodsThis cross-sectional analytic study included 165 IBD patients between 1 and 16 years old of both sexes who were attending the Pediatric Gastroenterology Clinic in the New Children’s University Hospital, Cairo University. All patients were screened for anti-HCV antibodies using ELISA. Factors related to IBD (severity, modalities of the treatment, and invasive procedures), to infection (blood transfusion history and family history of hepatitis), and liver enzymes were registered. The risk factors were evaluated by multivariate logistic regression analysis.ResultsPresent and/or past HCV infection was found in five (3%) of the IBD patients. The multivariate logistic regression to detect independent predictors of HCV +ve antibodies patients had statistically significant value with number of hospital admission related to IBD with p-value = 0.002, odd ratio (OR) = 1.467, and confidence interval (CI) = 95% (1.145–1.879) and with number of hospital admission unrelated to IBD with p-value = 0.024, OR = 0.750, and CI 95% (0.585–0.963).ConclusionThe frequency of HCV infection in PIBD patients was 3%. Thus, the frequency of HCV infection in PIBD patients is similar to that in the normal population of the developing countries, and it is strongly related to hospital admission due to IBD or non-IBD causes.

Serum cytokines MCP-1 and GCS-F as potential biomarkers in pediatric inflammatory bowel disease.

Inflammatory bowel diseases (IBDs) with the subtypes ulcerative colitis (UC) and Crohn disease (CD), are chronic autoimmune inflammatory disorders of the gastrointestinal tract. Cytokines are associated with the development and progression in pediatric IBD. We measured cytokine levels in pediatric IBD patients to assess their potential function as biomarkers in disease assessment. In this prospective cohort study, we enrolled 33 children with IBD. All patients were in stable remission for 3 months on enrollment. Patients who developed a relapse within six months after enrollment were classified as relapsers. Blood sampling was performed at enrolment and for relapsers in relapse and post-relapse. Serum concentrations of 14 cytokines, chemokines and growth factors (IL-1α, IL-1β, IL-6, IL-12p40, IP-10, TNF-α, IFN-γ, IL-10, IL-8, MIP-1α, MCP-1, MCP-3, G-CSF, GM-CSF) were measured simultaneously using multiplex bead-based sandwich immunoassay on Luminex 100 system. MCP-1 was significantly higher in CD patients compared to UC patients at each disease stage: stable remission (P<0.048), unstable remission (P<0.013), relapse (P<0.026) and post-relapse (P<0.024). G-CSF was significantly increased in UC patients developing a relapse and in post-relapse stage compared to UC patients in remission (P<0.02 and p<0.03, respectively). MCP-1 showed potential as a diagnostic biomarker in CD patients independent of disease activity as it was able to discriminate between subtypes of pediatric IBD. In UC patients, G-CSF was significantly elevated in relapsers indicating its use and role as a potential prognostic biomarker.

Retrospective Assessment of an Adalimumab Model-Informed Precision Dosing Support Tool for Use in Pediatric Inflammatory Bowel Disease.

Therapeutic drug monitoring in pediatric inflammatory bowel disease (IBD) has been used to achieve and maintain remission. Few guidelines exist to aid clinicians in the adjustment of anti-tumor necrosis factor therapies. The objective was to assess the agreement between real-world postinduction and posteriori analysis of retrospective data, using 2 novel pharmacokinetic (PK) models for adalimumab. A retrospective chart review was conducted in pediatric IBD patients treated with adalimumab. A Bayesian clinical decision support tool (InsightRX) was used. Postinduction serum concentration measurements of adalimumab were performed by drug-tolerant, homogenous shift mobility assay. Predicted serum adalimumab concentrations from both models were compared to the actual serum concentrations through a Bland-Altman analysis. Paired sample t test was used for equivalence. A total of 47 patients were included. Forty-one patients (87%) had Crohn disease, and 30 (64%) were male. Most were induced with 160 mg of adalimumab and maintained on 40 mg biweekly. No significant difference resulted between the de Klaver average prediction and mean population concentration (p = 0.294). Significant difference was observed between Ternant and mean population serum adalimumab concentration (p < 0.001). The Bland-Altman plot for the de Klaver method showed no proportional bias. Additionally, 49% of patients required a dose adjustment during maintenance therapy. The de Klaver model was able to provide less bias than the Ternant model and may aid in predicting serum adalimumab concentrations. Approximately half of the patients required dose adjustment during maintenance therapy to obtain a therapeutic drug concentration or achieve clinical remission.

Depression symptoms increase the risk for initiation or switching to biologic therapy in pediatric inflammatory bowel disease patients in remission

Background and aimsAnxiety and depression symptoms are common in IBD population, both adult and pediatric patients. Increased psychological distress might contribute to initiation and switching to biologic therapy in adult patients with IBD or other chronic inflammatory diseases. Aim of the present study are to evaluate anxiety and depression symptoms in IBD pediatric patients with disease remission and investigate their role in initiation or switching to biologic therapy.MethodsWe performed a retrospective analysis on IBD pediatric patients, assessing for anxiety (GAD-7) and depression (PHQ-9) symptoms. Demographic and disease characteristics were obtained from medical records.ResultsEighty-six patients [31 (36%) females - mean age = 15.6 (SD = 2.8) years] were included. Patients scored above cut-off (> 10) on PHQ-9 and GAD-7 were 17 (19.7%) and 18 (20.9%), respectively. No differences were found between UC and CD patients. Baseline clinically relevant depression symptoms were significantly associated with the odds of initiating or switching to biologic therapy within 2 years [OR = 4.5 (1.4–14.3)], even after confounders adjustment [4.2 (1.2–14.9)]. Relationship was not significant with anxiety symptoms.ConclusionAnxiety and depression symptoms is relatively common in pediatric IBD population, even with disease remission. Pediatric IBD patients with high depression symptoms are at increased risk of initiating or switching to biologic therapy. Mental health screening programs should be incorporated in routine clinical practice, especially for depression, regardless of disease activity and disease type. Early diagnosis and proper intervention for mental illness should be part of routine IBD management.

Characteristics of the Inflammatory Bowel Disease in Children: A Croatian Single-Centre Retrospective Study.

Inflammatory bowel diseases (IBDs), encompassing ulcerative colitis (UC) and Crohn's disease (CD), are chronic gastrointestinal disorders often diagnosed in youth, presenting unique features compared to adult-onset cases. We aimed to profile pediatric IBD patients in Croatia through a retrospective analysis of children up to 18 years old diagnosed with IBD at the University Hospital of Split from 1 January 2012, to 31 December 2021, utilizing data collected during hospitalization for diagnosis. Over a decade, 107 children were diagnosed, with 43.9% having UC, 55.1% CD, and 0.9% IBD-unclassified. Median age at diagnosis was 14.1 years, with UC patients being older (14.8 vs. 13.7 years, p = 0.044). Males constituted 60.7% of patients. Median symptom duration was 2.0 months, with CD patients experiencing a longer diagnostic delay (3.0 vs. 2.0 months, p = 0.003). The median incidence rate was 9.89 (95% CI 5.93-13.84) per 100,000 children/year, varying across age groups. Median (IQR) BMI z-score was -0.34 (-0.97-0.45). Common symptoms included diarrhea (60.7%) and abdominal pain (50.5%), with rectal bleeding more prevalent in UC (72.3% vs. 32.2%, p < 0.001). While our study offers valuable insights into pediatric IBD in Croatia, further prospective research is needed to clarify disease progression and development.

Growth hormone use in pediatric inflammatory bowel disease.

Impaired linear growth is a known complication of pediatric inflammatory bowel disease (IBD), but theuse of growth hormone (GH) in this population is not well-described. The primary aim of this study is to determine whether growth hormone use in pediatric IBD leads to improved height outcomes. This was a retrospective chart review of patients with IBD aged 0-21 years followed at a single center between 2018 and 2021 treated with at least 1 year of GH. Records collected included demographics, IBD phenotype, IBD disease activity scores, medications, weight z-score, height z-score, bone age, and details of GH therapy including testing for GH deficiency. The primary outcome measure was change in height z-score after 1 year of GH treatment. Forty-six patients were identified and 18 were excluded. Of the 28 patients included (7 female; 25.0 %), 26 (92.9 %) had a diagnosis of Crohn's disease (CD) and 2 (7.1 %) had ulcerative colitis (UC). The mean (SD) age at GH initiation was 9.6 (3.4) years. Among all participants, there was a significant mean difference in height z-score from baseline to 1 year on therapy (-2.25 vs.-1.50, respectively; difference, 0.75; 95 % CI, 0.56 to 0.94; p<0.001). Among the 19 subjects thatcompleted GH therapy there was a significant mean difference between baseline and final height z-scores (-2.41vs.-0.77, respectively; difference, 1.64; 95 % CI, 1.30 to 1.98; p<0.001). GH use was associated with improved height outcomes. The pediatric IBD patients in this cohort had significant improvements in height z-scores both after one year on therapy and at completion of GH therapy.

A Multifaced Aspect of Clostridium difficile Infection in Pediatric Patients with Inflammatory Bowel Disease: Case Series and Literature Review.

Children with inflammatory bowel disease (IBD) have an increased susceptibility to Clostridium difficile infection (CDI), with a rising incidence over time. Differentiating between CDI and IBD exacerbation is challenging due to overlapping symptoms. In our cohort of 55 pediatric IBD patients, 6 were diagnosed with CDI. Upon conducting a thorough patient evaluation and subsequent data analysis, an exhaustive review of the existing literature was undertaken. CDI is more prevalent in ulcerative colitis (UC) than Crohn's disease (CD) patients, as seen in our patients and in the existing literature. The management of a pediatric patient with IBD is itself a challenge for a clinician because of the chronic, possibly relapsing course, and substantial long-term morbidity. When CDI is added, it becomes even more demanding, since CDI leads to more severe disease in children with IBD. A multidisciplinary approach and intensive treatment for possible sepsis, anemia, hypoalbuminemia, and hydro-electrolytic and acid-base imbalances are frequently mandatory in patients with CDI and IBD, which leads to a significant health care burden in hospitalized children with IBD. After the infection is treated with antibiotic therapy, important considerations regarding the future treatment for the underlying IBD are also necessary; in most cases, a treatment escalation is required, as also seen in our study group.

Precision Dosing of Anti-TNF Therapy in Pediatric Inflammatory Bowel Disease.

This review focuses on recent advancements in anti-TNF therapeutic drug monitoring (TDM), pharmacogenetics and personalized drug selection for children with inflammatory bowel disease (IBD). Several real-world studies and one clinical trial in children have demonstrated that proactive TDM, targeting higher exposure concentrations (> 5µg/mL), can improve disease remission rates and enhance durability of the anti-TNF biologics. Recent data from both adult and pediatric IBD patients have revealed an association between a genetic polymorphism (HLA-DQA1*05) and the development of auto-drug antibodies. The impact of this association on clinical outcomes, considering more routine use proactive TDM and dose optimization in children, is still under investigation. Additionally, recent studies have identified potential inflammatory signatures and biomarkers that may serve as companion diagnostics for anti-TNF biologics. The effective management of anti-TNF therapies in children with IBD requires evidence-based precision dosing strategies, including routine TDM and proactive pharmacodynamic assessments.

The Role of Noninvasive Surrogates of Inflammation in Monitoring Pediatric Inflammatory Bowel Diseases: The Old and the New.

Effectiveness of limited available therapies for pediatric inflammatory bowel disease has reached stagnation. Previous non-invasive monitoring strategies have relied upon cumbersome tools to evaluate clinical symptoms and biochemical markers that do not reflect endoscopic activity or respond quickly to treatments. Novel, patient-centric, and highly accurate, monitoring strategies with a focus on intestinal ultrasound for a direct, precise monitoring of activity to achieve disease modification are now possible. Ultimately, research on the optimal tight control monitoring strategies, individualized to each pediatric inflammatory bowel disease patient, are in development and offer a hope to potential therapeutic ceiling breakthrough on the horizon.

Clinical characteristics and nursing diagnoses of pediatric patients hospitalized with inflammatory bowel disease: a single-center retrospective study in South Korea.

This study aimed to identify clinical characteristics of South Korean pediatric inflammatory bowel disease (IBD) in a children's hospital over the past 5 years, with a specific focus on comparing the features observed between Crohn's disease (CD) and ulcerative colitis (UC). Additionally, it aimed to examine the nursing diagnoses given to patients. This retrospective study analyzed the medical records of Korean pediatric patients under 18 years of age who were diagnosed with IBD and hospitalized at a children's hospital in Seoul, South Korea, from January 2017 to December 2021. The number of pediatric patients diagnosed with IBD steadily increased. This finding was particularly prominent for CD patients, the majority of whom were male. Pediatric patients with CD had significantly higher rates of abdominal pain and perianal lesions, while pediatric patients with UC had a higher rate of bloody stool. Laboratory findings indicated that CD patients had higher levels of inflammatory markers and lower albumin levels than UC patients. The nursing diagnoses given during hospitalization mostly related to safety and protection, physical comfort, and gastrointestinal function. This study provides insights into Korean pediatric IBD patients, enabling early detection and the development of nursing intervention strategies. From a comprehensive perspective, nursing care should not only address patients' physical needs but also their psychosocial needs.

Fatigue and Physical Activity Patterns in Children With Inflammatory Bowel Disease.

Fatigue is a common symptom in children with inflammatory bowel disease (IBD). Diagnostic tests to evaluate biological causes of fatigue commonly include markers of inflammation and hemoglobin (Hb), yet functional parameters have been inadequately studied in pediatric IBD. In this study, we compared fatigued and non-fatigued children with IBD from both a biological and functional point of view. A cross-sectional study of 104 pediatric IBD patients with mild to moderately active IBD was conducted. Fatigued children were defined as those with a Pediatric Quality of Life Inventory Multidimensional Fatigue Scale z score <-2.0. Non-fatigued children had a z score ≥-2.0. Disease-specific quality of life (measured with IMPACT-III score), C-reactive protein (CRP), fecal calprotectin (FC), hemoglobin z score (Hb z score), and physical activity tests including 6-minute walking distance z score (6MWD z score) and triaxial accelerometry (TA) were evaluated. Fatigued children (n = 24) had a significant lower IMPACT-III score than non-fatigued children (n = 80). Hb z scores, CRP, FC, and 6MWD z scores were not significantly different between groups. TA was performed in 71 patients. Wear time validation requirements were met in only 31 patients. Fatigued patients spent significant shorter median time in moderate-to-vigorous activity than non-fatigued patients (18.3 vs 37.3 minutes per day, P = 0.008). Biological parameters did not discriminate fatigued from non-fatigued patients. TA possibly distinguishes fatigued from non-fatigued patients; the potential association may provide a target for interventions to combat fatigue and improve quality of life.

Benefits of Paediatric to Adult Transition Programme in Inflammatory Bowel Disease: The BUTTERFLY Study of GETECCU and SEGHNP.

(1) Background: Transition is a planned movement of paediatric patients to adult healthcare systems, and its implementation is not yet established in all inflammatory bowel disease (IBD) units. The aim of the study was to evaluate the impact of transition on IBD outcomes. (2) Methods: Multicentre, retrospective and observational study of IBD paediatric patients transferred to an adult IBD unit between 2017-2020. Two groups were compared: transition (≥1 joint visit involving the gastroenterologist, the paediatrician, a programme coordinator, the parents and the patient) and no-transition. Outcomes within one year after transfer were analysed. The main variable was poor clinical outcome (IBD flare, hospitalisation, surgery or any change in the treatment because of a flare). Predictive factors of poor clinical outcome were identified with multivariable analysis. (3) Results: A total of 278 patients from 34 Spanish hospitals were included. One hundred eighty-five patients (67%) from twenty-two hospitals (65%) performed a structured transition. Eighty-nine patients had poor clinical outcome at one year after transfer: 27% in the transition and 43% in the no-transition group (p = 0.005). One year after transfer, no-transition patients were more likely to have a flare (36% vs. 22%; p = 0.018) and reported more hospitalisations (10% vs. 3%; p = 0.025). The lack of transition, as well as parameters at transfer, including IBD activity, body mass index < 18.5 and corticosteroid treatment, were associated with poor clinical outcome. One patient in the transition group (0.4%) was lost to follow-up. (4) Conclusion: Transition care programmes improve patients' outcomes after the transfer from paediatric to adult IBD units. Active IBD at transfer impairs outcomes.

Identifying Microbiome Dynamics in Pediatric IBD: More than a Family Matter.

Pediatric inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease that affects both children and adolescents. Symptoms can significantly affect a child's growth, development, and quality of life, making early diagnosis and effective management crucial. This study focuses on treatment-naïve pediatric IBD patients and their immediate families to identify the role of the microbiome in disease onset. Nine families with pediatric IBD were recruited, comprising seven drug-naïve Crohn's disease (CD) patients and two drug-naïve ulcerative colitis (UC) patients, as well as twenty-four healthy siblings/parents. Fecal samples were collected for 16S ribosomal RNA gene sequencing and bioinformatics analysis. We identified patterns of dysbiosis and hallmark microbial taxa among patients who shared ethnic, habitual, and dietary traits with themselves and their families. In addition, we examined the impact of the disease on specific microbial taxa and how these could serve as potential biomarkers for early detection. Our results suggest a potential role of maternal factors in the establishment and modulation of the early life microbiome, consistent with the current literature, which may have implications for understanding the etiology and progression of IBD.

Relationship between disease activity index and sleep disorders in children with inflammatory bowel diseases.

The aim of the study was to assess the prevalence of sleep disturbance in pediatric IBD patients and evaluate the relationship between clinical features of IBD, disease activity, inflammatory markers and quality of sleep. A total of 99 patients who were followed-up with the diagnosis of IBD (44 Crohn's disease (CD), 55 Ulcerative colitis (UC)) between 2015-2020 and 80 healthy controls were enrolled in the study. The clinical and demographic characteristics, laboratory parameters and disease activities were obtained from medical reports retrospectively. Pittsburgh sleep quality index (PSQI) was administered to all participants. PSQI score was significantly higher in patient group than the control group (P < 0.001). The sleep time of patient group, especially patients with UC was later than the control group (P = 0.008). Sleep duration was longer in control group than the patient group (P < 0.001). A positive strong correlation was obtained in disease activity index (r = 0.886; P < 0.001) and abdominal pain (r = 0.781; P < 0.001) with PSQI scores of CD patients. Disease activity index, rectal bleeding, diarrhea and number of stool had statistically significant positive strong correlation with PSQI scores of UC patients (P < 0.001). Pediatric Crohn's disease activity index and Pediatric ulcerative colitis activity index were the only independent risk factors affecting sleep disturbances (80% sensitivity and 91.67% specificity, 93.1% sensitivity and %96.15 specificity, respectively). Conclusion: Increased disease activity has adverse effects on sleep quality. PSQI and PCDAI were strong tests for predicting sleep disorders in pediatric patients with IBD. What is Known: •Sleep disturbances are common complaint in inflammatory bowel disease (IBD), even in clinical remission. •Pittsburgh sleep quality index (PSQI) was used to evaluate the subjective sleep quality of patients. What is New: •PSQI and Pediatric Crohn Disease Activity index (PCDAI) were strong tests for predicting sleep disorders in pediatric patients with IBD. •PSQI and PCDAI scores correlated significantly with the severity of the sleep disturbances.

Bacterial clade-specific analysis identifies distinct epithelial responses in inflammatory bowel disease

Abnormal immune responses to the resident gut microbiome can drive inflammatory bowel disease (IBD). Here, we combine high-resolution, culture-based shotgun metagenomic sequencing and analysis with matched host transcriptomics across three intestinal sites (terminal ileum, cecum, rectum) from pediatric IBD (PIBD) patients (n= 58) and matched controls (n= 42) to investigate this relationship. Combining our site-specific approach with bacterial culturing, we establish a cohort-specific bacterial culture collection, comprising 6,620 isolates (170 distinct species, 32 putative novel), cultured from 286 mucosal biopsies. Phylogeny-based, clade-specific metagenomic analysis identifies key, functionally distinct Enterococcus clades associated with either IBD or health. Strain-specific invitro validation demonstrates differences in cell cytotoxicity and inflammatory signaling in intestinal epithelial cells, consistent with the colonic mucosa-specific response measured in patients with IBD. This demonstrates the importance of strain-specific phenotypes and consideration of anatomical sites in exploring the dysregulated host-bacterial interactions in IBD.

Pediatric IBD patients show medication and disease activity dependent changes in NK cell and CD4 memory T cell populations.

CD4+ memory T cells facilitate long-termed adaptive immune responses while NK cells are predominately rapid effector cells with significant functions for both intestinal homeostasis and inflammation. We wanted to study both populations in health and pediatric inflammatory bowel disease (IBD) and correlate them with disease activity and medication. We performed flow cytometric analyses of peripheral blood CD4 + CD45RO+ memory T cells and CD3-CD16 + CD56+ NK cells in 30 patients with IBD and 31 age-matched controls and correlated percentages of subsets with disease activity (PUCAI/PCDAI) and medication. We found a significant reduction of peripheral NK cells in overall IBD patients with both clinical remission and disease activity, which was even more pronounced in patients treated with azathioprine. Otherwise, circulating CD4+ memory T cell populations were significantly enhanced in active IBD compared to controls. Enhancement of memory T cells was particularly found in new onset disease and correlated with disease activity scores. Our single center cohort confirms previous results showing enhanced memory T cell populations in pediatric IBD patients, which correlate with disease activity scores. CD4+ memory T cells are a relevant pathogenic leukocyte population for disease development and perpetuation in IBD. In addition, we found a decrease of NK cells in IBD patients, which was pronounced by use of azathioprine. Surveillance of both cellular populations could possibly serve as biomarker for therapy control in pediatric IBD.

Educating nurses caring for paediatric inflammatory bowel disease patients receiving biologics: the impact of a virtual event

Background: A virtual educational and networking event took place for registered nurses caring for administering biologic therapy in paediatric Inflammatory Bowel Disease (IBD) patients and their families. The aim was to establish the level of self-reported competencies of the nurses and to evaluate the impact that the event had on them. Methods: Participants were requested to complete an online questionnaire before and after the interprofessional education event. Results: Some 21 pre–event questionnaires were completed. Of these, 81% (17) reported no previous relevant training, 20% (4) did not feel competent in the administration of biologics and patient monitoring and 29% (6) did not feel competent to meet the patient's holistic needs. A total of 13 post-event evaluations were completed. All (13) agreed/strongly agreed with feeling more competent in caring for patients and 84.7% (11) agreed/strongly agreed with feeling more competent in administering and monitoring the biologic therapy. A total of 77% (10) of participants could identify changes to their practice post-event. Conclusion: This study highlighted the need for interprofessional education for nurses caring for paediatric inflammatory bowel disease patients, particularly where care is delivered in district general hospitals. Feedback demonstrated that virtual educational events are effective in raising self-reported nursing competencies and in ensuring high standards of practice.

Gene expression profiling in white blood cells reveals new insights into the molecular mechanisms of thalidomide in children with inflammatory bowel disease

Thalidomide has emerged as an effective immunomodulator in the treatment of pediatric patients with inflammatory bowel disease (IBD) refractory to standard therapies. Cereblon (CRBN), a component of E3 protein ligase complex that mediates ubiquitination and proteasomal degradation of target proteins, has been identified as the primary target of thalidomide. CRBN plays a crucial role in thalidomide teratogenicity, however it is unclear whether it is also involved in the therapeutic effects in IBD patients. This study aimed at identifying the molecular mechanisms underpinning thalidomide action in pediatric IBD. In this study, ten IBD pediatric patients responsive to thalidomide were prospectively enrolled. RNA-sequencing (RNA-seq) analysis and functional enrichment analysis were carried out on peripheral blood mononuclear cells (PBMC) obtained before and after twelve weeks of treatment with thalidomide. RNA-seq analysis revealed 378 differentially expressed genes before and after treatment with thalidomide. The most deregulated pathways were cytosolic calcium ion concentration, cAMP-mediated signaling, eicosanoid signaling and inhibition of matrix metalloproteinases. Neuronal signaling mechanisms such as CREB signaling in neurons and axonal guidance signaling also emerged. Connectivity Map analysis revealed that thalidomide gene expression changes were similar to those exposed to MLN4924, an inhibitor of NEDD8 activating enzyme, suggesting that thalidomide exerts its immunomodulatory effects by acting on the ubiquitin-proteasome pathway. In vitro experiments on cell lines confirmed the effect of thalidomide on candidate altered pathways observed in patients. These results represent a unique resource for enhanced understanding of thalidomide mechanism in pediatric patients with IBD, providing novel potential targets associated with drug response.