Daniela Elena Serban

Background: Crohn’s disease (CD) is characterized by gut microbiota alterations including reduced microbial diversity, loss of commensal species, and increased abundance of opportunistic taxa. Methods: This prospective study was conducted between 2022 and 2024 at the Emergency Clinical Hospital for Children, Cluj-Napoca. Children with CD and healthy controls were evaluated. The gut microbiota was analyzed using shotgun metagenomics. Bioinformatic processing assessed alpha and beta diversity, core microbiome composition, and differential taxa. Results: Ten patients with CD and eight healthy children were included; five patients were re-evaluated after a median interval of 14 weeks. The Shannon index was significantly lower in CD patients compared with controls (p = 0.037). Beta diversity analysis suggested partial separation between CD at diagnosis and controls (p = 0.041). An inverse correlation was observed between the Shannon index and the clinical score (p = 0.028). Ruminococcus gnavus was among the taxa contributing to group separation. At follow-up, all patients were in clinical remission, while 80% had achieved biological remission and mucosal healing. They showed persistently reduced alpha diversity and distinct microbial communities compared with controls (p = 0.028 and p = 0.005, respectively). Conclusions: Pediatric CD was correlated with dysbiosis that persisted despite remission. Reduced alpha diversity was associated with greater disease severity at diagnosis.

Background and Aims. Exclusive enteral nutrition (EEN) is a well-established first-line therapy for inducing remission in mild-to-moderate pediatric Crohn’s disease (pCD). While clinical remission (CR) and mucosal healing (MH) are widely accepted therapeutic goals, the concept of transmural healing (TH) has gained increasing recognition. This study aimed to evaluate the effectiveness of EEN in pCD patients from Romania, focusing on nutritional status, remission outcomes, and the impact of various factors on treatment efficacy. Methods. We conducted a retrospective observational study of pCD consecutive patients who received EEN for induction of remission between 2007 and 2017 at a referral center in Cluj-Napoca, Romania. CR was defined as a weighted Pediatric Crohn’s Disease Activity Index (wPCDAI) <12.5, MH as a fecal calprotectin level <250 microg/g, and TH as the combination of MH and imagistic remission assessed by intestinal ultrasonography. Statistical analyses included descriptive and comparative approaches, including logistic regression, with p <0.05 considered significant. Results. Twenty patients with pCD, representing 45% of the cohort, were included. The median age at diagnosis was 14.2 years (9.9–18.4), and 65% were male. EEN was administered with a mean duration of 7.84±1.26 weeks. Body mass index Z-scores significantly improved following EEN (p=0.02). Hypoalbuminemia, detected in 55% of patients at diagnosis, resolved completely after EEN (p=0.00015). CR was achieved in 82% of patients with active clinical disease, MH in 26% of patients with microscopic activity, and TH in 20% of patients with imagistic activity. Age at diagnosis, disease behavior, location, activity, and anti-Saccharomyces cerevisiae antibody status were not significantly associated with CR or MH. Disease activity at initiation, measured by the wPCDAI, was inversely associated with TH (p=0.004). Conclusions. This is the first study to report on EEN outcomes in pCD patients from Romania. EEN was effective in improving nutritional status and inducing CR, while MH was achieved in about one-quarter of patients. TH was also observed, though less frequently, and was negatively associated with higher baseline clinical disease activity. Regional factors may have influenced these outcomes.

Background/Objectives: Pediatric inflammatory bowel disease (pIBD), including Crohn’s disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBD-U), exhibits unique clinical features compared to adult-onset disease. This study aimed to describe phenotypic characteristics of pIBD in the north-west region of Romania over a 21-year period and to compare our findings with those of other studies worldwide. Methods: We conducted a retrospective study of children under 18 years of age, from the north-west region of Romania, diagnosed with pIBD between 2000 and 2020 at the Emergency Clinical Hospital for Children, Cluj-Napoca. Disease phenotype at diagnosis was established according to the Paris classification. Data were collected from the hospital records and analyzed using descriptive statistics and univariate analysis of categorical variables. A p-value < 0.05 was considered statistically significant. Results: Ninety-four patients were included (CD: 51.0%; UC: 43.6%; IBD-U: 5.4%), with a median age at diagnosis of 14 years (11–15.7). Very early-onset IBD accounted for 5.3% of cases. The likelihood of being diagnosed with CD after 10 years of age was significantly higher compared to UC (OR = 4.75, 95% CI: 1.10–29.07, p = 0.03). UC most frequently presented as pancolitis (51.2%), while CD most often involved the ileocolonic region (56.3%). Inflammatory behavior was the most common CD phenotype (69%). Upper gastrointestinal involvement was documented in 18.7% of CD cases, with detection rates increasing after 2014. Perianal disease and growth impairment were significantly associated with complicated CD behavior (p = 0.03, and p = 0.007 respectively). Our findings are broadly consistent with other published reports. Conclusions: This study provides the first detailed phenotypic characterization of pIBD in this region. Our findings reflect trends observed in other populations and underscore the importance of standardized diagnostic evaluation.

Background: Inflammatory bowel disease (IBD) represents a group of disorders with increasing incidence in the pediatric population worldwide. There are limited data on pediatric IBD (pIBD) epidemiology in Eastern Europe and none so far from Romania. The aim of our study was to evaluate incidence rates and time trends for pIBD in the north-west region of Romania and to compare them with results from studies on the same topic published worldwide. Methods: We performed a retrospective study of patients under 18 years of age diagnosed with pIBD in the time frame between 1 January 2000 and 31 December 2020 at the Emergency Clinical Hospital for Children in Cluj-Napoca. Age-adjusted incidence rates, annual percentage change (APC), average annual percentage chance (AAPC) and their corresponding 95% confidence intervals (CIs) were calculated for pIBD, Crohn’s disease (CD) and ulcerative colitis (UC). Temporal trends were plotted using Joinpoint regression. Results: Ninety-four patients were identified. For the entire studied period, the incidence rate for pIBD was 0.79/10⁵ (±0.74), 0.4/10⁵ for CD (±0.42) and 0.34/10⁵ for UC (±0.4). Time trends for incidence were positive, but statistical significance was found only for pIBD and CD. The APC observed for pIBD, CD and UC was 12 (95% CI: 6.5–17.7), 13.1 (95% CI: 8–18.5) and 5.67 (95% CI: 1.5–13.4), respectively. Comparison to other similar studies placed Romania among the countries with the lowest incidence of pIBD. Conclusions: Although pIBD incidence in our region appears to be low, there has been an important and significant increase in the incidence of overall pIBD and especially CD.

Background and Aims: Ulcerative proctitis [UP] is an uncommon presentation in paediatric patients with ulcerative colitis. We aimed to characterize the clinical features and natural history of UP in children, and to identify predictors of poor outcomes. Methods: This was a retrospective study involving 37 sites affiliated with the IBD Porto Group of ESPGHAN. Data were collected from patients aged <18 years diagnosed with UP between January 1, 2016 and December 31, 2020. Results: We identified 196 patients with UP (median age at diagnosis 14.6 years [interquartile range, IQR 12.5–16.0]), with a median follow-up of 2.7 years [IQR 1.7–3.8]. The most common presenting symptoms were bloody stools [95%], abdominal pain [61%] and diarrhoea [47%]. At diagnosis, the median paediatric ulcerative colitis activity index [PUCAI] score was 25 [IQR 20–35], but most patients exhibited moderate–severe endoscopic inflammation. By the end of induction, 5-aminosalicylic acid administration orally, topically or both resulted in clinical remission rates of 48%, 48%, and 73%, respectively. The rates of treatment escalation to biologics at 1, 3, and 5 years were 10%, 22%, and 43%, respectively. In multivariate analysis, the PUCAI score at diagnosis was significantly associated with initiation of systemic steroids, or biologics, and subsequent acute severe colitis events and inflammatory bowel disease-associated admission, with a score ≥35 providing an increased risk for poor outcomes. By the end of follow-up, 3.1% of patients underwent colectomy. Patients with UP that experienced proximal disease progression during follow-up [48%] had significantly higher rates of a caecal patch at diagnosis and higher PUCAI score by the end of induction, compared to those without progression. Conclusion: Paediatric patients with UP exhibit high rates of treatment escalation and proximal disease extension.

Background Maintaining of remission early in the disease course of Crohn’s disease (CD) is essential and has major impact on the future prognosis. This study aimed to identify baseline predictors to develop model allowing stratification of patients who will not benefit from long-term azathioprine (AZA) treatment and will require more intensive therapy. Methods This study was designed to develop clinical prediction rule using retrospective data analysis of pediatric CD patients included in prospective inception cohort. Clinical relapse was defined as necessity of re-induction of remission. Sequence of Cox models was fitted to predict risk of relapse. Results Out of 1190 CD patients from 13 European centers, 441 were included, 50.3% patients did not experience clinical relapse within 2 years of AZA treatment initiation. Median time to relapse was 2.11 (CI 1.59–2.46) years. Of all the tested parameters available at diagnosis, six were significant in multivariate analyses: C-reactive protein (p = 0.038), body mass index Z-score >0.8 SD (p = 0.002), abnormal sigmoid imaging (p = 0.039), abnormal esophageal endoscopy (p = 0.005), ileocolonic localization (p = 0.023), AZA dose in specific age category (p = 0.031). Conclusions Although the possibility of predicting relapse on AZA treatment appears limited, we developed predictive model based on six baseline parameters potentially helpful in clinical decision. Impact The possibility of predicting relapse on AZA treatment appears to be possible but limited. We identified six independent predictors available at diagnosis of early AZA/6-MP treatment failure in pediatric CD patients. Using combination of these factors, a model applicable to clinical practice was created. A web-based tool, allowing estimation of individual relapse risk in pediatric CD patients on a particular therapeutic regimen, has been developed.

Adult studies suggest that patients with isolated colonic Crohn’s disease (L2 CD) exhibit unique characteristics differentiating them from patients with ileo-cecal (L1) CD and ulcerative colitis (UC). We aimed to characterize clinical features and outcomes of paediatric patients with L2. Retrospective data was collected through the Porto IBD group of ESPGHAN on paediatric patients with L2, L1 or UC at different time-points. Outcome measures included time to 1^st flare, hospital admissions, initiation of anti-TNFa drug, stricture and surgery. Three hundred patients were included: 102 L1, 94 L2 and 104 UC. Rates of hematochezia at presentation were 14.7%, 44.7% and 95.2%, while rates of fever were 12.7%, 26.6% and 2.9%, for patients with L1, L2 and UC, respectively (Pst flare and admission were similar between groups, patients with L1 were commenced on anti-TNFa earlier. Moreover, stricturing phenotype and need for colectomy were very rare in patients with L2. Significant differences are observed in the clinical presentation and outcomes of paediatric patients with L2, compared to patients with L1 and UC.

Objectives: Adult studies suggest that patients with isolated colonic Crohn disease (L2 CD) exhibit unique characteristics differentiating them from patients with ileo‐caecal (L1) CD and ulcerative colitis (UC). We aimed to characterize clinical features and outcomes of paediatric patients with L2.Methods: Retrospective data was collected through the Porto Inflammatory Bowel Disease group of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) on Paediatric patients with L2, L1 or UC at different time‐points. Outcome measures included time to first flare, hospital admissions, initiation of anti‐tumor necrosis factor‐alpha (TNFα) drug, stricture and surgery.Results: Three hundred patients were included: 102 L1, 94 L2 and 104 UC. Rates of hematochezia at presentation were 14.7%, 44.7% and 95.2%, while rates of fever were 12.7%, 26.6% and 2.9%, for patients with L1, L2 and UC, respectively (P < 0.001 for all comparisons). Skip lesions were identified in 65% of patients with L2, and granulomas in 36%, similar to L1 patients. Rates of anti‐Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic (pANCA) positivity significantly differed between the three groups: 25.4% and 16.7% for patients with L2, compared with 55.2% and 2.3%, and 1.8% and 52.9% for patients with L1 and UC, respectively. Response rates to exclusive enteral nutrition were comparable between L1 and L2 (78.3–82.4%), as was the response to oral steroids (70.4–76.5%) in the three groups. While times to first flare and admission were similar between groups, patients with L1 were commenced on anti‐TNFα earlier. Moreover, stricturing phenotype and need for colectomy were very rare in patients with L2.Conclusions: Significant differences are observed in the clinical presentation and outcomes of Paediatric patients with L2, compared to patients with L1 and UC.

Background Isolated colonic (L2) Crohn’s disease (CD) in adults is thought to have unique clinical and genetic features compared with ileal (L1) CD and ulcerative colitis (UC). Similar studies in paediatrics are scarce. Our goal was to characterize the clinical features of paediatric patients with isolated colonic CD and compare them to patients with ileo-cecal CD and those with UC. Methods This was a multi-center retrospective study including 21 sites affiliated with the Porto IBD group and IBD interest group of ESPGHAN. Data of paediatric patients diagnosed between 2014–2017 with L1 or L2 CD, or with UC, was collected, including information on demographic, clinical and laboratory parameters at diagnosis, end of induction, 1 year and 3 years after diagnosis (or at last follow-up). Results Data was collected on 300 children (102 L1, 94 L2, 104 UC) with similar demographic features. At diagnosis, bloody stools were identified in 45% of L2 patients, compared with 15% and 95% of L1 and UC patients, respectively (P<0.001), while fever was documented in 27% of L2 patients, compared to 13% and 3% of L1 and UC patients, respectively (P<0.001). At the time of diagnosis, the median pediatric Crohn’s disease activity index for patients with L1 and L2 was 25 (IQR 17.5–37) and 27.5 (20–40), respectively, while the median pediatric ulcerative colitis activity index was 40 (30–55) for patients with UC. C-reactive protein levels were significantly higher among CD patients (both L1 and L2), compared to patients with UC, and calprotectin values were comparable. ASCA was positive in 55%, 25% and 2% (P<0.001) and pANCA in 2%, 17% and 53% (P<0.001) in L1, L2 and UC patients, respectively. Granulomas were identified in 36% of L2 patients, similar to patients with L1 (33%). For induction therapy, exclusive enteral nutrition, oral steroids and mesalazine were used in 50%, 45% and 38% of patients with L2 CD, compared with 72%, 28% and 9%, and 0%, 52% and 75% of L1 and UC patients, respectively (P<0.001). Steroid-free clinical remission at the end of induction was overall similar between groups, around 55%. At 1-year post-diagnosis, 62%, 68% and 40% were on an immunomodulator (P=0.03) and 41%, 26% and 22% were receiving anti-TNFα agent (P=0.01), of patients with L1, L2 and UC, respectively. While time to initiation of an anti-TNFα agent was significantly shorter in L1 patients compared with L2 and UC (P=0.03), time to admission and time to surgery were similar. Conclusion Paediatric patients with isolated colonic CD exhibit several clinical features which differentiate them from ileo-cecal CD and UC. Prospective studies are required to understand the pathogenesis of this unique entity and define short- and long-term outcomes.

Background Assessing the inflammation is important in the follow-up of paediatric patients with inflammatory bowel disease (IBD). We aim to evaluate the value of B cell-activating factor (BAFF) in paediatric IBD as a potential biomarker for follow-up. Method We determined BAFF in serum and faeces and faecal calprotectin (CP) in 32 IBD children-16 Crohn's disease (CD) and 16 ulcerative colitis (UC). Twenty-six healthy children and 10 children with irritable bowel syndrome (IBS) were included as controls. Results No differences were found in serum BAFF between IBD, IBS, and healthy group: 1037.35, 990.9 and 979.8 pg/ml, respectively, allp > 0.05, but faecal BAFF was higher in the IBD group: 15.1, 8.5 and 8.2 pg/ml, respectively,p < 0.05, and higher in the UC group (55.975 pg/ml) compared to the CD group (10.95 pg/ml),p = 0.015. Splitting the IBD group in relation to the CP level, the serum BAFF had no significantly different values between the subgroups, but the faecal BAFF was significantly higher in the >250 mu g/g subgroup. Cut-off values of BAFF were calculated. Conclusion Faecal BAFF is a promising marker for monitoring the children with IBD, higher levels of BAFF being correlated with high CP. Impact Faecal BAFF is a promising marker in monitoring the children with IBD, higher levels of BAFF being correlated with high faecal calprotectin. To our knowledge, this is the first paediatric study concerning BAFF evaluation in IBD. Faecal BAFF levels could be considered a potential non-invasive marker in monitoring IBD activity in paediatric population with clinically mild or inactive disease.