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Background and Objectives: Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), often necessitates long-term treatment and hospitalizations and also may require surgery. The macrophage-stimulating 1 (MST1) rs3197999 polymorphism is strongly associated with the risk of IBD but its exact clinical correlates remain under investigation. We aimed to characterize the relationships between the MST1 rs3197999 genotype and the clinical characteristics in children and adolescents with IBD within a multi-center cross-sectional study. Materials and Methods: Clinical data included serum C-reactive protein (CRP), albumin, activity indices (PUCAI, PCDAI), anthropometric data, pharmacotherapy details, surgery, and disease severity. Genotyping for rs3197999 was carried out using TaqMan hydrolysis probes. Results: The study included 367 pediatric patients, 197 with Crohn’s disease (CD) (40.6% female; a median age of 15.2 years [interquartile range 13.2–17.0]) and 170 with ulcerative colitis (UC) (45.8% female; a median age of 15.1 years [11.6–16.8]). No significant relationships were found between MST1 genotypes and age upon first biologic use, time from diagnosis to biological therapy introduction, PUCAI, PCDAI, or hospitalizations for IBD flares. However, in IBD, the height Z-score at the worst flare was negatively associated with the CC genotype (p = 0.016; CC: −0.4 [−1.2–0.4], CT: −0.1 [−0.7–0.8], TT: 0.0 [−1.2–0.7)]). The TT genotype was associated with higher C-reactive protein upon diagnosis (p = 0.023; CC: 4.3 mg/dL [0.7–21.8], CT 5.3 mg/dL [1.3–17.9], TT 12.2 mg/dL [3.0–32.9]). Conclusions: This study identified links between MST1 rs3197999 and the clinical characteristics of pediatric IBD: height Z-score and CRP. Further studies of the associations between genetics and the course of IBD are still warranted, with a focus on more extensive phenotyping.

Inflammatory bowel diseases (IBD) are chronic intestinal conditions of multifactorial aetiology including genetic susceptibility, immunological impairment, dysbiosis, and environmental factors. The diagnosis is based on both clinical and endoscopic features, wherein histopathological evaluation remains a gold diagnostic standard. However, fast, reliable, and non-invasive biological markers have been used for years for diagnosis as well as for disease activity monitoring. Currently, commonly used faecal calprotectin is the only biomarker approved and recommended by the European Crohn’s and Colitis Organization (ECCO). Nonetheless, other biological markers discriminating between functional and organic bowel conditions have been widely studied. Therefore, the aim of this manuscript was to review new potential biomarkers of inflammation in IBD. The aim of this study was to review currently available biomarkers of intestinal inflammation and increased gut permeability in IBD.

Background: Fecal calprotectin (FCP) is a highly sensitive biomarker of intestinal inflammation widely used in diagnostics and monitoring of inflammatory bowel disease (IBD). Immunohistochemical assessment of calprotectin in the bowel mucosa is not a diagnostic standard. Therefore, the aim of this study was to evaluate tissue calprotectin (TCP) as a potential marker providing added insight for pediatric patients with Crohn’s disease (CD). Methods: Fecal and tissue calprotectin were measured in children with CD. The values were correlated with disease activity and histopathological changes of the patients’ endoscopic biopsies. Disease activity was assessed using the Pediatric Crohn’s Disease Activity Index (PCDAI); fecal calprotectin (FCP) was measured with the ELISA test. Immunohistochemical (IHC) staining for calprotectin antigen was performed on the biopsy samples from six bowel segments, and the number of TCP cells was counted per high power field (HPF). Non-parametric statistical tests were used for data analysis. Results: Fifty-seven children with CD with a median age of 10.5 (1–17) years (yrs) were examined for fecal and tissue calprotectin. The patients’ median PCDAI score was 10 (0–63.5), while median FCP was 535 (30–600) μg/g. We observed a correlation between disease activity (PCDAI) and FCP, TCP in inflammatory lesions and in crypts. There was no association either between FCP and TCP or between TCP in epithelium and PCDAI. Conclusion: It seems that IHC detection of calprotectin in bowel mucosa to assess disease behavior may be useful. FCP is a gold-standard biomarker in the diagnosis, monitoring and prognosis of IBD, and its levels correlated well with clinical activity in our study group.

Summary: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10−8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10–5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10−10; OR = 1.47; 95% CI, 1.38–1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10−16; OR = 1.75; 95% CI, 1.64–1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes.

The incidence and prevalence rate of chronic inflammatory disorders is on the rise in the pediatric population. Recent research indicates the crucial role of interactions between the altered intestinal microbiome and the immune system in the pathogenesis of several chronic inflammatory disorders in children, such as inflammatory bowel disease (IBD) and autoimmune diseases, such as type 1 diabetes mellitus (T1DM) and celiac disease (CeD). Here, we review recent knowledge concerning the pathogenic mechanisms underlying these disorders, and summarize the facts suggesting that the initiation and progression of IBD, T1DM, and CeD can be partially attributed to disturbances in the patterns of composition and abundance of the gut microbiota. The standard available therapies for chronic inflammatory disorders in children largely aim to treat symptoms. Although constant efforts are being made to maximize the quality of life for children in the long-term, sustained improvements are still difficult to achieve. Additional challenges are the changing physiology associated with growth and development of children, a population that is particularly susceptible to medication-related adverse effects. In this review, we explore new promising therapeutic approaches aimed at modulation of either gut microbiota or the activity of the immune system to induce a long-lasting remission of chronic inflammatory disorders. Recent preclinical studies and clinical trials have evaluated new approaches, for instance the adoptive transfer of immune cells, with genetically engineered regulatory T cells expressing antigen-specific chimeric antigen receptors. These approaches have revolutionized cancer treatments and have the potential for the protection of high-risk children from developing autoimmune diseases and effective management of inflammatory disorders. The review also focuses on the findings of studies that indicate that the responses to a variety of immunotherapies can be enhanced by strategic manipulation of gut microbiota, thus emphasizing on the importance of proper interaction between the gut microbiota and immune system for sustained health benefits and improvement of the quality of life of pediatric patients.

Background: Magnetic resonance enterography (MRE) is an excellent way to study the small bowels. During such an examination, the colon is also seen within the field of study. The aim of this study was to evaluate the effectiveness of MRE in detecting characteristics of active inflammatory bowel disease (IBD) in the colon, in comparison to different features seen in colonoscopies. Methods: This retrospective study was conducted with 41 children. Features of active inflammation we considered were wall thickening; contrast enhancement; incorrect signal in the DWI sequence in the MRE; and presence of ulceration, erosion, erythema, spontaneous bleeding and a decrease of the vascular pattern seen in colonoscopy. The colon was divided into six segments: caecum, ascending, transverse, descending, sigmoid and rectum. Results: The sensitivity of MRE was, on average, 50–75%, and as high as 92–100%, depending on the segment. The most important feature for which there was the most dependencies was ulceration. In the analysis of intestinal wall thickness, the AUC value >0.8 was detected as ulceration (segments: cecum, ascending, descending colon, sigmoid), spontaneous bleeding (ascending colon and sigmoid) and decreased vascular pattern (ascending, transverse, descending colon). Conclusions: Evaluation of qualitative structural changes in MRE distinguishes patients with inflammation in colonoscopy from patients without lesions, with high diagnostic accuracy, albeit higher specificity than sensitivity.

Background: Recent data indicate that increased intestinal permeability plays a key role in the pathogenesis of inflammatory bowel diseases (IBD) and correlates with disease flare. Since zonulin related proteins (ZRP) are the proteins that increase permeability in the epithelial layer of the small intestine by reversibly modulating the intercellular tight junctions, they may serve as a new, noninvasive biomarker of disease activity. The aim of this study was to investigate fecal ZRP in pediatric IBD patients as well as its correlation with disease activity and fecal calprotectin (FCP). Methods: Ninety-four individuals: 47 Crohn’s disease (CD) patients, 41 ulcerative colitis (UC) patients, and 6 healthy controls were examined for fecal ZRP. Values were correlated to IBD type, disease activity for IBD patients, and FCP for all children included in the study. A stool specimen was collected the day before the visit to the hospital, then fecal ZRP and FCP were tested using the ELISA test. Non-parametric statistical tests were used for data analysis. Results: The level of fecal ZRP was higher among IBD patients compared to the control group (CG): medians for CD—113.3 (53.6–593.6) ng/mL; UC—103.6 (50.7–418.3) ng/mL; and CG—46.9 (31.8–123.0) ng/mL (p < 0.05). No difference in fecal ZRP concentration was observed between children with CD and those with UC (p = 0.55). A slight correlation between disease activity (PCDAI for CD and PUCAI for UC) and the fecal ZRP level was found for CD (p = 0.03/R = 0.33), but not UC (p = 0.62/R = 0.08), patients. A correlation between fecal ZRP and FCP was observed (R = 0.73, p = 0.00). Conclusions: Fecal ZRP levels are increased among those with IBD, are associated with CD activity, and strongly correlate with FCP. Further research into the role of intestinal permeability in IBD and the clinical usefulness of ZRP in IBD is warranted.

Background: Vedolizumab (vedo) is effective for induction and maintenance of remission in adults with inflammatory bowel disease (IBD). Pediatric data are still limited, especially for the youngest children with very early onset disease (VEO-IBD). The aim of this study was to assess the safety and efficacy of vedo in VEO-IBD. Methods: We performed a retrospective review of pediatric IBD patients with VEO-IBD (defined as aged Results: The study included 16 patients with VEO-IBD who have received vedo: 4/16 (25%) with CD, and 12/16 (75%) with UC at the median age of diagnosis 33.7 months (6.6 months–4.5 years). Median age at vedo initiation was 6.5 years (2.2–16.5 years). Among the analyzed individuals, 56.25% had failed more than one anti-tumor necrosis factor (TNF) alfa agent. Clinical response at 4th dose week was observed in 9/16 (56.3%) patients: mean baseline PCDAI score was 34.4 ± 1.9 and 10.6 ± 1.8 after induction therapy with vedo, while PUCAI score was 26 ± 6 vs. 18 ± 8, respectively. There was improvement in patients’ nutritional state: at baseline 2/16 (12.5%) children had body mass index (BMI) below 1 percentile and no child had such BMI after induction therapy with vedo. No infusion reactions or serious adverse events/infections were reported. Conclusion: Vedolizumab is safe and effective in the medical management of pediatric patients with VEO-IBD.

In recent years, there has been a significant increase in the incidence of Crohn’s disease. Despite significant medical progress, the treatment options available today do not meet the needs of all patients. Recent reports indicate that external environmental factors, including diet, are key in the pathomechanism of the disease. It was proven that the so-called Western dietary pattern is associated with an increased risk of disease. In the pediatric population, exclusive enteral nutrition is the only nutritional therapy option recommended today with proven high efficacy in inducing remission. Recent publications that indicate at least comparable efficacy and significantly better tolerability of a specialised elimination diet, the Crohn’s Disease Exclusion Diet (CDED), provide the basis for a change in recommendations. This article discusses the mechanism of action, principles of use, and scientific evidence evaluating the efficacy of CDED in the treatment of children with Crohn’s disease.

Background: Infusion reactions (IRs) are the most common adverse events (AEs) of infliximab (IFX) treatment in patients with inflammatory bowel disease (IBD). Prophylactic premedication (PM) with corticosteroids or antihistamines prior to IFX infusions has been used in clinical practice, but its efficacy is not known. The aim of this study was to assess the influence of steroid PM on IR incidence in pediatric patients with IBD receiving IFX. Methods: We performed a case–control study that included pediatric patients with IBD receiving IFX. Patients were divided into four subgroups according to the agent and PM they received: Remicade (original drug) + PM, and two biosimilars—Reshma +/− PM, and Flixabi—PM. At our site, until 2018, PM with steroids was used as a part of standard IFX infusion (PM+); however, since then, this method has no longer been administered (PM−). IRs were divided into mild/severe reactions. Differences between subgroups were assessed with the appropriate chi-square test. Multivariate logistic regression was used to assess associations between PM and IR incidence, correcting for co-medication usage. Results: There were 105 children (55 PM+, 44 male, mean age 15 years) included in the study who received 1276 infusions. There was no difference between the PM+ and PM− subgroups, either in incidence of IR (18.2% vs. 16.0% of patients, p > 0.05) or in percentage of infusions followed by IR (2.02% vs. 1.02% of infusions, p > 0.5). The OR of developing IR when using PM was 0.34, and the difference in IRs ratio in PM+ and PM− patients was not statistically significant (95% CI, 0.034–1.9). There were 11/18 (61.1%) severe IRs (anaphylactic shock) reported in all patients (both PM+ and PM−). Conclusion: At our site, the incidence of IR was low, and PM did not decrease the incidence of IR in pediatric patients with IBD receiving IFX. These results indicate that PM with steroids should not be a standard part of IFX infusion to prevent IR.

Introduction : Deep remission, defined as clinical remission with mucosal healing (MH), with anti-tumor necrosis factor (TNF)-α agents is a new target for therapy in Crohn’s disease (CD). Provided that the efficacy of infliximab (IFX) for induction of MH in CD has been demonstrated, there are much less data for adalimumab (ADA), and none concerning MH on histopathological examination. Aim : To assess the impact of biological therapy with ADA on both endoscopic and histopathological MH in paediatric patients with CD. Material and methods : Twenty-three children (10 boys and 13 girls) aged 13.0 ±9.3 years with moderate to severely active CD diagnosed at the mean age of 5.5 ±0.83 years were included into the study. Seven (30.4%) patients had been previously treated with infliximab and switched to ADA due to intolerance or loss of response. Colonoscopy and gastroscopy with sample collection were performed in all patients before and after induction treatment with ADA. Clinical activity of the disease was assessed using the Paediatric Crohn’s Disease Activity Index (PCDAI), and the endoscopic activity was scored using the Simple Endoscopic Score (SES-CD). Histological changes were evaluated by a self-adapted numerical scoring system. Results: Four (17.4%) patients reached clinical remission (PCDAI ≤ 10). When comparing data at baseline and at a week after ADA treatment, a significant decrease was observed in median PCDAI and in SES-CD score between the initial and control colonoscopies. We reported a decrease in histological scale, which was not statistically significant. A correlation was found between PCDAI and SES-CD score. Conclusions : Biological therapy with ADA has a positive impact on endoscopic mucosal healing in paediatric patients with CD, which is not associated with histological evidence of suppression of inflammation. Endoscopic MH correlates better than microscopic one with clinical remission.

Infliximab was the first monoclonal antibody used in the treatment of inflammatory bowel disease (IBD). Over several years, this antitumour necrosis factor (TNF) treatment proved its efficacy in both induction and maintenance therapy. In many cases this biological treatment stopped the progression of the disease, probably also decreasing morbidity and hospitalization rates, and improving patients’ comfort. When the patent on infliximab started to expire, the first biosimilar of a monoclonal antibody was introduced onto the pharmacological market. Biosimilar infliximab was studied in rheumatology and proved a high similarity to the reference drug. Based on extrapolation, biosimilars were approved to treat adult and paediatric IBD patients. Biosimilar infliximab, mainly because of its lower cost, has started to be in common use in Europe. The first studies have shown a similar efficacy and safety profile in comparison with reference drug. Biosimilar infliximab is raising hopes for improving the availability of this effective treatment.

A close relationship between inflammatory bowel diseases (IBD) and hepatobiliary disorders, such as autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC), is well established. Hepatobiliary manifestations occur in 30% of patients with IBD, and 5% develop chronic liver disease. The spectrum of symptoms of the overlap syndrome ranges from asymptomatic elevated liver function tests to serious diseases. The pathogenesis of liver complications in IBD is not fully recognized. It may either have an autoimmune background or be caused by intestinal inflammation, metabolic impairment, or drug toxicity. The aim of this review is to summarize AIH and PSC overlap syndrome in IBD.

Summary: Background: Previous studies have demonstrated the tolerability and efficacy of multimatrix mesalamine in inducing and maintaining remission in adults with mild-to-moderate ulcerative colitis (UC). We evaluated the safety and efficacy of low-dose and high-dose once-daily multimatrix mesalamine in children and adolescents with mild-to-moderate UC or those in remission. Methods: This prospective, randomised, parallel-group, phase 3 study (8-week double-blind acute [DBA] phase; 26-week double-blind maintenance [DBM] phase; and an additional 8-week, open-label acute [OLA] phase) was conducted in 33 sites across North America, Europe, and the Middle East between December 12, 2014, and November 28, 2018. Eligible patients aged 5–17 years and weighing 18–90 kg were randomised 1:1 to either low (900–2400 mg) or high (1800–4800 mg) oral doses of multimatrix mesalamine once daily, stratified by body weight. Interactive response technology was used for randomisation. The primary efficacy outcome was to estimate the clinical response of multimatrix mesalamine (two doses) in different weight groups. Efficacy and safety analyses were conducted in the safety analysis set (Clinicaltrials.gov: NCT02093663; Study completed). Findings: Overall, 107 patients were randomised into the DBA (n = 54) or DBM phase (n = 88; directly or after completing the double-blind or OLA phases); the overall safety analysis set included 105 patients. In the DBA phase, the high-dose group (n = 17; 65.4%) achieved a higher clinical response rate than the low-dose (n = 10; 37.0%) group; difference 28.3% (95% CI: 2.5–54.2; p = 0.039), odds ratio (OR) 3.21 (95% CI: 1.04–9.88). In the DBM phase at Week 26, similar proportions of patients maintained clinical response in the low-dose (n = 23; 54.8%) and high-dose (n = 24; 53.3%) groups: OR 0.99 (0.42–2.34); p = 0.981. Overall, 246 treatment-emergent adverse events (TEAEs) were reported in 73 patients (69.5%); 23 TEAEs in 14 patients (13.3%) were considered related to the study drug. No treatment-related deaths were reported. Interpretation: Our findings suggested that the benefit-risk ratio of once-daily multimatrix mesalamine in paediatric patients was favourable and comparable with that reported in adults with mild-to-moderate UC. Funding: Shire Development LLC, a Takeda company.

Problems with intimacy and sexuality are one of the major concerns of patients with inflammatory bowel diseases (IBD). Many symptoms, complications, and consequences of these disorders are likely to impact on body image, intimacy, and sexual function. Moreover, mood disorders, in particular depression, which is a major risk factor for sexual dysfunctions, are reported to be common in chronic illnesses such as IBD. However, despite this obvious relevance, sexual problems are rarely addressed in the clinical management of patients with IBD. The aim of this review was to discuss sexual problem in people with IBD.

Inflammatory bowel disease (IBD) is a heterogenous group of chronic inflammations in the gastrointestinal tract, which traditionally consists of two types: Crohn’s disease and ulcerative colitis. They differ when it comes to clinical, endoscopic, and histopathological changes. The exact aetiology of IBD has not been fully comprehended, but what is known so far is that the aetiopathogenesis of the disease is compound. Many articles have been written on the cellular/molecular background of IBD. Based on various molecular pathways, new forms of the disease have been discovered, including very early-onset IBD (VEO-IBD) or IBD coexisting with primary sclerosing cholangitis. The aim of this article is to present the molecular mechanisms leading to IBD, focusing on new forms of this disorder.

Within the last 20 years, tumour necrosis factor inhibitors have been proven to be effective in achieving and maintaining clinical and endoscopic remission in patients with Crohn’s disease and ulcerative colitis. Since 2013, when infliximab originator lost its patent protection, patients with inflammatory bowel diseases (IBDs) in Poland have also been treated with biosimilar drugs. Biosimilars are drugs with high similarity to their reference products in terms of physicochemical properties, including structure, safety, and efficacy. Biosimilars are approved for use on the basis of the same rigorous quality standards as their reference products. In 2018, also biosimilars of adalimumab have become available. Studies published to date have shown that biosimilars do not differ from reference drugs in terms of the efficacy and safety. There are numerous data to confirm that a single switch of biological drugs (mainly from reference to biosimilar drugs) has no effect on therapy efficacy and safety. However, a significantly lower cost of therapy with biosimilars not only allows us to treat a much larger number of patients but may also necessitate multiple switches from reference drugs to biosimilars (including biosimilars produced by different manufacturers). Recently, the first results have been published concerning multiple switches in patients with psoriasis and rheumatoid arthritis. However, no such data are currently available for patients with IBDs.

Background: Inflammatory bowel diseases in children are characterized by a wide variety of symptoms and often a severe clinical course. In the treatment, we aimed to induce and maintain remission. We focused on assessing the efficacy and safety of the concomitant use of two biologic therapies including: anti-TNF (infliximab, adalimumab) vedolizumab and ustekinumab in a refractory pediatric IBD cohort. Methods: Fourteen children (nine ulcerative colitis, one ulcerative colitis/IBD-unspecified, four Crohn’s disease) with a disease duration of 5.2 (8 months–14 years) years, initiated dual therapy at an age of 11.7 (3–17) years after failure of monotherapy with a biological drug. Five patients (36%) were treated with vedolizumab/adalimumab (VDZ + ADA), five (36%) with ustekinumab/adalimumab (UST + ADA), and three (21%) with infliximab/vedolizumab (IFX + VDZ). One patient (7%) was switched from a combination of vedolizumab and adalimumab to ustekinumab and adalimumab during follow-up. Results: A clinical improvement was obtained in ten children (73%; 5 UC, 1 UC/IBD-unspecified, 4 CD) on the PCDAI/PUCAI scale after 4 months of a second biological drug being added. The median fecal calprotectin decreased from 1610 µg/g (140–10,100) to 586 µg/g (5–3410; p = 0.028) between baseline and 4 months. Conclusions: Our clinical experience suggests that dual therapy may be an option for pediatric patients with moderate and severe courses of IBD with limited therapeutic options

Ulcerative colitis (UC) results from a complex interplay between the environment, gut microbiota, host genetics, and immunity. Runt-related transcription factor 3 (RUNX3) regulates Th1/Th2 balance and, thus, the synthesis of cytokines and inflammation. We aimed to analyze the dependence of RUNX3 promoter 2 (P2) methylation level on: age, sex, body mass index (BMI), C-reactive protein (CRP), serum albumin, disease duration, Pediatric Ulcerative Colitis Activity Index (PUCAI), the Paris classification, and exposure to medications. This multicenter, cross-sectional study recruited hospitalized children with UC. Methylation of RUNX3 P2 was measured with methylation-sensitive restriction enzymes in the whole blood DNA. Sixty-four children were enrolled, with a mean age of 14.5 ± 2.8 years. Half of them were female (51.6%), and the average BMI Z-score was −0.44 ± 1.14. The mean methylation of RUNX3 P2 was 54.1 ± 13.3%. The methylation level of RUNX3 P2 did not correlate with age, sex, nutritional status, CRP, albumin, PUCAI, or the extent of colitis (Paris E1–E4). RUNX3 P2 methylation did not differ between patients recruited within two and a half months of diagnosis and children who had UC for at least a year. Current or past exposure to biologics, immunosuppressants, or steroids was not associated with RUNX3 P2 methylation. Methylation of RUNX3 promoter 2 in whole blood DNA does not seem to be associated with the characteristics of UC in children.

(1) Background: The CDED + PEN (partial enteral nutrition) is a promising method of nutritional treatment in active Crohn’s disease (CD). An increase in fecal calprotectin (FCP) level—a marker of mucosal inflammation—happens to be the first evidence of Crohn’s disease exacerbation that appears ahead of clinical symptoms and usually co-exists with them. In this study, we present our own experience with using the CDED + PEN in the treatment of children with CD and an increased FCP level. (2) Methods: In total, 48 children (male/female: 27/21) aged 4–17 years (median value = 13.43; IQR = 4.00) were treated with CDED + PEN between June 2019 and July 2021. The main inclusion criteria for the study was active CD defined as an FCP level ≥ 250.00 µg/g. Patients with severe clinical manifestation of CD (PCDAI >40.00), as well as ones who started any new concomitant CD treatment later than at least 4 weeks before the start of dietary intervention, were excluded from the analysis. The PCDAI and fecal calprotectin level were assessed at weeks 0 and 12. The primary endpoint was ITT normalization of FCP level, i.e., a result < 250.00 µg/g at week 12. The Wilcoxon Matched Pairs Test was used for statistical analysis. (3) Results: The normalization of the FCP level was obtained in 17 children (35.42%) and an FCP level decrease of at least 50% occurred in 26 patients (54.17%). The reduction in fecal calprotectin level between week 0 and week 12 was statistically significant with a median value of 1045.00 µg/g; IQR = 1188.00, and 363.00 µg/g; IQR = 665.00, respectively (p < 0.05). Among 29 patients who were not in clinical remission at baseline, 16 (55.17%) achieved clinical remission (PCDAI < 10.00) at week 12 and 20 (68.97%) obtained a clinical response defined as at least a 12.50 point drop in PCDAI or remission. In this group, the reduction in PCDAI between baseline and week 12 was statistically significant (median value = 20.00 points; IQR = 7.50 and 5.00 points; IQR = 5.00, respectively (p < 0.05)). All patients with a normal FCP level at week 12 were in clinical remission and 16 (94.13%) of them had a normal CRP (C-reactive protein) value. In 10 children (20.83%) the full course of 12 weeks with CDED + PEN was not completed or the concomitant therapy had been started before week 12 due to the lack of efficacy/intolerance of nutritional treatment. (4) Conclusions: The 12-week course of treatment with the CDED + PEN has a beneficial effect on the fecal calprotectin level in children with active CD. The dietary intervention led to a significant decrease in the FCP level in the studied group and to the normalization of this parameter in every third patient.

Background: pediatric patients with inflammatory bowel diseases (IBD) who qualify for biological therapy represent a group of severely ill patients. They have never been successful with conventional medication. Biologic medications in monotherapy are frequently used in the disease course, however they result in a 1-year remission, which can be maintained in approximately 40% of IBD patients. Method: the present study aims to summarize the review of literature data on the use of therapy with a combination of two biological and small molecule drugs, anti-TNF (infliximab, adalimumab), vedolizumab and ustekinumab, as well as Janus kinase inhibitors (tofacitinib). The risks associated with the use of dual biological therapy and potential adverse effects are particularly important. The literature data was reviewed using the following terms: “use of combination biologic in paediatric IBD”, “combination biologics”, and “dual biologic for treatment of Inflammatory Bowel Disease”. Conclusion: the use of dual biological therapy is a new therapeutic option. In pediatric IBD, combining the different mechanisms of action of the two biological drugs seems to be safe and effective. Anti-TNF drugs with vedolizumab or ustekinumab may be a particularly beneficial combination. Nevertheless, the clarification and justification of potential advantages of combined biological therapies in further studies, such as randomized control trials, are needed.

The human leukocyte antigen (HLA) allele group HLA-DQA1*05 predisposes to ulcerative colitis (UC) and is associated with the development of antibodies against infliximab in patients with inflammatory bowel disease (IBD). Therefore, we hypothesized that the presence of HLA-DQA1*05 correlates with characteristics of pediatric IBD. Within a multi-center cohort in Poland, the phenotype at diagnosis and worst flare was established and HLA-DQA1*05 status was assessed enabling genotype-phenotype analyses. HLA-DQA1*05 was present in 221 (55.1%) out of 401 children with IBD (UC n = 188, Crohn’s disease n = 213). In UC, the presence of HLA-DQA1*05 was moderately associated with a large extent of colonic inflammation at diagnosis (E4 55% more frequent in HLA-DQA1*05-positive patients, p = 0.012). PUCAI at diagnosis (p = 0.078) and the time from UC diagnosis to the first administration of biologic treatment (p = 0.054) did not differ depending on HLA-DQA1*05 status. The number of days of hospitalization for exacerbation was analyzed in 98 patients for whom sufficient follow-up was available and did not differ depending on HLA-DQA1*05 carriership (p = 0.066). HLA-DQA1*05 carriers with CD were less likely to present with both stenosing and penetrating disease (B2B3, p = 0.048) and to have active disease proximal to the ligament of Treitz (L4a) at the worst flare (p = 0.046). Future research focusing on explaining and preventing anti-TNF immunogenicity should take into account that ADA may develop not only as an isolated reaction to anti-TNF exposure but also as a consequence of intrinsic differences in the early course of UC.

Deleted in malignant brain tumours 1 protein (DMBT1) and surfactant protein D (SFTPD) are antimicrobial peptides previously linked to inflammatory bowel disease (IBD) susceptibility. This study attempts to link the most potential IBD-associated polymorphisms in DMBT1 and SFTPD with the disease severity in children. A total of 406 IBD patients (Crohn’s disease (CD) n = 214 and ulcerative colitis (UC) n = 192) were genotyped using hydrolysis probe assay. Clinical expression was described by disease activity scales, albumin and C-reactive protein levels, localisation and behaviour (Paris classification), systemic steroid, immunosuppressive, biological, and surgical treatment, number of exacerbation-caused hospitalisations, relapses and nutritional status. IBD patients with the risk genotype (AA) in DMBT1 rs2981804 had more frequent biological treatment (AA: vs. AG/GG; p = 0.012), concomitant diseases (AA vs. AG vs. GG; p = 0.015) and cutaneous manifestations (AA vs. AG/GG, p = 0.008). In UC, rs2981804 genotypes might be linked with albumin concentrations at diagnosis (AA vs. AG vs. GG; p = 0.009). In CD, DMBT1 rs2981745 was significantly associated with the number of severe relapses per year of disease (p = 0.020) and time-to-immunosuppression (p = 0.045). SFTPD was seemingly found to be associated with age at first immunosuppression in IBD (CC vs. CT vs. TT; p = 0.048). In conclusion, selected polymorphisms of DMBT1 and SFTPD might be associated with some disease severity measures in children with IBD. However, the magnitude of associations and their clinical relevance might be minor.

Background: In spite of the introduction of peroral endoscopic myotomy (POEM), Heller myotomy (HM) remains the mainstay of treatment and the role of pneumatic dilatation (PD) is being debated. The aim of this study was to present a single-center experience in the diagnostic approach and treatment of esophageal achalasia (EA), including the long-term assessment of the QoL. Methods: Data collection was based on the retrospective analysis of clinical notes and prospective interviews with patients and their parents. Results: The study group consisted of 60 patients with EA (F: 26, M: 34), with a median age of 12.0 (1–17) years at diagnosis. The time from the first symptoms until the diagnosis was 1.0 year (0.5–2.0) and the most common were: regurgitation (91.3%), dysphagia (84.8%), and chest pain (47.8%). The diagnostic approach showed a high sensitivity for barium X-ray follow through, esophageal manometry, and endoscopy. Overall, a long-term good outcome of HM was achieved in 27 out of 37 patients (73%) and it was negatively affected by the time between the first symptoms and the diagnosis. Out of the 16 patients who underwent PD before HM, a good outcome was achieved in 14 patients (87.5%), compared to 13 out of 21 patients (62%) who only underwent HM (p = 0.22). Concomitant fundoplication was routinely performed, and 18% required post-operative endoscopic dilatation. At the end of the 12.1 (0.7–26.6)-year follow up, most patients had a good QoL, which significantly corresponded with the treatment outcomes. Conclusions: Patients suspected of EA should undergo a thorough clinical evaluation including a manometry, a barium X-ray, and an endoscopy. HM is a safe and effective treatment for achalasia and the outcome is not worsened by a preceding endoscopic PD. In most patients, HM alleviates symptoms, although an impaired QoL is common in long-term follow ups.

Background: Home artificial nutrition (HAN) is a developing method of treatment that reduces the need for hospitalizations. The epidemiology of pediatric HAN in Poland has not yet been covered in detail. This study is a longitudinal nationwide analysis of incidence, prevalence, and patients’ profile for HAN in Polish children. Methods: Assessment of National Health Fund (NFZ) data covering all pediatric patients treated with HAN in Poland between 2010 and 2018. Results: HAN was received by 4426 children, 65 patients were on home enteral nutrition (HEN) or home parenteral nutrition (HPN) at different times (HEN n = 3865, HPN n = 626). HAN was most frequently started before the child was 3 years old and long-term HAN programs (5–9 years) were reported. The most common principal diagnosis in HEN was food-related symptoms and signs. In HPN, it was postoperative gastrointestinal disorders. A regionally differentiated prevalence of HAN patients and centers was demonstrated. Mortality among patients was 24.9% for HEN, and 9.6% for HPN, and the main in-hospital cause of death was cardiac arrest. Conclusions: HAN’s use is increasing and evolving in Poland. Uneven distribution of patients and centers results in difficult access to the nutritional procedure which, together with the increasing number of patients, highlights the need for data analysis and development of nutrition centers.

This study was to investigate whether the clinical course of inflammatory bowel disease (IBD) in a Polish paediatric cohort fits a seasonal pattern and depends on insolation. Two hundred and fourteen patients diagnosed with Crohn’s disease (CD) and 192 with ulcerative colitis (UC) aged from 3 to 18 years, were recruited in seven centres of similar latitude. The seasons were defined as winter (December–February), spring (March–May), summer (June–August), autumn (September–November). The year was also divided depending on insolation threshold (3.0 kWh/m2/day). Patients diagnosed with IBD when the isolation was >3 kWh/m2/day had poorer nutritional status than those diagnosed while insolation was below threshold (lower standardised BMI at diagnosis (−0.81 ([−1.34]–[−0.03]) vs. −0.52 ([−1.15]–0.15); p = 0.0320) and worst flare (−0.93 ([−1.37]–[−0.05]) vs. −0.66 ([−1.23]–0.17); p = 0.0344), with the need for more frequent biological treatment (45.5% vs. 32.7%, p = 0.0100). Patients diagnosed in winter were significantly younger at diagnosis (11.4 vs. 13.0; padj = 0.0180) and first immunosuppressive treatment (11.3 vs. 13.3; padj = 0.0109) than those diagnosed in other seasons. CD patients diagnosed in months with higher insolation spent more days in hospital than those diagnosed in months with lower insolation [4.6 (1.8–11.8) vs. 2.9 (1.3–6.2); p = 0.0482]. CD patients diagnosed in summer had significantly more concomitant diseases. In patients with CD, the occurrence of the worst flare was more frequent in autumn. Furthermore, the season of birth was associated with Pediatric Crohn’s Disease Activity Index at worst flare and earlier surgery. In conclusion, several clinical parameters are associated with insolation, the season of diagnosis and season of birth in the clinical course of Crohn’s disease.

Introduction: Respiratory tract infections constitute the most frequent manifestation of X-linked agammaglobulinemia (XLA). There are not many papers elucidating gastrointestinal (GI) disorders, including inflammatory bowel disease (IBD), in such patients. The aim of the study was to evaluate the occurrence of gastrointestinal disorders and IBD compared to respiratory tract infections in XLA individuals. Material and methods : Of 1563 patients with primary immunodeficiencies diagnosed in the Department of Immunology, the Children’s Memorial Health Institute (CMHI), 66 boys had a provisional diagnosis of agammaglobulinemia. Forty-four subjects fulfilled definitive ESID (European Society for Immunodeficiencies) diagnostic criteria of XLA. A retrospective analysis of medical history of XLA patients was undertaken. Results : Recurrent respiratory tract infections, particularly bronchitis (73%) and pneumonia (59%), were the most common symptoms of XLA. The GI disorders constituted the next main manifestation (63.6%), followed by upper respiratory tract infections (URTI). Twenty-six of 28 XLA patients with GI disorders complained of diarrhea, which was resolved generally after immunoglobulin therapy introduction. Single but prolonged episodes of Campylobacter jejuni diarrhea were reported in two individuals. Inflammatory bowel disease of mild to moderate activity was diagnosed in 1 patient, and local enteritis of mild activity in another one. Conclusions : Gastrointestinal disorders were one of the main manifestations of XLA, reported almost as often as lower respiratory tract infections (LRTI). The most common GI symptom was diarrhea, which usually resolved after immunoglobulin therapy was started. Infections caused by Giardia lamblia were reported occasionally. Inflammatory bowel disease was diagnosed quite exceptionally, which presumably may be connected with normal T cell immunity.

Aim: To verify the impact of induction therapy with infliximab (IFX) on mucosal healing in children with ulcerative colitis (UC)., Methods: The study included all UC pediatric patients treated with IFX at our center over the last 10 years. The data were collected from patients' medical charts and analyzed retrospectively. A total of 16 patients with UC underwent colonoscopy with sample collection before and after three IFX injections. Pediatric Ulcerative Colitis Activity Index (PUCAI) was used to assess the clinical condition; endoscopic features were classified according to the Baron scale; and histological changes were evaluated according to the protocol of The British Society of Gastroenterology and Geboes Index. Clinical response was defined as a ≥ 20-point reduction in PUCAI index, and clinical remission as PUCAI index < 10 points. Endoscopic mucosal remission was defined as completely normal (score 0) on the Baron scale. Histological remission was defined as grade 0 in the Geboes Index. To assess correlation between variables, Spearman's rank correlation coefficient was used., Results: Clinical remission (PUCAI < 10) at week 8 was achieved in 68.75% of investigated subjects. Endoscopic mucosal remission at week 8 (Baron 0) was observed in 12.5% of patients. Histological remission (Geboes 0) after induction therapy with IFX was noticed in 18.75% cases. A general histological improvement, expressed by normal surface and crypt architecture, number of crypts, and lamina propria cellularity, was observed in six (37.5%) patients; there was no improvement in nine (56.25%) individuals, and worsening was observed in one (3.75%) case. Changes were not related to UC location. A reduction of inflammatory process was observed in 10 (62.5%) patients; there were no changes in four (25%) individuals, and the inflammation became more severe in two (12.5 %) cases. Simultaneous clinical, endoscopic and histological improvement of parameters assessing disease activity at week 8 was noticed in six (37.5%) patients. 55.5% of investigated patients with normal mucosa seen on endoscopy showed no inflammation on histology. A Baron score of 2 and 3 showed a good correlation with histology results (78.2% of patients with a Geboes Index ≥ 3)., Conclusion: IFX has a positive histological effect in more than one-third of UC patients. IFX reduces intestinal inflammation and improves clinical condition.