Jaroslaw Kierkus

Background/Objectives: Chronic diseases, such as inflammatory bowel disease (IBD), influence patients’ sexuality. Therefore, the aim of this study was to analyze the sexual functioning (SF) of patients with IBD. Methods: We perform a prospective survey study on male and female individuals with IBD using an anonymous questionnaire including 60 inquiries concerning patients’ intimate relationships and SF. The following statistical tests were used: chi-square test of independence, Spearman’s rank correlation coefficient, and Wilcoxon and Mann–Whitney U tests. A significance level of p = 0.05 was assumed as statistically significant. Results: There were 110 respondents with IBD (41% with Crohn’s disease and 57% with ulcerative colitis): 52 women (47%) and 58 men (53%), with a mean age of between 31 and 40 (45%). In 34% of respondents, the assessment of satisfaction with sex after diagnosis decreased, and the difference was statistically significant (p = 0.007). Statistically significant correlations were found between IBD clinical activity and the impact of the disease on sexual desire (p < 0.001), the need for sex after diagnosis (p < 0.001), satisfaction with sex after diagnosis (p = 0.003), the average frequency of intercourse (p = 0.004), the average duration of intercourse after diagnosis (p = 0.001), feeling guilty in the sexual sphere due to the disease (p = 0.006), assessment of one’s attractiveness since diagnosis (p = 0.032), and change in the partner’s erotic perception after diagnosis (p < 0.001). The more aggressive the course of the disease, the more negative the impact on patients’ sexuality. Conclusions: The diagnosis of IBD has a negative impact on patients’ SF—disease flare leads to a decrease in sexual needs, worse experiences and negative body image.

Background and Aims: In the LIBERTY phase 3 studies in Crohn’s disease (CD) or ulcerative colitis (UC), maintenance CT-P13 subcutaneous (SC) 120 mg was more effective than placebo after 1 year. Here we report 2-year data from the LIBERTY open-label extensions. Methods: Two randomized, placebo-controlled, double-blind studies evaluated the efficacy and safety of CT-P13 SC maintenance in moderate-to-severe CD or UC. Responders to CT-P13 intravenous induction were randomized at week (W) 10 to CT-P13 SC 120 mg or placebo biweekly, until W54. From W22, dose adjustment to CT-P13 SC 240 mg was permitted for loss of response. At W56, patients could enter an open-label extension, receiving CT-P13 SC 120 mg (or 240 mg if dose-adjusted), biweekly, until W102. Results: The extension comprised 278/343 (81.0%) and 348/438 (79.5%) patients in the CD and UC studies, respectively. In those continuing on-study, efficacy (non-responder imputation) was well maintained in the CT-P13 SC group at W102: 63.5% (as-observed: 70.5%) and 49.0% (as-observed: 58.8%) of CD patients (N = 192) achieved clinical remission and endoscopic response, respectively; 45.1% (as-observed: 60.1%) and 41.4% (as-observed: 52.4%) of UC patients (N = 237) achieved clinical remission and endoscopic-histologic mucosal improvement, respectively. No new safety signals were identified from longer-term CT-P13 SC treatment or starting CT-P13 SC 120 mg after placebo, with similar adverse event rates for patients undergoing dose adjustment to CT-P13 SC 240 mg from CT-P13 SC 120 mg or placebo. Conclusion: CT-P13 SC is an effective and well-tolerated long-term maintenance treatment in moderate-to-severe CD and UC. ClinicalTrials.gov identifiers: NCT03945019 (CD) and NCT04205643 (UC).

Enteral nutrition is a component of therapy for children whose ability to take in food by the natural route is impaired but whose gastrointestinal tract capacity still allows for nutrient digestion and absorption. According to guidelines, the optimum types of food for enteral feeding are ready-to-use commercial formulas (food for a special medical purpose, FSMP), which are classified into polymeric, oligomeric and amino acid/elemental. Using a blended kitchen diet as a sole food source is currently not universally recommended due to the higher risk of nutritional deficiencies and contamination with pathogenic microorganisms. However, in everyday practice, given isolated reports indicating their beneficial effects on gastrointestinal function, blended diets are attracting increasing interest and popularity. The so-called “real food” diets, available in some European countries and the USA, are a step towards the standardised and microbiologically safe use of natural nutrients in enteral nutrition. These fall into the category of industrial diets but, in addition to cow’s milk protein, they contain various other natural foods. This article summarises current knowledge on the efficacy and safety of “real food” diets. A small number of studies with limited reliability have been identified, making a joint summary of the obtained results impossible. Despite the limited scientific evidence, the descriptions of various clinical situations presented in the literature show a good clinical response in patients receiving “real food” diets. This suggests that such treatment should be attempted for children with significant gastrointestinal complaints and poor tolerance to standard enteral formulas.

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.

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

This study aimed to evaluate the C-reactive protein-to-albumin (CRP/albumin) ratio at diagnosis of pediatric inflammatory bowel disease (IBD). Serum CRP/albumin ratio was calculated for patients with Crohn’s disease (CD; n=186) and ulcerative colitis (UC; n=159) aged 3–18 years. Patients with CD differed in CRP/albumin ratio at diagnosis in groups with quiescent, mild, moderate, and severe disease (P=0.011). CRP/albumin ratio at diagnosis was significant in differentiating patients with severe CD from quiescent disease at diagnosis (area under the curve (AUC)=0.94, odds ratio (OR)=63.4, 95% confidence interval (CI) 7.1–569.1, P<0.0001). CRP/albumin ratio at diagnosis could moderately differentiate penetrating from non-penetrating disease behavior in CD at diagnosis (AUC=0.73, OR=6.3, 95% CI 2.0–19.3, P<0.001). Furthermore, CRP/albumin ratio at diagnosis weakly differentiated IBD patients in need of biological treatment in a step-up procedure (AUC=0.58, OR=2.1, 95% CI 1.3–3.4, P=0.022) and in need of surgery (AUC=0.63, OR=3.1, 95% CI 1.4–7.2, P=0.006). For the IBD, CRP/albumin ratio at diagnosis was weakly correlated with age at first immunosuppressive treatment (rho=0.20, P=0.018), time from diagnosis to first biological treatment (rho=−0.37, P<0.001), days spent in hospital (rho=0.26, P=0.007), number of severe relapses (rho=0.31, P=0.001), and Pediatric Crohn’s Disease Activity Index (rho=0.38, P=0.002). The present findings add to previous studies carried out in adult patients and show that the CRP/albumin ratio at diagnosis was not significantly associated with the course of either CD or UC in children. However, CRP/albumin ratio could differentiate patients with severe CD from those with quiescent disease.

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.