Santiago Jiménez

(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.

Background: Elimination of gluten-containing cereals and consumption of ultra-processed gluten-free foods might cause an unbalanced diet, deficient in fiber and rich in sugar and fat, circumstances that may predispose celiac children to chronic constipation. Aim: to evaluate if counseling with a registered dietitian (RD) was capable of improving eating and bowel habits in a celiac pediatric population. Methods: Dietetic, lipid profile and stool modifications were analyzed, comparing baseline assessments with those twelve months after receiving heathy eating and nutrition education sessions. At both time points, 3-day food records, a bowel habit record and a lipid panel were conducted. Calculated relative intake of macro- and micro-nutrients were compared with current recommendations by the European Food Safety Authority (EFSA). Student’s paired t-test, McNemar test, Mandasky test and Pearson correlation tests were used. Results: Seventy-two subjects (58.3% girls) with a mean (standard deviation (SD)) age of 10.2 (3.4) years were included. Baseline diets were imbalanced in macronutrient composition. Significant improvements were observed in their compliance with dietary reference values (DRVs), where 50% of the subjects met fat requirements after the education and 67% and 49% with those of carbohydrates and fiber, respectively (p < 0.001). Celiac children decreased red meat and ultra-processed foods consumption (p < 0.001) and increased fruits and vegetables intake (p < 0.001), leading to a reduction in saturated fat (p < 0.001) and sugar intake (p < 0.001). Furthermore, 92% of the patients achieved a normal bowel habit, including absence of hard stools in 80% of children constipated at baseline (p < 0.001). Conclusions: RD-led nutrition education is able to improve eating patterns in children with celiac disease (CD).

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014–2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6–8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn’s Disease activity index [wPCDAI] < 12.5). Faecal calprotectin (FC) levels (μg/g) decreased significantly after EEN (830 [IQR 500–1800] to 256 [IQR 120–585] p < 0.0001). Patients with wPCDAI ≤ 57.5, FC < 500 μg/g, CRP >15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6–8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn’s disease regardless of the location of disease and disease activity.

Cow's milk protein allergy (CMPA) is the most common allergy in the first year of life. Non-IgE mediated CMPA is characterized by digestive symptoms and tolerance development before the age of three. Gut microbiota composition in early life has been associated with food allergy. The ingestion of different foods/nutrients may mark different shifts in the microbial colonization of the infant intestine as well as the consumption of probiotics. Aim: To analyze changes in microbiota composition and metabolic and cytokine profiles in fecal samples from infants with non-IgE mediated CMPA after successful milk challenges, tolerance acquisition, and increasing dairy introduction in their diet. Methods: Twelve children with CMPA, aged between 1 and 2 years old, were recruited for the study. Participants were initially consuming hypoallergenic hydrolyzed formulas (four of them supplemented with the probiotic Lactobacillus rhamnosus GG), before being exposed to a standardized oral challenge (SOC) with cow's milk. Fecal samples were collected before, 1 week, and 1 month after performing the SOC. Changes in gut microbiota were determined by high-throughput amplicon sequencing of the 16S rRNA gene. Levels of lactobacilli were also determined by quantitative PCR (qPCR). Microbial metabolites were analyzed by chromatographic methods and fecal cytokines related to the Th1/Th2 balance were determined by immunoassay. Results: Lactic acid bacteria significantly increased in infants who outgrew non-IgE CMPA, after the introduction of milk. Microbial metabolites derived from the fermentation of proteins, such as branched chain fatty acids, and p-cresol, diminished. After the SOC, some cytokines related to inflammation (TNF-α, IFN-γ) increased. Accompanying the introduction of an unrestricted diet, we found significant differences in fecal microbial composition, metabolites, and cytokines between infants who did not consume the probiotic L. rhamnosus GG and those that did. Conclusions: These findings indicate that the introduction of intact milk proteins is followed by modifications in the infant gut environment through changes in immune mediators, microbiota, and its metabolic end-products. Consumption of probiotics during CMPA may contribute to gut homeostasis by fine-tuning these profiles.

The objective of this letter of reply is to provide answers to the doubts and critical issues that Martín Martinez and López Liñan

Cow’s milk protein allergy (CMPA) is the most common food allergy in infancy. Non-IgE mediated (NIM) forms are little studied and the responsible mechanisms of tolerance acquisition remain obscure. Our aim was to study the intestinal microbiota and related parameters in the fecal samples of infants with NIM-CMPA, to establish potential links between type of formula substitutes, microbiota, and desensitization. Seventeen infants between one and two years old, diagnosed with NIM-CMPA, were recruited. They were all on an exclusion diet for six months, consuming different therapeutic protein hydrolysates. After this period, stool samples were obtained and tolerance development was evaluated by oral challenges. A control group of 10 age-matched healthy infants on an unrestricted diet were included in the study. Microbiota composition, short-chain fatty acids, calprotectin, and transforming growth factor (TGF)-β₁ levels were determined in fecal samples from both groups. Infants with NIM-CMPA that consumed vegetable protein-based formulas presented microbiota colonization patterns different from those fed with an extensively hydrolyzed formula. Differences in microbiota composition and fecal parameters between NIM-CMPA and healthy infants were observed. Non-allergic infants showed a significantly higher proportion of Bacteroides compared to infants with NIM-CMPA. The type of protein hydrolysate was found to determine gut microbiota colonization and influence food allergy resolution in NIM-CMPA cases.

Summary: Background: Little is known about the impact of Epstein‐Barr virus (EBV) infection on clinical outcomes in adults with inflammatory bowel disease (IBD).Aim: To evaluate seroprevalence, seroconversion rate and complications associated with EBV infection in an adult IBD cohort attending a tertiary care hospital in Spain between 2006 and 2016.Methods: EBV serological status was determined. In seronegative patients, the seroconversion rate was evaluated. The complications associated with primary and latent EBV infection are described.Results: One thousand four hundred and eighty‐three patients over the age of 17 were included in the study (mean age at EBV serological status determination was 48.3). Overall seroprevalence of EBV was 97.4% (95% CI: 96.6%‐98.2%). The seroconversion rate was 29.7% (95% CI: 16.2‐45.9) after a mean of 47.5 months. There were no differences in seroconversion rates between patients 35 years or younger and patients older than 35 years. A 66‐year‐old man, on treatment with thiopurines, developed lymphoma and a hemophagocytic syndrome during a primary EBV infection. Overall, six patients (one with primary infection and five with prior EBV infection) developed lymphoma. In three of five patients with lymphoma and thiopurine use, EBV was associated to the development of lymphoma.Conclusions: There is a small percentage of adults with IBD at risk of primary EBV infection. The risks of seroconversion and its complications remain through adulthood. Our results suggest that, when considering the use of thiopurines in IBD, the information on EBV serological status should be taken into account at any age.

A growing incidence of pediatric IBD (PIBD) in southern Europe has been recently reported. The SPIRIT registry (1996-2009) confirmed these tendencies in Spain. Our aim is to obtain data from 1985 to 1995 and describe the complete picture of PIBD presentation changes in Spain in the last 25years. A retrospective survey of incident PIBD in the period 1985-1995 was performed. Patients' data were obtained from the hospitals' databases and compared with the published data from the 1996 to 2009 period. Seventy-eight IBD reference centers took part in this survey. Data from 495 patients were obtained: 278 CD (56.2%), 198 UC (40%), and 19 IBDU (3.8%); 51.7% were female, with higher predominance both in UC (58.6%) and in IBDU (57.9%), but not in CD (46.4%). Median (IQR) age at diagnosis was 12.9 (10.0-15.7) years, with significant differences among IBD subtypes: CD: 13.1 (10.8-16.0) vs UC: 12.4 (9.4-15.1) vs IBDU: 7.5 (3.0-13.0) (p≤0.001). These results are significantly different to the ones in the SPIRIT registry, with a higher proportion of IBDU, younger age and male predominance. The data from both periods taken together give a complete picture of a 25-year period. An annual increase of incident patients was observed, with a ten-fold increase over this period. These data extend the epidemiological trends to a full 25-year period (1985-2009). PIBD incidence in Spain has experienced a sixteen-fold increase. The IBD subtype, localization of the affected segment, age- and sex distribution observed are in accordance with our previously published ones of 1996-2009.

Although pediatric inflammatory bowel disease (IBD) diagnosis has increased in the last decades in Spain, there are no consistent epidemiologic data. Our aim was to describe the changing pattern of pediatric IBD incidence in Spain in the last 14 years. A retrospective survey of patients diagnosed below 18 years of age in the period 1996-2009 was performed. Patients' data were obtained from the hospitals' databases. To avoid reduced accrual of cases diagnosed by adult physicians, adult IBD units in referral centers were invited to participate. Seventy-eight centers participated in our survey. Rates of incidence were calculated using age-stratified population-based epidemiologic data. Incidence rates were compared for the last 14 years (1996-2009). In total, data from 2107 patients were obtained: 1,165 Crohn's disease (CD, 55.3%), 788 ulcerative colitis (UC, 37.4%), and 154 IBD unclassified. The sex distribution was 56.4% male, with higher predominance for CD (59.3%) as compared to UC (52.8%) and IBD unclassified (53.2%) (P = 0.012). The median age at diagnosis was 12.3 years (p25-75 9.7-14.6) with significant differences between diseases. IBD incidence increased from 0.97 to 2.8/100,000 inhabitants <18 years/year in the study period. Although this increase is more evident for CD (from 0.53 to 1.7), UC has also risen considerably (0.39 to 0.88). This is the first attempt to calculate the current incidence of pediatric IBD in Spain. A significant increase of incidence rates in the study period was observed. In the last 14 years pediatric IBD incidence has almost tripled, with a more important CD increase.

Objective Longer-term effects of prolonged selective interleukin-1β blockade with canakinumab were evaluated in the largest cohort of cryopyrin-associated periodic syndrome (CAPS) patients studied to date. Methods Adult and paediatric CAPS patients (n=166, including canakinumab-naive and pretreated patients from previous studies) received canakinumab subcutaneously 150 mg or 2 mg/kg (≤40 kg) every 8 weeks for up to 2 years. Response and relapse was assessed using scores for disease activity, skin rash and C-reactive protein (CRP) and/or serum amyloid A (SAA) levels. Results Complete response was achieved in 85 of 109 canakinumab-naive patients (78%; 79/85 patients within 8 days, and five patients between days 10 and 21). Of 141 patients with an available relapse assessment, 90% did not relapse, their CRP/SAA levels normalised (Conclusions Subcutaneous canakinumab 150 mg every 8 weeks was well tolerated and provided substantial disease control in children and adults across all CAPS phenotypes. Higher canakinumab doses in younger patients and more severe CAPS disease were efficacious in achieving complete responses without evidence of increased AE. Trial registration number: NCT00685373 (clinicaltrials.gov)