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Aims i] To evaluate the evolution of pregnancies and offspring after inflammatory bowel disease [IBD] surgery during pregnancy; and ii] to describe the indications, the surgical techniques, and the frequency of caesarean section concomitant with surgery. Methods Patients operated on due to IBD during pregnancy after 1998 were included. Participating clinicians were asked to review their databases to identify cases. Data on patients’ demographics, IBD characteristics, medical treatments, IBD activity, pregnancy outcomes, surgery, delivery, and foetal and maternal outcomes, were recorded. Results In all, 44 IBD patients were included, of whom 75% had Crohn’s disease; 18% of the surgeries were performed in the first trimester, 55% in the second, and 27% in the third trimester. One patient had complications during surgery, and 27% had postsurgical complications. No patient died. Of deliveries, 70% were carried out by caesarean section. There were 40 newborns alive. There were four miscarriages/stillbirths [one in the first, two in the second, and one in the third trimester]; two occurred during surgery, and another two occurred 2 weeks after surgery; 14% of the surgeries during the second trimester and 64% of those in the third trimester ended up with a simultaneous caesarean section or vaginal delivery. Of the 40 newborns, 61% were premature and 47% had low birth weight; 42% of newborns needed hospitalisation [25% in the intensive care unit]. Conclusions IBD surgery during pregnancy remains an extremely serious situation. Therefore, surgical management should be performed in a multidisciplinary team, involving gastroenterologists, colorectal surgeons, obstetricians, and neonatal specialists.

Aims The aims of this study were (a) to know the kinetics of antitumor necrosis factor (TNF) drug serum levels during the induction phase in patients with Crohn's disease; (b) to identify variables associated with these levels; and (c) to assess the relation between these levels and short-term effectiveness in Crohn's disease patients. Methods Patients with Crohn's disease naive to anti-TNF treatment were prospectively included. Remission was defined as a Crohn's disease activity index (CDAI) score 150 at study entry. At week 14, 52 out of 71 patients with CDAI > 150 at baseline (73%) had clinical remission. There were no differences in infliximab levels between patients with and without remission (8 vs. 9.1 mu g/mL, P > 0.05) or with and without response (7 vs. 11 mu g/mL, P > 0.05) at week 14. There was a trend to higher levels of adalimumab concentration in responders in comparison with nonresponders (13 vs. 6.7 mu g/mL, P = 0.05) and in patients who achieved remission in comparison with nonremitters (13.5 vs. 8.4 mu g/mL, P = 0.06). In the multivariate analysis, no variable was predictive of short-term remission, including infliximab and adalimumab serum levels. Conclusion Determining anti-TNF serum levels during the induction phase is not useful for predicting short-term remission in patients with Crohn's disease.

Background Crohn’s disease (CD) affects young adults on reproductive age. They are likely to desire pregnancy and are often concerned about the potential effects of inflammatory bowel disease on fertility. Aims to investigate the effect of CD in fertility, studying the ovarian reserve in women by serum anti-Müllerian hormone (AMH) and Sertoli cell function in men measured by serum Inhibine (IB). Methods Cross-sectional, prospective, case-control study, including CD patients, aged 18–40 yr, and healthy controls(HC) matched by gender and age(ratio 2:1). Morning IB was measured using ELISA. Serum AMH was measured by ECLIA. Sociodemographic and phenotypic features of CD patients and controls were collected. We defined impaired fertility potential as IB level < 89 pg/mL and AMH Results A total of 122 subjects were included:73 men(48 CD, 25 HC) and 49 women(21 CD, 28 HC). No statistical difference was found between mean serum AMH levels in CD and HC women(2,23±1,8 vs 2,86±1,9 ug/L, p=0,5). The rate of abnormal serum AMH levels according to age did not differ between groups (19% CD vs 25% HC, p=0,4). When classified according to age(30 yr), the serum AMH levels remained comparable in 30 yr, 9 CD(90%)vs 4 in HC(40%)(p=0.02). Serum IB levels were significantly lower in CD men vs HC (175.4 ±62.3 vs 234.12±75.56 ug/L, p=0.002). We did not find abnormal IB( Conclusion Women with CD did not have severe ovarian reserve alterations compared to a control population. However higher proportion of CD women showed low AMH (< 2 ug/L), especially those > 30 years. These data could be helpful for female CD patients who want to have children. Inhibine levels, as biomarker of Sertoli cell function, were lower in CD men compared to healthy controls.

Background Patients with Crohn’s disease (CD) responding to anti–tumor necrosis factor (anti-TNF) show great variability in serum drug levels, even within the therapeutic range. We aimed at exploring the role of inflammatory, genetic, and bacterial variables in relation to anti-TNF through levels in CD patients. Methods Consecutive CD patients receiving stable doses of infliximab or adalimumab were included. Clinical and analytical parameters were recorded. Cytokine response, bacterial DNA translocation, and several immune-related genes’ genotypes were evaluated, along with serum through anti-TNF drug levels. A linear regression analysis controlled by weight and drug regimen was performed. Results One hundred nineteen patients were initially considered. Five patients on infliximab and 2 on adalimumab showed antidrug antibodies in serum and were excluded. One hundred twelve patients were finally included (62 on infliximab, 50 on adalimumab). Fourteen patients on infliximab and 15 on adalimumab (22.6% vs 30%, P = 0.37) were receiving an intensified drug regimen. C-reactive protein (CRP), fecal calprotectin, Crohn’s Disease Activity Index, leukocyte count, and albumin levels in plasma were not significantly associated with infliximab or adalimumab levels in the multivariate analysis. Serum interleukin-10 (IL-10) levels were directly related to infliximab (Beta = 0.097, P < 0.0001) and adalimumab levels (Beta = 0.069, P = 0.0241). The best multivariate regression model explaining the variability of serum infliximab and adalimumab levels included IL-10. Predicted drug levels by this model robustly fitted with actual drug levels (R2 = 0.841 for infliximab, R2 = 0.733 for adalimumab). Conclusion Serum IL-10 is significantly related to serum anti-TNF levels in CD patients, showing how the disposition of anti-TNF drugs is significantly influenced by the degree of immunological activation.

Background The prevalence of sexual dysfunction (SD) in general population has been estimated up to 30% in women and 5% in men, and 50% and 25% in IBD patients, respectively. We aimed to compare the rates of SD in young patients with Crohn’s disease (CD) with healthy controls (HC), as well as to identify SD associated factors in CD patients. Methods This was a cross-sectional, case-control, observational study, including CD out-patients, aged 18–40 years-old, and HC paired by gender and age. Sociodemographic and disease features were recorded. SD was measured by the Index of Female Sexual Function(IFSF) in women, and by International Index of Erectile Function(IIFE-15) in men. Psychological functioning was evaluated using the Hospital Anxiety and Depression Scale [HAD], and quality of life in IBD by SIBDQ-9. Differences between groups were statistically compared. Results A total of 122 subjects were included:73 men(48 CD, 25 HC) and 49 women(21 CD, 28 HC). Nineteen percent of CD women and 8.3% of men had active disease according to Harvey-Bradshaw Index. Nineteen percent of CD women and 6.3% of men were receiving steroids, 23.8% and 14.6% immunosuppressants, and 71.4% and 72.9% biologics, respectively. CD women had more sedentary lifestyle than HC(38.1% vs 3.6%, p=0.005). In women SD rates were 35% in CD vs 12% in HC(p < 0.08). Mean IFSF values were lower in CD women(27 CD vs 30 HC, p=0.02), as well as in the desire item(3.5 CD vs 4.3 HC, p=0.005). SD in men did not show significant difference between groups. Mean IIFE values differed between CD and HC(53.6 vs 67.2, p=0.001), as well as erectile disfunction, orgasm and global satisfaction(p< 0.05)(Table 1). Main factors associated with an abnormal SD in CD women were high fecal calprotectine, current use of steroids, lower SIBDQ score and higher depression score(p Conclusion In our serie SD was numerically higher in CD patients compared to HS. SD in CD women, but not in men, was driven by disease activity, current steroid treatment and depression.

Background Granulocyte and monocyte apheresis is the main non-pharmacological treatment for inflammatory bowel disease (IBD), but we do not know how well accepted it is by patients in our setting. Aim To determine how granulocyte and monocyte apheresis is perceived by patients in clinical practice in Spain. Methods Outpatients treated with granulocyte and monocyte apheresis in five IBD Units in Spain were asked to fill in a 14-item questionnaire. Results Fifty-two patients completed the questionnaire (88% ulcerative colitis, 12% Crohn's disease; 44% female; age 35 years [IQR 23–51]). Granulocyte and monocyte apheresis was generally well tolerated and well accepted. Very few of the participants regarded the length of the sessions as a limitation. The gastrointestinal symptoms, however, were a frequent concern, both in terms of attending to receive treatment and during the sessions. Overall, 44% were satisfied with the treatment effectiveness. Sixty percent (60%) claimed to be satisfied with the therapy overall, but this was influenced by the patients’ clinical response to the therapy. Eighty-two percent (82%) of participants said they would agree to be treated with this technique again in the future, regardless of the response to the treatment. Conclusions Granulocyte and monocyte apheresis is well tolerated and accepted by patients with IBD. Although we found no significant differences according to type of IBD or apheresis regimen, patient perception was affected by clinical effectiveness.

Interleukin IL26 supports killing of microbes and the innate sensing of bacterial-derived DNA (bactDNA). We evaluated the relationship between IL26 serum levels and bactDNA translocation in Crohn's disease (CD). We ran a prospective study on CD patients in remission. IL26 common polymorphisms, serum cytokines and complement protein, amplified-bactDNA, and anti-TNF-α were evaluated. In vitro PBMC analysis was performed. Three hundred and thirteen patients were included (mean CDAI: 83.6 ± 32.8; mean fecal calprotectin: 55.4 ± 35.3 μg/g). A total of 106 patients (33.8%) showed bactDNA and 223 patients (71%) had a varIL26 genotype. BactDNA significantly correlated with increased IL26 levels compared with bactDNA-negative patients. PBMCs from varIL26 patients significantly reduced E. coli killing capacity compared with wtIL26-genotyped patients. The stimulation with a recombinant IL26 protein reduced pro-inflammatory cytokines in response to E. coli in the varIL26 cell supernatants. Serum anti-TNF-α levels in varIL26 vs wtIL26-genotyped patients on biologics were significantly lower in the presence of bactDNA. Cells from varIL26 vs wtIL26-genotyped patients cultured with E. coli DNA and infliximab showed a significant decrease in free anti-TNF-α concentration. A varIL26 genotype was associated with the initiation of anti-TNF-α in CD patients during the 6-month follow-up. IL26 polymorphisms may prevent bactDNA clearance and identify CD patients with a worse inflammatory evolution and response to therapy.BactDNA translocation in CD is associated with an increased risk of relapse. IL26 is sensitive to bactDNA and modulates the inflammatory response in CD patients. The varIL26 genotype is associated with reduced PMN capacity to kill bacteria. A varIL26 genotype is associated with decreased levels of anti-TNF-α in CD patients. IL26 may help explain the role of bactDNA as a risk factor of flare in CD patients.

Anti-TNF-α therapies interact with the tolerogenic response in patients with Crohn’s disease, modulating inflammation. However, drug levels and the genetic background may affect this interaction. Patients with Crohn’s disease in remission on biologic monotherapy were enrolled in this study. FoxP3+ lymphocytes, NOD2 genotype, serum cytokine, anti-TNF-α levels, and anti-drug antibodies were evaluated. Regulatory T cell response to infliximab was evaluated in vitro. Fifty-seven patients were included. Thirty-nine patients (68.4 %) were receiving non-intensified biologic therapy whereas 18 patients (31.6 %) were under an intensified biologic schedule due to loss of response. Eleven intensified patients (61.1 %) showed a variant NOD2 genotype vs 9 on non-intensified biologics (23 %, p

Background: The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. Methods: In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54 weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. Results: Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's disease patients treated with IFX. AntiIFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3 nM). The threshold level of ATI in order to classify the immunogenicity of the patients was 10 nM. We observed that 24% (12/50) of IFX-treated patients developed ATI (>10 nM) during the observation period (54 weeks). Serum concentration of ATI higher than 10 nM dramatically increased the probability (OR = 51.1; 95% CI: 20.4-128.0; p < 0.0001) of presenting low levels of IFX (

OBJECTIVES: We aimed at evaluating bacterial DNA (bactDNA) presence in blood of Crohn's disease (CD) patients in remission as an independent risk factor of flare at 6 months. METHODS: This is a prospective, multicenter study on CD patients with Crohn's disease activity index (CDAI)150 in the following 6 months. BactDNA in blood, the nucleotide-binding oligomerization domain containing 2 (NOD2) genotype, and serum cytokine levels were determined at baseline. RESULTS: A total of 288 patients were included. BactDNA was detected in 98 patients (34.0%). A variantNOD2 genotype was identified in 114 patients (39.6%). Forty patients (14%) relapsed during follow-up. Multivariate survival analysis identified bactDNA as an independent risk factor of flare (hazard ratio (HR) 8.75 (4.02-19.06) 95% confidence interval (CI)). Hospitalization, surgery, switch of treatment, initiation and escalation of anti-tumor necrosis factor (TNF) therapy, steroids initiation, and increased fecal calprotectin levels at 6 months were associated with bactDNA at baseline. A logistic regression analysis showed bactDNA as an independent and significant predictive factor of hospitalization (odds ratio (OR) 11.9 (3.4-42.3); P

Objective The aetiology of Crohn9s disease (CD) has been related to nucleotide-binding oligomerisation domain containing 2 (NOD2) and ATG16L1 gene variants. The observation of bacterial DNA translocation in patients with CD led us to hypothesise that this process may be facilitated in patients with NOD2/ATG16L1-variant genotypes, affecting the efficacy of anti-tumour necrosis factor (TNF) therapies. Design 179 patients with Crohn9s disease were included. CD-related NOD2 and ATG16L1 variants were genotyped. Phagocytic and bactericidal activities were evaluated in blood neutrophils. Bacterial DNA, TNFα, IFNγ, IL-12p40, free serum infliximab/adalimumab levels and antidrug antibodies were measured. Results Bacterial DNA was found in 44% of patients with active disease versus 23% of patients with remitting disease (p=0.01). A NOD2-variant or ATG16L1-variant genotype was associated with bacterial DNA presence (OR 4.8; 95% CI 1.1 to 13.2; p=0.001; and OR 2.4; 95% CI 1.4 to 4.7; p=0.01, respectively). This OR was 12.6 (95% CI 4.2 to 37.8; p=0.001) for patients with a double-variant genotype. Bacterial DNA was associated with disease activity (OR 2.6; 95% CI 1.3 to 5.4; p=0.005). Single and double-gene variants were not associated with disease activity (p=0.19). Patients with a NOD2-variant genotype showed decreased phagocytic and bactericidal activities in blood neutrophils, increased TNFα levels in response to bacterial DNA and decreased trough levels of free anti-TNFα. The proportion of patients on an intensified biological therapy was significantly higher in the NOD2-variant groups. Conclusions Our results characterise a subgroup of patients with CD who may require a more aggressive therapy to reduce the extent of inflammation and the risk of relapse.