The need for surgery in pediatric patients with inflammatory bowel disease treated with biologicals.

PURPOSE: Inflammatory bowel disease (IBD) in childhood often presents with a more extensive and more aggressive disease course than adult-onset disease. We aimed to evaluate if biological treatment started in childhood decreases the need for intestinal surgery over time. METHODS: This was a retrospective, single-center, cohort study. All pediatric patients with IBD initiated to biological therapy at the Children's Hospital, were included in the study and followed up to the first surgical procedure or re-operation in their adulthood or until 31.12.2021 when ≥ 18 of age. Data were collected from the pediatric registry of IBD patients with biologicals and medical charts. RESULTS: A total of 207 pediatric IBD patients were identified [150 with Crohn´s disease (CD), 31 with ulcerative colitis (UC), 26 with IBD unclassified (IBDU)] of which 32.9% (n = 68; CD 49, UC 13, IBDU 6) underwent intestinal surgery. At the end of a median follow-up of 9.0 years (range 2.0-25.9), patients reached a median age of 21.4 years (range 18-36). Patients who had intestinal surgery in childhood were more likely to have IBD-related surgery also in early adulthood. The duration of the disease at induction of the first biological treatment emerged as the only risk factor, with a longer duration in the surgical group than in patients with no surgery. CONCLUSION: Despite initiation of biological treatment, the risk of intestinal surgery remains high in pediatric IBD patients and often the need for surgery emerges after the transition to adult IBD clinics.

Drug levels of VEDOLIZUMAB in patients with pediatric-onset inflammatory bowel disease in a real-life setting.

Vedolizumab (VDZ) is used off-label in pediatric inflammatory bowel disease (PIBD). There are less data on drug levels to achieve and maintain remission in children. We aimed to study vedolizumab (VDZ) trough levels in a pediatric population in a real-life setting. We traced 50 patients with PIBD receiving VDZ treatment at our hospital, reviewed their treatment protocol, trough levels, and antidrug antibodies, and compared those to fecal calprotectin (FC) levels and achievement of corticosteroid-free maintenance therapy (CF). VDZ trough level was available from 198 samples during a median follow- up of 12.6 months. Proceeding to maintenance therapy was associated with a decline in FC but not with VDZ trough levels that were comparable between patients with FC < 100 µg/g (remission), 100-1000 µg/g, or > 1000 µg/g at 3 months (mean levels of 36.8, 28.6, and 27 µg/mL, respectively p = 0.188). At 3 months, patients achieving CF (41%) and those on corticosteroids had comparable VDZ trough levels (33 vs. 27.5 µg/mL, respectively). At 6 months, the trough level was similar in groups with FC < 100 µg/g or FC > 1000 µg/g (31.5 and 27.6 µg/mL, p = 0.859). Treatment intensification did not improve the achieved CF at 12 months. None developed drug antibodies nor discontinued the therapy for an adverse event.   Conclusion: VDZ was a well-tolerated and safe biologic treatment. A positive response on gut inflammation after induction predicted proceeding to maintenance therapy whereas trough levels did not. A VDZ trough level associated with clinical remission or continuing with VDZ treatment could not be determined. What is Known: • In pediatric inflammatory bowel disease, vedolizumab is still in off-label use. • The results on the relationship between drug levels of vedolizumab and clinical remission in pediatric patients are contradictory. What is New: • This real-life setting in pediatric-onset inflammatory bowel disease showed no benefit of therapy enhancement during a median follow-up of one year. • Trough levels of vedolizumab were not associated with therapy outcomes.

The Association between Genetics and Response to Treatment with Biologics in Patients with Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, and Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.

Genetic biomarkers could potentially lower the risk of treatment failure in chronic inflammatory diseases (CID) like psoriasis, psoriatic arthritis (PsA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis assessing the association between single nucleotide polymorphisms (SNPs) and response to biologics. Odds ratio (OR) with 95% confidence interval (CI) meta-analyses were performed. In total, 185 studies examining 62,774 individuals were included. For the diseases combined, the minor allele of MYD88 (rs7744) was associated with good response to TNFi (OR: 1.24 [1.02-1.51], 6 studies, 3158 patients with psoriasis or RA) and the minor alleles of NLRP3 (rs4612666) (OR: 0.71 [0.58-0.87], 5 studies, 3819 patients with RA or IBD), TNF-308 (rs1800629) (OR: 0.71 [0.55-0.92], 25 studies, 4341 patients with psoriasis, RA, or IBD), FCGR3A (rs396991) (OR: 0.77 [0.65-0.93], 18 studies, 2562 patients with psoriasis, PsA, RA, or IBD), and TNF-238 (rs361525) (OR: 0.57 [0.34-0.96]), 7 studies, 818 patients with psoriasis, RA, or IBD) were associated with poor response to TNFi together or infliximab alone. Genetic variants in TNFα, NLRP3, MYD88, and FcRγ genes are associated with response to TNFi across several inflammatory diseases. Most other genetic variants associated with response were observed in a few studies, and further validation is needed.

Crohn's disease is associated with higher rates of implant-related complications following primary total knee arthroplasty.

INTRODUCTION: In Western countries, there has been a rise in the prevalence of Crohn's Disease (CD) and primary total knee arthroplasty (TKA). This study delves deeper into the effects of CD on TKA patients by examining (1) the length of in-hospital stay (LOS); (2) the rates of readmission; (3) complications related to implants; and (4) the costs associated with care. METHODS: A retrospective analysis using the PearlDiver database was conducted, encompassing the time frame between January 1st, 2005 and March 31st, 2014, focusing on patients who underwent TKA and were either diagnosed with CD or not. Patients with CD were paired with control subjects at a 1:5 ratio based on age, gender, and medical comorbidities. The analysis comprised a total of 96,229 patients (CD = 16,039; non-CD = 80,190). RESULTS: Patients with CD had a notably longer hospital stay (3 v. 2 days, p < 0.0001) and faced significantly higher rates of 90-day readmissions and complications (19.80% v. 14.91%, OR: 1.40, p < 0.0001; 6.88% v. 4.88%, OR: 1.43, p < 0.0001 respectively). Additionally, CD patients incurred greater expenses on the surgery day ($18,365.98 v. $16,192.00) and within 90 days post-surgery ($21,337.46 v. $19,101.42). CONCLUSION: This study demonstrates longer in-hospital LOS, higher rates of readmissions, implant-related complications, and costs of care among CD patients following primary TKA.

The emerging roles of autophagy in intestinal epithelial cells and its links to inflammatory bowel disease.

Landmark genome-wide association studies (GWAS) identified that mutations in autophagy genes correlated with inflammatory bowel disease (IBD), a heterogenous disease characterised by prolonged inflammation of the gastrointestinal tract, that can reduce a person's quality of life. Autophagy, the delivery of intracellular components to the lysosome for degradation, is a critical cellular housekeeping process that removes damaged proteins and turns over organelles, recycling their amino acids and other constituents to supply cells with energy and necessary building blocks. This occurs under both basal and challenging conditions such as nutrient deprivation. An understanding of the relationship between autophagy, intestinal health and IBD aetiology has improved over time, with autophagy having a verified role in the intestinal epithelium and immune cells. Here, we discuss research that has led to an understanding that autophagy genes, including ATG16L, ATG5, ATG7, IRGM, and Class III PI3K complex members, contribute to innate immune defence in intestinal epithelial cells (IECs) via selective autophagy of bacteria (xenophagy), how autophagy contributes to the regulation of the intestinal barrier via cell junctional proteins, and the critical role of autophagy genes in intestinal epithelial secretory subpopulations, namely Paneth and goblet cells. We also discuss how intestinal stem cells can utilise autophagy. Importantly, mouse studies have provided evidence that autophagy deregulation has serious physiological consequences including IEC death and intestinal inflammation. Thus, autophagy is now established as a key regulator of intestinal homeostasis. Further research into how its cytoprotective mechanisms can prevent intestinal inflammation may provide insights into the effective management of IBD.

Symptoms and symptom clusters in patients newly diagnosed with inflammatory bowel disease: results from the IBSEN III Study.

BACKGROUND: Patients with inflammatory bowel disease report multiple symptoms, but the relationships among co-occurring symptoms are poorly understood. This study aimed to examine the prevalence of symptoms and explore symptom clusters and possible associations between symptom clusters and socio-demographic and clinical variables in patients newly diagnosed with inflammatory bowel disease. METHODS: The IBSEN III study is a prospective population-based inception cohort of patients with inflammatory bowel disease. This study used patient data from the three largest hospitals in the study catchment area. The Memorial Symptom Assessment Scale was used to assess the prevalence of symptoms. Symptom clusters were identified using principal component analysis. Possible associations between socio-demographic and clinical variables and symptom cluster membership were estimated using regression analysis. RESULTS: Of the 573 patients (age, ≥18 years) diagnosed with inflammatory bowel disease, 350 (61.1%) completed the questionnaire (responders). Eleven symptoms were reported by >50% of the responders. The three most prevalent symptoms were bloating (84%), drowsiness (81%), and lack of energy (81%). Three symptom clusters were identified: psychological (56% of the patients), impaired energy (28%), and physical (16%) clusters. Multinomial regression analysis revealed that vitamin D deficiency was significantly associated with the impaired energy cluster (odds ratio=2.49, 95% confidence interval [1.00-6.2], p=0.05). CONCLUSIONS: We found high symptom prevalence in patients newly diagnosed with inflammatory bowel disease. Three distinct symptom clusters were identified, and the psychological cluster includes >50% of the patients. Vitamin D deficiency is the only factor associated with cluster membership, namely the impaired energy cluster.

Isotretinoin and the risk of inflammatory bowel disease and irritable bowel syndrome: A large-scale global study.

INTRODUCTION: Risk of inflammatory bowel disease under isotretinoin is a scope of a long-standing controversy. The burden of isotretinoin-related irritable bowel syndrome has not been investigated. OBJECTIVE: To evaluate the risk of Crohn's disease, ulcerative colitis (UC), and irritable bowel syndrome in patients with acne starting isotretinoin vs oral antibiotics treatment. METHODS: A global population-based retrospective cohort study assigned 2 groups of patients with acne initiating isotretinoin (n = 77,005) and oral antibiotics (n = 77,005). Comprehensive propensity-score matching was conducted. RESULTS: The lifetime risk of Crohn's disease (hazard ratio [HR], 1.05; 95% CI, 0.89-1.24; P = .583) and UC (HR, 1.13; 95% CI, 0.95-1.34; P = .162) was comparable between study groups, whereas the lifetime risk of irritable bowel syndrome was lower in isotretinoin-prescribed patients (HR, 0.82; 95% CI, 0.76-0.89; P < .001). In time-stratified analysis, isotretinoin-related risk of UC was significantly increased during the first 6 months following drug initiation (HR, 1.93; 95% CI, 1.29-2.88; P = .001), but decreased afterward to level the risk of the comparator group. The absolute risk difference within the first 6 months was clinically marginal (5.0 additional UC cases/10,000 patients starting isotretinoin; 95% CI, 2.5-7.7). LIMITATIONS: Retrospective data collection. CONCLUSION: Isotretinoin does not confer an elevated risk of Crohn's disease, whilst it might be associated with a slight and transient increase in UC risk.

Predictors of pouch failure: A tertiary care inflammatory bowel disease centre experience.

AIM: Rates of pouch failure after total proctocolectomy with ileal pouch-anal anastomosis (IPAA) range from 5% to 18%. There is little consistency across studies regarding the factors associated with failure, and most include patients who underwent IPAA in the pre-biologic era. Our aim was to analyse a cohort of patients who underwent IPAA in the biologic era at a large-volume inflammatory bowel disease institution to better determine preoperative, perioperative and postoperative factors associated with pouch failure. METHODS: A retrospective cohort analysis was performed with data from an institutional review board approved prospective database with ulcerative colitis or unclassified inflammatory bowel disease patients who underwent total proctocolectomy with IPAA at Mount Sinai Hospital between 2008 and 2017. Preoperative, perioperative and postoperative data were collected and univariate and multivariate analyses were performed to identify factors associated with increased risk of pouch failure. RESULTS: Out of 664 patients included in the study, pouch failure occurred in 41 (6.2%) patients, a median of 23.3 months after final surgical stage. Of these, 17 (41.4%) underwent pouch excision and 24 (58.5%) had diverting ileostomies. The most common indications for pouch failure were Crohn's disease like pouch inflammation (CDLPI) (n = 17, 41.5%), chronic pouchitis (n = 6, 14.6%), chronic cuffitis (n = 5, 12.2%) and anastomotic stricture (n = 4, 9.8%). On multivariate analysis, pre-colectomy biologic use (hazard ratio [HR] 2.25, 95% CI 1.09-4.67), CDLPI (HR 3.18, 95% CI 1.49-6.76) and pouch revision (HR 2.59, 95% CI 1.26-5.32) were significantly associated with pouch failure. CONCLUSIONS: Pouch failure was significantly associated with CDLPI, preoperative biologic use and pouch revision; however, reassuringly it was not associated with postoperative complications.

Altered fecal bile acid composition in active ulcerative colitis.

BACKGROUND: Disturbed bile acid homeostasis associated with a rise of primary and a decline of secondary bile acids is a consistent finding in inflammatory bowel diseases (IBDs). Whether fecal bile acids may emerge as biomarkers for IBD diagnosis and disease severity is less clear. Our study aimed to identify associations of 18 fecal bile acid species with IBD entity and disease activity. METHODS: Stool samples of 62 IBD patients and 17 controls were collected. Eighteen fecal bile acid species were quantified by LC-MS/MS using stable isotope dilution. Lipid levels normalized to a dry weight of the fecal homogenates and ratios of single bile acid species to total bile acid levels were used for calculations. RESULTS: IBD patients exhibited altered primary and secondary bile acid ratios in stool, with notable distinctions between ulcerative colitis (UC) compared to Crohn's disease (CD) and healthy controls. Fecal calprotectin was negatively correlated with glycolithocholic acid (GLCA) and hyodeoxycholic acid (HDCA) in UC. These bile acids were reduced in stool of UC patients with fecal calprotectin levels > 500 µg/g compared to UC patients with low calprotectin levels. Moreover, negative associations of six secondary bile acids with C-reactive protein (CRP) existed in UC. In CD patients, fecal bile acids did not correlate with CRP or fecal calprotectin. Diarrhoea is common in IBD, and UC patients with diarrhoea had reduced deoxycholic acid (DCA), glycine conjugated DCA (GDCA) and lithocholic acid in stool in contrast to patients with normal stool consistency. Fecal bile acid levels were not associated with diarrhoea in CD patients. UC patients treated with mesalazine had increased levels of fecal GDCA whereas no such changes were observed in CD patients. Bile acid levels of CD and UC patients treated with biologicals or corticosteroids did not change. Relative levels of GHDCA (specificity: 79%, sensitivity: 67%) and glycochenodeoxycholic acid (specificity: 74%, sensitivity: 63%) were the most specific to distinguish UC from CD. CONCLUSION: Disrupted fecal bile acid homeostasis is associated with disease severity and disease symptoms in UC but not in CD, potentially aiding in distinguishing IBD subtypes and classifying the pathophysiology of diarrhoea in UC.

Fecal short chain fatty acids and urinary 3-indoxyl sulfate do not discriminate between patients with Crohn´s disease and ulcerative colitis and are not of diagnostic utility for predicting disease severity.

BACKGROUND: Urinary 3-indoxyl sulfate levels as well as fecal short chain fatty acid (SCFA) concentrations are surrogate markers for gut microbiota diversity. Patients with inflammatory bowel diseases (IBDs) and patients with primary sclerosing cholangitis (PSC), a disease closely associated with IBD, have decreased microbiome diversity. In this paper, the fecal SCFAs propionate, acetate, butyrate and isobutyrate of patients with IBD and patients with PSC-IBD and urinary 3-indoxyl sulfate of IBD patients were determined to study associations with disease etiology and severity. METHODS: SCFA levels in feces of 64 IBD patients and 20 PSC-IBD patients were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Urinary 3-indoxyl sulfate levels of 45 of these IBD patients were analysed by means of reversed-phase liquid chromatography-electrospray ionization-tandem mass spectrometry. Feces of 17 healthy controls and urine of 13 of these controls were analyzed in parallel. These cohorts had comparable sex distribution and age. RESULTS: Urinary 3-indoxyl sulfate concentrations (normalized to urinary creatinine levels) was increased (P = 0.030) and fecal isobutyrate levels (normalized to dry weight of the stool sample) of IBD patients were decreased (P = 0.035) in comparison to healthy controls. None of the analyzed metabolites differed between patients with Crohn´s disease (CD) and patients with ulcerative colitis (UC). Fecal acetate and butyrate positively correlated with fecal calprotectin (P = 0.040 and P = 0.005, respectively) and serum C-reactive protein (P = 0.024 and P = 0.025, respectively) in UC but not CD patients. UC patients with fecal calprotectin levels above 150 µg/g, indicating intestinal inflammatory activity, had higher fecal acetate (P = 0.016), butyrate (P = 0.007) and propionate (P = 0.046) in comparison to patients with fecal calprotectin levels < 50 µg/g. Fecal SCFA levels of PSC-IBD and IBD patients were comparable. CONCLUSIONS: Current findings suggest that analysis of urinary 3-indoxyl-sulfate as well as fecal SCFAs has no diagnostic value for IBD and PSC-IBD diagnosis or monitoring of disease severity.

Current management of bowel failure due to Crohn's disease in Spain: Results of a GETECCU survey. / Manejo actual del fracaso intestinal por enfermedad de Crohn en nuestro medio: resultados de una encuesta GETECCU.

INTRODUCTION: Intestinal failure is a rare pathology which requires knowledge and highly specialized multidisciplinary management. Crohn's disease (CD) being one of the most frequent causes in adults. MATERIAL AND METHODS: Survey format study carried out within the GETECCU group, included closed format questions about the diagnosis, management and current knowledge of intestinal failure in CD. RESULTS: Forty-nine doctors participated, belonging to different Spanish centers (19 cities). It was considered that a patient suffered from intestinal failure, in 67.3% (33/49 surveyed) when there was a disorder malabsorptive associated regardless of the intestinal length resected, with surgeries resective ileal repeated (40.8%, 20/49), the most frequent cause. It highlights frequent ignorance about the pathology (24.5%) did not know if there were patients in their center and also 40% did not know the pharmacological treatment. A total of 228 patients were registered for follow-up due to intestinal failure of any aetiology, 89 patients (39.5%) were identified with CD. Regarding the therapeutic management of patients with CD and intestinal failure (72.5%) were receiving total parenteral nutrition (NTP) and 24 patients (27%) with teduglutide. Regarding the response to the drug: 37.5% had no response to teduglutide, 37.5% partial response (reduce NTP) and 25% good response (withdrawal of home NTP). In questions related to knowledge about intestinal failure, it was considered limited (53.1%) or very limited (12.2%) by the surveyed. CONCLUSION: It is necessary to carry out a combined management of intestinal failure and CD in the context of a multidisciplinary approach.

Small intestine adenocarcinoma associated with Crohn´s disease.

This case report presents a patient diagnosed with small intestine adenocarcinoma associated with Crohn´s disease. Intestinal cancer is a feared and rare complication of idiopathic bowel diseases. The most important factors for dysplasia include extensive involvement of the intestine and a long-term inflammatory process.

Small-molecule Wnt inhibitors are a potential novel therapy for intestinal fibrosis in Crohns disease.

Intestinal fibrosis and stricture formation is an aggressive complication of Crohns disease (CD), linked to increased morbidity and costs. The present study investigates the contribution of Wingless-Int-1 (Wnt) signalling to intestinal fibrogenesis, considers potential cross-talk between Wnt and transforming growth factor ß1 (TGFß) signalling pathways, and assesses the therapeutic potential of small-molecule Wnt inhibitors. ß-catenin expression was explored by immunohistochemistry (IHC) in formalin-fixed paraffin embedded (FFPE) tissue from patient-matched nonstrictured (NSCD) and strictured (SCD) intestine (n=6 pairs). Functional interactions between Wnt activation, TGFß signalling, and type I collagen (Collagen-I) expression were explored in CCD-18Co cells and primary CD myofibroblast cultures established from surgical resection specimens (n=16) using small-molecule Wnt inhibitors and molecular techniques, including siRNA-mediated gene knockdown, immunofluorescence (IF), Wnt gene expression arrays, and western blotting. Fibrotic SCD tissue was marked by an increase in ß-catenin-positive cells. In vitro, activation of Wnt-ß-catenin signalling increased Collagen-I expression in CCD-18Co cells. Conversely, ICG-001, an inhibitor of ß-catenin signalling, reduced Collagen-I expression in cell lines and primary CD myofibroblasts. TGFß increased ß-catenin protein levels but did not activate canonical Wnt signalling. Rather, TGFß up-regulated WNT5B, a noncanonical Wnt ligand, and the Wnt receptor FZD8, which contributed directly to the up-regulation of Collagen-I through a ß-catenin-independent mechanism. Treatment of CCD-18Co fibroblasts and patient-derived myofibroblasts with the FZD8 inhibitor 3235-0367 reduced extracellular matrix (ECM) expression. Our data highlight small-molecule Wnt inhibitors of both canonical and noncanonical Wnt signalling, as potential antifibrotic drugs to treat SCD intestinal fibrosis. They also highlight the importance of the cross-talk between Wnt and TGFß signalling pathways in CD intestinal fibrosis.

Morphology of inflammatory bowel diseases (IBD).

Inflammatory bowel diseases (IBD) represent a group of chronic systemic inflammatory conditions with predilection to gastrointestinal tract and include Crohns disease and ulcerative colitis. If the IBD cannot be further specified, a term unclassified IBD is used. Histopathological diagnosis of IBD relies on identifying a chronic inflammatory pattern in proper topographic distribution, showing structural abnormalities of the intestinal mucosa and characteristic cellular composition of the inflammatory infiltrate. The intestinal involvement in Crohns disease is typically segmental, with predilection for terminal ileum and presence of epithelioid granulomas in histology. Ulcerative colitis shows a diffuse pattern of the inflammation and usually affects a rectum, with variable extension towards a terminal ileum. However, there is an expanding knowledge about etiopathogenesis, morphology and clinical presentation of IBD, which led to detailed phenotypic subclassification and defined many atypical variants. As a result, diagnosis of IBD became complex multidisciplinary process. The aim of this work is to present an overview of IBD morphology and to provide a base for histopathological diagnosis of IBD on both bioptic samples and surgical resections.

Surgical treatment of Crohns disease in children in the era of biological treatment.

INTRODUCTION: The incidence of Crohns disease in the paediatric population has been increasing and requires surgical treatment in addition to conservative therapy. While surgical treatment used to be the last step after the failure of all conservative therapies, nowadays it is a standard part of complex treatment. Surgery can enter the treatment process at any stage of the disease and, with a proper indication, timing and preoperative optimization, it can induce immediate remission in patients. On the other hand, with inadequate or improper preoperative preparation and indication, surgical treatment can cause serious or even life-threatening complications. The spectrum of patients undergoing surgery is changing in the era of biological therapy. The aim of this review was to summarize the current knowledge of the impact of biological (anti-TNF alpha) therapy on the development of postoperative complications in children and adolescents operated for Crohns disease. METHODS: We present a review based on literature available in MEDLINE-PubMed and Embase databases. CONCLUSION: According to current knowledge, no association was found between biological treatment in the preoperative period and the development of postoperative complications in paediatric patients. Surgical treatment of paediatric patients with Crohns disease is one of standard treatment modalities.

Rare and common variant discovery in complex disease: the IBD case study.

Complex diseases such as inflammatory bowel disease (IBD), which consists of ulcerative colitis and Crohn's disease, are a significant medical burden-70 000 new cases of IBD are diagnosed in the United States annually. In this review, we examine the history of genetic variant discovery in complex disease with a focus on IBD. We cover methods that have been applied to microsatellite, common variant, targeted resequencing and whole-exome and -genome data, specifically focusing on the progression of technologies towards rare-variant discovery. The inception of these methods combined with better availability of population level variation data has led to rapid discovery of IBD-causative and/or -associated variants at over 200 loci; over time, these methods have grown exponentially in both power and ascertainment to detect rare variation. We highlight rare-variant discoveries critical to the elucidation of the pathogenesis of IBD, including those in NOD2, IL23R, CARD9, RNF186 and ADCY7. We additionally identify the major areas of rare-variant discovery that will evolve in the coming years. A better understanding of the genetic basis of IBD and other complex diseases will lead to improved diagnosis, prognosis, treatment and surveillance.

Twenty-five years of biologicals in IBD: What´s all the hype about?

Twenty-five years ago the field was revolutionized by the introduction of infliximab as the first hybrid anti-TNF-antibody. Subsequently, other humanized anti-TNFs were developed and marketed, followed by antibodies to new targets including integrins (vedolizumab) and interleukin 12/23 (ustekinumab). All these so-called biologicals were shown in registrational trials to induce remission superior to placebo but consistently were effective in only a minority of patients. Even though in most trials only the responders were selected to continue on the respective medication for maintenance, many experienced a secondary loss of response and only a minority of usually <25% of the initial cohort achieved long-term (1 year) remission. In 'real life studies', the outcome was somewhat better, probably due to proper selection of patients and open, mostly retrospective study designs. A clear benefit of biologicals is apparent in otherwise treatment refractory patients, in extraintestinal manifestations and in Crohn´s disease (CD) with fistulizing complications. Biologicals achieve mucosal healing (MH) more often than corticosteroids or thiopurines, and MH is associated with improved prognosis. However, this does not justify escalating treatment until MH is reached since controlled trials proving this point of 'treat to target' are lacking both in ulcerative colitis and CD. Surgical rates have decreased with increasing use of biologicals, but disease progression has not been proven to improve. With the exception of opportunistic infections, serious adverse events are rare. In conclusion, biologicals have changed the scene considerably and expanded our armamentarium, but there is also a marketing hype fostering expectations without evidence.

Impact of the Crohn's disease digestive damage score (Lémann Index) on the perioperative course in patients with Crohn's disease and ileocolic anastomosis.

BACKGROUND: Risk factors influencing the high postoperative morbidity in Crohn`s disease are controversially discussed but the role of cumulative structural bowel damage, as assessed by the Crohn's disease digestive damage score (Lémann Index), has been neglected so far. Our aim was evaluating the influence of the Lémann Index on postoperative complications and investigating its suitability for surgical decision making. METHODS: A single-center, retrospective cohort study was conducted including Crohn`s disease patients who underwent ileocolic anastomosis. Lémann Indices were calculated and, additionally, categorized into three groups [0-3; 3-10; >10] due to the strong influence of previous bowel resections on high indices. A multivariate regression model was used to analyze the index`s influence on postoperative complications. RESULTS: Patients with higher Lémann Index were more likely to need open surgery (p < .001) or stoma creation (p = .03). Overall, of the 103 patients enrolled, 18 (17.5%) showed postoperative complications Clavien-Dindo > 2. The Lémann Index was higher in patients with complications compared to those without (median 6.15 [IQR 4.16-11.98] vs. 3.88 [1.63-12.63]), but not linearly associated with postoperative complications. After categorization, patients with Lémann Index 3-10 had an 8.42 (95% CI 1.8-54.55) times higher chance to develop a complication compared to patients with Lémann Index 0-3 (p = .01). CONCLUSIONS: The Lémann Index might affect surgical decision making but is not linearly associated with postoperative morbidity. However, medium indices (3-10) - mainly accounted for by high amounts of intraabdominal active Crohn`s lesions - showed significantly higher rates of complications, potentially defining a group at risk.

Self-monitoring with home based fecal calprotectin is associated with increased medical treatment. A randomized controlled trial on patients with inflammatory bowel disease.

OBJECTIVES: Self-monitoring of inflammatory bowel disease (IBD) with the assistant of telemedicine and home-based fecal calprotectin (FC) tests is evolving in the management of IBD. We performed a randomized controlled trial to investigate the compliance and effects of the model IBD-Home in patients with IBD. MATERIALS AND METHODS: Patients were randomized to IBD-Home + standard care (n = 84) or standard care alone (n = 74). Intervention with IBD-Home included IBDoc® FC test kits and a digital application used for answering symptom questionnaires (Abbvie/Telia). They were instructed to use these on demand during a 12-month period. Data was collected retrospectively from medical records. Patients who completed the intervention were phoned and asked to answer a survey about the experience of IBD-Home. RESULTS: The compliance to IBD-Home was low (29%). Women were more compliant compared with men (43% vs 17%, p < .001). A significantly higher proportion of patients in the IBD-Home group increased their medical treatment during the study period in comparison to control subjects (33% vs 15% p = .007) and there was an association between an increase in treatment and compliance to IBD home (multivariate odds ratio 3.22; 95th confidence interval 1.04 - 9.95). Overall patients reported a positive experience with slight technical difficulties. CONCLUSION: Self-monitoring with home based fecal calprotectin and a digital application was found feasible and appreciated by compliers. Compliance to the IBD-Home model was more common in women and associated with an increased treatment for IBD.

Hospitalization and surgery rates in patients with inflammatory bowel disease in Brazil: a time-trend analysis.

BACKGROUND: The prevalence of inflammatory bowel disease (IBD) is increasing globally, and the disease is frequently managed surgically. The aim of this study was to investigate the time trends and geographic distribution of IBD hospitalizations, surgeries and surgical-associated lethality. METHODS: Data from the Brazilian Health Public System were retrospectively collected regarding hospitalizations, in-hospital deaths, IBD-related surgical procedures and lethality from 2005 to 2015. RESULTS: This eleven-year period revealed decreases in the rates of hospitalization (24%), IBD-related surgeries (35%), and IBD-related surgical lethality (46%). Most surgeries were performed in Crohn's disease patients, and the predominant procedure was small bowel resection, mostly in young adults. A higher prevalence of ulcerative was observed throughout the country. The highest hospitalization and surgical rates were observed in the more industrialized regions of the South and the Southeast and in the municipalities integrated with metropolitan regions (MRs). The highest surgical-related lethality rates were seen in the less-developed regions and in municipalities not integrated with MRs. The length of hospital stay showed a slight increase throughout the period. CONCLUSIONS: Brazil follows the global trend of decreases in hospitalizations, lethality, surgeries, and surgical lethality associated with IBD. The unequal distribution of hospitalizations and surgeries, concentrated in the industrialized areas, but with a shift towards the Northeast and from urbanized to rural areas, indicates ongoing changes within the country. Reductions in the rates of IBD-related hospitalizations, surgeries and lethality suggest the effectiveness of decentralization and improvements in the quality of public health services and the advances in medical therapy during the study period.