How many biomarker measurements are needed to predict prognosis in Crohn's disease patients under infliximab?-A prospective study.

BACKGROUND: Timely stratification of Crohn's disease (CD) is essential for patients' management. The use of noninvasive accurate biomarkers is key to monitor treatment and to pursue mucosal healing, the ultimate treatment endpoint in CD. OBJECTIVE: We aimed to evaluate the performance of readily available biomarkers and develop risk matrices to predict CD progression. METHODS: Data from 289 CD patients receiving infliximab (IFX) maintenance therapy for 2 years was collected; those patients were included in DIRECT, a prospective multicenter observational study. Disease progression was evaluated using two composite outcomes incorporating clinical and drug-related factors, the first including IFX dose and/or frequency adjustments. Univariate and multivariable logistic regressions were used to calculate the odds ratios (OR) and to develop risk matrices. RESULTS: The isolated presence of anemia at least once during follow-up was a significant predictor of disease progression (OR 2.436 and 3.396 [p ≤ 0.001] for composite outcomes 1 and 2, respectively) regardless of confounding factors. Isolated highly elevated C-reactive protein (CRP; >10.0 mg/L) and fecal calprotectin (FC; >500.0 µg/g) in at least one visit were also significant predictors, while milder elevations (3.1-10.0 mg/L and 250.1-500.0 µg/g) were only relevant when detected in at least two visits (consecutive or not). The combination of biomarkers in risk matrices had good ability to predict progression; patients simultaneously presenting anemia, highly elevated CRP and FC at least once had 42%-63% probability of achieving the composite outcomes. CONCLUSION: The combined evaluation of hemoglobin, CRP, and FC in at least one time point and their incorporation into risk matrices seems to be the optimal strategy for CD management, as data from additional visits did not meaningfully influence the predictions and may delay decision-making.

Diagnosis of Bowel Endometriosis Using Endoscopic Ultrasound-guided Fine Needle Aspiration.

Endometriosis is a relatively common gynecological condition in women of reproductive age. The rectosigmoid region is the most commonly affected segment when the gastrointestinal tract is involved. A differential diagnosis of colorectal neoplasia is difficult because of the similar clinical, endoscopic, and radiology findings. A 42-year-old female presented with abdominal distention and was subsequently diagnosed with a large bowel obstruction in the rectum. A temporary colostomy was performed, and endoscopy revealed a rectal mass obstructing the rectum. The biopsy showed normal mucosa, and it was difficult to exclude rectal malignancies even after the imaging workup. Endoscopic ultrasound demonstrated a hypoechoic lesion below the rectal mucosa, and fine needle aspiration confirmed the diagnosis of bowel endometriosis. Bowel endometriosis is a challenging diagnosis. Endoscopic ultrasound- guided fine-needle aspiration is useful for acquiring adequate samples for histological confirmation and a definitive diagnosis of bowel endometriosis.

Transmural remission improves clinical outcomes up to 5 years in Crohn's disease.

INTRODUCTION: Evidence supporting transmural remission (TR) as a long-term treatment target in Crohn's disease (CD) is still unavailable. Less stringent but more reachable targets such as isolated endoscopic (IER) or radiologic remission (IRR) may also be acceptable options in the long-term. METHODS: Multicenter retrospective study including 404 CD patients evaluated by magnetic resonance enterography and colonoscopy. Five-year rates of hospitalization, surgery, use of steroids, and treatment escalation were compared between patients with TR, IER, IRR, and no remission (NR). RESULTS: 20.8% of CD patients presented TR, 23.3% IER, 13.6% IRR and 42.3% NR. TR was associated with lower risk of hospitalization (odds-ratio [OR] 0.244 [0.111-0.538], p < 0.001), surgery (OR 0.132 [0.030-0.585], p = 0.008), steroid use (OR 0.283 [0.159-0.505], p < 0.001), and treatment escalation (OR 0.088 [0.044-0.176], p < 0.001) compared to no NR. IRR resulted in lower risk of hospitalization (OR 0.333 [0.143-0.777], p = 0.011) and treatment escalation (OR 0.260 [0.125-0.540], p < 0.001), while IER reduced the risk of steroid use (OR 0.442 [0.262-0.745], p = 0.002) and treatment escalation (OR 0.490 [0.259-0.925], p = 0.028) compared to NR. CONCLUSIONS: TR improved clinical outcomes over 5 years of follow-up in CD patients. Distinct but significant benefits were seen with IER and IRR. This suggests that both endoscopic and radiologic remission should be part of the treatment targets of CD.

Inflammatory bowel disease and thromboembolic events: a c'lot to learn.

Background: Inflammatory bowel disease (IBD) is associated with a variety of extraintestinal manifestations including arterial and venous thromboembolism. Research evidences that IBD patients have about a 2- to 3-fold increase in the risk of venous thromboembolism when compared with the general population. Objectives: We intended to evaluate the coagulation parameters and the prevalence of thromboembolic events (TE) in IBD patients. It was also our aim to investigate the correlation between coagulation parameters and disease phenotype and activity in this population. Methods: This single center prospective observational study was performed between November 2016 and April 2020. The cohort included patients with 18 years of age or older, diagnosed with IBD and followed at a gastroenterology consultation, during a follow-up period of 36 months. Patients were evaluated in terms of IBD type, extent and disease behavior, clinical scores of IBD activity, medication, smoking history, family and personal history of TE, coagulation parameters, fecal calprotectin levels, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hospitalization due to TE, IBD-related hospitalization or surgery, pregnancy, or diagnosis of malignancy. Results: The study included 149 IBD patients (67 males and 82 females). Coagulation parameters were similar in CD and UC patients and only plasminogen was increased in CD patients [97.4 (17.0) versus 91.6 (13.3), p = 0.035], when comparing with UC patients. The determined values were in the range of the reference values described in literature for the standard population. During the follow-up period, none of the patients experienced a TE that demanded hospitalization. Conclusion: In our study, acquired and inherited risk factors for TE and changes in coagulation parameters did not show to influence prothrombotic predisposition in IBD patients. As such, the clinical relevance of measuring coagulation parameters in this population is questionable. Trial Registry: NCT05162339 (ClinicalTrials.gov ID).

Composite outcomes in observational studies of Crohn's disease: a systematic review and meta-analysis.

Background: This systematic review and meta-analysis aims to assess composite and aggregate outcomes of observational studies in Crohn's disease and to evaluate whether the number and type of variables included affect the frequency of the outcome. Methods: MEDLINE [via PubMed], Scopus and Web of Science were searched to identify observational studies that enrolled patients with Crohn's disease and evaluated a composite or aggregate outcome. The proportion of patients achieving the outcome was determined and a random-effects meta-analysis was performed to evaluate how the frequency of each outcome varies according to the reporting of predefined variables. Results: From 10,257 identified records, 46 were included in the qualitative analysis and 38 in the meta-analysis. The frequency for composite and aggregate outcomes was 0.445 [95% confidence interval (CI): 0.389-0.501] and 0.140 (95% CI: 0.000-0.211), respectively. When comparing composite outcomes by number of included variables, the frequency was 0.271 (95% CI: 0.000-0.405) and 0.698 (95% CI: 0.651-0.746), for one and six variables, respectively. The frequency of the composite outcome varied according to the identity of the variables being reported. Specific pairs of predefined variables had a significant effect in the frequency of composite outcomes. Conclusion: Composite outcomes with increasing number of predefined variables show an increase in frequency. Outcomes including variables such as 'Surgery' and 'Steroids' had higher frequencies when compared with the ones that did not include these variables. These results show that the frequency of composite outcomes is dependent on the number and type of variables being reported.

Incidence Trends of Inflammatory Bowel Disease in a Southern European Country: A Mirror of the Western World?

INTRODUCTION: Inflammatory bowel disease (IBD) affects people from all age categories worldwide. Although the incidence of the disease is stabilizing or decreasing in most Western world countries, its prevalence is still increasing because of the rise in life expectancy and better disease management. This work intends to identify the trends related to IBD incidence nationwide, analyzing regional, sex, and age distributions. METHODS: Data were provided by the Portuguese Shared Services of the Ministry of Health. This study consisted of a retrospective analysis of all first consultations coded for "Chronic enteritis/ulcerative colitis" (D94) in a primary healthcare setting, between 2017 and 2020, in Portugal. The primary outcome measure was the IBD incidence rate per 100,000 inhabitants. We also calculated the incidence rate per person-year and forecasted incidence until 2024. RESULTS: Between 2017 and 2019, the incidence rate of IBD in Portugal decreased from 54.9 to 48.6 per 100,000 inhabitants. The average incidence was 20 new cases of IBD per 1,000 person-year. It was predicted that, in December 2023, IBD incidence would reach 305.4 new cases (95% Prediction Interval 156.6-454.3), a similar result to the values forecasted for December 2021 (305.4, 95% Prediction Interval 197.3-413.6). DISCUSSION: The incidence of IBD slightly declined from 2017 to 2019, and it is posed to stabilize in the future. The presented data are of the utmost importance for the characterization of IBD in Southern European countries and the establishment of future health policies in the setting of compounding prevalence in the Western world.

The Magnitude of Crohn's Disease Direct Costs in Health Care Systems (from Different Perspectives): A Systematic Review.

BACKGROUND: The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, causing high impact on the quality of life of patients and an increasing burden for health care systems. In this systematic review, we reviewed the literature concerning the direct costs of Crohn's disease (CD) for health care systems from different perspectives: regional, economic, and temporal. METHODS: We searched for original real-world studies examining direct medical health care costs in Crohn's disease. The primary outcome measure was the mean value per patient per year (PPY) of total direct health care costs for CD. Secondary outcomes comprised hospitalization, surgery, CD-related medication (including biologics), and biologics mean costs PPY. RESULTS: A total of 19 articles were selected for inclusion in the systematic review. The studies enrolled 179 056 CD patients in the period between 1997 and 2016. The pooled mean total cost PPY was €6295.28 (95% CI, €4660.55-€8503.41). The pooled mean hospitalization cost PPY for CD patients was €2004.83 (95% CI, €1351.68-€2973.59). The major contributors for the total health expenditure were biologics (€5554.58) and medications (€3096.53), followed by hospitalization (€2004.83) and surgery (€1883.67). No differences were found between regional or economic perspectives, as confidence intervals overlapped. However, total costs were significantly higher after 2010. CONCLUSIONS: Our review highlighted the burden of CD for health care systems from different perspectives (regional, economic, and temporal) and analyzed the impact of the change of IBD treatment paradigm on total costs. Reducing the overall burden can depend on the increase of remission rates to further decrease hospitalizations and surgeries.

Subclinical Persistent Inflammation as Risk Factor for Crohn's Disease Progression: Findings From a Prospective Real-World Study of 2 Years.

BACKGROUND AND AIMS: Subclinical intestinal inflammation is common in Crohn's disease (CD). We aimed to explore its impact in the disease progression of infliximab-treated patients and the usefulness of fecal calprotectin (FC) and C-reactive protein (CRP) as surrogate minimally invasive biomarkers. METHODS: The registry-based, prospective, observational, multicenter DIRECT (study to investigate the correlation of fecal calprotectin with serum Drug levels and development of an antI-dRug antibodiEs among adult patients with inflammatory bowel disease reCeiving anti-TNF-alfa treatment or vedoluzimab treatment) study followed infliximab-treated CD patients for 2 years in a tertiary care setting. Persistent inflammation definition was based on FC (>150 µg/g, >250 µg/g, or >350 µg/g) or serum CRP (>3 µg/mL) concentrations over 2 consecutive or at least 3 visits. Patients were categorized according to a composite outcome reflecting disease progression that incorporated surgery; hospitalizations; new fistulae, abscess, or stricture; and treatment escalation. RESULTS: Of 322 DIRECT study patients, 180 asymptomatic, infliximab treated on maintenance regimen were included in the analysis. Patients developing the composite endpoint (n = 96) presented higher median levels of FC (205 [interquartile range, 98-515] µg/g; P = .045) but not of CRP (2.50 [interquartile range, 0.80-6.00] µg/mL; P = .895). Biomarker-defined persistent subclinical inflammation prevalence ranged from 24% to 81%. Considering FC >250 µg/g in 2 consecutive visits, prevalence was 50%, odds of achieving the endpoint were increased 3-fold (odds ratio, 2.996 [95% confidence interval, 1.557-5.776]), and time-to-outcome occurrence was significantly lower among subjects with persistent inflammation (median time: 11 months). Both clinical-related and treatment-related components were significantly associated with persistent inflammation. Definitions based on CRP >3 µg/mL, FC >150 µg/g, FC >350 µg/g, double biomarkers (FC >250 µg/g and/or CRP >3 µg/mL), or more visits did not improve predictive ability. CONCLUSIONS: Persistent inflammation, defined simply and readily by FC >250 µg/g over 2 consecutive visits, was associated with a significantly higher risk and shorter time to occurrence of a composite outcome reflecting disease progression in asymptomatic infliximab-treated CD patients.

Thiopurines: Use them or lose them? International survey on current and future use of thiopurines in inflammatory bowel disease.

BACKGROUND AND AIMS: The role of thiopurines in therapeutic algorithms of Crohn's disease (CD) and Ulcerative colitis (UC) is being questioned. This work aimed to investigate current practice and future perspectives of Inflammatory Bowel Disease (IBD) physicians regarding the efficacy, safety, and role of precision medicine with thiopurines in IBD. METHODS: A 29-questions web-based survey was developed and distributed to IBD physicians worldwide. RESULTS: We collected the complete answers of 408 physicians from 50 countries. Most participants were experienced physicians in IBD; 26.0% met our definition of "IBD expert". Four physicians reported to not use thiopurines in clinical practice. Most respondents used thiopurines in monotherapy and in combination therapy, both in CD and UC. Respondents tended to consider thiopurines as drugs with a good safety profile, with the agreement of 61.5% of the overall cohort. A minority of physicians (~6%) considered that thiopurines will not be used in the future in IBD patients, while 57.8% believed that these drugs will still be used, in mono and combination therapy. CONCLUSION: Despite the many emerging treatments in IBD, according to the beliefs of most physicians surveyed, thiopurines will still be an important part of the treatment algorithm of both CD and UC.

Age at Diagnosis Is Determinant for the Outcome of Inflammatory Bowel Disease: Is It a Myth?

INTRODUCTION: Patients with elderly-onset inflammatory bowel disease were previously associated with a less aggressive course of the disease. However, there are conflicting data that need further validation. We aimed to determine the association between age at diagnosis and the development of progressive disease in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: This cohort study included patients with CD and UC followed in 6 secondary and tertiary care centers in mainland Portugal. Patients were divided into a derivation (80%) cohort and a validation (20%) cohort. The primary outcome was progressive disease. Logistic regression analysis, receiver operating characteristic curves, and the areas under the curve (AUC) were performed. Odds ratios with 95% confidence intervals (CIs) were estimated. RESULTS: The derivation cohorts included 1245 patients with CD (68% with progressive disease) and 1210 patients with UC (37% with progressive disease), whereas the validation cohorts included 302 patients with CD and 271 patients with UC, respectively, with similar outcome proportions. In our final model, age at diagnosis older than 60 years was significantly associated with a lower risk of developing progressive disease (odds ratio 0.390, 95% CI 0.164-0.923, P = 0.032), with a high discriminative power (AUC 0.724, 95% CI 0.693-754) in patients with CD. However, according to this model, no significant associations were found between age at diagnosis and the risk of developing progressive disease in patients with UC. No differences were observed in the AUC values between the validation and the derivation cohorts. DISCUSSION: Patients with elderly-onset CD, but not patients with UC, were associated with a less progressive course of the disease.

Histologic Features of Colon Biopsies (Geboes Score) Associated With Progression of Ulcerative Colitis for the First 36 Months After Biopsy.

BACKGROUND & AIMS: In addition to findings from endoscopy, histologic features of colon biopsies have been associated with outcomes of patients with ulcerative colitis (UC). We investigated associations between Geboes scores (a system to quantify structural changes and inflammatory activity in colon biopsies) and UC progression, and the time period over which this association is valid. METHODS: We analyzed data from 399 asymptomatic patients with UC enrolled in the ACERTIVE study, followed at 13 inflammatory bowel disease (IBD) centers in Portugal through 31 December 2019. Blood and stool samples were collected and analyzed, and all patients underwent sigmoidoscopy within 24 h of sample collection. We assessed baseline endoscopic status (Mayo endoscopic subscore), histologic features of 2 sigmoid and 2 rectal biopsies (Geboes score), and concentration of fecal calprotectin (FC). The primary outcome was UC progression (surgical, pharmacologic, and clinical events). We generated survival curves for 36 months or less and more than 36 months after biopsy according to Geboes score using the Kaplan-Meier method and compared findings with those from a log rank test. Cox regression was adjusted for Mayo endoscopic subscore, Geboes score, and level of FC; results were expressed as adjusted hazard ratios (HR) with 95% CIs. RESULTS: Patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 had a higher frequency of, and a shorter time to UC progression, than patients with Geboes scores ≤2B.0, Geboes scores ≤3.0, or Geboes score ≤4.0 (P < .001). Disease progression occurred earlier in patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 compared with patients with Geboes scores ≤2B.0 (HR, 2.021; 95% CI, 1.158-3.526), Geboes scores ≤3.0 (HR, 2.007; 95% CI, 1.139-3.534), or Geboes scores ≤4.0 (HR, 2.349; 95% CI, 1.269-4.349), respectively, in the first 36 months after biopsy. Similar results were found for patients with concentrations of FC below 150 µg/g. CONCLUSIONS: We found histologic features of colon biopsies (Geboes score) to be an independent risk factor for progression of UC in the first 36 months after biopsy.

Clinical, Endoscopic and Histological Outcomes in Induction of Moderate-to-Severe Ulcerative Colitis: A Systematic Review with Meta-Analysis.

BACKGROUND AND AIMS: Interest in histology for ulcerative colitis [UC] has increased recently. This systematic review and meta-analysis aims to assess, for the first time, whether histological outcomes are more informative than endoscopic and clinical outcomes in distinguishing the impact of intervention over placebo in induction trials. METHODS: MEDLINE, ScienceDirect and Cochrane Central Register of Controlled Trials were searched to identify randomized placebo-controlled trials [RCTs] enrolling moderate-to-severe UC patients. Studies were assessed using the Quality Assessment Tool for Studies with Diverse Designs. We analysed the pooled proportion of patients achieving clinical, endoscopic and histological remission and response after a pharmacological intervention and compared the results with those of placebo-treated patients by using a random-effects model. RESULTS: From 889 identified records, 13 RCTs were included. The odds ratio [OR] for remission was higher in patients receiving intervention than in those under placebo for clinical (OR 2.13, 95% confidence interval [CI] 1.33-3.43), endoscopic [OR 1.46, 95% CI 0.19-11.18] and histological remission [OR 1.85, 95% CI 1.20-2.84]. Significant differences were observed for all response outcomes [clinical: OR 2.27, 95% CI 1.84-2.85; endoscopic: OR 2.16, 95% CI 1.51-3.10; histological: OR 3.63, 95% CI, 1.41-9.36]. No significant heterogeneity existed; no subgroup effects were found for duration of the induction or histological scale [p > 0.05]. Clinical and histological remission and endoscopic response were concordant in discriminating interventions from placebo. CONCLUSION: Histological outcomes are informative in trials of moderate-to-severe UC. Further studies analysing histology at the end of induction are needed to confirm its relevance in distinguishing the efficacy of an intervention over placebo in comparison to clinical and endoscopic outcomes and to explore its prognostic value.

Inflammatory Bowel Disease Reoperation Rate Has Decreased Over Time If Corrected by Prevalence.

INTRODUCTION: Despite the recent emergence of expensive biologic therapies, hospitalization and surgery remain important contributors for the overall costs of inflammatory bowel disease (IBD). In this study, we aimed to describe the burden of reoperations in patients with IBD by evaluating reoperation rates, charges, and risk factors over 16 years. METHODS: We performed a retrospective analysis of all hospital discharges, with focus on reoperations and with a primary diagnosis of IBD, in public hospitals between 2000 and 2015 in mainland Portugal from the Central Administration of the Health System's national registry. We collected data on patient, clinical, and healthcare charges. We used multivariate regressions to estimate the risk factors of IBD-related reoperations. RESULTS: We found that 5% of IBD-related hospitalizations were related to reoperations. The number of reoperations per year increased by approximately 200%. However, when corrected by the prevalence of the disease, IBD reoperation rates decreased. Mean IBD-related charges per hospitalization were 7,780 &OV0556; in 2000 and 10,592 &OV0556; in 2015, with total charges reaching 6.7 million euros by the end of the study. Risk factors for reoperation include urgent hospitalization, in patients with ulcerative colitis (odds ratio 1.94, 95% confidence interval 1.19-3.17, P = 0.008), and colic disease, in patients with Crohn's disease (odds ratio 1.57, 95% confidence interval 1.06-2.34, P = 0.025). DISCUSSION: To obtain an accurate scenario of reoperations among patients with IBD, it is mandatory to adjust the number of reoperations to the prevalence of the disease. Reoperation and its risk factors should be closely monitored to decrease the burden of IBD to the healthcare system.

Comparison of the Nancy Index With Continuous Geboes Score: Histological Remission and Response in Ulcerative Colitis.

BACKGROUND AND AIMS: Evidence has been supporting that histological activity of ulcerative colitis [UC] has relevance for the prediction of clinical outcomes in UC patients, such as clinical relapse. In this study, we aimed to compare two histological indexes-the continuous Geboes score [GS] and the Nancy index [NI] -regarding their definitions of histological remission and response, and to determine the ability of faecal calprotectin [FC] levels to discriminate between these histological statuses according to the NI. METHODS: A large cohort of UC patients [N = 422] who were previously enrolled in other studies was analysed. RESULTS: GS and NI were shown to be strongly correlated [correlation coefficient: 0.882, p <0.001], indicating high accordance in the classification of patients as having/not having histological remission and response. FC levels moderately correlated with NI regarding these histological statuses [correlation coefficient: 0.481, p <0.001], moderately predicted the absence of remission defined by NI >0 {area under the curve (AUC) 0.667 (95% confidence interval [CI] 0.609-0.724)}, and were good predictors of the absence of histological response defined by NI >1 (AUC 0.825 [95% CI 0.777-0.872]). The optimal FC cut-offs determined to predict the NI-defined histological remission and response were 91 µg/g and 106 µg/g, when maximising the negative predictive value [NPV]. CONCLUSIONS: Due to the higher applicability of the NI, this study encourages the systematic use of this histological index to assess histological remission and response in UC patients.

Comparing the Continuous Geboes Score With the Robarts Histopathology Index: Definitions of Histological Remission and Response and their Relation to Faecal Calprotectin Levels.

BACKGROUND AND AIMS: The histological status of ulcerative colitis [UC] patients in clinical and endoscopic remission has gained space as an important prognostic marker and a key component of disease monitoring. Our main aims were to compare two histological indexes-the continuous Geboes score [GS] and the Robarts Histopathology index [RHI]-regarding their definitions of histological remission and response, and the ability of faecal calprotectin [FC] levels to discriminate between these statuses. METHODS: This was an analysis of three prospective cohorts including 422 patients previously enrolled in other studies. RESULTS: The two continuous scores [GS and RHI] were shown to be significantly correlated [correlation coefficient of 0.806, p < 0.001] and particularly close regarding their definition of histological response: 95% and 88% of all patients classified as having/not having [respectively] histological response according to RHI also did so according to GS. Moreover, median FC levels in patients with histological response were lower than those in patients without histological response [GS: 73.00 vs 525.00, p < 0.001; RHI: 73.50 vs 510.00, p < 0.001]; a similar trend was observed when FC levels of patients in histological remission were compared to those of patients with histological activity [GS: 76.00 vs 228.00, p < 0.001; RHI: 73.50 vs 467.00, p < 0.001]. FC levels allowed us to exclude the absence of histological remission [according to RHI] and absence of histological response [according to RHI and GS], with negative predictive values varying from 82% to 96%. However, optimization of the FC cut-off to exclude the absence of histological remission, as for the continuous GS, falls within values that resemble those of the healthy population. CONCLUSION: The continuous GS and RHI histological scores are strongly correlated in their definitions of histological response. An absence of histological remission could only be excluded at physiological levels of FC.

Features of Fecal and Colon Microbiomes Associate With Responses to Biologic Therapies for Inflammatory Bowel Diseases: A Systematic Review.

BACKGROUND & AIMS: We performed a systematic review of changes in fecal and colon microbiomes of patients with inflammatory bowel diseases (IBDs) receiving treatment with monoclonal antibodies against tumor necrosis factor, integrins, or cytokines. We explored associations among microbiome composition and functions (at baseline and throughout the treatment) and therapy-related outcomes to determine whether colon or fecal microbiomes might be used as biomarkers of response to therapy. METHODS: We searched the PubMed, Web of Science, and Science Direct databases through February 2019 for studies of associations among the microbiomes of fecal or colon samples, biologic therapies, and IBDs. We used the critical appraisal skills program checklist to assess the quality of the study methods. RESULTS: From the 787 citations identified, 10 studies met the inclusion criteria. Changes in microbiomes of fecal or colon samples after treatment did not differ significantly among biologic agents; all produced decreases in relative abundances of Escherichia and Enterococcus and increases in genera that produce short-chain fatty acids. Fecal or colon microbiomes of patients who responded to therapy with antagonists of tumor necrosis factor or interleukins had higher α-diversity and increased relative abundances of different genera (Faecalibacterium, Roseburia, or Clostridium) from the Clostridiales order, either at baseline or during follow-up evaluation. Patients in remission after treatment with antibodies against integrins had decreased abundances of Roseburia. CONCLUSIONS: In a systematic review of 10 studies, we found evidence for consistent changes in microbiomes of fecal and colon samples from patients with IBD who responded to treatment with biologic agents. Prospective studies are needed to determine what changes are associated significantly with treatment, whether these changes are causes or effects of response, or whether the composition of the intestinal microbiome can be used to select treatments for patients with IBD.

Health-Related Quality of Life in Patients with Moderate to Severe Ulcerative Colitis: Surgical Intervention versus Immunomodulatory Therapy.

PURPOSE: Ulcerative colitis (UC) can be managed with immunomodulation or surgery. We aimed to understand whether these strategies had a different impact on patients' health-related quality of life (HRQoL). METHODS: This was a retrospective, cross-sectional study: patients who had a moderate to severe UC episode that prompted the utilization of immunomodulatory drugs or surgery were invited to complete a generic (short form [36] health survey [SF-36]) and a disease-specific (inflammatory bowel disease questionnaire [IBDQ]) survey. RESULTS: We included 157 patients, 65 (41.4%) surgically treated. The therapeutic procedure had a minimal impact on HRQoL: only the social dimension of the IBDQ and the physical function component of the SF-36 were significantly different between the study arms - lower for the surgically treated patients. The type of surgery had no impact, but the occurrence of pouchitis, namely, in a chronic form, was associated with a lower HRQoL. Regression analysis confirmed surgery as an independent predictor of lower scores in the social dimension of the IBDQ (-4.646, 95% CI -6.953 to -2.339) and in the physical functioning (-9.622, 95% CI -17.061 to -2.183) and physical role functioning (-3.669, 95% CI -7.339 to 0.001) dimensions of the SF36. CONCLUSIONS: Although usually feared by patients, surgery has a limited impact on UC patients HRQoL when compared to medical management with immunomodulatory drugs.

Hospitalization trends of the Inflammatory Bowel Disease landscape: A nationwide overview of 16 years.

INTRODUCTION: In this study, we aimed to determine the hospitalization rates of Inflammatory Bowel Disease (IBD) in a southern-european country and its associated charges over a period of 16 years. METHODS: We identified all discharges with a primary diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) between 2000 and 2015 in data provided by the Central Administration of Health Services (ACSS). National estimates of hospitalization rates were assessed and adjusted to gender, age, population, and hospitalizations. Hospitalization charges were also assessed. RESULTS: There were an estimated 31 358 and 16 669 discharges for CD and UC, respectively. From 2000 to 2015, hospitalization rates per 100000 habitants increased for CD (8.4-11.2) and remained stable for UC (4.4-4.9). The hospitalization rate for IBD increased slightly over time (12.8 per 100 000 habitants in 2000 and 16.1 in 2015). Annual total hospitalization charges amounted to 4.0M€ in 2000 and 5.7M€ in 2015. This increase was mainly due to a rise in the total expenses of CD-related hospitalizations. CONCLUSION: CD hospitalization rates per 100000 inhabitants increased over time while remaining constant for UC. Hospitalization charges for IBD increased approximately 2.0M€ during the study period, representing an important burden in the national healthcare system.

Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levels.

OBJECTIVE: Histological remission is being increasingly acknowledged as a therapeutic endpoint in patients with UC. The work hereafter described aimed to evaluate the concordance between three histological classification systems-Geboes Score (GS), Nancy Index (NI) and RobartsHistopathologyIndex (RHI), as well as to evaluate their association with the endoscopic outcomes and the faecal calprotectin (FC) levels. DESIGN: Biopsy samples from 377 patients with UC were blindly evaluated using GS, NI and RHI. The results were compared with the patients' Mayo Endoscopic Score and FC levels. RESULT: GS, NI and RHI have a good concordance concerning the distinction between patients in histological remission or activity. RHI was particularly close to NI, with 100% of all patients classified as being in remission with NI being identified as such with RHI and 100% of all patients classified as having activity with RHI being identified as such with NI. These scores could also predict the Mayo Endoscopic Score and the FC levels, with their sensitivity and specificity levels depending on the chosen cut-offs. Moreover, higher FC levels were statistically associated with the presence of neutrophils in the epithelium, as well as with ulceration or erosion of the intestinal mucosa. CONCLUSIONS: GS, NI and RHI histopathological scoring systems are comparable in what concerns patients' stratification into histological remission/activity. Additionally, FC levels are increased when neutrophils are present in the epithelium and the intestinal mucosa has erosions or ulcers. The presence of neutrophils in the epithelium is, indeed, the main marker of histological activity.

The timing of early therapeutic strategies has a significant impact on Crohn's disease prognosis.

BACKGROUND: Abdominal surgery and immunosuppressive pharmacological treatments are two different therapeutic options used to manage Crohn disease. This study aimed to determine whether the timing of these interventions had an impact on patients' prognosis. METHOD: This manuscript entails a retrospective analysis of a multicentric cohort involving 498 CD patients that had bowel surgery after diagnosis and prior to immunosuppression treatments. Two endpoints were considered: the occurrence of disabling disease and the need to undergo further bowel surgeries. RESULTS: Disabling disease affected 71% of all patients, whereas 39% needed reoperation. The odds ratios (OR) of being affected by disabling disease were higher when patients had upper tract involvement [3.412 [1.285-9.061]], perianal disease (2.270 [1.239-4.157]) and a longer time elapsed from diagnosis to first surgery (13-36 months: 2.576 [1.207-5.500]). On the other hand, the need to undergo further surgical interventions was significantly increased in smoking patients (2.294 [1.187-4.432]), but decreased in patients who started pharmacological therapy not later than six months after the first surgery (0.256 [0.093-0.704]). CONCLUSIONS: Our results suggest that the timing of therapeutic strategies does affects the CD outcomes: whereas an early surgery had a preventive effect on the occurrence of disabling events, the introduction of medication in the first semester after surgery had a preventive effect on the need for reoperation.