Achieving Histologic Normalization in Ulcerative Colitis Is Associated With a Reduced Risk of Subsequent Dysplasia.

BACKGROUND: Complete histologic normalization is associated with improved clinical outcomes in ulcerative colitis (UC). However, it is currently unknown what effect achieving histologic normalization has on the development of dysplasia. METHODS: We performed a retrospective analysis of 495 patients with a confirmed diagnosis of UC from a tertiary center. Patients were categorized according to the best histologic assessment they had during their disease course: histologic normalization, histologic quiescence, or persistent histologic activity. We assessed dysplasia rates in these patient groups after achieving histologic normalization or histologic quiescence, or 8 years after UC diagnosis in those with persistent histologic activity. Kaplan-Meier graphs and Cox regression analyses were performed to estimate this effect. RESULTS: The incidence rate of dysplasia development after achieving histologic normalization was statistically significantly less when compared with the incidence rate after achieving histologic quiescence (P = 0.001) and in those with persistent histologic activity 8 years after UC diagnosis (P = 0.033). In multivariate analysis, at any point throughout UC duration, dysplasia development was statistically lower in those with histologic normalization (adjusted hazard ratio [aHR], 0.32; 95% confidence interval [CI], 0.13-0.81) but not in those with histologic quiescence (aHR, 0.52; 95% CI, 0.25-1.10), compared with those with persistent histologic inflammation. When assessing the time after achieving histologic normalization, histologic quiescence, or 8 years post UC diagnosis in those with persistent histologic activity, we found that patients with histologic normalization had a subsequent decreased risk of developing dysplasia (aHR, 0.09; 95% CI, 0.01-0.72), compared with patients without normalization. CONCLUSIONS: Histologic normalization is associated with a decreased risk in patients with UC of developing subsequent dysplasia, compared with patients without histologic normalization. These findings have implications for surveillance intervals.

Follow-Up of Patients With Ulcerative Colitis and Histological Normalization.

The natural history of ulcerative colitis (UC) follows a relapsing and remitting course of inflammation and is accompanied by associated mucosal injury and historically, microscopic features of chronicity that were the sine qua non for the diagnosis.1 As goals for the management of UC have evolved to include objectively measured endoscopic improvement of the mucosa, there also has been a move to include histological endpoints in assessment of disease activity.2,3 However, there remain a number of unanswered questions about histology in UC and this is not yet a specific treatment goal.4.

Efficacy and safety of induction therapy with calcineurin inhibitors followed by vedolizumab maintenance in 71 patients with severe steroid-refractory ulcerative colitis.

BACKGROUND: Following induction therapy with a calcineurin inhibitor (CNI) in severe ulcerative colitis, transitioning to vedolizumab as maintenance therapy could be an option. AIM: To report on the largest cohort of patients successfully induced with CNIs who were transitioned to vedolizumab maintenance therapy. METHODS: This is a retrospective observational study of adult patients with severe steroid-refractory ulcerative colitis. Patients were included if they were induced with a CNI followed by maintenance therapy with vedolizumab between January 2014 and December 2018. The primary endpoint was colectomy-free survival. Secondary endpoints included survival without vedolizumab discontinuation as well as clinical, steroid-free and biochemical remission at week 14. RESULTS: A total of 71 patients (59% male) were treated with vedolizumab after induction therapy with CNIs for severe steroid-refractory colitis. Patients were followed for a median time of 25 months (IQR 16-36). Colectomy-free survival rates from vedolizumab initiation were 93% at 3 months, 67% at 1 year and 55% at 2 years. At the end of induction with vedolizumab at week 14, 50% of patients were in clinical remission, and 62% of patients had a normal CRP. At 1 and 2 years following vedolizumab initiation, 43% and 28% of patients were still on vedolizumab respectively. Vedolizumab was dose escalated to infusions every 4 weeks in 44% of patients. The median time to dose escalation was 5.6 months (IQR 4.1-8.2). No serious adverse events were recorded in our patient cohort. CONCLUSIONS: Transitioning to vedolizumab following induction of remission with CNIs is effective and safe.

Treatment De-Escalation in Patients With Inflammatory Bowel Disease.

Inflammatory bowel disease follows a relapsing and remitting course that can be augmented with the use of various pharmacologic therapies. Treatments used to induce or maintain remission may not be required indefinitely. The associated side-effect profile, adverse events, and costs are additional motivators for providers to treat patients with the lowest dose of effective medications. De-escalation of therapy, whether dose reduction or drug discontinuation, must be carefully considered on an individual patient basis. The steps for de-escalation include confirmation of deep remission, development of a maintenance strategy, discussion of the rescue threshold and treatment options in the event of relapse, and appropriate discussion with the patient of this plan.

Outcome of elective switching to vedolizumab in inflammatory bowel disease patients under tumor necrosis factor antagonist-maintained clinical remission.

BACKGROUND AND AIM: Vedolizumab (VDZ) has been used in inflammatory bowel disease (IBD) patients who failed anti-tumor necrosis factor (TNF) therapy. This study was to examine long-term outcome of IBD patients switching to VDZ from anti-TNF agents for reasons other than failure of therapy. METHODS: Inflammatory bowel disease patients at the University of Chicago IBD center who were in clinical remission with anti-TNF therapy and then electively changed to VDZ due to reasons other than loss of response were retrospectively analyzed. The primary outcome was the durability of clinical remission maintained by VDZ as assessed by Kaplan-Meier survival analysis. The proportion of patients in clinical and endoscopic remission at 6-12 months after switching to VDZ therapy was analyzed. RESULTS: A total of 41 patients (36 with Crohn's disease and 5 with ulcerative colitis) met the inclusion criteria and were in clinical remission at the time of switch. The majority of patients switched therapy due to adverse effects (56.1%) or infections (14.6%). During a median duration of 30 months (range 7-52) of VDZ therapy, 34 (82.9%) were in VDZ-maintained clinical remission. One (2.4%) and four (9.8%) patients discontinued VDZ due to flare and adverse effects, respectively. Endoscopic remission was present in 25 of 30 patients (83.3%) who had a follow-up colonoscopy. CONCLUSIONS: Vedolizumab was effective and safe in maintaining remission in IBD patients who switched from anti-TNF agents due to reasons other than failure of therapy. Our results suggest that switching anti-TNF remitters to VDZ treatment is a safe practice in specific patient populations.

Ustekinumab Is Effective for the Treatment of Chronic Antibiotic-Refractory Pouchitis.

BACKGROUND: Chronic antibiotic-refractory pouchitis (CARP) occurs in up to 15% of patients with ulcerative colitis (UC) following proctocolectomy with ileal pouch-anal anastomosis (IPAA). AIM: To investigate the effectiveness of ustekinumab in the treatment of CARP. METHODS: This was a retrospective single-center study of UC patients with an IPAA, who subsequently developed CARP and received ustekinumab with standard Crohn's disease (CD) dosing between 2016 and 2018. Patients with CD of the pouch were excluded. Demographic, clinical, and endoscopic data were collected. Outcomes included a change in the endoscopic subscore of the Pouchitis Disease Activity Index (PDAI), change in the ulcerated surface area, clinical response, and the number of bowel movements per 24 h. RESULTS: Twenty-four patients with CARP were included for analysis. Median follow-up time was 12.9 months (IQR 7.9-16). Twelve patients (50%) had a clinical response with the median number of bowel movements within 24 h decreasing from 8 (IQR, 5-12) to 6 (IQR, 5-8) P = 0.002. Thirteen patients had pouchoscopies available post-ustekinumab treatment. In these patients, the median endoscopic subscore of the PDAI decreased from 5 (IQR, 3-6) to 4 (IQR, 2-5), P = 0.016. Likewise, among these thirteen patients, nine (69%) had an ulcerated surface area > 10% before ustekinumab treatment; after treatment with ustekinumab, only four patients (31%) still had an ulcerated surface area of > 10%. CONCLUSIONS: This is the largest study of ustekinumab treatment for patients with chronic antibiotic-refractory pouchitis. We found that ustekinumab therapy led to the improvement in clinical and endoscopic endpoints.

Proposal to Update the Curriculum in Inflammatory Bowel Diseases for Categorical Gastroenterology Fellows.

Education in inflammatory bowel disease (IBD) varies widely between categorical gastroenterology (GI) programs and is largely related to the presence of expert clinicians, patient population, and the presence of an IBD center. The treatment of IBD is becoming increasingly complex at a rapid pace, widening this educational divide. This manuscript outlines all the current US educational offerings in IBD for GI fellows, including how to obtain supplemental education during the 3-year training period and beyond. It reviews how to assess trainee knowledge in the field of IBD and proposes 8 clinically anchored, entrustable professional activities that should help prioritize important aspects of IBD management to incorporate during categorical GI training.

A clinical predictive model for post-hospitalisation venous thromboembolism in patients with inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of venous thromboembolism (VTE) during hospitalisation and potentially post-discharge. AIMS: To determine the incidence and risk factors for post-discharge VTE in IBD patients and create a point of care predictive model to assess VTE risk. METHODS: Hospitalised IBD patients were identified from our institutional discharge database between 2009 and 2016, and were assessed for VTE by chart review. Risk factors for VTE within 3 months of discharge were determined by univariable and multivariable logistic regression. A point of care model was created using variables from the univariate analysis with P < 0.05, and internally validated by bootstrap methods. RESULTS: Sixty-six of 2161 eligible discharges (3%) were associated with VTE within 6 months of hospitalisation. The median time to event was 37 days (range 3-182 days). On multivariable analysis age >45 years (OR 3.76; 95% CI 1.80-7.89) and multiple admissions (OR 2.62; 95% CI 1.34-5.11) were independently associated with VTE risk. Our final model incorporated age >45 years, multiple admissions, intensive care unit admission, length of admission >7 days and central catheter and was able to discriminate between discharges associated with and without VTE (optimism-corrected c-statistic, 0.70; 95% CI 0.58-0.77). By limiting treatment to a high-risk group, extended thromboprophylaxis could be avoided in 92% of discharges with a miss rate of 1.6% (32/1982 discharges). CONCLUSION: Patients with IBD remain at risk of VTE after hospital discharge. Our model may help clinicians stratify which patients will benefit most from extended thrombophrophylaxis.

Differential risk of disease progression between isolated anastomotic ulcers and mild ileal recurrence after ileocolonic resection in patients with Crohn's disease.

BACKGROUND AND AIMS: It is standard of care to perform ileocolonoscopy within a year of ileocolonic resection for Crohn's disease (CD) and to guide management decisions based on the Rutgeert score (RS). The modified RS subdivides i2 into lesions confined to the anastomosis (i2a) or >5 aphthous lesions in the neoterminal ileum (i2b). There is uncertainty, however, if i2a lesions incur an increased risk of disease recurrence. The primary aim of this study was to compare the rates of endoscopic progression between i2a and i2b when compared with i0-i1. METHODS: This was a retrospective, single-center study including patients with CD who had an ileocolonoscopy ≤12 months after ileocolonic resection with primary anastomosis and who had >1 year of documented clinical follow-up after the index endoscopic evaluation. All consecutive eligible patients between 2004 and 2014 were included in the study. Demographic, disease, and treatment data were collected. Patients with i3 or i4 at index colonoscopy were excluded from further analyses. Outcomes included endoscopic progression and recurrent surgery. For patients with RS of i0 to i2, endoscopic progression was predefined as progression of the RS in subsequent colonoscopies to i3 or i4. Recurrent surgical interventions were defined as re-resection or stricturoplasty of the previous ileocolonic anastomosis. RESULTS: Two hundred seven CD patients (median age, 36 years [interquartile range, 26-48]) had an ileocolonoscopy ≤12 months after ileocolonic resection. At index colonoscopy, 95 patients (45.9%) had an RS of i0, 31 (14.9%) i1, 40 (19.3%) i2a, 25 (12.1%) i2b, 10 (4.8%) i3, and 6 (2.9%) i4. One hundred ninety-one patients had an RS of i0 to i2 and were included in the analyses for recurrent surgery. One hundred forty-nine patients had a second endoscopic evaluation and were included in the analysis for the primary outcome of endoscopic disease progression. Kaplan-Meier analyses were performed and found the hazard ratio (HR) of endoscopic progression to be significantly higher with i2b lesions when compared with i0 or i1 (HR, 6.22; 95% confidence interval [CI], 2.38-16.2; P = .0008). Patients with i2a did not have significantly higher rates of endoscopic progression when compared with i0 or i1 (HR, 2.30; 95% CI, .80-6.66; P = .12). Likewise, patients with i2b lesions had higher risk of needing recurrent surgery when compared with i0 or i1 (HR, 3.64; 95% CI, 1.10-12.1; P = .034), whereas patients with i2a lesions were not found to have a significantly elevated risk of recurrent surgery (HR, 1.43; 95% CI, .35-5.77; P = .62). CONCLUSION: Endoscopic lesions limited to the ileocolonic anastomosis (RS i2a) in patients with CD undergoing colonoscopy within 1 year of their resection were not associated with a significantly higher rate of progression to more severe disease, whereas those in the neoileum (RS i2b) were. Prospective studies are needed to confirm these findings.

Fluid balance, change in serum creatinine and urine output as markers of acute kidney injury post cardiac surgery: an observational study.

BACKGROUND: Acute kidney injury (AKI) is defined as oliguria or rise in serum creatinine but oliguria alone as a diagnostic criterion may over-diagnose AKI. OBJECTIVES: Given the association between fluid overload and AKI, we aimed to determine if positive fluid balance can complement the known parameters in assessing outcomes of AKI. DESIGN: Prospective observational study. SETTING: Teaching hospital in Vancouver, Canada. PATIENTS: 111 consecutive patients undergoing elective cardiac surgery from January to April 2012. MEASUREMENTS: Outcomes of cardiac surgery intensive care unit (CSICU) and hospital length of stay (LOS) in relation to fluid balance, urine output and serum creatinine. METHODS: All fluid input and output was recorded for 72 hours post-operatively. Positive fluid balance was defined as >6.5 cc/kg. Daily serum creatinine and hourly urine output were recorded and patients were defined as having AKI according to the AKIN criteria. RESULTS: Of the patients who were oliguric, those with fluid overload trended towards longer LOS than those without fluid overload [CSICU LOS: 62 and 39 hours (unadjusted p-value 0.02, adjusted p-value 0.58); hospital LOS: 13 and 9 days (unadjusted p-value: 0.05, adjusted p-value: 0.16)]. Patients with oliguria who were fluid overloaded had similar LOS to patients with overt AKI (change in serum creatinine ≥ 26.5 µmol/L), [CSICU LOS: 62 and 69 hours (adjusted p value: 0.32) and hospital LOS: 13 and 14 days (adjusted p value: 0.19)]. Patients with oliguria regardless of fluid balance had longer CSICU LOS (adjusted p value: 0.001) and patients who were fluid overloaded in the absence of AKI had longer hospital LOS (adjusted p value: 0.02). LIMITATIONS: Single centre, small sample, LOS as outcome. CONCLUSIONS: Oliguria and positive fluid balance is associated with a trend towards longer LOS as compared to oliguria alone. Fluid balance may therefore be a useful marker of AKI, in addition to urine output and serum creatinine.

CONTEXTE: L'insuffisance rénale aiguë (IRA) se définit comme une oligurie ou une élévation de la créatininémie. Par contre, l'oligurie comme unique critère diagnostique peut mener abusivement au diagnostic d'IRA. OBJECTIFS: Étant donné l'association entre l'hyperhydratation et l'IRA, nous cherchons à déterminer si une balance liquidienne positive peut complémenter les paramètres connus dans l'évaluation des résultats de l'IRA. TYPE D'ÉTUDE: Étude d'observation prospective. CONTEXTE: Hôpital universitaire à Vancouver, Canada. PARTICIPANTS: 111 patients consécutifs qui subissent une chirurgie cardiaque non urgente, entre janvier et avril 2012. MESURES: On a mis en parallèle les résultats de l'unité de soins intensifs en chirurgie cardiaque (USICC), de même que la durée de l'hospitalisation (soins actifs), avec la balance liquidienne, la diurèse et la créatininémie. MÉTHODES: On a mesuré les ingesta et excreta durant les 72 heures postopératoires. On a défini une balance liquidienne positive à >6,5 cc/kg. On a enregistré la créatininémie quotidienne et la diurèse aux heures, et on a déterminé que les patients souffraient d'IRA en nous basant sur les critères de l'Acute Kidney Injury Network (AKIN). RÉSULTATS: Parmi les patients oliguriques, ceux qui avaient une surcharge liquidienne tendaient davantage vers une hospitalisation prolongée que ceux qui n'en avaient pas [durée de soins actifs à l'USICC: 62 et 39 heures (valeur de p non ajustée: 0,02, valeur de p ajustée: 0,58); durée de soins actifs à l'hôpital: 13 et 9 jours (valeur de p non ajustée: 0,05, valeur de p ajustée: 0,16)]. Les patients présentant une oligurie qui présentaient aussi une surcharge liquidienne requéraient une durée de soins actifs similaire aux patients souffrant d'IRA (modification de la créatininémie ≥ 26,5 µmol/L), [soins actifs USICC: 62 et 69 heures (valeur de p ajustée: 0,32) soins actifs à l'hôpital: 13 et 14 jours (valeur de p ajustée: 0,19)]. Les patients présentant une oligurie, indépendamment de la balance liquidienne, bénéficiaient d'une durée de soins actifs à l'USICC prolongée (valeur p ajustée: 0,001), tandis que les patients en surcharge liquidienne, mais ne souffrant pas d'IRA bénéficiaient davantage de soins actifs à l'hôpital (valeur de p ajustée: 0,02). LIMITES DE L'ÉTUDE: Un seul centre, un échantillon restreint, les soins actifs considérés comme une issue. CONCLUSION: Les patients avec oligurie et une balance liquidienne positive ont nécessité des soins actifs prolongés à l'USICC, comparativement aux patients ne présentant qu'une oligurie. La balance liquidienne peut donc constituer un marqueur d'IRA, en plus de la diurèse et la créatininémie.