Older adults with acute severe ulcerative colitis have similar steroid non-response and colectomy rates as younger adults

BACKGROUND There is paucity of data on outcomes of acute severe ulcerative colitis(ASUC)in older adults(≥60 years of age).AIM To assess steroid non-response rates during the index admission for ASUC in older adults.Secondary outcomes were response to medical rescue therapy and colectomy rates;at index admission,3 and 12 mo.METHODS This retrospective multicentre cohort study included ASUC admissions who received intravenous steroids between January 2013 and July 2020 at two tertiary hospitals.Electronic medical records were reviewed to collect clinical,biochemical,and endoscopic data.A modified Poisson regression model was used for analysis.RESULTS Of 226 ASUC episodes,45(19.9%)occurred in patients≥60 years of age.Steroid non-response rates were comparable in older adults and patients<60 years of age[19(42.2%)vs 85(47%),P=0.618],crude risk ratio(RR)=0.89[95%confidence interval(CI):0.61-1.30],adjusted RR=0.99(0.44-2.21).Rates of response to medical rescue therapy in older adults was comparable to the younger cohort[76.5%vs 85.7%,P=0.46,crude RR=0.89(0.67-1.17)].Index admission colectomy[13.3%vs 10.5%,P=0.598,crude RR=1.27(0.53-2.99),adjusted RR=1.43(0.34-6.06)],colectomy at 3 mo[20%vs 16.6%,P=0.66,crude RR=1.18(0.61-2.3),adjusted RR=1.31(0.32-0.53)]and colectomy at 12 mo[20%vs 23.2%,P=0.682,crude RR=0.85(0.45-1.57),adjusted RR=1.21(0.29-4.97)],were similar between the two groups.CONCLUSION In older adults with ASUC,the steroid non-response rate,response to medical rescue therapy,and colectomy rate at index admission,3 and 12 mo is similar to patients less than 60 years of age.

Treatment of acute severe ulcerative colitis using accelerated infliximab regimen based on infliximab trough level:A case report

BACKGROUND Acute severe ulcerative colitis (ASUC) is a complication of ulcerative colitisassociated with high levels of circulating tumor necrosis factor alpha, due to theintense inflammation and faster stool clearance of anti-tumor necrosis factordrugs. Dose-intensified infliximab treatment can be beneficial and is associatedwith lower rates of colectomy. The aim of the study was to present a case of apatient with ASUC and megacolon, treated with hydrocortisone and acceleratedscheme of infliximab that was monitored by drug trough level.CASE SUMMARYA 22-year-old female patient diagnosed with ulcerative colitis, presented withdiarrhea, rectal bleeding, abdominal pain, vomiting, and distended abdomen.During investigation, a positive toxin for Clostridium difficile and colonic dilatationof 7 cm consistent with megacolon were observed. She was treated with oralvancomycin for pseudomembranous colitis and intravenous hydrocortisone forsevere colitis, which led to the resolution of megacolon. Due to the persistentsevere colitis symptoms, infliximab 5 mg/kg was prescribed, monitored by drugtrough level (8.8 μg/mL) and fecal calprotectin of 921 μg/g (< 30 μg/g). Based onthe low infliximab trough level after one week from the first infliximab dose, thepatient received a second infusion at week 1, consistent with the acceleratedregimen (infusions at weeks 0, 1, 2 and 6). We achieved a positive clinical andendoscopic response after 6 mo of therapy, without the need for a colectomy.CONCLUSIONInfliximab accelerated infusions can be beneficial in ASUC unresponsive to thetreatment with intravenous corticosteroids. Longitudinal studies are necessary todefine the best therapeutic drug monitoring and treatment regimen for thesepatients.

Development and validation of novel models for the prediction of intravenous corticosteroid resistance in acute severe ulcerative colitis using logistic regression and machine learning

Background The early prediction of intravenous corticosteroid(IVCS)resistance in acute severe ulcerative colitis(ASUC)patients remains an unresolved challenge.This study aims to construct and validate a model that accurately predicts IVCS resistance.Methods A retrospective cohort was established,with consecutive inclusion of patients who met the diagnosis criteria of ASUC and received IVCS during index hospitalization in Peking Union Medical College Hospital between March 2012 and January 2020.The primary outcome was IVCS resistance.Classification models,including logistic regression and machine learning-based models,were constructed.External validation was conducted in an independent cohort from Shengjing Hospital of China Medical University.Results A total of 129 patients were included in the derivation cohort.During index hospitalization,102(79.1%)patients responded to IVCS and 27(20.9%)failed;18(14.0%)patients underwent colectomy in 3 months;6 received cyclosporin as rescue therapy,and 2 eventually escalated to colectomy;5 succeeded with infliximab as rescue therapy.The Ulcerative Colitis Endoscopic Index of Severity(UCEIS)and C-reactive protein(CRP)level at Day 3 are independent predictors of IVCS resistance.The areas under the receiver-operating characteristic curves(AUROCs)of the logistic regression,decision tree,random forest,and extreme-gradient boosting models were 0.873(95%confidence interval[CI],0.704–1.000),0.648(95%CI,0.463–0.833),0.650(95%CI,0.441–0.859),and 0.604(95%CI,0.416–0.792),respectively.The logistic regression model achieved the highest AUROC value of 0.703(95%CI,0.473–0.934)in the external validation.Conclusions In patients with ASUC,UCEIS and CRP levels at Day 3 of IVCS treatment appeared to allow the prompt prediction of likely IVCS resistance.We found no evidence of better performance of machine learning-based models in IVCS resistance prediction in ASUC.A nomogrambased on the logistic regression model might aid in the management of ASUC patients.

Role of surgery in severe ulcerative colitis in the era of medical rescue therapy

Despite the growing use of medical salvage therapy,colectomy has remained a cornerstone in managing acute severe ulcerative colitis(ASC) both in children and in adults.Colectomy should be regarded as a life saving procedure in ASC,and must be seriously considered in any steroid-refractory patient.However,colectomy is not a cure for the disease but rather the substitution of a large problem with smaller problems,including fecal incontinence,pouchitis,irritable pouch syndrome,cuffitis,anastomotic ulcer and stenosis,missed or de-novo Crohn's disease and,in young females,reduced fecundity.This notion has led to the widespread practice of offering medical salvage therapy before colectomy in most patients without surgical abdomen or toxic megacolon.Medical salvage therapies which have proved effective in the clinical trial setting include cyclosporine,tacrolimus and infliximab,which seem equally effective in the short term.Validated predictive rules can identify a subset of patients who will eventually fail corticosteroid therapy after only 3-5 d of steroid therapy with an accuracy of 85%-95%.This accuracy is sufficiently high for initiat-ing medical therapy,but usually not colectomy,early in the admission without delaying colectomy if required.This approach has reduced the colectomy rate in ASC from 30%-70% in the past to 10%-20% nowadays,and the mortality rate from over 70% in the 1930s to about 1%.In general,restorative proctocolectomy(ileoanal pouch or ileal pouch-anal anastomosis),especially the J-pouch,is preferred over straight pullthrough(ileo-anal) or ileo-rectal anastomosis,which may still be considered in young females concerned about infertility.Colectomy in the acute severe colitis setting,is usually performed in three steps due to the severity of the inflammation,concurrent steroid treatment and the generally reduced clinical condition.The first surgical step involves colectomy and constructing an ileal stoma,the second-constructing the pouch and the third-closing the stoma.This review focuses on the role of surgical treatment in ulcerative colitis in the era of medical rescue therapy.