Management Of Severe Ulcerative Colitis Research Articles

Inpatient Therapy With Calcineurin Inhibitors in Severe Ulcerative Colitis.

Inpatient management of severe ulcerative colitis is complicated by the use of prior immunosuppressant therapies. Our aim was to determine the rate of 1-year colectomy among individuals receiving inpatient calcineurin inhibitor (CNI)-based therapy stratified by prior biologic therapy. A retrospective cohort study was performed between January 1, 2013 and April 1, 2018. Only individuals requiring inpatient administration of intravenous cyclosporine or oral tacrolimus were included in the analysis. Individuals were stratified according to prior biologic therapy exposure. The primary outcome of interest was 1-year risk of colectomy. Kaplan-Meier curves were generated for time-to-event data, and regression models were performed to examine the effects of covariates on the clinical endpoint. Sixty-nine (62.3% male) patients were treated with an inpatient CNI-based therapy and were included in the analysis. Fifteen (21.7%) patients were biologic-naïve, 42 (60.9%) patients had prior exposure to 1 class of biologic therapy, and 12 (17.4%) patients had prior exposure to 2 classes of biologic therapy (third-line CNI therapy). Third-line CNI therapy showed a greater risk of 1-year colectomy risk when compared with the risk for patients who were biologic-naïve (hazard ratio, 3.63; 95% confidence interval, 1.17-13.45; P = 0.025). In a multivariate proportional hazards model, third-line CNI therapy remained significantly associated with 1-year colectomy risk (hazard ratio, 7.94; 95% confidence interval, 1.97-39.76; P = 0.003). The use of CNI-based therapy in individuals exposed to multiple classes of prior biologic therapies leads to a significantly increased risk of 1-year colectomy. Future studies will be required to compare inpatient management strategies with the expanding novel therapies in UC.

Risk of postoperative complications among ulcerative colitis patients treated preoperatively with vedolizumab: a matched case-control study

BackgroundAlthough biologic agents have revolutionized the medical management of severe ulcerative colitis (UC), there is considerable controversy regarding adverse effects of vedolizumab on surgical outcomes. We evaluated 30-day postoperative morbidity in UC patients undergoing abdominal colectomy (AC) treated with vedolizumab before surgery.MethodsFrom 2007 to 2017, 285 patients were enrolled in prospectively maintained database evaluating the role of clinical, serologic markers with clinical phenotypes in UC. The patients treated with vedolizumab within 12 weeks of AC was queried, then matched 1:3:3 into 3 preoperative treatment groups based on age, gender and surgical treatment of UC; ileal pouch-anal anastomosis (IPAA) with ileostomy vs total colectomy with end stoma: a) vedolizumab (n = 25); b) anti-tumor necrosis factor (anti-TNF) (n = 74); and c) no biologics (n = 54). Thirty-day postoperative complications among patient groups were compared.ResultsThe 3 patient groups were well-matched in other characteristics including disease duration, disease extent, medication history and preoperative serological data. There were no significant differences in the overall incidence of postoperative complications among patients treated preoperatively with vedolizumab, anti-TNFs, or no biologics (44% vs. 45% vs. 37%; p = 0.67). Although there was no significant difference between patient cohorts in infectious complications (p = 0.20), postoperative ileus (POI) was significantly more common among the vedolizumab group (n = 9; 36%) compared to anti-TNF (n = 12; 16%) or no biologics (n = 5; 9%) (p = 0.01). Multivariable analysis showed that vedolizumab treatment prior to surgery was an independent risk factor for POI (OR: 5.16, 95% CI; 1.71–15.52; p = .004).ConclusionAlthough preoperative vedolizumab exposure did not influence the rate of overall 30-day postoperative complications, vedolizumab tends to increase incidence of POI.

Chinese research into severe ulcerative colitis has increased in quantity and complexity.

AIMTo investigate the current state of research output from Chinese studies into severe ulcerative colitis (SUC) using a bibliometric analysis of publications.METHODSThe contents of the Chinese periodical databases WANFANG, VIP, and China National Knowledge Infrastructure were searched for all papers regarding UC or SUC published in last the 15 years (from 2001 to 2015). The number of publications in each year was recorded to assess the temporal trends of research output. All SUC related publications were downloaded and the complexity of this research was evaluated with methods described previously. The number of patients with SUC reported each year was recorded and their clinical characteristics were analyzed using information available in the relevant papers.RESULTSThere were 13499 publications regarding UC published in Chinese medical journals between 2001 and 2015, of which 201 focused on SUC. The number of publications increased rapidly with more than half of all papers being published in the most recent 5-year period. There was a significant increase in analytical studies and clinical trials over the study period (P < 0.01), with research into the management of SUC, included pharmacotherapy, nutrition support as well as surgery, predominating. Almost half (46.2%) of the observational analytical studies and clinical trials focused on Traditional Chinese Medicine, with little research on the efficacy of cyclosporin and infliximab in disease management. About 6222 patients with SUC were reported in the 201 SUC relevant papers, with a ratio of male/female of 1.38. The number of patients reported in each 5-year period significantly increased. The colectomy rate and short-term mortality rate were 7.7% and 0.8% respectively. The most commonly employed operation was total proctocolectomy with ileal pouch-anal anastomosis.CONCLUSIONThe output and complexity of research related to SUC in China increased significantly over the previous 15 years, however few of these studies focused on salvage therapy.

Management of severe ulcerative colitis refractory to steroid therapy

Management of severe ulcerative colitis refractory to steroid therapy

Management of severe ulcerative colitis.

Acute severe steroid-refractory ulcerative colitis (ASUC) provides challenges for physicians and surgeons who manage these patients. When a patient is diagnosed with ASUC, they should be admitted for inpatient management including intravenous corticosteroids, venous thromboembolism prophylaxis, oral or enteral feeding if tolerated, and exclusion of infection including Clostridium difficile. Failure to improve by day 3 of corticosteroids requires escalation to medical rescue therapies such as infliximab or cyclosporine, or surgical management with colectomy. This chapter will review management of ASUC with a focus on the medical rescue options available.

Management of Severe Ulcerative Colitis in the Setting of Acute Myocardial Infarction

Management of Severe Ulcerative Colitis in the Setting of Acute Myocardial Infarction

Aspects in the Interdisciplinary Decision-Making for Surgical Intervention in Ulcerative Colitis and its Complications

Ulcerative colitis (UC) is a chronic inflammation of the large bowel, predominantly affecting young adults of 20 to 30 years of age. Even though the majority of patients with limited and extensive UC can be managed medically, 20 to 30 % will require surgical intervention at some point in their life to gain control of the inflammatory process. The most common reason for urgent and emergency surgery is a lack of response to maximal medical inpatient therapy after five to ten days. Other indications include hemorrhage, free perforation, sepsis, and toxic megacolon. Procedure of choice for the majority of surgeons is open or laparoscopic subtotal colectomy and end ileostomy, with or without exteriorization of the rectal stump. The laparoscopic approach requires more time, but allows for faster return of bowel function and discharge from the hospital. Creation of a definite restoration in form of a J pouch should be delayed for at least three months. Indications for elective surgical intervention include cancer, dysplasia associated lesion or mass, and stricture. Preferably, the J pouch and Brooke ileostomy are performed in two stages, with a takedown of the ileostomy several months later. A single-stage operation is associated with increased anastomotic dehiscence, sepsis, and long-term pouch failure. The laparoscopic creation of a J pouch is largely dependent on the surgeon's experience, but results in a number of advantages, including faster return of bowel function, tolerance of diet, and discharge. Regardless of emergency, urgent, or elective surgical intervention, early involvement of a team of gastroenterologist, surgeon, nutritionist, and stoma nurse is essential in the management of severe UC to maximize a satisfactory patient outcome.

Cyclosporine in the management of severe ulcerative colitis while breast-feeding

Cyclosporine in the management of severe ulcerative colitis while breast-feeding

Nursing management of patients with severe ulcerative colitis

Ulcerative colitis is a relapsing chronic disease that has an unpredictable course. A relapse in the condition requires timely intervention and expert monitoring. A severe flare-up will often necessitate admission to hospital. This article provides an overview of the medical management of severe ulcerative colitis and the nursing interventions required.

Medical treatment and management of severe ulcerative colitis

Severe colitis is a life-threatening complication of ulcerative colitis. Early recognition of the severity of the colitis and intensive treatment and monitoring have all contributed to improved outcome. Since their introduction in the 1950s, corticosteroids are the first line therapy for severe active ulcerative colitis (UC). Several prognostic parameters (such as stools movement per day, C-reactive protein, increased amount of intestinal gas or small bowel dilation, hypoalbuminemia, fever, etc.) help the physician to quickly introduce infliximab or cyclosporine or to refer the patient to the surgeon. This decision requires a careful evaluation of the patient and a medical/surgical team.

Historical evolution of the management of severe ulcerative colitis

Ulcerative colitis was first described in 1859, but it was not until the early 20th century that it became a well recognized clinical entity. The patients of the old series showed high mortality rate ranging from 30% in the severe forms to 60% in the fulminating forms. The introduction of corticosteroids in the 1950s dramatically improved the prognosis of patients with severe ulcerative colitis. The strategy based on intensive medical treatment, early detection of risk factors and early surgery progressively reduced the mortality rate to less than 1%. Tachycardia, fever, reduced number of intestinal sounds, hypoalbuminaemia, hypokalaemia metabolic alkalosis and elevated C-reactive protein were recognized to be the most useful risk factors. Plain abdominal X-ray remains the very reliable suitable tool to detect early complications of severe colitis. Once reduced the mortality near to zero, treatment has been addressed to avoid colectomy. Cyclosporine and Infliximab are currently used as rescue therapy, however, despite the high remission rates achieved with both drugs, about 50% of the treated patients ultimately will come to colectomy over the next few years.

Severe ulcerative colitis: At what point should we define resistance to steroids?

Corticosteroids are still the first-line treatment for active ulcerative colitis more than 50 years after the publication of trials assessing their beneficial effect, with about a 50% remission rate in cases of severe disease. The mortality related to severe attacks of ulcerative colitis has decreased dramatically, to less than 1%, in experienced centers, due to the appropriate use of intensive therapeutic measures (intravenous steroids, fluids and electrolytes, artificial nutritional support, antibiotics, etc), along with timely decision-making about second-line medical therapy and early identification of patients requiring colectomy. One of the most difficult decisions in the management of severe ulcerative colitis is knowing for how long corticosteroids should be administered before deciding that a patient is a non-responder. Studies assessing the outcome of acute attacks after steroid initiation have demonstrated that, in steroid-sensitive patients, the response generally occurs early on, in the first days of treatment. Different indexes to predict treatment failure, when applied on the third day of treatment, have demonstrated a high positive predictive value for colectomy. In contrast to this resolute approach, which is the most widely accepted, other authors have suggested that in some patients a complete and prolonged response to steroids may take longer. Either way, physicians taking care of these patients need to recognize that severe ulcerative colitis may be life-threatening, and they need to be careful with excessively prolonged medical treatment and delayed surgery.

Current management of severe ulcerative colitis

Approximately 15% of patients with ulcerative colitis develop an acute attack of severe colitis, and 30% of these patients require colectomy. Severe ulcerative colitis is therefore considered a medical emergency, the management of which requires close collaboration between gastroenterologists and surgeons. The mortality rate for patients with severe ulcerative colitis is now <1% in specialist centers, but it was high before intravenous steroid therapy and early surgery were introduced; indeed, mortality is still high in nonspecialized centers. As colectomy severely affects quality of life, therapy with intravenous ciclosporin and, more recently, infliximab has been introduced to try to avoid the need for surgery. Ciclosporin induces short-term remission, but the long-term benefit remains unsatisfactory as colectomy is often only delayed. A significant short-term reduction in the colectomy rate has, however, been observed after infliximab treatment. The use of infliximab versus ciclosporin in patients with severe ulcerative colitis remains to be defined. The timing of surgery remains a cardinal decision in the management of severe ulcerative colitis; increased morbidity resulting from prolonged ineffective medical treatment and, therefore, a delay in surgical treatment should be avoided.

Rapamycin decreases leukocyte migration in vivo and effectively reduces experimentally induced chronic colitis

Immunosuppressive calcineurin inhibitors, like cyclosporine (CsA), can be used for the clinical management of severe ulcerative colitis. However, patients treated with CsA are at a risk for developing kidney failure and may be more susceptible to colon cancer. Furthermore, severe neurotoxicity and hypertension are common problems. To avoid the side effects of CsA, new immunosuppressive drugs to treat colitis are needed. The aim of the present study was to test the immunosuppressive mammalian target of rapamycin inhibitor rapamycin in an experimental model of chronic colitis and to compare its effectiveness with CsA. Chronic colitis was established in Balb/c mice after four feeding cycles of dextran sodium sulfate. Because leukocyte recruitment to sites of intestinal inflammation is crucial for the development of chronic colitis, intravital microscopy was used to study the effect of rapamycin and CsA on leukocyte-endothelium interactions and leukocyte extravasation. To assess the degree of colitis, histological sections were evaluated. Both rapamycin and cyclosporine effectively reduced leukocyte sticking (>60%) in submucosal venules, as compared to controls. Furthermore, rapamycin, but not CsA, reduced (>35%) leukocyte extravasation in the mucosa. Both rapamycin and CsA treatments significantly improved the histologic inflammation score. Our in vivo results demonstrate that rapamycin reduces leukocyte sticking and extravasation during chronic colitis induction and proves to be as effective as CsA at reducing experimental chronic colitis. These results support the use of rapamycin in clinical trials to avoid serious side effects of CsA therapy in chronic colitis patients.

Cyclosporin therapy in severe ulcerative colitis: is it worth the effort?

Cyclosporin is advocated in the treatment of acute severe ulcerative colitis that has failed to respond to high-dose corticosteroid therapy. This approach is controversial, with critics highlighting the temporary nature of remissions and the potential for adverse effects. There have been few reports of the long-term outcome of those patients who do respond. The purpose of this study was to investigate the clinical outcome of all patients treated with cyclosporin at our institution over the past five years. We conducted a retrospective study of 46 patients who presented to a tertiary referral center. Initial responders were those who avoided colectomy; a sustained response was defined as a remission that lasted while the patient was taking oral cyclosporin and for three months after this therapy was discontinued. Thirty-two (69 percent) of 46 patients had an initial response to therapy, and 50 percent met criteria for a sustained response. Eleven of 23 sustained responders subsequently relapsed. At a mean of 22 months' follow-up, 26 percent of patients remain well and have never relapsed. Serious infective complications occurred in two patients, possibly attributable to therapy. No factors predictive of a likely response were identifiable on retrospective analysis. This study confirms the efficacy of cyclosporin in the management of severe ulcerative colitis. Although many initial responders subsequently relapse, such patients may benefit from having even a short time to adjust to the need for surgery. A substantial minority (26 percent) of all patients treated remain in long-term remission.

Review article: the management of severe ulcerative colitis.

Severe ulcerative colitis is a potentially life-threatening condition but the mortality has fallen dramatically over the past 30-40 years. It is now less than 2%, including surgical mortality, and should only be seen in patients with significant co-existing disease. Early recognition of the severity of the colitis, intensive medical therapy, close liaison between physician and surgeon, and prompt surgery when necessary have all contributed to this improved outcome. Despite the use of high-dose intravenous corticosteroids, 20-30% of patients will make a poor response and will require urgent surgery. The use of intravenous cyclosporin has proved effective at reducing the immediate surgical rate in this group of unresponsive patients and appears safe. Whether cyclosporin reduces the need for surgery in the longer term is much less certain. Clinical, radiological, endoscopic and laboratory parameters can now be used to predict the course of a severe attack. These help in the timing of urgent surgery and are potentially helpful in determining when to begin other therapies such as cyclosporin.

Refractory IBD: medical management

Refractory inflammatory bowel disease (IBD) can be defined as persistent acute symptomatic disease despite anti-inflammatory therapy or as chronically active disease requiring continuous treatment for relief of symptoms. Treatment options include azathioprine (AZA), 6-mercaptopurine (6-MP), methotrexate (MTX), cyclosporine (CYA), and experimental therapies that are cytokines or cytokine antagonists. AZA and 6-MP have identical actions in IBD. 6-MP is effective in about 75% of patients with inflammatory Crohn's disease. The mean time until the onset of action is 3.1 months. AZA is effective in ulcerative colitis as a steroid-sparing agent. Side-effects occur in 10–15% of patients on AZA or 6-MP for IBD. MTX induces symptomatic remission in about 40% of patients with Crohn's disease. The potential for hepatic fibrosis from MTX is a concern. CYA appears effective in the acute management of severe ulcerative colitis. CYA has not proven useful in the long-term management of Crohn's disease. Potentially serious side-effects include hypertension and renal insufficiency. The cytokine antagonist, anti-tumor-necrosis-factor-alpha antibody, and the anti-inflammatory cytokine, interleukin 10, appear promising for the treatment of Crohn's disease.

High resolution ultrasonography for the management of severe ulcerative colitis: Patient friendly but not user friendly

High resolution ultrasonography for the management of severe ulcerative colitis: Patient friendly but not user friendly

How I do it. Medical management of severe ulcerative colitis.

Providing some simple rules are applied, severe attacks of ulcerative colitis can be effectively managed with virtually no mortality. A proportion of patients (1 in 5) will come to surgery but the guidelines for surgical intervention are now clear. Joint management between medical and surgical teams is important and, possibly, the combination of a surgically aggressive physician with a medicallyminded surgeon is the ideal.

Controlled trial of intravenous metronidazole as an adjunct to corticosteroids in severe ulcerative colitis.

A prospective double blind controlled trial was undertaken to examine the role of metronidazole as an adjunct to corticosteroids in the management of severe ulcerative colitis. Thirty nine patients with severe ulcerative colitis were randomised on admission to hospital to receive either intravenous metronidazole 500 mg eight hourly (19 patients) or an identical intravenous placebo (20 patients). The two groups were similar with respect to age, sex, and the extent of colitis. In addition all patients received a standard intravenous regimen consisting of methyl prednisolone 16 mg six hourly and parenteral nutrition together with a twice daily hydrocortisone 100 mg enema. Treatment was continued for five days when the patients were formally assessed. Fourteen of 19 patients (74%) receiving metronidazole and 14/20 (70%) receiving placebo were substantially improved, or in remission at the end of five days. Five patients treated with metronidazole and six with placebo had no improvement and all proceeded to urgent colectomy with no operative mortality. There were three late deaths, one in the metronidazole and two in the placebo group. These results do not support the routine use of intravenous metronidazole in the treatment of severe ulcerative colitis.