Effectiveness and safety of tofacitinib for ulcerative colitis: two-year results of the ICC Registry

Background Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment. Aim The aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands. Methods Patients initiating tofacitinib treatment were included in the ICC Registry, a nationwide, observational registry. Patients were prospectively evaluated for up to 24 months. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] <= 2) at week 104. Secondary outcomes included biochemical remission (C-reactive protein (CRP) <= 5 mg/L and faecal calprotectin (FC) <= 250 mu g/g), safety, and discontinuation rate. Results We included 110 patients of whom 104 (94.5%) were anti-TNF experienced. After 104 weeks of tofacitinib, 31.8% (34/107) were in CSFR, 23.4% (25/107) in biochemical remission and 18.7% (20/107) in combined clinical and biochemical remission. Of the patients in CSFR at week 52, 76.5% (26/34) remained so after 104 weeks of treatment. Sixty-one patients (55.5%) discontinued tofacitinib after a median duration of 13 weeks (IQR 7-34). The main reasons for discontinuation were non-response (59%), loss of response (14.8%), and adverse events (18%). There were 33.9 possible tofacitinib-related adverse events per 100 patient-years during follow-up. Adverse events most probably related to tofacitinib were skin reactions and headaches. There were 6.4 herpes zoster infections per 100 patient-years. Conclusion Tofacitinib was effective in 31.8% of patients after 24 months of treatment.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Short-term and long-term outcomes of a disruption and disconnection of the pancreatic duct in necrotizing pancreatitis: a multicenter cohort study in 896 patients

INTRODUCTION: Necrotizing pancreatitis may result in a disrupted or disconnected pancreatic duct (DPD) with the potential for long-lasting negative impact on a patient's clinical outcome. There is a lack of detailed data on the full clinical spectrum of DPD, which is critical for the development of better diagnostic and treatment strategies. METHODS: We performed a long-term post hoc analysis of a prospectively collected nationwide cohort of 896 patients with necrotizing pancreatitis (2005-2015). The median follow-up after hospital admission was 75 months (P25-P75: 41-151). Clinical outcomes of patients with and without DPD were compared using regression analyses, adjusted for potential confounders. Predictive features for DPD were explored. RESULTS:  DPD was confirmed in 243 (27%) of the 896 patients and resulted in worse clinical outcomes during both the patient's initial admission and follow-up. During hospital admission, DPD was associated with an increased rate of new-onset intensive care unit admission (adjusted odds ratio [aOR] 2.52; 95% confidence interval [CI] 1.62-3.93), new-onset organ failure (aOR 2.26; 95% CI 1.45-3.55), infected necrosis (aOR 4.63; 95% CI 2.87-7.64), and pancreatic interventions (aOR 7.55; 95% CI 4.23-13.96). During long-term follow-up, DPD increased the risk of pancreatic intervention (aOR 9.71; 95% CI 5.37-18.30), recurrent pancreatitis (aOR 2.08; 95% CI 1.32-3.29), chronic pancreatitis (aOR 2.73; 95% CI 1.47-5.15), and endocrine pancreatic insufficiency (aOR 1.63; 95% CI 1.05-2.53). Central or subtotal pancreatic necrosis on computed tomography (OR 9.49; 95% CI 6.31-14.29) and a high level of serum C-reactive protein in the first 48 hours after admission (per 10-point increase, OR 1.02; 95% CI 1.00-1.03) were identified as independent predictors for developing DPD. DISCUSSION:  At least 1 of every 4 patients with necrotizing pancreatitis experience DPD, which is associated with detrimental, short-term and long-term interventions, and complications. Central and subtotal pancreatic necrosis and high levels of serum C-reactive protein in the first 48 hours are independent predictors for DPD.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1):a multicenter stepped-wedge cluster randomized controlled trial

Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018

Endoscopic Versus Surgical Step-Up Approach for Infected Necrotizing Pancreatitis (ExTENSION): Long-term Follow-up of a Randomized Trial

BACKGROUND & AIMS: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years. METHODS: In this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life. RESULTS: After a mean followup period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65-1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08-0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09-0.99). Pancreatic insufficiency and quality of life did not differ between groups. CONCLUSIONS: At long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Challenges in Inflammatory Bowel Disease care: from evidence to real world practice

Contains fulltext : 202631.pdf (publisher's version ) (Open Access)Radboud University, 24 mei 2019Promotor : Drenth, J.P.H. Co-promotor : Hoentjen, F

Prevalence and clinical characteristics of insulin-treated, anti-GAD-positive, type 2 diabetic subjects in an outpatient clinical department of a Dutch teaching hospital.

BACKGROUND: In clinical practice, type 1 and type 2 diabetic patients are sometimes difficult to distinguish. Type 1 diabetes has an immune-mediated pathogenesis, resulting in a loss of insulin-secreting beta-cells. Type 2 diabetes mellitus is characterised by a relative insulin insufficiency, without the presence of an autoimmune aetiology, initially due to insulin resistance and later also accompanied by defective insulin release. Latent autoimmune diabetes of the adult (LADA) is a subgroup of diabetes, somewhere on the borderland between type 1 and type 2 diabetes. LADA is characterised by a late-age onset and relatively mild progression, but with unmistakable signs of autoimmunity, such as the presence of the autoimmune antibodies anti-GAD65, anti-insulin antibodies, or anti-Ia-2ab. OBJECTIVE: To establish the prevalence of anti-GAD ina diabetic outpatient clinic of a Dutch, non-university,teaching hospital and to describe these patients clinical and laboratory features, especially of the metabolic syndrome. METHODS: We evaluated GAD65 antibodies and other parameters in 244 selected diabetic patients, who had been on oral therapy for at least three months before becoming insulin-dependent. RESULTS: Twenty-six patients (11.6%) were positive for GAD65 antibodies. These patients had a significantly lower BMI (27.8 +/- 4.5 vs 31.1 +/- 4.9; p<0.01); less often cerebrovascular accidents (19.2 vs 34.9%; p<0.01) and a higher HDL cholesterol (1.73 +/- 0.53 vs 1.21 +/- 0.38; p<0.05). In contrast, anti-GAD patients had a significantly higher prevalence of hypothyroidism (23.0 vs 6.6%; p<0.05). CONCLUSION: Anti-GAD-positive patients represent a sizable proportion of type 2 diabetes in a second-line outpatient clinic, and they are characterised by lower parameters of the metabolic syndrome, but higher prevalence of other autoimmune phenomena such as hypothyroidism

[Current options for percutaneous endoscopic access to the digestive tract]

Four patients, aged 67, 52, 56 and 64 years, respectively, undergoing percutaneous colostomy or jejunostomy are presented to illustrate current options for percutaneous endoscopic access to the digestive tract. The first patient had Parkinson's disease and required percutaneous jejunostomy for continuous post-pyloric administration of medication. The second patient had impaired gastric emptying due to gastric graft-versus-host disease following bone marrow transplantation. He was successfully treated with percutaneous jejunostomy, which was removed 2 years later after full recovery. The third patient had severe constipation due to the use ofmorphinomimetic analgesics. She received percutaneous caecostomy for colonic lavage and desufflation. The fourth patient had combined constipation and sphincteric insufficiency. Although the percutaneous endoscopic colostomy was clinically successful, the catheter had to be removed due to local pain and abscess formation