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Background and Aims There is paucity of data on safety and efficacy of anti-tumour necrosis factor [TNF] in elderly inflammatory bowel disease [IBD] patients. We aimed to compare the long-term treatment failure rates and safety of a first anti-TNF agent in IBD patients between different age groups [<40 years/40–59 years/≥60 years]. Methods IBD patients who started a first anti-TNF agent were identified through IBDREAM, a multicentre prospective IBD registry. Competing risk regression was used to study treatment failure, defined as time to drug discontinuation due to adverse events [AEs] or lack of effectiveness, with discontinuation due to remission as a competing risk. Results A total of 895 IBD patients were included; 546 started anti-TNF at age <40 [61.0%], 268 at age 40–59 [29.9%], and 81 at age ≥60 [9.1%]. Treatment failure rate was higher in the two older groups (subhazard rate [SHR] age ≥60 1.46, SHR age 40–59 1.21; p  = 0.03). The SHR in the elderly [>60] was 1.52 for discontinuation due to AEs and 1.11 for lack of effectiveness. Concomitant thiopurine use was associated with a lower treatment failure rate (SHR 0.78, 95% confidence interval [CI] 0.62–0.98, p  = 0.031). Serious adverse event [SAE] rate, as well as serious infection rate, were significantly higher in elderly IBD patients [61.2 versus 16.0 and 12.4 per 1000 patient-years, respectively] whereas the malignancy rate was low in all age groups. Conclusions Elderly IBD patients starting a first anti-TNF agent showed higher treatment failure rates, but concomitant thiopurine use at baseline was associated with lower failure rates. Elderly IBD patients demonstrated higher rates of SAEs and serious infections. [ABSTRACT FROM AUTHOR]

Objective: To describe the long-term consequences of necrotising pancreatitis, including complications, the need for interventions and the quality of life., Design: Long-term follow-up of a prospective multicentre cohort of 373 necrotising pancreatitis patients (2005-2008) was performed. Patients were prospectively evaluated and received questionnaires. Readmissions (ie, for recurrent or chronic pancreatitis), interventions, pancreatic insufficiency and quality of life were compared between initial treatment groups: conservative, endoscopic/percutaneous drainage alone and necrosectomy. Associations of patient and disease characteristics during index admission with outcomes during follow-up were assessed., Results: During a median follow-up of 13.5 years (range 12-15.5 years), 97/373 patients (26%) were readmitted for recurrent pancreatitis. Endoscopic or percutaneous drainage was performed in 47/373 patients (13%), of whom 21/47 patients (45%) were initially treated conservatively. Pancreatic necrosectomy or pancreatic surgery was performed in 31/373 patients (8%), without differences between treatment groups. Endocrine insufficiency (126/373 patients; 34%) and exocrine insufficiency (90/373 patients; 38%), developed less often following conservative treatment (p<0.001 and p=0.016, respectively). Quality of life scores did not differ between groups. Pancreatic gland necrosis >50% during initial admission was associated with percutaneous/endoscopic drainage (OR 4.3 (95% CI 1.5 to 12.2)), pancreatic surgery (OR 3.2 (95% CI 1.1 to 9.5) and development of endocrine insufficiency (OR13.1 (95% CI 5.3 to 32.0) and exocrine insufficiency (OR6.1 (95% CI 2.4 to 15.5) during follow-up., Conclusion: Acute necrotising pancreatitis carries a substantial disease burden during long-term follow-up in terms of recurrent disease, the necessity for interventions and development of pancreatic insufficiency, even when treated conservatively during the index admission. Extensive (>50%) pancreatic parenchymal necrosis seems to be an important predictor of interventions and complications during follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aim: More insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in disease management and patient counseling., Methods: A long-term post hoc analysis of a prospective cohort of patients with AP (2008-2015) was performed. Primary endpoints were recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. Cumulative incidence calculations and risk analyses were performed., Results: Overall, 1184 patients with a median follow-up of 9 years (IQR: 7-11) were included. RAP and CP occurred in 301 patients (25%) and 72 patients (6%), with the highest incidences observed for alcoholic pancreatitis (40% and 22%). Pancreatic cancer was diagnosed in 14 patients (1%). Predictive factors for RAP were alcoholic and idiopathic pancreatitis (OR 2.70, 95% CI 1.51-4.82 and OR 2.06, 95% CI 1.40-3.02), and no pancreatic interventions (OR 1.82, 95% CI 1.10-3.01). Non-biliary etiology (alcohol: OR 5.24, 95% CI 1.94-14.16, idiopathic: OR 4.57, 95% CI 2.05-10.16, and other: OR 2.97, 95% CI 1.11-7.94), RAP (OR 4.93, 95% CI 2.84-8.58), prior pancreatic interventions (OR 3.10, 95% CI 1.20-8.02), smoking (OR 2.33, 95% CI 1.14-4.78), and male sex (OR 2.06, 95% CI 1.05-4.05) were independently associated with CP., Conclusion: Disease progression was observed in a quarter of pancreatitis patients. We identified several risk factors that may be helpful to devise personalized strategies with the intention to reduce the impact of disease progression in patients with AP., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: Following an episode of acute biliary pancreatitis, cholecystectomy is advised to prevent recurrent biliary events. There is limited evidence regarding the optimal timing and safety of cholecystectomy in patients with necrotising biliary pancreatitis., Design: A post hoc analysis of a multicentre prospective cohort. Patients with biliary pancreatitis and a CT severity score of three or more were included in 27 Dutch hospitals between 2005 and 2014. Primary outcome was the optimal timing of cholecystectomy in patients with necrotising biliary pancreatitis, defined as: the optimal point in time with the lowest risk of recurrent biliary events and the lowest risk of complications of cholecystectomy. Secondary outcomes were the number of recurrent biliary events, periprocedural complications of cholecystectomy and the protective value of endoscopic sphincterotomy for the recurrence of biliary events., Results: Overall, 248 patients were included in the analysis. Cholecystectomy was performed in 191 patients (77%) at a median of 103 days (P25-P75: 46-222) after discharge. Infected necrosis after cholecystectomy occurred in four (2%) patients with persistent peripancreatic collections. Before cholecystectomy, 66 patients (27%) developed biliary events. The risk of overall recurrent biliary events prior to cholecystectomy was significantly lower before 10 weeks after discharge (risk ratio 0.49 (95% CI 0.27 to 0.90); p=0.02). The risk of recurrent pancreatitis before cholecystectomy was significantly lower before 8 weeks after discharge (risk ratio 0.14 (95% CI 0.02 to 1.0); p=0.02). The complication rate of cholecystectomy did not decrease over time. Endoscopic sphincterotomy did not reduce the risk of recurrent biliary events (OR 1.40 (95% CI 0.74 to 2.83))., Conclusion: The optimal timing of cholecystectomy after necrotising biliary pancreatitis, in the absence of peripancreatic collections, is within 8 weeks after discharge., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Background and Objective: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most prevalent complication after ERCP with an incidence of 3.5%. PEP severity is classified according to either the consensus criteria or the revised Atlanta criteria. In this international cohort study we investigated which classification is the strongest predictor of PEP-related mortality., Methods: We reviewed 13,384 consecutive ERCPs performed between 2012 and 2017 in eight hospitals. We gathered data on all pancreatitis-related adverse events and compared the predictive capabilities of both classifications. Furthermore, we investigated the correlation between the two classifications and identified reasons underlying length of stay., Results: The total sample consisted of 387 patients. The revised Atlanta criteria have a higher sensitivity (100 vs. 55%), specificity (98 vs. 72%) and positive predictive value (58 vs. 5%). There is a significant difference ( p  < 0.001) between the two classifications. In 124 patients (32%), the length of stay was influenced by concomitant diseases., Conclusion: The revised Atlanta classification is superior in predicting mortality and better reflects PEP severity. This has important implications for researchers, clinicians and patients. For the diagnosis of PEP pancreatitis, the consensus criteria remain the golden standard. However, the revised Atlanta criteria are preferable for defining PEP severity.

Background: This review discusses current insights with regard to biliary tract management during and after acute biliary pancreatitis., Methods: A MEDLINE and EMBASE search was done and studies were selected based on methodological quality and publication date. The recommendations of recent guidelines are incorporated in this review. In absence of consensus in the literature, expert opinion is expressed., Results: There is no role for early endoscopic retrograde cholangiopancreatography (ERCP) in patients with (predicted) mild biliary pancreatitis to improve outcome. In case of persisting choledocholithiasis, ERCP with stone extraction is scheduled electively when the acute event has subsided. Whether early ERCP with sphincterotomy is beneficial in patients with predicted severe pancreatitis remains subject to debate. Regardless of disease severity, in case of concomitant cholangitis urgent endoscopic sphincterotomy (ES) is recommended. As a definitive treatment to reduce the risk of recurrent biliary events in the long term, ES is inferior to cholecystectomy and should be reserved for patients considered unfit for surgery. After severe biliary pancreatitis, cholecystectomy should be postponed until all signs of inflammation have subsided. In patients with mild pancreatitis, cholecystectomy during the primary admission reduces the risk of recurrent biliary complications., Conclusion: Recent research has provided valuable data to guide biliary tract management in the setting of acute biliary pancreatitis with great value and benefit for patients and clinicians. Some important clinical dilemmas remain, but it is anticipated that on-going clinical trials will deliver some important insights and additional guidance soon., (Copyright © 2015 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

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.

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.