Impact on follow-up strategies in patients with primary sclerosing cholangitis.

BACKGROUND & AIMS: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival. METHODS: We collected retrospective data from 2975 PSC patients from 27 centres. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from 1 January 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality. RESULTS: A broad variety of different follow-up strategies were reported. All except one centre used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centres used scheduled endoscopic retrograde cholangiopancreatography (ERCP) in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, was 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years of follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed. CONCLUSIONS: Follow-up strategies vary considerably across centres. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumour detection and increased endoscopic treatment of asymptomatic benign biliary strictures.

Exploring stakeholders and their requirements in the process of home hemodialysis: A literature review.

Providing home hemodialysis (HHD) therapy is a complex process that not only requires the use of a complex technology but also involves a diverse group of stakeholders, and each stakeholder has their requirements and may not share a common interest. Bringing them together will require the alignment of their interests. A process management perspective can help to accomplish the alignment of their interests. To align their interests, it is crucial to identify interest groups and understand their interests. The main objective of this paper is to identify the stakeholders and represents their interests as a list of requirements in the HHD process. An extensive literature review has been carried out and PubMed was used for literature extraction. In total, 1848 articles were retrieved of which 80 have fulfilled the inclusion criteria. A large array of actors is identified and their interests/requirements at different stages of the HHD process are represented in the form of a list. They have both common and conflicting requirements in the HHD process. If these requirements are aligned and balanced, a stakeholder's driven treatment process will be developed and a real improvement will be achieved in the treatment process.

Total Synthesis, Stereochemical Assignment, and Divergent Enantioselective Enzymatic Recognition of Larreatricin.

A concise and efficient total synthesis of the lignan natural product larreatricin as well as an unambiguous assignment of configuration of its enantiomers are reported, resolving a long-held controversy. Enzyme kinetic studies revealed that different polyphenol oxidases show high and remarkably divergent enantioselective recognition of this secondary metabolite.

Acute Severe Ulcerative Colitis Flare Complicated by Myopericarditis and Infliximab-Induced Hepatitis.

Ulcerative colitis (UC) is an autoimmune disease associated with both intestinal and extraintestinal manifestations. The latter may include heart complications, such as myopericarditis leading to life-threatening arrythmias. Nowadays, UC is commonly treated with biologic medications and infliximab is the first line therapy in an outpatient setting, while it is also used as rescue therapy in acute severe UC. However, it has been associated with severe immunosuppression, cytomegalovirus (CMV) reactivation and drug-induced hepatitis. We report a case of UC flare in a biologic naïve patient admitted with myopericarditis, which was further complicated by positive CMV biopsies and infliximab-induced transaminitis. LEARNING POINTS: In acute inflammatory bowel disease (IBD) flare presentation with tachycardia and chest pain, an underlying myocardial injury should be investigated.Mucosal healing should be evaluated endoscopically in cases of partial response to biologics.Both cytomegalovirus (CMV) infection and infliximab-induced liver injury may lead to acute hepatitis.

PPARγ as a sensor of lipase activity and a target for the lipase inhibitor orlistat.

A PPARγ fluorescence polarization (FP) assay was used to measure the release of fatty acid products from triglyceride emulsions during digestion with pancreatic and yeast lipases in a real-time, homogenous assay. Using the same FP assay we show the anti-obesity drug Orlistat is a PPARγ ligand with an IC50 of 2.84 ± 0.16 µM. Analytical Mass Spectrometry confirms that Orlistat does not bind covalently to PPARγ. The PPARγ FP assay is shown to be a simple method for measuring real-time lipase activity using a number of triglyceride substrates including olive oil and grape seed oil emulsions. Incubation of Orlistat with the human intestinal epithelial cell line Caco-2, at concentrations of 1 - 100 µM, leads to induction of genes regulated by PPARγ. At 100 µM Orlistat, transcription of ß-defensin 1 (hDB1) & Adipose Differentiation Related Protein (ADRP) increase by up to 2.6 fold and 6.8 fold, respectively. Although at 1 µM and 100 µM Orlistat did not significantly increase defensin protein synthesis, at 10 µM Orlistat induced a 1.5 fold increase in hDB1 protein secretion in the human colonic adenocarcinoma cell line HT-29. Thus Orlistat is similar to the anti-diabetic drug Rosiglitazone in its ability to induce defensin gene expression. The antimicrobial peptide ß-defensin 1 protects against pathogenic micro-organisms in the gut and PPARγ suppresses inflammatory gene expression. These may be beneficial side effects of Orlistat consumption on gut epithelial cells.

ERCP for bile duct stones across a national service, demonstrating a high requirement for repeat procedures.

Background and study aims Bile duct stones (BDS) represent approximately 50 % of the requirement for endoscopic retrograde cholangiopancreatography (ERCP) within most services. Significant variation in outcome rates for BDS clearance at ERCP has been reported, and endoscopy societies have set standards for expected clearance rates. The aim of this study was to analyze procedure outcomes across a national service. Patients and methods Using verified hospital episode statistics (HES) data for the National Health Service (NHS) in England, we analyzed all patients having first ERCPs for BDS from 2015 to 2017, and followed these patients for at least 2 years. Results In total 37,468 patients underwent a first ERCP for BDS, with 69.8 % undergoing only one procedure. This figure of less than 70 % of BDS cleared at first ERCP is below the Key Performance Indicators as set by the British Society of Gastroenterology (> 75 %) and the European Society of Gastrointestinal Endoscopy (> 90 %). Of 55,556 ERCPs done for BDS, 52.9 % were repeat procedures, with 11,322 patients needing multiple procedures. For hospitals performing significant numbers of ERCPs (more than 600 for BDS during the study period) patients undergoing repeat ERCPs for BDS ranged from 9 % to 50 %. Conclusions In this nationwide study, the performance at clearing BDS at first ERCP was suboptimal, with high numbers of repeat procedures required. This may have a negative impact on both patient outcomes and experience, and increase pressure on endoscopy services. Apparent variation of outcome between acute hospital care providers requires further analysis.

Humans versus AI: whether and why we prefer human-created compared to AI-created artwork.

With the recent proliferation of advanced artificial intelligence (AI) models capable of mimicking human artworks, AI creations might soon replace products of human creativity, although skeptics argue that this outcome is unlikely. One possible reason this may be unlikely is that, independent of the physical properties of art, we place great value on the imbuement of the human experience in art. An interesting question, then, is whether and why people might prefer human-compared to AI-created artworks. To explore these questions, we manipulated the purported creator of pieces of art by randomly assigning a "Human-created" or "AI-created" label to paintings actually created by AI, and then assessed participants' judgements of the artworks across four rating criteria (Liking, Beauty, Profundity, and Worth). Study 1 found increased positive judgements for human- compared to AI-labelled art across all criteria. Study 2 aimed to replicate and extend Study 1 with additional ratings (Emotion, Story, Meaningful, Effort, and Time to create) intended to elucidate why people more-positively appraise Human-labelled artworks. The main findings from Study 1 were replicated, with narrativity (Story) and perceived effort behind artworks (Effort) moderating the label effects ("Human-created" vs. "AI-created"), but only for the sensory-level judgements (Liking, Beauty). Positive personal attitudes toward AI moderated label effects for more-communicative judgements (Profundity, Worth). These studies demonstrate that people tend to be negatively biased against AI-created artworks relative to purportedly human-created artwork, and suggest that knowledge of human engagement in the artistic process contributes positively to appraisals of art.

Changes in markers of inflammation, antioxidant capacity and oxidative stress in smokers following consumption of milk, and milk supplemented with fruit and vegetable extracts and vitamin C.

Two milk-based beverages delivering twice the average daily antioxidant intake were formulated, based on synergistic combinations of fruit and vegetable extracts, and containing vitamin C (1.00 mg/ml) for shelf stability. Smokers (n = 42) consumed prototype milk A, B or non-supplemented milk (no extracts or vitamin C; 200 ml) twice daily for 6 weeks. Fasting and post-prandial (2 h after milk consumption) blood samples were collected at baseline and the end of each treatment. Non-supplemented milk significantly reduced fasting inflammatory cytokines (interleukin (IL) 6, IL-1ß, tumour necrosis factor-α) compared to baseline. Both supplemented milk-based beverages significantly increased fasting plasma vitamin C concentrations and antioxidant potential and decreased serum uric acid, compared to non-supplemented milk. The beverages did not induce post-prandial oxidative stress or inflammation. Therefore, regular consumption of the supplemented milks may confer health benefits because of increased antioxidant potential or through mechanisms resulting from increased vitamin C or decreased uric acid concentrations.

The Application of Multicriteria Decision Analysis Methods in Health Care: A Literature Review.

OBJECTIVES: The main objectives of this article are 2-fold. First, we explore the application of multicriteria decision analysis (MCDA) methods in different areas of health care, particularly the adoption of various MCDA methods across health care decision making problems. Second, we report on the publication trends on the application of MCDA methods in health care. METHOD: PubMed was searched for literature from 1960 to 2019 in the English language. A wide range of keywords was used to retrieve relevant studies. The literature search was performed in September 2019. Articles were included only if they have reported an MCDA case in health care. RESULTS AND CONCLUSION: The search yielded 8,318 abstracts, of which 158 fulfilled the inclusion criteria and were considered for further analysis. Hybrid methods are the most widely used methods in health care decision making problems. When it comes to single methods, analytic hierarchy process (AHP) is the most widely used method followed by TOPSIS (technique for order preference by similarity to ideal solution), multiattribute utility theory, goal programming, EVIDEM (evidence and value: impact on decision making), evidential reasoning, discrete choice experiment, and so on. Interestingly, the usage of hybrid methods has been high in recent years. AHP is most widely applied in screening and diagnosing and followed by treatment, medical devices, resource allocation, and so on. Furthermore, treatment, screening and diagnosing, medical devices, and drug development and assessment got more attention in the MCDA context. It is indicated that the application of MCDA methods to health care decision making problem is determined by the nature and complexity of the health care problem. However, guidelines and tools exist that assist in the selection of an MCDA method.

Actinidin diversity: discovery of common and selective substrates for actinidin isoforms and Actinidia cultivars.

The actinidin proteinase family has a striking sequence diversity; isoelectric points range from 3.9 to 9.3. The biological drive for this variation is thought to be actinidin's role as a defense-related protein. In this study we map mutations in the primary sequence onto the 3D structure of the protein and show that the region with the highest diversity is close to the substrate binding groove. Non-conservative substitutions in the active site determine substrate preference and therefore create problems for quantification of actinidin activity. Here we use a peptide substrate library to compare two actinidin isoforms, one from the kiwiberry cultivar 'Hortgem Tahi' (Actinidia arguta), and the other from the familiar kiwifruit cultivar 'Hayward' (Actinidia chinensis var. deliciosa). Among 360 octamer substrates we find one substrate (RVAAGSPI) with the useful property of being readily cleaved by all the functionally active actinidins in a set of A. arguta and A. chinensis var. deliciosa isoforms. In addition, we find that two substrates (LPPKSQPP & ILRDKDNT) have the ability to differentiate different isoforms from a single fruit. We compare actinidins from 'Hayward' and A. arguta for their ability to digest the allergenic gluten peptide (PFPQPQLPY) but find the peptide to be indigestible by all sources of actinidin. The ability to inactivate salivary amylase is shown to be a common trait in Actinidia cultivars due to proteolysis by actinidin and is particularly strong in 'Hortgem Tahi'. A mixture of 10% 'Hortgem Tahi' extract with 90% saliva inactivates 100% of amylase activity within 5 minutes. Conceivably, 'Hortgem Tahi' might lower the glycaemic response in a meal rich in cooked starch.

Endoscopic biliary therapy in the era of bariatric surgery.

There is an increasing demand and availability of bariatric surgery, with a range of procedures performed, some leading to altered upper gastrointestinal anatomy. The patient population undergoing bariatric surgery is also at increased risk of gallstones and biliary stone disease. Endoscopy (ie, endoscopic retrograde cholangiopancreatography) is the cornerstone of management of biliary stone disease, but may be challenging after bariatric surgery. In this review the endoscopic, surgery assisted, or percutaneous options that may be considered are discussed, based on the details of surgical anatomy and available expertise.

Culture as a Moderator of Epistemically Suspect Beliefs.

A consistent finding reported in the literature is that epistemically suspect beliefs (e.g., paranormal beliefs) are less frequently endorsed by individuals with a greater tendency to think analytically. However, these results have been observed predominantly in Western participants. In the present work, we explore various individual differences known to predict epistemically suspect beliefs across both Western and Eastern cultures. Across four studies with Japanese (n = 666) and Western (n = 650) individuals, we find that the association between thinking style and beliefs varied as a function of culture. Specifically, while Westerners who scored higher on measures of Type-2 analytic thinking tended to endorse epistemically suspect beliefs less, this association was not observed in Japanese samples, suggesting that the often-observed negative association between analytic thinking and epistemically suspect beliefs may be exclusive to Western individuals. Additionally, we demonstrate that a tendency to think holistically (specifically with regards to causality) is positively associated with the endorsement of epistemically suspect beliefs within both samples. Overall, we discuss how various individual differences predict the endorsement of epistemically suspect beliefs across cultures.

UK Joint Advisory Group consensus statements for training and certification in endoscopic retrograde cholangiopancreatography.

Background and study aims Despite the high-risk nature of endoscopic retrograde cholangiopancreatography (ERCP), a robust and standardized credentialing process to ensure competency before independent practice is lacking worldwide. On behalf of the Joint Advisory Group (JAG), we aimed to develop evidence-based recommendations to form the framework of ERCP training and certification in the UK. Methods Under the oversight of the JAG, a modified Delphi process was conducted with stakeholder representation from the British Society of Gastroenterology, Association of Upper Gastrointestinal Surgeons, trainees and trainers. Recommendations on ERCP training and certification were formulated after formal literature review and appraised using the GRADE tool. These were subjected to electronic voting to achieve consensus. Accepted statements were peer-reviewed by JAG and relevant Specialist Advisory Committees before incorporation into the ERCP certification pathway. Results In total, 27 recommendation statements were generated for the following domains: definition of competence (9 statements), acquisition of competence (8 statements), assessment of competence (6 statements) and post-certification support (4 statements). The consensus process led to the following criteria for ERCP certification: 1) performing ≥ 300 hands-on procedures; 2) attending a JAG-accredited ERCP skills course; 3) in modified Schutz 1-2 procedures: achieving native papilla cannulation rate ≥80%, complete bile duct clearance ≥ 70 %, successful stenting of distal biliary strictures ≥ 75 %, physically unassisted in ≥ 80 % of cases; 4) 30-day post-ERCP pancreatitis rates ≤5 %; and 5) satisfactory performance in formative and summative direct observation of procedural skills (DOPS) assessments. Conclusions JAG certification in ERCP has been developed following evidence-based consensus to quality assure training and to ultimately improve future standards of ERCP practice.

Erratum: UK Joint Advisory Group consensus statements for training and certification in endoscopic retrograde cholangiopancreatography.

[This corrects the article DOI: 10.1055/a-1629-7540.].