Studies on smoking in patients with inflammatory bowel disease and liver transplant recipients

Hoe meer ze roken, hoe minder patiënten met colitis ulcerosa last hebben van hun ziekte. Dat blijkt uit het promotieonderzoek van Frans van der Heide. Ook bevestigt de promovendus eerdere studies waaruit blijkt dat rokers minder kans hebben om colitis ulcerosa te ontwikkelen. Maar op een verwante chronische darmziekte, de ziekte van Crohn, hebben rokers juist weer méér kans. Anders dan eerdere studies uitwijzen, lijkt roken het beloop van de ziekte van Crohn niet te beïnvloeden. Deze en andere conclusies uit het onderzoek van Van der Heide laten zien hoe complex het verband tussen roken en chronische darmziekten is. Nader inzicht in de interactie tussen de erfelijke aanleg en het rookgedrag kan wellicht het risico op het ontwikkelen en het beloop van chronische darmziekten helpen voorspellen, stelt de promovendus. Aanvullend onderzoek op dit vlak kan mogelijk helpen de behandeling van deze ziekten beter op de individuele patiënt af te stemmen. Van der Heide onderzocht ook de rol van roken na levertransplantatie. Hij stelt vast dat zich onder patiënten met een levertransplantatie veel rokers bevinden, en dat veel ex-rokers na een levertransplantatie weer beginnen met roken. Hij concludeert dat er een verband is tussen roken en het risico op kanker na een levertransplantatie. Van der Heide pleit er daarom voor dat patiënten na een levertransplantatie hulp krijgen bij het stoppen met roken en vaker worden gescreend op kanker

Immune Checkpoint Inhibitor-related Pancreatitis:A Case Series, Review of the Literature and an Expert Opinion

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies, but are associated with serious adverse events like pancreatitis. Current guidelines are limited to the first step in treating acute ICI-related pancreatitis with steroids but lack treatment advices for steroid dependent pancreatitis. We describe a case series of 3 patients who developed ICI-related pancreatitis with chronic features such as exocrine insufficiency and pancreatic atrophy at imaging. Our first case developed after treatment with pembrolizumab. The pancreatitis responded well after discontinuation of immunotherapy but imaging showed pancreatic atrophy and exocrine pancreatic insufficiency persisted. Cases 2 and 3 developed after treatment with nivolumab. In both, pancreatitis responded well to steroids. However during steroid tapering, pancreatitis recurred and the latter developed exocrine pancreatic insufficiency and pancreatic atrophy at imaging. Our cases demonstrate resemblances with autoimmune pancreatitis based on clinical and imaging findings. In line, both diseases are T-cell mediated and for autoimmune pancreatitis azathioprine is considered as maintenance therapy. Guidelines of other T-cell mediated diseases like ICI-related hepatitis suggest tacrolimus. After adding tacrolimus in case 2 and azathioprine in case 3, steroids could be completely tapered and no new episodes of pancreatitis have occurred. These findings support the idea that the treatment modalities for other T-cell mediated diseases are worthwhile options for steroid dependent ICI-related pancreatitis.</p

Gene trap mutation of murine Outer dense fiber protein-2 gene can result in sperm tail abnormalities in mice with high percentage chimaerism

<p>Abstract</p> <p>Background</p> <p>Outer dense fiber protein 2, Odf2, is a major component of the outer dense fibers, ODF, in the flagellum of spermatozoa. ODF are associated with microtubule doublets that form the axoneme. We recently demonstrated that tyrosine phosphorylation of Odf2 is important for sperm motility. In the course of a study of Odf2 using Odf2 mouse knockout lines we observed that males of a high percentage chimaerism, made using XL169 embryonic stem cells, were infertile, whereas mice of low-medium percentage chimaerism were fertile.</p> <p>Results</p> <p>XL169 ES cells have a β-geo gene trap cassette inserted in the Odf2 gene. To determine possible underlying mechanisms resulting in infertility we analyzed epididymal sperm and observed that >50% displayed bent tails. We next performed ultrastructural analyses on testis of high percentage XL169 chimaeric mice. This analysis showed that high percentage XL169 chimaeric mice produce elongating spermatids that miss one or more entire outer dense fibers in their midpiece and principal piece. In addition, we observed elongating spermatids that show thinning of outer dense fibers. No other obvious abnormalities or defects are present in elongating spermatids. Spermatozoa from the caput and cauda epididymis of XL169 mice of high percentage chimaerism show additional tail defects, including absence of one or more axonemal microtubule doublets and bent tails. Sperm with bent tails display abnormal motility.</p> <p>Conclusions</p> <p>Our results document the possible impact of loss of one Odf2 allele on sperm tail structure and function, resulting in a novel sperm tail phenotype.</p

Intraductal fully covered self-expandable metal stent versus multiple plastic stents for treating biliary anastomotic strictures after liver transplantation

Background and aims: Fully covered metal stents (FCSEMSs) are increasingly used for treatment of biliary anastomotic strictures (ASs) after liver transplantation (LT), requiring fewer endoscopic interventions than does treatment with multiple plastic stents (MPSs). Previous studies, however, have reported adverse events such as stent migration and pancreatitis. The intraductal FCSEMS (ID-FCSEMS) potentially avoids these disadvantages. This study aimed to assess the efficacy and safety of ID-FCSEMSs compared with MPSs for AS. Methods: The cohorts of LT patients treated for AS with endoscopic stenting between 2010 and 2019 from 2 Dutch liver transplantation centers were retrospectively analyzed. Patients treated with ID-FCSEMSs or MPSs were included. Results: 80 patients (44 with ID-FCSEMSs vs 36 with MPSs) were included, with a median follow-up time of 52 versus 64 months (P = .183). Stricture resolution was 93% in the ID-FCSEMS versus 97% in the MPS group (P = 1.000) after a median of 19 and 26 weeks, respectively (P = .031). The median number of ERCPs was 2 in the ID-FCSEMS group versus 4 in the MPS group (P &lt; .001). Stricture recurrence occurred in 33% of ID-FCSEMS versus 29% of MPS patients (P = .653) after a median of 24 and 55 weeks (P = .403). Stent migration occurred in 16% of ID-FCSEMS versus 39% of MPS patients (P = .020). Post-ERCP fever was observed in 34% of ID-FCSEMS patients compared with 14% of MPS patients (P = .038). No significant differences were found in pancreatitis rate between the groups, being 6.8% for ID-FCSEMSs and 5.6% for MPSs (P = .816). Conclusion: ID-FCSEMSs for the treatment of AS after LT provides similar stricture resolution and recurrence rates as MPSs, though with a significant reduction of procedures needed.</p

Systematic and fast scientific literature review for policy purposes :An exploration of using ASReview software about the effectiveness of policy instruments promoting sustainable agriculture

In the context of Article 3.1 of the compatibility law 2016 (Comptabiliteitswet) (CW 2016), which aims to bring about more scientific underpinning of policy, the House of Representatives in 2019 examined the extent to which policy proposals address the efficiency and effectiveness of the policy instruments to be deployed (Sneller &amp; Snels, 2019). They concluded that while they often address how these instruments should contribute to the objective, they often do not address to what extent.Making such statements about efficiency and effectiveness requires an understanding of scientific evidence. As a result, the Netherlands Environmental Assessment Agency (PBL) anticipates that they will receive more frequent questions from the government about what science says about the effectiveness of proposed policies. PBL already has a strong scientific orientation in its work and recognizes the great importance of a request for scientific foundation. But is also foresees that answering this type of question about scientific evidence for policy proposals can be difficult in practice. This is due to the short period in which these questions must generally be answered on the one hand and the time required for (systematic) literature review on the other. Conducting a (systematic) literature search using artificial intelligence (AI) could offer a solution to this problem and that is what this report is about.When using AI, the literature search is supported by a so-called learning algorithm, which learns as the process progresses to better and better assess what is relevant literature for the researcher. However, little experience has been gained with the use of such software in policy-oriented research. PBL therefore asked the UG to investigate how the open-source AI software ASReview could offer a solution in efficiently meeting the demand for scientific insights from the government. At PBL's request, the UG researched three substantive questions around the effectiveness of policy instruments for sustainable agriculture and used these to test the process of the AI supported literature review. In this research, the UG worked with a combination of AI-supported literature screening and sounding boards of academics who fed the search at the beginning and interpreted the results substantively at the end. Such a sounding board enables the distillation of substantive lessons in a relatively short time.The findings are: 1. It is possible to conduct a quick and good systematic literature search by combining AI-supported literature search with a sounding board of scientific experts. The search for scientific insights that could potentially provide substantiation yielded a database of 40.000 potentially relevant papers, from which a diverse set of 100 relevant papers were selected using AI. Using the sounding board of experts, an even smaller set of 12 papers was created from this list that were deemed most urgent for policymakers to study.2. Because the AI software ASReview puts content first and hides reputation of authors and journals during screening, objectivity and breadth is stimulated;3. However, ASReview does present other challenges that, if not taken into account, can compromise the objectivity of research in other ways;i) One of the main risks of using ASReview is what we call ‘trap formation’, especially when there is a short time frame for screening. This means that you end up on a particular 'track' of articles on a particular (sub)topic, which means that other also relevant articles are not found. The broader the query and the less time, the more this poses a risk to the efficiency and reliability of the screening. By using certain settings for the screening, this can be taken into account to a certain extent.ii) The amount of efficiency gains that can be achieved with ASReview depends on the breadth and multidisciplinarity of the research question. The topic of sustainable agriculture has many facets, both in terms of instruments and outcomes. This makes it more difficult for the program to quickly learn what is most relevant, so screening will take more time;iii) AI is not a fully automated process. Use of the program requires skill from the researcher to drive the algorithm and expert knowledge to start the process and expert knowledge to interpret the results.4. The content of this research has resulted in two sets of scientific articles: a Top 100 and a Top 12.5. The first end result of the Systematic Review is a list (Top 100) of relevant articles ranked by their "scientific recognition." Here, because of the requirement for speed in the process, scientific recognition is simply operationalized as a combination of the number of citations of the article per year and the impact factor of the journal (as a measure of the seriousness of the blind review process) in which they were published. While there are caveats to this method of ranking, it does provide a way to make a large amount of knowledge manageable within a relatively short period of time, and in doing so, gives policymakers and researchers a foothold that they can study "the most important first''. 6. The second end result is a selection from the top 100 by the scientific experts: which ones are most important for policy? The six multi-disciplinary scholars each selected three papers that they felt were most important for policymakers and researchers to take to task: combined, this yielded a set of 12 articles. The Top 12 is a manageable set of articles that was selected quickly, and can be studied in content in a short period of time while being largely systematic.7. In conclusion. What does the process tested here offer compared to what we might call "the standard quick search for scientific evidence" of a PBL staff member? This search often consists of manually consulting Google Scholar and/or individually contacting a scientific expert. Compared to manual searches via Scholar, searching the literature with ASReview offers the opportunity to systematically review a vast amount of studies for relevance. After each selection by the researcher, the entire database is reordered. Ultimately, it has been shown, this leads to a greater diversity of studies than a manual search process. Compared to contacting experts individually, the added value of utilizing a group of experts in this study is not only their diversity of expertise, but also that they all reflect on the same scientific dataset and choose from it (quickly and rationally) the most relevant ones for policy. This is a much more systematic process than asking for their scientific views separately.<br/

First Experimental Demonstration of Probabilistic Enumerative Sphere Shaping in Optical Fiber Communications

We transmit probabilistic enumerative sphere shaped dual-polarization 64-QAM at 350Gbit/s/channel over 1610km SSMF using a short blocklength of 200. A reach increase of 15% over constant composition distribution matching with identical blocklength is demonstrated

Limited diagnostic accuracy and clinical impact of single-operator peroral cholangioscopy for indeterminate biliary strictures

BACKGROUND: Single-operator peroral cholangioscopy (sPOCS) is considered a valuable diagnostic modality for indeterminate biliary strictures. Nevertheless, studies show large variation in its characteristics and measures of diagnostic accuracy. Our aim was to estimate the diagnostic accuracy of sPOCS visual assessment and targeted biopsies for indeterminate biliary strictures. Additional aims were: estimation of the clinical impact of sPOCS and comparison of diagnostic accuracy with brush cytology. METHODS: A retrospective single-center study of adult patients who underwent sPOCS for indeterminate biliary strictures was performed. Diagnostic accuracy was defined as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The clinical impact of sPOCS was assessed by review of medical records, and classified according to its influence on patient management. RESULTS: 80 patients were included, with 40 % having primary sclerosing cholangitis (PSC). Prior ERCP was performed in 88 %, with removal of a biliary stent prior to sPOCS in 55 %. The sensitivity, specificity, PPV, and NPV for sPOCS visual impression and targeted biopsies were 64 %, 62 %, 41 %, and 84 %, and 15 %, 65 %, 75 %, and 69 %, respectively. The clinical impact of sPOCS was limited; outcome changed management in 17 % of patients. Sequential brush cytology sensitivity, specificity, PPV, and NPV were 47 %, 95 %, 80 %, and 83 %. CONCLUSIONS: The diagnostic accuracy of sPOCS for indeterminate biliary strictures was found to be inferior to brush cytology, with a low impact on patient management. These findings are obtained from a select patient population with a high prevalence of PSC and plastic stents in situ prior to sPOCS