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Competing Interests: Michiel Bronswijk has received grants from Prion Medical, Taewoong, and Takeda, and has consultancy agreements with Prion Medical and Taewoong. Diederik Persyn, Thomas Billiet, and Ruben Spitaels declare no conflicts of interest. Hannah van Malenstein has consultancy agreements with Boston Scientific. Schalk Van der Merwe holds the Cook and Boston-Scientific chair in interventional endoscopy and holds consultancy agreements with Cook, Pentax, and Olympus.

Promising preclinical data suggested that bone marrow-derived mesenchymal stem cells (BM-MSC) can reduce hepatic fibrosis and stimulate liver regeneration. Preclinical studies moreover suggested that the immunomodulatory and anti-inflammatory functions of MSCs may reduce hepatic inflammation, improve liver function, and decrease infection incidences which are deemed especially important in the case of acute-on-chronic liver failure (ACLF). Studies in patients with decompensated cirrhosis demonstrated that injection of BM-MSC resulted in an improvement of biochemical tests and led to a survival benefit in ACLF. Most of these studies were performed in hepatitis B virus infected patients. However, two adequately powered studies performed in Europe could not confirm these data. A possible alternative to mobilize BM-MSC into the liver is the use of granulocyte colony-stimulating factor (G-CSF) which has proregenerative and immunomodulatory effects. In Indian studies, the use of G-CSF was associated with improvement of survival, although this finding could not be confirmed in European studies. Human allogeneic liver-derived progenitor cell therapy represents a potential treatment for ACLF, of which the main action is paracrine. These human liver-derived MSC can perform various functions, including the downregulation of proinflammatory responses. The clinical beneficial effect of these cells is further explored in patients with alcoholic cirrhosis and ACLF in Europe., Competing Interests: None declared., (Thieme. All rights reserved.)

Competing Interests: Michiel Bronswijk has consultancy agreements with Prion Medical – Taewoong. Schalk Van der Merwe holds the Cook and Boston-Scientific chair in interventional endoscopy and holds consultancy agreements with Cook, Pentax and Olympus. The remaining authors declare no COI relevant for this article.

Objectives: Combined biliary obstruction and gastric outlet obstruction (GOO) represent a challenging clinical scenario despite developments in therapeutic endoscopic ultrasonography (EUS) as GOO might impair EUS-guided biliary drainage. Little is known about the effectiveness of different therapeutic combinations used to treat double obstruction, especially regarding stent patency., Methods: All consecutive patients with double obstruction treated between 2016 and 2021 in three tertiary academic centres were eligible for inclusion. Five combinations involving enteral stenting (ES), EUS-guided gastroenterostomy (EUS-GE), hepaticogastrostomy (EUS-HGS), choledochoduodenostomy (EUS-CDS), and transpapillary biliary stenting (TPS) were evaluated for dysfunction during follow-up, either as proportions or dysfunction-free survival (DFS) using Kaplan-Meier estimates., Results: Ninety-three patients were included (male 46%; age 67 [interquartile range 60-76] years; pancreatic cancer 73%, metastatic 57%), resulting in 103 procedure combinations. Different combinations showed significantly different overall dysfunction rates ( p = 0.009), ranging from the null rate of EUS-GE+HG to the 18% rate of EUS-GE+TPS, 31% of EUS-GE+EUS-CD, 53% of ES+TPS and 83% of ES+EUS-CDS. Sub-analyses restricted to biliary dysfunction confirmed these trends. A multivariate Cox proportional-hazards regression of DFS, a stenosis distal to the papilla (HR 3.2 [1.5-6.9]) and ES+EUS-CDS (HR 5.6 [2-15.7]) independently predicted dysfunction., Conclusions: Despite a lack of statistical power per combination, this study introduces new associations beyond the increased risk of GOO recurrence with ES versus EUS-GE. EUS-CDS showed reduced effectiveness and frequent dysfunction in the context of GOO, especially when combined with ES. EUS-GE+HGS or EUS-GE+TPS in this setting might result in superior patency. These results suggest that a prospective evaluation of the optimal endoscopic approach to malignant double obstruction is needed., Competing Interests: Michiel Bronswijk has consultancy agreements with Taewoong/ Prion Medical, and reports travel grants from Taewoong, Norgine, and Prion Medical; Roy LJ van Wanrooij holds a consultancy agreement with Boston‐Scientific. Wim Laleman co‐chairs the Boston‐Scientific Chair in Therapeutic Biliopancreatic Endoscopy, and has consultancy agreements with Boston Scientific and Cook Medical. Hannah van Malenstein holds a consultancy agreement with Boston‐Scientific. Paul Fockens holds a consultancy agreement with Olympus and Cook Medical. Schalk van der Merwe co‐chairs the Boston‐Scientific Chair in Therapeutic Biliopancreatic Endoscopy, holds the Cook Medical chair in Portal Hypertension, and holds consultancy agreements with Boston Scientific, Cook Medical and Pentax. Rogier P Voermans reports a consultancy agreement and research grant from Boston‐Scientific. All other authors declare no conflict of interest., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Competing Interests: Competing interests The authors declare that they have no conflict of interest.

Objectives: Where palliative surgery or percutaneous drainage used to be the only option in patients with afferent loop syndrome, endoscopic management by EUS-guided gastroenterostomy has been gaining ground. However, EUS-guided hepaticogastrostomy might also provide sufficient biliary drainage. Our aim was to evaluate the feasibility of EUS-guided hepaticogastrostomy for the management of afferent loop syndrome and provide comparative data on the different approaches., Methods: The institutional databases were queried for all consecutive minimally invasive procedures for afferent loop syndrome. A retrospective, dual-centre analysis was performed, separately analysing EUS-guided hepaticogastrostomy, EUS-guided gastroenterostomy and percutaneous drainage. Efficacy, safety, need for re-intervention, hospital stay and overall survival were compared., Results: In total, 17 patients were included (mean age 59 years (± SD 10.5), 23.5% female). Six patients, which were ineligible for EUS-guided gastroenterostomy, were treated with EUS-guided hepaticogastrostomy. EUS-guided gastroenterostomy and percutaneous drainage were performed in 6 and 5 patients respectively. Clinical success was achieved in all EUS-treated patients, versus 80% in the percutaneous drainage group (p = 0.455). Furthermore, higher rates of bilirubin decrease were seen among patients undergoing EUS: > 25% bilirubin decrease in 10 vs. 1 patient(s) in the percutaneously drained group (p = 0.028), with > 50% and > 75% decrease identified only in the EUS group. Using the ASGE lexicon for adverse event grading, adverse events occurred only in patients treated with percutaneous drainage (60%, p = 0.015). And last, the median number of re-interventions was significantly lower in patients undergoing EUS (0 (IQR 0.0-1.0) vs. 1 (0.5-2.5), p = 0.045) when compared to percutaneous drainage., Conclusions: In the management of afferent loop syndrome, EUS seems to outperform percutaneous drainage. Moreover, in our cohort, EUS-guided gastroenterostomy and hepaticogastrostomy provided similar outcomes, suggesting EUS-guided hepaticogastrostomy as the salvage procedure in situations where EUS-guided gastroenterostomy is not feasible or has failed., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Upfront resection is becoming a rarer indication for pancreatic ductal adenocarcinoma, as biologic behavior and natural history of the disease has boosted indications for neoadjuvant treatments. Jaundice, gastric outlet obstruction and acute cholecystitis can frequently complicate this window of opportunity, resulting in potentially deleterious chemotherapy discontinuation, whose resumption relies on effective, prompt and long-lasting management of these complications. Although therapeutic endoscopic ultrasound (t-EUS) can potentially offer some advantages over comparators, its use in potentially resectable patients is primal and has unfairly been restricted for fear of potential technical difficulties during subsequent surgery. This is a narrative review of available evidence regarding EUS-guided choledochoduodenostomy, gastrojejunostomy and gallbladder drainage in the bridge-to-surgery scenario. Proof-of-concept evidence suggests no influence of t-EUS procedures on outcomes of eventual subsequent surgery. Moreover, the very high efficacy-invasiveness ratio over comparators in managing pancreatic cancer-related symptoms or complications can provide a powerful weapon against chemotherapy discontinuation, potentially resulting in higher subsequent resectability. Available evidence is discussed in this short paper, together with technical notes that might be useful for endoscopists and surgeons operating in this scenario. No published evidence supports restricting t-EUS in potential surgical candidates, especially in the setting of pancreatic cancer patients undergoing neoadjuvant chemotherapy. Bridge-to-surgery t-EUS deserves further prospective evaluation., Competing Interests: Conflict-of-interest statement: Michiel Bronswijk has consultancy agreements with Prion Medical and Taewoong. Schalk van der Merwe holds the Cook Medical and Boston Scientific chair in Interventional Endoscopy and holds consultancy agreements with Cook Medical, Pentax and Olympus. The remaining authors declare no conflict of interest relevant for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

The term cirrhosis-associated immune dysfunction (CAID) comprises the distinctive spectrum of immune alterations associated with the course of end-stage liver disease. Systemic inflammation and immune deficiency are the key components of CAID. Their severity is highly dynamic and progressive, paralleling cirrhosis stage. CAID involves two different immune phenotypes: the low-grade systemic inflammatory phenotype and the high-grade systemic inflammatory phenotype. The low-grade systemic inflammatory phenotype can be found in patients with compensated disease or clinical decompensation with no organ failure. In this phenotype, there is an exaggerated immune activation but the effector response is not markedly compromised. The high-grade systemic inflammatory phenotype is present in patients with acute-on-chronic liver failure, a clinical situation characterized by decompensation, organ failure and high short-term mortality. Along with high-grade inflammation, this CAID phenotype includes intense immune paralysis that critically increases the risk of infections and worsens prognosis. The intensity of CAID has important consequences on cirrhosis progression and correlates with the severity of liver insufficiency, bacterial translocation and organ failure. Therapies targeting the modulation of the dysfunctional immune response are currently being evaluated in preclinical and clinical studies., (© 2021. Springer Nature Limited.)

Telemedicine gained interest in liver transplant patients but focused until now on the early post-operative period. This prospective cohort study assessed feasibility, safety, and clinical beneficial effects of a telemedicine based remote monitoring program (TRMP) for the chronic follow-up of adult liver transplant recipients. Between November 2017 and August 2019, a total of 87 of the 115 selected patients (76%) started the TRMP. Over the 2 years study period, none of the patients switched to standard follow-up: 39/87 (45%) continued to do this autonomously and 48/87 (55%) stopped to report their data personally but communicated their lab values to the nurse. The other 28/115 (11%) patients who did not accept the TRMP continued the standard follow-up. There was no difference in educational level between the three groups. Remote monitoring did not result in an increase in liver graft rejection and need of hospitalization. TRMP was associated with a higher number of tacrolimus level determinations and tacrolimus blood level concentrations could be kept lower. In conclusion, our results show that in patients with a stable clinical condition there is a high willingness to participate in TRMP and that this approach is safe. Remote monitoring allowed a stringent follow-up of tacrolimus levels., (© 2021 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Objective: Respiratory compromise is a major cause of adverse events during procedural sedation; continuous monitoring is vital for identifying and halting decompensation. We performed a quality improvement investigation to assess patient safety during procedural sedation in gastroenterology and the impact of implementing capnography monitoring., Patients and Methods: Sedation-related adverse events and interventions were prospectively recorded during the endoscopic procedure and in recovery. Assuming rates in published literature, power analysis determined that at least 1332 patients were required to show a 20% improvement in patient safety. Recorded sedation-related adverse events (mild and severe oxygen desaturations, bradycardia and tachycardia) and interventions were anonymized and aggregated to evaluate the quality improvement. Patient safety under current care was determined before capnography (Medtronic) was implemented in combination with training., Results: Between February 2018 and April 2018, a baseline (1092 patients) for outcomes under current care was completed, with 11.45 events per 100 procedures recorded. Between May 2018 and July 2018, 1044 procedures including capnography monitoring were performed with 5.08 events per 100 procedures recorded. The distribution of American Society of Anesthesiologists scores and procedure types between baseline and capnography were comparable. The absolute difference between baseline and capnography was -6.4 events per 100 procedures [95% confidence interval (CI), -4.1 to -8.7; P ≤ 0.0001]. The 55% reduction in adverse events surpassed the 20% improvement in patient safety set as the goal of this quality improvement. After multivariate regression, the adjusted odds ratio for events after implementation of capnography was 0.46 (95% CI, 0.32-0.66)., Conclusions: Addition of capnography to current care significantly decreased procedure-related safety events., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Diffuse splanchnic thrombosis may render standard LTx difficult or even technically impossible. A 19-year-old woman with acute-on-chronic Budd-Chiari syndrome and complete splanchnic thrombosis underwent conventional LTx. Only limited anatomical portal inflow could be restored, and urgent re-transplantation for recurrent splanchnic vein thrombosis became necessary., Methods: At re-transplant, and in addition to the reestablishment of some portal inflow through the preserved original porto (native)-portal (graft) connection, a cavoportal shunt was created (first partial via 30% tapering of the vena cava, but eventually complete by total occlusion of the vena cava)., Results: The postoperative course was then uneventful, and interestingly, the native portomesenteric axis gradually reopened. Two years post-transplant, the liver graft is perfused via both physiological and non-physiological sources. Liver function is normal. There is no IVC syndrome and no residual PHT. She is leading a normal life., Conclusion: Creation of CPHT, in addition to the preservation of portal inflow from the native splanchnic system, should be considered in patients with diffuse splanchnic thrombosis, when sufficient physiological portal inflow cannot be restored at the time of LTx, but in whom the splanchnic circulation may reopen up later., (© 2021 Wiley Periodicals LLC.)

Background and Aims: EUS-guided gallbladder drainage (EUS-GBD) is emerging as a valuable treatment for acute cholecystitis (AC) in patients unfit for surgery. When lumen-apposing metal stents are used, large-caliber access to the gallbladder allows for subsequent direct peroral endoscopic cholecystoscopy (POEC) and eventual cholecystolithotomy (CL), offering a potentially "curative" solution for frailer patients. The aim of this series was to evaluate the outcome of these procedures in oncologic patients experiencing AC, with a specific focus on chemotherapy continuity., Methods: A prospective registry of all consecutive therapeutic EUS procedures performed in the San Raffaele Institute between December 2020 and April 2021 was searched for EUS-GBD + POEC-CL performed in chemotherapy candidates. Clinical and technical variables were prospectively registered, as were days of chemotherapy delay and postprocedural outcomes., Results: Three consecutive patients with a diagnosis of a malignancy (2 pancreatic cancers and 1 severe myeloproliferative disease with skeletal lesions) experienced AC and were primarily treated by EUS-GBD. After 4 weeks, they were systematically scheduled for POEC-CL and lumen-apposing metal stent exchange for a double-pigtail plastic stent. All procedures and revisions were successful, with rapid clinical improvement. All gallbladders were cleared of food debris and stones between 3 and 15 mm using grasping forceps, polypectomy snares, Dormia baskets, and mechanical lithotripsy. One mild adverse event without any clinical consequence was registered during POEC-CL. Revisions did not interfere with the chemotherapy schedule. Technical variables (eg, gastric vs duodenal drainage or need for coaxial double-pigtail plastic stent) are discussed., Conclusions: EUS-GBD and subsequent POEC-CL allows a highly effective and minimally invasive solution for AC. These initial experiences promote further evaluation of this approach for all those individuals in whom surgical interventions are undesirable, such as oncologic patients whose prognosis depends on chemotherapy continuity, although further prospective confirmation in this setting should be pursued., (© 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc.)

Competing Interests: Michiel Bronswijk received grants from Prion Medical, Taewoong and Takeda. Giuseppe Vanella received grants from Mylan and Alfa Sigma. Baki Topal declares no potential conflicts of interest. Schalk van der Merwe holds the Cook and Boston-Scientific chair in interventional endoscopy and holds consultancy agreements with Cook, Pentax and Olympus.

Severe alcoholic hepatitis is the most severe form of alcohol-related liver disease. Corticosteroids remain the first choice of treatment. However, they are only effective in a subset of patients and are associated with an increased infection risk. Furthermore, nonresponders to corticosteroids have a poor prognosis with a mortality of 70% over 6 months. As such, there is a high need for a more personalized use of corticosteroids and the development and identification of alternative therapeutic strategies. In this review, we summarize the recent and ongoing randomized controlled trials concerning the treatment of severe alcoholic hepatitis., Competing Interests: Conflict of interest statement Nothing declared, (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: In this paper, we propose a robust Bayesian method for the assessment of average bioequivalence based on data from conventional crossover studies. We evaluate and motivate empirically the need for robust methods in bioequivalence studies by comparing the results of robust and conventional statistical methods in a large data pool of bioequivalence studies., Methods: Robustness of the statistical methodology is achieved by replacing the normal distributions for residuals in the linear mixed model with skew-t distributions. In this way, the statistical model can accommodate skew and heavy-tailed data, particularly outliers, yielding robust statistical inference without the need for excluding outliers from the analysis. We performed a simulation study to investigate and compare the performance of the robust and conventional models., Results: Our study shows that in some trials, the distribution of residuals is skew and heavy-tailed. In the presence of outliers, the 90% confidence intervals for the ratio of geometric means tend to be narrower for the robust methods than for the conventional method. Our simulation study shows that the robust method has suitable frequentist properties and yields more precise confidence intervals and higher statistical power than the conventional maximum likelihood method when outliers are present in the data., Conclusions: As a sensitivity analysis, we recommend the fit of robust models for handling outliers that are occasionally encountered in crossover design bioequivalence data., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: The benefit of rapid on-site evaluation (ROSE) on the diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has never been evaluated in a randomized study. This trial aimed to test the hypothesis that in solid pancreatic lesions (SPLs), diagnostic accuracy of EUS-FNB without ROSE was not inferior to that of EUS-FNB with ROSE., Methods: A noninferiority study (noninferiority margin, 5%) was conducted at 14 centers in 8 countries. Patients with SPLs requiring tissue sampling were randomly assigned (1:1) to undergo EUS-FNB with or without ROSE using new-generation FNB needles. The touch-imprint cytology technique was used to perform ROSE. The primary endpoint was diagnostic accuracy, and secondary endpoints were safety, tissue core procurement, specimen quality, and sampling procedural time., Results: Eight hundred patients were randomized over an 18-month period, and 771 were analyzed (385 with ROSE and 386 without). Comparable diagnostic accuracies were obtained in both arms (96.4% with ROSE and 97.4% without ROSE, P = .396). Noninferiority of EUS-FNB without ROSE was confirmed with an absolute risk difference of 1.0% (1-sided 90% confidence interval, -1.1% to 3.1%; noninferiority P < .001). Safety and sample quality of histologic specimens were similar in both groups. A significantly higher tissue core rate was obtained by EUS-FNB without ROSE (70.7% vs. 78.0%, P = .021), with a significantly shorter mean sampling procedural time (17.9 ± 8.8 vs 11.7 ± 6.0 minutes, P < .0001)., Conclusions: EUS-FNB demonstrated high diagnostic accuracy in evaluating SPLs independently on execution of ROSE. When new-generation FNB needles are used, ROSE should not be routinely recommended. (ClinicalTrial.gov number NCT03322592.)., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Benign biliary strictures (BBS) are complications of chronic pancreatitis (CP). Endotherapy using multiple plastic stents (MPS) or a fully covered self-expanding metal stent (FCSEMS) are acceptable treatment options for biliary obstructive symptoms in these patients., Methods: Patients with symptomatic CP-associated BBS enrolled in a multicenter randomized noninferiority trial comparing 12-month treatment with MPS vs FCSEMS. Primary outcome was stricture resolution status at 24 months, defined as absence of restenting and 24-month serum alkaline phosphatase not exceeding twice the level at stenting completion. Secondary outcomes included crossover rate, numbers of endoscopic retrograde cholangiopancreatography (ERCPs) and stents, and stent- or procedure-related serious adverse events., Results: Eighty-four patients were randomized to MPS and 80 to FCSEMS. Baseline technical success was 97.6% for MPS and 98.6% for FCSEMS. Eleven patients crossed over from MPS to FCSEMS, and 10 from FCSEMS to MPS. For MPS vs FCSEMS, respectively, stricture resolution status at 24 months was 77.1% (54/70) vs 75.8% (47/62) (P = .008 for noninferiority intention-to-treat analysis), mean number of ERCPs was 3.9 ± 1.3 vs 2.6 ± 1.3 (P < .001, intention-to-treat), and mean number of stents placed was 7.0 ± 4.4 vs 1.3 ± .6 (P < .001, as-treated). Serious adverse events occurred in 16 (19.0%) MPS and 19 (23.8%) FCSEMS patients (P = .568), including cholangitis/fever/jaundice (9 vs 7 patients respectively), abdominal pain (5 vs 5), cholecystitis (1 vs 3) and post-ERCP pancreatitis (0 vs 2). No stent- or procedure-related deaths occurred., Conclusions: Endotherapy of CP-associated BBS has similar efficacy and safety for 12-month treatment using MPS compared with a single FCSEMS, with FCSEMS requiring fewer ERCPs over 2 years. (ClinicalTrials.gov, Number: NCT01543256.)., (Copyright © 2021. Published by Elsevier Inc.)

Infections, due to a dysfunctional immune response, pose a great risk to patients with decompensated cirrhosis and herald the beginning of the terminal phase of this disease. Infections typically result from breaches in innate immune barriers and inadequate clearance by immune cells. This leads to bacterial and bacterial product translocation to the systemic circulation, which is already primed by ongoing hepatic inflammation in patients with cirrhosis, who are particularly prone to developing organ failure in the presence of an infection. Early identification of bacterial infection, along with the prompt use of appropriate antibiotics, have reduced the mortality associated with certain infections in patients with decompensated cirrhosis. Judicious use of antibiotic therapy remains imperative given the emergence of multidrug-resistant infections in the cirrhotic population. Important research over the last few years has identified molecular targets on immune cells that may enhance their function, and theoretically prevent infections. Clinical trials are ongoing to delineate the beneficial effects of targeted molecules from their off-target effects. Herein, we review the mechanisms that predispose patients with cirrhosis to bacterial infections, the clinical implications of infections and potential targets for the prevention or treatment of infections in this vulnerable population., Competing Interests: Conflict of interest The authors do not report any conflict of interest in relation to the content of this article. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background and Study Aims: The international consensus Fukuoka guideline (Fukuoka ICG), The European evidence-based guideline on pancreatic cystic neoplasms (European EBG) and the American Gastroenterological Association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts (AGA IG) are 3 frequently cited guidelines for the risk stratification of neoplastic pancreatic cysts. The aim of this study was to assess the accuracy of detecting malignant cysts by strictly applying these guidelines retrospectively to a cohort of surgically resected pancreatic cysts., Patients and Methods: 72 resected cysts were included in the analysis. Invasive carcinoma, high grade dysplasia and neuro-endocrine tumour were considered as "malignant cysts" for the purpose of the study., Results: 32% of the resected cysts were malignant. The analysis showed that the Fukuoka ICG, European EBG and AGA IG had a sensitivity of 66,8%, 95,5%, 80%; a specificity of 26,8%, 11,3%, 43,8%; a positive predictive value of 31,8%, 35%, 47,1% and a negative predicted value of 61,1%, 83,3%, 77,8% respectively. The missed malignancy rate was respectively 11,3%, 1,5%, 7,7% and surgical overtreatment was respectively 48,4%, 59,1%, 34,6%., Conclusion: In this retrospective analysis, the European EBG had the lowest rate of missed malignancy at the expense of a high number of "unnecessary" resections. The Fukuoka ICG had the highest number of missed malignancy. The AGA IG showed the lowest rate of unnecessary surgery at the cost of a high number of missed malignancy. There is need to develop better biomarkers to predict the risk of malignancy., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

Background: The increasing rate of liver transplantation (LT) for nonalcoholic fatty liver disease (NAFLD) raises concerns on cardiovascular morbidity and mortality after LT in these patients., Methods: We collected variables regarding the presence of metabolic risk factors, NAFLD recurrence, cardiovascular morbidity, and overall survival at time of listing and after LT of 112 patients with NAFLD and a control group of 120 patients with hepatitis C (HCV)., Results: Metabolic syndrome and cardiovascular morbidity component rates (24.1% vs 12.5%) at the time of LT listing were higher in patients with NAFLD compared with patients with HCV (for all, P < .0390). Median follow-up after LT was 5.6 years in patients with NAFLD vs 13.5 years in patients with HCV (P = .0009). There was no difference in 6-weeks postoperative mortality (1.7% vs 2.5%) (P =1.0000). Metabolic syndrome components after LT were more frequent in patients with NAFLD than in patients with HCV (for all, P < .0008). The incidence of NAFLD 5 years after LT was higher in patients transplanted for NAFLD compared with HCV (43.5% vs 4.2%) (P < .0001). Patients with recurrent NAFLD more often had myocardial infarction compared with those without recurrence (8.3% vs 0%) (P = .0313). Five years after LT, cardiovascular morbidity was more frequent in the NAFLD group than in the HCV group (12.8% vs 9.3%) (P = .0256), whereas no difference in overall survival was observed., Conclusion: LT for NAFLD is associated with satisfactory 5-year outcomes; however, our data underscore the need for close monitoring and aggressive management of cardiovascular risk factors in these patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Neuregulin 4 (Nrg4), a novel adipokine enriched in brown adipose tissue has been observed to negatively regulate de novo hepatic lipogenesis and limit nonalcoholic fatty liver disease (NAFLD) progression to nonalcoholic steatohepatitis (NASH) in rodents. However, the role of Nrg4 in human NAFLD remains unclear to date. We analysed Nrg4 plasma levels and its association with liver disease severity together with the transcriptional profile of the Nrg4 pathway in liver and visceral adipose tissue (VAT) of NAFLD patients., Methods: Plasma Nrg4 levels were measured in 65 NAFLD patients and 43 healthy controls (HC). Hepatic steatosis and fibrosis were diagnosed and quantified with chemical shift MRI and transient elastography respectively. Furthermore, blood lipid levels, HOMA-IR and systemic pro-inflammatory cytokines (TNF-α, IL-6 and IFN-γ) were analysed. Microarray analyses to assess differences in the Nrg4 and its receptor family ErbB pathway in liver and VAT from an independent patient group with biopsy proven NAFL (simple steatosis) (n = 4), NASH (n = 5) and normal liver (n = 6) were performed., Results: Plasma Nrg4 levels were not significantly different between NAFLD patients and HC (p = 0.622). Furthermore, plasma Nrg4 levels did not correlate with the hepatic fat fraction (r = -0.028, p = 0.829) and were not significantly different between NAFLD patients with or without hepatic fibrosis (p = 0.087). Finally, the expression profile of 82 genes related to the Nrg4-ErbB pathway in liver and VAT was not significantly different between NAFL, NASH or obese controls., Conclusion: Our study does not support a role for Nrg4 in the pathophysiology of human NAFLD., Competing Interests: The authors have declared that no competing interests exist.

Background: Donor hepatectomy and liver implantation time reduce long-term graft and patient survival after liver transplantation. It is not known whether these surgical times influence early outcomes after liver transplantation., Methods: This single-center study evaluated the effect of donor hepatectomy and implantation time on the risk of nonanastomotic biliary strictures (NAS) occurring within 1 year and of early allograft dysfunction (EAD) after deceased-donor solitary liver transplantation, adjusting for other donors, recipient, and surgical factors., Results: Of 917 transplants performed between January 2000 and December 2016, 106 (11.56%) developed NAS and 247 (27%) developed EAD. Donor hepatectomy time (median 35 min, IQR: 26-46) was an independent risk factor of NAS [adjusted hazard ratio, 1.19; 95% CI, 1.04-1.35; P = 0.01]. Implantation time (median 80 min, IQR: 69-95) was independently associated with EAD [adjusted odds ratio (OR), 1.15; 95% CI,1.07-1.23; P < 0.0001). The risk of EAD was increased by anastomosis time of both portal vein (adjusted OR, 1.26; 95% CI, 1.12-14.42; P = 0.0001) and hepatic artery (adjusted OR, 1.13; 95% CI, 1.04-1.22; P = 0.005). The magnitude of these effects was similar in donation after circulatory death liver grafts., Conclusions: Donor hepatectomy and implantation time negatively affect short-term outcomes., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Giraffes are an important tourist attraction, and human presence to wildlife is increasing. This has an impact on an animal's behavior and its endocrine correlates. Studies on other species show alterations in movement patterns, vigilance, and stress-related hormone levels in the presence of humans. Limited information is available on how anthropogenic activities alter giraffe's behavior, social structure, and related endocrine parameters. The purpose of this study was to obtain insight into anthropogenic influences on giraffe's behavior and adrenal activity. We used GPS devices mounted onto giraffes to compare the distance walked in the presence or absence of human observers. We also conducted behavioral observations to assess their vigilance and collected fecal samples to analyze their fecal glucocorticoid metabolite (fGCM) concentrations. Giraffes walked significantly further distances in the presence of humans, but the cumulative time that observers were present decreased the hourly distance walked with an observer present, suggesting that the giraffes were becoming habituated. The number of observers present significantly increased the percentage of time spent on observing an observer as well as the number of unhabituated individuals present in the herd. The percentage of time spent observing a human observer did not decrease with the increase of habituation. Last, fGCM concentrations increased with human presence but decreased when individuals became habituated to human presence. More research is needed to understand the effect of anthropogenic influences in different scenarios (e.g., tourism, vehicles, hunting, etc.).

Competing Interests: M. Bronswijk received travel grants from Prion Medical, Taewoong, and Takeda. S. van der Merwe holds the Cook Chair in Interventional Endoscopy, the Boston Chair in Therapeutic EUS, as well as consultancy agreements with Pentax and Olympus.The other authors declare no competing interests regarding this specific paper.

Background: Although evidence suggests frequent gastrointestinal (GI) involvement during coronavirus disease 2019 (COVID-19), endoscopic findings are scarcely reported., Aims: We aimed at registering endoscopic abnormalities and potentially associated risk factors among patients with COVID-19., Methods: All consecutive patients with COVID-19 undergoing endoscopy in 16 institutions from high-prevalence regions were enrolled. Mann-Whitney U, χ 2 or Fisher's exact test were used to compare patients with major abnormalities to those with negative procedures, and multivariate logistic regression to identify independent predictors., Results: Between February and May 2020, during the first pandemic outbreak with severely restricted endoscopy activity, 114 endoscopies on 106 patients with COVID-19 were performed in 16 institutions (men=70.8%, median age=68 (58-74); 33% admitted in intensive care unit; 44.4% reporting GI symptoms). 66.7% endoscopies were urgent, mainly for overt GI bleeding. 52 (45.6%) patients had major abnormalities, whereas 13 bled from previous conditions. The most prevalent upper GI abnormalities were ulcers (25.3%), erosive/ulcerative gastro-duodenopathy (16.1%) and petechial/haemorrhagic gastropathy (9.2%). Among lower GI endoscopies, 33.3% showed an ischaemic-like colitis.Receiver operating curve analysis identified D-dimers >1850 ng/mL as predicting major abnormalities. Only D-dimers >1850 ng/mL (OR=12.12 (1.69-86.87)) and presence of GI symptoms (OR=6.17 (1.13-33.67)) were independently associated with major abnormalities at multivariate analysis., Conclusion: In this highly selected cohort of hospitalised patients with COVID-19 requiring endoscopy, almost half showed acute mucosal injuries and more than one-third of lower GI endoscopies had features of ischaemic colitis. Among the hospitalisation-related and patient-related variables evaluated in this study, D-dimers above 1850 ng/mL was the most useful at predicting major mucosal abnormalities at endoscopy., Trial Registration Number: ClinicalTrial.gov (ID: NCT04318366)., Competing Interests: Competing interests: GV received travel grants from Mylan and Alfasigma. GC is a consultant for Mylan. IB is consultant for Apollo Endosurgery, Cook Medical and Boston Scientific; board member for Endo Tools; research grant recipient from Apollo Endosurgery; had food and beverage compensation from Apollo Endosurgery, Cook Medical, Boston Scientific and Endo Tools. LR is a consultant for Cancer Prevention Pharmaceuticals; has received research grants from SLA Pharma AG and Takeda and receives funds from the Italian Association for Cancer Research (IG21723). MB received travel grants from Takeda, Taewoong Medical and Prion Medical. KWO has received lecture fees from Olympus, Medtronic and Mylan. He has received a research grant from Medtronic. LP received advisory board fees from Janssen and Takeda; presentation fees from AbbVie and Ferring; and personal fees from AbbVie, Ferring, Norgine and Takeda. SWVdM holds the Cook chair in interventional endoscopy and holds consultancy agreements with Boston Scientific, Cook, Pentax and Olympus. ES has received lecture or consultancy fees from Medtronic, Reckitt Benckiser, Takeda, Merck & Co, Bristol Myers Squibb, AbbVie, Amgen, Novartis, Fresenius Kabi, Sandoz, Sofar, Malesci, Janssen, Grifols, Aurora Pharma, Innovamedica, Johnson & Johnson, SILA, Unifarco, Alfasigma, Shire, EG Stada Group. MK has done consulting work for Boston Scientific, Interscope Med and AbbVie. He has received research grants from Boston Scientific, Emcision, Conmed, Pinnacle, Cook, Gore, Merit and Olympus. PR is supported by Clinical Mandate from Belgian Foundation against Cancer (Stichting tegen Kanker) and receives speaking and consultancy fees from MSD Belgium. GC is consultant for and had food and beverage compensation from Cook Medical, Boston Scientific and Olympus., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The unprecedented situation caused by the coronavirus disease 2019 (COVID-19) pandemic has profoundly affected endoscopic practice in regard to access, volume, and workflow. We aimed to assess the potential changes in the technical outcomes of endoscopic retrograde cholangiopancreatography (ERCP) procedures carried out in patients with confirmed SARS-CoV-2 infection., Methods: We conducted an international, multicenter, retrospective, matched case-control study of ERCP procedures carried out in patients with confirmed COVID-19. The main outcome was technical success of the procedure as assessed by the endoscopist, and the secondary outcome was the development of procedure-related adverse events. Each case was matched in a 1:4 ratio with controls extracted from each center's database in order to identify relevant changes in outcome measures compared with the pre-pandemic era., Results: Eighteen procedures performed in 16 COVID-19 patients [14 men, 65 years (9-82)] and 67 controls were included in the final analysis. Technical success was achieved in 14/18 COVID-19 cases, which was significantly lower as compared with the control group (14/18 versus 64/67, p  = 0.034), with an endoscopic reintervention required in 9/18 cases. However, the rate of procedure-related adverse events was low in both groups (1/18 versus 10/67, p  = 0.44). On multivariable analysis, COVID-19 status remained the only risk factor for technical failure of the procedure [odds ratio of 19.9 (95% confidence interval 1.4-269.0)]., Conclusions: The COVID-19 pandemic has affected the volume and practice of ERCP, resulting in lower technical success rates without significantly impacting patient safety. Prioritizing cases and following recommendations on safety measures can ensure good outcome with minimal risk in dedicated centers., Competing Interests: Conflict of interest statement: Michiel Bronswijk received travel grants from Taewoong, Takeda, and Prion Medical. Schalk van der Merwe holds the Cook chair in interventional endoscopy and holds consultancy agreements with Cook, Pentax and Olympus. Professor Guido Costamagna is a consultant for Cook Medical, Boston Scientific, and Olympus. Ivo Boškoski is a consultant for Apollo Endosurgery, Cook Medical, and Boston Scientific; board member for Endo Tools; research grant recipient from Apollo Endosurgery. Also, he has received food and beverage compensation from Apollo Endosurgery, Cook Medical, Boston Scientific, and Endo Tools. The other authors report no conflict of interest., (© The Author(s), 2020.)

Patients with heterotaxy syndrome (HS) can present with an associated complete dorsal pancreas agenesis (DPA). They are considered to be at increased risk for developing diabetes due to a reduced functional beta cell mass (FBM) as well as for chronic pancreatitis leading to unmanageable pain. We report the case of a young woman with chronic pancreatitis due to HS and associated DPA. She presented with a severe persisting upper abdominal pain refractory to nonsurgical treatment. Unlike in previously reported cases, she had a high FBM (ie, 150% of normoglycemic controls) as determined by hyperglycemic clamp. She underwent a total pancreatectomy followed within 24 hours by an intraportal autologous islet cell transplant containing 4 × 10 6 beta cells (4700 islet equivalent)/kg body weight. After surgery, the pain resolved, eliminating the need for analgesics. The intraportal implant established an adequate FBM (72% of controls at posttransplant month 2), achieving glycemic control without need for insulin administration. A hyperglycemic clamp can assess the utility and efficacy of an intraportal islet cell autotransplant following total pancreatectomy in patients with HS and complete DPA., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background and study aims  Endoscopic ultrasound-guided intrahepatic biliary drainage (EUS-IBD) struggles to find a place in management algorithms, especially compared to percutaneous drainage (PTBD). In the setting of hilar stenoses or postsurgical anatomy data are even more limited. Patients and methods  All consecutive EUS-IBDs performed in our tertiary referral center between 2012 - 2019 were retrospectively evaluated. Rendez-vous (RVs), antegrade stenting (AS) and hepatico-gastrostomies (HGs) were compared. The predefined subgroup of EUS-IBD patients with proximal stenosis/surgically-altered anatomy was matched 1:1 with PTBD performed for the same indications. Efficacy, safety and events during follow-up were compared. Results  One hundred four EUS-IBDs were included (malignancies = 87.7 %). These consisted of 16 RVs, 43 ASs and 45 HGs. Technical and clinical success rates were 89.4 % and 96.2 %, respectively. Any-degree, severe and fatal adverse events (AEs) occurred in 23.3 %, 2.9 %, and 0.9 % respectively. Benign indications were more common among RVs while proximal stenoses, surgically-altered anatomy, and disconnected left ductal system among HGs. Procedures were shorter with HGs performed with specifically designed stents (25 vs . 48 minutes, P  = 0.004) and there was also a trend toward less dysfunction with those stents (6.7 % vs . 30 %, P  = 0.09) compared with previous approaches. Among patients with proximal stenosis/surgically-altered anatomy, EUS-IBD vs. PTBD showed higher rates of clinical success (97.4 % vs. 79.5 %, P  = 0.01), reduced post-procedural pain (17.8 % vs. 44.4 %, p = 0.004), shorter median hospital stay (7.5 vs 11.5 days, P  = 0.01), lower rates of stent dysfunction (15.8 % vs. 42.9 %, P  = 0.01), and the mean number of reinterventions was lower (0.4 vs. 2.8, P  < 0.0001). Conclusions  EUS-IBD has high technical and clinical success with an acceptable safety profile. HGs show comparable outcomes, which are likely to further improve with dedicated tools. For proximal strictures and surgically-altered anatomy, EUS-IBD seems superior to PTBD., Competing Interests: Competing interests Dr. van der Merwe holds the Cook chair in Interventional endoscopy and holds consultancy agreements with Cook, Pentax and Olympus. Dr. Laleman co-chairs the Boston Scientific Chair in Therapeutic Biliopancreatic Endoscopy with Dr. van der Merwe and has consultancy agreements with Boston Scientific and Cook. Dr. Van Malenstein holds a consultancy agreement with Boston Scientific, (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The potential of microporous zeolites FAU and BEA, and mesoporous MCM-41, for prolonged release of atenolol in drug delivery systems was investigated both experimentally, using drug release studies, and theoretically using classical molecular dynamics simulations. Remarkably, zero-order release of atenolol was achieved from FAU (SiO 2 :Al 2 O 3  = 80:1) into phosphate buffer for 24 h followed by prolonged release for at least another 48 h. Experimental data also demonstrate the ability for all of the drug-zeolite combinations investigated to achieve prolonged release of atenolol, with the release rates determined by the combination of framework topology, aluminium content and drug release study media. Molecular dynamics simulations give an insight into the reasons for the different release rates observed for FAU and BEA. The results of this work emphasise the need for sophisticated models in order to explain subtle differences in release, such as those observed at different SiO 2 :Al 2 O 3 ratios., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Purpose: To prospectively evaluate the feasibility of solid gold marker placement in oesophageal cancer patients and to quantify inter-fractional and intra-fractional (baseline shift) marker motion during radiation treatment. Radiotherapy target margins and matching strategies were investigated., Materials/methods: Thirty-four markers were implanted by echo-endoscopy in 10 patients. Patients received a planning 4D CT, daily pre-treatment cone-beam CT (CBCT) and a post-treatment CBCT for at least five fractions. For fractions with both pre- and post-treatment CBCT, marker displacement between planning CT and pre-treatment CBCT (inter-fractional) and between pre-treatment and post-treatment CBCT (intra-fractional; only for fractions without rotational treatment couch correction) were calculated in left-right (LR), cranio-caudal (CC) and anterior-posterior (AP) direction after bony-anatomy and soft-tissue matching. Systematic/random setup errors were estimated; treatment margins were calculated., Results: No serious adverse events occurred. Twenty-three (67.6%) markers were visible during radiotherapy (n = 3 middle oesophagus, n = 16 distal oesophagus, n = 4 proximal stomach). Margins for inter-fractional displacement after bony-anatomy match depended on the localisation of the primary tumour and were 11.2 mm (LR), 16.4 mm (CC) and 8.2 mm (AP) for distal markers. Soft-tissue matching reduced the CC margin for these markers (16.4 mm to 10.5 mm). The mean intra-fractional shift of 12 distal markers was 0.4 mm (LR), 2.3 mm (CC) and 0.7 mm (AP). Inclusion of this shift resulted in treatment margins for distal markers of 12.8 mm (LR), 17.3 mm (CC) and 10.4 mm (AP) after bony-anatomy matching and 12.4 mm (LR), 11.4 mm (CC) and 9.7 mm (AP) after soft-tissue matching., Conclusion: This study demonstrated that the implantation of gold markers was safe, albeit less stable compared to other marker types. Inter-fractional motion was largest cranio-caudally for markers in the distal oesophagus, which was reduced after soft-tissue compared to bony-anatomy matching. The impact of intra-fractional baseline shifts on margin calculation was rather small., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Cirrhosis is a multisystemic disease wherein inflammatory responses originating from advanced liver disease and its sequelae affect distant compartments. Patients with cirrhosis are susceptible to bacterial infections, which may precipitate acute decompensation and acute-on-chronic liver failure, both of which are associated with high short-term mortality. Innate immune cells are an essential first line of defence against pathogens. Activation of liver macrophages (Kupffer cells) and resident mastocytes generate proinflammatory and vaso-permeating mediators that induce accumulation of neutrophils, lymphocytes, eosinophils and monocytes in the liver, and promote tissue damage. During cirrhosis progression, damage- and pathogen-associated molecular patterns activate immune cells and promote development of systemic inflammatory responses which may involve different tissues and compartments. The antibacterial function of circulating neutrophils and monocytes is gradually and severely impaired as cirrhosis worsens, contributing to disease progression. The mechanisms underlying impaired antimicrobial responses are complex and incompletely understood. This review focuses on the continuous and distinct perturbations arising in innate immune cells during cirrhosis, including their impact on disease progression, as well as reviewing potential therapeutic targets., Competing Interests: Conflict of interest The authors do not report any conflict of interest in relation to the content of this article. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Competing Interests: None

Background: Instead of choosing one endoscopic ultrasound (EUS) needle over the other, some advocate the use of fine-needle aspiration (FNA) and fine-needle biopsy (FNB) consecutively. We explored the yield of combined use of 20 G FNB and 25 G FNA needles in patients with a suspicious solid gastrointestinal lesion., Methods: Patients from the ASPRO study who were sampled with both needles during the same procedure were included. The incremental yield of dual sampling compared with the yield of single needle use on the diagnostic accuracy for malignancy was assessed for both dual sampling approaches - FNA followed by FNB, and vice versa., Results: 73 patients were included. There were 39 (53 %) pancreatic lesions, 18 (25 %) submucosal masses, and 16 (22 %) lymph nodes. FNA was used first in 24 patients (33 %) and FNB was used first in 49 (67 %). Generally, FNB was performed after FNA to collect tissue for ancillary testing (75 %), whereas FNA was used after FNB to allow for on-site pathological assessment (76 %). Diagnostic accuracy for malignancy of single needle use increased from 78 % to 92 % with dual sampling ( P  = 0.002). FNA followed by FNB improved the diagnostic accuracy for malignancy ( P  = 0.03), whereas FNB followed by FNA did not ( P  = 0.13)., Conclusion: Dual sampling only improved diagnostic accuracy when 25 G FNA was followed by 20 G FNB and not vice versa. As the diagnostic benefit of the 20 G FNB over the 25 G FNA needle has recently been proven, sampling with the FNB needle seems a logical first choice., Competing Interests: Dr. van Riet was a consultant for Cook Medical Devices during the UEGW in 2016. Dr. Bruno is a consultant and lectures for Cook Medical and Boston Scientific., (© Georg Thieme Verlag KG Stuttgart · New York.)

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives., (© 2019 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Background and Aim: A recently carried out randomized controlled trial showed the benefit of a novel 20-G fine-needle biopsy (FNB) over a 25-G fine-needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non-academic pathologists., Methods: This study was a side-study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re-reviewed by five expert academic and five non-academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and non-academic pathologists, target lesions, and cytology versus histological specimens., Results: Besides a higher diagnostic accuracy, FNB also provided for a better agreement on diagnosing malignancy (ĸ = 0.59 vs ĸ = 0.76, P < 0.001) and classification according to Bethesda (ĸ = 0.45 vs ĸ = 0.61, P < 0.001). This equally applied for expert academic and non-academic pathologists and for pancreatic and lymph node specimens. Sample quality was also rated higher for FNB, but agreement ranged from poor (ĸ = 0.04) to fair (ĸ = 0.55). Histology provided better agreement than cytology, but only when a core specimen was obtained with FNB (P = 0.004 vs P = 0.432)., Conclusion: This study shows that the 20-G FNB outperforms the 25-G FNA needle in terms of diagnostic agreement, independent of the background and experience of the pathologist. This endorses use of the 20-G FNB needle in both expert and lower volume EUS centers., (© 2019 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that could lead to serious health problems including liver failure, cancer, or death. The term NAFLD includes a spectrum of disease states with histological features ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). A key aspect within this research field is the identification of pathogenic factors that trigger inflammation, thus fueling the transition from nonalcoholic fatty liver to NASH. These inflammatory triggers may originate from within the liver as a result of innate immune cell activation and/or hepatocyte injury. Additionally, they may originate from other sites such as adipose tissue or the intestinal tract. In the current review, the authors will primarily focus on events within adipose tissue which may be of importance in triggering the disease progression. They specifically focus on the role of adipose tissue macrophages during NAFLD pathogenesis and how microenvironmental factors may shape their metabolic profile. They further dissect how redirecting the macrophage's metabolic profile alters their immunological functions. Finally, they discuss the opportunities and challenges of targeting macrophages to interfere in disease progression., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objectives: Portal vein aneurysm is an unusual vascular dilatation of the portal vein. The etiology, diagnosis and management are ill-defined., Methods: A case of a portal vein aneurysm complicated with complete thrombosis is presented with a literature review providing an overview of the etiology, clinical presentation and management., Results: Portal venous aneurysms represent approximately 3% of all venous aneurysms with a reported prevalence of 0.06%. The reported incidence is on the rise with increasing use of modern imaging techniques in clinical practice. Usually, portal vein aneurysms are incidental findings and patients are asymptomatic. They can be congenital or acquired and portal hypertension represents the most frequent cause of the acquired version. Various complications such as biliary tract compression, portal vein thrombosis, and rupture can occur. Treatment options are conservative management or surgery. Surgical treatment is currently reserved for symptomatic patients with severe abdominal pain, symptoms of pressure effect or with expanding aneurysms, and/or complications such as thrombosis or rupture., Conclusion: Conservative management seems the best option in the majority of patients. A multidisciplinary approach discussing the best option on a case-by-case base in light of their individual underlying risk and symptoms is advised.

Background: Older donors and recipients are increasingly considered for liver transplantation. Both donor and recipient age have a negative impact on outcomes. Large registry analyses show that older donors are frequently matched to older recipients. Whether age-related risks accumulate in a synergic negative effect on outcomes because of donor-recipient age matching is poorly understood., Methods: We investigated the impact of donor-recipient age interaction on patient and death-censored graft survival in multivariate Cox regressions in 849 transplants (January 2000 to December 2015)., Results: Donors 70 years or older did not affect long-term patient or graft survival. Recipient age independently increased the risk of death (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.02-1.05, P < 0.0001), but donor-recipient age interaction was noninfluential. The negative impact of recipient age on patient survival was significant as early as 6 months after transplantation (HR, 1.06; 95% CI, 1.03-1.09; P = 0.00008). The adjusted risk of death was significant for patients aged 60 to 69 years (HR, 1.995; 95% CI, 1.40-2.85; P < 0.0001) and 70 years or older (HR, 2.001; 95% CI, 1.10-2.66; P = 0.04). In contrast, the risk of graft loss was not influenced by recipient age (HR, 1.02; 95% CI, 0.996-1.04; P = 0.11) or age interaction., Conclusions: Older livers can be safely used in older recipients without jeopardizing graft and patient survival if other risk factors are minimized., Competing Interests: The authors declare no conflicts of interest.