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Abstract Background Malignant gastric outlet obstruction (GOO) is a debilitating condition that frequently occurs in patients with malignancies of the distal stomach and (peri)ampullary region. The standard palliative treatment for patients with a reasonable life expectancy and adequate performance status is a laparoscopic surgical gastrojejunostomy (SGJ). Recently, endoscopic ultrasound-guided gastroenterostomy (EUS-GE) emerged as a promising alternative to the surgical approach. The present study aims to compare these treatment modalities in terms of efficacy, safety, and costs. Methods The ENDURO-study is a multicentre, open-label, parallel-group randomized controlled trial. In total, ninety-six patients with gastric outlet obstruction caused by an irresectable or metastasized malignancy will be 1:1 randomized to either SGJ or EUS-GE. The primary endpoint is time to tolerate at least soft solids. The co-primary endpoint is the proportion of patients with persisting or recurring symptoms of gastric outlet obstruction for which a reintervention is required. Secondary endpoints are technical and clinical success, quality of life, gastroenterostomy dysfunction, reinterventions, time to reintervention, adverse events, quality of life, time to start chemotherapy, length of hospital stay, readmissions, weight, survival, and costs. Discussion The ENDURO-study assesses whether EUS-GE, as compared to SGJ, results in a faster resumption of solid oral intake and is non-inferior regarding reinterventions for persistent or recurrent obstructive symptoms in patients with malignant GOO. This trial aims to guide future treatment strategies and to improve quality of life in a palliative setting. Trial registration International Clinical Trials Registry Platform (ICTRP): NL9592. Registered on 07 July 2021.

ABSTRACT Continued circulation of A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage in poultry has resulted in the diversification in multiple genetic and antigenic clades. Since 2009, clade 2.3.4.4 hemagglutinin (HA) containing viruses harboring the internal and neuraminidase (NA) genes of other avian influenza A viruses have been detected. As a result, various HA-NA combinations, such as A/H5N1, A/H5N2, A/H5N3, A/H5N5, A/H5N6, and A/H5N8 have been identified. As of January 2023, 83 humans have been infected with A/H5N6 viruses, thereby posing an apparent risk for public health. Here, as part of a risk assessment, the in vitro and in vivo characterization of A/H5N6 A/black-headed gull/Netherlands/29/2017 is described. This A/H5N6 virus was not transmitted between ferrets via the air but was of unexpectedly high pathogenicity compared to other described A/H5N6 viruses. The virus replicated and caused severe lesions not only in respiratory tissues but also in multiple extra-respiratory tissues, including brain, liver, pancreas, spleen, lymph nodes, and adrenal gland. Sequence analyses demonstrated that the well-known mammalian adaptation substitution D701N was positively selected in almost all ferrets. In the in vitro experiments, no other known viral phenotypic properties associated with mammalian adaptation or increased pathogenicity were identified. The lack of transmission via the air and the absence of mammalian adaptation markers suggest that the public health risk of this virus is low. The high pathogenicity of this virus in ferrets could not be explained by the known mammalian pathogenicity factors and should be further studied. IMPORTANCE Avian influenza A/H5 viruses can cross the species barrier and infect humans. These infections can have a fatal outcome, but fortunately these influenza A/H5 viruses do not spread between humans. However, the extensive circulation and reassortment of A/H5N6 viruses in poultry and wild birds warrant risk assessments of circulating strains. Here an in-depth characterization of the properties of an avian A/H5N6 influenza virus isolated from a black-headed gull in the Netherlands was performed in vitro and in vivo, in ferrets. The virus was not transmissible via the air but caused severe disease and spread to extra-respiratory organs. Apart from the detection in ferrets of a mutation that increased virus replication, no other mammalian adaptation phenotypes were identified. Our results suggest that the risk of this avian A/H5N6 virus for public health is low. The underlying reasons for the high pathogenicity of this virus are unexplained and should be further studied.

One of the industrial-based uses of palm trees is the manufacture of palm sap syrup. This study aims to determine the effect of pandan leaves on the quality of palm sap syrup in terms of color, taste and smell. The research was carried out at the Minaesa Institute of Technology campus laboratory in Tomohon City. In this study, the population was 5 bottles of palm sap syrup using pandan leaf treatment consisting of 0 g control variables and independent variables (30 g, 40 g, 50 g, and 60 g). The generated data is processed by using statistical analysis of Completely Randomized Design. The results showed that the treatment of pandan leaves addition to palm sap syrup with an average sugar content of 60% which was stored for 45 days obtained the value from the organoleptic test (sensory analysis} of 2.85 to 3.4 (from ‘moderately like’ category to ‘like’ category). This study concluded that the addition of 30 g of pandan leaves is preferred by the panelists with a value of 3.0 to 3.7 for color, taste and smell (from ‘moderately like’ category to ‘like’ category).

Background and study aims Rectal nonsteroidal anti-inflammatory drug (NSAID) prophylaxis reduces incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Direct comparisons to the optimal timing of administration, before or after ERCP, are lacking. Therefore, we aimed to assess whether timing of rectal NSAID prophylaxis affects the incidence of post-ERCP pancreatitis. Patients and methods We conducted an analysis of prospectively collected data from a randomized clinical trial. We included patients with a moderate to high risk of developing post-ERCP pancreatitis, all of whom received rectal diclofenac monotherapy 100-mg prophylaxis. Administration was within 30 minutes before or after the ERCP at the discretion of the endoscopist. The primary endpoint was post-ERCP pancreatitis. Secondary endpoints included severity of pancreatitis, length of hospitalization, and Intensive Care Unit (ICU) admittance. Results We included 346 patients who received the rectal NSAID before ERCP and 63 patients who received it after ERCP. No differences in baseline characteristics were observed. Post-ERCP pancreatitis incidence was lower in the group that received pre-procedure rectal NSAIDs (8 %), compared to post-procedure (18 %) (relative risk: 2.32; 95% confidence interval: 1.21 to 4.46, P = 0.02). Hospital stays were significantly longer with post-procedure prophylaxis (1 day; interquartile range [IQR] 1–2 days vs. 1 day; IQR 1–4 days; P = 0.02). Patients from the post-procedure group were more likely to be admitted to the ICU (1 patient [0.3 %] vs. 4 patients [6 %]; P = 0.002). Conclusions Pre-procedure administration of rectal diclofenac is associated with a significant reduction in post-ERCP pancreatitis incidence compared to post-procedure use.

Abstract In 2016/2017, H5N8 highly pathogenic avian influenza (HPAI) virus of the Goose/Guangdong lineage spread from Asia to Europe, causing the biggest and most widespread HPAI epidemic on record in wild and domestic birds in Europe. We hypothesized that the wide dissemination of the 2016 H5N8 virus resulted at least partly from a change in tissue tropism from the respiratory tract, as in older HPAIV viruses, to the intestinal tract, as in low pathogenic avian influenza (LPAI) viruses, allowing more efficient faecal-oral transmission. Therefore, we determined the tissue tropism and associated lesions in wild birds found dead during the 2016 H5N8 epidemic, as well as the pattern of attachment of 2016 H5N8 virus to respiratory and intestinal tissues of four key wild duck species. We found that, out of 39 H5N8-infected wild birds of 12 species, four species expressed virus antigen in both respiratory and intestinal epithelium, one species only in respiratory epithelium, and one species only in intestinal epithelium. Virus antigen expression was association with inflammation and necrosis in multiple tissues. The level of attachment to wild duck intestinal epithelia of 2016 H5N8 virus was comparable to that of LPAI H4N5 virus, and higher than that of 2005 H5N1 virus for two of the four duck species and chicken tested. Overall, these results indicate that 2016 H5N8 may have acquired a similar enterotropism to LPAI viruses, without having lost the respirotropism of older HPAI viruses of the Goose/Guangdong lineage. The increased enterotropism of 2016 H5N8 implies that this virus had an increased chance to persist long term in the wild waterbird reservoir.

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

Abstract In this study, we explore the circulation of low pathogenic avian influenza (LPAI) viruses in wild birds and poultry in the Netherlands. Surveillance data collected between 2006 and 2016 was used to evaluate subtype diversity, spatiotemporal distribution and genetic relationships between wild bird and poultry viruses. We observed close species-dependent associations among hemagglutinin and neuraminidase subtypes. Not all subtypes detected in wild birds were found in poultry, suggesting transmission to poultry is selective and likely depends on viral factors that determine host range restriction. Subtypes commonly detected in poultry were in wild birds most frequently detected in mallards and geese. Different temporal patterns in virus prevalence were observed between wild bird species. Virus detections in domestic ducks coincided with the prevalence peak in wild ducks, whereas virus detections in other poultry types were made throughout the year. Genetic analysis of the surface genes demonstrated that most poultry viruses were related to locally circulating wild bird viruses, but no direct spatiotemporal link was observed. Results indicate prolonged undetected virus circulation and frequent reassortment events with local and newly introduced viruses within the wild bird population. Increased knowledge on LPAI virus circulation can be used to improve surveillance strategies.

Abstract Background Infected necrosis complicates 10% of all acute pancreatitis episodes and is associated with 15–20% mortality. The current standard treatment for infected necrotizing pancreatitis is the step-up approach (catheter drainage, followed, if necessary, by minimally invasive necrosectomy). Catheter drainage is preferably postponed until the stage of walled-off necrosis, which usually takes 4 weeks. This delay stems from the time when open necrosectomy was the standard. It is unclear whether such delay is needed for catheter drainage or whether earlier intervention could actually be beneficial in the current step-up approach. The POINTER trial investigates if immediate catheter drainage in patients with infected necrotizing pancreatitis is superior to the current practice of postponed intervention. Methods POINTER is a randomized controlled multicenter superiority trial. All patients with necrotizing pancreatitis are screened for eligibility. In total, 104 adult patients with (suspected) infected necrotizing pancreatitis will be randomized to immediate (within 24 h) catheter drainage or current standard care involving postponed catheter drainage. Necrosectomy, if necessary, is preferably postponed until the stage of walled-off necrosis, in both treatment arms. The primary outcome is the Comprehensive Complication Index (CCI), which covers all complications between randomization and 6-month follow up. Secondary outcomes include mortality, complications, number of (repeat) interventions, hospital and intensive care unit (ICU) lengths of stay, quality-adjusted life years (QALYs) and direct and indirect costs. Standard follow-up is at 3 and 6 months after randomization. Discussion The POINTER trial investigates if immediate catheter drainage in infected necrotizing pancreatitis reduces the composite endpoint of complications, as compared with the current standard treatment strategy involving delay of intervention until the stage of walled-off necrosis. Trial registration ISRCTN, 33682933. Registered on 6 August 2015. Retrospectively registered.

As high-throughput sequencing technologies are becoming more widely adopted for analysing pathogens in disease outbreaks there needs to be assurance that the different sequencing technologies and approaches to data analysis will yield reliable and comparable results. Conversely, understanding where agreement cannot be achieved provides insight into the limitations of these approaches and also allows efforts to be focused on areas of the process that need improvement. This manuscript describes the next-generation sequencing of three closely related viruses, each analysed using different sequencing strategies, sequencing instruments and data processing pipelines. In order to determine the comparability of consensus sequences and minority (sub-consensus) single nucleotide variant (mSNV) identification, the biological samples, the sequence data from 3 sequencing platforms and the *.bam quality-trimmed alignment files of raw data of 3 influenza A/H5N8 viruses were shared. This analysis demonstrated that variation in the final result could be attributed to all stages in the process, but the most critical were the well-known homopolymer errors introduced by 454 sequencing, and the alignment processes in the different data processing pipelines which affected the consistency of mSNV detection. However, homopolymer errors aside, there was generally a good agreement between consensus sequences that were obtained for all combinations of sequencing platforms and data processing pipelines. Nevertheless, minority variant analysis will need a different level of careful standardization and awareness about the possible limitations, as shown in this study.

Abstract Background Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP and may run a severe course. Evidence suggests that vigorous periprocedural hydration can prevent PEP, but studies to date have significant methodological drawbacks. Importantly, evidence for its added value in patients already receiving prophylactic rectal non-steroidal anti-inflammatory drugs (NSAIDs) is lacking and the cost-effectiveness of the approach has not been investigated. We hypothesize that combination therapy of rectal NSAIDs and periprocedural hydration would significantly lower the incidence of post-ERCP pancreatitis compared to rectal NSAIDs alone in moderate- to high-risk patients undergoing ERCP. Methods The FLUYT trial is a multicenter, parallel group, open label, superiority randomized controlled trial. A total of 826 moderate- to high-risk patients undergoing ERCP that receive prophylactic rectal NSAIDs will be randomized to a control group (no fluids or normal saline with a maximum of 1.5 mL/kg/h and 3 L/24 h) or intervention group (lactated Ringer’s solution with 20 mL/kg over 60 min at start of ERCP, followed by 3 mL/kg/h for 8 h thereafter). The primary endpoint is the incidence of post-ERCP pancreatitis. Secondary endpoints include PEP severity, hydration-related complications, and cost-effectiveness. Discussion The FLUYT trial design, including hydration schedule, fluid type, and sample size, maximize its power of identifying a potential difference in post-ERCP pancreatitis incidence in patients receiving prophylactic rectal NSAIDs. Trial registration EudraCT: 2015-000829-37. Registered on 18 February 2015. ISRCTN: 13659155. Registered on 18 May 2015.

During autumn–winter 2016–2017, highly pathogenic avian influenza A(H5N8) viruses caused mass die-offs among wild birds in the Netherlands. Among the ≈13,600 birds reported dead, most were tufted ducks (Aythya fuligula) and Eurasian wigeons (Anas penelope). Recurrence of avian influenza outbreaks might alter wild bird population dynamics.

Avian influenza viruses are pathogens of global concern to both animal and human health. Wild birds are the natural reservoir of avian influenza viruses and facilitate virus transport over large distances. Surprisingly, limited research has been performed to determine avian influenza host species and virus dynamics in wild birds on the African continent, including South Africa. This study described the first wild bird surveillance efforts for influenza A viruses in KwaZulu-Natal Province in South Africa after the 2017/2018 outbreak with highly pathogenic avian influenza virus H5N8 in poultry. A total of 550 swab samples from 278 migratory waterfowl were tested using real-time RT-PCR methods. Two samples (0.7%) were positive for avian influenza virus based on the matrix gene real-time RT-PCR but were negative for the hemagglutinin subtypes H5 and H7. Unfortunately, no sequence information or viable virus could be retrieved from the samples. This study shows that avian influenza viruses are present in the South African wild bird population, emphasizing the need for more extensive surveillance studies to determine the South African avian influenza gene pool and relevant local host species.