Unsuccessful Stent Graft Repair of a Hepatic Artery Aneurysm Presenting with Haemobilia:Case Report and Comprehensive Literature Review

AIMS: To discuss treatment strategies for non-traumatic, non-iatrogenic hepatic artery aneurysms (HAAs) in the presence of an arteriobiliary fistula, illustrated by a case and followed by a comprehensive review of the literature. METHODS: Following the PRISMA guidelines, 24 eligible HAA cases presenting with haemobilia were identified. Characteristics of patients, aneurysms, treatment strategies and their outcomes were collected. RESULTS: A 69 year old patient with no previous hepatobiliary intervention or trauma, presented with jaundice and haemobilia caused by a HAA. Initial treatment by endovascular stenting was chosen to prevent ischaemic liver complications. Unfortunately, this strategy failed because of stent migration due to ongoing infection leading to a type 1A endoleak. The patient had to be converted to open surgery with ligation of the HAA. The patient recovered uneventfully and no complications occurred during the following 12 months. COMPREHENSIVE LITERATURE REVIEW: Of the 24 cases, nine had a true HAA and 15 were pseudo/mycotic aneurysms, mainly caused by endocarditis or cholecystitis. The majority were located in the right hepatic artery. In 20 cases, an endovascular first approach was chosen with embolisation, none with covered stents. Three of these cases had to be converted to open surgery because of rebleeding. In all open (primary or secondary) cases, ligation of the HAA was performed. One patient in these series died. No liver ischaemia or abscesses were reported, although one patient developed an ischaemic gallbladder. CONCLUSIONS: Patients who present with a HAA and haemobilia may be treated safely by embolisation or open ligation. Using a covered stent graft in these patients can cause problems due to ongoing infection and should be monitored closely by imaging. Publication bias and lack of long term follow up imply cautious interpretation of these findings

Orally Delivered β-Glucans Aggravate Dextran Sulfate Sodium (DSS)-Induced Intestinal Inflammation

β-Glucans have beneficial health effects due to their immune modulatory properties. Oral administration of β-glucans affects tumour growth, microbial infection, sepsis, and wound healing. We hypothesized that pre-treatment with orally delivered soluble and particulate β-glucans could ameliorate the development of aggravate dextran sulfate sodium (DSS) induced intestinal inflammation. To study this, mice were orally pre-treated with β-glucans for 14 days. We tested curdlan (a particulate β-(1,3)-glucan), glucan phosphate (a soluble β-(1,3)-glucan), and zymosan (a particle made from Saccharomyces cerevisiae, which contains around 55% β-glucans). Weight loss, colon weight, and feces score did not differ between β-glucan and vehicle treated groups. However, histology scores indicated that β-glucan-treated mice had increased inflammation at a microscopic level suggesting that β-glucan treatment worsened intestinal inflammation. Furthermore, curdlan and zymosan treatment led to increased colonic levels of inflammatory cytokines and chemokines, compared to vehicle. Glucan phosphate treatment did not significantly affect cytokine and chemokine levels. These data suggest that particulate and soluble β-glucans differentially affect the intestinal immune responses. However, no significant differences in other clinical colitis scores between soluble and particulate β-glucans were found in this study. In summary, β-glucans aggravate the course of dextran sulfate sodium (DSS)-induced intestinal inflammation at the level of the mucosa

Genetic deletion of dectin-1 does not affect the course of murine experimental colitis

<p>Abstract</p> <p>Background</p> <p>It is believed that inflammatory bowel diseases (IBD) result from an imbalance in the intestinal immune response towards the luminal microbiome. Dectin-1 is a widely expressed pattern recognition receptor that recognizes fungi and upon recognition it mediates cytokine responses and skewing of the adaptive immune system. Hence, dectin-1 may be involved in the pathogenesis of IBD.</p> <p>Methods</p> <p>We assessed the responses of dectin-1 deficient macrophages to the intestinal microbiota and determined the course of acute DSS and chronic <it>Helicobacter hepaticus </it>induced colitis in dectin-1 deficient mice.</p> <p>Results</p> <p>We show that the mouse intestinal microbiota contains fungi and the cytokine responses towards this microbiota were significantly reduced in dectin-1 deficient macrophages. However, in two different colitis models no significant differences in the course of inflammation were found in dectin-1 deficient mice compared to wild type mice.</p> <p>Conclusions</p> <p>Together our data suggest that, although at the immune cell level there is a difference in response towards the intestinal flora in dectin-1 deficient macrophages, during intestinal inflammation this response seems to be redundant since dectin-1 deficiency in mice does not affect intestinal inflammation in experimental colitis.</p

Meta-Analysis of in vitro-Differentiated Macrophages Identifies Transcriptomic Signatures That Classify Disease Macrophages in vivo

Macrophages are heterogeneous leukocytes regulated in a tissue- and disease-specific context. While in vitro macrophage models have been used to study diseases empirically, a systematic analysis of the transcriptome thereof is lacking. Here, we acquired gene expression data from eight commonly-used in vitro macrophage models to perform a meta-analysis. Specifically, we obtained gene expression data from unstimulated macrophages (M0) and macrophages stimulated with lipopolysaccharides (LPS) for 2-4 h (M-LPSearly), LPS for 24 h (M-LPSlate), LPS and interferon-gamma (M-LPS+IFN gamma), IFN gamma (M-IFN gamma), interleukin-4 (M-IL4), interleukin-10 (M-IL10), and dexamethasone (M-dex). Our meta-analysis identified consistently differentially expressed genes that have been implicated in inflammatory and metabolic processes. In addition, we built macIDR, a robust classifier capable of distinguishing macrophage activation states with high accuracy (>0.95). We classified in vivo macrophages with macIDR to define their tissue- and disease-specific characteristics. We demonstrate that alveolar macrophages display high resemblance to IL10 activation, but show a drop in IFN gamma signature in chronic obstructive pulmonary disease patients. Adipose tissue-derived macrophages were classified as unstimulated macrophages, but acquired LPS-activation features in diabetic-obese patients. Rheumatoid arthritis synovial macrophages exhibit characteristics of IL10- or IFN gamma-stimulation. Altogether, we defined consensus transcriptional profiles for the eight in vitro macrophage activation states, built a classification model, and demonstrated the utility of the latter for in vivo macrophages

Machine learning for developing a prediction model of hospital admission of emergency department patients:Hype or hope?

Objective: Early identification of emergency department (ED) patients who need hospitalization is essential for quality of care and patient safety. We aimed to compare machine learning (ML) models predicting the hospitalization of ED patients and conventional regression techniques at three points in time after ED registration. Methods: We analyzed consecutive ED patients of three hospitals using the Netherlands Emergency Department Evaluation Database (NEED). We developed prediction models for hospitalization using an increasing number of data available at triage, similar to 30 min (including vital signs) and similar to 2 h (including laboratory tests) after ED registration, using ML (random forest, gradient boosted decision trees, deep neural networks) and multivariable logistic regression analysis (including spline transformations for continuous predictors). Demographics, urgency, presenting complaints, disease severity and proxies for comorbidity, and complexity were used as covariates. We compared the performance using the area under the ROC curve in independent validation sets from each hospital. Results: We included 172,104 ED patients of whom 66,782 (39 %) were hospitalized. The AUC of the multi-variable logistic regression model was 0.82 (0.78-0.86) at triage, 0.84 (0.81-0.86) at similar to 30 min and 0.83 (0.75-0.92) after similar to 2 h. The best performing ML model over time was the gradient boosted decision trees model with an AUC of 0.84 (0.77-0.88) at triage, 0.86 (0.82-0.89) at similar to 30 min and 0.86 (0.74-0.93) after similar to 2 h. Conclusions: Our study showed that machine learning models had an excellent but similar predictive performance as the logistic regression model for predicting hospital admission. In comparison to the 30-min model, the 2-h model did not show a performance improvement. After further validation, these prediction models could support management decisions by real-time feedback to medical personal

Development and External Validation of the International Early Warning Score for Improved Age- and Sex-Adjusted In-Hospital Mortality Prediction in the Emergency Department

Objectives: Early Warning Scores (EWSs) have a great potential to assist clinical decision-making in the emergency department (ED). However, many EWS contain methodological weaknesses in development and validation and have poor predictive performance in older patients. The aim of this study was to develop and externally validate an International Early Warning Score (IEWS) based on a recalibrated National Early warning Score (NEWS) model including age and sex and evaluate its performance independently at arrival to the ED in three age categories (18-65, 66-80, &gt; 80 yr). Design: International multicenter cohort study. Setting: Data was used from three Dutch EDs. External validation was performed in two EDs in Denmark. Patients: All consecutive ED patients greater than or equal to 18 years in the Netherlands Emergency department Evaluation Database (NEED) with at least two registered vital signs were included, resulting in 95,553 patients. For external validation, 14,809 patients were included from a Danish Multicenter Cohort (DMC). Measurements and Main Results: Model performance to predict in-hospital mortality was evaluated by discrimination, calibration curves and summary statistics, reclassification, and clinical usefulness by decision curve analysis. In-hospital mortality rate was 2.4% (n = 2,314) in the NEED and 2.5% (n = 365) in the DMC. Overall, the IEWS performed significantly better than NEWS with an area under the receiving operating characteristic of 0.89 (95% CIs, 0.89-0.90) versus 0.82 (0.82-0.83) in the NEED and 0.87 (0.85-0.88) versus 0.82 (0.80-0.84) at external validation. Calibration for NEWS predictions underestimated risk in older patients and overestimated risk in the youngest, while calibration improved for IEWS with a substantial reclassification of patients from low to high risk and a standardized net benefit of 5-15% in the relevant risk range for all age categories. Conclusions: The IEWS substantially improves in-hospital mortality prediction for all ED patients greater than or equal to18 years.</p

The association between presenting complaints and clinical outcomes in emergency department patients of different age categories

BACKGROUND AND IMPORTANCE: Although aging societies in Western Europe use presenting complaints (PCs) in emergency departments (EDs) triage systems to determine the urgency and severity of the care demand, it is unclear whether their prognostic value is age-dependent. OBJECTIVE: To assess the frequency and association of PCs with hospitalization and mortality across age categories. METHODS: An observational multicenter study using all consecutive visits of three EDs in the Netherlands Emergency department Evaluation Database. Patients were stratified by age category (0-18; 19-50; 51-65; 66-80; >80 years), in which the association between PCs and case-mix adjusted hospitalization and mortality was studied using multivariable logistic regression analysis (adjusting for demographics, hospital, disease severity, comorbidity and other PCs). RESULTS: We included 172  104 ED-visits. The most frequent PCs were 'extremity problems' [range across age categories (13.5-40.8%)], 'feeling unwell' (9.5-23.4%), 'abdominal pain' (6.0-13.9%), 'dyspnea' (4.5-13.3%) and 'chest pain' (0.6-10.7%). For most PCs, the observed and the case-mix-adjusted odds for hospitalization and mortality increased the higher the age category. The most common PCs with the highest adjusted odds ratios (AORs, 95% CI) for hospitalization were 'diarrhea and vomiting' [2.30 (2.02-2.62)] and 'feeling unwell' [1.60 (1.48-1.73)]. Low hospitalization risk was found for 'chest pain' [0.58 (0.53-0.63)] and 'palpitations' [0.64 (0.58-0.71)]. CONCLUSIONS: Frequency of PCs in ED patients varies with age, but the same PCs occur in all age categories. For most PCs, (case-mix adjusted) hospitalization and mortality vary across age categories. 'Chest pain' and 'palpitations,' usually triaged 'very urgent', carry a low risk for hospitalization and mortality

Exclusive enteral nutrition mediates gut microbial and metabolic changes that are associated with remission in children with Crohn’s disease

GD and AWW receive core funding support from the Scottish Government’s Rural and Environmental Science and Analytical Services (RESAS) Division. JW was funded by the Wellcome Trust [Grant No. 098051]. JVL is funded by MRC New Investigator Grant (MR/P002536/1) and ERC Starting Grant (715662). JK is funded by NIHR: II-OL-1116-10027, NIH: R01-CA204403-01A1, Horizon H2020: ITN GROWTH. Imperial Biomedical Research Centre, SAGES research grant. Infrastructure support for this research was provided by the NIHR Imperial biomedical Research Centre (BRC). Microbiota analyses were carried out using the Maxwell computer cluster at the University of Aberdeen. We thank the Illumina MiSeq team at the Wellcome Sanger Institute for their assistance. This work was partially described in the Ph.D. thesis of KD (Retrieved 2020, Pediatric inflammatory bowel disease Monitoring, nutrition and surgery, https://pure.uva.nl/ws/files/23176012/Thesis_complete_.pdf).Peer reviewedPublisher PD

Long-term outcomes after endoscopic treatment for Barrett's neoplasia with radiofrequency ablation +/- endoscopic resection:results from the national Dutch database in a 10-year period

OBJECTIVE: Radiofrequency ablation (RFA)±endoscopic resection (ER) is the preferred treatment for early neoplasia in Barrett’s oesophagus (BE). We aimed to report short-term and long-term outcomes for all 1384 patients treated in the Netherlands (NL) from 2008 to 2018, with uniform treatment and follow-up (FU) in a centralised setting. DESIGN: Endoscopic therapy for early BE neoplasia in NL is centralised in nine expert centres with specifically trained endoscopists and pathologists that adhere to a joint protocol. Prospectively collected data are registered in a uniform database. Patients with low/high-grade dysplasia or low-risk cancer, were treated by ER of visible lesions followed by trimonthly RFA sessions of any residual BE until complete eradication of BE (CE-BE). Patients with ER alone were not included. RESULTS: After ER (62% of cases; 43% low-risk cancers) and median 1 circumferential and 2 focal RFA (p25-p75 0–1; 1–2) per patient, CE-BE was achieved in 94% (1270/1348). Adverse events occurred in 21% (268/1386), most commonly oesophageal stenosis (15%), all were managed endoscopically. A total of 1154 patients with CE-BE were analysed for long-term outcomes. During median 43 months (22–69) and 4 endoscopies (1–5), 38 patients developed dysplastic recurrence (3%, annual recurrence risk 1%), all were detected as endoscopically visible abnormalities. Random biopsies from a normal appearing cardia showed intestinal metaplasia (IM) in 14% and neoplasia in 0%. A finding of IM in the cardia was reproduced during further FU in only 33%, none progressed to neoplasia. Frequent FU visits in the first year of FU were not associated with recurrence risk. CONCLUSION: In a setting of centralised care, RFA±ER is effective for eradication of Barrett’s related neoplasia and has remarkably low rates of dysplastic recurrence. Our data support more lenient FU intervals, with emphasis on careful endoscopic inspection. Random biopsies from neosquamous epithelium and cardia are of questionable value. NETHERLANDS TRIAL REGISTER NUMBER: NL7039