23 research outputs found

    Major prospects for exploring canine vector borne diseases and novel intervention methods using 'omic technologies

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    Canine vector-borne diseases (CVBDs) are of major socioeconomic importance worldwide. Although many studies have provided insights into CVBDs, there has been limited exploration of fundamental molecular aspects of most pathogens, their vectors, pathogen-host relationships and disease and drug resistance using advanced, 'omic technologies. The aim of the present article is to take a prospective view of the impact that next-generation, 'omics technologies could have, with an emphasis on describing the principles of transcriptomic/genomic sequencing as well as bioinformatic technologies and their implications in both fundamental and applied areas of CVBD research. Tackling key biological questions employing these technologies will provide a 'systems biology' context and could lead to radically new intervention and management strategies against CVBDs

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    Prevalence of esophageal motility abnormalities increases with longer disease duration in adult patients with eosinophilic esophagitis

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    During the natural course of eosinophilic esophagitis (EoE), the risk for esophageal stricture formation increases. It remains unknown whether motility abnormalities in EoE also develop over time. We aimed to determine the relationship between disease duration, clinical characteristics, and manometric pattern of EoE patients. We compared esophageal high-resolution manometry (HRM) measurements of 31 adult EoE patients with HRM data from 31 GERD controls and 31 healthy controls. Subsequently, we assessed differences in disease duration and clinical characteristics between EoE patients with normal and those with abnormal esophageal motility. In EoE patients, peristaltic integrity was more frequently failed (12 vs 6%) or weak (27 vs 15%; p < 0.001) compared with healthy controls; however, this pattern was also seen in GERD controls (failed 14%, weak 27%). We found no differences regarding symptoms and signs of EoE between EoE patients with normal (42%) and abnormal motility (58%). However, disease duration was longer in EoE patients with abnormal motility than in those with normal motility (13 (6-18) years vs 4 (1-11) years; p < 0.05). In EoE, but not GERD, disease duration was identified as a risk factor for abnormal motility (OR for each year 1.142; 95% CI 1.004-1.299), and with longer disease duration, the prevalence of abnormal motility increased from 36% (duration 0-5 years) to 83% (duration ≥16 years; p < 0.05). Weak and failed peristaltic integrity are more often present in adult EoE patients than in healthy controls. The prevalence of manometric abnormalities in EoE patients increases with longer disease duratio

    Oesophageal baseline impedance values are decreased in patients with eosinophilic oesophagitis

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    Background: Gastro-oesophageal reflux has been suggested to play a role in eosinophilic oesophagitis (EoO). Oesophageal acid exposure decreases baseline intraluminal impedance, a marker of mucosal integrity, in patients with gastro-oesophageal reflux disease (GORD). Objectives: The aim of this study was to assess oesophageal baseline impedance levels in EoO patients and to investigate their relationship with oesophageal acid exposure. Methods: Ambulatory 24-h pH-impedance monitoring was performed in 11 EoO patients and in 11 healthy controls with matched oesophageal acid exposure. We assessed baseline impedance levels in the distal, mid-, and proximal oesophageal impedance channels. Results: Baseline impedance levels in EoO patients were markedly lower compared to controls in the distal oesophagus (median (interquartile range): 988 (757-1978) vs. 2259 (1767-2896) Omega, p = 0.015), mid-oesophagus (1420 (836-2164) vs. 2614 (2374-3879) Omega, p = 0.003), and proximal oesophagus (1856 (1006-2625) vs. 2868 (2397-3439) Omega, p = 0.005). Whereas baseline impedance decreased from proximal to distal in healthy subjects (p = 0.037), no such gradient was seen in EoO patients (p = 0.123). Conclusions: Throughout the oesophagus, baseline impedance values are decreased in EoO patients, indicating impaired mucosal integrity. Our findings suggest that factors other than acid reflux are the cause of low baseline impedance in Eo

    Normative reference values for esophageal high-resolution manometry in healthy adults: A systematic review

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    Background and purpose: Establishing normative values of high-resolution esophageal manometry is necessary for accurate interpretation and comparison of measurements. In this systematic review, we aimed to summarize normal values for different esophageal high-resolution manometry systems. Moreover, we assessed the effect of body position, bolus consistency, and provocative maneuvers on these normative thresholds. We searched Medline, Embase, and the Cochrane Library from January 1st, 2006, to January 20th, 2020, for studies that reported normative data of high-resolution manometry in healthy volunteers. We assessed methodological quality of the included studies and planned a descriptive analysis. We analyzed data from 54 articles describing normative thresholds in high-resolution manometry using solid-state or water-perfused systems. Forty-six studies performed the manometry study in the supine position with liquid swallows, whereas sixteen studies described normative values in the upright position. Twelve studies assessed normative values for different bolus consistencies, and nine studies evaluated different provocative maneuvers. There is a considerable variety of normative values for esophageal high-resolution manometry depending on the equipment used and the protocols performed to obtain measurements. This should be taken into account when evaluating measurements in clinical practice and when comparing results of published research studies

    PPI-responsive esophageal eosinophilia cannot be distinguished from eosinophilic esophagitis by endoscopic signs

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    Eosinophilic esophagitis (EoE) is a chronic antigen-mediated disease histologically characterized by eosinophil-predominant inflammation. One-third of patients respond to proton pump inhibitor (PPI) treatment; this group is identified as having PPI-responsive esophageal eosinophilia (PPI-REE). If we could predict the response to PPIs on the basis of endoscopic signs, futile treatment efforts and additional endoscopies to assess treatment response can be prevented. To determine whether endoscopic signs can distinguish PPI-REE from EoE. Endoscopic images of 30 EoE and 30 PPI-REE patients were included. Baseline characteristics were compared between groups. Complete clinical remission after a PPI trial for at least 8 weeks was classified as PPI-REE. Per patient, at least three depersonalized images were incorporated into a slideshow. These images were scored by two experienced endoscopists according to a validated classification system. Characteristics were highly comparable between EoE and PPI-REE patients. Endoscopic signs were similar and did not enable differentiation between EoE and PPI-REE [presence of: rings (P=0.893), white exudates (P=0.209), furrows (P=0.371), edema (P=0.554), crepe paper esophagus (P=1.000), and strictures (P=0.071)]. Endoscopic signs at baseline endoscopy cannot distinguish EoE from PPI-REE before a PPI trial; the demographic and clinical characteristics in both groups are similar. Endoscopic features do not enable differentiation between PPI-REE and Eo

    The natural course of eosinophilic esophagitis and long-term consequences of undiagnosed disease in a large cohort

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    Background: Eosinophilic esophagitis (EoE) is a chronic esophageal inflammation that may lead to stricture formation. This narrowing can cause major complications including food impactions. Despite increasing interest in EoE accurate data on its natural course is scarce. Therefore, we aimed to investigate the natural course of EoE and to evaluate the association between undiagnosed disease and the occurrence of complications over two decades in a large cohort. Methods: We retrospectively analyzed charts of patients diagnosed with EoE between 1996 and 2015, collected from 15 hospitals throughout the Netherlands. Histologic, clinical, and endoscopic characteristics were identified and stratified by age and diagnostic delay. Results: We included 721 patients (524 males, 117 children (≤18 years)). Dysphagia and food impactions were more common in adults whereas children more often presented with vomiting and abdominal pain (all p < 0.001). The prevalence of fibrotic endoscopic features was higher in adults (76%) than in children (39%) (p < 0.001). As time with undiagnosed disease progressed the percentage of patients with strictures and food impactions increased from 19% and 24% (diagnostic delay ≤ 2 years) to 52% and 57% (diagnostic delay ≥ 21 years) (p < 0.001), respectively. In a multivariate logistic regression model, diagnostic delay (odds ratio (OR) = 1.09; 95% confidence interval (CI) = 1.05-1.13) and male gender (OR = 2.69, 95% CI = 1.61-4.50) were the major risk factors for stricture presence. Conclusion: During the natural course of EoE, progression from an inflammatory to a fibrostenotic phenotype occurs. With each additional year of undiagnosed EoE the risk of stricture presence increases with 9%

    Factors Associated With Achalasia Treatment Outcomes: Systematic Review and Meta-Analysis

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    Background & Aims: Identification of factors associated with achalasia treatment outcome might help physicians select therapies based on patient characteristics. We performed a systematic review and meta-analysis to identify factors associated with treatment response. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library through February 21, 2019, for randomized controlled trials and cohort, case–control, and cross-sectional studies that reported patient-specific outcomes of treatment (botulinum toxin injection, pneumatic dilation, peroral endoscopic myotomy, or laparoscopic Heller myotomy). We assessed the methodologic quality of the included studies using the quality in prognosis studies tool. We planned qualitative and quantitative analyses. Results: We analyzed data from 75 studies (8 randomized controlled trials, 27 prospective cohort studies, and 40 retrospective studies) on a total of 34 different factors associated with outcomes (3 demographic, 17 clinical, and 14 diagnostic factors). Qualitative assessment showed age, manometric subtype, and presence of a sigmoid-shaped esophagus as factors associated with outcomes of treatment for achalasia with a strong level of evidence. The cumulative evidence for the association with chest pain, symptom severity, and lower esophageal sphincter pressure was inconclusive. A meta-analysis confirmed that older age (mean difference, 7.9 y; 95% CI, 1.5–14.3 y) and manometric subtype 3 (odds ratio, 7.1; 95% CI, 4.1–12.4) were associated with clinical response. Conclusions: In a systematic review and meta-analysis, we found age and manometric subtype to be associated with outcomes of treatment for achalasia. This information should be used to guide treatment decisions

    Utility of Routine Esophageal Biopsies in Patients With Refractory Reflux Symptoms

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    INTRODUCTION: This study aimed to assess the diagnostic yield of routine esophageal biopsies in patients with refractory reflux symptoms. METHODS: We prospectively enrolled consecutive patients referred for upper endoscopy and collected histological, clinical, and endoscopic data. RESULTS: Of the 301 included patients, 14 (4.7%) patients met the clinicopathological diagnostic definition of eosinophilic esophagitis. Presence of dysphagia, food bolus impaction, atopic background, and typical endoscopic features were the factors with the strongest association and diagnostic accuracy for eosinophilic esophagitis. The diagnostic yield in patients lacking symptoms of dysphagia or endoscopic features was negligible (0% and 1.9%, respectively). DISCUSSION: Routine esophageal biopsy sampling in patients with refractory reflux symptoms has a low diagnostic yield. Esophageal biopsies should only be obtained in patients with refractory reflux symptoms who also present with dysphagia (see Visual abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B792)

    The natural course of giant paraesophageal hernia and long-term outcomes following conservative management

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    Background: Accurate information on the natural course of giant paraesophageal hernia is scarce, challenging therapeutic decisions whether or not to operate. Objective: We aimed to investigate the long-term outcomes, including hernia-related deaths and complications (e.g. volvulus, gastrointestinal bleeding, strangulation) of patients with giant paraesophageal hernia that were conservatively managed, and to determine factors associated with clinical outcome. Methods: We retrospectively analysed charts of patients diagnosed with giant paraesophageal hernia between January 1990 and August 2019, collected from a university hospital in The Netherlands. Included patients were subdivided into three groups based on primary therapeutic decision at diagnosis. Radiological, clinical and surgical characteristics, along with long-term outcomes at most recent follow-up, were collected. Results: We included 293 patients (91 men, mean age 70.3 ± 12.4 years) with a mean duration of follow-up of 64.0 ± 58.8 months. Of the 186 patients that were conservatively treated, a total hernia-related mortality of 1.6% was observed. Hernia-related complications, varying from uncomplicated volvulus to strangulation, occurred in 8.1% of patients. Only 1.1% of patients included in this study required emergency surgery. Logistic regression analysis revealed the presence of symptoms (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.8–20.6), in particular obstructive symptoms (vomiting, OR 15.7, 95% CI 4.6–53.6; epigastric pain, OR 4.4, 95% CI 1.2–15.8 and chest pain, OR 6.1, 95% CI 1.8–20.6) to be associated with the occurrence of hernia-related complications. Conclusions: Hernia-related death and morbidity is low in conservatively managed patients. The presence of obstructive symptoms was found to be associated with the occurrence of complications during follow-up. Conservative therapy is an appropriate therapeutic strategy for asymptomatic patients
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