5366 research outputs found
Sort by
Response to: 'Concerns about the evidence in relation to implementation of the ProFHER trial' by Handoll .
No full textPCTR1 ameliorates lipopolysaccharide-induced acute inflammation and multiple organ damage via regulation of linoleic acid metabolism by promoting FADS1/FASDS2/ELOV2 expression and reducing PLA2 expression.
No full textGram-negative bacterial infection causes an excessive inflammatory response and acute organ damage or dysfunction due to its outer membrane component, lipopolysaccharide (LPS). Protectin conjugates in tissue regeneration 1 (PCTR1), an endogenous lipid mediator, exerts fundamental anti-inflammation and pro-resolution during infection. In the present study, we examined the properties of PCTR1 on the systemic inflammatory response, organic morphological damage and dysfunction, and serum metabolic biomarkers in an LPS-induced acute inflammatory mouse model. The results show that PCTR1 reduced serum inflammatory factors and ameliorated morphological damage and dysfunction of the lung, liver, kidney, and ultimately improved the survival rate of LPS-induced acute inflammation in mice. In addition, metabolomics analysis and high performance liquid chromatography-mass spectrometry revealed that LPS-stimulated serum linoleic acid (LA), arachidonic acid (AA), and prostaglandin E2 (PGE2) levels were significantly altered by PCTR1. Moreover, PCTR1 upregulated LPS-inhibited fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and elongase of very long chain fatty acids 2 (ELOVL2) expression, and downregulated LPS-stimulated phospholipase A2 (PLA2) expression to increase the intrahepatic content of AA. However, these effects of PCTR1 were partially abrogated by a lipoxin A4 receptor (ALX) antagonist (BOC-2). In summary, via the activation of ALX, PCTR1 promotes the conversion of LA to AA through upregulation of FADS1, FADS2, and ELOVL2 expression, and inhibits the conversion of bound AA into free AA through downregulation of PLA2 expression to decrease the serum AA and PGE2 levels
Evidence from randomised trials linking intake of red meat to diseases-including cardiovascular disease and cancer-is weak.
No full textPushing the Limits in Donation After Circulatory Death Donor Selection: Optimizing Graft Rehabilitation With Ex Vivo Machine Perfusion.
No full textEffects of Epeleuton, a Novel Synthetic Second-Generation n-3 Fatty Acid, on Non-Alcoholic Fatty Liver Disease, Triglycerides, Glycemic Control, and Cardiometabolic and Inflammatory Markers.
No full textBackground Epeleuton is 15-hydroxy eicosapentaenoic acid ethyl ester, a second-generation synthetic n-3 fatty acid derivative of eicosapentaenoic acid. The primary objective was to assess the effect of epeleuton on markers of nonalcoholic fatty liver disease (NAFLD) with post hoc analyses of cardiometabolic markers. Methods and Results In a multicenter, randomized, double-blind, placebo-controlled trial, 96 adults with nonalcoholic fatty liver disease and body mass index 25 to 40 were randomized in a 1:1:1 ratio to receive epeleuton 2 g/day, epeleuton 1 g/day, or placebo for 16 weeks. A total of 27% of patients had diabetes mellitus. Primary end points of changes in alanine aminotransferase and liver stiffness did not improve at week 16. Secondary and post hoc analyses investigated changes in cardiometabolic markers. Epeleuton 2 g/day significantly decreased triglycerides, very-low-density lipoprotein cholesterol, and total cholesterol without increasing low-density lipoprotein cholesterol. Despite a low mean baseline hemoglobin A1C (HbA; 6.3±1.3%), epeleuton 2 g/day significantly decreased HbA (-0.4%; =0.026). Among patients with baseline HbA >6.5%, epeleuton 2 g/day decreased HbA by 1.1% (=0.047; n=26). Consistent dose-dependent reductions were observed for fasting plasma glucose, insulin, and insulin resistance indices. Epeleuton 2 g/day decreased circulating markers of cardiovascular risk and endothelial dysfunction. Epeleuton was well tolerated, with a safety profile not different from placebo. Conclusions While epeleuton did not meet its primary end points on alanine aminotransferase or liver stiffness, it significantly decreased triglycerides, HbA, plasma glucose, and inflammatory markers. These data suggest epeleuton may have potential for cardiovascular risk reduction and nonalcoholic fatty liver disease by simultaneously targeting hypertriglyceridemia, hyperglycemia, and systemic inflammation. Further trials are planned. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02941549
Chronic inflammation and other changes are significant components of clinically fibrotic strictures in Crohn's disease: a histological study of resected strictures clinically characterized as noninflamed.
No full textBACKGROUND
Strictures related to Crohn's disease due to fibrosis are a result of an exaggerated tissue remodelling response to inflammation, characterized by accumulation of collagen-rich extracellular matrix produced by mesenchymal cells.
OBJECTIVES
The objective of this study was to characterize histological changes seen in resected 'fibrotic' strictures to better understand individual components of intestinal stenosis.
METHODS
We identified patients undergoing surgery for ileal Crohn's disease secondary to symptomatic stricturing disease (Montreal B2) using the histopathology database at Queen Elizabeth Hospital in Birmingham, UK, between 2012 and 2017. Phenotypic data were recorded and resection specimens reviewed. Two independent pathologists applied the semiquantitative scoring system previously developed by us to the microscopic images. Data were analyzed using the possible maximum total score (%PMTS).
RESULTS
Forty-eight patients (M = 25) were included. with median disease duration of 7 years (range 0.25-39 years); nearly two-thirds had ileocolonic distribution (L3). In this cohort, despite presurgery diagnosis of noninflamed fibrosis, chronic inflammation was noted to be a prominent component of all strictures. The histological scoring showed presence of several other prominent findings such as muscular hyperplasia and volume expansion.There was statistically significant positive correlation between chronic inflammation and fibrosis and muscular hyperplasia.
CONCLUSION
The histological features of Crohn's disease-related strictures show multiple changes in multiple layers and not simply fibrosis. In our cohort, despite the observation prior to surgery that strictures were clinically considered fibrotic, the finding of chronic inflammation as a dominant component at a histological level in the resection is important. The findings might suggest that one of the main drivers of progressive fibrosis is the inflammatory component, which probably is never fully resolved
High-intensity Focused Ultrasound for the Treatment of Prostate Cancer: A National Cohort Study Focusing on the Development of Stricture and Fistulae.
No full textBACKGROUND
High-intensity focused ultrasound (HIFU) is a novel therapy for prostate cancer. Owing to a lack of long-term data, HIFU is recommended for use only in the context of research.
OBJECTIVE
To examine the trend for HIFU use nationally and rates of strictures and fistulae.
DESIGN, SETTING, AND PARTICIPANTS
Patients undergoing HIFU for prostate cancer between April 2007 and March 2018 were studied in an English national database (Hospital Episode Statistics). Data on complications were included for patients with a minimum of 1-yr follow-up. Analysis of complications was controlled for other interventions.
OUTCOME MEASURES AND STATISTICAL ANALYSIS
Descriptive analyses of HIFU rates and the incidence of strictures and fistulae were carried out. Cox and logistic regression models were built for urethral stricture incidence.
RESULTS AND LIMITATIONS
A total of 2320 HIFU treatments among 1990 patients were identified. The median age was 67yr (interquartile range 61-72). Some 1742 patients met the criteria for follow-up analysis. The highest-volume centre performed 1513 HIFU procedures, followed by 194 at the second highest. The number of HIFU procedures increased annually, rising from 196 to 283 per year. There were 208 patients (11.9%) who went on to have radiotherapy and 102 (5.9%) radical prostatectomy after HIFU. Following HIFU, stricture developed in 133/1290 patients (10.3%) and urinary fistula in 16/1240 (1.3%) before any further intervention. More recent years for HIFU were associated with a lower likelihood of stricture formation (2016/2017 vs 2007/2008: hazard ratio 0.30, 95% confidence interval 0.11-0.79; p=0.015). Limitations include the lack of staging information and unknown rates of HIFU outside of publicly funded health care.
CONCLUSIONS
HIFU is performed at a large number of low-volume centres and complication rates do not differ from those for established therapies.
PATIENT SUMMARY
This report highlights the trend for provision of high-intensity focused ultrasound treatment for prostate cancer in England. The results suggest that the rate of urethral structural complications may not be lower than that for established prostate cancer treatments
Lead-I ECG for detecting atrial fibrillation in patients with an irregular pulse using single time point testing: a systematic review and economic evaluation.
No full textBACKGROUND
Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with an increased risk of stroke and congestive heart failure. Lead-I electrocardiogram (ECG) devices are handheld instruments that can be used to detect AF at a single time point in people who present with relevant signs or symptoms.
OBJECTIVE
To assess the diagnostic test accuracy, clinical impact and cost-effectiveness of using single time point lead-I ECG devices for the detection of AF in people presenting to primary care with relevant signs or symptoms, and who have an irregular pulse compared with using manual pulse palpation (MPP) followed by a 12-lead ECG in primary or secondary care.
DATA SOURCES
MEDLINE, MEDLINE Epub Ahead of Print and MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, PubMed, Cochrane Databases of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects and the Health Technology Assessment Database.
METHODS
The systematic review methods followed published guidance. Two reviewers screened the search results (database inception to April 2018), extracted data and assessed the quality of the included studies. Summary estimates of diagnostic accuracy were calculated using bivariate models. An economic model consisting of a decision tree and two cohort Markov models was developed to evaluate the cost-effectiveness of lead-I ECG devices.
RESULTS
No studies were identified that evaluated the use of lead-I ECG devices for patients with signs or symptoms of AF. Therefore, the diagnostic accuracy and clinical impact results presented are derived from an asymptomatic population (used as a proxy for people with signs or symptoms of AF). The summary sensitivity of lead-I ECG devices was 93.9% [95% confidence interval (CI) 86.2% to 97.4%] and summary specificity was 96.5% (95% CI 90.4% to 98.8%). One study reported limited clinical outcome data. Acceptability of lead-I ECG devices was reported in four studies, with generally positive views. The de novo economic model yielded incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY) gained. The results of the pairwise analysis show that all lead-I ECG devices generated ICERs per QALY gained below the £20,000-30,000 threshold. Kardia Mobile (AliveCor Ltd, Mountain View, CA, USA) is the most cost-effective option in a full incremental analysis.
LIMITATIONS
No published data evaluating the diagnostic accuracy, clinical impact or cost-effectiveness of lead-I ECG devices for the population of interest are available.
CONCLUSIONS
Single time point lead-I ECG devices for the detection of AF in people with signs or symptoms of AF and an irregular pulse appear to be a cost-effective use of NHS resources compared with MPP followed by a 12-lead ECG in primary or secondary care, given the assumptions used in the base-case model.
FUTURE WORK
Studies assessing how the use of lead-I ECG devices in this population affects the number of people diagnosed with AF when compared with current practice would be useful.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42018090375.
FUNDING
The National Institute for Health Research Health Technology Assessment programme
