Influence of Cardiac CT based disease severity and clinical symptoms on the diagnostic performance of myocardial perfusion

Danish Heart Foundation (Grant No. 15-R99-A5837-22920)Health Research Fund of Central Denmark RegionNational Institute for Health Research Biomedical Research Centre at Barts

Influence of Cardiac CT based disease severity and clinical symptoms on the diagnostic performance of myocardial perfusion

Danish Heart Foundation (Grant No. 15-R99-A5837-22920)Health Research Fund of Central Denmark RegionNational Institute for Health Research Biomedical Research Centre at Barts

Inducing persistent flow disturbances accelerates atherogenesis and promotes thin cap fibroatheroma development in D374Y-PCSK9 hypercholesterolemic minipigs

BACKGROUND: -Although disturbed flow is thought to play a central role in the development of advanced coronary atherosclerotic plaques, no causal relationship has been established. We evaluated whether inducing disturbed flow would cause the development of advanced coronary plaques, including thin cap fibroatheroma (TCFA). METHODS AND RESULTS: -D374Y-PCSK9 hypercholesterolemic minipigs (N=5) were instrumented with an intracoronary shear-modifying stent (SMS). Frequency-domain optical coherence tomography was obtained at baseline, immediately post-stent, 19, and 34 weeks and used to compute shear stress metrics of disturbed flow. At 34 weeks, plaque type was assessed within serially-collected histological sections and co-registered to the distribution of each shear metric. The SMS caused a flow-limiting stenosis and blood flow exiting the SMS caused regions of increased shear stress on the outer curvature and large regions of low and multidirectional shear stress on the inner curvature of the vessel. As a result, plaque burden was ~3-fold higher downstream of the SMS compared to both upstream of the SMS and in the control artery (p<0.001). Advanced plaques were also primarily observed downstream of the SMS, in locations initially exposed to both low (p<0.002) and multidirectional (p<0.002) shear stress. TCFA regions demonstrated significantly lower shear stress that persisted over the duration of the study compared to other plaque types (p<0.005). CONCLUSIONS: -These data support a causal role for lowered and multidirectional shear stress in the initiation of advanced coronary atherosclerotic plaques. Persistently lowered shear stress appears to be the principal flow disturbance needed for the formation of TCFA

Effects of dietary phytoestrogens on plasma testosterone and triiodothyronine (T3) levels in male goat kids

<p>Abstract</p> <p>Background</p> <p>Exposure to xenoestrogens in humans and animals has gained increasing attention due to the effects of these compounds on reproduction. The present study was undertaken to investigate the influence of low-dose dietary phytoestrogen exposure, i.e. a mixture of genistein, daidzein, biochanin A and formononetin, on the establishment of testosterone production during puberty in male goat kids.</p> <p>Methods</p> <p>Goat kids at the age of 3 months received either a standard diet or a diet supplemented with phytoestrogens (3 - 4 mg/kg/day) for ~3 months. Plasma testosterone and total and free triiodothyronine (T₃) concentrations were determined weekly. Testicular levels of testosterone and cAMP were measured at the end of the experiment. Repeated measurement analysis of variance using the MIXED procedure on the generated averages, according to the Statistical Analysis System program package (Release 6.12, 1996, SAS Institute Inc., Cary, NC, USA) was carried out.</p> <p>Results</p> <p>No significant difference in plasma testosterone concentration between the groups was detected during the first 7 weeks. However, at the age of 5 months (i.e. October 1, week 8) phytoestrogen-treated animals showed significantly higher testosterone concentrations than control animals (37.5 nmol/l vs 19.1 nmol/l). This elevation was preceded by a rise in plasma total T₃that occurred on September 17 (week 6). A slightly higher concentration of free T₃was detected in the phytoestrogen group at the same time point, but it was not until October 8 and 15 (week 9 and 10) that a significant difference was found between the groups. At the termination of the experiment, testicular cAMP levels were significantly lower in goats fed a phytoestrogen-supplemented diet. Phytoestrogen-fed animals also had lower plasma and testicular testosterone concentrations, but these differences were not statistically significant.</p> <p>Conclusion</p> <p>Our findings suggest that phytoestrogens can stimulate testosterone synthesis during puberty in male goats by increasing the secretion of T₃; a hormone known to stimulate Leydig cell steroidogenesis. It is possible that feedback signalling underlies the tendency towards decreased steroid production at the end of the experiment.</p

Lectin-like bacteriocins from pseudomonas spp. utilise D-rhamnose containing lipopolysaccharide as a cellular receptor

Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, a novel member of this family from Pseudomonas aeruginosa, targets susceptible strains of this species through recognition of the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide that is predominantly a homopolymer of d-rhamnose. Structural and biophysical analyses show that recognition of CPA occurs through the C-terminal carbohydrate-binding domain of pyocin L1 and that this interaction is a prerequisite for bactericidal activity. Further to this, we show that the previously described lectin-like bacteriocin putidacin L1 shows a similar carbohydrate-binding specificity, indicating that oligosaccharides containing d-rhamnose and not d-mannose, as was previously thought, are the physiologically relevant ligands for this group of bacteriocins. The widespread inclusion of d-rhamnose in the lipopolysaccharide of members of the genus Pseudomonas explains the unusual genus-specific activity of the lectin-like bacteriocins

Reliable quantification of the potential for equations based on spot urine samples to estimate population salt intake: protocol for a systematic review and meta-analysis.

BACKGROUND: Methods based on spot urine samples (a single sample at one time-point) have been identified as a possible alternative approach to 24-hour urine samples for determining mean population salt intake. OBJECTIVE: The aim of this study is to identify a reliable method for estimating mean population salt intake from spot urine samples. This will be done by comparing the performance of existing equations against one other and against estimates derived from 24-hour urine samples. The effects of factors such as ethnicity, sex, age, body mass index, antihypertensive drug use, health status, and timing of spot urine collection will be explored. The capacity of spot urine samples to measure change in salt intake over time will also be determined. Finally, we aim to develop a novel equation (or equations) that performs better than existing equations to estimate mean population salt intake. METHODS: A systematic review and meta-analysis of individual participant data will be conducted. A search has been conducted to identify human studies that report salt (or sodium) excretion based upon 24-hour urine samples and spot urine samples. There were no restrictions on language, study sample size, or characteristics of the study population. MEDLINE via OvidSP (1946-present), Premedline via OvidSP, EMBASE, Global Health via OvidSP (1910-present), and the Cochrane Library were searched, and two reviewers identified eligible studies. The authors of these studies will be invited to contribute data according to a standard format. Individual participant records will be compiled and a series of analyses will be completed to: (1) compare existing equations for estimating 24-hour salt intake from spot urine samples with 24-hour urine samples, and assess the degree of bias according to key demographic and clinical characteristics; (2) assess the reliability of using spot urine samples to measure population changes in salt intake overtime; and (3) develop a novel equation that performs better than existing equations to estimate mean population salt intake. RESULTS: The search strategy identified 538 records; 100 records were obtained for review in full text and 73 have been confirmed as eligible. In addition, 68 abstracts were identified, some of which may contain data eligible for inclusion. Individual participant data will be requested from the authors of eligible studies. CONCLUSIONS: Many equations for estimating salt intake from spot urine samples have been developed and validated, although most have been studied in very specific settings. This meta-analysis of individual participant data will enable a much broader understanding of the capacity for spot urine samples to estimate population salt intake

Thoracic dysfunction in whiplash associated disorders: A systematic review

© 2018 Heneghan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Research investigating Whiplash Associated Disorder (WAD) has largely focused on the cervical spine yet symptoms can be widespread. Thoracic spine pain prevalence is reported ~66%; perhaps unsurprising given the forceful stretch/eccentric loading of posterior structures of the spine, and the thoracic spine’s contribution to neck mobility/function. Approximately 50% WAD patients develop chronic pain and disability resulting in high levels of societal and healthcare costs. It is time to look beyond the cervical spine to fully understand anatomical dysfunction in WAD and provide new directions for clinical practice and research. Purpose To evaluate the scope and nature of dysfunction in the thoracic region in patients with WAD. Methods A systematic review and data synthesis was conducted according to a pre-defined, registered (PROSPERO, CRD42015026983) and published protocol. All forms of observational study were included. A sensitive topic-based search strategy was designed from inception to 1/06/16. Databases, grey literature and registers were searched using a study population terms and key words derived from scoping search. Two reviewers independently searched information sources, assessed studies for inclusion, extracted data and assessed risk of bias. A third reviewer checked for consistency and clarity. Extracted data included summary data: sample size and characteristics, outcomes, and timescales to reflect disorder state. Risk of bias was assessed using the Newcastle-Ottawa Scale. Data were tabulated to allow enabling a semi-qualitative comparison and grouped by outcome across studies. Strength of the overall body of evidence was assessed using a modified GRADE. Results Thirty eight studies (n>50,000) which were conducted across a range of countries were included. Few authors responded to requests for further data (5 of 9 contacted). Results were reported in the context of overall quality and were presented for measures of pain or dysfunction and presented, where possible, according to WAD severity and time point post injury. Key findings include: 1) high prevalence of thoracic pain (>60%); higher for those with more severe presentations and in the acute stage, 2) low prevalence of chest pain

HLA-Cw*0602 associates with a twofold higher prevalence of positive streptococcal throat swab at the onset of psoriasis: a case control study

<p>Abstract</p> <p>Background</p> <p>The influence of streptococcal infections in the pathogenesis of psoriasis is not yet understood. <it>In vitro </it>data suggest that streptococcal factors influence T-cell function in psoriasis in a HLA-dependent manner, but studies designed to measure the HLA-C/Streptococci interaction are lacking. In the present study, we hypothesized that there is a statistical interaction between the result of streptococcal throat cultures and the presence of the HLA-Cw*0602 allele in psoriasis patients.</p> <p>Methods</p> <p>We performed a case control study using the "Stockholm Psoriasis Cohort" consisting of patients consecutively recruited within 12 months of disease onset (Plaque psoriasis = 439, Guttate psoriasis = 143), matched to healthy controls (n = 454) randomly chosen from the Swedish Population Registry. All individuals underwent physical examination including throat swabs and DNA isolation for HLA-Cw*0602 genotyping.</p> <p>The prevalence of positive streptococcal throat swabs and HLA-Cw*0602 was compared between patients and controls and expressed as odds ratios with 95% confidence intervals. Associations were evaluated separately for guttate and plaque psoriasis by Fisher's exact test.</p> <p>Results</p> <p>Regardless of disease phenotype, the prevalence of positive streptococcal throat swabs in HLA-Cw*0602 positive patients was twice the prevalence among HLA-Cw*0602 negative patients (OR = 5.8 C.I. = 3.57–9.67, p < 0.001), while no difference was observed among Cw*0602 positive versus negative controls.</p> <p>The corresponding odds ratios for the guttate and plaque psoriasis phenotypes were 3.5 (CI = 1.5–8.7, p = 0.01) and 2.3 (CI = 1.0–5.1, p = 0.02) respectively.</p> <p>Conclusion</p> <p>These findings suggest that among HLA-Cw*0602 positive psoriasis patients, streptococci may contribute to the onset or exacerbation of the inflammatory process independent of the disease phenotype. However, studies on the functional interaction between HLA-C and streptococcal factors are needed.</p

Effectiveness of preoperative staging in rectal cancer: digital rectal examination, endoluminal ultrasound or magnetic resonance imaging?

In rectal cancer, preoperative staging should identify early tumours suitable for treatment by surgery alone and locally advanced tumours that require therapy to induce tumour regression from the potential resection margin. Currently, local staging can be performed by digital rectal examination (DRE), endoluminal ultrasound (EUS) or magnetic resonance imaging (MRI). Each staging method was compared for clinical benefit and cost-effectiveness. The accuracy of high-resolution MRI, DRE and EUS in identifying favourable, unfavourable and locally advanced rectal carcinomas in 98 patients undergoing total mesorectal excision was compared prospectively against the resection specimen pathological as the gold standard. Agreement between each staging modality with pathology assessment of tumour favourability was calculated with the chance-corrected agreement given as the kappa statistic, based on marginal homogenised data. Differences in effectiveness of the staging modalities were compared with differences in costs of the staging modalities to generate cost effectiveness ratios. Agreement between staging and histologic assessment of tumour favourability was 94% for MRI (kappa=0.81, s.e.=0.05; kappa(W)=0.83), compared with very poor agreements of 65% for DRE (kappa=0.08, s.e.=0.068, kappa(W)=0.16) and 69% for EUS (kappa=0.17, s.e.=0.065, kappa(W)=0.17). The resource benefits resulting from the use of MRI rather than DRE was 67164 UK pounds and 92244 UK pounds when MRI was used rather than EUS. Magnetic resonance imaging dominated both DRE and EUS on cost and clinical effectiveness by selecting appropriate patients for neoadjuvant therapy and justifies its use for local staging of rectal cancer patients

Excision Repair Cross-Complementation Group 1 (ERCC1) Status and Lung Cancer Outcomes: A Meta-Analysis of Published Studies and Recommendations

Despite discrepant results on clinical utility, several trials are already prospectively randomizing non-small cell lung cancer (NSCLC) patients by ERCC1 status. We aimed to characterize the prognostic and predictive effect of ERCC1 by systematic review and meta-analysis.Eligible studies assessed survival and/or chemotherapy response in NSCLC or SCLC by ERCC1 status. Effect measures of interest were hazard ratio (HR) for survival or relative risk (RR) for chemotherapy response. Random-effects meta-analyses were used to account for between-study heterogeneity, with unadjusted/adjusted effect estimates considered separately.23 eligible studies provided survival results in 2,726 patients. Substantial heterogeneity was observed in all meta-analyses (I(2) always >30%), partly due to variability in thresholds defining 'low' and 'high' ERCC1. Meta-analysis of unadjusted estimates showed high ERCC1 was associated with significantly worse overall survival in platinum-treated NSCLC (average unadjusted HR = 1.61, 95%CI:1.23-2.1, p = 0.014), but not in NSCLC untreated with chemotherapy (average unadjusted HR = 0.82, 95%CI:0.51-1.31). Meta-analysis of adjusted estimates was limited by variable choice of adjustment factors and potential publication bias (Egger's p<0.0001). There was evidence that high ERCC1 was associated with reduced response to platinum (average RR = 0.80; 95%CI:0.64-0.99). SCLC data were inadequate to draw firm conclusions.Current evidence suggests high ERCC1 may adversely influence survival and response in platinum-treated NSCLC patients, but not in non-platinum treated, although definitive evidence of a predictive influence is lacking. International consensus is urgently required to provide consistent, validated ERCC1 assessment methodology. ERCC1 assessment for treatment selection should currently be restricted to, and evaluated within, clinical trials