Objectives
To estimate the MRI-derived myocardial extracellular volume (ECV) in healthy subjects together with reference normality interval.
Methods
The study was registered on PROSPERO and reported ...according to PRISMA. In October 2017, a systematic search (MEDLINE/EMBASE) was performed for articles reporting MRI-derived ECV in healthy subjects. The pooled ECV (pECV) with 95% confidence interval (CI) was calculated using the random-effect model; the normality interval was calculated as pECV ± 2 root mean square of all study standard deviations. The Newcastle-Ottawa scale was used for assessing study quality, subgroup/meta-regression analyses for technical/biological covariates, and Egger test for publication bias risk.
Results
Of 282 articles, 56 were analyzed totaling 1851 subjects with age 16–68 years, body mass index 23–28 kg/m
2
, and left ventricular ejection fraction 58–74%. Contrast dose varied from 0.075 to 0.200 mmol/kg. Heterogeneity was high (
I
2
= 92%). The pECV was 25.6% (95% CI 25.2–26.0%) with a normality interval of 19.6–31.6%. pECV was slightly increasing with age (
β
= 0.03%,
p
= 0.038) and slightly decreasing with the percentage of males (
β
= − 0.02%,
p
= 0.053). Sequence type significantly (
p
= 0.003) impacted on pECV: the normal interval was 19.9–31.9% for MOLLI and 20.3–33.5% for ShMOLLI. Contrast type/dose, time of acquisition, and magnetic field strength did not significantly impact pECV (
p
> 0.093). Quality was moderate or high in 48/56 studies (86%). No risk of publication bias (
p
= 0.728).
Conclusions
Myocardial pECV in healthy subjects was 25.6%, increasing by 0.03% for each year of age. The ECV normality interval was 19.9–31.9% for MOLLI and 20.3–33.5% for ShMOLLI.
Key Points
• The pooled estimate of normal MRI-derived ECV based on 1851 subjects was 25.6%, slightly increasing with age and slightly decreasing with the percentage of males.
• MRI-derived ECV was independent of contrast type/dose and field strength but dependent on the imaging sequence.
• The modeled normality reference interval of MRI-derived ECV was 19.9–31.9% for the MOLLI sequence and 20.3–33.5% for the ShMOLLI sequence.
Objectives
To review the diagnostic performance of MR coronary angiography (MRCA) for coronary artery disease (CAD).
Methods
Two independent reviewers searched on MEDLINE/EMBASE with the following ...inclusion criteria: 01/01/2000-03/23/2015 publication date; per-patient sensitivity/specificity for >50 % stenosis confirmed by conventional coronary angiography with raw data provided or retrievable; sample size >10. Quality was appraised using QUADAS2.
Results
Nine hundred eighteen studies were retrieved, 24 of them, including 1,638 patients, were selected. Using a bivariate model, the pooled sensitivity was 89 % (95 % confidence interval 86–92 %), the pooled specificity 72 % (63–79 %). Meta-regression did not show a significant impact on sensitivity/specificity for both year of publication and disease prevalence (
p
≥ 0.114). Sensitivity of contrast-enhanced examinations (95 %, 90–97 %) was higher (
p
= 0.005) than that of unenhanced examinations (87 %, 83–90 %). Specificity of whole-heart acquisition mode (78 %, 72–84 %) was higher (
p
= 0.006) than that of targeted mode (57 %, 45–69 %). Specificity at 3 T (83 %, 69–92 %) was higher (
p
= 0.067) than that at 1.5 T (68 %, 60–76 %). Risk of bias and concerns regarding applicability were low.
Conclusions
Sensitivity and specificity of MRCA for CAD were 89 % and 72 %, respectively. A specificity higher than 80 % may be obtained at 3 T. Whole-heart contrast-enhanced protocols should be preferred for a higher diagnostic performance.
Key Points
•
MRCA sensitivity and specificity for CAD are below those of CTA
.
•
Contrast administration increased sensitivity to 95
% (
90
–
97
%),
comparable with that of CTA
.
•
Whole
-
heart mode increased specificity to 78
% (
72
–
84
%),
comparable with that of CTA
.
•
Specificity at 3 T was borderline
-
significantly higher
(
p
=
0.067
)
than at 1.5 T
.
•
Whole
-
heart contrast
-
enhanced protocols are the best approach for MRCA
.
Abstract
The level of secretory acid sphingomyelinase (S-ASM), a key enzyme in the sphingolipid metabolism, is elevated in a variety of human diseases, including in the serum of obese adults. ...Alterations in S-ASM were also found to induce morphological changes in erythrocytes. Consequently, the inhibition of S-ASM by functional Inhibitors of ASM (FIASMA) may have broad clinical implications. The purpose of this study was to assess S-ASM activity in pediatric patients with obesity and healthy matched controls, as well as to investigate the erythrocyte morphology using transmission electron microscopy. We recruited 46 obese patients (mean age 11 ± 2.9 years) and 44 controls (mean age 10.8 ± 2.9 years). S-ASM activity was significantly higher (Wilcoxon signed-rank test p-value: 0.004) in obese patients (mean 396.4 ± 49.7 pmol/ml/h) than in controls (mean 373.7 ± 23.1 pmol/ml/h). No evidence of morphological differences in erythrocytes was found between the two populations. We then carried out a case–control study based on the spontaneous reporting system database to compare FIASMAs with NON-FIASMAs in terms of weight gain risk. Children who received FIASMA had a significantly lower frequency of weight gain reports than patients who took NON-FIASMA agents (p < 0.001). Our findings suggest there is an intriguing possibility that S-ASM may play a role in pediatric obesity. This pilot study could serve as the basis for future studies in this interesting field of research.
An immunosuppressive microenvironment in lung concurs to pre-malignant lesions progression to cancer. Here, we explore if perturbing lung microbiota, which contribute to immunosuppression, by ...antibiotics or probiotic aerosol interferes with lung cancer development in a mouse carcinogen-induced tumor model. Urethane-injected mice were vancomycin/neomycin (V/N)-aerosolized or live or dead L. rhamnosus GG (L.RGG)-aerosolized, and tumor development was evaluated. Transcriptional profiling of lungs and IHC were performed. Tumor nodules number, diameter and area were reduced by live or heat-killed L.RGG, while only a decrease in nodule diameter was observed in V/N-treated lungs. Both L.RGG and V/N reduced Tregs in the lung. In L.RGG-treated groups, the gene encoding the joining chain (J chain) of immunoglobulins was increased, and higher J chain protein and IgA levels were observed. An increased infiltration of B, NK and myeloid-derived cells was predicted by TIMER 2.0. The Kaplan–Meier plotter revealed an association between high levels of J chain mRNA and good prognosis in lung adenocarcinoma patients that correlated with increased B and CD4 T cells and reduced Tregs and M2 macrophages. This study highlights L.RGG aerosol efficacy in impairing lung cancer growth by promoting local immunity and points to this non-invasive strategy to treat individuals at risk of lung cancer.
Giant insular tumors are commonly not amenable to complete resection and are associated with a high postoperative morbidity rate. Transcortical approach and brain mapping techniques allow to identify ...peri-insular functional networks and, with neurophysiological monitoring, to reduce vascular-associated insults. Cognitive functions to be mapped are still under debate, and the analysis of the functional risk of surgery is currently limited to neurological examination. This work aimed to investigate the neurosurgical outcome (extent of resection, EOR) and functional impact of giant insular gliomas resection, focusing on neuropsychological and Quality of Life (QoL) outcomes.
In our retrospective analysis, we included all patients admitted in a five-year period with a radiological diagnosis of giant insular glioma. A transcortical approach was adopted in all cases. Resections were pursued up to functional boundaries defined intraoperatively by brain mapping techniques. We examined clinical, radiological, and intra-operative factors possibly affecting EOR and postoperative neurological, neuropsychological, and Quality of Life (QoL) outcomes.
We finally enrolled 95 patients in the analysis. Mean EOR was 92.3%. A Gross Total Resection (GTR) was obtained in 70 cases (73.7%). Five patients reported permanent morbidity (aphasia in 3, 3.2%, and superior quadrantanopia in 2, 2.1%). Suboptimal EOR associated with poor seizures control postoperatively. Extensive intraoperative mapping (inclusive of cognitive, visual, and haptic functions) decreased long-term neurological, neuropsychological, and QoL morbidity and increased EOR. Tumor infiltration of deep perforators (vessels arising either medial to lenticulostriate arteries through the anterior perforated substance or from the anterior choroidal artery) associated with a higher chance of postoperative ischemia in consonant areas, with the persistence of new-onset motor deficits 1-month post-op, and with minor EOR. Ischemic insults in eloquent sites represented the leading factor for long-term neurological and neuropsychological morbidity.
In giant insular gliomas, the use of a transcortical approach with extensive brain mapping under awake anesthesia ensures broad insular exposure and extension of the surgical resection preserving patients' functional integrity. The relation between tumor mass and deep perforators predicts perioperative ischemic insults, the most relevant risk factor for long-term and permanent postoperative morbidity.
Despite universities in the UK, USA and Australia having developed tools and strategies to enhance academic engagement, there is a paucity of information from universities and research hospitals ...where conceptual and theoretical research still appears more heterogeneous. In Italy, there is a growing recognition that more needs to be done to define strategies to improve research engagement. Italian research hospitals are represented by the Scientific Institute for Research, Hospitalization and Healthcare (named IRCCS from the Italian acronym of these organisations), representing the best of Italian research and the National Health Service System. This article provided a pilot description of research engagement in a representative Italian IRCCS hospital for the first time. A pilot study was developed, and a brief questionnaire was validated to explore research engagement. The identified clusters of researchers' engagement were provided to describe an initial theory-grounded framework. Based on the perspective of research administrators and the Ministry of Health during round tables, the developed questionnaire identified two clusters of researchers' engagement and measured "Project-oriented" and "Organisation-oriented" engagement. Among the responders, IRCCS senior researchers tended to have higher project-oriented engagement, while young researchers had slightly higher organisation-oriented engagement. The contribution of this article is a hypothesised two-level theory-grounded framework to study and improve research engagement activities and strategies in a research hospital, with the potential for an overlap with other European research institutions.
End-stage renal disease patients on dialysis (CKD-G5D) have a high mortality rate due to cardiovascular diseases (CVD). In these patients, inflammation, oxidative stress, and uremia increase the ...production of glycation products (AGEs) which in turn accelerate CVD onset and progression. Recently, attention has been given to the soluble receptor for AGEs (sRAGE) as a marker of inflammation, oxidative stress, atherosclerosis, and heart failure in CKD-G5D. However, its association with patient outcomes is still under debate. Our aim is to explore whether sRAGE may be a predictor of mortality in CKD-G5D. We studied 123 CKD-G5D for 24 months. Of these patients, 56 were on hemodialysis (HD) and 67 on peritoneal dialysis (PD). Demographic, anthropometric, biochemical, and clinical data were recorded. sRAGE was quantified by enzyme-linked immunosorbent assay. sRAGE was a predictor of mortality at 2-year follow-up. Each increase of 100 pg/mL in sRAGE levels was associated with an approximately 7% increased risk of mortality. Furthermore, in the entire study group, as well as in PD and HD patient subgroups, sRAGE was positively correlated with brain natriuretic peptide (BNP) levels. Mortality rates as well as sRAGE levels in patients who died did not differ between PD and HD patients. In conclusion, the positive association observed with BNP levels suggests a role for sRAGE as a prognostic factor for mortality in CKD-G5D patients displaying an active process of cardiac remodeling.
We evaluated the association between biomarkers and COVID-19 mortality. Baseline characteristics of 403 COVID-19 patients included sex and age; biomarkers, measured throughout the follow-up, included ...lymphocytes, neutrophils, ferritin, C-reactive protein, glucose, and LDH. Hazard ratios (HRs) and corresponding 95% credible intervals (CIs) were estimated through joint models (JMs) using a Bayesian approach. We fitted univariable (a single biomarker) and multivariable (all biomarkers) JMs. In univariable analyses, all biomarkers were significantly associated with COVID-19 mortality. In multivariable analysis, HRs were 1.78 (95% CI: 1.13-2.87) with a doubling of neutrophils levels, 1.49 (95% CI: 1.19-1.95) with a doubling of C-reactive protein levels, 2.66 (95% CI: 1.45-4.95) for an increase of 100 mg/dL of glucose, and 1.31 (95% CI: 1.12-1.55) for an increase of 100 U/L of LDH. No evidence of association was observed for lymphocytes and ferritin in multivariable analysis. Men had a higher COVID-19 mortality risk than women (HR = 1.75; 95% CI: 1.07-2.80) and age showed the strongest effect with a rapid increase from 60 years. These findings using JM confirm the usefulness of biomarkers in assessing COVID-19 severity and mortality. Monitoring trend patterns of such biomarkers can provide additional help in tailoring the appropriate care pathway.
Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the ...performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Advanced glycation end-products (AGE) can promote chronic kidney disease (CKD) progression and CKD-related morbidities. The soluble receptor for AGE (sRAGE) is a potential biomarker of inflammation ...and oxidative stress. Here, we explored the role of AGE, glycated albumin, sRAGE and its different forms, cRAGE and esRAGE, as prognostic factors for mortality in 111 advanced CKD patients. The median follow-up time was 39 months. AGE were quantified by fluorescence, sRAGE and its forms by ELISA. Malnutrition was screened by the Malnutrition Inflammation Score (MIS). The Cox proportional hazards regression model was used to assess the association of variables with all-cause mortality. Mean levels of sRAGE, esRAGE and cRAGE were 2318 ± 1224, 649 ± 454 and 1669 ± 901 pg/mL. The mean value of cRAGE/esRAGE was 2.82 ± 0.96. AGE were 3026 ± 766 AU and MIS 6.0 ± 4.7. eGFR correlated negatively with AGE, sRAGE, esRAGE and cRAGE, but not with cRAGE/esRAGE. Twenty-eight patients died. No difference was observed between diabetic and non-diabetic patients. Starting dialysis was not associated with enhanced risk of death. AGE, esRAGE and cRAGE/esRAGE were independently associated with all-cause mortality. AGE, esRAGE and cRAGE/esRAGE may help to stratify overall mortality risk. Implementing the clinical evaluation of CKD patients by quantifying these biomarkers can help to improve patient outcomes.
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