Mean platelet volume and coronary artery disease: a systematic review and meta-analysis

Background

Platelets with high hemostatic activity play an important role in the pathophysiology of coronary artery disease(CAD) and mean platelet volume(MPV) has been proposed as an indicator of platelet reactivity. Thus, MPV may emerge as a potential marker of CAD risk. The aim of this study was to conduct a systematic review and meta-analysis comparing mean difference in MPV between patients with CAD and controls and pooling the odds ratio of CAD in those with high versus low MPV.

Methods

Medline and Scopus databases were searched up to 12 March 2013. All observational studies that considered MPV as a study's factor and measured CAD as an outcome were included. Two reviewers independently selected the studies and extracted the data.

Results

Forty studies were included in this meta-analysis. The MPV was significantly larger in patients with CAD than controls with the unstandardized mean difference of 0.70 fL (95% CI: 0.55, 0.85). The unstandardized mean difference of MPV in patients with acute coronary event and in patients with chronic stable angina was 0.84 fL (95% CI: 0.63, 1.04) and 0.46 fL (95% CI: 0.11, 0.81) respectively. Patients with larger MPV (≥ 7.3 fL) also had a greater odds of having CAD than patients with smaller MPV with a pooled odds ratio of 2.28 (95% CI: 1.46, 3.58).

Conclusion

Larger MPV was associated with CAD. Thus, it might be helpful in risk stratification, or improvement of risk prediction if combining it with other risk factors in risk prediction models.     

Bringing prevost's sign into the third dimension: Artificial intelligence estimation of conjugate gaze adjusted length (CGAL) and correlation with acute ischemic stroke

Conjugate gaze deviation is associated with acute ischemic stroke (AIS), although previously only measured on a 2D plane. The current study evaluates 3D imaging efficacy to assess conjugate gaze deviation and correlate direction and strength of deviation to neuro-clinical findings.A retrospective analysis of 519 patients who had CT scans for suspected AIS at our institution. Direction and angle of eye deviation were calculated based on 2D axial images. Volumetric reconstruction of CT scans allowed for calculation of 3D conjugate gaze adjusted length (CGAL). Angle, direction, and vector strength of both 2D and 3D scans were calculated by an artificial intelligence algorithm and tested for agreement with hemispheric ischemia location. CGAL measurements were correlated to NIHSS scores. Follow up MRI data was used to evaluate the sensitivity and specificity of CGAL in the identification of AIS.The final analysis included 122 patients. A strong agreement was found between 3D gaze direction and hemispheric ischemia location. CGAL measurements were highly correlated with NIHSS score (r = .72, P = .01). A CGAL >0.25, >0.28, and >0.35 exhibited a sensitivity of 91%, 86%, and 82% and specificity of 66%, 89%, and 89%, respectively, in AIS identification. A CGAL >0.28 has the best sensitivity-specificity balance in the identification of AIS. A CGAL >0.25 has the highest sensitivity.Given CED''s correlation with NIHSS score a 1/4 deviation in the ipsilateral direction is a sensitive ancillary radiographic sign to assist radiologists in making a correct diagnosis even when not presented with full clinical data.     

Ceramides are associated with inflammatory processes in human mediastinal adipose tissue

Background and AimCeramides are poorly characterized in human adipose tissue. The aim of this study was to investigate concentrations of different ceramide species in human subcutaneous and visceral adipose tissue depots and to determine associations between ceramides and global gene expression profiles.Methods and ResultsConcentrations of six ceramide species were determined in plasma and in subcutaneous and mediastinal adipose tissue from 10 overweight subjects (BMI 29.4 ± 4.9 kg/m²). In the adipose tissue biopsies gene expression arrays were performed and relationships between ceramides and gene expression analyzed. Immunostaining of the two adipose tissue depots was performed in an independent group of 10 patients. Mediastinal adipose tissue contained significantly higher concentrations (p < 0.05) of all six ceramide species than the subcutaneous depot. Of the six ceramides in plasma, concentrations of only two (Cer d18:1/18:0 and Cer d18:1/22:0) correlated significantly (p < 0.05) with the corresponding species in mediastinal adipose tissue, but there were no significant correlations between ceramides in plasma and subcutaneous adipose tissue. Multivariate analysis identified significant correlations between the total ceramide concentration and global gene expression within mediastinal, but not subcutaneous adipose tissue, according to cross-validation. Gene ontology analysis of genes related to ceramides in the mediastinal depot revealed that genes positively correlated with ceramides were associated mainly with immune and inflammatory categories, while genes negatively correlated with ceramides were associated mainly with lipid and carbohydrate metabolism.ConclusionsCeramides in human mediastinal adipose tissue may be involved in inflammation and lipid and carbohydrate metabolism.     

Time Interval of Two Injections and First-Dose Dependent of Accelerated Blood Clearance Phenomenon Induced by PEGylated Liposomal Gambogenic Acid: The Contribution of PEG-Specific IgM

Repeated injection of PEGylated liposomes can cause the disappearance of long circulating property because of the induction of anti-PEG IgM antibody referred to as “accelerated blood clearance (ABC) phenomenon.” Although ABC phenomenon typically occurs when entrapped drugs are chemotherapeutic agent with low cytotoxic, there is little evidence of accelerated blood clearance of PEGylated herbal-derived compound on repeated injection. Herein, we investigated the blood concentration of PEGylated liposomal gambogenic acid (PEG-GEA-L), a model PEGylated liposomal herbal extract, on its repeated injection to rats. We found time interval between injections had considerable impact on the magnitude of ABC phenomenon induced by PEG-GEA-L. When time interval was prolonged from 3 days to 7 days, ABC phenomenon could be attenuated. Furthermore, its magnitude was enhanced accompanied by a marked rise in the accumulation of PEG-GEA-L in the liver and spleen in a first-dose–dependent manner. Consistently, the level of anti-PEG IgM significantly increased with the first dose of PEG-GEA-L and decreased with the extended time interval between injections, which implies anti-PEG IgM is a major contributor to the ABC phenomenon. Notably, the increased expression of liver anti-PEG IgM was accompanied by an increased expression of efflux transporters in the induction process of the ABC phenomenon.     

The Hypotonic Environmental Changes Affect Liposomal Formulations for Nose-to-Brain Targeted Drug Delivery

Systemic administration of drugs is ineffective in the treatment of central nervous system disorders because of the blood-brain barrier. Nasal administration has been suggested as an alternative administration route as drugs absorbed in the olfactory epithelium bypass the blood-brain barrier and reach the brain within minutes. However, the nasal mucosa properties (e.g., tonicity, pH) are not constant because of physiological and environmental factors, and this might limit the therapeutic outcome of nanocarrier-based formulations. To shine light on the impact of environmental ionic strength on nanocarrier-based formulations, we have studied how liposomal formulations respond to the change of tonicity of the external environment. Large unilamellar vesicles loaded with 6 different drugs were exposed to different hypotonic environments, creating an osmotic gradient within the inner core and external environment of the liposomes up to 650 mOsm/kg. Both size and polydispersity of liposomes were significantly affected by tonicity changes. Moreover, the release kinetics of hydrophilic and lipophilic drugs were largely enhanced by hypotonic environments. These results clearly demonstrate that the environmental ionic strength has an impact on liposomal formulation stability and drug release kinetics and it should be considered when liposomal formulations for nose-to-brain targeted drug delivery are designed.