Accuracy and reliability of PBV ASPECTS,CBV ASPECTS and NCCT ASPECTS in acute ischaemic stroke: a matched-pair analysis

Background and purposeTo investigate the reliability and accuracy of Alberta Stroke Program Early Computed Tomography Scores (ASPECTS) derived from flatpanel detector computed tomography pooled blood volume maps compared to non-contrast computed tomography and multidetector computed tomography perfusion cerebral blood volume maps.MethodsASPECTS from pooled blood volume maps were evaluated retrospectively by two experienced readers for 37 consecutive patients with acute middle cerebral artery (MCA) M1 occlusion who underwent flatpanel detector computed tomography perfusion imaging before mechanical thrombectomy between November 2016 and February 2019. For comparison with ASPECTS from non-contrast computed tomography and cerebral blood volume maps, a matched-pair analysis according to pre-stroke modified Rankin scale, age, stroke severity, site of occlusion, time from stroke onset to imaging and final modified thrombolysis in cerebral infarction (mTICI) was performed in a separate group of patients who underwent multimodal computed tomography prior to mechanical thrombectomy between June 2015 and February 2019. Follow-up ASPECTS were derived from either non-contrast computed tomography or from magnetic resonance imaging (in seven patients) one day after mechanical thrombectomy.ResultsInterrater agreement was best for non-contrast computed tomography ASPECTS (w-kappa = 0.74, vs. w-kappa = 0.63 for cerebral blood volume ASPECTS and w-kappa = 0.53 for pooled blood volume ASPECTS). Also, accuracy, defined as correlation between acute and follow-up ASPECTS, was best for non-contrast computed tomography ASPECTS (Spearman ρ = 0.86 (0.65–0.97), P < 0.001), while it was lower and comparable for pooled blood volume ASPECTS (ρ = 0.58 (0.32–0.79), P < 0.001) and cerebral blood volume ASPECTS (ρ = 0.52 (0.17–0.80), P = 0.001). It was noteworthy that cases of relevant infarct overestimation by two or more ASPECTS regions (compared to follow-up imaging) were observed for both acute pooled blood volume and cerebral blood volume ASPECTS but occurred more often for acute pooled blood volume ASPECTS (25% vs. 5%, P = 0.02).ConclusionNon-contrast computed tomography ASPECTS outperformed both pooled blood volume ASPECTS and cerebral blood volume ASPECTS in accuracy and reliability. Importantly, relevant infarct overestimation was observed more often in pooled blood volume ASPECTS than cerebral blood volume ASPECTS, limiting its present clinical applicability for acute stroke imaging.     

The effect of testosterone replacement therapy on bladder functions,histology, apoptosis,and Rho-kinase expression in bladder outlet obstruction and hypogonadism rat model

Background/aimThe effect of testosterone replacement therapy was investigated on bladder functions, histology, apoptosis as well as Rho-kinase expression in the rat bladder outlet obstruction (BOO) and hypogonadism models. Materials and methods30 mature male rats divided into 4 groups: sham group (n = 8), BOO group (n = 8), BOO + orchiectomy group (n = 7), BOO + orchiectomy + testosterone (T) treatment group (n = 7). Cystometric findings, apoptosis index, Rho-kinase (ROCK-2) expression, and smooth muscle/collagen ratio were compared. Results BOO did not change ROCK-2 expression level, compared to sham group (P > 0.05). However, when compared to BOO group (P < 0.01), BOO + orchiectomy led ROCK-2 increase. The testosterone treatment failed to reverse the up-regulation of ROCK-2 induced by orchiectomy although it tended to lower ROCK-2 level. Compared to sham group (P = 0.002), changes in maximal bladder capacity and leak point pressure were higher (P = 0.026, P = 0.001), and bladder compliance was lower in BOO group. Also, the apoptosis index was different between the two groups (P = 0.380). Smooth muscle/collagen ratio was higher in BOO + orchiectomy + T group than in BOO + orchiectomy group (P = 0.010).ConclusionsThe research draws attention to alternating treatment approaches in case of the presence of hypogonadism and BOO.     

Evaluation of important human CYP450 isoforms and P-glycoprotein phenotype changes and genotype in type 2 diabetic patients,before and after intensifying treatment regimen using Geneva cocktail

The present study evaluates the influence of type 2 diabetes (T2D) on important CYP450 (CYP) isoforms and P-glycoprotein (Pgp) transporter activities before and 3 months after an intensifying treatment regimen involving 40 patients. Results have been compared with 21 non-T2D healthy participants (the control group). CYPs and Pgp activities were assessed after administering the Geneva cocktail. The mean metabolic ratios (MR) for CYP2B6 (1.81 ± 0.93 versus 2.68 ± 0.87), CYP2C19 (0.420 ± 0.360 versus 0.687 ± 0.558) and CYP3A4/5 (0.487 ± 0.226 versus 0.633 ± 0.254) significantly decreased in T2D patients compared to the control group (p < 0.05). CYP2C9 (0.089 ± 0.037 versus 0.069 ± 0.017) activities slightly increased in diabetic patients, and no difference was observed regarding CYP1A2 (0.154 ± 0.085 versus 0.136 ± 0.065), CYP2D6 (1.17 ± 0.56 versus 1.24 ± 0.83), and Pgp activities in comparison to the control group. Three months after the intensifying treatment regimen, MRs of CYP2C9 (0.080 ± 0.030) and CYP3A4/5 (0.592 ± 0.268) improved significantly and were not statistically different compared to the control group (P > 0.05). Several covariables, such as inflammatory markers (IL-1β and IL-6), genotypes, diabetes and demographic-related factors, were considered in the analyses. The results indicate that chronic inflammatory status associated with T2D modulates CYP450 activities in an isoform-specific manner.