The Association Between Illness Severity Scores and In-hospital Mortality After Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: The purpose of this study was to examine the association with in-hospital mortality of 8 illness severity scores in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In a retrospective cohort study, we investigated the association with in-hospital mortality of admission Hunt and Hess (HH) score, Fisher grade, severity of illness and risk of mortality scores, and serial Glasgow coma scale (GCS) score in patients with aSAH. We also explored the changes in GCS between admission and discharge using a multivariate model adjusting for age, clinical vasospasm, and external ventricular drain status. RESULTS: Data from 480 patients with aSAH, of which 383 (79.8%) aneurysms were in the anterior circulation, were included in analysis. Patients were female (n=340, 70.8%) with a median age of 56 (interquartile range: 48 to 66) years. The majority (n=332, 69.2%) had admission HH score 3 to 5, Fisher grade 3 to 4 (n=437, 91%), median severity of illness 3 (range: 1 to 4), median risk of mortality 3 (range: 1 to 4), and median admission GCS of 13 (interquartile range: 7 to 15). Overall, 406 (84.6%) patients received an external ventricular drain, 469 (97.7%) underwent aneurysm repair, and 60 died (12.5%). Compared with admission HH score, GCS 24 hours after admission (area under the curve: 0.84, 95% confidence interval [CI]: 0.79-0.88) and 24 hours after aneurysm repair (area under the curve: 0.87, 95% CI: 0.82-0.90) were more likely to be associated with in-hospital mortality. Among those who died, the greatest decline in GCS was noted between 24 hours after aneurysm repair and discharge (-3.38 points, 95% CI: -4.17, -2.58). CONCLUSIONS: Compared with admission HH score, GCS 24 hours after admission (or 24 h after aneurysm repair) is more likely to be associated with in-hospital mortality after aSAH.

Associations Between Transcranial Doppler Vasospasm and Clinical Outcomes After Aneurysmal Subarachnoid Hemorrhage: A Retrospective Observational Study.

OBJECTIVE: The objective is to examine the relationship between transcranial Doppler cerebral vasospasm (TCD-vasospasm), and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In a retrospective cohort study, using univariate and multivariate analysis, we examined the association between TCD-vasospasm (defined as Lindegaard ratio >3) and patient's ability to ambulate without assistance, the need for tracheostomy and gastrostomy tube placement, and the likelihood of being discharged home from the hospital. RESULTS: We studied 346 patients with aSAH; median age 55 years (Interquartile range IQR 46,64), median Hunt and Hess 3 [IQR 1-5]. Overall, 68.6% (n=238) had TCD-vasospasm, and 28% (n=97) had delayed cerebral ischemia. At hospital discharge, 54.3% (n=188) were able to walk without assistance, 5.8% (n=20) had received a tracheostomy, and 12% (n=42) had received a gastrostomy tube. Fifty-three percent (n=183) were discharged directly from the hospital to their home. TCD-vasospasm was not associated with ambulation without assistance at discharge (adjusted odds ratio, aOR 0.54, 95% 0.19,1.45), tracheostomy placement (aOR 2.04, 95% 0.23,18.43), gastrostomy tube placement (aOR 0.95, 95% CI 0.28,3.26), discharge to home (aOR 0.36, 95% CI 0.11,1.23). CONCLUSION: This single-center retrospective study finds that TCD-vasospasm is not associated with clinical outcomes such as ambulation without assistance, discharge to home from the hospital, tracheostomy, and gastrostomy feeding tube placement. Routine screening for cerebral vasospasm and its impact on vasospasm diagnostic and therapeutic interventions and their associations with improved clinical outcomes warrant an evaluation in large, prospective, case-controlled, multi-center studies.

Numerical simulation of the transport of nanoparticles as drug carriers in hydromagnetic blood flow through a diseased artery with vessel wall permeability and rheological effects.

The present study considers the mathematical modelling of unsteady non-Newtonian hydro-magnetic nano-hemodynamics through a rigid cylindrical artery featuring two different stenoses (composite and irregular). The Ostwald-De Waele power-law fluid model is adopted to simulate the non-Newtonian characteristics of blood. Inspired by drug delivery applications for cardiovascular treatments, blood is considered doped with a homogenous suspension of biocompatible nanoparticles. The arterial vessel exhibits the permeability effect (lateral influx/efflux), and an external magnetic field is also applied in the radial direction to the flow. A combination of the Buongiorno and Tiwari-Das nanoscale models is adopted. The strongly nonlinear nature of the governing equations requires a robust numerical method, and therefore the finite difference technique is deployed to solve the resulting equations. Validation of solutions for the pure blood case (absence of nanoparticles) is included. Comprehensive solutions are presented for shear-thickening (n = 1.5) and shear-thinning (n = 0.5) blood flow for the effects of crucial nanoscale thermophysical, solutal parameters, and hydrodynamic parameters. Comparison of profiles (velocity, temperature, wall shear stress, and flow rate) is also made for composite and irregular stenosis. Colour visualization of streamline plots is included for pure blood and nano mediated blood both with and without applied magnetic field. The inclusion of nanoparticles (Cu/blood) within blood increases the axial velocity of blood. By applying external magnetic field in the radial direction, axial velocity is significantly damped whereas much less dramatic alterations are computed in blood temperature and concentration profiles. The simulations are relevant to the diffusion of nano-drugs in magnetic targeted treatment of stenosed arterial diseases.

Numerical simulation of the transport of nanoparticles as drug carriers in hydromagnetic blood flow through a diseased artery with vessel wall permeability and rheological effects.

The present study considers the mathematical modeling of unsteady non-Newtonian hydro-magnetic nano-hemodynamics through a rigid cylindrical artery featuring two different stenoses (composite and irregular). The Ostwald-De Waele power-law fluid model is adopted to simulate the non-Newtonian characteristics of blood. Inspired by drug delivery applications for cardiovascular treatments, blood is considered doped with a homogenous suspension of biocompatible nanoparticles. The arterial vessel exhibits the permeability effect (lateral influx/efflux), and an external magnetic field is also applied in the radial direction to the flow. A combination of the Buongiorno and Tiwari-Das nanoscale models is adopted. The strongly nonlinear nature of the governing equations requires a robust numerical method, and therefore the finite difference technique is deployed to solve the resulting equations. Validation of solutions for the pure blood case (absence of nanoparticles) is included. Comprehensive solutions are presented for shear-thickening (n = 1.5) and shear-thinning (n = 0.5) blood flow for the effects of crucial nanoscale thermophysical, solutal parameters, and hydrodynamic parameters. Comparison of profiles (velocity, temperature, wall shear stress, and flow rate) is also made for composite and irregular stenosis. Colour visualization of streamline plots is included for pure blood and nano mediated blood both with and without applied magnetic field. The inclusion of nanoparticles (Cu/blood) within blood increases the axial velocity of blood. By applying external magnetic field in the radial direction, axial velocity is significantly damped whereas much less dramatic alterations are computed in blood temperature and concentration profiles. The simulations are relevant to the diffusion of nano-drugs in magnetic targeted treatment of stenosed arterial diseases.

Computational simulation of rheological blood flow containing hybrid nanoparticles in an inclined catheterized artery with stenotic, aneurysmal and slip effects.

Influenced by nano-drug delivery applications, the present article considers the collective effects of hybrid biocompatible metallic nanoparticles (Silver and Copper), a stenosis and an aneurysm on the unsteady blood flow characteristics in a catheterized tapered inclined artery. The non-Newtonian Carreau fluid model is deployed to represent the hemorheological characteristics in the arterial region. A modified Tiwari-Das volume fraction model is adopted for nanoscale effects. The permeability of the arterial wall and the inclination of the diseased artery are taken into account. The nanoparticles are also considered to have various shapes (bricks, cylinders, platelets, blades) and therefore the influence of different shape parameters is discussed. The conservation equations for mass, linear momentum and energy are normalized by employing suitable non-dimensional variables. The transformed equations with associated boundary conditions are solved numerically using the FTCS method. Key hemodynamic characteristics i.e. velocity, temperature, flow rate, wall shear stress (WSS) in stenotic and aneurysm region for a particular critical height of the stenosis, are computed. Hybrid nanoparticles (Ag-Cu/Blood) accelerate the axial flow and increase temperatures significantly compared with unitary nanoparticles (Ag/blood), at both the stenosis and aneurysm segments. Axial velocity, temperature and flow rate are all enhanced with greater nanoparticle shape factor. Axial velocity, temperature, wall shear stress and flow rate magnitudes are always comparatively higher at the aneurysm region compared with the stenotic segment. The simulations provide novel insights into the performance of different nanoparticle geometries and also rheological behaviour in realistic nano-pharmaco-dynamic transport and percutaneous coronary intervention (PCI).

Computational simulations of hybrid mediated nano- hemodynamics (Ag-Au/Blood) through an irregular symmetric stenosis.

This article examines theoretically and numerically the unsteady two-dimensional blood flow through a diseased artery featuring an irregular stenosis. An appropriate geometric model is adopted to simulate the irregular stenotic artery. Inspired by drug delivery applications for blood vessels, the impact of hybrid nanoparticles on blood flow using a modified Tiwari-Das model is discussed. The blood is examined to have a homogenous suspension of hybrid nanoparticles. Reynolds' viscosity model is applied in the formulation to represent the temperature dependency of blood. The two-dimensional governing conservation equations for momentum and heat transfer with buoyancy effect are simplified by considering the mild stenotic approximation. A finite-difference technique is deployed to numerically discretize the transformed non-dimensional model. Extensive graphical results for blood flow characteristics are obtained by MATLAB code. Comprehensive visualization of the effects of hemodynamic, geometric and nanoscale parameters on transport characteristics is provided. The problem is conducted for silver and silver-gold hybrid mediated blood flow models, and experimental values of blood and these biocompatible metallic nanoparticles. A comparison between silver and hybrid nanofluid is obtained which promotes the use of hybrid nanoparticles in successfully achieving clinically more beneficial results associated with nano-drug delivery in diseased hemodynamics. Enhancement in viscosity parameter induces axial flow acceleration in the stenotic region while lower thermal conductivity decreases the temperature magnitudes. Furthermore, with time variation, the pressure gradient is found to be lower in coronary arteries comparatively to femoral arteries. The simulations are relevant to transport phenomenon in nano-drug targeted delivery in haematology.

Micropolar pulsatile blood flow conveying nanoparticles in a stenotic tapered artery: NON-Newtonian pharmacodynamic simulation.

Two-dimensional rheological laminar hemodynamics through a diseased tapered artery with a mild stenosis present is simulated theoretically and computationally. The effect of different metallic nanoparticles homogeneously suspended in the blood is considered, motivated by drug delivery (pharmacology) applications. The Eringen micropolar model has been discussed for hemorheological characteristics in the whole arterial region. The conservation equations for mass, linear momentum, angular momentum (micro-rotation), and energy and nanoparticle species are normalized by employing suitable non-dimensional variables. The transformed equations are solved numerically subject to physically appropriate boundary conditions using the finite element method with the variational formulation scheme available in the FreeFEM++ code. A good correlation is achieved between the FreeFEM++ computations and existing results. The effect of selected parameters (taper angle, Prandtl number, Womersley parameter, pulsatile constants, and volumetric concentration) on velocity, temperature, and micro-rotational (Eringen angular) velocity has been calculated for a stenosed arterial segment. Wall shear stress, volumetric flow rate, and hemodynamic impedance of blood flow are also computed. Colour contours and graphs are employed to visualize the simulated blood flow characteristics. It is observed that by increasing Prandtl number (Pr), the micro-rotational velocity decreases i.e., microelement (blood cell) spin is suppressed. Wall shear stress decreases with the increment in pulsatile parameters (B and e), whereas linear velocity increases with a decrement in these parameters. Furthermore, the velocity decreases in the tapered region with elevation in the Womersley parameter (α). The simulations are relevant to transport phenomena in pharmacology and nano-drug targeted delivery in hematology.

Computational fluid dynamic simulation of two-fluid non-Newtonian nanohemodynamics through a diseased artery with a stenosis and aneurysm.

This article presents a two-dimensional theoretical study of hemodynamics through a diseased permeable artery with a mild stenosis and an aneurysm present. The effect of metallic nanoparticles on the blood flow is considered, motivated by drug delivery (pharmacology) applications. Two different models are adopted to mimic non-Newtonian characteristics of the blood flow; the Casson (viscoplastic) fluid model is deployed in the core region and the Sisko (viscoelastic) fluid model employed in the peripheral (porous) region. The revised Buongiorno two-component nanofluid model is utilized for nanoscale effects. The blood is considered to contain a homogenous suspension of nanoparticles. The governing equations are derived by extending the Navier-Stokes equations with linear Boussinesq approximation (which simulates both heat and mass transfer). Natural (free) double-diffusive convection is considered to simulate the dual influence of thermal and solutal buoyancy forces. The conservation equations are normalised by employing appropriate non-dimensional variables. The transformed equations are solved numerically using the finite element method with the variational formulation scheme available in the FreeFEM++ code. A comprehensive mesh-independence study is included. The effect of selected parameters (thermophoresis, Brownian motion, Grashof number, thermo-solutal buoyancy ratio, Sisko parameter ratio, and permeability parameter) on velocity, temperature, nanoparticle concentration, and hemodynamic pressure have been calculated for two clinically important cases of arteries with stenosis and an aneurysm. Skin-friction coefficient, Nusselt number, volumetric flow rate, and resistance impedance of blood flow are also computed. Colour contours and graphs are employed to visualize the simulated blood flow characteristics. It is observed that by increasing the thermal buoyancy parameter, i.e. Grashof number (Gr), the nanoparticle concentration and temperature decrease, whereas velocity increases with an increment in the Brownian motion parameter (Nb). Furthermore, velocity decreases in the peripheral porous region with elevation in the Sisko material ratio (m) and permeability parameter (k'). The simulations are relevant to transport phenomena in pharmacology and nano-drug targeted delivery in haematology.

EZH2-shRNA-mediated upregulation of p21waf1/cip1 and its transcriptional enhancers with concomitant downmodulation of mutant p53 in pancreatic ductal adenocarcinoma.

PURPOSE: Enhancer of zeste homologue 2 (EZH2), a component of the chromatin modification protein complex, is upregulated in pancreatic ductal adenocarcinoma (PDAC), whereas loss of p53 and its downstream target, p21(waf1/cip1), is also observed frequently. We sought to investigate the role of the p53-p21(waf1/cip1) pathway in relation to EZH2-mediated inhibition of PDAC. METHODS: The PANC-1 cell line was utilized in chromatin immunoprecipitation, gene profiling, Western blot, cell invasion, cell proliferation, and tumor xenograft assays. RESULTS: Western blot analysis with antibodies that recognize both wild-type and mutant p53 did not show any alterations in band intensity; however, antibody that detects only mutant p53 showed a band of significantly lesser intensity with EZH2 knockdown. Western blot analysis further revealed a significant upregulation of p21(waf1/cip1). Gene expression profile analysis indicated significantly enhanced transcripts of transcriptional inducers of p21(waf1/cip1), with downregulation of mutant p53 transcript, corroborating the Western blot analysis. PANC-1 cells expressing EZH2-short hairpin RNA displayed markedly attenuated growth in SCID mice. CONCLUSION: Downregulation of mutant p53 with concomitant enhanced expression of p21(waf1/cip1) and its transcriptional trans-activators may contribute toward EZH2-mediated suppression of PDAC.