Study protocol of validating a numerical model to assess the blood flow in the circle of Willis

Introduction We developed a zero-dimensional (0D) model to assess the patient-specific haemodynamics in the circle of Willis (CoW). Similar numerical models for simulating the cerebral blood flow (CBF) had only been validated qualitatively in healthy volunteers by magnetic resonance (MR) angiography and transcranial Doppler (TCD). This study aims to validate whether a numerical model can simulate patient-specific blood flow in the CoW under pathological conditions. Methods and analysis This study is a diagnostic accuracy study. We aim to collect data from a previously performed prospective study that involved patients with aneurysmal subarachnoid haemorrhage (aSAH) receiving both TCD and brain Computerd Tomography angiography (CTA) at the same day. The cerebral flow velocities are calculated by the 0D model, based on the vessel diameters measured on the CTA of each patient. In this study, TCD is considered the gold standard for measuring flow velocity in the CoW. The agreement will be analysed using Pearson correlation coefficients. Ethics and dissemination This study protocol has been approved by the Medical Ethics Review Board of the University Medical Center Groningen: METc2019/103. The results will be submitted to an international scientific journal for peer-reviewed publication. Trial registration number NL8114

Patient-Specific Cerebral Blood Flow Simulation Based on Commonly Available Clinical Datasets

Cerebral hemodynamics play an important role in the development of cerebrovascular diseases. In this work, we propose a numerical framework for modeling patient-specific cerebral blood flow, using commonly available clinical datasets. Our hemodynamic model was developed using Simscape Fluids library in Simulink, based on a block diagram language. Medical imaging data obtained from computerized tomography angiography (CTA) in 59 patients with aneurysmal subarachnoid hemorrhage was used to extract arterial geometry parameters. Flow information obtained from transcranial Doppler (TCD) measurement was employed to calibrate input parameters of the hemodynamic model. The results show that the proposed numerical model can reproduce blood flow in the circle of Willis (CoW) per patient per measurement set. The resistance at the distal end of each terminal branch was the predominant parameter for the flow distribution in the CoW. The proposed model may be a promising tool for assessing cerebral hemodynamics in patients with cerebrovascular disease

Validation of a cerebral hemodynamic model with personalized calibration in patients with aneurysmal subarachnoid hemorrhage

This study aims to validate a numerical model developed for assessing personalized circle of Willis (CoW) hemodynamics under pathological conditions. Based on 66 computed tomography angiography images, investigations were obtained from 43 acute aneurysmal subarachnoid hemorrhage (aSAH) patients from a local neurovascular center. The mean flow velocity of each artery in the CoW measured using transcranial Doppler (TCD) and simulated by the numerical model was obtained for comparison. The intraclass correlation coefficient (ICC) over all cerebral arteries for TCD and the numerical model was 0.88 (N = 561; 95% CI 0.84–0.90). In a subgroup of patients who had developed delayed cerebral ischemia (DCI), the ICC had decreased to 0.72 but remained constant with respect to changes in blood pressure, Fisher grade, and location of ruptured aneurysm. Our numerical model showed good agreement with TCD in assessing the flow velocity in the CoW of patients with aSAH. In conclusion, the proposed model can satisfactorily reproduce the cerebral hemodynamics under aSAH conditions by personalizing the numerical model with TCD measurements. Clinical trial registration: [http://www.trialregister.nl/], identifier [NL8114]

The Role of Hemodynamics through the Circle of Willis in the Development of Intracranial Aneurysm:A Systematic Review of Numerical Models

Background: The role of regional hemodynamics in the intracranial aneurysmal formation, growth, and rupture has been widely discussed based on numerical models over the past decades. Variation of the circle of Willis (CoW), which results in hemodynamic changes, is associated with the aneurysmal formation and rupture. However, such correlation has not been further clarified yet. The aim of this systematic review is to investigate whether simulated hemodynamic indices of the CoW are relevant to the formation, growth, or rupture of intracranial aneurysm. Methods: We conducted a review of MEDLINE, Web of Science, and EMBASE for studies on the correlation between hemodynamics indices of the CoW derived from numerical models and intracranial aneurysm up to December 2020 in compliance with PRISMA guidelines. Results: Three case reports out of 1046 publications met our inclusion and exclusion criteria, reporting 13 aneurysms in six patients. Eleven aneurysms were unruptured, and the state of the other two aneurysms was unknown. Wall shear stress, oscillatory shear index, von-Mises tension, flow velocity, and flow rate were reported as hemodynamic indices. Due to limited cases and significant heterogeneity between study settings, meta-analysis could not be performed. Conclusion: Numerical models can provide comprehensive information on the cerebral blood flow as well as local flow characteristics in the intracranial aneurysm. Based on only three case reports, no firm conclusion can be drawn regarding the correlation between hemodynamic parameters in the CoW derived from numerical models and aneurysmal formation or rupture. Due to the inherent nature of numerical models, more sensitive analysis and rigorous validations are required to determine its measurement error and thus extend their application into clinical practice for personalized management. Prospero registration number: CRD42021125169

Skeletal muscle atrophy and myosteatosis are not related to long-term aneurysmal subarachnoid hemorrhage outcome

The prognosis of aneurysmal subarachnoid hemorrhage (aSAH) is highly variable. This study aims to investigate whether skeletal muscle atrophy and myosteatosis are associated with poor outcome after aSAH. In this study, a cohort of 293 consecutive aSAH-patients admitted during a 4-year period was retrospectively analyzed. Cross-sectional muscle measurements were obtained at the level of the third cervical vertebra. Muscle atrophy was defined by a sex-specific cutoff value. Myosteatosis was defined by a BMI-specific cutoff value. Poor neurological outcome was defined as modified Rankin Scale 4–6 at 2 and 6-month follow-up. Patient survival state was checked until January 2021. Generalized estimating equation was performed to assess the effect of muscle atrophy / myosteatosis on poor neurological outcome after aSAH. Cox regression was performed to analyze the impact of muscle atrophy and myosteatosis on overall survival. The study found that myosteatosis was associated with poor neurological condition (WFNS 4–5) at admission after adjusting for covariates (odds ratio [OR] 2.01; 95%CI 1.05,3.83; P = .03). It was not associated with overall survival (P = .89) or with poor neurological outcomes (P = .18) when adjusted for other prognostic markers. Muscle atrophy was not associated with overall survival (P = .58) or neurological outcome (P = .32) after aSAH. In conclusion, myosteatosis was found to be associated with poor physical condition directly after onset of aSAH. Skeletal muscle atrophy and myosteatosis were however irrelevant to outcome in the Western-European aSAH patient. Future studies are needed to validate these finding

Filaggrin loss-of-function mutations and atopic dermatitis as risk factors for hand eczema in apprentice nurses:part II of a prospective cohort study

BACKGROUND/OBJECTIVES: Environmental exposure and personal susceptibility both contribute to the development of hand eczema. In this study, we investigated the effect of loss-of-function mutations in the filaggrin gene (FLG), atopic dermatitis and wet work exposure on the development of hand eczema in apprentice nurses. METHODS: Dutch apprentice nurses were genotyped for the four most common FLG mutations; atopic dermatitis and hand eczema history were assessed by questionnaire. Exposure and hand eczema during traineeships were assessed with diary cards. RESULTS: The prevalence of hand eczema during traineeships was higher among subjects with a history of hand eczema reported at inclusion. Hand washing during traineeships and at home increased the risk of hand eczema. After adjustment for the effects of exposure and FLG mutations, an odds ratio of 2.5 (90% confidence interval 1.7–3.7) was found for a history of atopic dermatitis. In this study, an increased risk of hand eczema conferred by FLG mutations could not be shown, but subjects with concomitant FLG mutations and atopic dermatitis showed the highest risk of hand eczema during traineeships. CONCLUSION: A history of atopic dermatitis, a history of hand eczema and wet work exposure were the most important factors increasing the risk of hand eczema during traineeships

Beam tests of a large-scale TORCH time-of-flight demonstrator

The TORCH time-of-flight detector is designed to provide particle identification in the momentum range 2-10 GeV/c over large areas. The detector exploits prompt Cherenkov light produced by charged particles traversing a 10 mm thick quartz plate. The photons propagate via total internal reflection and are focused onto a detector plane comprising position-sensitive Micro-Channel Plate Photo-Multiplier Tubes (MCP-PMT) detectors. The goal is to achieve a single-photon timing resolution of 70 ps, giving a timing precision of 15 ps per charged particle by combining the information from around 30 detected photons. The MCP-PMT detectors have been developed with a commercial partner (Photek Ltd, UK), leading to the delivery of a square tube of active area 53 $\times$ 53mm$^2$ with a granularity of 8 $\times$ 128 pixels equivalent. A large-scale demonstrator of TORCH, having a quartz plate of dimensions 660 $\times$ 1250 $\times$ 10 mm$^3$ and read out by a pair of MCP-PMTs with custom readout electronics, has been verified in a test beam campaign at the CERN PS. Preliminary results indicate that the required performance is close to being achieved. The anticipated performance of a full-scale TORCH detector at the LHCb experiment is presented.Comment: 12 pages, 7 figures, Paper submitted to Nuclear Instruments & Methods in Physics Research, Section A - Special Issue VCI 201

Effect of high-dose dexamethasone on perioperative lactate levels and glucose control:a randomized controlled trial

INTRODUCTION: Blood lactate levels are increasingly used to monitor patients. Steroids are frequently administered to critically ill patients. However, the effect of steroids on lactate levels has not been adequately investigated. We studied the effect of a single intraoperative high dose of dexamethasone on lactate and glucose levels in patients undergoing cardiac surgery. METHODS: The Dexamethasone for Cardiac Surgery (DECS) trial was a multicenter randomized trial on the effect of dexamethasone 1 mg/kg versus placebo on clinical outcomes after cardiac surgery in adults. Here we report a pre-planned secondary analysis of data from DECS trial participants included at the University Medical Center Groningen. The use of a computer-assisted glucose regulation protocol--Glucose Regulation for Intensive care Patients (GRIP)--was part of routine postoperative care. GRIP aimed at glucose levels of 4 to 8 mmol/L. Primary outcome parameters were area under the lactate and glucose curves over the first 15 hours of ICU stay (AUC₁₅). ICU length of stay and mortality were observed as well. RESULTS: The primary outcome could be determined in 497 patients of the 500 included patients. During the first 15 hours of ICU stay, lactate and glucose levels were significantly higher in the dexamethasone group than in the placebo group: lactate AUC₁₅ 25.8 (13.1) versus 19.9 (11.2) mmol/L × hour, P <0.001 and glucose AUC₁₅ 126.5 (13.0) versus 114.4 (13.9) mmol/L × hour, P <0.001. In this period, patients in the dexamethasone group required twice as much insulin compared with patients who had received placebo. Multivariate and cross-correlation analyses suggest that the effect of dexamethasone on lactate levels is related to preceding increased glucose levels. Patients in the placebo group were more likely to stay in the ICU for more than 24 hours (39.2%) compared with patients in the dexamethasone group (25.0%, P = 0.001), and 30-day mortality rates were 1.6% and 2.4%, respectively (P = 0.759). CONCLUSIONS: Intraoperative high-dose dexamethasone increased postoperative lactate and glucose levels in the first 15 hours of ICU stay. Still, patients in the dexamethasone group had a shorter ICU length of stay and similar mortality compared with controls. TRIAL REGISTRATION: ClinicalTrials.gov NCT00293592 . Registered 16 February 2006