A computational study of the effects of size, location, and number of tears on haemodynamics in surgically repaired type A aortic dissection.

Objective: This study aimed to comprehensively examine the roles of size, location, and number of tears in the progression of surgically repaired type A aortic dissection (TAAD) by assessing haemodynamic changes through patient-specific computational fluid dynamic (CFD) simulations. Methods: Two patient-specific TAAD geometries with replaced ascending aorta were reconstructed based upon computed 15 tomography (CT) scans, after which 10 hypothetical models (5 per patient) with different tear configurations were artificially created. CFD simulations were performed on all the models under physiologically realistic boundary conditions. Results: Our simulation results showed that increasing either the size or number of the re-entry tears reduced the luminal pressure difference (LPD) and maximum time-averaged wall shear stress (TAWSS), as well as areas exposed to abnormally high or low TAWSS values. Models with a large re-entry tear outperformed the others by reducing the maximum LPD by 1.88 mmHg and 7.39 mmHg, for patients 1 and 2, respectively. Moreover, proximally located re-entry tears in the descending aorta were more effective at reducing LPD than distal re-entry tears. Discussion: These computational results indicate that the presence of a relatively large re-entry tear in the proximal descending aorta might help stabilize post-surgery aortic growth. This finding has important implications for the management and risk stratification of surgically repaired TAAD patients. Nevertheless, further validation in a large patient cohort is needed.

Geometry and flow in ascending aortic aneurysms are influenced by left ventricular outflow tract orientation: Detecting increased wall shear stress on the outer curve of proximal aortic aneurysms.

BACKGROUND: The geometrical characterization of ascending thoracic aortic aneurysms in clinical practice is limited to diameter measurements. Despite growing interest in hemodynamic assessment, its relationship with ascending thoracic aortic aneurysm pathogenesis is poorly understood. This study examines the relationship between geometry of the ventriculo-aortic junction and blood flow patterns in ascending thoracic aortic aneurysm disease. METHODS: Thirty-three patients with ascending thoracic aortic aneurysms (exclusions: bicuspid aortic valves, connective tissue disease) underwent 4-dimensional flow magnetic resonance imaging. After image segmentation, geometrical parameters were measured, including aortic curvature, tortuosity, length, and diameter. A unique angular measurement made by the trajectory of the left ventricular outflow tract axis and the proximal aorta was also conducted. Velocity profiles were quantitatively and qualitatively analyzed. In addition, 11 patients (33%) underwent wall shear stress mapping of the ascending thoracic aortic aneurysm region using computational fluid dynamics simulation. RESULTS: Greater left ventricular outflow tract aortic angles were associated with larger aortic diameters at the levels of the sinus (coefficient = 0.387, P = .014) and ascending aorta (coefficient = 0.284, P = .031). Patients with left ventricular outflow tract aortic angles greater than 60° had marked asymmetric flow acceleration on the outer curvature in the proximal aorta, ascertained from 4-dimensional flow analysis. For patients undergoing computational fluid dynamics assessment, regression analysis found that higher left ventricular outflow tract aortic angles were associated with significantly higher wall shear stress values in the outer curve of the aorta (coefficient 0.07, 95% confidence interval 0.04-0.11, P = .002): Angles greater than 50° yielded time-averaged wall shear stress values greater than 2.5 Pa, exhibiting a linear relationship. CONCLUSIONS: Our findings strengthen the hypothesis of flow-mediated ascending thoracic aortic aneurysm disease progression and that left ventricular outflow tract aortic angle may be a predictor of disease severity.

Multiscale Modelling of Nanoparticle Distribution in a Realistic Tumour Geometry Following Local Injection.

Radiosensitizers have proven to be an effective method of improving radiotherapy outcomes, with the distribution of particles being a crucial element to delivering optimal treatment outcomes due to the short range of effect of these particles. Here we present a computational model for the transport of nanoparticles within the tumour, whereby the fluid velocity and particle deposition are obtained and used as input into the convection-diffusion equation to calculate the spatio-temporal concentration of the nanoparticles. The effect of particle surface charge and injection locations on the distribution of nanoparticle concentration within the interstitial fluid and deposited onto cell surfaces is assessed. The computational results demonstrate that negatively charged particles can achieve a more uniform distribution throughout the tumour as compared to uncharged or positively charged particles, with particle volume within the fluid being 100% of tumour volume and deposited particle volume 44.5%. In addition, varying the injection location from the end to the middle of the tumour caused a reduction in particle volume of almost 20% for negatively charged particles. In conclusion, radiosensitizing particles should be negatively charged to maximise their spread and penetration within the tumour. Choosing an appropriate injection location can further improve the distribution of these particles.

Modelling of Nanoparticle Distribution in a Spherical Tumour during and Following Local Injection.

Radio-sensitizing nanoparticles are a potential method to increase the damage caused to cancerous cells during the course of radiotherapy. The distribution of these particles in a given targeted tumour is a relevant factor in determining the efficacy of nanoparticle-enhanced treatment. In this study, a three-part mathematical model is shown to predict the distribution of nanoparticles after direct injection into a tumour. In contrast with previous studies, here, a higher value of diffusivity for charged particles was used and the concentration profile of deposited particles was studied. Simulation results for particle concentrations both in the interstitial fluid and deposited onto cells are compared for different values of particle surface charges during and after injection. Our results show that particles with a negative surface charge can spread farther from the injection location as compared to uncharged particles with charged particles occupying 100% of the tumour volume compared to 8.8% for uncharged particles. This has implications for the future development of radiosensitizers and any associated trials.

Fluid-Structure Interaction Simulations of Repaired Type A Aortic Dissection: a Comprehensive Comparison With Rigid Wall Models.

This study aimed to evaluate the effect of aortic wall compliance on intraluminal hemodynamics within surgically repaired type A aortic dissection (TAAD). Fully coupled two-way fluid-structure interaction (FSI) simulations were performed on two patient-specific post-surgery TAAD models reconstructed from computed tomography angiography images. Our FSI model incorporated prestress and different material properties for the aorta and graft. Computational results, including velocity, wall shear stress (WSS) and pressure difference between the true and false lumen, were compared between the FSI and rigid wall simulations. It was found that the FSI model predicted lower blood velocities and WSS along the dissected aorta. In particular, the area exposed to low time-averaged WSS ( ≤ 0.2   P a ) was increased from 21 cm2 (rigid) to 38 cm2 (FSI) in patient 1 and from 35 cm2 (rigid) to 144 cm2 (FSI) in patient 2. FSI models also produced more disturbed flow where much larger regions presented with higher turbulence intensity as compared to the rigid wall models. The effect of wall compliance on pressure difference between the true and false lumen was insignificant, with the maximum difference between FSI and rigid models being less than 0.25 mmHg for the two patient-specific models. Comparisons of simulation results for models with different Young's moduli revealed that a more compliant wall resulted in further reduction in velocity and WSS magnitudes because of increased displacements. This study demonstrated the importance of FSI simulation for accurate prediction of low WSS regions in surgically repaired TAAD, but a rigid wall computational fluid dynamics simulation would be sufficient for prediction of luminal pressure difference.

High Wall Shear Stress can Predict Wall Degradation in Ascending Aortic Aneurysms: An Integrated Biomechanics Study.

Background: Blood flow patterns can alter material properties of ascending thoracic aortic aneurysms (ATAA) via vascular wall remodeling. This study examines the relationship between wall shear stress (WSS) obtained from image-based computational modelling with tissue-derived mechanical and microstructural properties of the ATAA wall using segmental analysis. Methods: Ten patients undergoing surgery for ATAA were recruited. Exclusions: bicuspid aortopathy, connective tissue disease. All patients had pre-operative 4-dimensional flow magnetic resonance imaging (4D-MRI), allowing for patient-specific computational fluid dynamics (CFD) analysis and anatomically precise WSS mapping of ATAA regions (6-12 segments per patient). ATAA samples were obtained from surgery and subjected to region-specific tensile and peel testing (matched to WSS segments). Computational pathology was used to characterize elastin/collagen abundance and smooth muscle cell (SMC) count. Results: Elevated values of WSS were predictive of: reduced wall thickness [coef -0.0489, 95% CI (-0.0905, -0.00727), p = 0.022] and dissection energy function (longitudinal) [-15,0, 95% CI (-33.00, -2.98), p = 0.048]. High WSS values also predicted higher ultimate tensile strength [coef 0.136, 95% CI (0 0.001, 0.270), p = 0.048]. Additionally, elevated WSS also predicted a reduction in elastin levels [coef -0.276, 95% (CI -0.531, -0.020), p = 0.035] and lower SMC count ([oef -6.19, 95% CI (-11.41, -0.98), p = 0.021]. WSS was found to have no effect on collagen abundance or circumferential mechanical properties. Conclusions: Our study suggests an association between elevated WSS values and aortic wall degradation in ATAA disease. Further studies might help identify threshold values to predict acute aortic events.

Association of hemodynamic factors and progressive aortic dilatation following type A aortic dissection surgical repair.

Type A aortic dissection (TAAD) involves the ascending aorta or the arch. Acute TAAD usually requires urgent replacement of the ascending aorta. However, a subset of these patients develops aortic rupture due to further dilatation of the residual dissected aorta. There is currently no reliable means to predict the risk of dilatation following TAAD repair. In this study, we performed a comprehensive morphological and hemodynamic analysis for patients with and without progressive aortic dilatation following surgical replacement of the ascending aorta. Patient-specific models of repaired TAAD were reconstructed from post-surgery computed tomography images for detailed computational fluid dynamic analysis. Geometric and hemodynamic parameters were evaluated and compared between patients with stable aortic diameters (N = 9) and those with aortic dilatation (N = 8). Our results showed that the number of re-entry tears and true/false lumen pressure difference were significantly different between the two groups. Patients with progressive aortic dilatation had higher luminal pressure difference (6.7 [4.6, 10.9] vs. 0.9 [0.5, 2.3] mmHg; P = 0.001) and fewer re-entry tears (1.5 [1, 2.8] vs. 5 [3.3, 7.5]; P = 0.02) compared to patients with stable aortic diameters, suggesting that these factors may serve as potential predictors of aneurysmal dilatation following surgical repair of TAAD.

[Effects of potassium-solubilizing bacteria promoting the growth of Lycium barbarum seedlings under salt stress.] / 盐胁迫下解钾菌对枸杞幼苗的促生效应.

We investigated the effects of potassium-releasing bacteria on physiological and bioche-mical characteristics of Lycium barbarum (Cultivar Ningqi 1) under salt stress, with an experiment with treatments following randomized block design. The treatments included control (CK), 100 mmol·L-1 NaCl stress (NaCl), 100 mmol·L-1NaCl stress+KSBGY01 bacteria (NaCl-M1), 100 mmol·L-1NaCl stress+KSBGY02 bacteria (NaCl-M2), and 100 mmol·L-1NaCl stress+KSBGY01+KSBGY02 (NaCl-M3). We measued chlorophyll content, polyphenol content, superoxide anion (O2-·) content, hydrogen peroxide (H2O2) content, soluble sugar content, antioxidant enzyme activity and sucrose metabolic enzyme activity of Lycium barbarum seedlings. Results showed that the presence of potassium bacteria increased the values of flavonoids (FLAV), fluorescence excitation than anthocyanins relative index (FERARI), anthocyanins (ANTH-RB), nitrogen balance index (NBI-G), decreased the contents of O2-· and H2O2, and improved soluble sugar content, catalase (CAT) activity, sucrose phosphate synthase (SPS) activity, sucrose synthase (SS) activity and invertase (INV) activity of leaves in Lycium barbarum seedlings under salt stress. Among all the treatments, the highest values of ANTH-RB and NBI-G, soluble sugar content, and activities of CAT, SPS, SS, and INV presented in NaCl-M2 treatment, the highest values of SPAD, FLAV, and FERARI presented in NaCl-M3 treatment, the highest activity of superoxide dismutase (SOD) presented in NaCl-M1 treatment, the highest activity of glutathione peroxidase (GSH-Px) presented in NaCl treatment, and the highest peroxisome (POD) activity presented in CK. The 14 significant physiological and biochemical indicators in the leaves of L. barbarum seedling were analyzed by grey system correlation degree method. Our results suggested that the weighted correlation degree of phy-siological and biochemical indices of L. barbarum inoculated potassium-solubilizing bacteria was higher than that under CK and NaCl treatments. The highest weighted correlation was observed in NaCl-M2 treatment. Therefore, adding KSBGY02 potassium-solubilizing bacteria could alleviate the salt stress for L. barbarum seedlings.

ITRAQ-based proteomics analysis of tanshinone IIA on human ectopic endometrial stromal cells of adenomyosis.

PURPOSE: Adenomyosis is a diffuse or localized disease. Our previous study has indicated that tanshinone IIA (TSIIA) inhibits the proliferation, migration, and induces apoptosis of ectopic endometrial stromal cells (EESCs) of adenomyosis. However, the complex molecular mechanism of TSIIA in adenomyosis remains unclear. The objective of this study was to explore the complex molecular mechanism of TSIIA on EESCs. METHODS: In our present study, we used the proteomics approach iTRAQ (isobaric tags for relative and absolute quantitation) combined with LC-MS/MS (liquid chromatography-mass spectrometry) to investigate changes in the protein profile of EESCs treated with TSIIA. Differential proteins were analyzed by employing bioinformatics tools and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In TSIIA treated EESCs, the protein expression levels of TNFRSF10D, PLEKHM1, FECH, and TPM1A were detected by western blotting. RESULTS: Quantitative results revealed 267 significantly differential proteins in TSIIA pretreated EESCs. Gene Ontology (GO) analysis presented an overview of dysregulated proteins in the biological process (BP), cell component (CC), and molecular function (MF) categories. Interestingly, we observed that differential proteins in the extracellular matrix (ECM)-receptor interaction pathway and estrogen signaling pathway were all involved in the focal adhesion pathway, which plays essential roles in the TSIIA-mediated inhibition of EESC proliferation and migration. Furthermore, some significantly differential proteins, which may be potential targets for the treatment of adenomyosis in the future, were validated by western blotting. CONCLUSIONS: Our study provides a useful method to detect the detailed mechanism underlying the efficacy of TSIIA on EESCs.

MR-labelled liposomes and focused ultrasound for spatiotemporally controlled drug release in triple negative breast cancers in mice.

Rationale: Image-guided, triggerable, drug delivery systems allow for precisely placed and highly localised anti-cancer treatment. They contain labels for spatial mapping and tissue uptake tracking, providing key location and timing information for the application of an external stimulus to trigger drug release. High Intensity Focused Ultrasound (HIFU or FUS) is a non-invasive approach for treating small tissue volumes and is particularly effective at inducing drug release from thermosensitive nanocarriers. Here, we present a novel MR-imageable thermosensitive liposome (iTSL) for drug delivery to triple-negative breast cancers (TNBC). Methods: A macrocyclic gadolinium-based Magnetic Resonance Imaging (MRI) contrast agent was covalently linked to a lipid. This was incorporated at 30 mol% into the lipid bilayer of a thermosensitive liposome that was also encapsulating doxorubicin. The resulting iTSL-DOX formulation was assessed for physical and chemical properties, storage stability, leakage of gadolinium or doxorubicin, and thermal- or FUS-induced drug release. Its effect on MRI relaxation time was tested in phantoms. Mice with tumours were used for studies to assess both tumour distribution and contrast enhancement over time. A lipid-conjugated near-infrared fluorescence (NIRF) probe was also included in the liposome to facilitate the real time monitoring of iTSL distribution and drug release in tumours by NIRF bioimaging. TNBC (MDA-MB-231) tumour-bearing mice were then used to demonstrate the efficacy at retarding tumour growth and increasing survival. Results: iTSL-DOX provided rapid FUS-induced drug release that was dependent on the acoustic power applied. It was otherwise found to be stable, with minimum leakage of drug and gadolinium into buffers or under challenging conditions. In contrast to the usually suggested longer FUS treatment we identified that brief (~3 min) FUS significantly enhanced iTSL-DOX uptake to a targeted tumour and triggered near-total release of encapsulated doxorubicin, causing significant growth inhibition in the TNBC mouse model. A distinct reduction in the tumours' average T1 relaxation times was attributed to the iTSL accumulation. Conclusions: We demonstrate that tracking iTSL in tumours using MRI assists the application of FUS for precise drug release and therapy.

Thermosensitive Liposome-Mediated Drug Delivery in Chemotherapy: Mathematical Modelling for Spatio-temporal Drug Distribution and Model-Based Optimisation.

Thermosensitive liposome-mediated drug delivery has shown promising results in terms of improved therapeutic efficacy and reduced side effects compared to conventional chemotherapeutics. In order to facilitate our understanding of the transport mechanisms and their complex interplays in the drug delivery process, computational models have been developed to simulate the multiple steps involved in liposomal drug delivery to solid tumours. In this study we employ a multicompartmental model for drug-loaded thermosensitive liposomes, with an aim to identify the key transport parameters in determining therapeutic dosing and outcomes. The computational model allows us to not only examine the temporal and spatial variations of drug concentrations in the different compartments by utilising the tumour cord concept, but also assess the therapeutic efficacy and toxicity. In addition, the influences of key factors on systemic plasma concentration and intracellular concentration of the active drug are investigated; these include different chemotherapy drugs, release rate constants and heating duration. Our results show complex relationships between these factors and the predicted therapeutic outcome, making it difficult to identify the "best" parameter set. To overcome this challenge, a model-based optimisation method is proposed in an attempt to find a set of release rate constants and heating duration that can maximise intracellular drug concentration while minimising systemic drug concentration. Optimisation results reveal that under the operating conditions and ranges examined, the best outcome would be achieved with a low drug release rate at physiological temperature, combined with a moderate to high release rate at mild hyperthermia and 1 h heating after injection.

Dissection Level Within Aortic Wall Layers is Associated with Propagation of Type B Aortic Dissection: A Swine Model Study.

OBJECTIVE: Haemodynamic and geometric factors play pivotal roles in the propagation of acute type B aortic dissection (TBAD). The aim of this study was to evaluate the association between dissection level within all aortic layers and the propagation of acute TBAD in porcine aorta. METHODS: In twelve pigs, two models of TBAD were created. In model A (n = 6), the aortic wall tear was superficial and close to the intima (thin intimal flap), whereas in model B (n = 6) it was deep and close to the adventitia (thick intimal flap). Dissection propagation was evaluated using angiography or computed tomography scans, and the haemodynamic measurements were acquired using Doppler wires. Most pigs were followed up at 1, 3, 6, 12, 18, and up to 24 months; four animals were euthanised at three and six months, respectively (two from each group). RESULTS: Both models were successfully created. No statistical difference was observed for the median antegrade propagation distance intra-operatively between the two models (p = .092). At 24 months, the longitudinal propagation distance was significantly greater in model B than in model A (p = .016). No statistical difference in retrograde propagation was noted (p = .691). Over time, aortic wall dissection progressed most notably over the first three months in model A, whereas it continued over the first 12 months in model B. Flow velocity was significantly greater in the true lumen than in false lumen at the level of the primary tear (p = .001) and in the middle of the dissection (p = .004). The histopathological images at three and six months demonstrated the fibres were stretched linearly at the outside wall of false lumen in both models, while the depth of intimal tears developed to be superficial and similar at the distal dissection. CONCLUSION: In this swine model of TBAD, a deeper intimal tear resulted in greater dissection propagation.

Castleman disease in the hepatic-gastric space: A case report.

BACKGROUND: Castleman disease, also known as giant lymph node hyperplasia, was first reported in 1956. It is a rare benign proliferative pathological change of the lymph nodes. CASE SUMMARY: The patient, a 33-year-old woman, had epigastric distension for half a year. Examinations were performed in a local hospital. Computed tomography scan showed round soft tissue nodules, about 5.45 cm in diameter, in the hepatic-gastric space. Endoscopic ultrasound and endoscopic ultrasound guided fine needle aspiration was performed on the patient. Rapid on-site evaluation, hematoxylin eosin staining and histopathology of the puncture smear was performed. According to the Diff-Quik staining and hematoxylin eosin staining results of preoperative endoscopic ultrasound guided fine needle aspiration puncture smears as well as the immunohistochemistry results, Castleman disease was highly suspected. A sufficient preoperative evaluation was made, and a precise surgical plan was developed. Postoperative pathology confirmed Castleman disease. CONCLUSION: Endoscopic ultrasound guided fine needle aspiration can extract internal tissues of the tumor for histological and cytological examinations and provide accurate diagnosis as much as possible. Therefore, a sufficient preoperative evaluation can be made, and a precise surgical plan can be developed.

Computational modelling of drug delivery to solid tumour: Understanding the interplay between chemotherapeutics and biological system for optimised delivery systems.

Drug delivery to solid tumour involves multiple physiological, biochemical and biophysical processes taking place across a wide range of length and time scales. The therapeutic efficacy of anticancer drugs is influenced by the complex interplays among the intrinsic properties of tumours, biophysical aspects of drug transport and cellular uptake. Mathematical and computational modelling allows for a well-controlled study on the individual and combined effects of a wide range of parameters on drug transport and therapeutic efficacy, which would not be possible or economically viable through experimental means. A wide spectrum of mathematical models has been developed for the simulation of drug transport and delivery in solid tumours, including PK/PD-based compartmental models, microscopic and macroscopic transport models, and molecular dynamics drug loading and release models. These models have been used as a tool to identify the limiting factors and for optimal design of efficient drug delivery systems. This article gives an overview of the currently available computational models for drug transport in solid tumours, together with their applications to novel drug delivery systems, such as nanoparticle-mediated drug delivery and convection-enhanced delivery.

Hemodynamic evaluation using four-dimensional flow magnetic resonance imaging for a patient with multichanneled aortic dissection.

The hemodynamic function of multichanneled aortic dissection (MCAD) requires close monitoring and effective management to avoid potentially catastrophic sequelae. This report describes a 47-year-old man who underwent endovascular repair based on findings from four-dimensional (4D) flow magnetic resonance imaging of an MCAD. The acquired 4D flow data revealed complex, bidirectional flow patterns in the false lumens and accelerated blood flow in the compressed true lumen. The collapsed abdominal true lumen expanded unsatisfactorily after primary tear repair, which required further remodeling with bare stents. This case study demonstrates that hemodynamic analysis using 4D flow magnetic resonance imaging can help understand the complex pathologic changes of MCAD.

Image-guided thermosensitive liposomes for focused ultrasound drug delivery: Using NIRF-labelled lipids and topotecan to visualise the effects of hyperthermia in tumours.

Image guided drug delivery using imageable thermosensitive liposomes (iTSLs) and high intensity focused ultrasound (FUS or HIFU) has attracted interest as a novel and non-invasive route to targeted delivery of anti-cancer therapeutics. FUS-induced hyperthermia is used as an externally applied "trigger" for the release of a drug cargo from within thermosensitive drug carriers. It is suggested that sub-ablative hyperthermia significantly modifies the permeability of tumour vasculature and enhances nanoparticle uptake. Here we describe the preparation and use of magnetic resonance imaging (MRI) and near infrared fluorescence (NIRF) labelled thermosensitive liposomes for imaging and tracking of biodistribution and drug release in a murine cancer model. We prepared iTSLs to encapsulate topotecan (Hycamtin®), a chemotherapeutic agent which when released in tumours can be monitored by an increase in its intrinsic drug fluorescence. FUS was applied using feedback via subcutaneously placed fine-wire thermocouples to maintain and monitor hyperthermic temperatures. iTSL accumulation was detected within tumours using NIRF imaging immediately after liposome administration. Mild FUS-induced hyperthermia (3 min at 42 °C, 30 min post i.v. administration) greatly enhanced iTSLs uptake. A co-localised enhancement of topotecan fluorescence emission was also observed immediately after application of FUS indicating rapid triggered drug release. The phenomena of increased iTSL accumulation and concomitant topotecan release appeared to be amplified by a second mild hyperthermia treatment applied one hour after the first. MRI in vivo also confirmed enhanced iTSLs uptake due to the FUS treatments. Our imaging results indicate the effects of hyperthermia on the uptake of carriers and drug. FUS-induced hyperthermia combined with real time imaging could be used as a tool for tumour targeted drug delivery.

Incidence and risk factors for retrograde type A dissection and stent graft-induced new entry after thoracic endovascular aortic repair.

OBJECTIVE: Stent graft (SG)-induced new entry (SINE) and retrograde type A dissection (RTAD) are serious device-related complications occurring after thoracic endovascular aortic repair (TEVAR) for Stanford type B aortic dissection (TBAD) and may lead to endograft-related complications including retrograde dissection and death. The purpose of this study was to investigate the incidence and risk factors for the development of RTAD and SINE after TEVAR for TBAD and to identify the complications associated with this. METHODS: From April 2005 to October 2013, there were 997 patients who underwent TEVAR for TBAD; 852 were followed up (0-6 years; mean, 2.6 years), and 59 SINEs developed in 53 patients. The oversizing ratio and incidence of RTAD and SINE were compared between proximal bare stent (PBS) and non-PBS groups and RTAD and SINE and non-RTAD and non-SINE groups. The baseline characteristics and SG configurational factors potentially affecting both RTAD and distal SINE were analyzed. RESULTS: There was no significant difference between PBS and non-PBS groups in the incidence of RTAD. A greater oversizing ratio was related to a higher distal SINE rate. SINE was seen more frequently in smokers and in patients with hypertension, Marfan syndrome, and TEVAR in the chronic phase and less frequently in complicated dissection cases. Device-related factors for SINE were SG with a connecting bar and SG length <165 mm. The SG length <165 mm increased the overall proximal and distal SINE incidence in multivariate analysis. CONCLUSIONS: The presence of a PBS is not associated with a higher RTAD rate, whereas the use of an SG with a connecting bar and length <165 mm increases the risk of RTAD and SINE after TEVAR.

The effect of tumour size on drug transport and uptake in 3-D tumour models reconstructed from magnetic resonance images.

Drug transport and its uptake by tumour cells are strongly dependent on tumour properties, which vary in different types of solid tumours. By simulating the key physical and biochemical processes, a numerical study has been carried out to investigate the transport of anti-cancer drugs in 3-D tumour models of different sizes. The therapeutic efficacy for each tumour is evaluated by using a pharmacodynamics model based on the predicted intracellular drug concentration. Simulation results demonstrate that interstitial fluid pressure and interstitial fluid loss vary non-linearly with tumour size. Transvascular drug exchange, driven by the concentration gradient of unbound drug between blood and interstitial fluid, is more efficient in small tumours, owing to the low spatial-mean interstitial fluid pressure and dense microvasculature. However, this has a detrimental effect on therapeutic efficacy over longer periods as a result of enhanced reverse diffusion of drug to the blood circulation after the cessation of drug infusion, causing more rapid loss of drug in small tumours.

Hemodynamic Functions of Fenestrated Stent Graft under Resting, Hypertension, and Exercise Conditions.

The aim of this study was to assess the hemodynamic performance of a patient-specific fenestrated stent graft (FSG) under different physiological conditions, including normal resting, hypertension, and hypertension with moderate lower limb exercise. A patient-specific FSG model was constructed from computed tomography images and was discretized into a fine unstructured mesh comprising tetrahedral and prism elements. Blood flow was simulated using Navier-Stokes equations, and physiologically realistic boundary conditions were utilized to yield clinically relevant results. For a given cycle-averaged inflow of 2.08 L/min at normal resting and hypertension conditions, approximately 25% of flow was channeled into each renal artery. When hypertension was combined with exercise, the cycle-averaged inflow increased to 6.39 L/min but only 6.29% of this was channeled into each renal artery, which led to a 438.46% increase in the iliac flow. For all the simulated scenarios and throughout the cardiac cycle, the instantaneous flow streamlines in the FSG were well organized without any notable flow recirculation. This well-organized flow led to low values of endothelial cell activation potential, which is a hemodynamic metric used to identify regions at risk of thrombosis. The displacement forces acting on the FSG varied with the physiological conditions, and the cycle-averaged displacement force at normal rest, hypertension, and hypertension with exercise was 6.46, 8.77, and 8.99 N, respectively. The numerical results from this study suggest that the analyzed FSG can maintain sufficient blood perfusion to the end organs at all the simulated conditions. Even though the FSG was found to have a low risk of thrombosis at rest and hypertension, this risk can be reduced even further with moderate lower limb exercise.