AI-SCoRE (artificial intelligence-SARS CoV2 risk evaluation): a fast, objective and fully automated platform to predict the outcome in COVID-19 patients.

PURPOSE: To develop and validate an effective and user-friendly AI platform based on a few unbiased clinical variables integrated with advanced CT automatic analysis for COVID-19 patients' risk stratification. MATERIAL AND METHODS: In total, 1575 consecutive COVID-19 adults admitted to 16 hospitals during wave 1 (February 16-April 29, 2020), submitted to chest CT within 72 h from admission, were retrospectively enrolled. In total, 107 variables were initially collected; 64 extracted from CT. The outcome was survival. A rigorous AI model selection framework was adopted for models selection and automatic CT data extraction. Model performances were compared in terms of AUC. A web-mobile interface was developed using Microsoft PowerApps environment. The platform was externally validated on 213 COVID-19 adults prospectively enrolled during wave 2 (October 14-December 31, 2020). RESULTS: The final cohort included 1125 patients (292 non-survivors, 26%) and 24 variables. Logistic showed the best performance on the complete set of variables (AUC = 0.839 ± 0.009) as in models including a limited set of 13 and 5 variables (AUC = 0.840 ± 0.0093 and AUC = 0.834 ± 0.007). For non-inferior performance, the 5 variables model (age, sex, saturation, well-aerated lung parenchyma and cardiothoracic vascular calcium) was selected as the final model and the extraction of CT-derived parameters was fully automatized. The fully automatic model showed AUC = 0.842 (95% CI: 0.816-0.867) on wave 1 and was used to build a 0-100 scale risk score (AI-SCoRE). The predictive performance was confirmed on wave 2 (AUC 0.808; 95% CI: 0.7402-0.8766). CONCLUSIONS: AI-SCoRE is an effective and reliable platform for automatic risk stratification of COVID-19 patients based on a few unbiased clinical data and CT automatic analysis.

Kidney failure: aims for the next 10 years and barriers to success.

Although in some parts of the world acute and chronic kidney diseases are preventable or treatable disorders, in many other regions these diseases are left without any care. The nephrology community needs to commit itself to reduction of this divide between high-income and low-income regions. Moreover, new and exciting developments in fields such as pharmacology, genetic, or bioengineering, can give a boost, in the next decade, to a new era of diagnosis and treatment of kidney diseases, which should be made available to more patients.

Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial.

BACKGROUND: Autosomal dominant polycystic kidney disease slowly progresses to end-stage renal disease and has no effective therapy. A pilot study suggested that the somatostatin analogue octreotide longacting release (LAR) could be nephroprotective in this context. We aimed to assess the effect of 3 years of octreotide-LAR treatment on kidney and cyst growth and renal function decline in participants with this disorder. METHODS: We did an academic, multicentre, randomised, single-blind, placebo-controlled, parallel-group trial in five hospitals in Italy. Adult (>18 years) patients with estimated glomerular filtration rate (GFR) of 40 mL/min per 1·73 m(2) or higher were randomly assigned (central allocation by phone with a computerised list, 1:1 ratio, stratified by centre, block size four and eight) to 3 year treatment with two 20 mg intramuscular injections of octreotide-LAR (n=40) or 0·9% sodium chloride solution (n=39) every 28 days. Study physicians and nurses were aware of the allocated group; participants and outcome assessors were masked to allocation. The primary endpoint was change in total kidney volume (TKV), measured by MRI, at 1 year and 3 year follow-up. Analyses were by modified intention to treat. This study is registered with ClinicalTrials.gov, NCT00309283. FINDINGS: Recruitment was between April 27, 2006, and May 12, 2008. 38 patients in the octreotide-LAR group and 37 patients in the placebo group had evaluable MRI scans at 1 year follow-up, at this timepoint, mean TKV increased significantly less in the octreotide-LAR group (46·2 mL, SE 18·2) compared with the placebo group (143·7 mL, 26·0; p=0·032). 35 patients in each group had evaluable MRI scans at 3 year follow-up, at this timepoint, mean TKV increase in the octreotide-LAR group (220·1 mL, 49·1) was numerically smaller than in the placebo group (454·3 mL, 80·8), but the difference was not significant (p=0·25). 37 (92·5%) participants in the octreotide-LAR group and 32 (82·1%) in the placebo group had at least one adverse event (p=0·16). Participants with serious adverse events were similarly distributed in the two treatment groups. However, four cases of cholelithiasis or acute cholecystitis occurred in the octreotide-LAR group and were probably treatment-related. INTERPRETATION: These findings provide the background for large randomised controlled trials to test the protective effect of somatostatin analogues against renal function loss and progression to end-stage kidney disease. FUNDING: Polycystic Kidney Disease Foundation.

Validation of a patient-specific hemodynamic computational model for surgical planning of vascular access in hemodialysis patients.

Vascular access dysfunction is one of the main causes of morbidity and hospitalization in hemodialysis patients. This major clinical problem points out the need for prediction of hemodynamic changes induced by vascular access surgery. Here we reviewed the potential of a patient-specific computational vascular network model that includes vessel wall remodeling to predict blood flow change within 6 weeks after surgery for different arteriovenous fistula configurations. For model validation, we performed a multicenter, prospective clinical study to collect longitudinal data on arm vasculature before and after surgery. Sixty-three patients with newly created arteriovenous fistula were included in the validation data set and divided into four groups based on fistula configuration. Predicted brachial artery blood flow volumes 40 days after surgery had a significantly high correlation with measured values. Deviation of predicted from measured brachial artery blood flow averaged 3% with a root mean squared error of 19.5%, showing that the computational tool reliably predicted patient-specific blood flow increase resulting from vascular access surgery and subsequent vascular adaptation. This innovative approach may help the surgeon to plan the most appropriate fistula configuration to optimize access blood flow for hemodialysis, potentially reducing the incidence of vascular access dysfunctions and the need of patient hospitalization.

Intermediate volume on computed tomography imaging defines a fibrotic compartment that predicts glomerular filtration rate decline in autosomal dominant polycystic kidney disease patients.

Total kidney and cyst volumes have been used to quantify disease progression in autosomal dominant polycystic kidney disease (ADPKD), but a causal relationship with progression to renal failure has not been demonstrated. Advanced image processing recently allowed to quantify extracystic tissue, and to identify an additional tissue component named "intermediate," appearing hypoenhanced on contrast-enhanced computed tomography (CT). The aim of this study is to provide a histological characterization of intermediate volume, investigate its relation with renal function, and provide preliminary evidence of its role in long-term prediction of functional loss. Three ADPKD patients underwent contrast-enhanced CT scans before nephrectomy. Histological samples of intermediate volume were drawn from the excised kidneys, and stained with hematoxylin and eosin and with saturated picrosirius solution for histological analysis. Intermediate volume showed major structural changes, characterized by tubular dilation and atrophy, microcysts, inflammatory cell infiltrate, vascular sclerosis, and extended peritubular interstitial fibrosis. A significant correlation (r = -0.69, P < 0.001) between relative intermediate volume and baseline renal function was found in 21 ADPKD patients. Long-term prediction of renal functional loss was investigated in an independent cohort of 13 ADPKD patients, followed for 3 to 8 years. Intermediate volume, but not total kidney or cyst volume, significantly correlated with glomerular filtration rate decline (r = -0.79, P < 0.005). These findings suggest that intermediate volume may represent a suitable surrogate marker of ADPKD progression and a novel therapeutic target.

Influence of bicuspid valve geometry on ascending aortic fluid dynamics: a parametric study.

Bicuspid aortic valve (BAV) predisposes to aortic aneurysms with a high prevalence. A first hypothesis for this phenomenon is related to fibrillin deficiency (genetic hypothesis). The present article focused on a complementary, hemodynamic hypothesis stating that it is the peculiar fluid dynamics of blood in the ascending aorta of patients with BAV configurations that leads to aneurysm formation. To corroborate this hypothesis, a parametric study was performed based on numerical simulations of ascending aorta hemodynamics with different configurations of orifice area and valve orientation. The resulting wall shear stress (WSS) distributions and degree of asymmetry of the blood jet were investigated, and surrogate indices introduced. The results showed that WSS was more pronounced in subjects with BAV morphologies, also in the nonstenotic case. In particular, a maximum WSS of 3Pa was found (vs. 1.5Pa in subjects with a tricuspid configuration). It is localized at the mid-ascending aorta, the segment more prone to dilate as shown by the index related to maximum WSS (0.869 in BAV vs. 0.322 in tricuspid). Moreover, the asymmetry of the blood flow was found larger for decreasing valve area, the related index at mid-ascending aorta being more than three times higher than that found for tricuspid configuration (0.70 vs. 0.20). Further, WSS and flow asymmetry were higher also at the sinus of Valsalva and sinotubolar junction for a latero-lateral (LL) BAV configuration in keeping with the clinical observation on association between BAV configurations and different aortic aneurysm morphology. These findings may help explain the higher risk of aneurysm formation in BAV patients. The proposed indices will require validation prior to application in clinical settings.

Shear stress reverses dome formation in confluent renal tubular cells.

BACKGROUND/AIMS: It has been shown that MDCK cells, a cell line derived from canine renal tubules, develop cell domes due to fluid pumped under cell monolayer and focal detachment from the adhesion surface. In vitro studies have shown that primary cilia of kidney tubular epithelial cells act as mechanosensors, increasing intracellular calcium within seconds upon changes in fluid shear stress (SS) on cell membrane. We then studied the effect of prolonged SS exposure on cell dome formation in confluent MDCK cell monolayers. METHODS: A parallel plate flow chamber was used to apply laminar SS at 2 dynes/cm(2) to confluent cell monolayers for 6 hours. Control MDCK cell monolayers were maintained in static condition. The effects of Ca(2+) blockade and cell deciliation on SS exposure were also investigated. RESULTS: Seven days after reaching confluence, static cultures developed liquid filled domes, elevating from culture plate. Exposure to SS induced almost complete disappearance of cell domes (0.4±0.8 vs. 11.4±2.8 domes/mm(2), p < 0.01, n=14). SS induced dome disappearance took place within minutes to hours, as shown by time-lapse videomicroscopy. Exposure to SS importantly affected cell cytoskeleton altering actin stress fibers expression and organization, and the distribution of tight junction protein ZO-1. Dome disappearance induced by flow was completely prevented in the presence of EGTA or after cell deciliation. CONCLUSIONS: These data indicate that kidney tubular cells are sensitive to apical flow and that these effects are mediated by primary cilia by regulation of Ca(2+) entry in to the cell. SS induced Ca(2+) entry provokes contraction of cortical actin ring that tenses cell-cell borders and decreases basal stress fibers. These processes may increase paracellular permeability and decrease basal adhesion making dome disappear. Elucidation of the effects of apical fluid flow on tubular cell function may open new insights on the pathophysiology of kidney diseases associated with cilia dysfunction.

Scan-Rescan reproducibility of carotid bifurcation geometry from routine contrast-enhanced MR angiography.

PURPOSE: To demonstrate the feasibility of rapid and reliable geometric characterization of normal carotid bifurcation geometry from routine 3D contrast-enhanced magnetic resonance (MR) angiograms. MATERIALS AND METHODS: Repeat scans of 61 participants, acquired as part of the Atherosclerosis Risk in Communities (ARIC) Carotid MRI substudy, were digitally segmented using automated 3D level set methods, relying on an operator only to select the branch endpoints and thresholds for the 3D lumen surface initialization. Geometric factors characterizing the 3D lumen geometry were then extracted automatically. RESULTS: Of 122 scans, 117 could be segmented within 5 minutes each, with 40% being of sufficiently high quality to require less than 2 minutes each. Irrespective of scan quality, geometric factors were found to be highly reproducible, with intraclass correlation coefficients (ICCs) typically above 0.9. The reconstructed lumen surfaces were reproducible to <0.3 mm on average, comparable to previous MRI-based reproducibility studies. Owing to the automated nature of the analysis, operator reliability was near-perfect (ICC >0.99), with lumen surface differences <0.1 mm. CONCLUSION: The 3D geometry of the carotid bifurcation can be characterized rapidly and with a high degree of consistency, even for suboptimal image qualities. This bodes well for large-scale retrospective or prospective studies aimed at teasing out the influence of local vs. systemic risk factors for early atherosclerosis.

Sirolimus therapy to halt the progression of ADPKD.

Activation of mammalian target of rapamycin (mTOR) pathways may contribute to uncontrolled cell proliferation and secondary cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD). To assess the effects of mTOR inhibition on disease progression, we performed a randomized, crossover study (The SIRENA Study) comparing a 6-month treatment with sirolimus or conventional therapy alone on the growth of kidney volume and its compartments in 21 patients with ADPKD and GFR>or=40 ml/min per 1.73 m2. In 10 of the 15 patients who completed the study, aphthous stomatitis complicated sirolimus treatment but was effectively controlled by topical therapy. Compared with pretreatment, posttreatment mean total kidney volume increased less on sirolimus (46+/-81 ml; P=0.047) than on conventional therapy (70+/-72 ml; P=0.002), but we did not detect a difference between the two treatments (P=0.45). Cyst volume was stable on sirolimus and increased by 55+/-75 ml (P=0.013) on conventional therapy, whereas parenchymal volume increased by 26+/-30 ml (P=0.005) on sirolimus and was stable on conventional therapy. Percentage changes in cyst and parenchyma volumes were significantly different between the two treatment periods. Sirolimus had no appreciable effects on intermediate volume and GFR. Albuminuria and proteinuria marginally but significantly increased during sirolimus treatment. In summary, sirolimus halted cyst growth and increased parenchymal volume in patients with ADPKD. Whether these effects translate into improved long-term outcomes requires further investigation.

Biomarkers for Traumatic Brain Injury: Data Standards and Statistical Considerations.

Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.

Prognostic Value of a Combination of Circulating Biomarkers in Critically Ill Patients with Traumatic Brain Injury: Results from the European CREACTIVE Study.

Individualized patient care is essential to reduce the global burden of traumatic brain injury (TBI). This pilot study focused on TBI patients admitted to intensive care units (ICUs) and aimed at identifying patterns of circulating biomarkers associated with the disability level at 6 months from injury, measured by the extended Glasgow Outcome Scale (GOS-E). The concentration of 107 biomarkers, including proteins related to inflammation, innate immunity, TBI, and central nervous system, were quantified in blood samples collected on ICU admission from 80 patients. Patients were randomly selected among those prospectively enrolled in the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) observational study. Six biomarkers were selected to be associated with indicators of primary or secondary brain injury: three glial proteins (glial cell-derived neurotrophic factor, glial fibrillary acidic protein, and S100 calcium-binding protein B) and three cytokines (stem cell factor, fibroblast growth factor [FGF] 23 and FGF19). The subjects were grouped into three clusters according to the expression of these proteins. The distribution of the 6-month GOS-E was significantly different across clusters (p < 0.001). In two clusters, the number of 6-month deaths or vegetative states was significantly lower than expected, as calculated according to a customization of the corticosteroid randomization after significant head injury (CRASH) scores (observed/expected [O/E] events = 0.00, 95% confidence interval [CI]: 0.00-0.90 and 0.00, 95% CI: 0.00-0.94). In one cluster, less-than-expected unfavorable outcomes (O/E = 0.50, 95% CI: 0.05-0.95) and more-than-expected good recoveries (O/E = 1.55, 95% CI: 1.05-2.06) were observed. The improved prognostic accuracy of the pattern of these six circulating biomarkers at ICU admission upon established clinical parameters and computed tomography results needs validation in larger, independent cohorts. Nonetheless, the results of this pilot study are promising and will prompt further research in personalized medicine for TBI patients.

Hospitals with and without neurosurgery: a comparative study evaluating the outcome of patients with traumatic brain injury.

BACKGROUND: We leveraged the data of the international CREACTIVE consortium to investigate whether the outcome of traumatic brain injury (TBI) patients admitted to intensive care units (ICU) in hospitals without on-site neurosurgical capabilities (no-NSH) would differ had the same patients been admitted to ICUs in hospitals with neurosurgical capabilities (NSH). METHODS: The CREACTIVE observational study enrolled more than 8000 patients from 83 ICUs. Adult TBI patients admitted to no-NSH ICUs within 48 h of trauma were propensity-score matched 1:3 with patients admitted to NSH ICUs. The primary outcome was the 6-month extended Glasgow Outcome Scale (GOS-E), while secondary outcomes were ICU and hospital mortality. RESULTS: A total of 232 patients, less than 5% of the eligible cohort, were admitted to no-NSH ICUs. Each of them was matched to 3 NSH patients, leading to a study sample of 928 TBI patients where the no-NSH and NSH groups were well-balanced with respect to all of the variables included into the propensity score. Patients admitted to no-NSH ICUs experienced significantly higher ICU and in-hospital mortality. Compared to the matched NSH ICU admissions, their 6-month GOS-E scores showed a significantly higher prevalence of upper good recovery for cases with mild TBI and low expected mortality risk at admission, along with a progressively higher incidence of poor outcomes with increased TBI severity and mortality risk. CONCLUSIONS: In our study, centralization of TBI patients significantly impacted short- and long-term outcomes. For TBI patients admitted to no-NSH centers, our results suggest that the least critically ill can effectively be managed in centers without neurosurgical capabilities. Conversely, the most complex patients would benefit from being treated in high-volume, neuro-oriented ICUs.

Comparative finite element model analysis of ascending aortic flow in bicuspid and tricuspid aortic valve.

In bicuspid aortic valve (BAV) disease, the role of genetic and hemodynamic factors influencing ascending aortic pathology is controversial. To test the effect of BAV geometry on ascending aortic flow, a finite element analysis was undertaken. A surface model of aortic root and ascending aorta was obtained from magnetic resonance images of patients with BAV and tricuspid aortic valve using segmentation facilities of the image processing code Vascular Modeling Toolkit (developed at the Mario Negri Institute). Analytical models of bicuspid (antero-posterior [AP], type 1 and latero-lateral, type 2 commissures) and tricuspid orifices were mathematically defined and turned into a volumetric mesh of linear tetrahedra for computational fluid dynamics simulations. Numerical simulations were performed with the finite element code LifeV. Flow velocity fields were assessed for four levels: aortic annulus, sinus of Valsalva, sinotubular junction, and ascending aorta. Comparison of finite element analysis of bicuspid and tricuspid aortic valve showed different blood flow velocity pattern. Flow in bicuspid configurations showed asymmetrical distribution of velocity field toward the convexity of mid-ascending aorta returning symmetrical in distal ascending aorta. On the contrary, tricuspid flow was symmetrical in each aortic segment. Comparing type 1 BAV with type 2 BAV, more pronounced recirculation zones were noticed in the latter. Finally, we found that in both BAV configurations, maximum wall shear stress is highly localized at the convex portion of the mid-ascending aorta level. Comparison between models showed asymmetrical and higher flow velocity in bicuspid models, in particular in the AP configuration. Asymmetry was more pronounced at the aortic level known to be more exposed to aneurysm formation in bicuspid patients. This supports the hypothesis that hemodynamic factors may contribute to ascending aortic pathology in this subset of patients.

Outflow conditions for image-based hemodynamic models of the carotid bifurcation: implications for indicators of abnormal flow.

Computational fluid dynamics (CFD) models have become very effective tools for predicting the flow field within the carotid bifurcation, and for understanding the relationship between local hemodynamics, and the initiation and progression of vascular wall pathologies. As prescribing proper boundary conditions can affect the solutions of the equations governing blood flow, in this study, we investigated the influence to assumptions regarding the outflow boundary conditions in an image-based CFD model of human carotid bifurcation. Four simulations were conducted with identical geometry, inlet flow rate, and fluid parameters. In the first case, a physiological time-varying flow rate partition at branches along the cardiac cycle was obtained by coupling the 3D model of the carotid bifurcation at outlets with a lumped-parameter model of the downstream vascular network. Results from the coupled model were compared with those obtained by imposing three fixed flow rate divisions (50/50, 60/40, and 70/30) between the two branches of the isolated 3D model of the carotid bifurcation. Three hemodynamic wall parameters were considered as indicators of vascular wall dysfunction. Our findings underscore that the overall effect of the assumptions done in order to simulate blood flow within the carotid bifurcation is mainly in the hot-spot modulation of the hemodynamic descriptors of atherosusceptible areas, rather than in their distribution. In particular, the more physiological, time-varying flow rate division deriving from the coupled simulation has the effect of damping wall shear stress (WSS) oscillations (differences among the coupled and the three fixed flow partition models are up to 37.3% for the oscillating shear index). In conclusion, we recommend to adopt more realistic constraints, for example, by coupling models at different scales, as in this study, when the objective is the outcome prediction of alternate therapeutic interventions for individual patients, or to test hypotheses related to the role of local fluid dynamics and other biomechanical factors in vascular diseases.

PROSAFE: a European endeavor to improve quality of critical care medicine in seven countries.

BACKGROUND: Long-lasting shared research databases are an important source of epidemiological information and can promote comparison between different healthcare services. Here we present PROSAFE, an advanced international research network in intensive care medicine, with the focus on assessing and improving the quality of care. The project involved 343 ICUs in seven countries. All patients admitted to the ICU were eligible for data collection. METHODS: The PROSAFE network collected data using the same electronic case report form translated into the corresponding languages. A complex, multidimensional validation system was implemented to ensure maximum data quality. Individual and aggregate reports by country, region, and ICU type were prepared annually. A web-based data-sharing system allowed participants to autonomously perform different analyses on both own data and the entire database. RESULTS: The final analysis was restricted to 262 general ICUs and 432,223 adult patients, mostly admitted to Italian units, where a research network had been active since 1991. Organization of critical care medicine in the seven countries was relatively similar, in terms of staffing, case mix and procedures, suggesting a common understanding of the role of critical care medicine. Conversely, ICU equipment differed, and patient outcomes showed wide variations among countries. CONCLUSIONS: PROSAFE is a permanent, stable, open access, multilingual database for clinical benchmarking, ICU self-evaluation and research within and across countries, which offers a unique opportunity to improve the quality of critical care. Its entry into routine clinical practice on a voluntary basis is testimony to the success and viability of the endeavor.

Developing regulatory-compliant electronic case report forms for clinical trials: experience with the demand trial.

The use of electronic case report forms (CRF) to gather data in randomized clinical trials has grown to progressively replace paper-based forms. Computerized form designs must ensure the same data quality expected of paper CRF, by following Good Clinical Practice rules. Electronic data capture (EDC) tools must also comply with applicable statutory and regulatory requirements. Here the authors focus on the development of computerized systems for clinical trials implementing FDA and EU recommendations and regulations, and describe a laptop-based electronic CRF used in a randomized, multicenter clinical trial.

Rethinking turbulence in blood.

Blood flow, normally laminar, can exhibit high frequency fluctuations suggesting turbulence, which has important implications for the pathophysiology of vascular diseases and the design of blood-bearing devices. According to the classical model of turbulence in a homogeneous fluid, these fluctuations can be attributed to the cascade of eddies down to the Kolmogorov length scale, which, for apparent turbulence in blood, is reported to be on the order of tens of microns. On the other hand, blood is a suspension of mostly red blood cells (RBC), the size and concentration of which would seem to preclude the formation of eddies down to these scales. Assuming dissipation occurs instead via cell-cell interactions mediated by the plasma, here we show how turbulent velocity fluctuations, normally ascribed to turbulent (Reynolds) stresses, could give rise to viscous shear stresses. This may help to resolve fundamental inconsistencies in the understanding of mechanical hemolysis, and it provides a physical basis for the forces actually experienced by formed elements in the blood under nominally turbulent flow. In summary, RBC must be acknowledged as equal players if a satisfactory definition of turbulence in blood is to be achieved.

Geometry of the carotid bifurcation predicts its exposure to disturbed flow.

BACKGROUND AND PURPOSE: That certain vessels might be at so-called geometric risk of atherosclerosis rests on assumptions of wide interindividual variations in disturbed flow and of a direct relationship between disturbed flow and lumen geometry. In testing these often-implicit assumptions, the present study aimed to determine whether investigations of local risk factors in atherosclerosis can indeed rely on surrogate geometric markers of disturbed flow. METHODS: Computational fluid dynamics simulations were performed on carotid bifurcation geometries derived from MRI of 25 young adults. Disturbed flow was quantified as the surface area exposed to low and oscillatory shear beyond objectively-defined thresholds. Interindividual variations in disturbed flow were contextualized with respect to effects of uncertainties in imaging and geometric reconstruction. Relationships between disturbed flow and various geometric factors were tested via multiple regression. RESULTS: Relatively wide variations in disturbed flow were observed among the 50 vessels. Multiple regression revealed a significant (P<0.002) relationship between disturbed flow and both proximal area ratio (beta approximately 0.5) and bifurcation tortuosity (beta approximately -0.4), but not bifurcation angle, planarity, or distal area ratio. These findings were shown to be insensitive to assumptions about the flow conditions and to the choice of disturbed flow indicator and threshold. CONCLUSIONS: Certain geometric features of the young adult carotid bifurcation are robust surrogate markers of its exposure to disturbed flow. It may therefore be reasonable to consider large-scale retrospective or prospective imaging studies of local risk factors for atherosclerosis without the need for time-consuming and expensive flow imaging or CFD studies.

Modeling hemodynamics in intracranial aneurysms: Comparing accuracy of CFD solvers based on finite element and finite volume schemes.

Image-based computational fluid dynamics (CFD) has shown potential to aid in the clinical management of intracranial aneurysms, but its adoption in the clinical practice has been missing, partially because of lack of accuracy assessment and sensitivity analysis. To numerically solve the flow-governing equations, CFD solvers generally rely on 2 spatial discretization schemes: finite volume (FV) and finite element (FE). Since increasingly accurate numerical solutions are obtained by different means, accuracies and computational costs of FV and FE formulations cannot be compared directly. To this end, in this study, we benchmark 2 representative CFD solvers in simulating flow in a patient-specific intracranial aneurysm model: (1) ANSYS Fluent, a commercial FV-based solver, and (2) VMTKLab multidGetto, a discontinuous Galerkin (dG) FE-based solver. The FV solver's accuracy is improved by increasing the spatial mesh resolution (134k, 1.1m, 8.6m, and 68.5m tetrahedral element meshes). The dGFE solver accuracy is increased by increasing the degree of polynomials (first, second, third, and fourth degree) on the base 134k tetrahedral element mesh. Solutions from best FV and dGFE approximations are used as baseline for error quantification. On average, velocity errors for second-best approximations are approximately 1 cm/s for a [0,125] cm/s velocity magnitude field. Results show that high-order dGFE provides better accuracy per degree of freedom but worse accuracy per Jacobian nonzero entry as compared with FV. Cross-comparison of velocity errors demonstrates asymptotic convergence of both solvers to the same numerical solution. Nevertheless, the discrepancy between underresolved velocity fields suggests that mesh independence is reached following different paths.

Convolutional Neural Networks Promising in Lung Cancer T-Parameter Assessment on Baseline FDG-PET/CT.

Aim: To develop an algorithm, based on convolutional neural network (CNN), for the classification of lung cancer lesions as T1-T2 or T3-T4 on staging fluorodeoxyglucose positron emission tomography (FDG-PET)/CT images. Methods: We retrospectively selected a cohort of 472 patients (divided in the training, validation, and test sets) submitted to staging FDG-PET/CT within 60 days before biopsy or surgery. TNM system seventh edition was used as reference. Postprocessing was performed to generate an adequate dataset. The input of CNNs was a bounding box on both PET and CT images, cropped around the lesion centre. The results were classified as Correct (concordance between reference and prediction) and Incorrect (discordance between reference and prediction). Accuracy (Correct/[Correct + Incorrect]), recall (Correctly predicted T3-T4/[all T3-T4]), and specificity (Correctly predicted T1-T2/[all T1-T2]), as commonly defined in deep learning models, were used to evaluate CNN performance. The area under the curve (AUC) was calculated for the final model. Results: The algorithm, composed of two networks (a "feature extractor" and a "classifier"), developed and tested achieved an accuracy, recall, specificity, and AUC of 87%, 69%, 69%, and 0.83; 86%, 77%, 70%, and 0.73; and 90%, 47%, 67%, and 0.68 in the training, validation, and test sets, respectively. Conclusion: We obtained proof of concept that CNNs can be used as a tool to assist in the staging of patients affected by lung cancer.