Constrictive versus compressive bladder outflow obstruction in men: Does it matter?

INTRODUCTION: Bladder outflow obstruction (BOO) is a urethral resistance (UR) at a level above a clinically relevant threshold. UR is currently graded in terms of the existence and severity of the BOO based on maximum flowrate and associated detrusor pressure only. However, the pressure-flow relation throughout the course of voiding includes additional information that may be relevant to identify the type of BOO. This study introduces a new method for the distinction between the provisionally called compressive and constrictive types of BOO and relates this classification to underlying patient and urodynamic differences between those BOO types. METHODS: In total, 593 high-quality urodynamic pressure-flow studies in men were included in this study. Constrictive BOO was identified if the difference Δp between the actual minimal urethral opening pressure (pmuo) and the expected pmuo according to the linearized passive urethral resistance relation (linPURR) nomogram was >25 cmH2O. Compressive BOO is identified in the complementary case where the pressure difference Δp ≤ 25 cmH2O. Differences in urodynamic parameters, patient age, and prostate size were explored. RESULTS: In 81 (13.7%) of the cases, constrictive BOO was found. In these patients, the prostate size was significantly smaller when compared to patients diagnosed with compressive BOO, while displaying a significantly lower maximum flowrate, higher detrusor pressure at maximal flowrate and more postvoid residual (PVR). CONCLUSION: This study is an initial step in the validation of additional subtyping of BOO. We found significant differences in prostate size, severity of BOO, and PVR, between patients with compressive and constrictive BOO. Subtyping of voiding-outflow dynamics may lead to more individualized management in patients with BOO.

Computational Requirements for Modeling Thermal Conduction in Polymeric Phase-Change Materials: Periodic Hard Spheres Case.

This research focuses on modeling heat transfer in heterogeneous media composed of stacked spheres of paraffin as a perspective polymeric phase-change material. The main goal is to study the requirements of the numerical scheme to correctly predict the thermal conductivity in a periodic system composed of an indefinitely repeated configuration of spherical particles subjected to a temperature gradient. Based on OpenFOAM, a simulation platform is created with which the resolution requirements for accurate heat transfer predictions were inferred systematically. The approach is illustrated for unit cells containing either a single sphere or a configuration of two spheres. Asymptotic convergence rates confirming the second-order accuracy of the method are established in case the grid is fine enough to have eight or more grid cells covering the distance of the diameter of a sphere. Configurations with two spheres can be created in which small gaps remain between these spheres. It was found that even the under-resolution of these small gaps does not yield inaccurate numerical solutions for the temperature field in the domain, as long as one adheres to using eight or more grid cells per sphere diameter. Overlapping and (barely) touching spheres in a configuration can be simulated with high fidelity and realistic computing costs. This study further extends to examine the effective thermal conductivity of the unit cell, particularly focusing on the volume fraction of paraffin in cases with unit cells containing a single sphere. Finally, we explore the dependence of the effective thermal conductivity for unit cells containing two spheres at different distances between them.

Quantifying bladder outflow obstruction in men: A comparison of four approximation methods exploiting large data samples.

INTRODUCTION: A pressure flow study (PFS), part of the International Continence Society standard urodynamic test, is regarded gold standard for the classification and quantification of the urethral resistance (UR), expressed in the bladder outflow obstruction (BOO). For men with benign prostatic hyperplasia, the minimum urethral opening pressure (pmuo ), found at the end of the passive urethral resistance relation is considered the relevant parameter describing BOO. However, in clinical practice, direct measurements of pmuo are easily confounded by terminal dribbling. For that reason, alternative methods were developed to derive pmuo , and thereby assess BOO using the maximum urine flow rate (Qmax ) and the corresponding pressure (pdetQmax ) instead. These methods were never directly compared against a large data set. With the increasing variety of treatments becoming available more precise grading of UR may become of relevance. The current study compares four well-known methods to approximate pmuo and examines the relation between pmuo and pdetQmax . METHODS: In total, 1717 high-quality PFS of men referred with lower urinary tract symptoms between 2003 and 2020 without earlier lower urinary tract surgery were included. From these recordings, pmuo was calculated according to three one-parameter methods. In addition, a three-parameter method (3PM) was used, based on a fit through the lowest pressure flank of the pressure-flow plot. The estimated pmuo 's were compared with a precisely assessed pmuo . A difference of <10 cmH2 O between an estimate and the actual pmuo was considered accurate. A comparison between the four approximation methods and the actual pmuo was visualized using a Bland-Altman plot. The differences between the actual and the estimated slope were assessed and dependency on pmuo was analyzed. RESULTS: A total of 1717 studies were analyzed. In 55 (3.2%) PFS, 3PM analysis was impossible because all pressures after Qmax were higher than pdetQmax . The 3PM model was superior in predicting pmuo , with 75.9% of the approximations within a range of +10 or -10 cmH2 O of the actual pmuo . Moreover, pmuo according to urethral resistance A (URA) and linearized passive urethral resistance relation (linPURR) appear equally reliable. Bladder outflow obstruction index (BOOI) was significantly less accurate when compared to all others. Bland-Altman analysis showed a tendency of BOOI to overestimate pmuo in men with higher grades of UR, while URA tended to underestimate pmuo in those cases. The slope between pmuo and pdetQmax -Qmax increased with larger pmuo , as opposed to the constant relation proposed within BOOI. Although significant differences were found, the clinical relevance of those differences is not known. CONCLUSION: Of the four methods to estimate pmuo and quantify BOO, 3PM was found the most accurate and BOOI the least accurate. As 3PM is not generally available and performance in lower quality PFS is unknown, linPURR is (for now) the most physiologically accurate.

Aneurysm-on-a-Chip: Setting Flow Parameters for Microfluidic Endothelial Cultures Based on Computational Fluid Dynamics Modeling of Intracranial Aneurysms.

Intracranial aneurysms are pouch-like extrusions from the vessels at the base of the brain which can rupture and cause a subarachnoid hemorrhage. The pathophysiological mechanism of aneurysm formation is thought to be a consequence of blood flow (hemodynamic) induced changes on the endothelium. In this study, the results of a personalized aneurysm-on-a-chip model using patient-specific flow parameters and patient-specific cells are presented. CT imaging was used to calculate CFD parameters using an immersed boundary method. A microfluidic device either cultured with human umbilical vein endothelial cells (HUVECs) or human induced pluripotent stem cell-derived endothelial cells (hiPSC-EC) was used. Both types of endothelial cells were exposed for 24 h to either 0.03 Pa or 1.5 Pa shear stress, corresponding to regions of low shear and high shear in the computational aneurysm model, respectively. As a control, both cell types were also cultured under static conditions for 24 h as a control. Both HUVEC and hiPSC-EC cultures presented as confluent monolayers with no particular cell alignment in static or low shear conditions. Under high shear conditions HUVEC elongated and aligned in the direction of the flow. HiPSC-EC exhibited reduced cell numbers, monolayer gap formation and cells with aberrant, spread-out morphology. Future research should focus on hiPSC-EC stabilization to allow personalized intracranial aneurysm models.

Development and application of a volume penalization immersed boundary method for the computation of blood flow and shear stresses in cerebral vessels and aneurysms.

A volume-penalizing immersed boundary method is presented for the simulation of laminar incompressible flow inside geometrically complex blood vessels in the human brain. We concentrate on cerebral aneurysms and compute flow in curved brain vessels with and without spherical aneurysm cavities attached. We approximate blood as an incompressible Newtonian fluid and simulate the flow with the use of a skew-symmetric finite-volume discretization and explicit time-stepping. A key element of the immersed boundary method is the so-called masking function. This is a binary function with which we identify at any location in the domain whether it is 'solid' or 'fluid', allowing to represent objects immersed in a Cartesian grid. We compare three definitions of the masking function for geometries that are non-aligned with the grid. In each case a 'staircase' representation is used in which a grid cell is either 'solid' or 'fluid'. Reliable findings are obtained with our immersed boundary method, even at fairly coarse meshes with about 16 grid cells across a velocity profile. The validation of the immersed boundary method is provided on the basis of classical Poiseuille flow in a cylindrical pipe. We obtain first order convergence for the velocity and the shear stress, reflecting the fact that in our approach the solid-fluid interface is localized with an accuracy on the order of a grid cell. Simulations for curved vessels and aneurysms are done for different flow regimes, characterized by different values of the Reynolds number (Re). The validation is performed for laminar flow at Re = 250, while the flow in more complex geometries is studied at Re = 100 and Re = 250, as suggested by physiological conditions pertaining to flow of blood in the circle of Willis.

Analysis of errors occurring in large eddy simulation.

We analyse the effect of second- and fourth-order accurate central finite-volume discretizations on the outcome of large eddy simulations of homogeneous, isotropic, decaying turbulence at an initial Taylor-Reynolds number Re(lambda)=100. We determine the implicit filter that is induced by the spatial discretization and show that a higher order discretization also induces a higher order filter, i.e. a low-pass filter that keeps a wider range of flow scales virtually unchanged. The effectiveness of the implicit filtering is correlated with the optimal refinement strategy as observed in an error-landscape analysis based on Smagorinsky's subfilter model. As a point of reference, a finite-volume method that is second-order accurate for both the convective and the viscous fluxes in the Navier-Stokes equations is used. We observe that changing to a fourth-order accurate convective discretization leads to a higher value of the Smagorinsky coefficient C(S) required to achieve minimal total error at given resolution. Conversely, changing only the viscous flux discretization to fourth-order accuracy implies that optimal simulation results are obtained at lower values of C(S). Finally, a fully fourth-order discretization yields an optimal C(S) that is slightly lower than the reference fully second-order method.

Nonlocal modulation of the energy cascade in broadband-forced turbulence.

Classically, large-scale forced turbulence is characterized by a transfer of energy from large to small scales via nonlinear interactions. We have investigated the changes in this energy transfer process in broadband forced turbulence where an additional perturbation of flow at smaller scales is introduced. The modulation of the energy dynamics via the introduction of forcing at smaller scales occurs not only in the forced region but also in a broad range of length scales outside the forced bands due to nonlocal triad interactions. Broadband forcing changes the energy distribution and energy transfer function in a characteristic manner leading to a significant modulation of the turbulence. We studied the changes in this transfer of energy when changing the strength and location of the small-scale forcing support. The energy content in the larger scales was observed to decrease, while the energy transport power for scales in between the large and small scale forcing regions was enhanced. This was investigated further in terms of the detailed transfer function between the triad contributions and observing the long-time statistics of the flow. The energy is transferred toward smaller scales not only by wave numbers of similar size as in the case of large-scale forced turbulence, but by a much wider extent of scales that can be externally controlled.