Full-lung simulations of mechanically ventilated lungs incorporating recruitment/derecruitment dynamics.

This study developed and investigated a comprehensive multiscale computational model of a mechanically ventilated ARDS lung to elucidate the underlying mechanisms contributing to the development or prevention of VILI. This model is built upon a healthy lung model that incorporates realistic airway and alveolar geometry, tissue distensibility, and surfactant dynamics. Key features of the ARDS model include recruitment and derecruitment (RD) dynamics, alveolar tissue viscoelasticity, and surfactant deficiency. This model successfully reproduces realistic pressure-volume (PV) behavior, dynamic surface tension, and time-dependent descriptions of RD events as a function of the ventilation scenario. Simulations of Time-Controlled Adaptive Ventilation (TCAV) modes, with short and long durations of exhalation (T Low - and T Low +, respectively), reveal a higher incidence of RD for T Low + despite reduced surface tensions due to interfacial compression. This finding aligns with experimental evidence emphasizing the critical role of timing in protective ventilation strategies. Quantitative analysis of energy dissipation indicates that while alveolar recruitment contributes only a small fraction of total energy dissipation, its spatial concentration and brief duration may significantly contribute to VILI progression due to its focal nature and higher intensity. Leveraging the computational framework, the model may be extended to facilitate the development of personalized protective ventilation strategies to enhance patient outcomes. As such, this computational modeling approach offers valuable insights into the complex dynamics of VILI that may guide the optimization of ventilation strategies in ARDS management.

Splitting of a three-dimensional liquid plug at an airway bifurcation.

Employing the moving particles' semi-implicit (MPS) method, this study presents a numerical framework for solving the Navier-Stokes equations for the propagation and the split of a liquid plug through a three-dimensional air-filled bifurcating tube, where the inner surface is coated by a thin fluid film, and surface tension acts on the air-liquid interface. The detailed derivation of a modified MPS method to handle the air-liquid interface of liquid plugs is presented. When the front air-liquid interface of the plug splits at the bifurcation, the interface deforms quickly and causes large wall shear stress. We observe that the presence of a transverse gravitational force causes asymmetries in plug splitting, which becomes more pronounced as the capillary number decreases or the Bond number increases. We also observe that there exists a critical capillary number below which the plug does not split into two daughter tubes but propagates into the lower daughter tube only. In order to deliver the plug into the upper daughter tube, the driving pressure to push the plug is required to overcome the hydrostatic pressure due to gravity. These tendencies agree with our previous experimental and theoretical studies.

Surfactant-Mediated Airway and Acinar Interactions in a Multi-Scale Model of a Healthy Lung.

We present a computational multi-scale model of an adult human lung that combines dynamic surfactant physicochemical interactions and parenchymal tethering between ~16 generations of airways and subtended acini. This model simulates the healthy lung by modeling nonlinear stress distributions from airway/alveolar interdependency. In concert with multi-component surfactant transport processes, this serves to stabilize highly compliant interacting structures. This computational model, with ~10 k degrees of freedom, demonstrates physiological processes in the normal lung such as multi-layer surfactant transport and pressure-volume hysteresis behavior. Furthermore, this model predicts non-equilibrium stress distributions due to compliance mismatches between airway and alveolar structures. This computational model provides a baseline for the exploration of multi-scale interactions of pathological conditions that can further our understanding of disease processes and guide the development of protective ventilation strategies for the treatment of acute respiratory distress syndrome (ARDS).

Cell trapping in Y-junction microchannels: A numerical study of the bifurcation angle effect in inertial microfluidics.

The majority of microfluidic technologies for cell sorting and isolation involve bifurcating (e.g., Y- or T-shaped junction) microchannels to trap the cells of a specific type. However, the microfluidic trapping efficiency remains low, independently of whether the cells are separated by a passive or an active sorting method. Using a custom computational algorithm, we studied the migration of separated deformable cells in a Y-junction microchannel, with a bifurcation angle ranging from 30° to 180°. Single or two cells of initially spherical shape were considered under flow conditions corresponding to inertial microfluidics. Through the numerical simulation, we identified the effects of cell size, cytoplasmic viscoelasticity, cortical tension, flow rate, and bifurcation angle on the critical separation distance for cell trapping. The results of this study show that the trapping and isolation of blood cells, and circulating tumor cells in a Y-junction microchannel was most efficient and least dependent on the flow rate at the bifurcation angle of 120°. At this angle, the trapping efficiency for white blood cells and circulating tumor cells increased, respectively, by 46% and 43%, in comparison with the trapping efficiency at 60°. The efficiency to isolate invasive tumor cells from noninvasive ones increased by 32%. This numerical study provides important design criteria to optimize microfluidic technology for deformability-based cell sorting and isolation.

Microscale to mesoscale analysis of parenchymal tethering: the effect of heterogeneous alveolar pressures on the pulmonary mechanics of compliant airways.

In the healthy lung, bronchi are tethered open by the surrounding parenchyma; for a uniform distribution of these peribronchial structures, the solution is well known. An open question remains regarding the effect of a distributed set of collapsed alveoli, as can occur in disease. Here, we address this question by developing and analyzing microscale finite-element models of systems of heterogeneously inflated alveoli to determine the range and extent of parenchymal tethering effects on a neighboring collapsible airway. This analysis demonstrates that micromechanical stresses extend over a range of ∼5 airway radii, and this behavior is dictated primarily by the fraction, not distribution, of collapsed alveoli in that region. A mesoscale analysis of the microscale data identifies an effective shear modulus, Geff, that accurately characterizes the parenchymal support as a function of the average transpulmonary pressure of the surrounding alveoli. We demonstrate the use of this formulation by analyzing a simple model of a single collapsible airway surrounded by heterogeneously inflated alveoli (a "pig-in-a-blanket" model), which quantitatively demonstrates the increased parenchymal compliance and reduction in airway caliber that occurs with decreased parenchymal support from hypoinflated obstructed alveoli. This study provides a building block from which models of an entire lung can be developed in a computationally tenable manner that would simulate heterogeneous pulmonary mechanical interdependence. Such multiscale models could provide fundamental insight toward the development of protective ventilation strategies to reduce the incidence or severity of ventilator-induced lung injury. NEW & NOTEWORTHY A destabilized lung leads to airway and alveolar collapse that can result in catastrophic pulmonary failure. This study elucidates the micromechanical effects of alveolar collapse and determines its range of influence on neighboring collapsible airways. A mesoscale analysis reveals a master relationship that can that can be used in a computationally efficient manner to quantitatively model alveolar mechanical heterogeneity that exists in acute respiratory distress syndrome (ARDS), which predisposes the lung to volutrauma and/or atelectrauma. This analysis may lead to computationally tenable simulations of heterogeneous organ-level mechanical interactions that can illuminate novel protective ventilation strategies to reduce ventilator-induced lung injury.

Rapid Turnover and High Production Rate of Myeloid Cells in Adult Rhesus Macaques with Compensations during Aging.

Neutrophils, basophils, and monocytes are continuously produced in bone marrow via myelopoiesis, circulate in blood, and are eventually removed from circulation to maintain homeostasis. To quantitate the kinetics of myeloid cell movement during homeostasis, we applied 5-bromo-2'-deoxyuridine pulse labeling in healthy rhesus macaques (Macaca mulatta) followed by hematology and flow cytometry analyses. Results were applied to a mathematical model, and the blood circulating half-life and daily production, respectively, of each cell type from macaques aged 5-10 y old were calculated for neutrophils (1.63 ± 0.16 d, 1.42 × 109 cells/l/d), basophils (1.78 ± 0.30 d, 5.89 × 106 cells/l/d), and CD14+CD16- classical monocytes (1.01 ± 0.15 d, 3.09 × 108 cells/l/d). Classical monocytes were released into the blood circulation as early as 1 d after dividing, whereas neutrophils remained in bone marrow 4-5 d before being released. Among granulocytes, neutrophils and basophils exhibited distinct kinetics in bone marrow maturation time and blood circulation. With increasing chronological age, there was a significant decrease in daily production of neutrophils and basophils, but the half-life of these granulocytes remained unchanged between 3 and 19 y of age. In contrast, daily production of classical monocytes remained stable through 19 y of age but exhibited a significant decline in half-life. These results demonstrated relatively short half-lives and continuous replenishment of neutrophils, basophils, and classical monocytes during homeostasis in adult rhesus macaques with compensations observed during increasing chronological age.

Reduced-Dimension Modeling Approach for Simulating Recruitment/De-recruitment Dynamics in the Lung.

Acute respiratory distress syndrome is a pulmonary disease that requires the use of mechanical ventilation for patient recovery. However, this can lead to development of ventilator-induced lung injury caused by the over-distension of alveolar tissue and by the repetitive closure (de-recruitment) and reopening (recruitment) of airways. In this study, we developed a multi-scale model of the lung from a reduced-dimension approach to investigate the dynamics of ventilation in the lung during airway collapse and reopening. The model consisted of an asymmetric network geometry with 16 generations of liquid-lined airways with airflow driven by a variable pleural pressure. During the respiratory cycle changes in airway radii and film thickness yield the formation of liquid plugs that propagate and rupture throughout the airway network. Simulations were conducted with constant surface tension values [Formula: see text] dyn/cm. It was observed that the time onset of plug creation and rupture depended on the surface tension, as well as the plug aggregation/splitting behavior at bifurcations. Additionally, the plug propagation behavior was significantly influenced by presence of plugs in adjacent airways (i.e. parent and daughters) that affected the driving pressure distribution locally at bifurcations and resulted in complex aggregation and splitting behavior. This model provides an approach that has the ability to simulate normal and pathophysiological lung conditions with the potential to be used in personalized clinical medicine.

[A case of bladder cancer with metastasis to the bone of the hand].

Metastasis to the bone of the hand is rare. In addition, metastasis to the bone of the hand from bladder cancer is extremely rare. We herein report a case of distal phalanx metastasis from bladder cancer. A 64- year-old man who was diagnosed with bladder cancer (cT2bN0M0) received total cystectomy (pT3bN2). Two months after the surgery, a roentgenogram revealed lung metastasis. Then we administered 2 cycles of chemotherapy using gemcitabine and cisplatin. Computed tomography revealed a partial response. However, several months after chemotherapy, we noted that his left ring finger was swollen and showed erythema. We made a diagnosis of metastasis to the distal phalanx of the left ring finger and amputated the finger. Pathological findings showed no conflict with metastasis from bladder cancer. Postoperative course was good, but he died about three months after the diagnosis of metastasis.

A model of surfactant-induced surface tension effects on the parenchymal tethering of pulmonary airways.

We developed a computational model of lung parenchyma, which is comprised of individual alveolar chamber models. Each alveolus is modeled by a truncated octahedron. Considering the force balance between the elastin and collagen fibers laying on the alveolar membrane and the pressures acting on the membrane, we computed the deformations of the parenchyma with a finite element method. We focused on the effect of surfactant on the force of parenchymal tethering an airway. As the lung inflates, the parenchyma becomes stiffer and the tethering force becomes stronger. As the alveolar surfactant concentration is reduced, the lung volume at a fixed alveolar pressure decreases, and thus, the tethering force becomes weaker. The distortion of parenchyma caused by the deformation of an airway extends widely around the airway. The displacement of parenchyma decays with distance from the airway wall, but deviates from the prediction based on a theory for a continuum material. Using results obtained from the present lung parenchyma model, we also developed a simple 1-dimensional model for parenchyma tethering force on an airway, which could be utilized for the analysis of liquid/gas transports in an axis-symmetric elastic airway. The effective shear modulus was calculated from the pressure-volume relation of parenchyma. By manipulating the pressure-volume curve, this simple model may be used to predict the parenchyma tethering force in diseased lungs.

[Early initiation of antiplatelet therapy after urological surgery : a prospective study].

In recent times, the number of patients receiving antiplatelet drugs for the prevention of cardiovascular and cerebrovascular diseases has been increasing. We examined the possibility of early initiation of antiplatelet therapy after urological operations. Between April 2008 and February 2009, 62 patients who received antiplatelet drugs and underwent urological surgeries (open surgery, transurethral surgery and laparoscopic surgery) and prostate biopsies were examined. Of the 62 patients, 59 were randomized into 2 groups ; 32 patients receiving antiplatelet treatment initiation within 24 hours (early group) and 29 patients receiving this treatment more than 24 hours (late group) after the urological operation. The end point of this study was the re-cessation of antiplatelet therapy because of the development of postoperative complications (hematuria, blood loss, etc.) and cardiovascular and cerebrovascular events within 1 month. There was no significant difference in the urological events observed between these groups, including 2 of the 32 (6.3%) patients in the early group and 3 of the 27 (11.1%) in the late group. Cardiovascular and cerebrovascular diseases were not noted in any of the patients within 1 month. In conclusion, we think that it is possible to initiate antiplatelet therapy within 24 hours after urological operations and prostate biopsies in the absence of active blood loss. Early initiation may prevent the risk of cardiovascular and cerebrovascular disease in the future.

[Clinical studies on renal cell carcinoma].

PURPOSE: We reviewed 193 patients of renal cell carcinoma treated at Osaka Police Hospital between 1990 and 2006. METHODS: The patients consisted of 140 males and 53 females. The median age was 62 years, ranging from 26 to 88 years. Median follow-up period was 53 months. TNM system and pathologic findings were classified in accordance with the Japanese General Rules for Clinical and Pathological Studies on Renal Cell Carcinoma. Survival rates were calculated using the Kaplan-Meier method, and differences in survival curves were estimated with the log-rank test. Independent prognostic factors were analyzed using the Cox proportional hazards model. RESULTS & CONCLUSIONS: The overall 3, 5, 10 and 15-year cause-specific survival rates were 92.6, 91.1, 86.1, 72.2%, respectively. Univariate analysis indicated age, chief complaint, performance status, tumor size, anemia, CRP, tumor extent, grade, infiltrating pattern, venous involvement, lymph node metastasis, distant metastasis, stage to be significant prognostic factors. Moreover, multivariate analysis with Cox's proportional hazard model revealed high age (60 < or =), positive CRP, and T4 to be independent poor prognosticators for cause specific survival. Using these three risk factors, patients with 0, 1, 2, and 3 poor risk factors were classified as 0, 1, 2, and 3 risk groups, respectively. The overall 5 and 10-year cause specific survival rates in 0, 1, 2, and 3 risk groups were 100 and 100%, 90.8 and 83.8%, 71.6 and 34.1%, 0 and 0%, respectively. The overall 5 and 10-year cause specific survival rates (69.2 and 33.0%) especially in 2 and 3 risk groups were significantly poor prognosis, comparing with those (94.8 and 91.9%) in 0 and 1 risk group (p< 0.0001). Thus, the intensity of the follow up period and the necessity of postoperative adjuvant therapy for a patient are recommended for 2 and 3 risk groups.

Biofluid mechanics of special organs and the issue of system control. Sixth International Bio-Fluid Mechanics Symposium and Workshop, March 28-30, 2008 Pasadena, California.

In the field of fluid flow within the human body, focus has been placed on the transportation of blood in the systemic circulation since the discovery of that system; but, other fluids and fluid flow phenomena pervade the body. Some of the most fascinating fluid flow phenomena within the human body involve fluids other than blood and a service other than transport--the lymphatic and pulmonary systems are two striking examples. While transport is still involved in both cases, this is not the only service which they provide and blood is not the only fluid involved. In both systems, filtration, extraction, enrichment, and in general some "treatment" of the fluid itself is the primary function. The study of the systemic circulation has also been conventionally limited to treating the system as if it were an open-loop system governed by the laws of fluid mechanics alone, independent of physiological controls and regulations. This implies that system failures can be explained fully in terms of the laws of fluid mechanics, which of course is not the case. In this paper we examine the clinical implications of these issues and of the special biofluid mechanics issues involved in the lymphatic and pulmonary systems.

The effect of viscoelasticity on the stability of a pulmonary airway liquid layer.

The lungs consist of a network of bifurcating airways that are lined with a thin liquid film. This film is a bilayer consisting of a mucus layer on top of a periciliary fluid layer. Mucus is a non-Newtonian fluid possessing viscoelastic characteristics. Surface tension induces flows within the layer, which may cause the lung's airways to close due to liquid plug formation if the liquid film is sufficiently thick. The stability of the liquid layer is also influenced by the viscoelastic nature of the liquid, which is modeled using the Oldroyd-B constitutive equation or as a Jeffreys fluid. To examine the role of mucus alone, a single layer of a viscoelastic fluid is considered. A system of nonlinear evolution equations is derived using lubrication theory for the film thickness and the film flow rate. A uniform film is initially perturbed and a normal mode analysis is carried out that shows that the growth rate g for a viscoelastic layer is larger than for a Newtonian fluid with the same viscosity. Closure occurs if the minimum core radius, R(min)(t), reaches zero within one breath. Solutions of the nonlinear evolution equations reveal that R(min) normally decreases to zero faster with increasing relaxation time parameter, the Weissenberg number We. For small values of the dimensionless film thickness parameter epsilon, the closure time, t(c), increases slightly with We, while for moderate values of epsilon, ranging from 14% to 18% of the tube radius, t(c) decreases rapidly with We provided the solvent viscosity is sufficiently small. Viscoelasticity was found to have little effect for epsilon>0.18, indicating the strong influence of surface tension. The film thickness parameter epsilon and the Weissenberg number We also have a significant effect on the maximum shear stress on tube wall, max(tau(w)), and thus, potentially, an impact on cell damage. Max(tau(w)) increases with epsilon for fixed We, and it decreases with increasing We for small We provided the solvent viscosity parameter is sufficiently small. For large epsilon approximately 0.2, there is no significant difference between the Newtonian flow case and the large We cases.

[A case report: retroperitoneoscopic nephrectomy for a giant hydronephrosis of a horseshoe kidney].

A 30-year-old female was referred to our hospital complaining of left flank pain. She was diagnosed with a giant hydronephrosis in a horseshoe kidney. We performed a retroperitoneoscopic nephrectomy on the non-functioning moiety of the horseshoe kidney. After the placement of a ureteral catheter, she underwent a retroperitoneal nephrectomy. The feeding vessels consisted of four arteries and four veins. The thin isthmus of the horseshoe kidney was divided using scissors, without the need for electrocautery, and hemostasis was achieved using monopolar shears. Laparoscopic nephrectomy on a horseshoe kidney is a difficult surgery given the aberrant vessels and isthmus, so it tends to be avoided for reasons of safety. However, if appropriate preoperative imaging is carried out and the procedure is conducted in a careful manner, it can be made a safe and minimally invasive operation.

[Primary signet-ring cell carcinoma of the urinary bladder: a case report].

We report a case of signet-ring cell carcinoma of the urinary bladder. A 60-year-old man was hospitalized because of total macrohematuria. Cystoscopic examination revealed a non-papillary sessile tumor on the posterior wall of the urinary bladder. The pathological diagnosis was stage pT1 signet ring cell carcinoma. Upper gastrointestinal endoscopy and computed tomographic scanning revealed no involvement of other organs. Radical cystectomy and creation of an ileal neobladder were performed. The histopathological stage was pT3aN0M0. Adjuvant chemotherapy (TS-1) was performed and the patient is currently free from disease at eight months after the surgery. This disease is usually diagnosed at an advanced stage and has a poor prognosis. To our knowledge, this is the first case report on the creation of an ileal neobladder for the treatment of primary signet-ring cell carcinoma of the urinary bladder.

[Scrotal hematoma associated with idiopathic thrombocytosis: a case report].

We report a case of acute scrotal hematoma associated with idiopathic thrombocytosis. A 75-year-old man visited our hospital for the treatment of a left scrotal mass that had been increasing in size; the mass had developed after the puncture of left testicular hydrocele. The patient was diagnosed with acute scrotal hematoma on the basis of ultrasonography findings. The patient underwent an emergency operation for the removal of the hematoma. On 2 days after the surgery we noticed an increase in the size of the hematoma. The patient had a 4-year clinical history of idiopathic thrombocytosis for which he had not received any treatment. Although the platelet count was slightly high at the time of the operation, complete hemostasis did not occur because of the existence of platelet dysfunction. The second hematoma was treated conservatively. To our knowledge, this is the first case report on the acute scrotal hematoma associated with idiopathic thrombocytosis.

Effects of respiratory rate and tidal volume on gas exchange in total liquid ventilation.

Using a rabbit model of total liquid ventilation (TLV), and in a corresponding theoretical model, we compared nine tidal volume-respiratory rate combinations to identify a ventilator strategy to maximize gas exchange, while avoiding choked flow, during TLV. Nine different ventilation strategies were tested in each animal (n = 12): low [LR = 2.5 breath/min (bpm)], medium (MR = 5 bpm), or high (HR = 7.5 bpm) respiratory rates were combined with a low (LV = 10 ml/kg), medium (MV = 15 ml/kg), or high (HV = 20 ml/kg) tidal volumes. Blood gases and partial pressures, perfluorocarbon gas content, and airway pressures were measured for each combination. Choked flow occurred in all high respiratory rate-high volume animals, 71% of high respiratory rate-medium volume (HRMV) animals, and 50% of medium respiratory rate-high volume (MRHV) animals but in no other combinations. Medium respiratory rate-medium volume (MRMV) resulted in the highest gas exchange of the combinations that did not induce choke. The HRMV and MRHV animals that did not choke had similar or higher gas exchange than MRMV. The theory predicted this behavior, along with spatial and temporal variations in alveolar gas partial pressures. Of the combinations that did not induce choked flow, MRMV provided the highest gas exchange. Alveolar gas transport is diffusion dominated and rapid during gas ventilation but is convection dominated and slow during TLV. Consequently, the usual alveolar gas equation is not applicable for TLV.

[Renal transection conservatively treated three times by selectively transarterial embolization (TAE): a case report].

A 12-year-old-man presented with left flank pain after a traffic accident on October 14, 2006. Computed tomography (CT) revealed major left renal hematoma and transection (IIIb). Selectively transarterial embolization (TAE) was performed to control upper transected renal bleeding on the same day, and again to do rebleeding two days later. Because CT revealed left perirenal urinoma caused by upper transected kidney on October 18, TAE was performed for the upper transected kidney not to function. Five months after left renal injury, CT demonstrated the left kidney successfully preserved without hydronephrosis, urinoma and hematoma. The patient was well and could be conservatively treated without hypertension and other complications. In previous reports, only a part of renal injury (III) cases with conservative treatment converted to nephrectomy, whereas approximately half of them with surgical treatment resulted in nephrectomy. Therefore, it is important to treat them as conservatively as possible and to preserve renal function, even in cases of major renal blunt injury.

Liquid and surfactant delivery into pulmonary airways.

We describe the mechanisms by which liquids and surfactants can be delivered into the pulmonary airways. These are instilled and transported throughout the lung in clinical therapies such as surfactant replacement therapy, partial liquid ventilation and drug delivery. The success of these treatments is contingent on the liquid distribution and the delivery to targeted regions of the lung. The targeting of a liquid plug can be influenced by a variety of factors such as the physical properties of the liquid, the interfacial activity, the gravitational orientation, instillation method and propagation speed. We provide a review of experimental and theoretical studies that examine these effects in single tubes or channels, in tubes with single bifurcations and in the whole lung.

Pulsatile flow and oxygen transport past cylindrical fiber arrays for an artificial lung: computational and experimental studies.

The influence of time-dependent flows on oxygen transport from hollow fibers was computationally and experimentally investigated. The fluid average pressure drop, a measure of resistance, and the work required by the heart to drive fluid past the hollow fibers were also computationally explored. This study has particular relevance to the development of an artificial lung, which is perfused by blood leaving the right ventricle and in some cases passing through a compliance chamber before entering the device. Computational studies modeled the fiber bundle using cylindrical fiber arrays arranged in in-line and staggered rectangular configurations. The flow leaving the compliance chamber was modeled as dampened pulsatile and consisted of a sinusoidal perturbation superimposed on a steady flow. The right ventricular flow was modeled to depict the period of rapid flow acceleration and then deceleration during systole followed by zero flow during diastole. Experimental studies examined oxygen transfer across a fiber bundle with either steady, dampened pulsatile, or right ventricular flow. It was observed that the dampened pulsatile flow yielded similar oxygen transport efficiency to the steady flow, while the right ventricular flow resulted in smaller oxygen transport efficiency, with the decrease increasing with Re. Both computations and experiments yielded qualitatively similar results. In the computational modeling, the average pressure drop was similar for steady and dampened pulsatile flows and larger for right ventricular flow while the pump work required of the heart was greatest for right ventricular flow followed by dampened pulsatile flow and then steady flow. In conclusion, dampening the artificial lung inlet flow would be expected to maximize oxygen transport, minimize work, and thus improve performance.