Cell-Based Therapy for the Deficient Urinary Sphincter

When sterile culture techniques of mammalian cells first became state of the art, there was tremendous anticipation that such cells could be eventually applied for therapeutic purposes. The discovery of adult human stem or progenitor cells further motivated scientists to pursue research in cell-based therapies. Although evidence from animal studies suggests that application of cells yields measurable benefits, in urology and many other disciplines, progenitor-cell-based therapies are not yet routinely clinically available. Stress urinary incontinence (SUI) is a condition affecting a large number of patients. The etiology of SUI includes, but is not limited to, degeneration of the urinary sphincter muscle tissue and loss of innervation, as well as anatomical and biomechanical causes. Therefore, different regimens were developed to treat SUI. However, at present, a curative functional treatment is not at hand. A progenitor-cell-based therapy that can tackle the etiology of incontinence, rather than the consequences, is a promising strategy. Therefore, several research teams have intensified their efforts to develop such a therapy for incontinence. Here, we introduce candidate stem and progenitor cells suitable for SUI treatment, show how the functional homogeneity and state of maturity of differentiated cells crucial for proper tissue integration can be assessed electrophysiologically prior to their clinical application, and discuss the trophic potential of adult mesenchymal stromal (or stem) cells in regeneration of neuronal function.     

Experimental and Numerical Investigation of an Axial Rotary Blood Pump

Left ventricular assist devices (LVADs) have become a standard therapy for patients with severe heart failure. As low blood trauma in LVADs is important for a good clinical outcome, the assessment of the fluid loads inside the pump is critical. More specifically, the flow features on the surfaces where the interaction between blood and artificial material happens is of great importance. Therefore, experimental data for the near‐wall flows in an axial rotary blood pump were collected and directly compared to computational fluid dynamic results. For this, the flow fields based on unsteady Reynolds‐averaged Navier–Stokes simulations‐computational fluid dynamics (URANS‐CFD) of an axial rotary blood pump were calculated and compared with experimental flow data at one typical state of operation in an enlarged model of the pump. The focus was set on the assessment of wall shear stresses (WSS) at the housing wall and rotor gap region by means of the wall‐particle image velocimetry technique, and the visualization of near‐wall flow structures on the inner pump surfaces by a paint erosion method. Additionally, maximum WSS and tip leakage volume flows were measured for 13 different states of operation. Good agreement between CFD and experimental data was found, which includes the location, magnitude, and direction of the maximum and minimum WSS and the presence of recirculation zones on the pump stators. The maximum WSS increased linearly with pressure head. They occurred at the upstream third of the impeller blades and exceeded the critical values with respect to hemolysis. Regions of very high shear stresses and recirculation zones could be identified and were in good agreement with simulations. URANS‐CFD, which is often used for pump performance and blood damage prediction, seems to be, therefore, a valid tool for the assessment of flow fields in axial rotary blood pumps. The magnitude of maximum WSS could be confirmed and were in the order of several hundred Pascal.     

Older patients with low Charlson score and high-risk prostate cancer benefit from radical prostatectomy

Introduction

The aim of the study was to identify the appropriate level of Charlson comorbidity index (CCI) in older patients (>70 years) with high-risk prostate cancer (PCa) to achieve survival benefit following radical prostatectomy (RP).

Methods

We retrospectively analyzed 1008 older patients (>70 years) who underwent RP with pelvic lymph node dissection for high-risk prostate cancer (preoperative prostate-specific antigen >20 ng/mL or clinical stage ≥T2c or Gleason ≥8) from 14 tertiary institutions between 1988 and 2014. The study population was further grouped into CCI < 2 and ≥2 for analysis. Survival rate for each group was estimated with Kaplan–Meier method and competitive risk Fine-Gray regression to estimate the best explanatory multivariable model. Area under the curve (AUC) and Akaike information criterion were used to identify ideal ‘Cut off’ for CCI.

Results

The clinical and cancer characteristics were similar between the two groups. Comparison of the survival analysis using the Kaplan–Meier curve between two groups for non-cancer death and survival estimations for 5 and 10 years shows significant worst outcomes for patients with CCI ≥ 2. In multivariate model to decide the appropriate CCI cut-off point, we found CCI 2 has better AUC and p value in log rank test.

Conclusion

Older patients with fewer comorbidities harboring high-risk PCa appears to benefit from RP. Sicker patients are more likely to die due to non-prostate cancer-related causes and are less likely to benefit from RP.

     

Establishment and characterization of two distinct malignant mesothelioma cell lines with common clonal origin

We describe two newly established malignant mesothelioma (MM) cell lines derived from a pleural effusion of a male. One cell line, designated as MM-Z03E, reveals an epithelioid cobblestone morphology, while the second one, designated as MM-Z03S and subcloned after in vivo selection, exhibits a sarcomatoid storiform growth pattern. Both cell lines showed the immunologic profile characteristic for MM (i.e., expression of cytokeratin, CK18, calretinin, and vimentin in both phenotypes). Cytogenetics, multicolor fluorescence in situ hybridization, comparative genomic hybridization, and oligonucleotide array CGH were performed on both cell lines. Aberrations shared by both cell lines included chromosomal losses of 1q34 approximately qter, 4, 9p, 10p, 13, 14, 16q, 18, and 22, as well as a complex structural aberration involving chromosome 17. Aberrations exclusive to MM-Z03E included gains of 3q11q27 and 5p, while gain of 9q and losses of 3q27qter, 11q, and 18 in MM-Z03S were exclusive to MM-Z03E. Both cell lines were able to develop solid transplant tumors in nude mice within 16 weeks, and immunophenotyping of tumor xenografts revealed an overall retained expression profile of the markers used. Remarkably, one xenograft from MM-Z03E revealed overexpression of p53 and widely invasive growth. In conclusion, both cell lines are useful in vivo and in vitro model systems to study the underlying genetic mechanisms of biphasic differentiation in MM, which can be of certain value considering the increasing relevance of assessing MM tumor biology for the clinical management of this disease.     

The wear and tear on health: What is the role of occupation?

Health is well known to show a clear gradient by occupation. Although it may appear evident that occupation can affect health, there are multiple possible sources of selection that can generate a strong association, other than simply a causal effect of occupation on health. We link job characteristics to German panel data spanning 29 years to characterize occupations by their physical and psychosocial burden. Employing a dynamic model to control for factors that simultaneously affect health and selection into occupation, we find that selection into occupation accounts for at least 60% of the association. The effects of occupational characteristics such as physical strain and low job control are negative and increase with age: late‐career exposure to 1 year of high physical strain and low job control is comparable to the average health decline from ageing 16 and 6 months, respectively.     

Effect of reverse total shoulder arthroplasty humeral inclination on glenohumeral range of motion,deltoid force,and glenoid strain: a biomechanical study

BackgroundReverse total shoulder arthroplasty (RSA) primarily varies between 2 implant design options: a 135 humeral stem inclination that closely resembles anatomic orientation, versus the Grammont-style 155 humeral stem inclination that further medializes and distalizes the center of rotation (COR). The purpose of this study was to compare deltoid force, glenoid strain, and simulated glenohumeral range of motion (ROM) between RSA 135 and RSA 155 designs, with a series of standardized permutations of glenosphere offset and rotator cuff pathology.MethodsTwelve fresh-frozen cadaveric shoulder specimens were studied using a shoulder simulator. Native shoulder motion profiles for reproducible abduction range of motion were established using a customized testing device. Optical 3-dimensional tracking and pressure sensors were used to accurately record glenohumeral range of motion (ROM), deltoid force, and glenoid strain for RSA 135 and RSA 155 designs. For each cohort, all combinations of glenosphere offsets and rotator cuff tendon involvement were evaluated.ResultsThere was no significant difference in the overall abduction ROM between the 155 and the 135 humeral stem implants (P = .75). Resting abduction angle and maximum abduction angle were significantly greater with a 155 + STD (standard offset) construct than with a 135 + STD construct (P < .001 and P = .01, respectively). Both stem inclinations decreased combined deltoid force requirements as compared the native shoulder with a massive cuff tear. Effective glenoid strain did not vary significantly between 135 + STD and 155 + STD constructs (P = .66).ConclusionOverall, range of motion between the 135 and the 155 humeral stem inclinations was not significantly different. The cumulative deltoid force was lower in RSA shoulders when compared to native shoulders with massive rotator cuff tears, highlighting the utility of both implant designs. The Grammont-style 155 stem coupled with a 2.5 mm inferior offset glenosphere required less deltoid force to reach maximum abduction than did the more anatomic, lateralized 135 stem coupled with a 4 mm lateral offset glenosphere.Level of EvidenceBasic Science, Biomechanics Controlled Laboratory Study     

Comparison of Hemodynamics in the Ascending Aorta Between Pulsatile and Continuous Flow Left Ventricular Assist Devices Using Computational Fluid Dynamics Based on Computed Tomography Images

This study aims to investigate differences in hemodynamic conditions in the thoracic aorta for pulsatile and continuous‐flow left ventricular assist devices (LVADs) using computational fluid dynamics (CFD). Patient‐specific models were reconstructed from three patients with continuous‐flow LVAD (HeartMate II, Thoratec Corporation) and three patients with biventricular assist devices (Excor, Berlin Heart) where only the aortic part was included in the simulations. CFD simulations were performed with constant inflow for the continuous‐flow LVADs and time‐varying inflow for the pulsatile devices. Differences in flow patterns, wall shear stress (WSS), and dynamic pressure in the ascending aorta were compared for both cases. Retrograde flow patterns were observed in all cases proximal to the location of the outflow cannula anastomosis site. On average, dynamic pressures derived from the retrograde flow velocities were higher in the continuous‐flow group with large variations dependent on the angle of the cannula anastomosis relative to the ascending aorta (continuous group: 0.14 ± 0.2 mm Hg, pulsatile group: 0.013 ± 0.008 mm Hg). Elevated WSS contralaterally to the anastomosis site was observed in three of the six models with higher values for the continuous cases. Lower WSS and reduced pressure in the ascending aorta, both favorable hemodynamic conditions, were found in pulsatile versus continuous‐flow LVADs by means of CFD. These findings indicate, along with clinical observations reported by others, the superior performance of pulsatile LVADs.