Reversed shoulder arthroplasty as treatment for late or ancient chronic glenohumeral dislocation.

Chronic glenohumeral dislocation is a rare entity and several treatment options have been proposed. The aim of this study is to report the long-term follow-up of the reversed shoulder arthroplasty in patients with chronic glenohumeral dislocation. A retrospective analysis of all patients between January 2002 and December 2012 that were treated with a reversed shoulder arthroplasty for chronic anterior glenohumeral dislocations was performed. Pre-operative CT evaluation of the bone loss and fatty degeneration of the rotator cuff muscles was performed. Pre- and postoperative Constant-Murley score was evaluated. 6 patients (4 males and 2 females) with anterior glenohumeral dislocations were evaluated. Average age was 73 years (between 65-86 years). The average time of dislocation was 18 weeks (between 4 and 52 weeks). Average time of follow-up was 39 months (between 12 and 90 months). The CM improved from 33 (between 17 and 45) pre-op to 76 postop (between 55 and 89). No postoperative complications were observed. Reversed shoulder arthroplasty gives good results in case of chronic glenohumeral dislocation.

Influence of valve size, orientation and downstream geometry of an aortic BMHV on leaflet motion and clinically used valve performance parameters.

The aim of this study was to reconcile some of our own previous work and the work of others to generate a physiologically realistic numerical simulation environment that allows to virtually assess the performance of BMHVs. The model incorporates: (i) a left ventricular deformable model to generate a physiological inflow to the aortic valve; (ii) a patient-specific aortic geometry (root, arch and descending aorta); (iii) physiological pressure and flow boundary conditions. We particularly studied the influence of downstream geometry, valve size and orientation on leaflet kinematics and functional indices used in clinical routine. Compared to the straight tube geometry, the patient-specific aorta leads to a significant asynchronous movement of the valve, especially during the closing of the valve. The anterior leaflet starts to close first, impacts the casing at the closed position and remains in this position. At the same time, the posterior leaflet impacts the pivoting mechanisms at the fully open position. At the end of systole, this leaflet subsequently accelerates to the closed position, impacting the casing with an angular velocity of approximately -477 rad/s. The valve size greatly influences the transvalvular pressure gradient (TPG), but does not change the overall leaflet kinematics. This is in contrast to changes in valve orientation, where changing valve orientation induces large differences in leaflet kinematics, but the TPG remains approximately the same.

Validation of a numerical FSI simulation of an aortic BMHV by in vitro PIV experiments.

In this paper, a validation of a recently developed fluid-structure interaction (FSI) coupling algorithm to simulate numerically the dynamics of an aortic bileaflet mechanical heart valve (BMHV) is performed. This validation is done by comparing the numerical simulation results with in vitro experiments. For the in vitro experiments, the leaflet kinematics and flow fields are obtained via the particle image velocimetry (PIV) technique. Subsequently, the same case is numerically simulated by the coupling algorithm and the resulting leaflet kinematics and flow fields are obtained. Finally, the results are compared, revealing great similarity in leaflet motion and flow fields between the numerical simulation and the experimental test. Therefore, it is concluded that the developed algorithm is able to capture very accurately all the major leaflet kinematics and dynamics and can be used to study and optimize the design of BMHVs.

A statistical shape model of trochlear dysplasia of the knee.

BACKGROUND: Trochlear dysplasia is known as the primary predisposing factor for patellar dislocation. Current methods to describe trochlear dysplasia are mainly qualitative or based on a limited number of discrete measurements. The purpose of this study is to apply statistical shape analysis to take the full geometrical complexity of trochlear dysplasia into account. METHODS: Statistical shape analysis was applied to 20 normal and 20 trochlear dysplastic distal femur models, including the cartilage. RESULTS: This study showed that the trochlea was anteriorized, proximalized and lateralized and that the mediolateral width and the notch width were decreased in the trochlear dysplastic femur compared to the normal femur. The first three principal components of the trochlear dysplastic femurs, accounting for 79.7% of the total variation, were size, sulcus angle and notch width. Automated classification of the trochlear dysplastic and normal femora achieved a sensitivity of 85% and a specificity of 95%. CONCLUSIONS: This study shows that shape analysis is an outstanding method to visualise the location and magnitude of shape abnormalities. Improvement of automated classification and subtyping within the trochlear dysplastic group are expected when larger training sets are used. CLINICAL RELEVANCE: Classification of trochlear dysplasia, especially borderline cases may be facilitated by automated classification. Furthermore, the identification of a decreased notch width in association with an increased sulcus angle can also contribute to the diagnosis of trochlear dysplasia.

Computational models for wall shear stress estimation in scaffolds: a comparative study of two complete geometries.

Fluid mechanical stimuli are known to upregulate cell differentiation and matrix formation. Since wall shear stress plays an important role various studies tried to estimate the scaffold fluid dynamic environment. However, because of the geometrical complexity, nearly all studies created their CFD model based on a submodel of the entire scaffold assuming that the model covers heterogeneity sufficiently. However to the authors' knowledge no study exist providing guidelines in this matter. In a previous study we demonstrated that submodels are influenced by the boundary conditions, inevitable when flow channels are chopped off. For the current study we therefore developed µCT based models of two complete scaffold geometries (one titanium and one hydroxyapatite). Imposing a 0.04 ml/min flow rate resulted in a surface area averaged wall shear stress of 1.41 mPa for titanium and 1.09 mPa for hydroxyapatite. In order to get insight in required model size we subdivided the domain in regions of different size. From our results we propose a model size between 6 and 10 times the average pore size. The wall shears stress should be calculated on a region at least one pore size away from the boundaries. These guidelines could be of use for computationally more costly simulations where it is not possible to simulate the complete scaffold domain.

Absence of the Birt-Hogg-Dubé gene product is associated with increased hypoxia-inducible factor transcriptional activity and a loss of metabolic flexibility.

Under conditions of reduced tissue oxygenation, hypoxia-inducible factor (HIF) controls many processes, including angiogenesis and cellular metabolism, and also influences cell proliferation and survival decisions. HIF is centrally involved in tumour growth in inherited diseases that give rise to renal cell carcinoma (RCC), such as Von Hippel-Lindau syndrome and tuberous sclerosis complex. In this study, we examined whether HIF is involved in tumour formation of RCC in Birt-Hogg-Dubé syndrome. For this, we analysed a Birt-Hogg-Dubé patient-derived renal tumour cell line (UOK257) that is devoid of the Birt-Hogg-Dubé protein (BHD) and observed high levels of HIF activity. Knockdown of BHD expression also caused a threefold activation of HIF, which was not as a consequence of more HIF1α or HIF2α protein. Transcription of HIF target genes VEGF, BNIP3 and CCND1 was also increased. We found nuclear localization of HIF1α and increased expression of VEGF, BNIP3 and GLUT1 in a chromophobe carcinoma from a Birt-Hogg-Dubé patient. Our data also reveal that UOK257 cells have high lactate dehydrogenase, pyruvate kinase and 3-hydroxyacyl-CoA dehydrogenase activity. We observed increased expression of pyruvate dehydrogenase kinase 1 (a HIF gene target), which in turn leads to increased phosphorylation and inhibition of pyruvate dehydrogenase. Together with increased protein levels of GLUT1, our data reveal that UOK257 cells favour glycolytic rather than lipid metabolism (a cancer phenomenon termed the 'Warburg effect'). UOK257 cells also possessed a higher expression level of the L-lactate influx monocarboxylate transporter 1 and consequently utilized L-lactate as a metabolic fuel. As a result of their higher dependency on glycolysis, we were able to selectively inhibit the growth of these UOK257 cells by treatment with 2-deoxyglucose. This work suggests that targeting glycolytic metabolism may be used therapeutically to treat Birt-Hogg-Dubé-associated renal lesions.

In vitro, in vivo and numerical assessment of the working principle of the truCCOMS continuous cardiac output catheter system.

The truCCOMS cardiac output monitor system provides a continuous and instantaneous measurement of cardiac output, derived from the amount of energy required for heating a filament to maintain a fixed 2 degrees C blood temperature difference between two thermistors located distally on a pulmonary artery catheter. Clinical studies, however, reported relatively poor accuracy of the cardiac output estimation, possibly due to linearly assumed power-cardiac output relationship used for calibration of the catheters. We experimentally studied the shape of the truCCOMS calibration relationship (i) in a hydraulic bench model of the right heart and (ii) in vivo intact animal model. The results showed a nonlinear relationship between the power input into the heating element and the cardiac output; which could satisfactorily be described with an exponential relationship. Comparison of the performance of the same catheters in vitro and in vivo showed that the in vitro determined calibration relationship should not be used for in vivo measurements. Finally, we also simulated the working principle of the catheter using a simplified numerical model of the blood flow and heat transfer around the catheter. The computed results also suggested a pronounced nonlinear relationship between power and cardiac output in pulsatile conditions. We conclude that the observed over- and underestimation of high- and low flows, respectively, by the current truCCOMS system is likely to arise from its linear calibration relationship. An appropriate calibration scheme accounting for the intrinsic nonlinear power-cardiac output relationship and the difference between in vitro and in vivo conditions should improve the clinical performance of the system.

Noninvasive assessment of left ventricular and myocardial contractility in middle-aged men and women: disparate evolution above the age of 50?

End-systolic elastance (E(es)) is a frequently used index of left ventricular (LV) contractility. However, because of its inherent dependence on LV geometry, E(es) cannot be used to compare myocardial contractile state between ventricles with different geometries, which is the case in any cross-sectional study. Various normalization methods for E(es) have been proposed in the literature, but a standardized method is still lacking. In this study, we introduced a novel alternative normalization technique and compared it with three previously suggested methods. We tested all normalization methods to assess the age- and sex-related differences in myocardial contractility in a large population sample of 2,184 middle-aged (ages, 35-55 yr) untreated subjects free from overt cardiovascular disease. Ventricular contractility E(es) was determined using a previously validated noninvasive single-beat method, based on two-dimensional echocardiographic and brachial blood pressure measurements. Myocardial contractility was estimated as 1) E(es).end-diastolic volume (EDV); 2) E(es).LV mass (LVM); 3) 0.433.E(es).LVM/relative wall thickness (RWT), based on a theoretical LV model; and 4) 0.0941.E(es).LVM(0.455).RWT(-0.159), a novel semiempirical expression derived in this study. Because of the difference in their underlying assumptions, the various myocardial contractility indexes do not provide consistent information with respect to sex differences. Despite these discrepancies, it was found that myocardial contractility in women appears to be better preserved after the age of 50 yr compared with that in men. The physiological mechanisms behind this potentially clinically important phenomenon at population level require further investigation.

Nonlinear isochrones in murine left ventricular pressure-volume loops: how well does the time-varying elastance concept hold?

The linear time-varying elastance theory is frequently used to describe the change in ventricular stiffness during the cardiac cycle. The concept assumes that all isochrones (i.e., curves that connect pressure-volume data occurring at the same time) are linear and have a common volume intercept. Of specific interest is the steepest isochrone, the end-systolic pressure-volume relationship (ESPVR), of which the slope serves as an index for cardiac contractile function. Pressure-volume measurements, achieved with a combined pressure-conductance catheter in the left ventricle of 13 open-chest anesthetized mice, showed a marked curvilinearity of the isochrones. We therefore analyzed the shape of the isochrones by using six regression algorithms (two linear, two quadratic, and two logarithmic, each with a fixed or time-varying intercept) and discussed the consequences for the elastance concept. Our main observations were 1) the volume intercept varies considerably with time; 2) isochrones are equally well described by using quadratic or logarithmic regression; 3) linear regression with a fixed intercept shows poor correlation (R(2) < 0.75) during isovolumic relaxation and early filling; and 4) logarithmic regression is superior in estimating the fixed volume intercept of the ESPVR. In conclusion, the linear time-varying elastance fails to provide a sufficiently robust model to account for changes in pressure and volume during the cardiac cycle in the mouse ventricle. A new framework accounting for the nonlinear shape of the isochrones needs to be developed.

A comparative study of preload-adjusted maximal and peak power: assessment of ventricular performance in clinical practice.

This study was performed to determine whether preload-adjusted peak power can act as a surrogate for preload-adjusted maximal power in the assessment of left ventricular performance in the clinical setting. Ninety-nine consecutive patients who had undergone elective coronary artery bypass grafting were studied. Fifty-five of these patients were divided into four study groups. Afterload was changed with phenylephrine (n = 12) or glyceryl trinitrate (n = 13), preload was increased with intravenous colloid (n = 18), and contractility was increased with dobutamine (n = 12). There was excellent correlation between the two indices (r = 0.99, y = 1.0168x + 0.0769; p < 0.0001). Manipulation of neither preload nor afterload affected the indices. Both indices increased significantly during dobutamine infusion (p = 0.002). In conclusion, preload-adjusted peak power can be used as a substitute for preload-adjusted maximal power in the determination of ventricular performance in clinical practice.

Glycosphingolipids are required for sorting melanosomal proteins in the Golgi complex.

Although glycosphingolipids are ubiquitously expressed and essential for multicellular organisms, surprisingly little is known about their intracellular functions. To explore the role of glycosphingolipids in membrane transport, we used the glycosphingolipid-deficient GM95 mouse melanoma cell line. We found that GM95 cells do not make melanin pigment because tyrosinase, the first and rate-limiting enzyme in melanin synthesis, was not targeted to melanosomes but accumulated in the Golgi complex. However, tyrosinase-related protein 1 still reached melanosomal structures via the plasma membrane instead of the direct pathway from the Golgi. Delivery of lysosomal enzymes from the Golgi complex to endosomes was normal, suggesting that this pathway is not affected by the absence of glycosphingolipids. Loss of pigmentation was due to tyrosinase mislocalization, since transfection of tyrosinase with an extended transmembrane domain, which bypassed the transport block, restored pigmentation. Transfection of ceramide glucosyltransferase or addition of glucosylsphingosine restored tyrosinase transport and pigmentation. We conclude that protein transport from Golgi to melanosomes via the direct pathway requires glycosphingolipids.