Methods This phase 3 study was done in 72 institutions, across 13 countries. Patients with angiogenesis inhibitor- naive, metastatic soft-tissue sarcoma, progressing despite previous standard chemotherapy, were randomly assigned by an interactive voice randomisation system in a 2:1 ratio in permuted blocks (with block sizes of six) to receive either pazopanib 800 mg once daily or placebo, with no subsequent cross-over. Patients, investigators who gave the treatment, those assessing outcomes, and those who did the analysis were masked to the allocation. The primary
Minimally invasive, catheter – based, intravascular imaging has been routinely used to help determine the severity of vascular disease in patients, localize obstructions and culprit vascular lesions and assess the success of interventions or treatments aimed at resolving vascular complications. X-ray angiography, used for decades, has been shown to be a safe and effective method for detecting narrowed or blocked vessels. However, the technique can only visualize the diameter of the lumen of the vessel and provides no other structural or anatomical information. Given our evolving understanding of atherosclerosis, alternative techniques have been sought that enable imaging of the vessel wall. Intravascular ultrasound (IVUS) was introduced in the 70’s and produces circumferential tomographic images thereby providing anatomical information of the vessel wall (Bom et al 1972). In IVUS a transducer emits ultrasound between 20 – 40 MHz and then receives the ultrasound that is backscattered by the surrounding tissue. While the operating acoustical frequency of the device dictates the upper limit on the spatial resolution of the IVUS images, 40 – 20 µm for 20 – 40 MHz transducers respectively, practically the resolution of IVUS is usually poorer than 100 µm. This method relies on abrupt changes in the acoustical impedance that produce strong back reflections of ultrasound thus providing the contrast observed in IVUS images. For example, the leading edges of the intima and the blood – filled lumen of an artery have a strong acoustical impedance mismatch and this boundary is well visualized by ultrasound. However, different anatomical features of the vascular wall and plaque have comparable echogenicity and thus are poorly distinguished based on the amplitude of backscattered ultrasound. The limitations in resolution and contrast of various soft-tissue components that make-up the vessel wall and plaque have lead to two milestones in intravascular imaging. Optical coherence tomography (OCT) was developed because it offered higher resolution (~10 µm) over the established IVUS technology (Zysk et al 2007, Farooq et al 2009). In the same time, the detailed features of the backscattered ultrasound were analyzed to improve the soft-tissue contrast of IVUS (Nair et al 2002, Murashige et al 2005, Kawasaki et al 2001). The reliability and clinical utility of improving soft-tissue contrast using autoregressive, Fourier and wavelet methods of modeling of the backscattered ultrasound signal are being actively investigated with several groups reporting improved accuracy and reproducibility of IVUS for measuring tissue properties compared to conventional IVUS images based solely on the amplitude of the backscattered ultrasound signal (Nasu et al 2006, Mehta et al 2007, Honda and Fitzgerald 2008). Concurrent with these developments in IVUS, OCT has evolved rapidly as a high resolution intravascular imaging methodology.
Keywords: softtissue deformation · non-linear model · linear systems · domain decomposition
Image-guided therapy has revolutionized medicine, in its ability to provide care that is both efficient and effective. However, images acquired during an inter- vention are either incomplete, under-exploited, or can induce adverse outcomes. This can be due, for instance, to the lack of dimensionality of X-ray images and the associated radiation exposure for the patient. In the same time, the scien- tific computing community developed a particular interest in medical models which attempt to provide numerical simulation to reproduce living anatomy or physiology of the specific patient. The main challenge is to combine numerical models with data extracted from intra-operative images and deliver efficient per- operative guidance to clinicians.
2. Modeling the face softtissue
A project for computer-aided maxillofacial surgery has been developed for several years in the TIMC (Grenoble, France) laboratory, in collaboration with the Purpan Hospital of Toulouse, France. In that context, a Finite Element model of the face softtissue has been developed to simulate the morphological modifications resulting from bones repositioning. In Chabanas et al 2003, we mainly presented our methodology to generate patient-specific Finite Element models. A generic mesh was built, organized in two layers of hexahedrons and wedges elements. The principle was then to conform this generic model to the morphology of each patient. Using elastic registration, nodes of the mesh were non-rigidly displaced to fit the skin and skull surfaces of the patient reconstructed from a pre-operative CT scan.
larly, another factor is possible weight change (i.e loss or gain) between the preoperative and postoperative acquisitions. Of course, such factors would be difficult to remove totally. How- ever, other sources of discrepancy may be attributed to certain limitations of our approach. Firstly, we considered uniform tissue materials properties throughout the trunk instead of more realistic nonuniform physical properties. Indeed, the soft tissues were approximated by a uniform volumetric mesh and no differentiation was made between actual softtissue layers (i.e. skin, fat, muscles). This may have affected the accuracy of the simulation. Secondly, materials property coefficients were tuned manually since we have not yet implemented a rigorous method to provide them to the simulator. Finally, a monolithic/non-articulated or- ganization of the bone structures was used, and this does not reflect the exact configuration of the spine.
Trabectedin is approved in Europe for the treatment of patients with advanced soft-tissue sarcoma (STS) after failure of anthra- cyclines and ifosfamide, or when they are not eligible to receive these agents. In this setting, the 6-month progression-free rate is about 35–40% (Garcia-Carbonero et al, 2004; Yovine et al, 2004; Le Cesne et al, 2005; Demetri et al, 2009; Blay et al, 2013).The identification of predictive biomarkers of the clinical benefit of trabectedin in STS patients is thus a crucial issue to identify potential responders.
Mots clés Pédiatrie · Infection cutanée · Réanimation · Choc septique
Abstract Necrotizing softtissue infection in children with or without necrotizing fasciitis is a rare bacterial infection. Vari- cella and trauma represent the most frequent predisposing factors. These infections must be early diagnosed, before the occurrence of any complication, including extension necrosis of softtissue and septic shock. Magnetic resonance imaging and computed tomography-scan are helpful to deli- mit necrosis extent in deeper tissues. However, indications should be discussed according to infection localisation and imaging timing should not delay appropriate care. Group A β-hemolytic streptococcus is the most common microorga- nism associated with these infections, although incidence of Staphylococcus aureus is increasing. Death occurs in 5-20% of patients. Good prognosis is related to early diagnosis, antibiotic treatment and surgery. This emergent multidisci- plinary approach is sometimes difficult to manage in paedia- trics because of the rarity of these infections.
Polyvinyl chloride-plastisol: a softtissue-mimicking phantom dedicated to multi-modality elastography
S. Chatelin a, *, A. Nahas a , E. Breton a , A. Arulrajah a,b , M. Schmidt a , S. Gioux a , C. Giraudeau b ,
B. Wach a , L. Meylheuc a,c , and J. Vappou a
In this paper, the static interaction forces between a medical needle and softtissue during CT (Computerized Tomography) guided insertion are studied. More precisely a set of linearly independent elements describing the forces (a basis) is identified. This forms a generic basis from which any forces that act on a static needle (that is not fixed at its base and that is inserted into human tissue) can be described accurately. To achieve this purpose, the same needle was inserted 62 times into fresh porcine shoulder tissue and CT scans were acquired after each push to determine the final trajectory of the nee- dle. From this set of trajectories, a generic static force basis was determined by using static Beam, B-spline theories and Principal Component Analysis (PCA). This generic basis was first validated on theoretical simulations and then on 20 different needles inserted into in-vivo human tissues during real clinical interventions. Such a basis could be of use to highlight the forces acting all along the length of a needle inserted into a complex tissue and enables models of needle deflection to be developed. These models could be
A B S T R A C T
Controlling microarchitecture in polymer scaffolds is a priority in material design for softtissue applications. This paper reports for the ﬁrst time the elaboration of alginate foam-based scaffolds for mesenchymal stem cell (MSC) delivery and a comparative study of various surfactants on the ﬁnal device performance. The use of surfactants permitted to obtain highly interconnected porous scaffolds with tunable pore size on surface and in cross-section. Their mechanical properties in compression appeared to be adapted to softtissue engineering. Scaffold structures could sustain MSC proliferation over 14 days. Paracrine activity of scaffold-seeded MSCs varied with the scaffold structure and growth factors release was globally improved in comparison with control alginate scaffolds. Our results provide evidence that exploiting different surfactant types for alginate foam preparation could be an original method to obtain biocompatible scaffolds with tunable architecture for softtissue engineering.
error estimates and to address the ﬁrst technical diﬃculties. We focus on two-dimensional linear elasticity (plane strain) problems, with simple boundary conditions (prescribed displacements and tractions), and we assume triangular meshes. This is somehow restrictive in comparison to current practice in softtissue simulation. Among the existing a posteriori error estimates, we focus on Dual Weighted Residuals (DWR), as presented in, e.g. , [17,18] . Indeed this method allows to estimate the error for a given quantity of interest. As a matter of fact, for the majority of applications, controlling the error in the energy norm is not relevant, and the error must be controlled for a speciﬁc quantity of interest to the user ( e.g. , shear stress or strain intensity at speciﬁc locations). The DWR method is conveniently implemented in the standard ﬁnite element library FEniCS  and we make use of the implementation described in detail in the paper of Rognes and Logg  , with some modiﬁcations. Our adaptive algorithm has been made freely available and can be downloaded from the Figshare repository. 1
behaviour of this tissue layer during the loading. In particular, it was observed that the gluteus maximus and hamstring muscles did not al- ways remain underneath the IT, but instead, in certain subjects, slided out of plane, leaving the IT on the fat tissue. This observation is close to previous reported results. Sonenblum et al. observed that the gluteus maximus had a posterior and lateral displacement between simulated unloaded and loaded sittings in an MRI [ 17 , 32 ]. This contributes to the decrease of the thickness of softtissue muscle under the ischial tu- berosity. These results should be further investigated because, if con- firmed, it could question the assumptions, commonly made by teams developing finite element model of the buttock that deep tissue injury initiates in the muscle underlying the bone. Because the localised tissue strain is obviously directly linked to the morphology of the bones future work focusing on the relationship between localised softtissue strains and bone morphology and surface orientation is also useful for better understanding the determinants of the onset of PU.
The development of new anticancer drugs has strongly contributed to improve patients’ outcomes. However, the question can be raised whether the sometimes minor benefits are worth the cost to both the individuals and the society. The aim of this medico-economic study was to evaluate trabectedin cost-effectiveness compared with end-stage care in the treatment of soft-tissue sarcoma. We retrospectively analysed data from 45 patients treated with trabectedin for softtissue sarcoma. Real-life data of clinical benefits and costs of trabectedin were compared with simulated end-stage treatment. Univariate and probabilistic sensitivity analyses identified key drivers of the incremental cost-effectiveness ratio. Trabectedin was associated with longer progression-free survival (4.0 months versus 1.6 months) and higher costs (€24,780 versus €15,490) compared with end-stage treatment. The incremental cost per year of progression-free survival gained with trabectedin was €46,104 (95% confidence interval; €45,039 - €47,169). The results were relatively insensitive to changes. Trabectedin was cost-effective in the context of an orphan disease, when used to treat patients with a short life expectancy and few therapeutic options.
Cancers in neonates comprises only 2% of childhood malignancies  and their presen- tation, clinical behavior, and treatment often differ from others neoplasms. They correspond to a varied group of tumors. The main are teratomas and neuroblastomas, followed by softtissue sarcomas (STS), leukaemias, renal and then brain tumors. Their characteristics render the diagnosis challenging for the pathologists as normal developing tissues in fetal and neo- natal period presents rapid cell proliferation and features similar to neoplasia  . In those situations, molecular analysis can be a real help for tumor diagnosis. Another difference in infants compared to children is the immaturity of their renal and hepatic metabolisms and this make them especially vulnerable to side effects of therapy  . Therefore, diagnostic and therapeutic issues require a multidisciplinary approach because of the particular immaturity and vulnerability of this population.
This study aimed to monitor the bioaccumulation of 5 trace elements (TEs: Zn, Fe, Cu, Cd, and Pb) in the softtissue of the Ark shell (Arca noae), seasonally sampled in Bizerte lagoon, northern Tunisia, in order to assess the nutritional quality of this bivalve and to promote its consumption as marine resource in Tunisia. The levels of all trace metals analyzed in Arca noae are below maximum admissible level which makes this species a healthy and safe food for human consumption.
Filtering with zero-padding of the difference between the reprojected image and the truncated data easily implements the extrapolation of the truncated data by the full-FOV acquisition through the image space ( Cho et al. , 2009 ). Most impor- tantly, we found that an extra apodization is needed to get the desired uniformity in the solution. Note that this step formally makes the criterion non-symmetrical, but this seems minor as we never experienced any convergence issue. Finally, we designed our optimization criterion using only a small quadratic regularization term. Although our reconstruction framework would handle more sophisticated sparsity-enforcing penalties such as the image total variation (TV) ( Bian, Han, et al. , 2010 ), the reconstructed images using TV show modified textures in the soft-tissue contrast window, that are often undesirable in practice. However, we did not find the need to move from smooth regularization to TV.
Methods: This observational, prospective, national study was carried out among a French national representative database of primary rheumatologists to evaluate the prevalence and intensity of pain caused by intra-and peri- articular injections, synovial fluid aspirations, softtissue injections, and spinal injections. For each physician, data were collected over 1 month, for up to 40 consecutive patients (>18-years-old) for whom a synovial fluid aspiration, an intra or peri-articular injection or a spinal injection were carried out during consultations. Statistical analysis was carried out in order to compare patients who had suffered from pain whilst undergoing the procedure to those who had not. Explanatory analyses were conducted by stepwise logistic regression with the characteristics of the patients to explain the existence of pain.
Mots clés Toxidermie · Infection nécrosante de la peau et des parties molles · Fasciite nécrosante · Nécrolyse épidermique · Syndrome de Lyell · DRESS · Réanimation
Abstract Dermatological emergencies are a rare cause of intensive care unit admission but are associated with a high mortality rate and a high risk of long-term sequelae for sur- vivors. They predominantly consist of necrotizing softtissue infections (NSTI) and severe cutaneous adverse reactions (SCARs), including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS) and the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. These diseases are often difficult to diagnose and require a pluridisciplinary approach together with heavy and specific nurse care, frequently leading to transfer to expert centers. NSTI management during the early phase combines a surgi- cal debridement of all infected tissues and the prompt initia- tion of a broad-spectrum empiric antibiotherapy. Presence of severity signs whether local (necrosis, crepitations, intense pain) or general (sepsis/septic shock) should prompt urgent surgical exploration. It ’s readiness is the main modifiable prognostic factor, guidelines on adjunctive therapies (intra- venous immunoglobulins, hyperbaric oxygen, negative pres- sure wound dressings, ...) being to date based on weak evi- dence. The key initial step of SCARs management is the identification and removal of all culprit drugs. TEN mana- gement is mainly supportive and includes the correction of dehydration and associated metabolic disorders, hypother- mia prevention, prevention and treatment of infections, anal- gesia, anxiolysis and skin care. Infectious and respiratory complications are the main cause of death during the acute phase. No specific treatment has proven its efficacy. The diagnosis of DRESS syndrome may be difficult and its management should involve a multidisciplinary team, depending on the clinical presentation. Severity is related to possible organ involvement (cardiac, hepatic, and renal).
Fig. 12. Feature error that corresponds to the pose of a target region with
respect to the current probe frame - case of a deformable phantom
method was validated in simulation by tracking the warping motion of an US volumetric image captured from in-vivo softtissue. 4D US-based visual servoing tasks were performed successfully in the simulated deformations of a 3D US image. Furthermore, robotic experiments demonstrated non- rigid motion compensation with a deformable TM phantom in real time.
The global frame positioning mosaicing took approximately 1 min on a 2GHz P4 and 12 min if the non-rigid deformations are compensated. The imaged tissue is really soft and non-linear deformations occur. Figure 2(b) illustrates the gain we obtain by taking into account those non-rigid deformations. Some details are lost if we only use rigid deformations and appear again on our final mosaic. The results shown here prove the feasibility of mosaicing for in-vivo soft-tissue mi- croscopy. Current work is dedicated to the validation of the proposed approach. 6 Conclusion