The importance of taking care of osteoporosis

Consequences in terms of mortality and morbidity of osteoporotic fractures are serious and recent data show that mortality of osteoporosis is often a witness of poor health. Prevalent fracture is one of the most important risk factors for incident fracture. The risk of subsequent fractures is highest immediately after initial fractures. It is essential to treat postmenopausal osteoporotic women who had experienced a fragility fracture. Efforts to raise awareness of osteoporosis among the general public and medical profession are essential because only a minority of women is taken care and treated after a typical osteoporotic fracture. We have effective treatments, varied and adapted to all situations encountered in clinical practice for the management of osteoporosis. All available treatments showed an effect on vertebral fractures and some demonstrated an effect on nonvertebral fractures or hip fractures. The lack of adherence is perfectly demonstrated in osteoporosis. As for all patients affected by a chronic disease, patient education should become part of the global care of patients with osteoporosis.     

Genital human Papillomavirus infection in patients with autoimmune inflammatory diseases

Treatment advances achieved over the last few years have radically changed the management of patients with autoimmune inflammatory diseases requiring conventional or biological immunosuppressive therapy. These diseases and the drugs used to treat them increase the rate of infections, including genital infections due to the human Papillomavirus (HPV). Genital HPV infections have been extensively studied in organ transplant recipients, HIV-infected patients, and patients with congenital immune deficiencies. Although genital HPV infections usually manifest as benign lesions of the external genital organs (condylomata), they are associated with an increased risk of cancer. Very few data are available on genital HPV infections associated with autoimmune inflammatory diseases or their treatments. Here, we review the published information on this topic.     

Relationship between functional connectivity and sensory impairment: Red flag or red herring?

Resting-state functional magnetic resonance imaging (fMRI) can be used to study the functional connectivity in the somatosensory system. However, the relationship between sensory network connectivity, sensory deficits, and structural abnormality remains poorly understood. Previously, we investigated the motor network in children with congenital hemiparesis due to middle cerebral artery strokes (MCA, n = 6) or periventricular lesions (PL, n = 8). In the present study, we validate the use of interleaved resting-state data from blocked fMRI designs to investigate the somatosensory network in these patients. The approach was validated by assessing the predicted "crossed-over" connectivity between the cerebral cortex and the cerebellum. Furthermore, the impact on the volume of gray-matter (GM) in primary (S1) and secondary (S2) somatosensory cortex on functional connectivity measures was investigated. We were able to replicate the well-known "crossed-over" pattern of functional connectivity between cerebral and cerebellar cortex. The MCA group displayed more sensory deficit and significantly reduced functional connectivity in the lesioned S2 (but not in lesioned S1) when compared with the PL group. However, when accounting for GM volume loss, this difference disappeared. This study demonstrates the applicability of analyzing resting-state connectivity in patients with brain lesions. Reductions of functional connectivity within the somatosensory network were associated with sensory deficits, but were fully explained by the underlying GM damage.     

Integration of proprioceptive signals and attentional capacity during postural control are impaired but subject to improvement in dyslexic children

Children with developmental dyslexia suffer from delayed reading capabilities and may also exhibit attentional and sensori-motor deficits. The objective of this study was twofold. First, we aimed at investigating whether integration of proprioceptive signals in balance control was more impaired in dyslexic children when the attentional demand was varied. Secondly, we checked whether this effect was reduced significantly by using a specific treatment to improve eye control deficits and certain postural signs that are often linked to dyslexia (Quercia et al. in J Fr Ophtalmol 28:713–723, 2005, J Fr Ophtalmol 30:380–89, 2007). Thirty dyslexic and 51 treated dyslexic children (>3 months of treatment) were compared with 42 non-dyslexic children in several conditions (mean age: 136.2 ± 23.6, 132.2 ± 18.7 and 140.2 ± 25 months, respectively). Co-vibration of ankle muscles was effected in order to alter proprioceptive information originating from the ankle. In two vibration conditions, ankle muscles were either not vibrated or vibrated at 85 Hz without illusion of any movement. These two vibration conditions were combined with two attentional conditions. In the first such condition, children maintained balance while merely fixing their gaze on a point in front of them. In the second condition, they had to look for smaller or larger stars in a panel showing forty of each kind. Balance was assessed by means of a force plate. Results indicated that the mean velocity (i.e. the total length) of the center of pressure (CoP) displacement in the 85-Hz vibration condition increased significantly more (compared with no vibration) in the dyslexic and the treated dyslexic groups than in the control group, irrespective of the attention task. Interestingly, in the condition without vibration, the attentional performance of treated children was similar to that of the control group, whereas the attentional performance of the untreated dyslexic children was significantly impaired. Altogether, these results suggest that integration of proprioceptive signals in balance control and attentional capacity are impaired in dyslexic children. However, attention capacity during the control of stance could be improved significantly.     

Secretome from senescent melanoma engages the STAT3 pathway to favor reprogramming of naive melanoma towards a tumor-initiating cell phenotype

Here, we showed that the secretome of senescent melanoma cells drives basal melanoma cells towards a mesenchymal phenotype, with characteristic of stems illustrated by increased level of the prototype genes FN1, SNAIL, OCT4 and NANOG. This molecular reprogramming leads to an increase in the low-MITF and slow-growing cell population endowed with melanoma-initiating cell features. The secretome of senescent melanoma cells induces a panel of 52 genes, involved in cell movement and cell/cell interaction, among which AXL and ALDH1A3 have been implicated in melanoma development. We found that the secretome of senescent melanoma cells activates the STAT3 pathway and STAT3 inhibition prevents secretome effects, including the acquisition of tumorigenic properties. Collectively, the findings provide insights into how the secretome of melanoma cells entering senescence upon chemotherapy treatments increases the tumorigenicity of naïve melanoma cells by inducing, through STAT3 activation, a melanoma-initiating cell phenotype that could favor chemotherapy resistance and relapse.     

Assessment of reproducibility of thigh marker ranking during walking and landing tasks

The aim of this paper is to analyse the repeatability of marker deformation and marker ranking across subjects and motor tasks. A method based on the solidification of the thigh with optimized rototranslation was applied which used 26 markers placed on the left thigh. During five trials of landing and five trials of walking for eight participants, the deformation between the actual positions of the 26 markers and the recalled positions from solidification were calculated. Markers were then sorted and ranked from the most deformed to the least deformed. Like previous studies, marker deformation found in this paper is subject and movement-dependant. The reproducibility of the marker rankings was assessed using Kendall's coefficient of concordance. Results highlighted that the marker ranking was similar between the trials of landing and between the trials of walking. Moreover, for walking and landing the rankings were consistent across the eight subjects.     

Ultrasound elastic tensor imaging: comparison with MR diffusion tensor imaging in the myocardium

We have previously proven the feasibility of ultrasound-based shear wave imaging (SWI) to non-invasively characterize myocardial fiber orientation in both in vitro porcine and in vivo ovine hearts. The SWI-estimated results were in good correlation with histology. In this study, we proposed a new and robust fiber angle estimation method through a tensor-based approach for SWI, coined together as elastic tensor imaging (ETI), and compared it with magnetic resonance diffusion tensor imaging (DTI), a current gold standard and extensively reported non-invasive imaging technique for mapping fiber architecture. Fresh porcine (n = 5) and ovine (n = 5) myocardial samples (20?×?20?×?30?mm(3)) were studied. ETI was firstly performed to generate shear waves and to acquire the wave events at ultrafast frame rate (8000 fps). A 2.8?MHz phased array probe (pitch = 0.28?mm), connected to a prototype ultrasound scanner, was mounted on a customized MRI-compatible rotation device, which allowed both the rotation of the probe from?-90° to 90° at 5° increments and co-registration between two imaging modalities. Transmural shear wave speed at all propagation directions realized was firstly estimated. The fiber angles were determined from the shear wave speed map using the least-squares method and eigen decomposition. The test myocardial sample together with the rotation device was then placed inside a 7T MRI scanner. Diffusion was encoded in six directions. A total of 270 diffusion-weighted images (b = 1000?s mm(-2), FOV = 30?mm, matrix size = 60?×?64, TR = 6?s, TE = 19?ms, 24 averages) and 45 B(0)?images were acquired in 14?h 30 min. The fiber structure was analyzed by the fiber-tracking module in software, MedINRIA. The fiber orientation in the overlapped myocardial region which both ETI and DTI accessed was therefore compared, thanks to the co-registered imaging system. Results from all ten samples showed good correlation (r(2)?= 0.81, p < 0.0001) and good agreement (3.05° bias) between ETI and DTI fiber angle estimates. The average ETI-estimated fractional anisotropy (FA) values decreased from subendocardium to subepicardium (p < 0.05, unpaired, one-tailed t-test, N = 10) by 33%, whereas the corresponding DTI-estimated FA values presented a change of?-10% (p > 0.05, unpaired, one-tailed t-test, N = 10). In conclusion, we have demonstrated that the fiber orientation estimated by ETI, which assesses the shear wave speed (and thus the stiffness), was comparable to that measured by DTI, which evaluates the preferred direction of water diffusion, and have validated this concept within the myocardium. Moreover, ETI was shown capable of mapping the transmural fiber angles with as few as seven shear wave propagation directions.     

Supersonic shear wave elastography of in vivo pig kidney: influence of blood pressure, urinary pressure and tissue anisotropy

The in vivo influence of renal anisotropy and of urinary and vascular pressure on elasticity values using ultrasonic supersonic shear wave elastography was studied in pigs. Experiments were conducted in agreement with the European Commission guidelines and directives of the French Research Ministry. Six kidneys in three pigs were studied in vivo. Elasticity of renal cortex and medulla was quantified through the shear modulus (μ) by using the supersonic shear imaging technique with an 8 MHz linear ultrasound probe. All measurements were done peroperatively both in the axis and perpendicular to the main axis of pyramids, in normal condition, after progressive increase of urinary pressure, and after renal artery and renal vein ligation. In normal conditions, cortical (C) and medullary (M) elasticity values were always higher when acquisitions were realized with the ultrasound main axis perpendicular to main pyramid axis (C_//: 7.7 ± 2.3 kPa; M_//: 8.7 ± 2.5 kPa) than parallel (C_⊥: 6.9 ± 1.4 kPa; M_⊥: 6.6 ± 2.3 kPa), demonstrating an effect of renal anisotropy. In renal cortex, two bands were separated, inner cortex showing higher elasticity values (IC_⊥: 8.1 ± 1.9 kPa) than outer cortex (OC_⊥: 6.9 ± 1.4 kPa). Renal artery and renal vein ligation induced a decrease and an increase of elasticity respectively. Parenchymal elasticity increased linearly with elevation of urinary pressure. Intrarenal elasticity values vary with tissue anisotropy and, with vascular and urinary pressure levels. These parameters have to be taken into account for interpretation of tissue changes. Separation of outer and inner cortex could be attributable to perfusion differences.     

Cost effectiveness of denosumab compared with oral bisphosphonates in the treatment of post-menopausal osteoporotic women in Belgium

Background: Denosumab has recently been shown to be well tolerated, to increase bone mineral density (BMD) and to significantly reduce the risk of hip, vertebral and non-vertebral fractures in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial. It is becoming increasingly important to evaluate not only the therapeutic value of a new drug but also the cost effectiveness compared with the most relevant treatment alternatives. Objective: The objective of this study was to estimate the cost effectiveness of denosumab compared with oral bisphosphonates (branded and generic drugs) in the treatment of post-menopausal osteoporotic women in Belgium. Methods: Cost effectiveness of 3 years of treatment with denosumab was compared with branded risedronate and branded and generic alendronate using an updated version of a previously validated Markov microsimulation model. The model was populated with relevant cost, adherence and epidemiological data for Belgium from a payer perspective and the results were presented as costs per QALY gained (&U20AC;, year 2009 values). Analyses were performed in populations (aged ≥60 years) in which osteoporosis medications are currently reimbursed in many European countries, i.e. those with BMD T-score of -2.5 or less or prevalent vertebral fracture. Patients receiving denosumab were assumed to have a 46% lower risk of discontinuation than those receiving oral bisphosphonates, and the effect of denosumab after treatment cessation was assumed to decline linearly to zero over a maximum of 1 year. Results: Denosumab was cost effective compared with all other therapies, assuming a willingness to pay of &U20AC;40?000 per QALY gained. In particular, denosumab was found to be cost effective compared with branded alendronate and risedronate at a threshold value of &U20AC;30?000 per QALY and denosumab was dominant (i.e. lower cost and greater effectiveness) compared with risedronate from the age of 70 years in women with a T-score of -2.5 or less and no prior fractures. The cost effectiveness of denosumab compared with generic alendronate was estimated at &U20AC;38?514, &U20AC;22?220 and &U20AC;27?862 per QALY for women aged 60, 70 and 80 years, respectively, with T-scores of -2.5 or less. The equivalent values were &U20AC;37?167, &U20AC;19?718 and &U20AC;19?638 per QALY for women with prevalent vertebral fractures. Conclusion: This study suggests, on the basis of currently available data, that denosumab is a cost-effective strategy compared with oral bisphosphonates (including generic alendronate) for the treatment of post-menopausal osteoporotic women, aged ≥60 years in Belgium. Denosumab therefore appears to have the potential to become a first-line treatment for post-menopausal women with osteoporosis. However, further studies would be required to evaluate the long-term safety and adherence of denosumab in real-world clinical practice as well as head-to-head effectiveness compared with oral bisphosphonates.     

Anatomical study of the lateral femoral cutaneous nerve with special reference to minimally invasive anterior approach for total hip replacement

Background  Lesion of the lateral femoral cutaneous nerve (LFCN) represents the main complication during minimally invasive anterior approach dissection to the hip joint. The aim of this anatomical study was to describe the different presentation features of the LFCN at the thigh and particularly to determine the potential location of damage during minimally invasive anterior approach for total hip replacement. Methods  The LFCN was dissected bilaterally at the thigh under the inguinal ligament in 17 formalin-preserved cadavers. Branching patterns of the nerve were recorded and distances from the LFCN to the anterior superior iliac spine (ASIS) and the anterior margin of the tensor fascia lata (TFL) were measured to clarify skin incision positioning during minimally invasive anterior approach for total hip replacement. Results  The LFCN divided proximal to the inguinal ligament in 13 cases and distal to it in 21 cases. In the distal group the mean distance from the ASIS to the nerve division was 34.5 mm (10–72 mm). The gluteal branch crossed the anterior margin of the TFL 44.5 mm (24–92 mm) distally to the ASIS. In 18 cases the femoral branch did not cross the TFL and was located in the intermuscular space between TFL and sartorius. In the remaining 16 cases, this branch crossed the anterior margin of the TFL 46 mm (27–92 mm) distally to the ASIS. During minimally invasive anterior approach along the anterior border of the TFL, the LFCN was found to be potentially at risk between 27 and 92 mm below the ASIS. We used those informations to describe a map of “danger zones” for the LFCN or its two main branches. Conclusion  According to this study, numerous anatomical variations of the LFCN at the thigh should be considered when performing anterior approach to the hip joint. Different mechanisms of injury during surgery should be considered especially during minimally invasive total hip replacement, such as section of the gluteal or the femoral branch where it crosses the anterior margin of the TFL or stretching of the femoral branch due to retractors positioned into the intermuscular space between sartorius and TFL. According to the map of “danger zones” reported, the author policy consists of positioning the skin incision as lateral and distal to the ASIS as possible.