A prognostic classification of proximal humerus fractures: the cephalic extension staging.

PURPOSE: Recent publications emphasized the role of dorsomedial metaphyseal extension of humeral head as predictor of ischemia after complex proximal humerus fractures (PHFs). We evaluated on preoperative 3D CT scan of PHFs the surface of this metaphyseal extension and its prognostic value on the occurrence of avascular necrosis (AVN). METHODS: We followed a series of 25 fixations of complex PHF which had a preoperative 3D CT scan and measured the surface area of the posterior metaphyseal extension (PME) of the head. Using approximations, we calculated the ratio between the PME surface area (PMS) and the articular surface area of the head (HS). The PMS/HS ratio was analyzed against the risk of AVN. RESULTS: The measurement of the PMS/HS ratio emphasizes the significance of PME. The incidence of AVN is correlated with the magnitude of PME. Therefore, we include the PME as a fifth element in the characterization of complex PHFs and we propose a 4-stage prognostic classification based on the number of extensions of the humeral head. The head may have 3 extensions: posteromedial (PME), lesser tuberosity (LTE) and greater tuberosity (GTE). The risk of AVN decreases with the number of extensions of the head. CONCLUSION: Our study demonstrates a correlation between the occurrence of AVN and the size of PME in complex PHF cases. We propose a four-stage classification system to facilitate treatment decision-making between fixation and prosthesis.

Evaluation of intraoperative bleeding in shoulder arthroscopy with preoperative injection of epinephrine saline: a retrospective comparative study.

BACKGROUND: Several studies report the positive effects of epinephrine saline irrigation in shoulder arthroscopy. Cardiovascular adverse effects have been described. The Wide Awake Local Anesthesia No Tourniquet limits bleeding. The aim of this study is to evaluate the effects of epinephrine saline infiltrations of the shoulder on arthroscopic visual comfort. METHOD: We carried out a retrospective comparative study in 2 groups of patients. We included all patients admitted to the department for a rotator cuff surgery. Our exclusion criteria were any other surgical indication and patient refusal. The protocol consisted in making 3 preoperative shoulder infiltrations of 20 mL of epinephrine saline at 0.005 mg/mL. Injections were performed in all patients in group 1, and no specific treatment was performed in group 2 (control group). Data collection was performed the same way in both groups. The main judgment criterion was the evaluation of the surgeon's overall visual comfort using the visual analog scale (VAS) at the end of the procedure. We also evaluated the intraoperative discomfort related to bleeding every 15 minutes by an objective scale (the visual numeric rating scale [VNRS]), as well as the cumulative bleeding time, operating time, the quantity of irrigation fluid used, the blood pressure at the times of the bleeding, the mean blood pressure during the surgery, and the presence of thromboembolic and cardiovascular adverse events. RESULTS: We included 30 patients in group 1 and 30 patients in the control group. The mean VAS value at the end of the intervention was significantly higher in group 1 than in the control group: VAS = 10 in group 1 vs. VAS = 5 in group 2 (P < .0001) (higher is better). We also observed a significant decrease in VNRS between the 2 groups: VNRS = 0.25 in group 1 vs. VNRS = 1.00 in group 2 (P < .0001) (lower is better). The bleeding time was significantly lower in patients in group 1 (1 minute 39 seconds) compared with patients in group 2 (9 minutes 57 seconds) (P < .0001). No significant difference was demonstrated concerning the operating times, the quantity of irrigation fluid used, and the blood pressure data of the 2 groups. No adverse effects were observed. CONCLUSION: The infiltration of low doses of epinephrine as performed in Wide Awake Local Anesthesia No Tourniquet procedures seems effective in improving visualization in arthroscopy by reducing the bleeding. It can be a simple, efficient, and cost-effective technique with no iatrogenic risk to improve the surgeon's comfort in arthroscopic procedures.

Spiropyrimidinetriones: a Class of DNA Gyrase Inhibitors with Activity against Mycobacterium tuberculosis and without Cross-Resistance to Fluoroquinolones.

Described here is a series of spiropyrimidinetrione (SPT) compounds with activity against Mycobacterium tuberculosis through inhibition of DNA gyrase. The SPT class operates via a novel mode of inhibition, which involves Mg2+-independent stabilization of the DNA cleavage complex with DNA gyrase and is thereby not cross-resistant with other DNA gyrase-inhibiting antibacterials, including fluoroquinolones. Compound 22 from the series was profiled broadly and showed in vitro cidality as well as intracellular activity against M. tuberculosis in macrophages. Evidence for the DNA gyrase mode of action was supported by inhibition of the target in a DNA supercoiling assay and elicitation of an SOS response seen in a recA reporter strain of M. tuberculosis. Pharmacokinetic properties of 22 supported evaluation of efficacy in an acute model of M. tuberculosis infection, where modest reduction in CFU numbers was seen. This work offers promise for deriving a novel drug class of tuberculosis agent without preexisting clinical resistance.

Four Questions Nurses Can Ask to Predict PTSD 1 Year After a Motor Vehicle Crash.

BACKGROUND: The role of nurses in screening for posttraumatic stress disorder is crucial in trauma units. OBJECTIVES: To create and evaluate an easy and brief tool for nurses to predict chronic posttraumatic stress disorder 1 year after a motor vehicle crash. METHODS: We performed a 1-year follow-up multicenter study from 2007 to 2015, including 274 patients injured in a motor vehicle crash who were hospitalized in an orthopedic trauma unit. Nurses administered the DEPITAC questionnaire. Posttraumatic stress disorder was measured by the Post-Traumatic Stress Disorder Checklist of symptoms during the first year following the crash. A multivariable logistic regression model was implemented to select items significantly associated with posttraumatic stress disorder to improve the DEPITAC questionnaire. Predictive performance to predict posttraumatic stress disorder 1 year after the motor vehicle crash was examined for these different models. RESULTS: Of 274 patients studied, a total of 75.9% completed the questionnaire at 1 year of follow-up. We found that only two questions and two simple elements of the patient's medical record (other injury or a person dying during the crash, perception of vital threat, number of children, and length of stay in trauma) predicted posttraumatic stress disorder 1 year after a motor vehicle crash. CONCLUSIONS: The brevity of this evaluation, simple scoring rules, and screening test performance suggest that this new screening tool can be easily administered in the acute care setting by nurses.

A Central Amygdala-Globus Pallidus Circuit Conveys Unconditioned Stimulus-Related Information and Controls Fear Learning.

The central amygdala (CeA) is critically involved in a range of adaptive behaviors, including defensive behaviors. Neurons in the CeA send long-range projections to a number of extra-amygdala targets, but the functions of these projections remain elusive. Here, we report that a previously neglected CeA-to-globus pallidus external segment (GPe) circuit plays an essential role in classical fear conditioning. By anatomic tracing, in situ hybridization and channelrhodopsin (ChR2)-assisted circuit mapping in both male and female mice, we found that a subset of CeA neurons send projections to the GPe, and the majority of these GPe-projecting CeA neurons express the neuropeptide somatostatin. Notably, chronic inhibition of GPe-projecting CeA neurons with the tetanus toxin light chain (TeLC) completely blocks auditory fear conditioning. In vivo fiber photometry revealed that these neurons are selectively excited by the unconditioned stimulus (US) during fear conditioning. Furthermore, transient optogenetic inactivation or activation of these neurons selectively during US presentation impairs or promotes, respectively, fear learning. Our results suggest that a major function of GPe-projecting CeA neurons is to represent and convey US-related information through the CeA-GPe circuit, thereby regulating learning in fear conditioning.SIGNIFICANCE STATEMENT The central amygdala (CeA) has been implicated in the establishment of defensive behaviors toward threats, but the underlying circuit mechanisms remain unclear. Here, we found that a subpopulation of neurons in the CeA, which are mainly those that express the neuropeptide somatostatin, send projections to the globus pallidus external segment (GPe), and this CeA-GPe circuit conveys unconditioned stimulus (US)-related information during classical fear conditioning, thereby having an indispensable role in learning. Our results reveal a previously unknown circuit mechanism for fear learning.

Comparison of "Bilboquet" device and locking plate for surgical treatment of proximal humerus complex fractures at two years follow-up.

PURPOSE: Surgical treatment of three or four part fractures of the proximal humerus is complex. Different conservative techniques have been described. The main goal of this study was to compare the clinical and radiological outcomes of Bilboquet and locking plate at two year follow-up. METHODS: This is a retrospective, comparative study, with a continuous series of 41 patients. Bony fixation was achieved with a Bilboquet device in 22 patients or a locking plate in 19 patients. Patient evaluation included clinical data: shoulder range of motion, Constant-Murley shoulder score and DASH (Disabilities of the Arm, Shoulder and Hand) score, and imaging using standard shoulder X-rays. RESULTS: Of the 41 patients included, 1 patient was lost to follow-up in the locking plate group. At a mean follow-up of 24 months patients in Bilboquet group showed a Constant score higher than in locking plate (p = 0.02). Range of motion and DASH score were not significantly different between the two groups. avascular necrosis occured in three patients of Bilboquet group (14%) versus in two patients in the locking plate group (11%) (p > 0.5). Complication and reintervention rate were non-significantly higher in the locking plate group than in the Bilboquet group (37 vs 14%). CONCLUSION: Bilboquet and locking plate give good functional outcomes in complex proximal humerus fractures. However, the Bilboquet device appears to provide better functional results than locking plate at mid-term follow-up.

First insights for targeted therapies in odontogenic myxoma.

OBJECTIVE: Odontogenic myxoma (OM) occasionally responds poorly to surgical treatment. The MAPK pathway is constitutively activated in several neoplasms and we aimed to test if the MAPK pathway is activated in OM, in order to pave the way for an alternative therapy for aggressive and recurrent cases. MATERIALS AND METHODS: The immunoexpression of phosphorylated ERK1/2 (pERK1/2) was assessed in OM. We established a 3D organotypic culture model for the in vitro study and patient-derived xenografts (PDX) in mice for the in vivo study. The MEK inhibitor U0126 was used to inhibit phosphorylation of ERK1/2 in the in vitro and in vivo models. RESULTS: All OM showed strong pERK1/2 immunoexpression, consistent with MAPK pathway activation. Treatment of the 3D culture with U0126 resulted in a reduced pERK1/2/ERK1/2 ratio. Consistent with the in vitro results, all PDX of animals treated with U0126 showed a decreased volume fold change compared with controls. CONCLUSIONS: The MAPK pathway is activated in OM and its inhibition leads to tumor shrinkage in PDX and cell culture models. CLINICAL RELEVANCE: Our results offer a pre-clinical frame for OM-targeted therapy. Further work is needed to determine if this initial finding holds clinical promise.

Impact of scapular notching on glenoid fixation in reverse total shoulder arthroplasty: an in vitro and finite element study.

BACKGROUND: The high incidence of scapular notching in reverse total shoulder arthroplasty (RTSA) has spurred several methods to minimize bone loss. However, up to 93% of RTSAs accompanying scapular notching have been reported to maintain good implant stability for over 10 years. This study was conducted to investigate the relationship between scapular notching and glenoid fixation in RTSA. METHODS: Cadaveric testing was performed to measure the notch-induced variations in strain on the scapular surface and micromotion at the bone-prosthesis interface during arm abductions of 30°, 60°, and 90°. Finite element analysis was used to further study the bone and screw stresses as well as the bone-prosthesis micromotion in cases with a grade 4 notch during complicated arm motions. RESULTS: The notch resulted in an apparent increase in inferior screw stress in the root of the screw cap and at the notch-screw conjunction. However, the maximum stress (172 MPa) along the screw after notching is still much less than the fatigue strength of the titanium screw (600 MPa) under cyclic loading. The bone-prosthesis micromotion results did not present significant notch-induced variations. CONCLUSIONS: Scapular notching will lead to few impacts on the stability of an RTSA on the glenoid side. This finding may explain the long-term longevity of RTSA in cases of severe scapular notching. The relationship between scapular notching and weak regions along the inferior screw may explain why fractures of the inferior screw are sometimes reported in patients with RTSA clinically.

Body Composition Adjusted Dosing of Gemcitabine-Nab-Paclitaxel in Pancreatic Cancer Does Not Predict Toxicity Compared to Body Surface Area Dosing.

Combination gemcitabine and nab-paclitaxel (Gem-Nab-P) is a common regimen used to treat metastatic pancreatic ductal adenocarcinoma (PDAC). Toxicity from this regimen is associated with significant morbidity. Currently, Gem-Nab-P is dosed using estimated body surface area, derived from height and weight. This study investigates whether skeletal muscle assessment could be a useful tool in the dosing of Gem-Nab-P in metastatic PDAC. This study included 52 patients who had received first-line treatment with Gem-Nab-P for PDAC. Demographic and chemotherapy treatment information was gathered from medical records and body composition analysis was performed using single slice computed tomography methods, at spinal level L3. Patients who experienced first-cycle chemotherapy-associated toxicity did not have a different median skeletal muscle area (SkMA) to those who did not (128.6 cm2 vs. 111.4 cm2, P = 0.2). There was also no difference in the gemcitabine dose to SkMA ratio (14.1 mg/cm2 vs. 14.4 mg/cm2, P = 0.8), nab-paclitaxel to SkMA ratio (1.8 mg/cm2 vs. 1.8 mg/cm2, P = 0.6) or combined dose equivalent to SkMA ratio (2.8 mg/cm2 vs. 2.9 mg/cm2, P = 0.9) between the patients that experienced first cycle toxicity versus those that did not. This study suggests that a PDAC patient's SkMA is unlikely to be a useful addition to conventional body surface area in the dosing of first-line Gem-Nab-P, to reduce first-cycle toxicity.

Bringing benign ectomesenchymal odontogenic tumours to the lab: An in vitro study using an organotypic culture model.

BACKGROUND: Benign neoplasms exhibit most of the cellular phenomena considered hallmarks of cancer, except the capacity to metastasize. Thus, the elucidation of the mechanisms associated with the progression of benign neoplasms may complement and clarify the mechanisms involved in carcinogenesis. Benign odontogenic tumours often result in facial deformities and morbidities, and have complex pathogenesis, mainly due to the diversity of interactions between the odontogenic epithelium and the ectomesenchyme. Primary cell culture of such tumours is not only difficult to be established and maintained, but also tumour cells lose characteristic cellular morphology. Considering gene expression, growth, migration, proliferation and cellular morphology are controlled by cell-cell interactions and cell-extracellular matrix interactions, cell culture in 3D substrates has gained space as a way to overcome some of the limitations of traditional monolayer cell culture systems. METHODS: In this study, fragments obtained from mesenchymal odontogenic tumours were cultured in type I collagen scaffolds. Invasion tests were performed in these models, as well as phenotypic characterization of the cultured tumours. RESULTS: The results obtained for the odontogenic myxoma and the cemento-ossifying fibroma demonstrate a good reproduction of the growth pattern of these tumours under ex vivo conditions. Microscopic evaluation showed maintenance of cell viability in the explants for more than 30 days, without the presence of necrosis. CONCLUSION: This is the first study involving long-term 3D primary cultures of benign odontogenic tumours, which is expected to support complex approaches to cell and molecular biology, and to serve as an experimental model for testing molecular therapies.

Resolution limits of quantum ghost imaging.

Quantum ghost imaging uses photon pairs produced from parametric downconversion to enable an alternative method of image acquisition. Information from either one of the photons does not yield an image, but an image can be obtained by harnessing the correlations between them. Here we present an examination of the resolution limits of such ghost imaging systems. In both conventional imaging and quantum ghost imaging the resolution of the image is limited by the point-spread function of the optics associated with the spatially resolving detector. However, whereas in conventional imaging systems the resolution is limited only by this point spread function, in ghost imaging we show that the resolution can be further degraded by reducing the strength of the spatial correlations inherent in the downconversion process.

Patients' perceptions of faecal calprotectin testing in inflammatory bowel disease: results from a prospective multicentre patient-based survey.

INTRODUCTION: Despite its success, there appears to be practical issues with Faecal Calprotectin (FC) testing in Inflammatory Bowel Diseases (IBD), including sample collection, delivery and processing delays. Patients' perception and barriers to FC testing are yet to be explored in clinical practice. METHOD: A prospective patient survey was undertaken at IBD units in UK, Europe and Australia. A 9-point patient-based questionnaire was completed in clinic and included demographics, previous FC testing and FC sample difficulty rating score. Predictors of testing difficulty were derived using multivariable logistic regression analysis. RESULTS: A total of 585 patients with IBD completed the survey; 306 males with a median age of 43 years (IQR: 31-54). There were 446 patients (76%) who had prior FC testing experience. Of these, 37% (n = 165) rated FC testing difficult; 'sample collection' (n = 106; 67%) being the most common reason reported. Multivariable regression analysis identified age <49 years (odds ratio (OR): 2.5, CI:1.6-4.0), disease duration <35 months (OR 1.4, CI:0.9-2.1) and testing location (UK centre: OR 1.9, CI:1.2-3.1) as predictors of a difficult FC rating score. CONCLUSIONS: A total of 37% of patients find FC testing challenging, in particular those aged <49 years, disease duration <35 months. Further studies understanding and addressing these practical issues may aid higher FC uptake in clinic.

Safety of raltegravir-based antiretroviral therapy in HIV-infected patients receiving multi-kinase inhibitors.

Background The risk of pharmacokinetic interaction is important in HIV-infected cancer patients receiving concomitantly highly active antiretroviral therapy (HAART) and anti-cancer systemic treatments. We aimed to evaluate the safety profile of raltegravir-based HAART in cancer patients receiving multi-kinase inhibitors (MKIs). Patients and Methods We conducted a retrospective medical record review of adult, HIV-infected cancer patients treated in our institutions from January 2010 to December 2015. Patients eligible for the present analysis were those receiving a raltegravir-based HAART at the time of the initiation of a MKI for the treatment of advanced solid tumors. Treatment-related toxicity, virological outcomes and pharmacokinetic profile of MKIs were examined. Results Twelve patients (7 males, median age 55 years) were identified. Seven had sarcoma/GIST, 3 had hepatocellular carcinoma, one had pancreatic neuroendocrine tumor, and one had NSCLC. Patients received the following MKIs: imatinib (n = 3), sorafenib (n = 3), pazopanib (n = 3), sunitinib (n = 2) and erlotinib (n = 1). The mean CD4+ count at baseline was 929 cells/mm3, and 860 cells/mm3 after completion of MKI treatment. In all patients, HIV viral loads remained below the limit of detection (40 copies/ mm3) during the whole MKI treatment. No virological failure occurred. No unexpected or serious adverse event related either to raltegravir-based HAART or to MKIs was observed. The trough plasma concentrations of MKIs were assessed in 8 patients, and were found normal in all but one case (not related to raltegravir-based HAART). Conclusions The present data represent the first documentation of the concomitant use of raltegravir-containing HAART and MKIs in HIV-infected adult patients with advanced non-AIDS defining malignancies, with a reassuring safety profile.

Metformin use in diabetics with diverticular disease is associated with reduced incidence of diverticulitis.

BACKGROUND AND AIMS: There is no current, evidence-based therapy to prevent acute diverticulitis in patients with diverticular disease. Metformin has been shown to have anti-inflammatory effects in a number of disease states, in both animal models and in human observational studies. The potential therapeutic efficacy of metformin in diverticular disease has not been investigated. This study aims to describe the relationship between metformin use and diverticular disease in patients with diabetes mellitus. METHODS: This was a retrospective case-control study. It compared metformin and other hypoglycaemic medication use in diabetic patients with uncomplicated diverticulosis to those with acute diverticulitis. Patients were identified using hospital International Classification of Diseases 10 (ICD-10) data, and radiology, pathology and scanned medical record databases were used to confirm diagnoses and collect all information. Chi square tests were used to determine significance of difference in categorical variables, and Mann-Whitney tests were used for continuous data. RESULTS: There were 174 patients with uncomplicated diverticulosis and 175 patients with acute diverticulitis. A diagnosis of acute diverticulitis was associated with a significantly lower incidence of metformin use, than a diagnosis of uncomplicated diverticular disease (44% compared to 60%, respectively, p = .002). Other oral hypoglycaemic drugs and insulin were not associated with a lower incidence of diverticulitis (p = .12 and p = .24, respectively). CONCLUSION: Metformin use is associated with reduced incidence of diverticulitis in diabetic patients with diverticular disease. The utility of metformin as a therapeutic agent to reduce the risk of diverticulitis in patients with diverticular disease warrants further randomised, prospective, interventional investigation.

Fervent Hype behind Magnesium Batteries: An Open Call to Synthetic Chemists-Electrolytes and Cathodes Needed.

Magnesium metal is a superior anode which has double the volumetric capacity of lithium metal and has a negative reduction potential of -2.37 V vs. the standard hydrogen electrode. A major benefit of magnesium is the apparent lack of dendrite formation during charging which is one of the crucial concerns of using a lithium metal anode. In this Review, we highlight the foremost research in the development of electrolytes and cathodes and discuss some of the significant challenges which must be overcome in realizing a practical magnesium battery.

Body composition analysis using abdominal scans from routine clinical care in patients with Crohn's Disease.

OBJECTIVE: Crohn's Disease is associated with body composition changes, which have important treatment and prognostic implications. Measurement of body composition usually requires dedicated scanning or measurement, with retrospective analysis of existing datasets impossible. We sought to determine whether single slice analysis of abdominal scans, obtained during routine clinical care, in patients with Crohn's Disease accurately predicts body composition compartments. MATERIALS AND METHODS: Abdominal CT images of patients with Crohn's disease were analyzed and comparison was made with total body fat-free mass, total body fat mass, femoral neck t-score, and other parameters reported from DXA, the reference method. RESULTS: Thirty-seven subjects were identified, 15 male and 22 female, with a mean age of 43.8 years. There was significant correlation (Pearson r = 0.923, p < 0.001) between skeletal muscle area from CT and total fat-free mass measured by DXA. Similarly, total body fat mass correlated strongly (r = 0.928, p < 0.0001) with subcutaneous fat area. In this cohort of ambulatory Crohn's Disease patients, low muscle mass/sarcopenia was prevalent and predictive of lower bone mineral density. CONCLUSIONS: Fat mass, fat-free mass, and appendicular skeletal muscle index can be predicted by analysis of a single CT slice in patients with Crohn's Disease. Similar to published data from healthy subjects, the L3 vertebral body level provided the most robust correlation with most parameters. This study represents the first published use of routinely obtained abdominal imaging to demonstrate this relationship - and to predict body composition components - in patients with inflammatory bowel disease.

Understanding overpressure in the FAA aerosol can test by C3H2F3Br (2-BTP).

Thermodynamic equilibrium calculations, as well as perfectly-stirred reactor (PSR) simulations with detailed reaction kinetics, are performed for a potential halon replacement, C3H2F3Br (2-BTP, C3H2F3Br, 2-Bromo-3,3,3-trifluoropropene), to understand the reasons for the unexpected enhanced combustion rather than suppression in a mandated FAA test. The high pressure rise with added agent is shown to depend on the amount of agent, and is well-predicted by an equilibrium model corresponding to stoichiometric reaction of fuel, oxygen, and agent. A kinetic model for the reaction of C3H2F3Br in hydrocarbon-air flames has been applied to understand differences in the chemical suppression behavior of C3H2F3Br vs. CF3Br in the FAA test. Stirred-reactor simulations predict that in the conditions of the FAA test, the inhibition effectiveness of C3H2F3Br at high agent loadings is relatively insensitive to the overall stoichiometry (for fuel-lean conditions), and the marginal inhibitory effect of the agent is greatly reduced, so that the mixture remains flammable over a wide range of conditions. Most important, the flammability of the agent-air mixtures themselves (when compressively preheated), can support low-strain flames which are much more difficult to extinguish than the easy-to extinguish, high-strain primary fireball from the impulsively released fuel mixture. Hence, the exothermic reaction of halogenated hydrocarbons in air should be considered in other situations with strong ignition sources and low strain flows, especially at preheated conditions.

Long term exposure to antiangiogenic therapy, bevacizumab, induces osteonecrosis.

PURPOSE: Bevacizumab, a monoclonal VEGF-A antibody, has been identified as an aetiology of osteonecrosis of the femoral head. Long exposure to anti VEGF therapy induced chronic hypoperfusion of normal tissues. Osteonecrosis is a musculo-skeletal disease secondary to cellular death of bone component mainly induced by corticosteroids, alcohol use, or connective tissue disorders. METHODS: The medical records of patients with metastatic colorectal carcinoma receiving Bevacizumab between January 2006 and November 2013 were retrospectively reviewed and we had looked for osteonecrosis. Every disorder of musculoskeletal mobility were examined by orthopaedist and evaluated by imaging. RESULTS: We report on osteonecrosis of humeral and femoral head in patient with metastatic colon adenocarcinoma receiving a long-term exposure to anti angiogenic based treatment (>6 months), lack of other factors predisposing to osteonecrosis. These observations, according to literature, suggests that long exposure to anti VEGF-A, Bevacizumab, promote bone hypoperfusion and may induced osteonecrosis either on the femoral head or the humeral head with an incidence of 4 out of 1000 patients. CONCLUSIONS: With an incidence of 4 out of 1000 patients osteonecrosis is a rare side effect of anti-angiogenic agent. With the increasing utilisation and duration of exposure of anti-VEGF therapy some rare side effect due to chronic ischemia may appear. The clinician should be aware about uncommon symptoms.

Repulsive Guidance Molecules a, b and c Are Skeletal Muscle Proteins, and Repulsive Guidance Molecule a Promotes Cellular Hypertrophy and Is Necessary for Myotube Fusion.

Repulsive guidance molecules (RGMs) compose a family of glycosylphosphatidylinositol (GPI)-anchored axon guidance molecules and perform several functions during neural development. New evidence has suggested possible new roles for these axon guidance molecules during skeletal muscle development, which has not been investigated thus far. In the present study, we show that RGMa, RGMb and RGMc are all induced during skeletal muscle differentiation in vitro. Immunolocalization performed on adult skeletal muscle cells revealed that RGMa, RGMb and RGMc are sarcolemmal proteins. Additionally, RGMa was found to be a sarcoplasmic protein with a surprisingly striated pattern. RGMa colocalization with known sarcoplasmic proteins suggested that this axon guidance molecule is a skeletal muscle sarcoplasmic protein. Western blot analysis revealed two RGMa fragments of 60 and 33 kDa, respectively, in adult skeletal muscle samples. RGMa phenotypes in skeletal muscle cells (C2C12 and primary myoblasts) were also investigated. RGMa overexpression produced hypertrophic cells, whereas RGMa knockdown resulted in the opposite phenotype. RGMa knockdown also blocked myotube formation in both skeletal muscle cell types. Our results are the first to show an axon guidance molecule as a skeletal muscle sarcoplasmic protein and to include RGMa in a system that regulates skeletal muscle cell size and differentiation.

New dynamic three-dimensional MRI technique for shoulder kinematic analysis.

PURPOSE: To establish a new imaging technique using dynamic MRI three-dimensional (3D) volumetric acquisition in real-time, on six normal shoulders for the analysis of the 3D shoulder kinematics during continuous motion. MATERIALS AND METHODS: At first, a standard static acquisition was performed. Then, fast images were obtained with a multi-slice 3D balanced gradient echo sequence to get a real time series during the initial phase of shoulder abduction. Subsequently, the images were reconstructed; registered and the translational patterns of the humeral head relative to the glenoid and the size of the subacromial space were calculated. Additionally, the intraobserver reproducibility was tested. RESULTS: The maximal abduction was on average 43° (30° to 60°) and the mean width of the subacromial space was 7.7 mm (SD: ±1.2 mm). Difference between extreme values and average values was low, respectively 2.5 mm on X-axis, 2 mm on Y-axis, 1.4 mm for the width of the subacromial space and 1.2° for the measure of the glenohumeral abduction. CONCLUSION: This study reported a dynamic MRI protocol for the monitoring of shoulder 3D kinematics during continuous movement. The results suggest that there is no superior shift of the humeral head during the first phase of abduction.