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Sankhala K.K.,Translational and Clinical Research
Expert Opinion on Investigational Drugs | Year: 2017

Introduction: Activating mutations in the genes encoding the tyrosine receptor kinases KIT and platelet-derived growth factor receptor occur in 85%–90% of patients with gastrointestinal stromal tumors (GIST). Although imatinib and other tyrosine kinase inhibitors have revolutionized the treatment of GIST, most patients progress within a few years. Areas covered: Monoclonal antibodies and small-molecule inhibitors targeting specific signaling pathways or proteins associated with resistance to existing treatments are being explored as alternative treatment approaches for GIST. Other alternative approaches include inhibiting more general regulators of protein folding, chromatin packaging, and cell-cycle regulation; nontargeted approaches are also being evaluated in select patient populations. This review summarizes preclinical and clinical data from agents using these accessory pathways. Expert opinion: As we learn more about GIST biology, it is becoming clear that treatment strategies will become more personalized, as reflected by the fact that several trials are enrolling specific subpopulations of patients with GIST. Going forward, researchers should evaluate these new drugs alone or in combination with other types of drugs to better meet patient needs. © 2017 Informa UK Limited, trading as Taylor & Francis Group.


News Article | February 28, 2017
Site: www.cemag.us

A National Institute for Materials Science-Osaka University joint research team has developed a mesh which can be wrapped around injured peripheral nerves to facilitate their regeneration and restore their functions. The team — consisting of Mitsuhiro Ebara, MANA associate principal investigator, Mechanobiology Group, NIMS, and Hiroyuki Tanaka, assistant professor, Orthopaedic Surgery, Osaka University Graduate School of Medicine — created a mesh that incorporates vitamin B12, a substance vital to the normal functioning of nervous systems, which is very soft and degrades in the body. When the mesh was applied to injured sciatic nerves in rats, it promoted nerve regeneration and recovery of their motor and sensory functions. The team is currently considering clinical application of the mesh to treat peripheral nerve disorders such as carpal tunnel syndrome (CTS). Artificial nerve conduits have been developed in the past to treat peripheral nerve injuries, but they merely form a cross-link to the injury site and do not promote faster nerve regeneration. Moreover, their application is limited to relatively few patients suffering from a complete loss of nerve continuity. Vitamin B12 has been known to facilitate nerve regeneration, but oral administration of it has not proven to be very effective, and no devices capable of delivering vitamin B12 directly to affected sites had been available. Therefore, it had been hoped to develop such medical devices to actively promote nerve regeneration in the many patients who suffer from nerve injuries but have not lost nerve continuity. The NIMS-Osaka University joint research team recently developed a special mesh that can be wrapped around an injured nerve which releases vitamin B12 (methylcobalamin) until the injury heals. By developing very fine mesh fibers (several hundred nanometers in diameter) and reducing the crystallinity of the fibers, the team successfully created a very soft mesh that can be wrapped around a nerve. This mesh is made of a biodegradable plastic which, when implanted in animals, is eventually eliminated from the body. In fact, experiments demonstrated that application of the mesh directly to injured sciatic nerves in rats resulted in regeneration of axons and recovery of motor and sensory functions within six weeks. The team is currently negotiating with a pharmaceutical company and other organizations to jointly study clinical application of the mesh as a medical device to treat peripheral nerve disorders, such as CTS. This study was supported by the JSPS KAKENHI program (Grant Number JP15K10405) and AMED’s Project for Japan Translational and Clinical Research Core Centers (also known as Translational Research Network Program). This research was published online in the April 2017 issue of Acta Biomaterialia.


News Article | February 28, 2017
Site: phys.org

Conceptual diagram showing a nanofiber mesh incorporating vitamin B12 and its application to treat a peripheral nerve injury. Credit: National Institute for Materials Science A research team consisting of Mitsuhiro Ebara, MANA associate principal investigator, Mechanobiology Group, NIMS, and Hiroyuki Tanaka, assistant professor, Orthopaedic Surgery, Osaka University Graduate School of Medicine, developed a mesh which can be wrapped around injured peripheral nerves to facilitate their regeneration and restore their functions. This mesh incorporates vitamin B12—a substance vital to the normal functioning of nervous systems—which is very soft and degrades in the body. When the mesh was applied to injured sciatic nerves in rats, it promoted nerve regeneration and recovery of their motor and sensory functions. The team is currently considering clinical application of the mesh to treat peripheral nerve disorders such as carpal tunnel syndrome (CTS). Artificial nerve conduits have been developed in the past to treat peripheral nerve injuries, but they merely form a cross-link to the injury site and do not promote faster nerve regeneration. Moreover, their application is limited to relatively few patients suffering from a complete loss of nerve continuity. Vitamin B12 has been known to facilitate nerve regeneration, but oral administration of it has not proven to be very effective, and no devices capable of delivering vitamin B12 directly to affected sites had been available. Therefore, it had been hoped to develop such medical devices to actively promote nerve regeneration in the many patients who suffer from nerve injuries but have not lost nerve continuity. The NIMS-Osaka University joint research team recently developed a special mesh that can be wrapped around an injured nerve which releases vitamin B12 (methylcobalamin) until the injury heals. By developing very fine mesh fibers (several hundred nanometers in diameter) and reducing the crystallinity of the fibers, the team successfully created a very soft mesh that can be wrapped around a nerve. This mesh is made of a biodegradable plastic which, when implanted in animals, is eventually eliminated from the body. In fact, experiments demonstrated that application of the mesh directly to injured sciatic nerves in rats resulted in regeneration of axons and recovery of motor and sensory functions within six weeks. The team is currently negotiating with a pharmaceutical company and other organizations to jointly study clinical application of the mesh as a medical device to treat peripheral nerve disorders, such as CTS. This study was supported by the JSPS KAKENHI program (Grant Number JP15K10405) and AMED's Project for Japan Translational and Clinical Research Core Centers (also known as Translational Research Network Program). This research was published online in the April 2017 issue of Acta Biomaterialia on February 5, 2017. Explore further: Laser therapy on the repair of a large-gap transected sciatic nerve in a reinforced nerve conduit More information: Koji Suzuki et al. Electrospun nanofiber sheets incorporating methylcobalamin promote nerve regeneration and functional recovery in a rat sciatic nerve crush injury model, Acta Biomaterialia (2017). DOI: 10.1016/j.actbio.2017.02.004


Rajaee S.S.,Cedars Sinai Medical Center | Kanim L.E.A.,Cedars Sinai Medical Center | Kanim L.E.A.,Translational and Clinical Research | Bae H.W.,Cedars Sinai Medical Center
Bone and Joint Journal | Year: 2014

Using the United States Nationwide Inpatient Sample, we identified national trends in revision spinal fusion along with a comprehensive comparison of comorbidities, inpatient complications and surgical factors of revision spinal fusion compared to primary spinal fusion. In 2009, there were 410 158 primary spinal fusion discharges and 22 128 revision spinal fusion discharges. Between 2002 and 2009, primary fusion increased at a higher rate compared with revision fusion (56.4% vs 51.0%; p < 0.001). In 2009, the mean length of stay and hospital charges were higher for revision fusion discharges than for primary fusion discharges (4.2 days vs 3.8 days, p < 0.001; USD $91 909 vs. $87 161, p < 0.001). In 2009, recombinant human bone morphogenetic protein (BMP) was used more in revision fusion than in primary fusion (39.6% vs 27.6%, p < 0.001), whereas interbody devices were used less in revision fusion (41.8% vs 56.6%, p < 0.001). In the multivariable logistic regression model for all spinal fusions, depression (odds ratio (OR) 1.53, p < 0.001), psychotic disorders (OR 1.49, p < 0.001), deficiency anaemias (OR 1.35, p < 0.001) and smoking (OR 1.10, p = 0.006) had a greater chance of occurrence in revision spinal fusion discharges than in primary fusion discharges, adjusting for other variables. In terms of complications, after adjusting for all significant comorbidities, this study found that dural tears (OR 1.41; p < 0.001) and surgical site infections (OR 3.40; p < 0.001) had a greater chance of occurrence in revision spinal fusion discharges than in primary fusion discharges (p < 0.001). A p-value < 0.01 was considered significant in all final analyses. © 2014 The British Editorial Society of Bone & Joint Surgery.

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