Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

BACKGROUND: Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. METHODS: We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. RESULTS: We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. CONCLUSIONS: Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.

Sequential blinded treatment decisions in ALK-positive non-small cell lung cancers in the era of precision medicine.

Next-generation ALK TKIs have become the new standard of care in first-line setting in advanced ALK-positive NSCLC patients. However, sequential strategies at progression are relevant, as may have an impact on patients' outcome. In this commentary we discuss whether genomic-tailored strategies at progression would be more suitable for improving outcome of ALK-positive NSCLC patients.

Prevalence of pain and relative diagnostic performance of screening tools for neuropathic pain in cancer patients: A cross-sectional study.

BACKGROUND: Neuropathic pain can be overlooked in cancer patients. The advent of screening tools can help in recognizing it. However, little is known about their relative diagnostic performance and factors that affect it. This study evaluated the prevalence of neuropathic pain using several diagnostic strategies in cancer patients undergoing chemotherapy. METHODS: Patients attending the Oncology Unit of the investigators' site to continue their chemotherapy schedule were systematically screened for this cross-sectional study. Before starting chemotherapy drugs, pain specialists made a clinical diagnosis of neuropathic pain (either disease related, treatment related or comorbid) and medical oncologists administered three validated screening tools. Their relative diagnostic performance and the impact of some pain features on it were analysed using multivariate statistical methods. RESULTS: From a total of 358 patients, 194 (54.2%) suffered from pain and 73 (20.4%) had a clinical diagnosis of pure neuropathic or mixed pain. Among the screening tools, the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) was more specific (93.4%), although less sensitive (68.1%) than the Douleur Neuropathique in 4 Questions (DN4) (sensitivity: 87.5%, specificity: 88.4%). Interestingly, the specificities of these two instruments did not differ in patients with mild pain, while the DN4 remained to be more sensitive than the LANSS regardless of pain severity. CONCLUSIONS: Neuropathic pain is common in cancer patients undergoing chemotherapy. The DN4 might be of great help for the early detection of patients at risk because of incipient chemotherapy-related neuropathies and the LANSS to rule out neuropathic pain in patients with complex pain conditions.

The corrosion of nickel-titanium rotary endodontic instruments in sodium hypochlorite.

AIM: To evaluate the corrosion resistance of nickel-titanium (NiTi) endodontic rotary instruments immersed in 5.25% sodium hypochlorite (NaOCl) solution. METHODOLOGY: The corrosion performance of NiTi instruments (S1 25 mm, ProTaper Dentsplay Maillefer, Ballaigues, Switzerland) was evaluated using commercial 5.25% NaOCl solution (pH = 12.3), and the same solution partially neutralized adding H2SO4 to reach pH = 10.1. Electrochemical measurements were carried out using a potentiostat equipped with a five-channel zero resistance ammeter (ZRA) for galvanic current measurements. The instruments were sectioned into three parts (cutting part, noncutting part and shank) and degreased with acetone and rinsing with demineralized water prior to being immersed in NaOCl solution for testing. Each set of the three parts constituted one 'virtual' instrument through the ZRA, giving access to the galvanic currents that circulate between the three parts. Nine instruments were employed to check the reproducibility of the electrochemical measurements. RESULTS: The corrosion potential (E(corr)) of the NiTi alloy reached the passive domain in approximately 20 s of immersion in the solution having a pH 10.1. After this initial period the potential remained steady, indicating that stable passivation was achieved. However, at pH 12.3 no stationary state was achieved even after 6000 s of immersion time. Thus, the alloy was not stable in this medium from a corrosion point of view. CONCLUSIONS: The corrosion resistance of NiTi alloy was enhanced by lowering the pH of NaOCl solution to 10.1, which allows the system to reach the stability domain of the passivating species TiO2 and NiO2.

[Biodistribution of 99mTC-HMPAO in healthy rats and B16 melanoma carriers]. / Biodistribución de 99mTc-HMPAO en ratones sanos y portadores de melanoma B16.

Scintigraphic studies carried out in melanoma patients have demonstrated that the 99mTc-HMPAO complex makes it possible to locate the lesion. A biodistribution and pharmacokinetic study of the 99mTc-HMPAO complex was carried out in B16-melanoma tumor healthy and carrier mice after an intravenous injection. Radioactivity was measured in the liver, kidneys, spleen, stomach, brain, blood and tumor. It was seen that at 15 minutes of the injections, 40% of the total activity distributed in the animal body was recorded in the tumor. An interesting effect observed is an increase in the tissue distribution curves in both experimental groups at 1-2 hours post-injection. According to the seriated imaging study results with 99mTc-HMPAO in B16 melanoma bearing mice, the best image is obtained 10-30 minutes after the injection.

A dual embryonic origin for vertebrate mechanoreceptors.

Neuromasts, the mechanoreceptors of the lateral line system of fishes and aquatic amphibians, have previously been thought to develop exclusively from embryonic epidermal placodes. Use of fate mapping techniques shows that neuromasts of the head and body of zebrafish, Siamese fighting fish, and Xenopus are also derived from neural crest. Neural crest migrates away from the neural tube in developing vertebrates to form much of the peripheral nervous system, pigment cells, and skeletal elements of the head. The data presented here demonstrate that neuromasts are derived from both neural crest and epidermal placodes.

Penfigoide ampollar localizado post ligadura. / Localized bullous pemphigoid post ligation

El penfigoide ampollar puede presentar un amplio espectro de manifestaciones clinicas como formas vesiculosas, hiperqueratosicas y cicatrizales localizadas y formas atipicas con deposito de IgA en la union dermoepidermica.Los limites de la entidad son imprecisos superponiendose de alguna forma con el penfigoide cicatrizal,el herpes gestationis, la epidermolisis ampollar adquirida y la dermatitis herpetiforme. El penfigoide localizado a su vez reconoce dos formas clinicas, una cicatrizal localizada especialmente en cabeza y cuello - tipo Brunstein Perry - y otra que se localiza generalmente en miembros y las ampollas no son seguidas de cicatrices, tendiendo a curar espontaneamente sin recrudescencia posterior. Se comunica el caso de una paciente de edad avanzada que presento ampollas localizadas en un miembro, a posteriori de la aplicacion de una ligadura, que curaran espontaneamente en dos semanas. Se discuten los mecanismos involucrados en el desencadenamiento de la enfermedad y la ubicacion nosologica del cuadro dentro del penfigoide ampollar localizado

Experiencias con dextranomero reticulado en ulceras cronicas de miembros inferiores. / Experience with reticulate dextranomer in chronic ulcers of lower limbs

Se presenta un trabajo realizado con microesferas de dextranomero reticulado en ulceras de miembros inferiores de evolucion cronica y resistente a diversos tratamientos habituales Se trataron 6 pacientes, teniendose en cuenta las siguientes variables: 1o.) tamano de la lesion, 2o.) profundidad, 3o.) infeccion sobreagregada, 4o.) dolor, 5o.) olor, 6o.)edema La evolucion fue optima en cinco de los pacientes excluyendo a uno con lepra tuberculoide, en el cual no se observo mejoria alguna. La granulacion aparecio aproximadamente entre el quinto y el decimo dia de iniciado el tratamiento