Emerging targets for cancer treatment: S100A9/RAGE.

Developing better treatments that work for the majority of patients with brain metastasis (BM) is highly necessary. Complementarily, avoiding those therapeutic procedures that will not benefit a specific patient is also very relevant. In general, existing therapies for patients with BM could be improved in terms of molecular stratification and therapeutic efficacy. By questioning the benefit of whole brain radiotherapy as provided nowadays and the lack of biomarkers detecting radioresistance, we identified S100A9 and receptor for advanced glycation end-products (RAGE) as a liquid biopsy biomarker and a potential target for a radiosensitizer, respectively. Both of them are being clinically tested as part of the first comprehensive molecular strategy to personalized radiotherapy in BM.

Brain metastasis models: What should we aim to achieve better treatments?

Brain metastasis is emerging as a unique entity in oncology based on its particular biology and, consequently, the pharmacological approaches that should be considered. We discuss the current state of modelling this specific progression of cancer and how these experimental models have been used to test multiple pharmacologic strategies over the years. In spite of pre-clinical evidences demonstrating brain metastasis vulnerabilities, many clinical trials have excluded patients with brain metastasis. Fortunately, this trend is getting to an end given the increasing importance of secondary brain tumors in the clinic and a better knowledge of the underlying biology. We discuss emerging trends and unsolved issues that will shape how we will study experimental brain metastasis in the years to come.

Immunotherapy in NSCLC patients with brain metastases. Understanding brain tumor microenvironment and dissecting outcomes from immune checkpoint blockade in the clinic.

BACKGROUND: Brain metastases are frequent complications in patients with non-small-cell lung cancer (NSCLC) associated with significant morbidity and poor prognosis. Our goal is to give a global overlook on clinical efficacy from immune checkpoint inhibitors in this setting and to review the role of biomarkers and molecular interactions in brain metastases from patients with NSCLC. METHODS: We reviewed clinical trials reporting clinical outcomes of patients with NSCLC with brain metastases as well as publications assessing the tumor microenvironment and the complex molecular interactions of tumor cells with immune and resident cells in brain metastases from NSCLC biopsies or preclinical models. RESULTS: Although limited data are available on immunotherapy in patients with brain metastases, immune checkpoint inhibitors alone or in combination with chemotherapy have shown promising intracranial efficacy and safety results. The underlying mechanism of action of immune checkpoint inhibitors in the brain niche and their influence on tumor microenvironment are still not known. Lower PD-L1 expression and less T CD8+ infiltration were found in brain metastases compared with matched NSCLC primary tumors, suggesting an immunosuppressive microenvironment in the brain. Reactive astrocytes and tumor associated macrophages are paramount in NSCLC brain metastases and play a role in promoting tumor progression and immune evasion. CONCLUSIONS: Discordances in the immune profile between primary tumours and brain metastases underscore differences in the tumour microenvironment and immune system interactions within the lung and brain niche. The characterization of immune phenotype of brain metastases and dissecting the interplay among immune cells and resident stromal cells along with cancer cells is crucial to unravel effective immunotherapeutic approaches in patients with NSCLC and brain metastases.

Manejo anestésico para la resección de masa mediastínica anterior (MMA) en paciente pediátrico. Descripción de un caso clínico / Anesthetic management during anterior mediastinal mass resection in a pediatric patient. A case report

Las complicaciones inducidas por anestesia general (AG) y relajación neuromuscular (RNM) en cirugía de masa mediastínica anterior pueden ser graves, sobre todo si existe clínica de compresión de la vía aérea o grandes vasos, como disnea u ortopnean entre otros. Es preferible realizar el procedimiento en ventilación espontánea para evitar el colapso respiratorio o cardiovascular por decúbito supino o por pérdida de la presión negativa intratorácica con la AG y RNM. En caso de precisar decúbito supino y RNM se realizarán paso a paso con técnicas de rescate preparadas (posición de rescate, broncoscopio, esternotomía). Una correcta evaluación preoperatoria, adecuada planificación y abordaje multidisciplinar permiten realizar una anestesia y cirugía seguras. Presentamos el caso de un niño con antecedentes de ortopnea severa con diagnóstico de masa mediastínica anterior, linfoma linfoblástico (parada respiratoria y colapso cardiovascular en sedación para punción lumbar y biopsia de médula ósea) que no responde al tratamiento médico y precisa cirugía de resección bajo AG con RNM

Complications induced by general anesthesia (GA) and neuromuscular relaxation (NMR) in anterior mediastinal mass (AMM) resection can be serious, especially when there are signs of compression of the airway or large vessels (dyspnea, orthopnea, etc.) (1). It is preferable to perform the procedure in spontaneous ventilation to avoid respiratory or cardiovascular collapse due to the supine position or to loss of negative intrathoracic pressure with GA and NMR. If the supine position and NMR are unavoidable, procedures should be performed in a step-wise manner, and rescue strategies should be prepared (rescue position, bronchoscope, sternotomy). Correct preoperative evaluation, adequate planning, and a multidisciplinary approach will ensure patient safety. We present the case of a child with a history of severe orthopnea and a diagnosis of AMM and lymphoblastic lymphoma (respiratory arrest and cardiovascular collapse during sedation for lumbar puncture and bone marrow biopsy) that did not respond to medical treatment and required resection surgery under GA with NMR

Anesthetic management during anterior mediastinal mass resection in a pediatric patient. A case report. / Manejo anestésico para la resección de masa mediastínica anterior (MMA) en paciente pediátrico. Descripción de un caso clínico.

Complications induced by general anesthesia (GA) and neuromuscular relaxation (NMR) in anterior mediastinal mass (AMM) resection can be serious, especially when there are signs of compression of the airway or large vessels (dyspnea, orthopnea, etc.) (1). It is preferable to perform the procedure in spontaneous ventilation to avoid respiratory or cardiovascular collapse due to the supine position or to loss of negative intrathoracic pressure with GA and NMR. If the supine position and NMR are unavoidable, procedures should be performed in a step-wise manner, and rescue strategies should be prepared (rescue position, bronchoscope, sternotomy). Correct preoperative evaluation, adequate planning, and a multidisciplinary approach will ensure patient safety. We present the case of a child with a history of severe orthopnea and a diagnosis of AMM and lymphoblastic lymphoma (respiratory arrest and cardiovascular collapse during sedation for lumbar puncture and bone marrow biopsy) that did not respond to medical treatment and required resection surgery under GA with NMR.

[Ultrasound study of the vagal nerve as a diagnostic tool in Guillain-Barre syndrome]. / Estudio ultrasonografico del nervio vago como herramienta diagnostica en el sindrome de Guillain-Barre.

TITLE: Estudio ultrasonografico del nervio vago como herramienta diagnostica en el sindrome de Guillain-Barre.

Study of graphene dispersions in sodium dodecylsulfate by steady-state fluorescence of pyrene.

HYPOTHESIS: Aqueous solutions of ionic surfactants allow the exfoliation of graphene, that can be explained considering the adsorption model of ionic surfactants to hydrophobic surfaces. For many years, pyrene has been used as a fluorescent probe because its sensitivity to the micro-environment. The study of pyrene fluorescence in the presence of different graphene dispersions in an ionic surfactant, would improve the knowledge of the graphene-surfactant interactions. EXPERIMENTS: Different dispersions of graphene in sodium dodecylsulfate were prepared at different weight ratios 0.5, 1 and 2%. The dispersions have been studied by Raman spectroscopy, scanning electron microscopy and transmission electron microscopy. The influence of the dispersions on the pyrene fluorescence has been investigated. FINDINGS: The graphene sheets modified by the surfactant quench the fluorescence of pyrene, which depends on the amount of graphene, the concentration of surfactant and the weight ratio. For surfactant concentrations below the critical micelle concentration, the quenching effect is higher as the weight ratio increases. Once this concentration is reached, the fluorescence increases slightly and then levels off. This behavior has been explained by the adsorption model. For a constant surfactant concentration, two straight lines can be observed in the Stern-Volmer plots whose cut-off point is approximately 20 mg L-1 of graphene.