Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism.

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis.

We report a medium-throughput drug-screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere.

Development and assessment of competency-based neurotrauma course curriculum for international neurosurgery residents and neurosurgeons.

OBJECTIVE: Traumatic brain injuries (TBIs) are a significant disease burden worldwide. It is imperative to improve neurosurgeons' training during and after their medical residency with appropriate neurotrauma competencies. Unfortunately, the development of these competencies during neurosurgeons' careers and in daily practice is very heterogeneous. This article aimed to describe the development and evaluation of a competency-based international course curriculum designed to address a broad spectrum of needs for taking care of patients with neurotrauma with basic and advanced interventions in different scenarios around the world. METHODS: A committee of 5 academic neurosurgeons was involved in the task of building this course curriculum. The process started with the identification of the problems to be addressed and the subsequent performance needed. After this, competencies were defined. In the final phase, educational activities were designed to achieve the intended learning outcomes. In the end, the entire process resulted in competency and outcomes-based education strategy, including a definition of all learning activities and learning outcomes (curriculum), that can be integrated with a faculty development process, including training. Further development was completed by 4 additional academic neurosurgeons supported by a curriculum developer specialist and a project manager. After the development of the course curriculum, template programs were developed with core and optional content defined for implementation and evaluation. RESULTS: The content of the course curriculum is divided into essentials and advanced concepts and interventions in neurotrauma care. A mixed sample of 1583 neurosurgeons and neurosurgery residents attending 36 continuing medical education activities in 30 different cities around the world evaluated the course. The average satisfaction was 97%. The average usefulness score was 4.2, according to the Likert scale. CONCLUSIONS: An international competency-based course curriculum is an option for creating a well-accepted neurotrauma educational process designed to address a broad spectrum of needs that a neurotrauma practitioner faces during the basic and advanced care of patients in different regions of the world. This process may also be applied to other areas of the neurosurgical knowledge spectrum. Moreover, this process allows worldwide standardization of knowledge requirements and competencies, such that training may be better benchmarked between countries regardless of their income level.

Variability of Clinical and Angiographic Results Based on the Treatment Preference (Endovascular or Surgical) of Centers Participating in the Subarachnoid Hemorrhage Database of the Working Group of the Spanish Society of Neurosurgery.

OBJECTIVES: Since the introduction of endovascular treatment for cerebral aneurysms, hospitals in which subarachnoid hemorrhage is treated show different availability and/or preferences towards both treatment modalities. The main aim is to evaluate the clinical and angiographic results according to the hospital's treatment preferences applied. METHODS: This study was conducted based on use of the subarachnoid hemorrhage database of the Vascular Pathology Group of the Spanish Neurosurgery Society. Centers were classified into 3 subtypes according to an index in the relationship between endovascular and surgical treatment as: endovascular preference, high endovascular preference, and elevated surgical preference. The clinical results and angiographic results were evaluated among the 3 treatment strategies. RESULTS: From November 2004 to December 2017, 4282 subarachnoid hemorrhage patients were selected for the study: 630 (14.7%) patients from centers with surgical preference, 2766 (64.6%) from centers with endovascular preference, and 886 (20.7%) from centers with high endovascular preference. The surgical preference group obtained the best angiographic results associated with a greater complete exclusion (odds ratio: 1.359; 95% confidence interval: 1.025-1.801; P = 0.033). The surgical preference subgroup obtained the best outcome at discharge (65.45%), followed by the high endovascular preference group (61.5%) and the endovascular preference group (57.8%) (odds ratio: 1.359; 95% confidence interval: 1.025-1.801; P = 0.033). CONCLUSIONS: In Spain, there is significant variability in aneurysm exclusion treatment in aneurysmal subarachnoid hemorrhage. Surgical centers offer better results for both surgical and endovascular patients. A multidisciplinary approach and the maintenance of an elevated quality of surgical competence could be responsible for these results.

Transcranial cerebellar herniation following craniotomy: Case report and literature review / Herniación cerebelosa transcraneal tras una craneotomía: reporte de un caso y revisión de la literatura

To report a case of post-surgical encephalocele through craniotomy burr holes following the resection of a meningioma of the posterior fossa. A 49-year-old female presented in the emergency room with cephalea. The MRI showed a meningioma of the convexity of the posterior fossa. A resection was performed and the bone flap replaced. The patient recovered uneventfully and was discharged. After 30 days the patient consulted referring cephalea, vomiting and imbalance. Brain MRI revealed a trans-cranial cerebellar herniation through the craniotomy burr holes. An urgent surgery was performed to repair the encephalocele. Post-surgical brain MRI was performed and did not show complications. Post-surgical encephalocele is an uncommon complication after the resection of a posterior fossa lesion. To avoid this complication, it is recommended thorough dural and bony closure, particularly in the posterior fossa surgeries and in high-risk patients

Reportamos un caso de un encefalocele posquirúrgico tras la realización de una craneotomía para la resección de un meningioma de fosa posterior. Se trata de una mujer de 49 años que acude al servicio de urgencias por cefalea. Se realizó una resonancia magnética (RM) cerebral que mostró un meningioma de la convexidad en fosa posterior. Se realizó su resección quirúrgica y reposición del colgajo óseo. La paciente se recuperó sin incidencias y fue dada de alta. Treinta días más tarde consultó por cefalea, vómitos e inestabilidad. Se realizó una RM que mostró una herniación cerebelosa a través de los orificios de trépano de la craneotomía, por lo que se llevó a cabo una reparación quirúrgica urgente del encefalocele. Se realizó una RM posquirúrgica, la cual no mostró complicaciones. El encefalocele posquirúrgico es una complicación poco frecuente tras la resección de un meningioma de fosa posterior. Para evitar esta complicación se recomienda realizar un cierre dural y una reposición ósea cuidadosos, particularmente en las cirugías de fosa posterior y en pacientes con alto riesgo

Transcranial cerebellar herniation following craniotomy: Case report and literature review.

To report a case of post-surgical encephalocele through craniotomy burr holes following the resection of a meningioma of the posterior fossa. A 49-year-old female presented in the emergency room with cephalea. The MRI showed a meningioma of the convexity of the posterior fossa. A resection was performed and the bone flap replaced. The patient recovered uneventfully and was discharged. After 30 days the patient consulted referring cephalea, vomiting and imbalance. Brain MRI revealed a trans-cranial cerebellar herniation through the craniotomy burr holes. An urgent surgery was performed to repair the encephalocele. Post-surgical brain MRI was performed and did not show complications. Post-surgical encephalocele is an uncommon complication after the resection of a posterior fossa lesion. To avoid this complication, it is recommended thorough dural and bony closure, particularly in the posterior fossa surgeries and in high-risk patients.

Protocolo de consenso en el tratamiento antitrombótico (anticoagulación y antiagregación) durante el periodo perioperatorio y periprocedimiento en neurocirugía / Antithrombotic treatment consensus protocol (anticoagulation and antiplatelet therapy) during the perioperative and periprocedural period in neurosurgery

El uso de medicación antitrombótica (antiagregante y/o anticoagulante) se encuentra ampliamente extendido. El manejo de los pacientes neuroquirúrgicos que reciben este tipo de terapia continúa siendo, a día de hoy, un problema de especial importancia. Los pacientes en tratamiento antitrombótico pueden necesitar atención neuroquirúrgica bien por presentar sangrados secundarios a dicho tratamiento, lesiones neuroquirúrgicas no hemorrágicas pero que precisen intervención urgente, o simplemente procedimientos neuroquirúrgicos electivos. Además, las consecuencias de la reintroducción de la anticoagulación temprana (sangrado o resangrado) o tardía (trombóticas o tromboembólicas) pueden ser devastadoras. En este documento presentamos el protocolo de consenso en el tratamiento antitrombótico durante el periodo perioperatorio y periprocedimiento, tanto en cirugía emergente como en procedimientos electivos de neurocirugía

The use of antithrombotic medication (antiplatelet and/or anticoagulant therapy) is widespread. Currently, the management of neurosurgical patients receiving this type of therapy continues to be a problem of special importance. Patients receiving antithrombotic treatment may need neurosurgical care because of bleeding secondary to such treatment, non-haemorrhagic neurosurgical lesions requiring urgent attention, or simply elective neurosurgical procedures. In addition, the consequences of reintroducing early (bleeding or rebleeding) or late (thrombotic or thromboembolic) anticoagulation can be devastating. In this paper we present the antithrombotic treatment consensus protocol during the perioperative and periprocedural period, both in emergent surgery and in elective neurosurgical procedures

[Antithrombotic treatment consensus protocol (anticoagulation and antiplatelet therapy) during the perioperative and periprocedural period in neurosurgery]. / Protocolo de consenso en el tratamiento antitrombótico (anticoagulación y antiagregación) durante el periodo perioperatorio y periprocedimiento en neurocirugía.

The use of antithrombotic medication (antiplatelet and/or anticoagulant therapy) is widespread. Currently, the management of neurosurgical patients receiving this type of therapy continues to be a problem of special importance. Patients receiving antithrombotic treatment may need neurosurgical care because of bleeding secondary to such treatment, non-haemorrhagic neurosurgical lesions requiring urgent attention, or simply elective neurosurgical procedures. In addition, the consequences of reintroducing early (bleeding or rebleeding) or late (thrombotic or thromboembolic) anticoagulation can be devastating. In this paper we present the antithrombotic treatment consensus protocol during the perioperative and periprocedural period, both in emergent surgery and in elective neurosurgical procedures.

Criterios para la formación y capacitación en Neurorradiología Intervencionista-Neurointervencionismo, acordados por el Grupo Español de Neurorradiología Intervencionista (GENI), la Sociedad Española de Neurorradiología (SENR) y los grupos expertos en patología vascular de las sociedades españolas de Neurocirugía (SENEC) y Neurología (SEN). Bases para la obtención de una acreditación de centros y especialistas en Neurorradiología Intervencionista-Neurointervencionismo / Criteria for education and training in Interventionist-Neuro-Interventionism Neuroradiology, agreed by the Spanish Interventionist Neuroradiology Group (GENI) of the Spanish Neuroradiology Society (SENR) and the Expert Group of the Spanish Neurosurgery (SENEC) and Neurology (SEN). A basis for obtaining Accreditation in centres and specialists in Interventionist-Neuro-Interventionism Neuroradiology

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¿Era el actual superávit de neurocirujanos previsible en 2009? Análisis de la situación sobre la base de los datos del Informe de oferta y necesidad de especialistas médicos en España (2008-2025) / No disponible

Introducción En el año 2009 el Ministerio de Sanidad y Consumo (MSC), en el Informe de oferta y necesidad de especialistas médicos en España (2008-2025), categorizó el escenario de nuestra especialidad como de déficit moderado de especialistas. Sin embargo, la neurocirugía española vive actualmente una situación caracterizada por un excedente de neurocirujanos. Objetivos Determinar si, tras el informe del MSC, era posible en el año 2009 prever el exceso actual de neurocirujanos, así como cuál será la proyección más probable de oferta y demanda en el año 2017.Material y métodos A partir de los datos crudos extraídos del informe del MSC, del estudio sobre la edad de los neurocirujanos españoles realizado por la Junta Directiva de la SENEC en 2001 y de las tasas de mortalidad anual para los distintos rangos de edad ofrecidas por el Instituto Nacional de Estadística, realizamos una predicción de la evolución de la oferta y la demanda de (..) (AU)

Fístula de líquido cefalorraquídeo recidivante postraumática asociada a meningocele esfenoidal. Técnica abierta-endoscópica / Cerebrospinal fluid fistula associated with posttraumatic recurrent sphenoidal meningocele. Open-endoscopic technique

Introducción. Las fístulas de líquido cefalorraquídeo surgen tras la ruptura de las barreras que separan la cavidad nasal y senos paranasales de los espacios subaracnoideos: base craneal, duramadre y membrana aracnoidea. Aproximadamente el 80% surgen en el contexto de traumatismos craneofaciales con fracturas de la base craneal. La elección del abordaje y técnica quirúrgica más adecuada en cada caso es esencial para la obtención de resultados quirúrgicos globales satisfactorios. El desarrollo de la cirugía endoscópica endonasal ha supuesto un arma terapéutica menos invasiva y eficaz, siendo las fístulas de líquido cefalorraquídeo una indicación bien establecida para su tratamiento definitivo. Caso clínico. Se presenta el caso de una paciente con fístula de líquido cefalorraquídeo recurrente con meningoencefalocele asociado tratada vía endoscópica. Discusión. Se discute el tratamiento conservador versus quirúrgico de las fístulas de líquido cefalorraquídeo. Ventajas y desventajas de los distintos tipos de abordajes relacionados con el manejo definitivo(AU)

Introduction. Cerebrospinal fluid fistulas arise after the breakdown of the barriers that separate the nasal cavity and paranasal sinuses of the subarachnoid space, skull base, dura and arachnoid membrane. Approximately 80% arise in the context of craniofacial trauma with fractures of the skull base. The choice of approach, appropriate surgical technique in each case is essential to achieve a good overall surgical outcome. Development of endoscopic endonasal surgery has become a less invasive and effective therapeutic tool, with cerebrospinal fluid fistulas being a well-established indication for definitive treatment. Case report. A case of a patient with cerebrospinal fluid fistula associated with recurrent meningoencephalocele, treated endoscopically. Discussion. We discuss the surgical versus conservative treatment of spinal fluid fistulas, and the advantages and disadvantages of different types of approaches related to definitive management(AU)

[Was the current surplus of neurosurgeons predictable in 2009? Analysis of the situation based on the Report of supply and demand of medical specialists in Spain (2008-2025)]. / ¿Era el actual superávit de neurocirujanos previsible en 2009? Análisis de la situación sobre la base de los datos del Informe de oferta y necesidad de especialistas médicos en España (2008-2025).

INTRODUCTION: In 2009 the Spanish Ministry of Health (SMH) published the report of supply and demand of medical specialists in Spain (2008-2025), in which our specialty was considered as presenting a moderate deficit of consultants. However, Spanish neurosurgery is currently in a situation of having a surplus of neurosurgeons. OBJECTIVES: To determine whether it was possible to predict the current excess of neurosurgeons in 2009 and to forecast the most likely perspective of supply and demand in 2017. MATERIAL AND METHODS: Raw data extracted from the SMH report, information on the ages of the Spanish neurosurgeons obtained from the study performed by our Board of Directors in 2001, and annual mortality rates for different age ranges provided by the National Institute of Statistics, were used to predict the evolution of supply and demand of neurosurgeons for the periods 2008-2012 and 2013-2017. RESULTS: The current situation of an excess of specialists was predictable in 2009, and if appropriate measures are not taken, a surplus of more than 100 neurosurgeons is likely in 2017, with an unemployment rate above 26% in the worst scenario. CONCLUSIONS: In order to match the actual and future demand of specialists, it is necessary and urgent to reduce the number of neurosurgical in-training positions. To achieve this goal, it is essential to obtain periodical and up-to-date structural information of the different Neurosurgery Departments and Units, and to revisit the accreditation terms of the more than fifty current teaching units.

Una nueva etapa / A New Phase

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