Risk Factors and Reconstruction Techniques for Persistent Cerebrospinal Fluid Leak in Patients Undergoing Endoscopic Endonasal Approach to the Posterior Fossa.

Background High-flow skull base dural defects are associated with an increased risk of postoperative cerebrospinal fluid (CSF) leaks. Objective This study aimed to identify the risk factors for persistent postoperative CSF leak after endoscopic endonasal surgery (EES) and determine the ideal reconstruction strategy after initial failed repair. Methods Patients with CSF leak after intradural EES between October 2000 and February 2017 were identified. Cases with persistent CSF leak were compared with patients with similar pathologic diagnosis without a persistent leak to identify additional risk factors. Results Two hundred and twenty-three out of 3,232 patients developed postoperative CSF leak. Persistent leaks requiring more than one postoperative repair occurred in 7/223 patients (3.1%). All seven had undergone intradural approach to the posterior fossa for resection of recurrent/residual clival chordomas. This group was matched with 25 patients with recurrent/residual clival chordoma who underwent EES without postoperative CSF leak (control group). Age, gender, history of diabetes, smoking, or radiotherapy were not statistically different between the groups. Obesity (body mass index > 30) was significantly more common in the group with persistent leak (86%) compared with controls (36%) ( p = 0.02). All patients with a persistent CSF leak developed meningitis ( p = 0.001). Five patients with persistent leak required a pericranial flap to achieve definitive repair. Conclusion Multiple recurrent CSF leak after EES primarily occurs following resection of recurrent/residual posterior fossa chordoma. Obesity is a major risk factor and meningitis is universal with persistent leak. Flap necrosis may play a role in the development of persistent CSF leaks, and the use of secondary vascularized flaps, specifically extracranial-pericranial flaps, should be considered as an early rescue option in obese patients.

Keyhole Endoscopic-Assisted Transcervical Approach to the Upper and Middle Retrostyloid Parapharyngeal Space: An Anatomic Feasibility Study.

Objectives The aim of this study was to describe the anatomical nuances, feasibility, limitations, and surgical exposure of the parapharyngeal space (PPS) through a novel minimally invasive keyhole endoscopic-assisted transcervical approach (MIKET). Design Descriptive cadaveric study. Setting Microscopic and endoscopic high-quality images were taken comparing the MIKET approach with a conventional combined transmastoid infralabyrinthine transcervical approach. Participants Five colored latex-injected specimens (10 sides). Main Outcome Measures Qualitative anatomical descriptions in four surgical stages; quantitative and semiquantitative evaluation of relevant landmarks. Results A 5 cm long inverted hockey stick incision was designed to access a corridor posterior to the parotid gland after independent mobilization of nuchal and cervical muscles to expose the retrostyloid PPS. The digastric branch of the facial nerve, which runs 16.5 mm over the anteromedial part of the posterior belly of the digastric muscle before piercing the parotid fascia, was used as a landmark to identify the main trunk of the facial nerve. MIKET corridor was superior to the crossing of the accessory nerve over the internal jugular vein within 17.3 mm from the jugular process. Further exposure of the occipital condyle, vertebral artery, and the jugular bulb was achieved. Conclusion The novel MIKET approach provides in the cadaver straightforward access to the upper and middle retrostyloid PPS through a natural corridor without injuring important neurovascular structures. Our work sets the anatomical nuances and limitations that should guide future clinical studies to prove its efficacy and safety either as a stand-alone procedure or as an adjunct to other approaches, such as the endonasal endoscopic approach.

Cognitive deficits in adult patients with high-grade glioma: A systematic review.

INTRODUCTION: High-grade gliomas cause cognitive impairment in those who suffer from them. However, there is a lack of precise data describing the cognitive deficit that occurs in this population, which would allow to better focus neuropsychological evaluations and make better clinical decisions in favor of the patient's recovery and quality of life. For this purpose, a systematic review of the literature was carried out to search for studies on neurocognitive alterations in patients with malignant brain tumors. MATERIALS AND METHODS: The systematic review was conducted under the criteria of the PRISMA guideline for reporting systematic review and meta-analysis reports, with a search of the PubMed database (MEDLINE). Descriptive and analytical observational studies between 2015 and 2020 were considered. RESULTS: 506 articles were identified, of which 16 met the inclusion criteria and were selected in the qualitative synthesis and described in the manuscript. CONCLUSIONS: High-grade gliomas cause significant alterations in cognitive domains such as language, attention, memory, empathy and executive functions. However, more studies focused on describing the neuropsychological alterations in this population are needed in order to make better clinical treatment and rehabilitation decisions.

Serious and infrequent neurological complications in hospitalized patients with COVID19.

BACKGROUND: SARS-CoV-2 virus infection may affect other organs including the nervous system with variable neurological manifestations, even some research has reported that SARS-CoV-2 can be found in the brain parenchyma and / or in the cerebrospinal fluid (CSF). Although these reports of neurological involvement secondary to COVID-19 has increased, the clinical manifestations and the forms of neurological invasion is not fully understood. OBJECTIVES: In this paper, we report a case series of patients with SARS-CoV-2 infection with involvement of the nervous system and its neurological complications. In addition, a bibliographic review was developed in different databases with the aim of expanding information on neurological complications and the pathophysiological mechanisms of invasion to the nervous system. CASE REPORT: Case 1, a 79 year old male developed an infarct of the head of the caudate nucleus and thrombosis of the superior longitudinal sinus. Case 2, a 62 year old female developed an intraparenchymal hemorrhage in the left parietal lobe while hospitalized and COVID19 encephalitis was diagnosed. Case 3, a 59 year old healthy male developed a Fisher IV subarachnoid hemorrhage by aneurysmal origin of the right middle cerebral artery and right temporal intraparenchymal hematoma, due to rapid and severe neurological impairment new brain images was performed showing a right cerebellar ischemic stroke leading to compression of the cistern and brainstem. CONCLUSIONS: In these cases, the surgery goal was relieved symptoms, neurologic functional recovery, and life survival. We considered its diffusion and knowledge as imperative for all practitioners involved in the care of this patient.

PR-LncRNA signature regulates glioma cell activity through expression of SOX factors.

Long non-coding RNAs (LncRNAs) have emerged as a relevant class of genome regulators involved in a broad range of biological processes and with important roles in tumor initiation and malignant progression. We have previously identified a p53-regulated tumor suppressor signature of LncRNAs (PR-LncRNAs) in colorectal cancer. Our aim was to identify the expression and function of this signature in gliomas. We found that the expression of the four PR-LncRNAs tested was high in human low-grade glioma samples and diminished with increasing grade of disease, being the lowest in glioblastoma samples. Functional assays demonstrated that PR-LncRNA silencing increased glioma cell proliferation and oncosphere formation. Mechanistically, we found an inverse correlation between PR-LncRNA expression and SOX1, SOX2 and SOX9 stem cell factors in human glioma biopsies and in glioma cells in vitro. Moreover, knock-down of SOX activity abolished the effect of PR-LncRNA silencing in glioma cell activity. In conclusion, our results demonstrate that the expression and function of PR-LncRNAs are significantly altered in gliomagenesis and that their activity is mediated by SOX factors. These results may provide important insights into the mechanisms responsible for glioblastoma pathogenesis.

Síndrome de Cola de Caballo asociado a tratamiento quiropráctico: Reporte de 3 casos y revisión de la literatura / Horsetail syndrome associated with chiropractic treatment: Report of 3 cases and review of the literature

El síndrome de cola de caballo (SCC) es una urgencia quirúrgica poco frecuente con una incidencia estimada de hasta 1,8 casos por millón de habitantes, producida por la compresión de las raíces nerviosas en el extremo inferior del canal espinal. La manipulación espinal puede desempeñar un papel etiogénico, provocando la movilización y extrusión del disco. El diagnóstico temprano y el tratamiento oportuno son cruciales, ya que el pronóstico suele ser desfavorable si el tratamiento quirúrgico se retrasa produciendo un daño neurológico permanente. El objetivo de este trabajo es identificar los potenciales factores de riesgo para la manipulación espinal y optimizar esta práctica, evitando así posibles complicaciones derivadas del tratamiento quiropráctico. Presentamos 3 casos de SCC, observados y tratados en nuestro centro, en los que se sugiere una estrecha relación entre la manipulación espinal quiropráctica y la aparición de dicho síndrome. Tras realizarles una RM en la que se observó una hernia discal L5-S1 causante del SCC, los 3 pacientes fueron tratados quirúrgicamente de forma urgente. Los casos presentados demostraron la existencia de una asociación patogénica entre la manipulación espinal y el desarrollo del SCC, al producirse dicho síndrome en las horas siguientes a la manipulación debida a la protusión abrupta de un disco demostrado por RM.

Introduction: Cauda equine syndrome (CES) is a rare surgical emergency with an estimated incidence of up to 1.8 cases per million. It is caused by compression of the nerve roots at the lowest point of the spinal canal. Spinal manipulation can play a pathogenic role, resulting in mobilization and extrusion of the disc. Early diagnosis and timely treatment are crucial, since the prognosis is usually unfavorable and permanent neurological damage likely if surgical treatment is delayed. Objective: The aim of this study was to identify potential risk factors associated with spinal manipulation and, thereby, optimize this practice to reduce the risk of complications from chiropractic treatment. Methods: We present three cases of CES, observed and treated at our center, in which a close relationship between chiropractic spinal manipulation and the appearance of CES was apparent. Results: After magnetic resonance imaging (MRI) revealed an L5-S1 herniated disc causing the SCC, all three patients underwent urgent surgical treatment. Conclusion: The three presented cases demonstrate a strong pathogenic relationship between spinal manipulation and the development of CES, when this syndrome occurs within hours of spinal manipulation, secondary to MRI-documented acute disc protrusion.

High expression of MKP1/DUSP1 counteracts glioma stem cell activity and mediates HDAC inhibitor response.

The elucidation of mechanisms involved in resistance to therapies is essential to improve the survival of patients with malignant gliomas. A major feature possessed by glioma cells that may aid their ability to survive therapy and reconstitute tumors is the capacity for self-renewal. We show here that glioma stem cells (GSCs) express low levels of MKP1, a dual-specificity phosphatase, which acts as a negative inhibitor of JNK, ERK1/2, and p38 MAPK, while induction of high levels of MKP1 expression are associated with differentiation of GSC. Notably, we find that high levels of MKP1 correlate with a subset of glioblastoma patients with better prognosis and overall increased survival. Gain of expression studies demonstrated that elevated MKP1 impairs self-renewal and induces differentiation of GSCs while reducing tumorigenesis in vivo. Moreover, we identified that MKP1 is epigenetically regulated and that it mediates the anti-tumor activity of histone deacetylase inhibitors (HDACIs) alone or in combination with temozolomide. In summary, this study identifies MKP1 as a key modulator of the interplay between GSC self-renewal and differentiation and provides evidence that the activation of MKP1, through epigenetic regulation, might be a novel therapeutic strategy to overcome therapy resistance in glioblastoma.

Oncogenic activity of SOX1 in glioblastoma.

Glioblastoma remains the most common and deadliest type of brain tumor and contains a population of self-renewing, highly tumorigenic glioma stem cells (GSCs), which contributes to tumor initiation and treatment resistance. Developmental programs participating in tissue development and homeostasis re-emerge in GSCs, supporting the development and progression of glioblastoma. SOX1 plays an important role in neural development and neural progenitor pool maintenance. Its impact on glioblastoma remains largely unknown. In this study, we have found that high levels of SOX1 observed in a subset of patients correlate with lower overall survival. At the cellular level, SOX1 expression is elevated in patient-derived GSCs and it is also higher in oncosphere culture compared to differentiation conditions in conventional glioblastoma cell lines. Moreover, genetic inhibition of SOX1 in patient-derived GSCs and conventional cell lines decreases self-renewal and proliferative capacity in vitro and tumor initiation and growth in vivo. Contrarily, SOX1 over-expression moderately promotes self-renewal and proliferation in GSCs. These functions seem to be independent of its activity as Wnt/ß-catenin signaling regulator. In summary, these results identify a functional role for SOX1 in regulating glioma cell heterogeneity and plasticity, and suggest SOX1 as a potential target in the GSC population in glioblastoma.

Targeting SOX2 as a Therapeutic Strategy in Glioblastoma.

Glioblastoma is the most common and malignant brain cancer in adults. Current therapy consisting of surgery followed by radiation and temozolomide has a moderate success rate and the tumor reappears. Among the features that a cancer cell must have to survive the therapeutic treatment and reconstitute the tumor is the ability of self-renewal. Therefore, it is vital to identify the molecular mechanisms that regulate this activity. Sex-determining region Y (SRY)-box 2 (SOX2) is a transcription factor whose activity has been associated with the maintenance of the undifferentiated state of cancer stem cells in several tissues, including the brain. Several groups have detected increased SOX2 levels in biopsies of glioblastoma patients, with the highest levels associated with poor outcome. Therefore, SOX2 silencing might be a novel therapeutic approach to combat cancer and particularly brain tumors. In this review, we will summarize the current knowledge about SOX2 in glioblastoma and recapitulate several strategies that have recently been described targeting SOX2 in this malignancy.

Accidentes biológicos en estudiantes de Medicina de la Universidad Industrial de Santander, Bucaramanga, Colombia / Biological accidents among Medical students from Universidad Industrial de Santander, Bucaramanga, Colombia

Introducción: Los accidentes biológicos representan un riesgo ocupacional significativo para los trabajadores de la salud, y para los estudiantes de medicina. Objetivos: Establecer la prevalencia de accidentes biológicos y los factores y comportamientos asociados en la población de estudiantes de medicina. Materiales y métodos: Se encuestaron los estudiantes de medicina del área clínica de la Universidad Industrial de Santander. El instrumento de encuesta preguntaba sobre utilización de elementos de protección, caracterización y comportamientos asociados al último accidente biológico sufrido. La información obtenida fue analizada mediante porcentajes y promedios. Para evaluar los factores asociados al accidente se calcularon Razones de Prevalencia y sus IC 95%. Resultados: Se encuestaron 330 estudiantes. El uso rutinario de guantes se reportó en un 99,3%, de doble guante en 13,9%, tapabocas en 77,4% y de gafas en 30,7%. La prevalencia de accidentes biológicos fue de 18%, la cual aumentaba de acuerdo al año de estudio. El accidente no fue reportado en 48% de los casos. Se encontró una asociación positiva entre el sufrimiento de al menos un accidente biológico durante lo cursado de la carrera y el uso completo de medidas de protección en tercer y cuarto año, RP=2,92 (IC 95% 0,95 – 8,93); y negativa para quinto y sexto año, RP=0,84 (IC 95% 0,50-1,41, p=0,0479). Conclusiones: Los accidentes biológicos son frecuentes en nuestros estudiantes de medicina. Se debe insistir desde los primeros semestres en la importancia del uso de elementos de protección, el reporte del accidente y los protocolos postexposición.

Introduction: Biological accidents represent a significant occupational risk to healthcare workers including medical students. Objectives: To establish the prevalence of biological accidents, and its associated factors and behaviors among medical students. Materials and methods: Medical students in clinical clerkships from Universidad Industrial de Santander were surveyed. The survey instrument asked about the use of protective elements, the characteristics and behaviors associated to the last biological accident suffered by the student. Gathered data were analyzed as percentages and means. To evaluate associated factors, Prevalence Ratios and its CI 95% were calculated. Results: Three hundred thirty students were surveyed. Routine use of gloves was reported by 99.3%, double gloving by 13.9%, disposable masks by 77.4% and protective eyewear by 30.7%. Prevalence of biological accidents was 18.0%, which increased with seniority. Accidents were not reported to the occupational health office in 48% of cases. A positive association was found between suffering at least one accident during the career and the complete use of protective elements in third and fourth year students, PR=2.92 (CI 95% 0.95-8.93); while for fifth and sixth year students it was negative, PR=0.84 (CI 95% 0.50-1.41, p=0.0479). Conclusions: Biological accidents are frequent among our medical students. The importance of using protective elements must be emphasized during the first years of training. Medical students must be educated about the key role of reporting accidents and about post-exposure protocols.