Relevance of Thymic Stromal Lymphopoietin on the Pathogenesis of Glioblastoma: Role of the Neutrophil.

Glioblastoma multiforme (GBM) is the most predominant and malignant primary brain tumor in adults. Thymic stromal lymphopoietin (TSLP), a cytokine primarily generated by activated epithelial cells, has recently garnered attention in cancer research. This study was aimed to elucidate the significance of TSLP in GBM cells and its interplay with the immune system, particularly focused on granulocyte neutrophils. Our results demonstrate that the tumor produces TSLP when stimulated with epidermal growth factor (EGF) in both the U251 cell line and the GBM biopsy (GBM-b). The relevance of the TSLP function was evaluated using a 3D spheroid model. Spheroids exhibited increased diameter, volume, and proliferation. In addition, TSLP promoted the generation of satellites surrounding the main spheroids and inhibited apoptosis in U251 treated with temozolomide (TMZ). Additionally, the co-culture of polymorphonuclear (PMN) cells from healthy donors with the U251 cell line in the presence of TSLP showed a reduction in apoptosis and an increase in IL-8 production. TSLP directly inhibited apoptosis in PMN from GBM patients (PMN-p). Interestingly, the vascular endothelial growth factor (VEGF) production was elevated in PMN-p compared with PMN from healthy donors. Under these conditions, TSLP also increased VEGF production, in PMN from healthy donors. Moreover, TSLP upregulated programed death-ligand 1 (PDL-1) expression in PMN cultured with U251. On the other hand, according to our results, the analysis of RNA-seq datasets from Illumina HiSeq 2000 sequencing platform performed with TIMER2.0 webserver demonstrated that the combination of TSLP with neutrophils decreases the survival of the patient. In conclusion, our results position TSLP as a possible new growth factor in GBM and indicate its modulation of the tumor microenvironment, particularly through its interaction with PMN.

Is Indirect Decompression and Fusion More Effective than Direct Decompression and Fusion for Treating Degenerative Lumbar Spinal Stenosis With Instability? A Systematic Review and meta-Analysis.

Study design: Systematic Review and Meta-analysis.Objective: Surgical alternatives to treat lumbar spinal stenosis and instability include indirect (ALIF, OLIF, and LLIF) and direct (TLIF or posterior lumbar interbody fusion) decompression and fusion interventions. Although both approaches have proven to be effective in reducing symptoms, it is unknown if there is any difference in effectiveness between them. In this systematic review and meta-analysis, we aimed to evaluate postoperative pain and disability in patients treated whit indirect vs direct decompression and fusion approaches.Methods: We conducted a systematic review of the literature consulting several databases and identified studies that enrolled patients diagnosed with degenerative lumbar spinal stenosis and instability treated with indirect or direct decompression and fusion techniques. Our primary endpoints were the visual analogue scale, Oswestry Disability Index, and the Japanese Orthopedics Association Back Pain Evaluation Questionnaire 1 year after the procedure. Secondary outcomes included complication rate, blood loss, and surgical time.Results: Nine retrospective and comparative studies were included enrolling a total of 1004 participants. Both surgical strategies had satisfactory clinical outcomes with no significant difference at 1 year. Although the complication rate was similar for both groups, the profile of the adverse events was different. In addition, patients treated with indirect decompression and fusion had significantly less blood loss and operative times.Conclusions: Indirect and direct decompression and fusion techniques are similarly effective in treating patients with lumbar spinal stenosis and instability. The ID group had significantly lower intraoperative blood loss and surgical time values.

Aplicación de un método in house para el estudio de la esclerosis múltiple / Application of an in-house method for the study of multiple sclerosis

Resumen El método de referencia para el estudio bioquímico de la esclerosis múltiple (EM) es el isoelectroenfoque (IEE) y la evaluación de las cadenas livianas libres (CLL) podría brindar una información adicional de relevancia. Por lo tanto, se propone evaluar la presencia de las CLL y la aplicabilidad de los estados de polimerización en el estudio de la EM. Se puso a punto un método compuesto por una separación electroforética en gel de poliacrilamida al 12,5% con posterior electrotransferencia (PAGE-WB) y se realizó la evaluación de 121 pacientes con sospecha de EM en simultáneo al IEE. Los patrones de PAGE-WB relacionados con la EM fueron el aumento de la concentración de monómeros Kappa o dímeros Lambda en líquido cefalorraquídeo (LCR) en comparación con el suero. Este método tuvo una muy alta significación de asociación con el IEE (p<0,0001) con sensibilidad del 95%, especificidad del 90%, VPP 83% y VPN 97%. La síntesis intratecal de CLL quedó evidenciada por el aumento de intensidad del monómero Kappa y/o el dímero Lambda observado en LCR. La técnica de PAGE-WB para CLL demostró ser un método alternativo para detectar la síntesis intratecal en pacientes con sospecha de EM.

Abstract The reference method for the biochemical study of multiple sclerosis (MS) is isoelectric focusing (IEF) and the evaluation of free light chains (FLC) could provide additional information of relevance. Therefore, it is proposed here to evaluate the presence of FLC and the applicability of the polymerisation states in the study of MS. A method consisting of a 12.5% polyacrylamide gel electrophoretic separation with a subsequent electrotransfer (PAGE-WB) was developed and the evaluation of 121 patients with suspected MS was carried out simultaneously with the IEF. MS-related PAGE-WB patterns were the increase in the concentration of Kappa monomers or Lambda dimers in CSF compared to serum. This method had a very high significance of association with the IEF (p<0.0001) with 95% sensitivity, 90% specificity, 83% PPV and 97% NPV. Intrathecal synthesis of FLC was evidenced by the increased intensity of the Kappa monomers and/or Lambda dimers observed in CSF. The PAGE-WB technique for FLC proved to be an alternative method to detect intrathecal synthesis in patients with suspected MS.

Resumo O método de referência para o estudo bioquímico da esclerose múltipla (EM) é a focalização isoelétrica (IEE) e a avaliação de cadeias leves livres (CLL) poderiam fornecer informações adicionais de relevância. Assim, propõe-se avaliar a presença das CLL e a aplicabilidade dos estados de polimerização no estudo de EM. Foi desenvolvido um método que consiste na separação eletroforética em gel de poliacrilamida a 12,5% com posterior eletrotranferência (PAGE-WB) e a avaliação de 121 pacientes com suspeita de EM foi realizada paralelamente à IEE. Os padrões de PAGE-WB relacionados com a EM foram o aumento na concentração de monômeros Kappa ou dímeros Lambda em líquido cefalorraquidiano (LCR) em comparação com o soro. Este método teve uma associação de significância muito alta com o IEE (p<0,0001) com sensibilidade de 95%, especificidade de 90%, VPP 83% e VPN 97%. A síntese intratecal de CLL foi evidenciada pelo aumento de intensidade do monômero Kappa e/ou dímero Lambda observado em LCR. A técnica PAGE-WB para CLL mostrou-se um método alternativo para detectar a síntese intratecal em pacientes com suspeita de EM.

Callosotomía posterior: un nuevo abordaje en Cirugía de Epilepsia / Posterior callosotomy: a new approach in Epilepsy Surgery

Objetivo: describir la nueva técnica de callosotomía posterior utilizada en cirugía de epilepsia, junto a sus indicaciones, ventajas comparativas y sus resultados. Métodos: se muestran en secuencias de video dos casos de callosotomía posterior, en pacientes con epilepsia refractaria severa, con crisis tipo "drop attacks" (pérdida súbita del tono postural), presentando traumatismos a repetición, con potencial riesgo de vida. Ambos pacientes, una mujer de 35 años y un varón de 24 años de edad, presentaban una malformación congénita del desarrollo cortical denominada doble corteza. Un caso fue operado en posición semisentada, con abordaje parafalcino derecho, el segundo en decúbito ventral, con abordaje parafalcino izquierdo. Se realizó una incisión vertical parasagital de 7cm, a 2 cm de la línea media, con límite inferior en el inion y superior en la unión de la sutura sagital y lambdoidea. Se realizó una craneotomía de 5 x 5cm, exponiendo el seno longitudinal superior. La anatomía venosa de la región permite sin inconvenientes el desplazamiento lateral occipito-parietal. Se realizó una callosotomía que incluyó esplenio y cuerpo llegando anteriormente al sector que une ambas áreas motoras suplementarias. Resultados: no se presentaron complicaciones postoperatorias. El síndrome de desconexión apareció en un caso, desapareciendo en un periodo de 2 semanas. Se obtuvo una reducción del 90% de crisis, mejorando la calidad de vida y otorgando un mayor grado de independencia a ambos pacientes. Conclusión: la callosotomía posterior es un procedimiento seguro, poco invasivo y altamente efectivo contra las crisis de drop attacks en epilepsias refractarias

Objective: to describe the new technique of posterior callosotomy applied to epilepsy surgery, including its indication, comparative advantages and results. Methods: two surgical cases are presented on video sequences, including patients with refractory epilepsy, with "drop attack" type seizures (loss of postural tone), presenting with recurring trauma and a potential life risk. Both patients, a 35 years-old woman and a 24 years-old man suffered from a congenital malformation of cortical development known as double cortex. One of the cases was operated in a semi-sitting position, trough a right parafalcine approach, and the other one in a prone position trough a left parafalcine approach. A 7cm parasagittal vertical incision, 2cm lateral to midline was performed, considering its upper limit at the union of the lambdoid and parasagittal suture, and its lower limit at the inion. A craniotomy of 4 by 4cm was performed, exposing the superior sagittal sinus. The venous regional anatomy allows an easy parieto-occipital lateral retraction. The callosotomy included the splenium and the body reaching anteriorly up to the region where we find both supplementary motor areas. Results: no postoperative complications were found. One case presented with a disconnection syndrome, resolving in 2 weeks. A 90% reduction of the seizure frequency was achieved, improving the quality of life and the degree of Independence of the patients. Conclusions: posterior callosotomy is a safe, less invasive and highly effective procedure against drop attack type seizures in refractory Epilepsy

¿Cómo entrenar para el uso del exoscopio? Utilización de un novedoso simulador de exoscopíade bajo costo por residentes de neurocirugía / How to train for the use of the exoscope? Use of a novel low-cost exoscopy simulator by neurosurgery residents

Introducción: Analizar el impacto del entrenamiento en una estación de simulación en exoscopía (ESA) de bajo costo, utilizado por un grupo de residentes de neurocirugía. Materiales y métodos: Se reclutaron 6 residentes de neurocirugía, todos ellos sin experiencia previa en exoscopía. Se desarrolló una estación de simulación en exoscopía compuesta por una computadora, una webcam y una fuente de luz. Todos los participantes realizaron un tutorial introductorio, un ejercicio inicial de 5 suturas (cada sutura fue clasificada en forma binaria como correcta e incorrecta), evaluando el tiempo necesario para completar dicho ejercicio y la eficacia (definida como la relación entre suturas correctas y el total). Posteriormente se realizaron 3 sesiones de entrenamiento semanal de 1 hora cada una y una evaluación final con las mismas características que la inicial. Ambas evaluaciones fueron estudiadas por un neurocirujano senior que realizó un análisis, así como la puntuación de cada ejercicio de los participantes. Resultados: El tiempo promedio de realización del ejercicio inicial fue de 31 minutos con 59 segundos, con una eficacia promedio del 70%. Luego del entrenamiento el promedio de tiempo fue 18 minutos y 12 segundos, con una eficacia del 80%. Conclusión: El entrenamiento en este simulador demostró una notable mejoría en los tiempos y la calidad de la técnica exoscópica si se compara el principio del entrenamiento con su final. Por los beneficios obtenidos y su bajo costo creemos que será útil su implementación para acercar dicha técnica a todos los neurocirujanos que se encuentren interesados en ella.

Introduction: To analyze the impact of training in a low-cost simulation station of exoscopy, used by residents of neurosurgery. Materials and methods: Six residents of neurosurgery were recruited, all of them having no previous experience in the use of the exoscope. An exoscopy simulation station, including a computer, a webcam and a light source, was developed. All the participants performed an introductory tutorial, an initial exercise of 5 sutures (each suture was classified as correct and incorrect), evaluating the time to complete this exercise and the efficacy (defined as the relation between correct sutures and the total). Posteriorly, 3 training sessions of 1 hour and a final evaluation with the same characteristics as the initial one were performed by all the participants. Both evaluations were studied by a senior neurosurgeon who gave individualized punctuation and feedback to the participant. Results: The average time of the initial exercise was 31 minutes 59 seconds, with an average efficiency of 70%. After training, the average time was 18 minutes, 12 seconds, with an efficiency of 80%. Conclusion: The simulator training demonstrated the improvement of the exoscopic technique of the evaluated residents. Because of the benefits that were observed, and also its low cost, we believe that the implementation of this device will be useful to all neurosurgeons interested in this technique

Catheter fragment retrieved from an arterial branch of the right middle cerebral artery.

BACKGROUND: Cerebral emboli is a rare complication of endovascular procedures and foreign bodies in the cerebrovascular system can lead to stroke. When an intravascular foreign body is identified, endovascular retrieval should be attempted due to its high success rate and minimal morbidity. CASE DESCRIPTION: A 59-year-old male patient underwent cine-coronario-graphy through a trans-radial approach because of angina. During the study, a 6Fr catheter fragment ruptured, detached and migrated to a right middle cerebral artery branch. We recovered it with a coronary balloon. CONCLUSION: A coronary angioplasty balloon is an option for retrieving foreign objects or device fragments that have migrated into cerebral vasculature.

¿Es posible diferenciar líquido cefalorraquídeo de otras secreciones? Utilidad de la proteína Beta Trace como biomarcador de fístulas de líquido cefalorraquídeo / Is it possible to differentiate cerebrospinal fluid from other secretions? Usefulness of Beta Trace protein as a biomarker of cerebrospinal fluid fistulas

Objetivo: Describir el uso de la proteína Beta Trace (PBT) como marcador de líquido cefalorraquídeo (LCR) en una serie de casos de pacientes con sospecha de fístula de LCR (FLCR). Materiales y Métodos: Se realizó un estudio retrospectivo con datos recolectados en forma prospectiva, observacional y descriptiva. Se revisaron las historias clínicas, estudio por imágenes y datos de laboratorio de una serie de 19 pacientes con sospecha de FLCR en los cuales se había realizado la detección de la PBT mediante electroforesis bidimensional, entre julio 2015-julio 2018. Resultado: La edad promedio fue de 48,1 años, 9 fueron hombres y 10 mujeres, 10 pacientes provenían de neurocirugía, 7 de otorrinolaringología (ORL), y 2 de traumatología (OyT). De las 19 muestras, 14 fueron positivas para la detección de PBT. Cinco casos (26.32%) presentaron antecedente de meningitis, todos ellos con PBT positivo. De los casos positivos, 14 fueron tratados, 3 sin cirugía y 11 con cirugía. La principal causa fue post quirúrgica (n=9). El seguimiento promedio fue de 13,79 meses, 13 casos tuvieron resultado "favorable" y uno "desfavorable". Los 5 casos con PBT negativa fueron tratados con medidas no quirúrgicas. Todos con resultado "favorable". Conclusión: La PBT permitió, en los casos positivos, detectar LCR en las secreciones estudiadas, y en los negativos, descartarla.

Objective: To describe the use of beta-trace protein (BTP) as a cerebrospinal fluid (CSF) marker in patients with suspected CSF leakage. Methods and Materials: A retrospective study was conducted using data previously collected for a prospective, observational study. Data included the case records, imaging studies and laboratory data from a series of 19 patients with suspected CSF leakage in whom two-dimensional electrophoresis was performed for BTP detection, between July 2015 and July 2018. Results: Average patient age was 48.1 years old, with nine males and ten females. Ten patients were from neurosurgery, seven from otorhinolaryngology (ENT), and two from traumatology. Of the 19 samples, 14 were positive for BTP. Nine of the patients (47.4%) sustained their CSF leakage during surgery. Five patients (26.3%) had a history of meningitis, all with positive BTP. All 14 BTP-positive cases were treated, three without and 11 with surgery. Average post-operative follow-up was 13.8 months, with 13 patients experiencing a "favorable" and one "unfavorable" outcome. All five patients who screened negative for BTP were treated non-surgically and had a favorable outcome. Conclusions: In patients in whom BTP was identified, the marker was useful for detecting CSF in the secretions studied. Amongst those who screened negative for BTP, its absence helped to rule out the presence of a CSF leak.

El rol de la proteína beta trace en distintas áreas de la Medicina / The role of beta trace protein in different areas of Medicine / O papel da proteína beta trace em diferentes áreas da Medicina

La proteína beta trace (PBT), también llamada Prostaglandina D2 Sintasa de tipo lipocalina, es una glicoproteína de peso molecular entre 23 y 29 kDa que convierte la prostaglandina H2 en prostaglandina D2. La misma está asociada a diferentes entidades clínicas. Por sus características moleculares puede ser un indicador útil de la alteración precoz en la filtración glomerular; por el aumento de su síntesis y su concomitante elevación en suero, un predictor de riesgo cardiovascular; y por su alta concentración en líquido cefalorraquídeo (LCR), un biomarcador de fístula de LCR. Puede medirse en distintos líquidos biológicos, como suero, orina y LCR. El objetivo de esta revisión fue actualizar los conocimientos de esta proteína para evaluar su utilidad en distintas áreas de la Medicina. La trascendencia de PBT en el campo de la bioquímica como posible biomarcador dependerá de la patología de base del paciente.

The beta trace protein (BTP), also called Prostaglandin D2 Synthase lipocalin type PGDS, is a glycoprotein between 23 and 29 kDa of low molecular weight that converts prostaglandin H2 in prostaglandin D2. BTP is a protein that has multiple clinical associations. Due to the characteristics of the molecule, it may indicate an early alteration in glomerular filtration; by the serum increase of its synthesis, it is a predictor of cardiovascular risk, and for its high concentration in cerebrospinal fluid (CSF), it is a marker of leakage. This protein can be measured in different biological fluids such as serum, urine, and CSF. The objective of this review is to update the knowledge about this protein as a biomarker. The significance of BTP in the field of biochemistry as a possible biomarker will depend on the patient's underlying pathology.

A proteína beta trace (PBT), também chamada de Prostaglandina D2, sintase de lipocalina é uma glicoproteína de peso molecular entre 23 e 29 kDa, que converte prostaglandina H2 em prostaglandina D2. PBT é uma proteína que está associada a várias entidades clínicas. Devido às características moleculares, pode ser uma indicação útil da alteração precoce na filtração glomerular, devido ao aumento de sua síntese e sua concomitante elevação em soro, um preditor de risco cardiovascular e, devido à sua alta concentração no líquido cefalorraquidiano (LCR), é um biomarcador da fístula LCR. É uma proteína que pode ser medida em diferentes fluidos biológicos, como soro, urina e LCR, e o objetivo desta revisão foi atualizar os conhecimentos desta proteína para avaliar sua utilidade em diversas áreas da medicina. A importância de PBT no campo da bioquímica como possível biomarcador dependerá da patologia subjacente do paciente.

Nuevos enfoques en el abordaje a la base de cráneo / NEW REGARDS RELATED TO THE APPROACH TO THE SKULL BASE

Los abordajes tradicionales a la base de cráneo incluyen incisiones transcraneales con grandes resecciones óseas, retracción y manipulación del cerebro generando altos índices de morbimortalidad. Los abordajes endoscópicos cambian el enfoque de la base de cráneo permitiendo crear corredores más directos, disminuyendo las complicaciones. Esto comprende un verdadero trabajo en equipo entre Neurocirujanos y Otorrinolaringólogos experimentados. El objetivo de este artículo fue analizar y describir algunos de los abordajes endoscópicos ampliados de base de cráneo.

Traditional approaches to the skull base include transcranial incisions with large bone resections, brain retraction and manipulation, generating high rates of morbidity and mortality. Endoscopic approaches shift the focus of the skull base allowing to create more direct corridors, reducing complications.True teamwork is necessary between experienced Neurosurgeons and Otolaryngologists. The aim of this paper was to analyze and describe some of the extended endoscopic skull base approaches.

Fístula dural cavernosa. presentación de 3 casos y revisión bibliográfica / Cavernous dural fistula. presentation of 3 cases and bibliographic review

Objetivo: Describir la etiología, forma de presentación, evolución y conducta terapéutica adoptada en tres casos de fístulas durales cavernosas (FDC) y realizar una revisión bibliográfíca. Materiales y métodos: Se presentan tres casos de FDC, una, post-traumática; otra, secundaria a trombosis del seno cavernoso contralateral; y la tercera sin causa conocida. Todos los pacientes se presentaron con proptosis, diplopía, quemosis, ptosis palpebral e inyección conjuntival. Dos de ellos referían disminución de la agudeza visual. Ante la sospecha clínica, se realizaron estudios por imágenes no invasivos en dos pacientes, y el diagnóstico fue confirmado por angiografía digital cerebral en los tres casos. La conducta terapéutica consistió en la oclusión del seno cavernoso con coils a través de un acceso venoso femoral transoftálmico en el primer caso, anticoagulación como tratamiento de la trombosis de seno cavernoso contralateral en el segundo y compresión ocular diaria por 3 meses en el tercero. Resultados: En todos los casos, se logró la resolución completa de los síntomas. Conclusiones: La FDC es una entidad diferenciada del resto de las fístulas durales. Se dispone de diversas estrategias terapéuticas, con resultados favorables. También se observa una alta tasa de remisión espontánea. En dos de los casos presentados, el manejo de forma conservadora fue eficaz para la resolución del cuadro. En el caso que requirió tratamiento endovascular para el cierre de la fistula, el acceso por vía venosa femoral transoftálmica constituyó un abordaje efectivo para lograr la oclusión de la misma.

Objective: To describe the etiology, presentation, evolution and therapeutic approach adopted in three cases of dural cavernous fistulas (DCCF) and to perform a literature review.Materials and methods: Three cases of DCCF are report, one, post-traumatic lession; another secondary to contralateral cavernous sinus thrombosis; and the third with unknown etiology. All patients presented with proptosis, diplopia, chemosis, ptosis and conjunctival injection. Two of them concerned vision impairment. Noninvasive imaging studies were performed in two patients, and the diagnosis were confirmed by cerebral angiography digital in all three cases. The therapeutic approach consisted of cavernous sinus occlusion with coils through a femoral venous access in the first case, anticoagulation treatment of contralateral cavernous sinus thrombosis in the second and ocular compression daily for 3 months in the third. Results: Complete resolution of symptoms was achieved in all cases.Conclusions: The FDC is a distinct entity from the rest of the dural fistulas. It has several therapeutic strategies, with favorable results. A high rate of spontaneous remission is also observed. In two cases, conservative management was effective in the resolution of the picture. In the case requiring endovascular treatment for closure of the fistula, femoral vein transoftálmic acces was an effective approach to achieve occlusion of it.