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The solitary fibrous tumor/ hemangiopericytoma (TFS/HP) is a rare mesenchymal extraaxial tumour. TFS/HP can sometimes be difficult to distinguish from other extra-axial tumors like meningioma, which can be clinically and radiologically indistinguishable. Molecular analysis with STAT6 (signal transducer and activator of transcription 6) nuclear expression or NAB2-STAT6 (NGFI-A binding protein 2) fusion is recommended to confirm the diagnosis. We present 3 cases, 2 women and 1 male, with pathological diagnosis of meningothelial meningioma in the first case; cases 2 and 3 with radiological suspicion of meningioma. The pathological review with molecular study certified the diagnosis of TFS/HP. For differential diagnosis between meningeal TFS/HP and meningioma, it is recommended to look for STAT6 expression as a first step, or NAB2-STAT6 fusion in order to confirm TFS/HP. The review of biopsy samples must be guaranteed in all patients, including those who were studied in Pathology Services Level 3.El tumor fibroso solitario/ hemangiopericitoma (TFS/HP) es un tumor extraaxial de origen mesenquimático de infrecuente observación, que usualmente se confunde con el meningioma, del cual puede ser clínica y radiológicamente indistinguible. El análisis molecular con la detección de la expresión nuclear STAT6 (signal transducer and activator of transcription 6) o la fusión NAB2-STAT6 (NGFI-A binding protein 2) es recomendable para confirmar el diagnóstico. Presentamos 3 casos clínicos, 2 mujeres y 1 varón, con diagnóstico anatomopatológico de meningioma meningotelial en el primer caso; y los casos 2 y 3 con sospecha radiológica de meningioma. La revisión anatomopatológica con estudio molecular permitió certificar el diagnóstico de TFS/HP. Para el diagnóstico diferencial entre TFS/HP meníngeo y meningioma, se recomienda buscar la expresión de STAT6 como primer paso o la fusión NAB2-STAT6. La revisión de las muestras de biopsia debe estar garantizada en todos los pacientes, inclusive en aquellas que fueron estudiadas en Servicios de Patología Nivel 3.

Up to 15% of all strokes affect young patients and the incidence of ischemic stroke in this population is rising. Nevertheless, there is limited information of cerebrovascular events in this population both in our country and in Latin America. The aim of our study was to evaluate the clinical characteristics and risk factors of young adults with stroke in Argentina. This is a prospective, multicenter study of stroke in young adults (18 - 55 years) in Argentina. Patients presenting with a cerebrovascular event within 180 days were included. Stroke subtypes were classified according to TOAST criteria. A total number of 311 patients were enrolled (men 53.9%, mean age: 43.3 years). Ischemic strokes occurred in 91.8% (brain infarcts 82.6%, transient ischemic attack 9.2%) and hemorrhagic strokes in 8.2%. The most frequent vascular risk factors (including ischemic and hemorrhagic strokes) were: hypertension 120 (41%), smoking 92 (31.4%), dyslipidemia 81 (27.6%) and, overweight/obesity: 74 (25.3%). Stroke subtypes were: large artery disease 12.3%, cardioembolism 7.5%, small artery occlusion 11.5%, other defined etiology 27.1%, and undetermined etiology 41.6%. Our study demonstrates that vascular risk factors are very frequent in young adults with stroke. Our findings underline that urgent strategies are required for primary and secondary stroke prevention in this group of patients.Aproximadamente un 15% de todos los ataques cerebrovasculares afectan a pacientes jóvenes y su incidencia estaría en aumento. Existe escasa información sobre el ataque cerebral en esta población tanto en nuestro país como en Latinoamérica. El objetivo de nuestro estudio fue evaluar las características clínicas y los factores de riesgo de los adultos jóvenes con ictus en Argentina. Realizamos un estudio prospectivo y multicéntrico en adultos jóvenes (18-55 años) en Argentina, que presentaron un evento cerebrovascular dentro de los 180 días previos. Los subtipos de ictus se clasificaron según los criterios de TOAST. Se incluyeron un total de 311 pacientes (hombres 53.9%, edad media: 43,3 años). Los ataques cerebrovasculares isquémicos ocurrieron en el 91.8% (infartos cerebrales 82.6%, ataque isquémico transitorio 9.2%) y los eventos hemorrágicos correspondieron al 8.2%. Los factores de riesgo vascular más frecuentes (incluyendo los eventos isquémicos y hemorrágicos) fueron: hipertensión 120 (41%), tabaquismo 92 (31.4%), dislipidemia 81 (27.6%) y sobrepeso/obesidad: 74 (25.3%). Los subtipos de ictus isquémicos fueron: arteriopatía de gran vaso 12.3%, cardioembolismo 7.5%, oclusión de pequeña arteria 11.5%, otra etiología definida 27.1% y etiología indeterminada 41.6%. Los factores de riesgo vascular son muy frecuentes en los adultos jóvenes con ictus. Nuestros hallazgos subrayan que se requieren estrategias urgentes para la prevención primaria y secundaria del ictus en este grupo particular de pacientes en nuestro país.

During platelet activation, arachidonic acid (AA) is released from membrane phospholipids and metabolized to thromboxane A2 (TXA2) through the actions of cyclooxygenase-1 (COX-1) and TXA2 synthase. Note, TXA2 binds to the platelet TXA2 receptor, causing shape change, secretion and platelet aggregation.1 Also, COX-1 (599aa; 70 kDa) has cyclooxygenase and peroxidase activities and it is functionally active as a homodimer, with each COX-1 monomer consisting of four highly conserved domains: an N-terminal signal peptide, a dimerization domain, a membrane-binding domain (MBD) and a large C-terminal catalytic domain2 (Figure 1A). Irreversible COX-1 inhibition by aspirin is a widely established anti-platelet therapy in cardiovascular disease., Fundación Mutua Madrileña, Grant/Award Number: AP172142019; Fundación Séneca, Grant/Award Number: 19873/GERM/15; Gerencia Regional de Salud, Grant/Award Numbers: 1647/A/17, 2061A/19; Instituto de Salud Carlos III (ISCIII) & Feder, Grant/Award Numbers: CB15/00055, PI17/01966, PI18/00598, PI20/00926, PI17/01311; Junta de Castilla y León; British Heart Foundation, Grant/Award Number: PG/17/40/33028; Ayuda a Grupos de Trabajo en Patología Hemorrágica; Premio López Borrasca 2019; Sociedad Española de Trombosis y Hemostasia.

Al examinar la evolucion reciente del mercado de trabajo en Espana, uno de 10s fenomenos resenados con mas frecuencia es el incremento brusco de la poblacion activa femenina, tanto en terminos relatives como absolutos, durante 10s dos ultimos anos. Segun las cifras disponibles sobre el volumen de mano de obra, se habria producido una inexplicable explosion en la participacion laboral de la mujer, de modo que entre el cuarto trimestre de 1985 y el mismo periodo de 1987 la poblacion activa femenina crecio un 17,O por ciento, mientras que la masculina 10 hizo s610 en un 1,3 por ciento. A su vez, estos incrementos han repercutido de modo muy diferente en 10 que respecta a la composicion de la poblacion ocupada y desempleada. Durante el bienio senalado, el numero de mujeres con una ocupacion ha crecido un 13,l por ceinto, mientras que el de varones 10 ha hecho en un 6,3 por ciento. En cambio, la poblacion desempleada femenina crecio fuertemente (un 28,2 por ciento), cuando la masculina disminuyo en un 18,9 por ciento.' En cualquier caso, la tasa de actividad femenina seguia siendo a finales de 1987 de un 32,l por ciento (frente a un 67,6 por ciento de 10s varones), con una tasa de desempleo del 27,9 por ciento (16,O por ciento de 10s

According to reports from the literature,1,2 depending on the location where cavernomas appear, range from the very common locations to unusual. Cavernous malformations arising from the optic nerve and chiasm are rare, with only few cases reported to date.3-5 We present a case of a 28-yr-old man who suddenly started with sever visual loss in the right eye and homonymous lateral hemianopia in the left eye. Because of the acute symptomatology, a brain MRI was immediately performed in order to diagnose the etiology. The MRI showed a chiasmatic mass with right extension, heterogeneous on T1 and T2 sequences, without enhancement after gadolinium. The surgery was carried out a week after the diagnosis. A right pterional transsylvian approach was performed and the cavernoma was resected with microsurgical maneuvers, preserving the optic nerve fibers, chiasm, and optic tract. The patient evolved favorably, improving the visual deficit in the postoperative period as can be observed in the postoperative visual field study 7 mo after the surgery. The patient signed an informed consent for the procedure and agreed with the use of his images and surgical video for research and academic purposes. Our surgical case emphasizes the importance of a prompt diagnosis and surgery for chiasmatic cavernomas3 associated to visual loss, providing early decompression of the optic apparatus and improvement of the visual field defects after surgery.

China y los países vecinos han incursionado en uno de los proyectos de infraestructura más importantes de la historia. Se trata de la iniciativa Una franja Una Ruta, también conocida como la Ruta de la Seda. Su propósito es incrementar y hacer más eficiente el comercio en la región de Asia, Eurasia, África y Europa. Además, existe evidencia que sugiere que China está realizando intentos por mejorar su relación comercial con países de América Latina y el Caribe. El caso de México es interesante ya que su estrecha relación comercial con Estados Unidos y la falta de complementariedad con el mercado chino lleva a que la Ruta de la Seda sea de poco interés para el gobierno mexicano.

Background: Acute myeloid leukemia (AML) remains a major clinical challenge due to poor overall survival, which is even more dramatic in elderly patients. TIGIT, an inhibitory receptor that interacts with CD155 and CD112 molecules, is considered as a checkpoint in T and NK cell activation. This receptor shares ligands with the co-stimulatory receptor DNAM-1 and with TACTILE. The aim of this work was to analyze the expression of DNAM-1, TIGIT and TACTILE in NK cells and T cell subsets in AML patients. Methods: We have studied 36 patients at the time of diagnosis of AML and 20 healthy volunteers. The expression of DNAM-1, TIGIT and TACTILE in NK cells and T cells, according to the expression of CD3 and CD56, was performed by flow cytometry. Results: NK cells, CD56&minus, T cells and CD56+ T (NKT-like) cells from AML patients presented a reduced expression of DNAM-1 compared with healthy volunteers. An increased expression of TIGIT was observed in mainstream CD56&minus, T cells. No differences were observed in the expression of TACTILE. Simplified presentation of incredibly complex evaluations (SPICE) analysis of the co-expression of DNAM-1, TIGIT and TACTILE showed an increase in NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE. Low percentages of DNAM-1&minus, TIGIT+TACTILE+ NK cells and DNAM-1&minus, TIGIT+TACTILE+ CD56&minus, T cells were associated with a better survival of AML patients. Conclusions: The expression of DNAM-1 is reduced in NK cells and in CD4+ and CD8+ T cells from AML patients compared with those from healthy volunteers. An increased percentage of NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE is associated with patient survival, supporting the role of TIGIT as a novel candidate for checkpoint blockade.

Epilepsy is a common symptom in patients with primary central nervous system (CNS) tumors. Seizures are reported in 15–95% of patients with brain tumors, depending on the type of tumor [1]. Seizures are the presenting symptom in 15–50% of patients with gliomas, and up to 75% will have at least one seizure at some point in the disease course [2]. The recognition and classification of epileptic seizures and providing effective treatment are essential to preserve the quality of life of patients with glial tumors. In a previous study, we found that 63% of patients with glial tumors experienced seizures at some point in the disease course. Sixty two percent of seizures were focal onset, while 38% were generalized onset seizures [3]. However, considering the tumor etiology of seizures, we were unable to verify the results. Therefore, the goal of this study was to present the results of a larger cohort of patients with primary glial tumors and epilepsy based on a more rigorous examination approach. The primary objectives of this study were to classify and quantify epileptic seizures as a symptom of onset or later in the course of the disease and the correlation between ILAE 1981 and 2017 classifications [5,6]. The secondary objectives were to quantify: 1) the cases in which epileptic seizures were reclassified; 2) patients who received antiepileptic drugs (AEDs) as monotherapy; 3) patients whose antiepileptic treatment on admission was modified; and (4) patients whose seizures were controlled with the prescribed AEDs.

Resumen Introduccion El infarto isquemico secundario a anomalia del desarrollo venoso es infrecuente y su fisiopatologia no se conoce con certeza. Caso clinico Presentamos el caso de un paciente con antecedente de adenocarcinoma de prostata, quien durante el posoperatorio mediato presento cefalea intensa y crisis generalizadas tonico-clonicas. El resultado de la tomografia de cerebro inicial fue interpretado como metastasis. La resonancia magnetica y la tomografia computarizada evidenciaron una anomalia del desarrollo venoso e isquemia periferica a la malformacion. Conclusion Es importante evitar el sesgo diagnostico de los hallazgos en las neuroimagenes de pacientes oncologicos y, asi, plantear los diagnosticos diferenciales, incluso los infrecuentes.

Natural killer (NK) cells are lymphocytes of the innate immune response characterized by their role in the destruction of tumor cells. Activation of NK cells depend on a fine balance between activating and inhibitory signals mediated by different receptors. In recent years, a family of paired receptors that interact with ligands of the Nectin/Nectin-like (Necl) family has attracted great interest. Two of these ligands, Necl-5 (usually termed CD155 or PVR) and Nectin-2 (CD112), frequently expressed on different types of tumor cells, are recognized by a group of receptors expressed on T and NK cells that exert opposite functions after interacting with their ligands. These receptors include DNAM-1 (CD226), TIGIT, TACTILE (CD96) and the recently described PVRIG. Whereas activation through DNAM-1 after recognition of CD155 or CD112 enhances NK cell-mediated cytotoxicity against a wide range of tumor cells, TIGIT recognition of these ligands exerts an inhibitory effect on NK cells by diminishing IFN-γ production, as well as NK cell-mediated cytotoxicity. PVRIG has also been identified as an inhibitory receptor that recognizes CD112 but not CD155. However, little is known about the role of TACTILE as modulator of immune responses in humans. TACTILE control of tumor growth and metastases has been reported in murine models, and it has been suggested that it negatively regulates the anti-tumor functions mediated by DNAM-1. In NK cells from patients with solid cancer and leukemia, it has been observed a decreased expression of DNAM-1 that may shift the balance in favor to the inhibitory receptors TIGIT or PVRIG, further contributing to the diminished NK cell-mediated cytotoxic capacity observed in these patients. Analysis of DNAM-1, TIGIT, TACTILE and PVRIG on human NK cells from solid cancer or leukemia patients will clarify the role of these receptors in cancer surveillance. Overall, it can be speculated that in cancer patients the TIGIT/PVRIG pathways are upregulated and represent novel targets for checkpoint blockade immunotherapy.

Resumen Introduccion Los meningiomas son los tumores primarios mas frecuentes del sistema nervioso central y son de consulta frecuente en neurooncologia. Metodos Se realizo una revision bibliografica extensa y actualizada con el objetivo de favorecer el mejor abordaje de esta patologia. Resultados Los meningiomas son tumores extraaxiales originados a partir de las celulas de la aracnoides y representan el 36,4% de los tumores primarios intracraneanos. Los meningiomas pueden ser incidentales, pequenos y de lento crecimiento, o masas extensas y/o de crecimiento progresivo. La primera alteracion genetica descripta fue la perdida del cromosoma 22; en los ultimos anos se han descripto diversas mutaciones geneticas, tales como las mutaciones del promotor de transcriptasa reversa de la telomerasa (TERT), implicadas en la progresion maligna. Las neuroimagenes suelen tener caracteristicas distintivas en la tomografia computarizada y la resonancia magnetica. Por anatomia patologica se los clasifica en grados i , ii y iii de la Organizacion Mundial de la Salud y existen diversos subtipos con diferentes caracteristicas, evolucion y pronostico. La neurocirugia y el grado de reseccion son el pilar del tratamiento y el predictor de progresion. En pacientes seleccionados se podria considerar la embolizacion prequirurgica. La radioterapia puede ser adyuvante o como tratamiento unico en los irresecables; al igual que en los grados ii y anaplasicos. En relacion con la terapia farmacologica, solo bevacizumab, sunitinib y vatalinib han mostrado una potencial actividad clinica. Conclusiones Describimos en detalle las caracteristicas mas relevantes, la evaluacion y las opciones terapeuticas disponibles para pacientes con meningiomas.

Resumen Los cambios generados en los ultimos anos en el tratamiento de pacientes con tumores primarios del SNC nos obligan a considerar seriamente el «timing» o «los tiempos» en los que estos tratamientos son instaurados. A su vez, es aceptado el concepto que, para maximizar la efectividad del tratamiento de los pacientes con cancer, este debiera ser comenzado lo antes posible. Entre los factores que intervienen en la determinacion de este «tiempo» se menciona la complejidad que tiene la evaluacion de estos pacientes antes de iniciar los tratamientos. El objetivo del siguiente trabajo, a partir de una revision sistematica de la literatura, es desarrollar recomendaciones en cuanto a la distribucion de los tiempos desde la primera evaluacion del paciente hasta la instauracion del tratamiento. Este trabajo esta dirigido a los profesionales comprometidos en la evaluacion y tratamiento de los pacientes con tumores primarios del SNC.

Introduction: Thromboxane A2 [TxA2] is generated from arachidonic acid by cyclooxigenase-1 (COX-1) (prostaglandin H synthase-1) and thromboxane synthase. Aspirin, which irreversibly inhibits COX-1, is a widely used antiplatelet therapy with proven clinical efficacy. Inherited platelet disorders (IPD) are rare diseases caused by alterations of relevant genes in platelet formation and/or function. Despite the relevance of the TxA2 pathway in platelet physiology, few patients with mutations in PTGS1, the gene encoding COX-1, have been identified ( Objective: Characterization of a patient with aspirin-like platelet defect and moderate bleeding, enrolled in the Spanish multicentric project "Functional and molecular characterization of patients with IPD". Methods: The index case is a 13-year-old adopted girl of Asian origin, referred because of moderate chronic bleeding (BAT-ISTH=6) and an aspirin-like platelet dysfunction. No coagulation defect or other relevant clinical symptoms were present. Platelet phenotyping included: blood count, PFA-100; platelet aggregation [LTA], glycoproteins (GP), activation and secretion of granules by flow cytometry (FC), TxA2 synthesis by enzyme-immunoassay, synthesis of eicosanoids by tandem gas chromatography with mass spectrometry (LC-MS), western-blot (WB) of platelet lysates, and immunofluorescence (IF) assays. The patient's DNA was analyzed with a HTS-gene panel (Bastida et al, Haematologica 2018). A HEK 293T cell transfection model was established to further assess the pathogenicity of the candidate variant found in the patient. Results: The index case has normal platelet size and count (206x109/L; 11.4 fL). PFA-100 times were normal for COL-ADP and prolonged for COL-EPI (>300s). The FC analysis showed normal expression of GPs (Ib/IX, IIb/IIIa, Ia, GPVI) and reduced fibrinogen*488 binding (20-30%) in response to ADP, TRAP and low dose CRP (2ug/mL). P-selectin and CD63 secretion with agonists was comparable to those of controls. LTA was normal with ristocetin (1.25mg/mL) and TRAP (25uM), reduced by 40-50% with ADP (10uM) and collagen (3ug/mL) and absent with epinephrine (10uM), low dose collagen (1ug/mL) and arachidonic acid (1.6mM). LTA with U46619 (5uM), a direct agonist of the TxA2 receptor, was normal, suggesting a defect in TxA2 synthesis. Indeed, TxA2 levels in LTA supernatants in the patient were very low (5ng/mL; G, [p.Asn143Ser] in PTGS1. This variant, not previously described, affects a conserved residue in the catalytic domain of COX-1, which is one of the three N-glycosylation sites in the enzyme. The variant was not associated with reduced COX-1 expression as evaluated by WB in platelet lysates, and by IF in spread washed platelets and leukocytes. HEK 293T cells transfected with wild-type COX-1 construct (validated by RT-PCR and WB), displayed substantial TxA2 synthesis (500ng/mL; 2.5x105 transfected cells) in response to arachidonic acid. In contrast, similar transfection of p.143Ser COX-1 mutant almost abrogated this TxA2 production (≈50-75ng/mL in 2.5x105 transfected cells). Conclusion: We have identified a novel autosomal dominant COX-1 variant, p.Asn143Ser, associated with functional haploinsufficiency of the enzyme and platelet aggregation defects. To our knowledge, this case represents the third description of variants in PTGS1 (Nance, JTH 2016; Sivapalaratnam, Blood 2018), which cause platelet dysfunction and bleeding. Disclosures Almarza: Rocket Pharmaceuticals: Equity Ownership, Patents & Royalties, Research Funding. Bueren:Rocket Pharmaceuticals, Inc.: Consultancy, Equity Ownership, Patents & Royalties: Inventor on patents on lentiviral vectors filled by CIEMAT, CIBERER and F.J.D and may be entitled to receive financial benefits from the licensing of such patents, Research Funding.

BACKGROUND AND OBJECTIVES: Chemosensitization using plerixafor combined with FLAG-IDA (PLERIFLAG regimen) showed promising results (48% CR/CRi) in a phase 2 trial for primary refractory and early relapsed (duration of first CR Patients: Of the 540 patients in the data base we analysed 300 patients relapsed or resistant to induction therapy, which had all data available. 241 patients were treated with FLAG-IDA, 41 with FLAGO-Ida, and 42 with PLERIFLAG. Differences between treatment cohorts were tested using Fisher exact test. Treatment cohorts (PLERIFLAG vs FLAG-IDA vs FLAGO-IDA) were similar in Age (p=0.5), Sex (p=0.5), FLT3-ITD mutated (p=0.5), EPI/HOVON cytogenetics score (p=0.5) and previous myelodisplasia (p=0.2). The three cohorts differed in time to relapse (p=0.001), previous stem cell transplantation (0.001), HOVON score (p=0.03) and SALFLAGE score (0.001). RESULTS There were no differences in terms of CR+CRi between the three types of treatment adjusted by Hovon risk score (Pleriflag: 48%, FLAG-IDA: 50% or FLAGO-IDA: 58%; Chrochan Maentel-Haenszel test, p=0.466) or SALFLAGE score (Chrochan-Maentel-Haenszel test, p=0.23). More patients were allografted in the PLERIFLAG (61%) group even not achieving CR/Cri, as compared to FLAG-IDA (38%) or FLAGO-Ida (61% vs 38% vs. 18%, p=0.0001). To compare PLERIFLAG against the other two types of salvage treatment we performed a Propensity Score in a proportion 1:3. We adjust variables like age, previous allogeneic transplant, time to relapse (refractory, 12 months), karyotype using MRC, and FLT3-ITD status. Karyotype risk was considered by HOVON criteria (inv16, t(8;21) vs others), and SALFLAGE (inv 16, intermediate risk, and unfavourable risk by MRC risk plus t(8;21)). The propensity score analyses showed that Compared to FLAG-IDA, PLERIFLAG was associated to increased survival (median OS 10.56 months vs. 5.6, p=0.03), but not improved EFS (2.83 months vs 1.41 months, p=0.8). The benefit in OS but not in EFS could be explained in part by frequent use of Allo SCT in patients who had not achieve CR/CRi in the PLERIFLAG cohort. In conclusion, our historical control study show that PLERIFLAG regimen is an acceptable therapeutic option for first relapsed/refractory adult AML patients. Disclosures Esteve: Jazz Pharmaceuticals: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Novartis: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy; Roche: Consultancy; Astellas: Consultancy, Speakers Bureau. Salamero:Novartis: Honoraria; Pfizer: Honoraria; Celgene: Honoraria; Daichii Sankyo: Honoraria. Perez Encinas:CELGENE: Consultancy; JANSSEN: Consultancy; GILEAD SCIENCES: Research Funding. Montesinos:Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research support, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Research support, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Research support, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research support, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Other: Research support; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Research support, Research Funding, Speakers Bureau; Teva: Membership on an entity's Board of Directors or advisory committees, Other: Research support, Research Funding, Speakers Bureau.

La tomografía por emisión de positrones con metionina carbono 11 (11C-metionina PET/TC) se utiliza en la evaluación de los tumores primarios del sistema nervioso central. Describimos nuestra experiencia sobre los primeros 4 pacientes con tumores de la serie glial estudiados con 11C-metionina PET/TC. Este es un estudio descriptivo, observacional y prospectivo. Se presentan 4 pacientes entre 38-50 años de edad con diagnóstico de gliomas (clasificación de la OMS). A todos se les realizó RM y 11C-metionina PET/TC para evaluar actividad tumoral y diferenciar progresión tumoral de pseudoprogresión. Caso 1, gliomatosis cerebri grado II posradioterapia. Caso 2, glioblastoma grado IV postratamiento RT + temozolomida. Caso 3, oligodendroglioma grado II posradioterapia en 1993. Caso 4, oligoastrocitoma anaplásico grado III postratamiento RT + temozolomida. El patrón de captación de la 11C-metionina comparativamente con la RM, demostró progresión tumoral en los casos 1, 3 y 4; en el caso 2 mostró captación aunque el diagnóstico final fue pseudoprogresión. A diferencia del PET con 18fluordeoxiglucosa, la captación de 11C-metionina en el tejido cerebral normal y en la pseudoprogresión es baja, y los gliomas se visualizan como áreas metabólicamente activas. En los casos presentados, el 11C-metionina PET/TC proveyó información valiosa sobre el comportamiento y extensión de la lesión, aunque en uno de los casos presentados no diferenció progresión tumoral de pseudoprogresión. El 11C-metionina PET/TC sería una herramienta útil en el estudio y seguimiento de los pacientes con gliomas.

Resumen El tratamiento quirurgico de los tumores gliales del sistema nervioso central es un marcador pronostico y uno de los pilares respecto del tiempo libre de progresion y sobrevida del paciente. Sin embargo, el riesgo de secuelas neurologicas posquirurgicas aumenta con el grado de reseccion y localizacion del tumor. Basandonos en las caracteristicas de las neuroimagenes tumorales y posquirurgicas, confeccionamos esta guia para la planificacion prequirurgica, incluyendo algunos comentarios del acto quirurgico y el seguimiento posquirurgico, con el objetivo de clasificar y definir porcentajes de reseccion adecuadamente.

Background: Fabry disease (FD) is an underdiagnosed cause of stroke in youngadults, but the frequency of this association is largely unknown. We estimatedthe prevalence of FD in a nationwide cohort of young adults who had stroke andtransient ischemic attack (TIA) in Argentina. Methods: This was a prospective, multicenterstudy of stroke and FD in young adults (18-55 years) conducted in Argentinabetween 2011 and 2015. Patients were enrolled if they had had a TIA or an ischemicor hemorrhagic stroke within the previous 180 days. FD was diagnosed bymeasuring α-galactosidase A activity (males) and through genetic studies (females).Results: We enrolled 311 patients (54% men, mean age: 41 years). Ischemic eventsoccurred in 89% of patients (80% infarcts, 9% TIA) and hemorrhagic strokes in11%. One female (.3% of the total group, 1% of the cryptogenic ischemic strokes)had the pathogenic mutation c.888G>A/p.Met296Ile /Exon 6 on the GAL gene.Her only other manifestation of FD was angiokeratoma. Eighteen females hadnonpathogenic intronic variations: c.-10C>T, c.-12G>A, or both. Two patients hadthe nonpathogenic mutation D313Y, while a third had the likely benign mutationS126G. Conclusions: FD was identified in 1 patient (.3%) in this first LatinAmerican study. The patient presented with a late-onset oligo-symptomatic formof the disease. A large number of nonpathogenic mutations were present in ourcohort, and it is essential that they not be mistaken for pathogenic mutations to avoid unnecessary enzyme replacement treatment. Fil: Reisin, Ricardo C.. Hospital Británico de Buenos Aires; Argentina Fil: Mazziotti, Julieta. Hospital Británico de Buenos Aires; Argentina Fil: León Cejas, Luciana. Hospital Británico de Buenos Aires; Argentina Fil: Zinnerman, Alberto. Hospital Posadas; Argentina Fil: Bonardo, Pablo. Hospital Británico de Buenos Aires; Argentina Fil: Fernandez Pardal, M.. Hospital Británico de Buenos Aires; Argentina Fil: Martinez, A.. Hospital Posadas; Argentina Fil: Riccio, Patricia. Fundación Favaloro; Argentina Fil: Ameriso, Sebastián. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Bendersky, Eduardo. INAREPS; Argentina Fil: Nofal, Pedro. Sanatorio Parque Tucumán; Argentina Fil: Cairola, Patricia. CEMIC; Argentina Fil: Jure, Lorena. Sanatorio Parque Rosario; Argentina Fil: Sotelo, Andrea. Sanatorio Adventista del Plata; Argentina Fil: Rozenfeld, Paula Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: Ceci, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: Casas Parera, Ignacio Faustino. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Sánchez Luceros, Analía Gabriela. Academia de Medicina; Argentina

Cancer is primarily considered a disease of old age. Immunosenescence refers to the age-associated changes in the immune system, and its contribution to the increased risk of cancer in old individuals has been discussed for many years. Natural killer (NK) cells are cytotoxic innate immune cells specialized in defence against tumour and virus-infected cells. NK cell cytotoxicity is the result of a fine balance between activating and inhibitory receptors. Several activating receptors have been identified that recognize different ligands frequently found over-expressed on tumour cells or virus-infected cells. The most important NK cell inhibitory receptors interact with major histocompatibility complex class I molecules expressed on almost all nucleated cells preventing NK cell-mediated lysis of healthy cells. NK cell immunosenescence is characterized by a redistribution of NK cell subsets, a diminished expression of several activating receptors and lower per-cell cytotoxicity. Altered expression of activating receptors has also been described in young and elderly cancer patients probably due to chronic exposure to ligands on tumour cells. Thus, the effect of both age and cancer may act synergistically to diminish NK cell-mediated tumour immunosurveillance. Different strategies harnessing the power of NK cells to target tumour cells have been designed including adoptive therapy with autologous or allogeneic expanded NK cells. In addition, checkpoint blockade of inhibitory receptors and the use of agonist antibodies to stimulate activating receptors are emerging areas of research. In this context, the effect of immunosenescence should be considered to improve the efficiency of cancer immunotherapy.

Resumen Introduccion La prevalencia de embarazos en la poblacion con tumores gliales es desconocida. Casos clinicos Este es un estudio descriptivo, observacional, retrospectivo sobre 140 pacientes con tumores gliales diagnosticados entre enero de 2002 y septiembre de 2011; 49 fueron mujeres, 28 en edad fertil. Solo se registraron 3 embarazos. Dos fueron primigestas. Solamente un embarazo fue planificado. Todas se encontraban en tratamiento por epilepsia secundaria. Solo una paciente presento una crisis parcial motora durante el embarazo. Una paciente recibio temozolomida durante el primer mes de embarazo. Todos los embarazos llegaron a termino. Un parto fue vaginal. Un recien nacido presento sindrome de Down, y uno pie Bot y retraso madurativo. Conclusiones Los resultados de esta experiencia amplian los conocimientos sobre la maternidad en pacientes neurooncologicas.

La presencia de anticuerpos IgG en suero, con blanco en los canales de acuaporina-4, es específica de la neuromielitis óptica (NMO). El 60% de los pacientes con NMO presentan lesiones cerebrales en la resonancia magnética (RM); en un 8% (mayoría niños) estas lesiones se consideraron "atípicas". Presentamos dos pacientes con NMO y lesiones en el SNC de alta expresión de acuaporina-4. Caso 1: varón de 50 años, que comenzó con pérdida de visión en ojo derecho (OD). Recibió tratamiento empírico con metilprednisolona 1 g/d x 3 días. Al mes presentó dolor generalizado y hemiparesia derecha; nuevamente recibió metilprednisolona 1 g/d x 5 días e IgG IV 400 mg/kg/d × 5 días. Recuperó la deambulación persistiendo el dolor y fenómenos paroxísticos en los 4 miembros. Potenciales evocados visuales: P100, ojo izquierdo (OI) 123 mseg. OD sin respuesta. La RM de cerebro (FLAIR) mostró hiperintensidad en nervio óptico derecho, hipotálamo y comisura blanca anterior. RM cervical: lesión medular extensa (5 cuerpos vertebrales). Caso 2: mujer de 53 años, con disminución de la agudeza visual en ambos ojos y parestesias en miembros inferiores que remitieron espontáneamente. Evolucionó al mes con cuadriparesia e incontinencia esfinteriana. Recibió metilprednisolona 1 g/d x 5 días, sin mejoría. Potenciales evocados visuales: P100 OI 124 mseg. OD 128 mseg. RM cerebro: (FLAIR) hiperintensidad hipotalámica y periacueductal. RM cervical: lesión medular extensa (7 cuerpos vertebrales). Anticuerpos anti-acuaporina-4 positivos en ambos pacientes (inmunofluorescencia indirecta). Las lesiones consideradas "atípicas", como aquí, en sitios con alta densidad de proteínas canales de agua AQP4 deberán considerarse para el diagnóstico diferencial.Disease-specific aquaporin-4 antibodies (NMO-IgG) are the main effector of lesions in neuromyelitis optica (NMO) patients. Brain MRI lesions are detected in 60% of them, with 8% (almost infants) at sites of high aquaporin-4 expression. Patient 1: A fifty-year-old male with loss of vision in the right eye. Empiric treatment with metilprednisolone 1g/d for 3 days was indicated. After 30 days he complained of generalized pain, and a right hemiparesis was evident. The patient received bolus of metilprednisolone 1g/d for 5 days plus IgG 400 mg/kg/d IV for 5 days. He recovered ambulation but persisted with pain and paroxysmal phenomena (Lhermitte). Visual Evoked Potentials (VEP): P100 left eye 123 ms, right eye without response. Brain MRI (FLAIR) showed hyperintensity in the right optic nerve, hypothalamus and anterior white commissure. Cervical MRI showed extensive spinal cord lesion to an extension of 5 vertebral bodies. Patient 2: A fifty-three-year-old female who referred decreased visual acuity in both eyes and paresthesia in lower limbs which subsided spontaneously. One month later the patient evolved with cuadriparesis and sphincter incontinence. No improvement was observed with bolus of metilprednisolone 1g/d for 5 day. VEP: P100 left eye 124 ms, right eye 128 ms. Brain MRI (FLAIR) disclosed hypothalamic and periaqueductal hyperintensity. Cervical MRI showed extensive spinal cord lesion to an extension of 7 vertebral bodies. NMO-IgG antibodies were positive in both patients (indirect immunofluorescence assay). NMO brain lesions at sites of high aquaporin-4 expression, once considered "atypical" for their topography and infrequency in adults, should be borne in mind when considering differential diagnosis.

With funding provided by Microsoft Research, the Inter-American Development Bank and selected universities from the region, the LACCIR Federation promotes collaborative research in ICT and computer science within Latin America and the Caribbean (LAC). The focus is on applications for social and economic needs that are common throughout the LAC region. LACCIR aims to generate leverage between research teams and validate and generalize the research outcomes and their transfer to the society at large. This scientific collaboration allows researchers to address common problems and opportunities for the region. Thus, regional scientific collaboration becomes a possible source of solutions for its own social and economic needs. This paper describes the LACCIR organization, its main activities and some selected on-going research initiatives.

Introduction: Multiple Myeloma (MM) is an incurable disease. In young patients, autologous bone marrow transplantation (ABMT) remains a cornerstone treatment after induction therapy. Induction therapy has varied during time, from alkylating polychemotherapy (VBAD,VCMP) or VAD chemotherapy (AVAD) to Velcade-Dexametasone based regimens (VD). We present results of follow-up of a large cohort of patients treated with ABMT. We described overall survival (OS; from transplant to death by any cause) and progression free survival (PFS; from transplant to death by any case or progressive disease defined by reappearance by inmunofixation, or duplication of monoclonal peak after ABMT) , and the impact of induction therapy regiments. Patients: 183 patients transplanted from 2002 to 2017. The median age of the patients was 59 years (33-72). Before 2008 all the patients were treated in alkylating based chemotherapy (42 patients). After 2008 patients were treated with VD based regimens (141patients). Only 12 patients received maintenance therapy based in PETHEMA trials 2005 and 2012. No one patient received a planed second transplant; only 32 patients received a second transplant after relapse as consolidation therapy. Results: Median follow-up of patients still alive is 3.65 years (0.15-14.77). Median OS of all patients was 9.12 years (95% confidence interval (CI): 6.28-NR); Median PFS was 3.02 years(95% CI: 2.46-3.76). At 13 years only 2% of patients remains progression free (CI: 0.00-17%). There were significant differences between patients treated before and after VD regimens. The median OS of patients treated with APVAD was significantly shorter compared to VD (6.22 years, CI[3.39-12] vs. NR, CI[6.28-NR], p=0.025) (HR=0.49, p=0.01). Conclusions: VD schemes of induction before ABMT have improved remarkably OS inpatients with Myeloma; nonetheless, plateau is not observed in EFS. Further analysis must address if EFS could represent a strong indicator of OS, mainly due to novel effective salvage therapies after relapse/refractoriness could be a confounding factor. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Resumen Introduccion En los ultimos anos se sucedieron cambios en la neurooncologia que mejoraron la calidad de vida y sobrevida de pacientes con tumores primarios (TP) del SNC. Objetivos Presentar las caracteristicas clinicas de una cohorte de pacientes con TP de SNC de la serie glial. Material y metodos Entre los anos 2002-2009 se realizo el seguimiento de 148 pacientes con TP de SNC. Se analizaron solo los tumores de la serie glial intracraneanos. Este es un estudio descriptivo. Resultados Setenta y nueve pacientes (52 varones y 27 mujeres) presentaron tumores de la serie glial. El mayor numero de casos se presentaron en la cuarta decada. Segun la histopatologia: 34 glioblastomas multiformes (GBM), 6 astrocitomas GIII, 9 astrocitomas GII, 5 astrocitomas GI, 3 gliomas de tronco, 1 glioma cordoide, 16 oligodendrogliomas GII y 5 oligodendrogliomas GIII. La localizacion mas frecuente fue en el lobulo frontal. Los sintomas de inicio, en orden de frecuencia, fueron: crisis comiciales, cefalea, afasias, deficits cognitivos, motores o sensitivos, patologia de pares y sindrome de hipertension endocraneana. En 27 pacientes el tratamiento fue quirurgico/radioterapia/quimioterapia (Qx/Rt/Qt), 20 Rt/Qt, 6 Qx, 6 Qt, 5 Rt, 5 Qx/Qt, 4 Qx/Rt, y 6 pacientes no realizaron tratamiento. El 51% de los pacientes tuvieron reseccion parcial o completa del tumor. Las crisis epilepticas (parciales [62%] y generalizadas [38%]) fueron controladas completamente en el 66% de los casos con monoterapia. Conclusiones El GBM fue el tumor mas frecuente y el lobulo frontal el mas comprometido. El sintoma prevalente fueron las crisis epilepticas. Obtuvimos un porcentaje bajo de pacientes con reseccion parcial o completa del tumor.

Introduction Camptocormia is characterized by an abnormal posture of the trunk with marked forward flexion of the thoracolumbar spine, which accentuates during standing and walking and abates in the recumbent position. Material/methods Case report. Results We describe a 62-year-old woman with L1 vertebral body collapse and partial compression of the cauda equine underwent surgery decompression and stabilization with instrumentation technique. She was discharged 5 days later with ambulation preserved but with camptocormia. Electromyography of lumbar and lower thoracic paraspinal muscles showed denervation. Discussion A pathophysiological mechanism triggered by surgery with instrumentation technique resulted in denervation and atrophy of paraspinal muscles.

The objective of the study was to assess the cost of multiple sclerosis (MS) patients in Argentina categorized by disease severity using a societal perspective.Method:Cross-sectional study including MS patients from 21 MS centers in 12 cities of Argentina. Patients were stratified by disease severity using the expanded disability status scale (EDSS) (group 1 with EDSS score between 0 and 3; group 2 with EDSS >3 and 3 and 3 y 3 y

It is well-known that physical activities contribute to keep the people healthy. However, the modern life style impacts negatively on the amount of physical activity that we do during the day. Many times the people do not perform enough exercise because they are not aware of the amount of physical activity that they have done. In order to make the persons aware of this aspect of his life, this article presents a mobile application that monitors the amount of exercise they do every day and it informs properly to the user. The system, named AMOPA, allows caregivers or doctors monitoring particular patients, to access this information remotely in order to support the person being monitored. The system was evaluated using laboratory tests, and the results indicate a good performance and accuracy in the detection of the people physical activities. Moreover, the monitored process has a low impact on the energy consumption of the devices used to capture and process the information.

Positron emission tomography (PET) with 11C-methionine (11C-methionine PET/CT) is a new technique used to evaluate primary central nervous system (CNS) tumors. We describe our experience regarding the first 4 patients with glial tumors and 11C-methionine PET/CT. This is a descriptive, observational and prospective study of 4 patients between 38-50 years of age, with different gliomas (WHO classification). MRI and 11C-methionine PET/CT were performed in all cases. Case 1, gliomatosis cerebri grade II post-radiotherapy. Case 2, oligodendroglioma grade II diagnosed and treated with radiotherapy in 1993. Case 3, glioblastoma grade IV post-radiotherapy + temozolomide. Case 4, anaplastic oligoastrocytoma grade III post-radiotherapy + temozolomide. The pattern of 11C-methionine uptake compared with MRI showed tumor progression in cases 1, 3 and 4, and in case 2 showed uptake although the final diagnosis was pseudoprogression. Unlike 18fluordeoxiglucose PET/TC, 11C-methionine uptake in normal brain tissue and pseudoprogression is low, and gliomas are displayed as metabolically active areas. The 11C-methionine PET/CT provided valuable information on the tumoral behavior and extension, although in one case presented did not differentiate tumor progression from pseudoprogression. 11C-methionine PET/CT could be a useful tool in the study and follow-up to patients with gliomas.

We analyzed the value of new NCCN-IPI index in patients affected of Large B cell lymphoma (LBCL) treated with DA-EPOCH-R in order to assess the validity of this index in patients treated homogenously with dose adjusted R-EPOCH. Patients and protocol: We analyzed the use of NCCN-IPI (Zhou et al, 2014) index in a retrospective cohort of 98 DLBCL patients treated with -EPOCH. These patients were included in DA-EPOCH using IPI(Shipp M.A., 1993) as criteria of inclusion, including only patients (95 patients, 96%)with suspected bad prognosis based in IPI (2-5) and 3 patients with primary mediastinal large B cell lymphoma (PMLBCL). R-EPOCH was administered as reported previously(Wilson et al, 2013). Only 10 patients (10%) were Ann Arbor stage I or II. Results: The median age of the cohort was 57,13(15-82), 47 woman, 75 patients alived. The median follow-up of the patients alive is 6,7 years (1,3-11). Ann Arbor stage was IVB in 44 patients, and IVA in 21. Responses during treatment: Complete response (CR): 81 (82%), refractory during treatment: 7 (7%), death during treatment: 7 (7%). The number of patients who relapsed after treatment was 19 (20%). The median overall (OS) survival of all patients was not reached, (at 5 years, 0.669, CI: 0.562-0.798). The progression free survival (PFS) at 5 years is 0.62, CI: 0.483-0.795. We classify by the new NCCN-IPI the patients in Low-Intermediate risk (L-I)(3 patients, 3%), High-Intermediate risk (H-I)(38, 44%) and High risk (HR) (45, 52%). The OS at 5 years in H-I is 0.839 (CI: 0.73-0.96) and HR was 0.56 (CI: 0.421-0.754), p=0.025. The PFS at 5 years in H-I is 0.65 (CI: 0.518-0.826) and HR is 0.57 (CI: 0.43-0.755), p=0.4. Conclusions: NCCN-IPI discriminates well prognosis between HR/H-I patients with DLBCNHL treated with DA-EPOCH-R. The results of this retrospective analysis of high and intermediate high-risk patients compares better than the published in patients treated with R-CHOP. PFS were similar in H-I and HR; differences in OS could be explain by differences in outcome after salvage treatment with autologous stem cell Disclosures No relevant conflicts of interest to declare.

IMPLICATIONS We describe a technique of one-lung high-frequency jet ventilation surgery with continuous monitoring of airway pressures that achieves satisfactory operating conditions with less complications than other similar approaches.

Disease-specific aquaporin-4 antibodies (NMO-IgG) are the main effector of lesions in neuromyelitis optica (NMO) patients. Brain MRI lesions are detected in 60% of them, with 8% (almost infants) at sites of high aquaporin-4 expression. Patient 1: A fifty-year-old male with loss of vision in the right eye. Empiric treatment with metilprednisolone 1g/d for 3 days was indicated. After 30 days he complained of generalized pain, and a right hemiparesis was evident. The patient received bolus of metilprednisolone 1g/d for 5 days plus IgG 400 mg/kg/d IV for 5 days. He recovered ambulation but persisted with pain and paroxysmal phenomena (Lhermitte). Visual Evoked Potentials (VEP): P100 left eye 123 ms, right eye without response. Brain MRI (FLAIR) showed hyperintensity in the right optic nerve, hypothalamus and anterior white commissure. Cervical MRI showed extensive spinal cord lesion to an extension of 5 vertebral bodies. Patient 2: A fifty-three-year-old female who referred decreased visual acuity in both eyes and paresthesia in lower limbs which subsided spontaneously. One month later the patient evolved with cuadriparesis and sphincter incontinence. No improvement was observed with bolus of metilprednisolone 1g/d for 5 day. VEP: P100 left eye 124 ms, right eye 128 ms. Brain MRI (FLAIR) disclosed hypothalamic and periaqueductal hyperintensity. Cervical MRI showed extensive spinal cord lesion to an extension of 7 vertebral bodies. NMO-IgG antibodies were positive in both patients (indirect immunofluorescence assay). NMO brain lesions at sites of high aquaporin-4 expression, once considered atypical for their topography and infrequency in adults, should be borne in mind when considering differential diagnosis.