How we approach the treatment of patients with high-risk neuroblastoma with naxitamab: experience from the Hospital Sant Joan de Déu in Barcelona, Spain.

Naxitamab [humanized 3f8 (hu3F8)] is a humanized monoclonal antibody (mAb) targeting the disialoganglioside GD2. It was approved in 2020 by the United States Food and Drug Administration (FDA) in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) for treatment of pediatric and adult patients with relapsed/refractory high-risk neuroblastoma, limited to the bone or bone marrow (BM). The team at Sant Joan de Déu Children's Hospital in Barcelona, Spain, have been using naxitamab to treat neuroblastoma under clinical trial protocols [e.g. Trial 201, and hu3F8, irinotecan, temozolomide, and sargramostim (GM-CSF) (HITS) study] and compassionate use since 2017. The team has experience with two primary regimens: naxitamab with GM-CSF only, or naxitamab in combination with irinotecan, temozolomide, and GM-CSF (chemoimmunotherapy). This article aims to provide a practical overview of the team's experience with naxitamab to date, including preparing the treatment room and selecting the team. Adverse event management, including the use of ketamine to manage pain during anti-GD2 mAb infusions, is also discussed. We hope this will provide practical information for other health care providers considering offering this treatment.

Vertebral fractures are increased in rheumatoid arthritis despite recent therapeutic advances: a case-control study.

Prevalence and risk factors of vertebral fractures in postmenopausal RA women were assessed in 323 patients and compared with 660 age-matched women. Of patients, 24.15% had at least one vertebral fracture vs.16.06% of controls. Age, glucocorticoids and falls were the main fracture risks. Vertebral fractures were associated with disease severity. INTRODUCTION: There is little quality data on the updated prevalence of fractures in rheumatoid arthritis (RA) that may have changed due to advances in the therapeutic strategy in recent years. This study was aimed at analysing the prevalence and risk factors of vertebral fractures in postmenopausal women with RA and comparing it with that of the general population. METHODS: We included 323 postmenopausal women diagnosed with RA from 19 Spanish Rheumatology Departments, randomly selected and recruited in 2018. Lateral radiographs of the thoracic and lumbar spine were obtained to evaluate morphometric vertebral fractures and the spinal deformity index. We analysed subject characteristics, factors related to RA, and fracture risk factors. The control group consisted of 660 age-matched Spanish postmenopausal women from the population-based Camargo cohort. RESULTS: Seventy-eight (24.15%) RA patients had at least one vertebral fracture. RA patients had increased fracture risk compared with controls (106 of 660, 16.06%) (p = 0.02). Logistic regression analysis showed that age (OR 2.17; 95% CI 1.27-4.00), glucocorticoids (OR 3.83; 95% CI 1.32-14.09) and falls (OR 3.57; 95% CI 1.91-6.86) were the independent predictors of vertebral fractures in RA patients. The subgroup with vertebral fractures had higher disease activity (DAS28: 3.15 vs. 2.78, p = 0.038) and disability (HAQ: 0.96 vs. 0.63, p = 0.049), as compared with those without vertebral fractures. CONCLUSION: The risk of vertebral fracture in RA is still high in recent years, when compared with the general population. The key determinants of fracture risk are age, glucocorticoids and falls. Patients with vertebral fractures have a more severe RA.

Identification of a novel HLA-A allele, A*3120.

A novel human leukocyte antigen (HLA)-A allele, HLA-A*3120, was first identified in a National Marrow Donor Program (NMDP) donor. The A*3120 allele resulted from a single nucleotide substitution (T to G) at codon 92 of exon 3 of A*310102. The substitution caused an amino acid change (serine to alanine). This novel allele was also seen in two other unrelated NMDP donors.

[Neural bases of contextual modulation in associative learning]. / Sustratos neurales de la modulación contextual en el aprendizaje asociativo.

INTRODUCTION AND DEVELOPMENT: The contextual cues can modulate the conditioned response in numerous paradigms of learning. The brain mechanisms necessary for this contextual effect on learning are unknown. The objective of this review is to show the known aspects of the neurobiology of contextual learning and the contextual modulation of learning. CONCLUSIONS: The results indicate that the hippocampus and amygdala participate in a different way in the context-learning relation, depending on the contextual cues and the behavioural paradigm used. Others areas, like nucleus accumbens, striatum, and several cortical areas, also could operate in some contextual learning.

Sustratos neurales de la modulación contextual en el aprendizaje asociativo / Neural bases of contextual modulation in associative learning

Introducción y desarrollo. Las señales contextuales pueden modular la respuesta condicionada en numerosos paradigmas de aprendizaje. Los mecanismos cerebrales necesarios para este efecto contextual sobre el aprendizaje se desconocen. El objetivo de esta revisión es mostrar los aspectos conocidos de la neurobiología del aprendizaje contextual y de la modulacióncontextual del aprendizaje. Conclusiones. Los resultados sugieren que el hipocampo y la amígdala intervienen diferencialmenteen la relación contexto-aprendizaje, dependiendo de los estímulos contextuales y el paradigma comportamentalempleados. Otras regiones, como el núcleo accumbens, el estriado y varias áreas corticales, también parecen actuar en ciertas formas de aprendizaje contextual

Introduction and development. The contextual cues can modulate the conditioned response in numerous paradigmsof learning. The brain mechanisms necessary for this contextual effect on learning are unknown. The objective of this review is to show the known aspects of the neurobiology of contextual learning and the contextual modulation of learning.Conclusions. The results indicate that the hippocampus and amygdala participate in a different way in the context-learning relation, depending on the contextual cues and the behavioural paradigm used. Others areas, like nucleus accumbens, striatum, and several cortical areas, also could operate in some contextual learning

Réplica. Otros factores que condicionan la toxicidad a largo plazo de la 3'4 metilenodioximetanfetamina (‘éxtasis’) / Reply. Other factors that condition the long-term toxicity of 3, 4 methylenedioxymethamphetamine (ectasy)

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[3,4-methylenedioxymethamphetamine ('ecstasy'): its long-term emotional and cognitive effects, and serotonin depletion]. / 3,4-metilenodioximetanfetamina ('éxtasis'): efectos emocionales y cognitivos a largo plazo y deplecion serotoninérgica.

AIMS: The main objective of this study is to describe the different neuropsychological deficits associated to the consumption of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy'), as well as the growing evidence that attributes these deficits to the selective axonal damage to serotoninergic cells brought about by this substance. DEVELOPMENT: MDMA is an amphetamine derivative that, like its precursor, has properties as a stimulant. Part of its chemical structure is similar to that of the hallucinogen mescaline with which it shares the capacity to alter perception. Nevertheless, the primary pharmacological effect of this substance, which is what usually leads to its use and abuse, is chiefly linked to an intense positive emotional state. This effect on the individual's mood is also usually accompanied by numerous feelings of empathy, sociability and closeness, which turn this drug into a powerful entactogenic agent (a term used in psychotherapy to describe a state of wellbeing, closeness and emotional self-awareness produced by certain compounds). The antidepressant and entactogenic effects induced by an acute dose of MDMA can be accounted for by the notable increase in serotonin bioavailability triggered by the drug. Repeated consumption of MDMA, however, ends up affecting many functions that have been related to the serotoninergic systems, such as sleep, appetite, attention and memory, or one's emotional state. CONCLUSIONS: Most of the neuropsychological disorders found in individuals who take ecstasy on a regular basis can be explained by the selective neurodegeneration processes that the drug appears to produce in the serotonin terminals of the brain in the long run.

3, 4-metilenodioximetanfetamina (‘éxtasis’): efectos emocionales y cognitivos a largo plazo y depleción serotoninérgica / 3, 4-methylenedioxymethamphetamine (‘ecstasy’): its long-term emotional and cognitive effects, and serotonin depletion

Objetivo. El principal objetivo de este trabajo es describirlos diferentes déficit neuropsicológicos asociados al consumode 3,4-metilenodioximetanfentamina (MDMA o ‘éxtasis’), así comolas numerosas evidencias que atribuyen estos déficit al dañoaxonal selectivo de las células serotoninérgicas inducido por estasustancia. Desarrollo. La MDMA es un derivado de la anfetaminaque posee, al igual que ésta, propiedades estimulantes. Parte de suestructura química es similar a la del alucinógeno mescalina, conel que comparte, además, la capacidad de alterar la percepción.No obstante, el efecto farmacológico primario de esta sustancia, elcual suele inducir su uso y abuso, se relaciona principalmente conun intenso estado emocional positivo. Esta acción sobre el estadoanímico suele acompañarse, además, por numerosas sensacionesde empatía, sociabilidad y cercanía que convierten a esta droga enun potente agente entactógeno (término empleado en psicoterapiapara describir el estado de bienestar, de proximidad y de autoconcienciaemocional que inducen algunos compuestos). Los efectosantidepresivos y entactógenos que provoca una dosis aguda deMDMA se deben al notable incremento en la biodisponibilidad deserotonina que provoca esta droga. Sin embargo, el consumo repetidode MDMA acaba afectando a numerosas funciones que se hanasociado a los sistemas serotoninérgicos, como el sueño, el apetito,la atención y memoria, o el estado emocional. Conclusiones. Lamayor parte de las alteraciones neuropsicológicas halladas en losconsumidores habituales de éxtasis puede explicarse por los procesosde neurodegeneración selectiva que parece producir estadroga a largo plazo en los terminales serotoninérgicos del cerebro

Aims. The main objective of this study is to describe the different neuropsychological deficits associated to theconsumption of 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy’), as well as the growing evidence that attributesthese deficits to the selective axonal damage to serotoninergic cells brought about by this substance. Development. MDMA isan amphetamine derivative that, like its precursor, has properties as a stimulant. Part of its chemical structure is similar tothat of the hallucinogen mescaline with which it shares the capacity to alter perception. Nevertheless, the primary pharmacologicaleffect of this substance, which is what usually leads to its use and abuse, is chiefly linked to an intense positiveemotional state. This effect on the individual’s mood is also usually accompanied by numerous feelings of empathy, sociabilityand closeness, which turn this drug into a powerful entactogenic agent (a term used in psychotherapy to describe a state ofwellbeing, closeness and emotional self-awareness produced by certain compounds). The antidepressant and entactogeniceffects induced by an acute dose of MDMA can be accounted for by the notable increase in serotonin bioavailability triggeredby the drug. Repeated consumption of MDMA, however, ends up affecting many functions that have been related to theserotoninergic systems, such as sleep, appetite, attention and memory, or one’s emotional state. Conclusions. Most of theneuropsychological disorders found in individuals who take ecstasy on a regular basis can be explained by the selectiveneurodegeneration processes that the drug appears to produce in the serotonin terminals of the brain in the long runAims. The main objective of this study is to describe the different neuropsychological deficits associated to the consumption of 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy’), as well as the growing evidence that attributes these deficits to the selective axonal damage to serotoninergic cells brought about by this substance. Development. MDMA is an amphetamine derivative that, like its precursor, has properties as a stimulant. Part of its chemical structure is similar to that of the hallucinogen mescaline with which it shares the capacity to alter perception. Nevertheless, the primary pharmacological effect of this substance, which is what usually leads to its use and abuse, is chiefly linked to an intense positive emotional state. This effect on the individual’s mood is also usually accompanied by numerous feelings of empathy, sociability and closeness, which turn this drug into a powerful entactogenic agent (a term used in psychotherapy to describe a state of wellbeing, closeness and emotional self-awareness produced by certain compounds). The antidepressant and entactogenic effects induced by an acute dose of MDMA can be accounted for by the notable increase in serotonin bioavailability triggered by the drug. Repeated consumption of MDMA, however, ends up affecting many functions that have been related to the serotoninergic systems, such as sleep, appetite, attention and memory, or one’s emotional state. Conclusions. Most of the neuropsychological disorders found in individuals who take ecstasy on a regular basis can be explained by the selective neurodegeneration processes that the drug appears to produce in the serotonin terminals of the brain in the long run

Psicofarmacología de la nicotina y conducta adictiva / Psycopharmacology of nicotine and addiction

Objetivo: El principal objetivo de este trabajo es describir los aspectos fundamentales de la psicofarmacología de la nicotina para poder comprender las peculiares propiedades adictivas de esta sustancia. Material y métodos: Se revisa la psicofarmacología de la nicotina. En primer lugar, se analizan los mecanismos esenciales de actuación de la nicotina en el cerebro que parecen explicar los procesos de dependencia, tolerancia y abstinencia asociados al tabaquismo. Se describen también los mecanismos de acción y los efectos de varias de las terapias sustitutivas de la nicotina del tabaco. Finalmente, se comentan algunos recientes hallazgos acerca de la relación entre nicotina y ciertos trastornos psiquiátricos y neurodegenerativos, que pueden ayudar a entender la compleja e imbricada acción de esta sustancia en nuestro cerebro. Resultados: El tabaco es una droga adictiva, como lo es la cocaína, la heroína, las anfetaminas y algunos derivados, o el alcohol. La nicotina presente en esta droga es la responsable de tal conducta adictiva al inducir numerosos cambios bioquímicos y estructurales en el sistema nervioso central. La insidiosa e intensa dependencia a la nicotina que provoca el consumo de tabaco tiene serias repercusiones médicas, debidas no sólo a los efectos indeseables de la propia nicotina, sino también a los de los numerosos compuestos tóxicos que contiene el tabaco. Conclusiones: Las características farmacológicas de la nicotina, muy diferentes a las de otras drogas, explican el distintivo perfil adictivo de esta sustancia

Objective: The main aim of this work is to describe the fundamental aspects of the psychopharmacology of nicotine, in order to understand the addictive properties peculiar to this substance. Material and methods: The psychopharmacology of nicotine and addiction it is reviewed. Firstly, this review will show the essential mechanisms of the action of nicotine on the brain, which seem to explain the processes of dependence, tolerance and abstinence associated to smoking. For this reason, and also because this addiction causes serious health problems, this report will also describe the action mechanisms and the effects of some of the therapeutic substitutes for nicotine in tobacco. Finally, there is a breakdown of some recent finds regarding the relation between nicotine and certain psychiatric and neurodegenerative disorders, which can help the understanding of the complex action of this substance on the brain. Results: Tobacco is an addictive drug, like cocaine, heroine, amphetamines and various derivatives, or alcohol. The nicotine present in this drug is responsible for this addictive behaviour as it induces numerous biochemical and structural changes in the central nervous system. On another level, the insidious and intense dependence on nicotine which provokes the consumption of tobacco has serious medical repercussions, not only due to the unwanted effects of the nicotine itself, but also due to the numerous toxic compounds contained in tobacco. Conclusions: The pharmacological characteristics of nicotine -- very different from those of other drugs -- explain the distinctive addictive profile of this substance