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BACKGROUND: Cushing's syndrome due to ectopic ACTH secretion is a rare clinical condition resulting from a dysregulated ACTH secretion by neuroendocrine tumors, which can have various localizations and different histological differentiations. The overall incidence of endogenous Cushing's syndrome is 0.7-2.4 per million people per year. Children account for just 10% of all new cases that are reported each year. CASE REPORT: When the patient first presented clinically, she was a 17-year-old girl who displayed symptoms of schizophrenia (delirium, psychotic episodes, and hallucinations). Blood tests showed diabetes mellitus and hypokalemia. She was also affected by high blood pressure and osteoporosis complicated by D9-D10 and L1-L5 vertebral collapses. For these reasons, she was treated with aripiprazole, insulin glargine, potassium chloride, spironolactone, enalapril, and calcium carbonate. After two months of treatment, she was referred to the pediatrician endocrinologist, who diagnosed hypercortisolism after prescribing hormone tests (Table 1). After receiving her diagnosis, she began taking 1000 mg of metyrapone and had a whole-body CT scan, which revealed bilateral adrenal hyperplasia. The results of the 68Ga-PET/DOTATOC and 18FDG-PET scans were negative. The clinical course was intermittent in the months that followed, with hypercortisolism and eucortisolism alternating. After one year of treatment, a 68Ga-PET/DOTATOC showed a nodule in the thymic lodge (Fig. 1). The patient underwent a thymectomy. Unfortunately, after surgery, she continued to have high levels of cortisol, for which she continued metyrapone 750 mg/die. 68Ga-PET/DOTATOC repeated three months after surgery showed again an uptake corresponding to the thymic lodge (Fig. 2). In order to remove the neuroendocrine lesion, she had a new surgery, which resulting a finally resolutive. ACTH levels were monitored before, during, and post-surgery (Table 2). The laboratory provided the ACTH results very quickly and thoracic surgeons waited for hormonal results before concluding the procedure. The adopted strategy permitted us to monitor the outcome of the surgery. CONCLUSION: The heterogeneity of ectopic Cushing's syndrome makes diagnosis difficult. Treatment of ectopic Cushing's syndrome requires close clinical, biochemical, and instrumental observation. Metyrapone is a drug able to control hypercortisolism in a lasting way with a good level of safety. 68Ga-PET/DOTATOC proves to be a tracer with good sensitivity and specificity for the identification of ACTH-secreting neuroendocrine lesions. The short half-life of ACTH is found to be a strategy to monitor the complete surgical resection of the neuroendocrine lesion. A multidisciplinary approach improves therapeutic success and reduces the risk of recurrence.
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BACKGROUNDPredicting immune effector cell-associated neurotoxicity syndrome (ICANS) in patients infused with CAR T cells is still a conundrum. This complication, thought to be consequent to CAR T cell activation, arises a few days after infusion, when circulating CAR T cells are scarce and specific CAR T cell-derived biomarkers are lacking.METHODSCAR+ extracellular vesicle (CAR+EV) release was assessed in human CD19.CAR T cells cocultured with CD19+ target cells. A prospective cohort of 100 patients with B cell lymphoma infused with approved CD19.CAR T cell products was assessed for plasma CAR+EVs as biomarkers of in vivo CD19.CAR T cell activation. Human induced pluripotent stem cell-derived (iPSC-derived) neural cells were used as a model for CAR+EV-induced neurotoxicity.RESULTSIn vitro release of CAR+EVs occurs within 1 hour after target engagement. Plasma CAR+EVs are detectable 1 hour after infusion. A concentration greater than 132.8 CAR+EVs/µL at hour +1 or greater than 224.5 CAR+EVs/µL at day +1 predicted ICANS in advance of 4 days, with a sensitivity and a specificity outperforming other ICANS predictors. ENO2+ nanoparticles were released by iPSC-derived neural cells upon CAR+EV exposure and were increased in plasma of patients with ICANS.CONCLUSIONPlasma CAR+EVs are an immediate signal of CD19.CAR T cell activation, are suitable predictors of neurotoxicity, and may be involved in ICANS pathogenesis.TRIAL REGISTRATIONNCT04892433, NCT05807789.FUNDINGLife Science Hub-Advanced Therapies (financed by Health Ministry as part of the National Plan for Complementary Investments to the National Recovery and Resilience Plan [NRRP]: E.3 Innovative health ecosystem for APC fees and immunomonitoring).
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Antígenos CD19 , Vesículas Extracelulares , Inmunoterapia Adoptiva , Linfoma de Células B , Humanos , Vesículas Extracelulares/inmunología , Vesículas Extracelulares/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Antígenos CD19/inmunología , Linfoma de Células B/inmunología , Linfoma de Células B/terapia , Linfoma de Células B/sangre , Adulto , Anciano , Receptores Quiméricos de Antígenos/inmunología , Estudios ProspectivosRESUMEN
The introduction of novel drugs (PD-1 inhibitors and/or brentuximab vedotin) into salvage regimens has improved the response rate and the outcome of patients with relapsed/refractory Hodgkin lymphoma. However, the impact of new drugs on the outcome has not been adequately investigated so far. We retrospectively analyzed 42 consecutive patients treated at our institution with high-dose chemotherapy/autologous stem cell transplantation after either one standard chemotherapy represented by BEGEV (n = 28) or >1 salvage therapy (ST) comprising novel drugs (n = 14). With a median follow-up of 24 months, the 2-year cumulative incidence of relapse was similar between the two cohorts: 26% for 1 ST and 18% for >1 ST (p = 0.822). Consistently, overall survival and progression-free survival did not differ among the two groups: 3-year overall survival was 91% and 89% (p = 0.731), respectively, and 3-year progression-free survival was 74% and 83% (p = 0.822) for only one and more than one salvage regimens, respectively. Of note, the post-transplant side effects and engraftment rates were similar between the 1 ST and >1 ST cohorts. In conclusion, consolidation with high-dose chemotherapy/autologous stem cell transplantation is a safe and curative option, even for patients achieving disease response after more than one rescue line of therapy.
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Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/tratamiento farmacológico , Estudios Retrospectivos , Trasplante Autólogo , Inhibidores de Puntos de Control InmunológicoRESUMEN
Typical hemolytic uremic syndrome (HUS) is mainly caused by Shiga toxin-producing Escherichia coli (STEC) releasing Shiga toxin 2 (Stx2). Two different structures of this AB5 toxin have been described: uncleaved, with intact B and A chains, and cleaved, with intact B and a nicked A chain consisting of two fragments, A1 and A2, connected by a disulfide bond. Despite having the same toxic effect on sensitive cells, the two forms differ in their binding properties for circulating cells, serum components and complement factors, thus contributing to the pathogenesis of HUS differently. The outcome of STEC infections and the development of HUS could be influenced by the relative amounts of uncleaved or cleaved Stx2 circulating in patients' blood. Cleaved Stx2 was identified and quantified for the first time in four out of eight STEC-infected patients' sera by a method based on the inhibition of cell-free translation. Cleaved Stx2 was present in the sera of patients with toxins bound to neutrophils and in two out of three patients developing HUS, suggesting its involvement in HUS pathogenesis, although in association with other bacterial or host factors.
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Infecciones por Escherichia coli , Escherichia coli Shiga-Toxigénica , Humanos , Toxina Shiga II , Toxina Shiga , Neutrófilos , Bacterias , Infecciones por Escherichia coli/microbiologíaRESUMEN
BACKGROUND: Presenting symptoms of childhood cancers might mimic those of rheumatic diseases. However, the evidence available to guide differential diagnosis remains scarce. Preventing wrong or delayed diagnosis is therefore important to avoid incorrect administration of glucocorticoid or immunosuppressive therapy and worsening of prognosis. As such, we aimed to assess the prevalence and characteristics of presenting musculoskeletal manifestations in patients at cancer onset and to identify the factors that differentiate childhood malignancies with arthropathy from juvenile idiopathic arthritis. METHODS: We did a multicentre, cross-sectional study at 25 paediatric haemato-oncology centres and 22 paediatric rheumatology centres in Italy. We prospectively recruited patients who were younger than 16 years that were newly diagnosed with cancer or juvenile idiopathic arthritis. We excluded patients with glucocorticoid pre-treatment (>1 mg/kg per day of oral prednisone or equivalent for ≥2 consecutive weeks). We collected data for patients with a new diagnosis of cancer or juvenile idiopathic arthritis using an electronic case report form on a web-based platform powered by the Cineca Interuniversity Consortium. The primary outcome was to describe the frequency and characteristics of musculoskeletal manifestations at cancer onset; and the secondary outcome was to identify factors that could discriminate malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, from juvenile idiopathic arthritis using multivariable logistic regression analysis. FINDINGS: Between May 1, 2015, and May 31, 2018, 1957 patients were eligible, of which 1277 (65%) had cancer and 680 (35%) had juvenile idiopathic arthritis. Musculoskeletal symptoms occurred in 324 (25% [95% CI 23·0-27·8]) of 1277 patients with cancer, of whom 207 had arthropathy. Patients with malignant bone tumours had the highest frequency of musculoskeletal symptoms (53 [80%] of 66), followed by patients with Langerhans histiocytosis (16 [47%] of 34), leukaemia (189 [32%] of 582), soft-tissue sarcomas (16 [24%] of 68), and neuroblastoma (21 [19%] of 109). In the 324 patients with cancer and musculoskeletal symptoms, the most common complaints were joint pain (199 [61%]), followed by limb bone pain (112 [35%]). Joint involvement had a prevalent monoarticular pattern (100 [48%] of 207) and oligoarticular pattern (86 [42%] had 2-4 joints involved and 20 [10%] had >4 joints involved), with the most frequently involved joints being the hip (88 [43%] of 207) and knee (81 [39%]). On multivariable analysis, limb bone pain was the independent variable most strongly associated with cancer (odds ratio [OR] 87·80 [95% CI 18·89-408·12]), followed by weight loss (59·88 [6·34-565·53]), thrombocytopenia (12·67 [2·40-66·92]), monoarticular involvement (11·30 [4·09-31·19]), hip involvement (3·30 [1·13-9·61]), and male sex (2·40 [1·03-5·58]). Factors independently associated with juvenile idiopathic arthritis were morning stiffness (OR 0·04 [95% CI 0·01-0·20]), joint swelling (0·03 [0·01-0·09]), and involvement of the small hand joints (0·02 [0-1·05]). INTERPRETATION: Our study provides detailed information about presenting musculoskeletal manifestations of childhood cancers and highlights the clinical and laboratory features that are most helpful in the differential diagnosis with juvenile idiopathic arthritis. FUNDING: Associazione Lorenzo Risolo.
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Este trabalho tece uma reflexão baseada em lembranças de experiências emocionais com um paciente. A autora aborda a problemática do entrar em contato com a realidade psíquica: o deslocar da observação do mundo externo para um mundo interno, neste caso, povoado de emoções assustadoras. Partindo da afirmação de Bion, pela qual a observação da realidade psíquica resulta na modificação da mesma realidade, é feita a hipótese de que a possibilidade de desenvolvimento da mente estaria associada à percepção desta como um espaço interno passível de observação e conhecimento. Fatores que podem influenciar o processo são considerados: frustração, intuição, conhecimento, trabalho psíquico, todos implicados no processo do pensar.
This work weaves a reflection based on memories of emotional experiences with a patient. The author addresses the problem of getting in touch with psychic reality: the shifting of observation from the outside world to an internal world, in this case likely to be populated with frightening emotions. Starting from the assertion of Bion, whereby the observation of the psychic reality results in the modification of it, it is made the hypothesis that the possibility of the development of a mind would be associated with the perception of the same as an internal space capable of observation and knowledge. Factors that can influence the process are considered: frustration, intuition, knowledge, psychic work all implicated in the process of thinking.
Este trabajo teje una reflexión basada en memorias de experiencias emocionales con un paciente. El autor aborda el problema de entrar en contacto con la realidad psíquica: el desplazamiento de la observación desde el mundo exterior hacia un mundo interno, en este caso probable que esté poblada de emociones aterradoras. A partir de la afirmación de Bion, mediante la cual la observación de la realidad psíquica resulta en la modificación de la misma, se hace la hipótesis de que la posibilidad del desarrollo de una mente se asociaría a la percepción de la misma como un espacio interno capaz de observación y conocimiento. Se consideran factores que pueden influir en el proceso: frustración, intuición, conocimiento, trabajo psíquico, todo implicado en el proceso de pensar.
Ce travail tisse une réflexion basée sur des souvenirs d'expériences émotionnelles avec un patient. L'auteur aborde le problème de la mise en contact avec la réalité psychique: le déplacement de l'observation du monde extérieur vers un monde intérieur, dans ce cas susceptible d'être peuplé d'émotions effrayantes. À partir de laffirmation de Bion, auquel cas lobservation de la réalité psychique aboutit à la modification, il est fait lhypothèse que la possibilité du développement dun esprit serait associée à la perception du même comme un espace interne capable dobservation et connaissances. Les facteurs qui peuvent influencer le processus sont considérés: la frustration, l'intuition, la connaissance, le travail psychique tous impliqués dans le processus de la pensée.
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Pensamiento , Emociones , PsicoanálisisRESUMEN
O trabalho apresenta uma atividade desenvolvida pela equipe editorial do Jornal de Psicanálise na interface entre cinema e psicanálise. Um grupo de analistas se interessou pelo convite da equipe para conversar sobre o filme Festa de Família, do diretor Thomas Vinterberg. A conversa foi gravada e transcrita. Pensamos ser importante explorar as maneiras pelas quais a psicanálise pode ser difundida. Esta atividade demonstrou que um filme pode servir como estímulo para uma agradável e instigante conversa psicanalítica e trouxe à tona toda a riqueza deste tipo de encontro onde a possibilidade de trocar experiências de forma espontânea, tal qual pensamos possa ocorrer no próprio trabalho analítico, pode ter lugar. Foi possível ter a dimensão de um trabalho implicado, no qual a psicanálise esteve presente de forma viva e atuante, encarnada na fala de cada colega...
The paper presents an activity developed by the editorial staff of the Jornal de Psicanálise, in the interface between cinema and psychoanalysis. A group of analysts interested in the team invitation chose to talk about The Celebration, a film directed by Thomas Vinterberg. The conversation was recorded and then transcribed. This activity demonstrated that a film can work as a stimulus for an enjoyable and thought-provoking psychoanalytic conversation and brought up all the wealth of this kind of meeting, in which the possibility of exchanging experiences spontaneously took place, as it is thought to occur in the analytic work itself. It was possible to realize the magnitude of an involving job in which psychoanalysis was presented in an active and living form, incarnate in the speech of each colleague...
Este trabajo presenta una actividad desarrollada por el equipo editorial del Jornal de Psicanálise en la interface entre cine y psicoanálisis, que consistió en un encuentro de analistas para conversar sobre la película La Celebración [Festen] del director Thomas Vinterberg. La discusión fue grabada y transcripta. Pensamos que es importante ampliar las maneras por las cuales el psicoanálisis puede ser difundido. Esta actividad mostró que una película puede servir de gatillo para una agradable y estimulante charla psicoanalítica, y quedó evidente la enorme riqueza de este tipo de reunión, donde la posibilidad de intercambiar experiencias de manera espontánea, como nos parece que ocurre en el propio trabajo analítico, tiene lugar. Hubo un trabajo implicado, en el cual el psicoanálisis estuvo presente de forma viva y actuante, encarnado en el discurso de cada colega...
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Recursos Audiovisuales , Familia/psicología , PsicoanálisisRESUMEN
O objetivo do trabalho é descrever movimentos grupais em um seminário eletivo sobre contratransferência e enactment solicitado por membros filiados da SBPSP, na sua maioria residentes fora da capital paulista. Foi criado um formato experimental com carga horária condensada em dois encontros, no início e no fim do semestre, complementados por comunicação por correio eletrônico no período intermediário. O coordenador indicou um texto para cada mês do debate digital e uma bibliografia complementar. O ritmo inicialmente acelerado das mensagens foi brecando conforme o conteúdo estudado foi se aproximando da pessoa real do analista. No transcorrer da troca de 110 emails, contradições entre real/virtual, presença/ausência, conexão/desconexão, exposição/ocultamento, proximidade/distância, comunicação/confusão, típicas da cultura informatizada, foram configurando um interessante modelo para pensar os paradoxos do próprio setting psicanalítico. O estudo das transformações de impasses clínicos em conhecimento intersubjetivo evidenciou a reversão de perspectiva pela qual a contratransferência é vista, tanto no processo de uma análise como na história do movimento psicanalítico.
The objective of this work is to describe group movements inside a countertransference and enactment elective seminar, requested by Brazilian Psychoanalytical Society of São Paulo sbpsp, members which were in most nonresidents of São Paulo. An experimental format with condensed hours was created, with two meetings at the beginning and the end of the semester, added by electronic communication in the meantime. The coordinator recommended a text for each month of digital debate, as well as some complementary bibliography. The initially accelerated rhythm of the messages began to slow down as the content studied became closer to the real person of the analyst. Throughout the 110 emails exchange process, contradictions between real/virtual, presence/absence, connection/disconnection, exposure/hiding, proximity/distance, communication/ confusion, typical of the information culture, began configuring an interesting model to think over paradoxes of the psychoanalytical setting itself. The study of the transformations of clinical impasses into intersubjective knowledge revealed the reversion of perspective by which countertransference is seen, both in the process of an analysis and in the history of the psychoanalytical movement.
El objetivo del presente trabajo reside en describir los movimientos grupales en un seminario electivo sobre contratransferencia y enactment solicitado por miembros afiliados a la Sociedad Brasileña de Psicoanálisis de São Paulo SBPSP, que en su mayoría habitan fuera de la capital paulista. Se creó un programa experimental con una carga horaria distribuida en dos encuentros presenciales, al inicio y al final del semestre, y con comunicación por correo electrónico durante el período intermedio. El coordinador recomendó un texto para cada mes del debate virtual y bibliografía complementaria. El ritmo inicialmente acelerado de los mensajes fue frenándose conforme el contenido estudiado, aproximándose a la persona real del analista. Durante el transcurso del intercambio de 110 emails las oposiciones entre real/virtual, presencia/ausencia, conexión/desconexión, exposición/ocultamiento, proximidad/distancia, comunicación /confusión; típicas de la cultura informatizada, fueron configurando un interesante modelo para pensar en las paradojas del propio setting psicoanalítico. El estudio de las transformaciones de impases clínicos en conocimiento intersubjetivo evidenció la reversión de perspectiva a través de la cual la contratransferencia es vista, tanto en el proceso de un análisis como en la historia del movimiento psicoanalítico.