RESUMEN
Infant-type hemispheric glioma (IHG) is a rare pediatric brain tumor with variable response to chemotherapy and radiotherapy. Molecular insights into IHG can be useful in identifying potentially active targeted therapy. A male fetus was found to have congenital hydrocephalus at the gestational age of 37 weeks. Fetal MRI showed a 2.6 × 2.0-cm tumor located at the frontal horn of the left lateral ventricle, involving the left basal nuclei and thalamus. Tumor biopsy at the age of 2 days revealed an IHG consisting of spindle tumor cells with strong expression of GFAP and ALK. Targeted RNA sequencing detected a novel fusion gene of SOX5::ALK. After initial chemotherapy with cyclophosphamide, carboplatin, and etoposide for 2 cycles, the tumor size progressed markedly and the patient underwent a subtotal resection of brain tumor followed by treatment with lorlatinib, an ALK tyrosine kinase inhibitor with central nervous system (CNS) activity. After 3 months of treatment, reduction of tumor size was observed. After 14 months of treatment, partial response was achieved, and the infant had normal growth and development. In conclusion, we identified a case of congenital IHG with a novel SOX5::ALK fusion that had progressed after chemotherapy and showed partial response and clinical benefit after treatment with the CNS-active ALK inhibitor lorlatinib.
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Aminopiridinas , Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Glioma , Lactamas , Neoplasias Pulmonares , Pirazoles , Lactante , Niño , Masculino , Humanos , Recién Nacido , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Quinasa de Linfoma Anaplásico/genética , Lactamas Macrocíclicas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/terapia , Glioma/tratamiento farmacológico , Factores de Transcripción SOXDRESUMEN
BACKGROUND: Neuroblastoma varies widely in risk. Risk indicators in infants with incidental neuroblastoma refine treatment confidence for observation or intervention. The potential of functional imaging, particularly PET/CT, remains to be defined. PROCEDURE: A retrospective review of infants under 18 months diagnosed with incidental neuroblastoma from 2008 to May 2022 in our institute was conducted. Before October 2015, incidental patients were treated similarly to symptomatic cases, undergoing biopsy or surgical excision upon diagnosis (early cohort). Post October 2015 (late cohort), treatment decisions were guided by PET/CT findings, with 18F-DOPA PET/CT confirming diagnosis and staging. For tumors with low 18F-FDG uptake, an expectant observation approach was considered. Patient characteristics, diagnostic methods, image findings at diagnosis, treatment courses, and responses were compared between cohorts. RESULTS: Thirty infants less than 18 months were identified with incidental neuroblastoma and completed PET/CT at diagnosis. The early and late cohorts each comprised 15 patients. In the late cohort, nine out of 15 patients (60%) presented with localized FDG non-avid tumors were offered the option of expectant observation. Of these, seven patients opted for observation, thereby avoiding surgery. Treatment outcomes were comparable between early and late cohorts, except for one mortality of a patient who, despite showing 18F-FDG activity, declined treatment. CONCLUSIONS: This study demonstrates the potential utility of 18F-DOPA and 18F-FDG PET/CT scans in aiding clinical decision-making for infants with localized, incidental neuroblastoma. Given the concerns regarding radiation exposure, such imaging may be valuable for cases with suspected metastasis, initial large tumor size, or growth during follow-up.
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Dihidroxifenilalanina , Fluorodesoxiglucosa F18 , Neuroblastoma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Humanos , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/terapia , Neuroblastoma/patología , Lactante , Masculino , Femenino , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Retrospectivos , Dihidroxifenilalanina/análogos & derivados , Recién Nacido , Hallazgos Incidentales , Estudios de Factibilidad , Estudios de Seguimiento , Toma de Decisiones Clínicas , PronósticoRESUMEN
BACKGROUND: Myeloablative, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) improves outcome in some high-risk malignant solid tumors and lymphomas in children and young adults. METHODS: We performed 16 peripheral blood stem cell (PBSC) harvests in 12 children and 2 young adult patients with a high-risk malignant solid tumor or refractory/relapsed Hodgkin's lymphoma from August 2015 to December 2020. In our chemotherapy mobilization protocol, we used an absolute neutrophil count (ANC) of >1 × 109/L following the nadir after chemotherapy as the criterion for undertaking the apheresis. RESULTS: The median CD34+ cell count per kg body weight of the 33 apheresis products was 4.92 × 106 cells/kg (range, 0.34-22.53 × 106 cells/kg). Thirteen of the 14 patients (93%) had successful PBSC collections that met their goals for PBSCT. Three patients did not receive PBSCT due to disease progression prior to transplantation. Prompt engraftment occurred in all the remaining 11 patients with 17 PBSCTs. CONCLUSION: Our data suggest that ANC can be helpful as a surrogate parameter in clinical decision-making when the peripheral blood CD34+ count is unavailable.
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Encapsulated cell therapy (ECT) shows significant potential for treating neurodegenerative disorders including Alzheimer's and Parkinson's, which currently lack curative medicines and must be managed symptomatically. This novel technique encapsulates functional cells with a semi-permeable membrane, providing protection while enabling critical nutrients and therapeutic substances to pass through. Traditional ECT procedures, on the other hand, pose difficulties in terms of cell survival and retrieval. We introduce the Microtube Array Membrane (MTAM), a revolutionary technology that solves these constraints, in this comprehensive overview. Microtube Array Membrane has distinct microstructures that improve encapsulated cells' long-term viability by combining the advantages of macro and micron scales. Importantly, the MTAM platform improves biosafety by allowing the entire encapsulated unit to be retrieved in the event of an adverse reaction. Our findings show that MTAM-based ECT has a great potential in a variety of illness situations. For cancer treatment, hybridoma cells secreting anti-CEACAM 6 antibodies inhibit triple-negative breast cancer cell lines for an extended period of time. In animal brain models of Alzheimer's disease, hybridoma cells secreting anti-pTau antibodies successfully reduce pTau buildup, accompanied by improvements in memory performance. In mouse models, MTAM-encapsulated primary cardiac mesenchymal stem cells dramatically improve overall survival and heart function. These findings illustrate the efficacy and adaptability of MTAM-based ECT in addressing major issues such as immunological isolation, cell viability, and patient safety. We provide new possibilities for the treatment of neurodegenerative illnesses and other conditions by combining the potential of ECT with MTAM. Continued research and development in this subject has a lot of promise for developing cell therapy and giving hope to people suffering from chronic diseases.
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Encéfalo , Tratamiento Basado en Trasplante de Células y Tejidos , Animales , Ratones , Humanos , Transporte Biológico , Línea Celular , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: The decision to treat children with benign epilepsy with centrotemporal spikes (BECTS) using antiseizure medications (ASM) is controversial. Our goal is to compare the effect of ASM treatment on the alteration of electroencephalographic (EEG) functional connectivity and power across four frequency bands in children with BECTS. METHODS: Children with BECTS with two-year follow-up were retrospectively divided into ASM versus non-ASM groups. The network properties of the EEGs as based on network-based statistic and graph theory were evaluated by the following indices: global efficiency, clustering coefficient, betweenness centrality, and nodal strength in four frequency bands (delta, theta, alpha, and beta). EEG power including absolute power (AP) and relative power (RP) was analyzed in four frequency bands. RESULTS: In children with BECTS with ASM treatment, there was no significant change in EEG connectivity across all bands before and after two years of ASM. In children with BECTS without ASM treatment, there was a significant increase of global efficiency, clustering coefficient, and nodal strength but not the betweenness centrality in the delta band after two years of follow-up. A decrease in AP in the delta and theta bands and a decrease in RP in the theta band were found in the ASM group after two years of treatment. CONCLUSIONS: Our results suggest that ASM may play a role in modulating the development of increasing overall brain connectivity and in downregulating overt synaptic activity, but not intrinsic focal connectivity, in the early years of BECTS. The changes in the EEG power indicate that ASM significantly normalized slow-wave band power.
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Anticonvulsivantes , Electroencefalografía , Epilepsia Rolándica , Humanos , Epilepsia Rolándica/tratamiento farmacológico , Epilepsia Rolándica/fisiopatología , Femenino , Niño , Masculino , Anticonvulsivantes/farmacología , Estudios Retrospectivos , Preescolar , Estudios de Seguimiento , Ondas Encefálicas/efectos de los fármacos , Ondas Encefálicas/fisiología , Red Nerviosa/efectos de los fármacos , Red Nerviosa/fisiopatología , Encéfalo/fisiopatología , Encéfalo/efectos de los fármacosRESUMEN
BACKGROUND: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a progressive fatal disorder caused by deposition of mutant transthyretin (TTR) amyloids mainly in the nerves and heart. Autonomic dysfunction is a major disabling manifestation, affecting 90% of patients with late-onset ATTRv-PN. The current study aimed to investigate brain functional alterations associated with dysautonomia due to peripheral autonomic nerve degeneration in ATTRv-PN. METHODS: Resting-state functional MRI data were acquired from 43 ATTRv-PN patients predominantly of A97S (p.A117S) genotype, and the functional connectivity of central autonomic regions was assessed. RESULTS: Compared with age-matched healthy controls, the ATTRv-PN patients exhibited (1) reduced functional connectivity of the central autonomic regions such as hypothalamus, amygdala, anterior insula, and middle cingulate cortex with brain areas of the limbic, frontal, and somatosensory systems, and (2) correlations of reduced functional autonomic connectivity with the severity of autonomic dysfunction especially orthostatic intolerance, decreased heart rate variability, and greater clinical disability. CONCLUSIONS: Our findings provide evidence linking peripheral autonomic dysfunction with altered connectivity in the central autonomic network in ATTRv-PN.
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In this study, we investigated the prevalence of mental health problems among patients with cancer and whether oncology nurse navigation improved their mental health outcomes and medical experience. In this randomized controlled clinical trial, we recruited 128 outpatients with cancer via purposive sampling from a teaching hospital in northern Taiwan. Participants were randomly assigned to the navigation group (N = 61) or the usual care group (N = 67). Data were collected from January 2019 to July 2020 using questionnaires, including the self-reported Distress Thermometer, Hospital Anxiety and Depression Scale, Demoralization Scale, and Patient Assessment of Chronic Illness Care. Data were collected at baseline and after three and six months of the intervention. Descriptive and analytical statistical analyses were performed. The prevalence rates of anxiety, depression, distress, and demoralization were 17.9%, 15.7%, 29.7%, and 29.7%, respectively. After three months, the participants in the navigation group exhibited significantly reduced levels of anxiety, demoralization, and emotional distress (reduced by 92%, 75%, and 58%, respectively) and reported a better medical experience (odds ratio = 1.40) than those in the usual care group.
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Neoplasias , Enfermería Oncológica , Humanos , Femenino , Masculino , Taiwán , Neoplasias/psicología , Persona de Mediana Edad , Enfermería Oncológica/métodos , Salud Mental , Ansiedad , Navegación de Pacientes , Adulto , Anciano , DepresiónRESUMEN
OBJECTIVE: To evaluate the muscle thickness and walking test in people with haemophilia A (PWH) and their correlation to joint health and functional impairments. DESIGN: Cross-sectional study. RESULTS: 29 severe/moderate PWH were enrolled. Muscle thickness of quadriceps and medial gastrocnemius were measured using ultrasound. Joint health and functional capacity were assessed using Haemophilia Joint Health Score (HJHS), Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US), 6-Minute Walking test (6MWT), Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL), and Haemophilia Activities List (HAL). Quadriceps muscle thickness significantly correlated with HJHS knee, HEAD-US knee, and HAL. Calf muscle thickness significantly correlated with the HJHS ankle. After adjusted age and BMI, calf muscle thickness was inversely associated with the HJHS ankle. 6MWT was found to significantly correlate with HJHS total, HEAD-US total, Haem-A-QoL, and HAL. CONCLUSION: Muscle thickness and the distance of 6MWT were linked to assessment of joint health, quality of life and activity participation in PWH. Ultrasound measurement of muscle thickness and walking test appear to be useful tools for the assessment of joint health and functional status in PWH.