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1.
Int J Clin Oncol ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599412

RESUMO

BACKGROUND: The practice of cancer diagnosis disclosure to children has been changed with the times. The regulations of clinical trials in the 2000s might change the practice in Japan. However, the perspective of this topic among children and adults has not been investigated in detail. METHODS: We studied changes in the practice of information sharing with children with cancer at pediatric cancer centers and the perspective of cancer diagnosis disclosure to children among school children, their parents and pediatric oncologists in the last 20 years by comparing the results of questionnaire surveys conducted in 1998, 2008 and 2018. RESULTS: This study revealed that the performing rate has increased with the times, but the institutions actively performing for children aged 7-9 years were 36.4% even in the 2018 survey. More than 70% of children wished diagnosis disclosure if they suffer from cancer in the series of surveys, while the ratio of parents who tell cancer diagnosis to their children hovered at 34.5 to 53.7% (p < 0.001 in all surveys). The ratio of pediatric oncologists having the policy to perform diagnosis disclosure proactively increased from 9.3 to 60.0%, while that of parents having the same policy stayed at 5.3% even in 2018. CONCLUSIONS: The performing rate of information sharing with children with cancer was significantly changed in the last 20 years. The opinion gaps were observed between parents and children and between parents and pediatric oncologists.

2.
J Neurosurg ; : 1-6, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34653973

RESUMO

OBJECTIVE: Sufficient thermal increase capable of generating thermocoagulation is indispensable for an effective clinical outcome in patients undergoing magnetic resonance-guided focused ultrasound (MRgFUS). The skull density ratio (SDR) is one of the most dominant predictors of thermal increase prior to treatment. However, users currently rely only on the average SDR value (SDRmean) as a screening criterion, although some patients with low SDRmean values can achieve sufficient thermal increase. The present study aimed to examine the numerical distribution of SDR values across 1024 elements to identify more precise predictors of thermal increase during MRgFUS. METHODS: The authors retrospectively analyzed the correlations between the skull parameters and the maximum temperature achieved during unilateral ventral intermediate nucleus thalamotomy with MRgFUS in a cohort of 55 patients. In addition, the numerical distribution of SDR values was quantified across 1024 elements by using the skewness, kurtosis, entropy, and uniformity of the SDR histogram. Next, the authors evaluated the correlation between the aforementioned indices and a peak temperature > 55°C by using univariate and multivariate logistic regression analyses. Receiver operating characteristic curve analysis was performed to compare the predictive ability of the indices. The diagnostic performance of significant factors was also assessed. RESULTS: The SDR skewness (SDRskewness) was identified as a significant predictor of thermal increase in the univariate and multivariate logistic regression analyses (p < 0.001, p = 0.013). Moreover, the receiver operating characteristic curve analysis indicated that the SDRskewness exhibited a better predictive ability than the SDRmean, with area under the curve values of 0.847 and 0.784, respectively. CONCLUSIONS: The SDRskewness is a more accurate predictor of thermal increase than the conventional SDRmean. The authors suggest setting the SDRskewness cutoff value to 0.68. SDRskewness may allow for the inclusion of treatable patients with essential tremor who would have been screened out based on the SDRmean exclusion criterion.

3.
Intern Med ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34471023

RESUMO

A 77-year-old woman presented with systemic lymphadenopathy and bilateral pleural effusion. Angioimmunoblastic T-cell lymphoma (AITL) was diagnosed based on the results of a lymph node biopsy. AITL cells expressed the aberrant antigen of CD56. The bilateral pleural effusion was attributed to chylothorax, not the infiltration of lymphoma cells into the pleura, as determined by the pleural fluid analysis. We therefore diagnosed her with CD56-positive AITL complicated by chylothorax. She achieved complete remission by multidrug chemotherapy. AITL is commonly complicated by pleural effusion, but rarely by chylothorax. This is the first case of CD56-positive AITL complicated by chylothorax.

4.
Sci Rep ; 11(1): 13945, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230563

RESUMO

Acute gastroenteritis associated with diarrhea is considered a serious disease in Africa and South Asia. In this study, we examined the trends in the causative pathogens of diarrhea and the corresponding gut microbiota in Ghana using microbiome analysis performed on diarrheic stools via 16S rRNA sequencing. In total, 80 patients with diarrhea and 34 healthy adults as controls, from 2017 to 2018, were enrolled in the study. Among the patients with diarrhea, 39 were norovirus-positive and 18 were rotavirus-positive. The analysis of species richness (Chao1) was lower in patients with diarrhea than that in controls. Beta-diversity analysis revealed significant differences between the two groups. Several diarrhea-related pathogens (e.g., Escherichia-Shigella, Klebsiella and Campylobacter) were detected in patients with diarrhea. Furthermore, co-infection with these pathogens and enteroviruses (e.g., norovirus and rotavirus) was observed in several cases. Levels of both Erysipelotrichaceae and Staphylococcaceae family markedly differed between norovirus-positive and -negative diarrheic stools, and the 10 predicted metabolic pathways, including the carbohydrate metabolism pathway, showed significant differences between rotavirus-positive patients with diarrhea and controls. This comparative study of diarrheal pathogens in Ghana revealed specific trends in the gut microbiota signature associated with diarrhea and that pathogen-dependent dysbiosis occurred in viral gastroenteritis.


Assuntos
Disbiose/microbiologia , Disbiose/virologia , Gastroenterite/microbiologia , Gastroenterite/virologia , Microbioma Gastrointestinal , Adolescente , Adulto , Bactérias/classificação , Biodiversidade , Estudos de Casos e Controles , Criança , Pré-Escolar , Diarreia/microbiologia , Diarreia/virologia , Fezes/microbiologia , Feminino , Gana , Humanos , Masculino , Filogenia , Rotavirus/fisiologia
5.
Pediatr Int ; 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34157204

RESUMO

BACKGROUND: Social awareness on cancer can be changed with cancer education and proper distribution of cancer information. This study addressed the current situation and historical change of children's perception of cancer. METHODS: Questionnaire surveys were conducted among healthy school children aged 10 to 15 years in 2008 and 2018. Knowledge of cancer was questioned and compared with that of asthma, tuberculosis or measles. Furthermore, the children were asked their resources of health information. RESULTS: The numbers of participants and collection rates were 438 and 63.9% in 2008, and 320 and 44.7% in 2018. Children's perception of cancer was significantly changed in the last decade. The proportion of respondents answering "cancer affects children" was changed from 78.3 to 89.5% (P=0.0001), "cancer is preventable", from 42.0 to 49.7% (P=0.0425) and "cancer is curable", from 52.4 to 66.0% (P=0.0003). Significantly more junior high school students answered that cancer is preventable than elementary school children in 2018 (55.9 vs. 42.7%, P=0.0028). The major resources of information on health were television, parents and books. The proportion of children choosing the Internet significantly increased from 15.3 to 47.8% (P<0.0001). Significantly more junior high school students selected television and the Internet than elementary school children (94.5 vs. 86.9%, P=0.0202 for television; 57.1 vs. 37.9%, P=0.0007 for the Internet). CONCLUSION: The proportion of children correctly perceiving cancer information had increased in the last decade. Junior high school students better understood the information. The Internet is of increasing importance as an information resource for school children.

6.
Mov Disord ; 36(8): 1955-1959, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34050695

RESUMO

BACKGROUND: The efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for the treatment of focal hand dystonia (FHD) is not well known. OBJECTIVE: We aimed to prospectively investigate the efficacy of MRgFUS thalamotomy for the treatment of FHD. METHODS: We performed MRgFUS thalamotomy of the ventro-oral (Vo) nucleus in 10 patients with FHD. We evaluated the scores of the Writer's Cramp Rating Scale (WCRS, 0-30; higher scores indicating greater severity), Tubiana Musician's Dystonia Scale (TMDS, 0-5; lower scores indicating greater severity), and Arm Dystonia Disability Scale (ADDS, 0%-100%; lower scores indicating greater disability) at baseline and 3 and 12 months post-treatment. RESULTS: WCRS, TMDS, and ADDS scores significantly improved from 6.3 ± 2.7, 1.4 ± 0.5, and 58.7% ± 14.3% at baseline to 1.6 ± 3.1 (P = 0.011), 5.0 ± 0 (P = 0.0001), and 81.6% ± 22.9% (P = 0.0229) at 12 months, respectively. There was one prolonged case of dysarthria at 12 months. CONCLUSION: We show that MRgFUS Vo-thalamotomy significantly improved FHD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Distúrbios Distônicos , Distúrbios Distônicos/diagnóstico por imagem , Distúrbios Distônicos/cirurgia , Humanos , Espectroscopia de Ressonância Magnética , Projetos Piloto , Resultado do Tratamento
7.
J Neurosurg ; : 1-9, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33668032

RESUMO

OBJECTIVE: In transcranial magnetic resonance imaging-guided focused ultrasound (TcMRgFUS), a high skull density ratio (SDR) is advantageous to achieve a sufficiently high temperature at the target. However, it is not easy to estimate the temperature rise because the SDR shows different values depending on the reconstruction filter used. The resolution characteristic of a computed tomography (CT) image depends on a modulation transfer function (MTF) defined by the reconstruction filter. Differences in MTF induce unstable SDRs. The purpose of this study was both to standardize SDR by developing a method to correct the MTF and to enable effective patient screening prior to TcMRgFUS treatment and more accurate predictions of focal temperature. METHODS: CT images of a skull phantom and five subjects were obtained using eight different reconstruction filters. A frequency filter (FF) was calculated using the MTF of each reconstruction filter, and the validity of SDR standardization was evaluated by comparing the variation in SDR before and after FF correction. Subsequently, FF processing was similarly performed using the CT images of 18 patients who had undergone TcMRgFUS, and statistical analyses were performed comparing the relationship between the SDRs before and after correction and the maximum temperature in the target during TcMRgFUS treatment. RESULTS: The FF was calculated for each reconstruction filter based on one manufacturer's BONE filter. In the CT images of the skull phantom, the SDR before FF correction with five of the other seven reconstruction filters was significantly smaller than that with the BONE filter (p < 0.01). After FF correction, however, a significant difference was recognized under only one condition. In the CT images of the five subjects, variation of the SDR due to imaging conditions was significantly improved after the FF correction. In 18 cases treated with TcMRgFUS, there was no correlation between SDR before FF correction and maximum temperature (rs = 0.31, p > 0.05); however, a strong positive correlation was observed after FF correction (rs = 0.71, p < 0.01). CONCLUSIONS: After FF correction, the difference in SDR due to the reconstruction filter used is smaller, and the correlation with temperature is stronger. Therefore, the SDR can be standardized by applying the FF, and the maximum temperature during treatment may be predicted more accurately.

8.
Pediatr Int ; 63(12): 1451-1457, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33527619

RESUMO

BACKGROUND: The quality of end-of-life (Q-EOL) care is influenced by various factors such as resources for palliative care (PC). We introduced a multi-professional expert team (MET) in 2014, which provides home-based care for children and adolescents with incurable cancer. This study investigated the impacts of the outreach activities by the MET on Q-EOL care of pediatric oncology patients. METHODS: This observational study retrospectively examined 112 patients receiving end-of-life care between 1989 and 2018 at a pediatric cancer center in Japan. Some of the indicators of Q-EOL care before and after the introduction of the outreach activities by the MET were compared. The subjects were 92 in pre-MET and 20 in post-MET periods. RESULTS: The median number of days for which the patients stayed at home during the final seven or 30 days were significantly prolonged in the post-MET period (0.0 vs 1.5 days, P = 0.020, 3.0 vs 12.0 days, P = 0.042). The change was more significant in hematologic malignancies than solid and central nervous system tumors. Patients receiving longer PC before their deaths could stay at home longer during the last 7 days. The ratio of patients receiving PC for more than 2 months was significantly increased in post-MET period (60.9 vs 90.0%, P = 0.014). More patients also greeted their deaths at home in the post-MET period (3.3 vs 25.0%, P < 0.001). CONCLUSIONS: The activities of the MET transformed the end-of-life care of children and adolescents with incurable cancer. Earlier transitions to PC from curative treatment were associated with longer home-based care and more deaths at home.

9.
Int J Hematol ; 113(6): 893-902, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33641058

RESUMO

Approximately 90% of pediatric acute lymphoblastic leukemia (ALL) cases are curable with intensified chemotherapy, but very high-risk patients may require hematopoietic stem cell transplantation (HSCT). A suitable indication for HSCT in the first complete remission (CR1) should be defined to protect patients from long-term complications. We report the outcomes of HSCT in CR1 from the Japan Association of Childhood Leukemia Study (JACLS) ALL-02 study and reassess indications for HSCT. Of 1114 patients, 71 (6.4%) received HSCT in CR1. Indications included high-risk cytogenetic abnormalities and non-CR on day 33. Patients with B-cell precursor (BCP) ALL and a prednisolone poor response (PPR) received HSCT when leukocyte antigen-matched siblings were available. The 4-year overall survival (OS) of transplanted patients was 78.8% (confidence interval 67.3-86.6). Multivariate analysis revealed that cord blood transplantation was associated with poor OS. For BCP-ALL patients with PPR who achieved CR1 after induction therapy, HSCT in CR1 showed excellent outcomes (4-year OS 90.9%) but demonstrated no survival advantage as the outcome with chemotherapy was also excellent (4-year OS 97.0%). This study suggests that in BCP-ALL patients PPR is not an indication for HSCT in CR1. Precise evaluation of treatment responses would increase sophistication of indications for HSCT in CR1.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Prednisolona/administração & dosagem , Adolescente , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Prednisolona/efeitos adversos , Indução de Remissão , Taxa de Sobrevida
11.
Neurosurgery ; 88(4): 751-757, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33469648

RESUMO

BACKGROUND: Several feasibility studies and a randomized, controlled, multicenter trial have demonstrated the safety and efficacy of unilateral transcranial magnetic resonance-guided focused ultrasound (FUS) lesioning of the ventral intermediate thalamic nucleus in treating essential tremor. OBJECTIVE: To evaluate the safety and efficacy of FUS thalamotomy in a Japanese patient cohort through a prospective, multicenter, single-arm confirmatory trial. METHODS: A total of 35 patients with disabling refractory essential tremor underwent unilateral FUS thalamotomy and were followed up for 12 post-treatment months. Safety was measured as the incidence and severity of treatment-related adverse events. Efficacy was measured as the tremor severity and quality of life improvements using the Clinical Rating Scale for Tremor and Questionnaire for Essential Tremor. RESULTS: The mean skull density ratio (SDR) was 0.47. There was a significant decrease in the mean postural tremor score of the treated hand from baseline to 12 mo by 56.4% (95% CI: 46.7%-66.1%; P < .001), which was maintained at last follow-up. Quality of life improved by 46.3% (mean overall Questionnaire for Essential Tremor score of 17.4 [95% CI: 12.1-22.7]) and there were no severe adverse events. The most frequent adverse event was gait disturbance and all events resolved. CONCLUSION: Unilateral FUS thalamotomy allowed significant and sustained tremor relief and improved the quality of life with an outstanding safety profile. The observed safety and efficacy of FUS thalamotomy were comparable to those reported in a previous multicenter study with a low SDR, and inclusion of the low SDR group did not affect effectiveness.


Assuntos
Tremor Essencial/diagnóstico por imagem , Tremor Essencial/cirurgia , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Tálamo/diagnóstico por imagem , Tálamo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Tremor Essencial/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento
12.
Allergy Asthma Immunol Res ; 13(1): 141-153, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33191682

RESUMO

PURPOSE: ImmunoCAP® (ImmunoCAP) and IMMULITE® 2000 3gAllergy™ (3gAllergy) systems are major quantitative allergen-specific immunoglobulin E (sIgE) assay methods. Due to the heterogeneous nature of allergenic extracts and differences in the assay format, quantitation of allergen-sIgEs is not expected to correlate well between different methods. However, we have recently reported good agreement between the methods in the diagnosis of egg allergy. This study aimed to determine and correlate the predictive values of sIgE by the two systems in the diagnosis of milk and wheat allergies. METHODS: Children who had undergone oral food challenge (OFC) for the diagnosis of milk and wheat allergies were enrolled. The OFCs were performed to diagnose either true allergy in the 1-year-old group (A) or tolerance in the 2- to 6-year-old group (B). Milk, casein and ß-lactoglobulin, and wheat and ω-5 gliadin sIgE values were measured using the 2 systems. The predictive accuracy of each sIgE for the OFC outcome was assessed using receiver operating characteristic (ROC) curves. The probability of a positive OFC outcome was estimated by logistic regression analysis. RESULTS: A total of 395 patients were recruited from 7 primary care clinics and 19 hospitals in Japan. Milk and wheat OFCs were performed for 87 and 102 group A patients, and 124 and 82 group B patients, respectively. ROC analysis yielded similar areas under the curve for the 2 assays (0.7-0.9). The log-transformed sIgE data showed a strong linear correlation with the estimated probabilities (R > 0.9). CONCLUSIONS: The 2 systems may be interchangeable for diagnosis of milk and wheat allergies in young children.

13.
Int J Hematol ; 112(6): 795-806, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32862292

RESUMO

Minimal residual disease of leukemia may reside in the bone marrow (BM) microenvironment and escape the effects of chemotherapeutic agents. This study investigated interactions between B cell precursor (BCP)-acute lymphoblastic leukemia (ALL) cells and BM mesenchymal stromal cells (BM-MSCs) in vitro. Five BCP-ALL cell lines established from pediatric patients and primary samples from a BCP-ALL patient were examined by flow cytometry and immunocytochemistry for expression of specific cell surface markers and cell adhesion proteins. The cell lines developed chemoresistance to commonly used anti-leukemic agents through adhesion to MSC-TERT cells in long-term culture. The change in chemosensitivity after adhering to BM-MSCs was associated with the expression of CD34, CD133, P-glycoprotein and BCRP/ABCG2, and downregulation of CD38. Similar phenotypic changes were observed in primary samples obtained by marrow aspiration or biopsy from a BCP-ALL patient. BM-MSC-adhering leukemia cells also showed deceleration of cell proliferation and expressed proteins in the Cadherin and Integrin pathways. These results suggest that BCP-ALL cells residing in the BM microenvironment may acquire chemoresistance by altering their phenotype to resemble that of cancer stem cells. Our results indicate that cell adhesion could be potentially targeted to improve the chemosensitivity of residual BCP-ALL cells in the BM microenvironment.


Assuntos
Antineoplásicos/farmacologia , Células da Medula Óssea/citologia , Comunicação Celular , Células-Tronco Mesenquimais/fisiologia , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/fisiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Microambiente Tumoral , Antígenos CD , Caderinas/metabolismo , Adesão Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Criança , Humanos , Imunofenotipagem , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo
14.
Acta Neurochir (Wien) ; 162(10): 2513-2517, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32617679

RESUMO

We report the case of a patient with hypothalamic hamartoma (HH) who was successfully treated with magnetic resonance-guided focused ultrasound (MRgFUS) for ablation as a disconnection surgery. A 26-year-old man with gelastic epilepsy had been diagnosed with HH at 3 years of age, and antiepileptic drugs were administered due to worsening episodes. Magnetic resonance imaging showed a sessile parahypothalamic hamartoma and MRgFUS ablation was performed, creating an oval-shaped lesion at the boundary area of the HH. Dramatic improvements in seizure symptoms were noted, and he was seizure-free on decreased antiepileptic drugs without any adverse events over the 1-year follow-up period.


Assuntos
Hamartoma/cirurgia , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Doenças Hipotalâmicas/cirurgia , Cirurgia Assistida por Computador/métodos , Adulto , Feminino , Hamartoma/diagnóstico por imagem , Humanos , Doenças Hipotalâmicas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino
15.
BMC Neurol ; 20(1): 160, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349706

RESUMO

BACKGROUND: We report the first case of transcranial magnetic resonance-guided focused ultrasound (MRgFUS) for mesial temporal lobe epilepsy (MTLE). CASE PRESENTATION: The target was located 20 mm lateral from the midline and 15 mm above the skull base (left hippocampus). Despite the application of maximal energy, the ablation temperature did not exceed 50 °C, probably because of the low number of effective transducer elements with incident angles below 25 degrees. The skull density ratio was 0.56. Post-operative magnetic resonance imaging did not reveal any lesion and the patient remained almost seizure-free for up to 12 months. CONCLUSIONS: This preliminary case report suggests that MRgFUS may be effective for treating cases of MTLE. Therefore, the safety and feasibility of MRgFUS should be evaluated in future studies with larger numbers of participants and longer follow-up duration.


Assuntos
Técnicas de Ablação/métodos , Epilepsia do Lobo Temporal/cirurgia , Hipocampo/cirurgia , Imageamento por Ressonância Magnética , Ultrassonografia de Intervenção/métodos , Adulto , Feminino , Humanos
16.
Proc Natl Acad Sci U S A ; 117(10): 5394-5401, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32094176

RESUMO

As a prototype of genomics-guided precision medicine, individualized thiopurine dosing based on pharmacogenetics is a highly effective way to mitigate hematopoietic toxicity of this class of drugs. Recently, NUDT15 deficiency was identified as a genetic cause of thiopurine toxicity, and NUDT15-informed preemptive dose reduction was quickly adopted in clinical settings. To exhaustively identify pharmacogenetic variants in this gene, we developed massively parallel NUDT15 function assays to determine the variants' effect on protein abundance and thiopurine cytotoxicity. Of the 3,097 possible missense variants, we characterized the abundance of 2,922 variants and found 54 hotspot residues at which variants resulted in complete loss of protein stability. Analyzing 2,935 variants in the thiopurine cytotoxicity-based assay, we identified 17 additional residues where variants altered NUDT15 activity without affecting protein stability. We identified structural elements key to NUDT15 stability and/or catalytical activity with single amino acid resolution. Functional effects for NUDT15 variants accurately predicted toxicity risk alleles in patients treated with thiopurines with far superior sensitivity and specificity compared to bioinformatic prediction algorithms. In conclusion, our massively parallel variant function assays identified 1,152 deleterious NUDT15 variants, providing a comprehensive reference of variant function and vastly improving the ability to implement pharmacogenetics-guided thiopurine treatment individualization.


Assuntos
Antimetabólitos/administração & dosagem , Antimetabólitos/toxicidade , Mercaptopurina/administração & dosagem , Mercaptopurina/toxicidade , Variantes Farmacogenômicos , Pirofosfatases/genética , Alelos , Substituição de Aminoácidos , Relação Dose-Resposta a Droga , Determinação de Ponto Final , Estabilidade Enzimática , Células HEK293 , Humanos , Mutação de Sentido Incorreto , Medicina de Precisão , Conformação Proteica em alfa-Hélice/genética , Pirofosfatases/química , Risco
17.
Blood Cancer J ; 10(2): 23, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32107374

RESUMO

This study was a second multicenter trial on childhood ALL by the Japan Childhood Leukemia Study Group (JACLS) to improve outcomes in non-T ALL. Between April 2002 and March 2008, 1138 children with non-T ALL were enrolled in the JACLS ALL-02 trial. Patients were stratified into three groups using age, white blood cell count, unfavorable genetic abnormalities, and treatment response: standard risk (SR), high risk (HR), and extremely high risk (ER). Prophylactic cranial radiation therapy (PCRT) was abolished except for CNS leukemia. Four-year event-free survival (4yr-EFS) and 4-year overall survival (4yr-OS) rates for all patients were 85.4% ± 1.1% and 91.2% ± 0.9%, respectively. Risk-adjusted therapy resulted in 4yr-EFS rates of 90.4% ± 1.4% for SR, 84.9% ± 1.6% for HR, and 66.5% ± 4.0% for ER. Based on NCI risk classification, 4yr-EFS rates were 88.2% in NCI-SR and 76.4% in NCI-HR patients, respectively. Compared to previous trial ALL-97, 4yr-EFS of NCI-SR patients was significantly improved (88.2% vs 81.2%, log rank p = 0.0004). The 4-year cumulative incidence of isolated (0.9%) and total (1.5%) CNS relapse were significantly lower than those reported previously. In conclusion, improved EFS in NCI-SR patients and abolish of PCRT was achieved in ALL-02.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/mortalidade , Irradiação Craniana/mortalidade , Recidiva Local de Neoplasia/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Risco Ajustado/métodos , Adolescente , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/terapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Taxa de Sobrevida
18.
J Neurosurg ; 132(2): 568-573, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30771772

RESUMO

OBJECTIVE: This study evaluated changes of fractional anisotropy (FA) in the ventral intermediate nucleus (VIM) of the thalamus after transcranial MR-guided focused ultrasound (TcMRgFUS) thalamotomy and their associations with clinical outcome. METHODS: Clinical and radiological data of 12 patients with medically refractory essential tremor (mean age 76.5 years) who underwent TcMRgFUS thalamotomy with VIM targeting were analyzed retrospectively. The Clinical Rating Scale for Tremor (CRST) score was calculated before and at 1 year after treatment. Measurements of the relative FA (rFA) values, defined as ratio of the FA value in the targeted VIM to the FA value in the contralateral VIM, were performed before thalamotomy, and 1 day and 1 year thereafter. RESULTS: TcMRgFUS thalamotomy was well tolerated and no long-term complications were noted. At 1-year follow-up, 8 patients demonstrated relief of tremor (improvement group), whereas in 4 others persistent tremor was noted (recurrence group). In the entire cohort, mean rFA values in the targeted VIM before treatment, and at 1 day and 1 year after treatment, were 1.12 ± 0.15, 0.44 ± 0.13, and 0.82 ± 0.22, respectively (p < 0.001). rFA values were consistently higher in the recurrence group compared with the improvement group, and the difference reached statistical significance at 1 day (p < 0.05) and 1 year (p < 0.01) after treatment. There was a statistically significant (p < 0.01) positive correlation between rFA values in the targeted VIM at 1 day after thalamotomy and CRST score at 1 year after treatment. Receiver operating characteristic curve analysis revealed that the optimal cutoff value of rFA at 1 day after thalamotomy for prediction of symptomatic improvement at 1-year follow-up is 0.54. CONCLUSIONS: TcMRgFUS thalamotomy results in significant decrease of rFA in the targeted VIM, at both 1 day and 1 year after treatment. Relative FA values at 1 day after treatment showed significant correlation with CRST score at 1-year follow-up. Therefore, FA may be considered a possible imaging biomarker for early prediction of clinical outcome after TcMRgFUS thalamotomy for essential tremor.


Assuntos
Imagem de Tensor de Difusão/métodos , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/cirurgia , Ultrassonografia de Intervenção/métodos , Núcleos Ventrais do Tálamo/diagnóstico por imagem , Núcleos Ventrais do Tálamo/cirurgia , Idoso , Idoso de 80 Anos ou mais , Anisotropia , Imagem de Tensor de Difusão/tendências , Feminino , Humanos , Masculino , Projetos Piloto , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia de Intervenção/tendências
19.
Int J Hematol ; 109(4): 477-482, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30689137

RESUMO

ETV6-RUNX1-positive B precursor acute lymphoblastic leukemia (B-ALL) is a common subtype of pediatric B-ALL that has shown excellent outcomes in contemporary clinical trials for pediatric B-ALL. Examinations of the possibility of reducing therapeutic intensity may thus be explored. This prospective study examined outcomes in 205 pediatric patients with ETV6-RUNX1-positive B-ALL uniformly treated following the Japan Association of Childhood Leukemia Study Group (JACLS) ALL-02 protocol. The JACLS ALL-02 protocol does not employ minimal residual disease detected by polymerase chain reaction (PCR-MRD)-based risk stratification; however, 4-year event-free survival (EFS) and overall survival (OS) were 94.4 ± 1.6 and 97.5 ± 1.1%, respectively. In particular, 92 of 205 (44.9%) patients were successfully treated with a less intensive regimen involving only two cycles of high dose methotrexate and one course of re-induction therapy comprising vincristine, L-asparaginase (L-asp), pirarubicin, and prednisolone. Multivariate analysis revealed that discontinuation of L-asp and poor response to prednisolone was, respectively, associated with poor EFS (HR 6.3; 95% CI 1.3-27.0) and OS (HR 17.5; 95% CI 2.3-130), suggesting that the majority of ETV6-RUNX1-positive B-ALL cases may be cured by a less-intensive chemotherapy regimen if the risk stratification system including PCR-MRD monitoring and insufficient use of L-asp is avoided.


Assuntos
Asparaginase/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Prednisolona/administração & dosagem , Criança , Pré-Escolar , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Masculino , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Medição de Risco , Taxa de Sobrevida
20.
J Neurosurg ; 131(2): 384-386, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30239322

RESUMO

Musician's dystonia (MD) is a type of focal hand dystonia that develops only while playing musical instruments and interferes with skilled and fine movements. Lesioning of the ventro-oral (Vo) nucleus of the thalamus (Vo-thalamotomy) using radiofrequency can cause dramatic improvement in MD symptoms. Focused ultrasound (FUS) can make intracranial focal lesions without an incision. The authors used MRI-guided FUS (MRgFUS) to create a lesion on the Vo nucleus to treat a patient with MD. Tubiana's MD scale (TMDS) was used to evaluate the condition of musical play ranging from 1 to 5 (1: worst, 5: best). The patient was a 35-year-old right-handed man with involuntary flexion of the right second, third, and fourth fingers, which occurred while playing a classical guitar. Immediately after therapeutic sonications of FUS Vo-thalamotomy, there was dramatic improvement in the MD symptoms. The TMDS scores before; at 0 and 1 week after; and at 1, 3, 6, and 12 months after MRgFUS Vo-thalamotomy were 1, 4, 4, 5, 5, 5, and 5, respectively. No complications were observed. Focused ultrasound Vo-thalamotomy can be an effective treatment for MD.


Assuntos
Distúrbios Distônicos/diagnóstico por imagem , Distúrbios Distônicos/cirurgia , Imageamento por Ressonância Magnética/métodos , Ultrassonografia de Intervenção/métodos , Núcleos Ventrais do Tálamo/diagnóstico por imagem , Núcleos Ventrais do Tálamo/cirurgia , Adulto , Humanos , Masculino , Radiocirurgia/métodos
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