RESUMEN
BACKGROUND: This study analyzed data from two consecutive protocols for children newly diagnosed with acute lymphoblastic leukemia (ALL) to determine the clinical impact of minimal/measurable residual disease (MRD) and recently identified tumor genetic subtypes. METHODS: Genetic subtypes were determined by sequential approaches including DNA indexing, reverse transcriptase-polymerase chain reaction, multiplex ligation-dependent probe amplification, and RNA-sequencing. MRD was assessed by flow cytometry. The Taiwan Pediatric Oncology Group TPOG-ALL-2013 study enrolled patients who received MRD-directed therapy. RESULTS: The 5-year event-free survival (EFS) and overall survival rates in the 2013 cohort were 77.8% and 86.9% compared to those of the 2002 cohort, which were 62.4% and 76.5%. Among patients treated with MRD-guided therapy, those with ETV6-RUNX1 fusion and high hyperdiploidy had the highest 5-year EFS (91.4% and 89.6%, respectively). The addition of dasatinib improved outcomes in patients with BCR-ABL1 ALL. Recently identified subtypes like DUX4-rearranged, ZNF384-rearranged, MEF2D-rearranged, and PAX5alt subtypes were frequently positive for MRD after remission induction, and these patients consequently received intensified chemotherapy. Treatment intensification according to the MRD improved the outcomes of patients presenting DUX4 rearrangements. In high-risk or very-high-risk subtypes, the TPOG-ALL-2013 regimen did not confer significant improvements compared to TPOG-ALL-2002, and the outcomes of BCR-ABL1-like, MEF2D-rearranged, and KMT2A-rearranged ALL subtypes (in addition to those of T-cell ALL) were not sufficiently good. Novel agents or approaches are needed to improve the outcomes for these patients. CONCLUSIONS: The TPOG-ALL-2013 study yielded outcomes superior to those of patients treated in the preceding TPOG-ALL-2002 study. This study provides important data to inform the design of future clinical trials in Taiwan. PLAIN LANGUAGE SUMMARY: MRD-directed therapy improved the outcomes for pediatric ALL, especially standard-risk patients. Genomic analyses and MRD might be used together for risk-directed therapy of childhood ALL. Our work provides important data to inform the design of future clinical trials in Taiwan.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Humanos , Neoplasia Residual/genética , Neoplasia Residual/diagnóstico , Pronóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Dasatinib/uso terapéutico , Inducción de RemisiónRESUMEN
Imatinib is a crucial therapeutic strategy against chronic myeloid leukemia. Though superficial edema is a common adverse effect of imatinib, massive fluid retention is rarely reported. Here, we report the case of an adolescent who had tolerated imatinib for a long time, and then presented with massive pleural/pericardial effusion during an episode of Campylobacter jejuni bacteremia. A stepwise and comprehensive survey excluded all other plausible causes of disease. The Naranjo scale was used to assess the probability of an adverse effect of medication, and the score turned out to be 9, indicating severe fluid retention to be a definite reaction to imatinib. Drug discontinuation, antibiotic administration, and invasive procedures improved this condition. After this episode, the patient could tolerate imatinib again, illustrating the transient and reversible nature of this reaction. Since prolonged imatinib usage is crucial for chronic myeloid leukemia control, alertness to drug-related adverse effects is recommended, even if the subject has previously shown a good tolerance to the drug due to various physical conditions, especially physiological stressors, like infection or inflammation.
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Antineoplásicos , Bacteriemia , Campylobacter , Leucemia Mielógena Crónica BCR-ABL Positiva , Derrame Pericárdico , Adolescente , Antineoplásicos/efectos adversos , Bacteriemia/tratamiento farmacológico , Dasatinib/uso terapéutico , Humanos , Mesilato de Imatinib/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológicoRESUMEN
MicroRNAs (miRNAs) are small non-coding RNAs of â¼ 22 nucleotides that are involved in negative regulation of mRNA at the post-transcriptional level. Previously, we developed miRTarBase which provides information about experimentally validated miRNA-target interactions (MTIs). Here, we describe an updated database containing 422 517 curated MTIs from 4076 miRNAs and 23 054 target genes collected from over 8500 articles. The number of MTIs curated by strong evidence has increased â¼1.4-fold since the last update in 2016. In this updated version, target sites validated by reporter assay that are available in the literature can be downloaded. The target site sequence can extract new features for analysis via a machine learning approach which can help to evaluate the performance of miRNA-target prediction tools. Furthermore, different ways of browsing enhance user browsing specific MTIs. With these improvements, miRTarBase serves as more comprehensively annotated, experimentally validated miRNA-target interactions databases in the field of miRNA related research. miRTarBase is available at http://miRTarBase.mbc.nctu.edu.tw/.
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Bases de Datos Genéticas , MicroARNs/metabolismo , ARN Mensajero/metabolismo , Minería de Datos , Humanos , ARN Mensajero/química , Interfaz Usuario-ComputadorRESUMEN
BACKGROUND: Nationwide newborn screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency has been implemented in Taiwan since 1987 and the G6PD enzyme activity levels were applied for diagnosis confirmation. As the reference value of G6PD enzyme activity was not available for infants aged 7-90 days, this study was performed to determine the enzyme level in different genotypes. METHODS: Between January 1, 2016 and June 30, 2017, 410 term infants aged 7-90 days old visiting National Taiwan University Hospital Hsinchu branch were enrolled. The comparisons of G6PD enzyme activities among genotype groups were performed. RESULTS: G6PD enzyme activity was negatively correlated with age (R = -0.212, p = 0.01). For infants under 30 days of age, the G6PD enzyme activity levels were 1.4 ± 0.9 U/g Hb in hemizygotes (n = 76), 6.5 ± 2.0 U/g Hb in heterozygotes (n = 47), and 13.6 ± 3.7 U/g Hb in those without G6PD mutations (n = 70). Among infants more than 30 days old, G6PD enzyme activity levels were 0.9 ± 0.5 U/g Hb in hemizygotes (n = 46), 6.0 ± 2.7 U/g Hb in heterozygotes (n = 23), and 11.7 ± 3.4 U/g Hb in those without G6PD mutations (n = 148). G6PD levels differed significantly among the groups defined by genotypes. CONCLUSION: We determined G6PD enzyme activity levels in infants aged between 7 and 90 days in Taiwan. Completing the reference data and determining the cutoff values for different G6PD deficiency disease statuses will help pediatricians to make accurate diagnoses.
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Deficiencia de Glucosafosfato Deshidrogenasa/diagnóstico , Deficiencia de Glucosafosfato Deshidrogenasa/metabolismo , Glucosafosfato Deshidrogenasa/metabolismo , Tamizaje Neonatal , Femenino , Genotipo , Glucosafosfato Deshidrogenasa/genética , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Humanos , Lactante , Recién Nacido , Masculino , Mutación , Valores de Referencia , TaiwánRESUMEN
BACKGROUND: To eliminate cranial irradiation (CrRT)-related sequelae and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, the Taiwan Pediatric Oncology Group (TPOG) introduced a modified central nervous system (CNS)-directed regimen characterized by delayed triple intrathecal therapy (TIT) and the omission of CrRT for all children with newly diagnosed acute lymphoblastic leukemia (ALL). METHODS: This study compared the treatment outcomes of patients overall and patients with a non-CNS-1 status (CNS-2, CNS-3, or TLP with blasts) in 2 treatment eras, one before and another after the revision of the TPOG-ALL-2002 protocol by the introduction of the modification (era 1 [2002-2008] with CrRT and era 2 [2009-2012] with delayed first TIT and no CrRT). RESULTS: There were no statistically significant differences in major outcomes between the 903 patients treated in era 1 and the 444 patients treated in era 2: the 5-year event-free survival (EFS) rates were 75.7% ± 1.4% and 72.1% ± 2.4%, respectively (P = .260), and the cumulative risks of isolated CNS relapse were 4.0% ± 0.7% and 4.1% ± 1.0%, respectively (P = .960). There were also no differences between non-CNS-1 patients treated in era 1 (n = 76) and era 2 (n =28): the 5-year EFS rates were 52.3% ± 5.8% and 62.9% ± 9.4%, respectively (P = .199), and the cumulative risks of isolated CNS relapse were 6.3% ± 3.1% and 3.6% ± 3.5%, respectively (P = .639). Notably, TLP with blasts was completely eliminated after the first TIT was delayed in era 2. CONCLUSIONS: The delay of the first TIT until the clearance of circulating blasts and the total omission of CrRT did not compromise survival or CNS control in patients with childhood ALL, including those with a non-CNS-1 status.
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Antineoplásicos/administración & dosificación , Irradiación Craneana/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Antineoplásicos/uso terapéutico , Neoplasias del Sistema Nervioso Central , Niño , Preescolar , Irradiación Craneana/efectos adversos , Femenino , Humanos , Lactante , Recién Nacido , Inyecciones Espinales , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Análisis de Supervivencia , Tiempo de Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: Infection is a major complication in pediatric patients with acute lymphoblastic leukemia during chemotherapy. In this study, the infection characteristics were determined and risk factors analyzed based on the Taiwan Pediatric Oncology Group (TPOG) acute lymphoblastic leukemia (ALL) protocol. PROCEDURE: We retrospectively reviewed fever events during chemotherapy in 252 patients treated during two consecutive clinical trials at a single institution between 1997 and 2012. Patients were classified as standard, high, and very high risk by treatment regimen according to the TPOG definitions. We analyzed the characteristics and risk factors for infection. RESULTS: Fever occurred in 219 patients (86.9%) with a mean of 2.74 episodes per person. The fever events comprised 64% febrile neutropenia, 39% clinically documented infections, and 44% microbiologically documented infections. The microbiologically documented infections were mostly noted during the induction phase and increased in very high risk patients (89 vs. 24% and 46% in standard-risk and high-risk patients, respectively). Younger age and higher risk (high-risk and very high risk groups) were risk factors for fever and microbiologic and bloodstream infections. Female gender and obesity were additive risk factors for urinary tract infection (odds ratios = 3.52 and 3.24, P < 0.001 and P = 0.004, respectively). CONCLUSIONS: Infections developed primarily during the induction phase, for which younger age and higher risk by treatment regimen were risk factors. Female gender and obesity were additive risk factors for urinary tract infection.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neutropenia Febril , Leucemia-Linfoma Linfoblástico de Células Precursoras , Infecciones Urinarias , Adolescente , Factores de Edad , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Preescolar , Neutropenia Febril/inducido químicamente , Neutropenia Febril/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Obesidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Factores de Riesgo , Factores Sexuales , Infecciones Urinarias/inducido químicamente , Infecciones Urinarias/epidemiologíaRESUMEN
BACKGROUND: Reinduction therapy has improved the outcomes in children with acute lymphoblastic leukemia (ALL). We sought to determine the optimal course(s) of reinduction therapy for standard-risk (SR, or "low-risk" in other groups) patients. Also, we evaluated outcomes using triple intrathecal therapy without cranial radiation (CrRT) for central nervous system (CNS) preventive therapy. PROCEDURE: From 2002 to 2012, all newly diagnosed children with ALL in Taiwan were enrolled in Taiwan Pediatric Oncology Group ALL-2002 protocol. SR patients were randomized to receive single or double reinduction courses. The patients enrolled before 2009 received CrRT, while those enrolled later did not. The Kaplan-Meier method was used to estimate survival rates and the difference between two groups was compared by the two-sided log-rank test. RESULTS: In 1,366 eligible patients, the 5-year overall survival (OS) was 81.6 ± 1.1% (standard error) and 5-year event-free survival (EFS) was 74.3 ± 1.2%. In SR patients, the 5-year OS for one and two reinduction courses was 91.6 ± 2.1% and 93.7 ± 1.8%, respectively, and the 5-year EFS was 85.2 ± 2.7% and 89.8 ± 2.3%, respectively. There were no significant differences in survival between these two groups. Patients with MLL or BCR-ABL1 had the worst outcomes: 5-year EFS was 23.4 and 31.8% and 5-year OS was 28.6 and 44.7%, respectively. There was no significant difference in CNS relapse or survival between the era with or without CrRT. CONCLUSIONS: For SR patients, one-course reinduction was adequate. Triple intrathecal therapy alone successfully prevented CNS relapse.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/prevención & control , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Niño , Preescolar , Terapia Combinada , Irradiación Craneana , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
This work develops a composite system of reduced graphene oxide (rGO)-iron oxide nanoparticles (rGO-IONP) that can synergistically induce physical and chemical damage to methicillin-resistant Staphylococcus aureus (MRSA) that are present in subcutaneous abscesses. rGO-IONP was synthesized by the chemical deposition of Fe(2+)/Fe(3+) ions on nanosheets of rGO in aqueous ammonia. The antibacterial efficacy of the as-prepared rGO-IONP was evaluated in a mouse model with MRSA-infected subcutaneous abscesses. Upon exposure to a near-infrared laser in vitro, rGO-IONP synergistically generated localized heat and large amounts of hydroxyl radicals, which inactivated MRSA. The in vivo results reveal that combined treatment with localized heat and oxidative stress that is caused by hydroxyl radicals accelerated the healing of wounds associated with MRSA-infected abscesses. The above results demonstrate that an rGO-IONP nanocomposite system that can effectively inactivate multiple-drug-resistant bacteria in subcutaneous infections was successfully developed. FROM THE CLINICAL EDITOR: The emergence of methicillin-resistant S. aureus (MRSA) has posed a significant problem in the clinical setting. Thus, it is imperative to develop new treatment strategies against this. In this study, the authors described the use of reduced graphene oxide (rGO)-iron oxide nanoparticles (rGO-IONP) to induce heat and chemical damage to MRSA. This approach may provide a platform the design of other treatment modalities against multiple-drug-resistant bacteria.
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Antibacterianos/uso terapéutico , Compuestos Férricos/uso terapéutico , Grafito/uso terapéutico , Radical Hidroxilo/metabolismo , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Nanocompuestos/uso terapéutico , Infecciones Estafilocócicas/terapia , Animales , Antibacterianos/química , Femenino , Compuestos Férricos/química , Grafito/química , Calor , Hipertermia Inducida/métodos , Rayos Infrarrojos , Ratones Endogámicos BALB C , Nanocompuestos/química , Nanocompuestos/ultraestructura , Estrés Oxidativo/efectos de los fármacos , Fototerapia/métodos , Infecciones Estafilocócicas/metabolismoRESUMEN
BACKGROUND/PURPOSE: Mutations in the tet oncogene family member 2 gene (TET2) are frequently found in adult patients with acute myeloid leukemia (AML). Reports of TET2 mutations in children are limited. We assessed the prevalence of TET2 mutations in Taiwanese children with AML and analyzed their prognosis. METHODS: Between 1997 and 2010, a total of 69 consecutive children with AML were enrolled at the National Taiwan University Hospital. The analysis for TET2 mutations was performed using direct sequencing. Clinical characteristics and overall survival (OS) were compared between patients with and without TET2 alterations. RESULTS: Intronic and missense mutations were identified. No nonsense or frameshift mutations were observed. Two putative disease-causing missense mutations (S609C and A1865G) were identified in one patient. We estimated the prevalence of TET2 mutations in the current patient population to be 1.4%. The most common polymorphism was I1762V (45%), followed by V218M (12%), P29R (6%), and F868L (6%). Patients with polymorphism I1762V had an increased 10-year survival rate compared with patients without I1762V (48.4% vs. 25.7%, p = 0.049) by Chi-square test; OS was not different when examined using the Kaplan-Meier method (p = 0.104). CONCLUSION: The prevalence of TET2 mutations in children with AML compared with adults with AML was lower and less complex. Patient prognosis associated with TET2 mutations in children requires further investigation.
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Proteínas de Unión al ADN/genética , Leucemia Mieloide Aguda/genética , Proteínas Proto-Oncogénicas/genética , Adolescente , Niño , Preescolar , Dioxigenasas , Femenino , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Mutación Missense , Pronóstico , Análisis de Secuencia de ADN , Tasa de Supervivencia , Taiwán/epidemiologíaRESUMEN
BACKGROUND/PURPOSE: Although Down syndrome (DS) patients have a higher risk of developing transient myeloproliferative disorder (TMD) and acute leukemia, very little data is available on long-term outcome in Taiwanese patients. The current study was designed to determine the clinical characteristics and treatment outcome of DS patients with TMD or acute leukemia (AL). METHODS: In 25 consecutive DS patients with TMD or AL enrolled from 1990 to 2012, clinical manifestations and treatment protocols were investigated and GATA1 (GATA binding protein 1) mutations were identified. Among 16 DS-acute myeloid leukemia (DS-AML) patients, clinical outcomes were compared between survivors and nonsurvivors. RESULTS: Most of our DS patients had TMD (32%), acute megakaryoblastic leukemia (24%), or acute erythromegakaryoblastic leukemia (16%). The median follow-up time was 22.5 months (1-230 months). The age was younger and the hemoglobin (Hb) level and platelet count were higher in TMD patients than in leukemia patients. Among DS-AML patients, the Hb level was higher in survivors than nonsurvivors (8.8 ± 2.7 g/dL vs. 5.8 ± 2.4 g/dL; p = 0.044) and the age was older in relapsed patients than in nonrelapsed patients (43.8 ± 18 months old vs. 21.6 ± 8.6 months old; p = 0.025). The 3-year overall survival (OS) rate was 44%, higher in patients receiving appropriate chemotherapy than in those receiving inadequate treatment (63.6% vs. 0%, p = 0.001), and higher in those diagnosed with TMD or AL after 2008 than before 2008 (33.3% vs. 75%; p = 0.119). CONCLUSION: Outcome in DS-AML patients is optimal if appropriate treatment is provided. With modification of the treatment strategy in 2008, OS increased in Taiwan.
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Síndrome de Down/complicaciones , Factor de Transcripción GATA1/genética , Leucemia Mieloide Aguda/epidemiología , Reacción Leucemoide/epidemiología , Preescolar , Síndrome de Down/epidemiología , Síndrome de Down/genética , Quimioterapia , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Reacción Leucemoide/genética , Masculino , Mutación , Estudios Retrospectivos , Tasa de Supervivencia , Taiwán , Resultado del TratamientoRESUMEN
BACKGROUND: Childhood acute lymphoblastic leukemia (ALL), a heterogeneous disease that includes multiple subtypes is defined by cell lineage and chromosome anomalies. Previous genome-wide association studies have reported several ARID5B and IKZF1 single nucleotide polymorphisms (SNPs) associated with the incidence of ALL. High-resolution melting (HRM) analysis is a rapid and convenient technique to detect SNPs; we thereby detected SNPs in ARID5B and IKZF1 genes. METHODS: We enrolled 79 pediatric ALL patients and 80 healthy controls. Polymorphic variants of IKZF1 (rs6964823, rs4132601, and rs6944602) and ARID5B (rs7073837, rs10740055, and rs7089424) were detected by HRM, and SNPs were analyzed for association with childhood ALL. RESULTS: The distribution of genotype rs7073837 in ARID5B significantly differed between ALL and controls (P=0.046), while those of IKZF1 (rs6964823, rs4132601, and rs6944602) and ARID5B (rs10740055 and rs7089424) did not. We analyzed the association for SNPs with B lineage ALL to find rs7073837 in ARID5B, conferring a higher risk for B lineage ALL (odds ratio, OR=1.70, 95% confidence interval, CI=1.01-2.87, P=0.049). CONCLUSION: HRM is a practical method to detect SNPs in ARID5B and IKZF1 genes. We found that rs7073837 in ARID5B correlated with a risk for childhood B lineage ALL.
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Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Variación Genética , Factor de Transcripción Ikaros/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Sitios de Carácter Cuantitativo , Factores de Transcripción/genética , Adolescente , Alelos , Estudios de Casos y Controles , Niño , Preescolar , Frecuencia de los Genes , Genotipo , Humanos , Lactante , Recién Nacido , Técnicas de Amplificación de Ácido Nucleico , Polimorfismo de Nucleótido Simple , TaiwánRESUMEN
BACKGROUND: Diabetes mellitus is a major endocrinopathy for patients with thalassemia major. Although diabetes mellitus is multifactorial, iron loading is its primary cause and its management poses a clinical challenge. Detecting the pre-diabetes stage is critical because clinical diabetes can potentially be reversed or prevented. PROCEDURE: Patients with thalassemia major who received regular blood transfusion therapy from 1994 to 2010 were evaluated for the incidence of diabetes mellitus and glucose dysregulation. The association between patients' clinical, biochemical, and image parameters was also evaluated. RESULTS: The patients with diabetes were significantly older, had higher ferritin levels, a smaller pancreas volume, and lower cardiac T2* magnetic resonance imaging (MRI) values than the patients without diabetes. The pancreas T2* MRI values were higher in the patients without diabetes, but the difference was not statistically significant. The liver iron concentration did not differ between the patients with and without diabetes. The prevalence of hepatitis C infection and hypogonadism was also higher in the patients with diabetes. In the patients without diabetes, the cardiac T2* MRI values were higher in patients with normal fasting glucose levels (P = 0.03), and the homeostasis model assessment of insulin resistance level was associated with hepatitis C infection (P = 0.024, r = 0.32) and hypogonadism (P = 0.034, r = 0.301). CONCLUSIONS: Fasting glucose and insulin levels were appropriate screening tools for evaluating glucose dysregulation and complemented the MRI findings. The cardiac T2* and pancreas volumes were significant predictors of diabetes.
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Diabetes Mellitus/epidemiología , Talasemia beta/complicaciones , Adolescente , Adulto , Niño , Femenino , Humanos , Incidencia , Imagen por Resonancia Magnética , Masculino , Miocardio/patología , Páncreas/patología , Adulto JovenRESUMEN
BACKGROUND: Gaucher disease (GD) is a lysosomal storage disorder characterized by deficient glucocerebrosidase activity that results from biallelic mutations in the GBA1 gene. Its phenotypic variability allows GD to be classified into 3 subtypes based on the presence and extent of neurological manifestations. Enzyme replacement therapy (ERT) has been available for all patients with GD in Taiwan since 1998. Newborn screening (NBS) for GD has been available since 2015. This study attempted to unveil the clinical features of patients diagnosed with GD during different eras in Taiwan. MATERIALS AND METHODS: Data from the health records of two tertiary hospitals responsible for two-thirds of the patients with GD in Taiwan were used. The study population included all patients identified as having GD between 1998, and April 2022, in these two hospitals for review. A total of 42 individuals were included, six of whom were diagnosed by NBS. RESULTS: Our cohort presented a higher proportion of GD3 individuals, both by clinical suspicion and by NBS diagnosis, than that reported worldwide. The major subtypes that were recognized following NBS diagnosis were GD2 and GD3. The majority of GD patients carry at least one p.Leu483Pro variant. The 5-year survival rates were 0% for GD2 patients and 100% for patients with other subtypes. Patients diagnosed during the post-NBS era were free of symptoms on initial presentation, except for those with the GD2 subtype. For those diagnosed earlier, ERT was shown to be effective in terms of improved hemograms and prevented bone crises. However, the neurological symptoms in GD3 patients progressed despite ERT intervention. CONCLUSION: ERT is essential in reversing the hematological presentations and preventing the skeletal complications of GD. Timely diagnosis of GD with NBS allows for early intervention with ERT to prevent disease progression and complications. However, the need for effective intervention for neurological dysfunction remains unmet.
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Enfermedad de Gaucher , Enfermedades por Almacenamiento Lisosomal , Recién Nacido , Humanos , Enfermedad de Gaucher/tratamiento farmacológico , Enfermedad de Gaucher/genética , Taiwán , Progresión de la Enfermedad , Terapia de Reemplazo EnzimáticoRESUMEN
Systemic fungal infections have high morbidity and mortality rates in neonates, especially neonates with an extremely low birth weight (ELBW). Here, we describe a 21-day-old ELBW female infant with an amphotericin B-unresponsive congenital Candida albicans infection that was treated with caspofungin. Blood sterilization was performed during the first episode, but a second episode of candidemia occurred after the discontinuation of caspofungin. Blood sterilization was again performed during the second round of caspofungin treatment, but fungal endocarditis and renal fungal balls still developed during the second episode. Caspofungin can be considered for invasive candidiasis in premature infants, especially in life-threatening situations. As for the focal lesions, more aggressive treatments other than just parenteral antibiotics should be considered. The literature regarding caspofungin therapy for neonatal candidiasis is also reviewed.
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Antifúngicos/uso terapéutico , Candida albicans/aislamiento & purificación , Candidemia/tratamiento farmacológico , Equinocandinas/uso terapéutico , Candida albicans/efectos de los fármacos , Candidemia/diagnóstico , Candidemia/microbiología , Caspofungina , Equinocandinas/efectos adversos , Resultado Fatal , Femenino , Humanos , Recien Nacido con Peso al Nacer Extremadamente Bajo , Recién Nacido , LipopéptidosRESUMEN
BACKGROUND: Sequencing technologies, such as whole-exome sequencing (WES) and whole-genome sequencing (WGS), have been increasingly applied to medical research in recent years. Which countries, journals, and institutes (called entities) contributed most to the fields (WES/WGS) remains unknown. Temporal bar graphs (TBGs) are frequently used in trend analysis of publications. However, how to draw the TBG on the Sankey diagram is not well understood in bibliometrics. We thus aimed to investigate the evolution of article entities in the WES/WGS fields using publication-based TBGs and compare the individual research achievements (IRAs) among entities. METHODS: A total of 3599 abstracts downloaded from icite analysis were matched to entities, including article identity numbers, citations, publication years, journals, affiliated countries/regions of origin, and medical subject headings (MeSH terms) in PubMed on March 12, 2022. The relative citation ratio (RCR) was extracted from icite analysis to compute the hT index (denoting the IRA, taking both publications and citations into account) for each entity in the years between 2012 and 2021. Three types of visualizations were applied to display the trends of publications (e.g., choropleth maps and the enhanced TBGs) and IRAs (e.g., the flowchart on the Sankey diagram) for article entities in WES/WGS. RESULTS: We observed that the 3 countries (the US, China, and the UK) occupied most articles in the WES/WGS fields since 2012, the 3 entities (i.e., top 5 journals, research institutes, and MeSH terms) were demonstrated on the enhanced TBGs, the top 2 MeSH terms were genetics and methods in WES and WGS, and the IRAs of 6 article entities with their hT-indices were succinctly and simultaneously displayed on a single Sankey diagram that was never launched in bibliographical studies. CONCLUSION: The number of WES/WGS-related articles has dramatically increased since 2017. TBGs, particularly with hTs on the Sankey, are recommended for research on a topic (or in a discipline) to compare trends of publications and IRAs for entities in future bibliographical studies.
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Exoma , Genoma Humano , Bibliometría , Humanos , Secuenciación del Exoma , Secuenciación Completa del GenomaRESUMEN
Identification of specific leukemia subtypes is a key to successful risk-directed therapy in childhood acute lymphoblastic leukemia (ALL). Although RNA sequencing (RNA-seq) is the best approach to identify virtually all specific leukemia subtypes, the routine use of this method is too costly for patients in resource-limited countries. This study enrolled 295 patients with pediatric ALL from 2010 to 2020. Routine screening could identify major cytogenetic alterations in approximately 69% of B-cell ALL (B-ALL) cases by RT-PCR, DNA index, and multiplex ligation-dependent probe amplification. STIL-TAL1 was present in 33% of T-cell ALL (T-ALL) cases. The remaining samples were submitted for RNA-seq. More than 96% of B-ALL cases and 74% of T-ALL cases could be identified based on the current molecular classification using this sequential approach. Patients with Philadelphia chromosome-like ALL constituted only 2.4% of the entire cohort, a rate even lower than those with ZNF384-rearranged (4.8%), DUX4-rearranged (6%), and Philadelphia chromosome-positive (4.4%) ALL. Patients with ETV6-RUNX1, high hyperdiploidy, PAX5 alteration, and DUX4 rearrangement had favorable prognosis, whereas those with hypodiploid and KMT2A and MEF2D rearrangement ALL had unfavorable outcomes. With the use of multiplex ligation-dependent probe amplification, DNA index, and RT-PCR in B-ALL and RT-PCR in T-ALL followed by RNA-seq, childhood ALL can be better classified to improve clinical assessments.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Niño , Humanos , Proteínas de Fusión Oncogénica/genética , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Aneuploidia , ADNRESUMEN
Aneuploidy occurs within a significant proportion of childhood B-cell acute lymphoblastic leukemia (B-ALL). Some copy number variations (CNV), associated with novel subtypes of childhood B-ALL, have prognostic significance. A total of 233 childhood B-ALL patients were enrolled into this study. Focal copy number alterations of ERG, IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A/2B, and the Xp22.33/Yp11.31 region were assessed by Multiplex Ligation-dependent Probe Amplification (MLPA). The MLPA telomere kit was used to identify aneuploidy through detection of whole chromosome loss or gain. We carried out these procedures alongside measurement of DNA index in order to identify, aneuploidy status in our cohort. MLPA telomere data and DNA index correlated well with aneuploidy status at higher sensitivity than cytogenetic analysis. Three masked hypodiploid patients, undetected by cytogenetics, and their associated copy number neutral loss of heterozygosity (CN-LOH) were identified by STR and SNP arrays. Rearrangements of TCF3, located to 19p, were frequently associated with 19p deletions. Other genetic alterations including iAMP21, IKZF1 deletions, ERG deletions, PAX5AMP, which have clinical significance or are associated with novel subtypes of ALL, were identified. In conclusion, appropriate application of MLPA aids the identifications of CNV and aneuploidy in childhood B-ALL.
Asunto(s)
Variaciones en el Número de Copia de ADN/genética , Patología Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Pronóstico , Adolescente , Aneuploidia , Linfocitos B/patología , Niño , Preescolar , Aberraciones Cromosómicas , ADN de Neoplasias/sangre , Femenino , Humanos , Lactante , Masculino , Reacción en Cadena de la Polimerasa Multiplex/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologíaRESUMEN
PURPOSE OF THE STUDY: While the outcomes of cardiopulmonary resuscitation (CPR) for pediatric in-hospital cardiac arrest (IHCA) are reported for many regions, none is reported for Asian countries. We report the outcomes of CPR for pediatric IHCA in a tertiary medical center in Taiwan and also identify prognostic factors associated with poor outcome. METHODS: Data were retrieved retrospectively from 2000 to 2003 and prospectively from 2004 to 2006 from our web-based registry system. We evaluated patients younger than 18 years of age who had IHCA and received CPR. The primary outcome was survival to hospital discharge, and the secondary outcomes were sustained return of spontaneous circulation (ROSC), and favorable neurological outcomes as assessed by pediatric cerebral performance categories (PCPC). RESULTS: We identified 316 patients and the overall hospital survival was 20.9% and 16.1% had favorable neurological outcomes. Sixty-four patients ever supported with ECMO. We further analyzed 252 patients who underwent conventional CPR only and most had cardiac disease (133/252, 52.8%). The second most common preexisting condition was hematologic or oncologic disease (43/252, 17.1%). Of the 252 patients, 153 (60.7%) achieved sustained ROSC, 50 (19.8%) survived to discharge, and 39 patients (15.5%) had favorable neurological outcomes. CPR during off-work hours resulted in inferior chances of reaching sustained ROSC. Multivariate analysis showed that long CPR duration, hematology/oncology patients, and pre-arrest vasoactive drug infusion were significantly associated with decreased hospital survival (p<0.05). CONCLUSIONS: Outcomes of CPR for pediatric patients with IHCA in Taiwan were comparable to corresponding reports in Western countries, but more hematology/oncology patients were included. Long CPR duration, hematologic or oncologic underlying diseases, and vasoactive agent infusion prior IHCA were associated with poor outcomes. The concept of palliative care should be proposed to families of terminally ill cancer patients in order to avoid unnecessary patient suffering. Also, establishing a balanced duty system in the future might increase chances of sustained ROSC.
Asunto(s)
Reanimación Cardiopulmonar , Paro Cardíaco/terapia , Adolescente , Factores de Edad , Niño , Preescolar , Estudios de Cohortes , Bases de Datos Factuales , Paro Cardíaco/etiología , Paro Cardíaco/mortalidad , Humanos , Lactante , Recién Nacido , Recuperación de la Función , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Taiwán , Resultado del TratamientoRESUMEN
Tracheobronchial compression by cardiovascular structures complicates the course after surgery of congenital heart disease. A 2-month-old boy with ventricular septal defect, pulmonary atresia, and velocardiofacial syndrome had severe left main bronchus obstruction due to external compression by an anomalously oriented ascending aorta. The patient's hypoxemic episodes necessitated extracorporeal membrane oxygenation. We inserted a stent in the left bronchus to open the airway, but the stent was crushed by the anomalous aorta. We later surgically rerouted the aorta and finally restored the patency of the left main bronchus. However, the patient died of fungemia, without being weaned from extracorporeal membrane oxygenation. We conclude that surgery is necessary instead of stent implantation to relieve the external compression of the left bronchus from a vessel with systemic arterial pressure.