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BACKGROUND: To evaluate the relationships among hip instability, pain, and morphology of the iliofemoral ligament (ILFL) in patients with developmental dysplasia of the hip (DDH) using ultrasonography (US). METHODS: We reviewed 86 patients (109 hips) with DDH (Group D), 40 patients (46 hips) with borderline hip dysplasia (BDDH) (Group B) and 20 patients (23 hips) without hip pain and bony abnormality (control group). Group D was classified into three subgroups-the severe (group SP), moderate (group MP), and none/mild (group NMP) hip pain groups-using the visual analogue scale (VAS). For evaluating hip instability and ILFL morphology, the distance between the anterior edge of the anterior inferior iliac spine (AIIS) and the horizontal line to the femoral head, and ILFL thickness were measured using US. The difference between the distance in the neutral position and Patrick position was calculated and defined as the femoral head translation distance (FTD). RESULTS: FTD and ILFL thickness in group D were significantly larger than those in the control group and group B (P < 0.05). There was a significant positive correlation between FTD and ILFL thickness in three groups (r = 0.57, P < 0.05; r = 0.55, P < 0.05; r = 0.62, P < 0.05, respectively). FTD and ILFL thickness in group SP were significantly larger than those in group NMP (P < 0.05). FTD and ILFL thickness in group D had significantly negative correlations with the lateral center edge (r = -0.54, P < 0.05; r = -0.40, P < 0.05, respectively) and vertical-center-anterior angle (r = -0.51, P < 0.05; r = -0.43, P < 0.05, respectively). CONCLUSIONS: Acetabular bony deficiency, especially in the anterior and lateral region can result in antero-posterior hip instability, leading to thickened ILFL and hip pain, even in patients with BDDH. These findings may facilitate our understanding and treatment of patients with DDH. When hip instability is suspected, hip US examination may help confirm the diagnosis and assist in providing objective clinical diagnostic evidence.
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AIM: The MEAM regimen consisting of ranimustine (MCNU), etoposide (ETP), cytarabine (Ara-C), and melphalan (MEL) is widely used before auto-peripheral blood stem cell transplantation (auto-PBSCT) for malignant lymphoma in Japan. The MEAM regimen generally consists of 200-400 mg/m2 for 4 days, but we decided to increase the dosage of Ara-C from the standard to 2 g/m2 for 2 days with the aim of increasing drug transferability to the central nervous system. We evaluate the safety and therapeutic efficacy of high-dose Ara-C MEAM therapy. METHODS: The high-dose Ara-C MEAM protocol consisted of MCNU 300 mg/m2 on day -7, ETP 200 mg/m2 on days -6, -5, -4, -3 and Ara-C 2 g/m2 on day -4 -3, and MEL 140 mg/m2 on day -2. We retrospectively analyzed 37 cases of malignant lymphoma at our institution between May 2014 and July 2020. RESULTS: All patients got engraftment and there were no cases of treatment-related mortality. In all cases, the 3-year overall survival (OS) and progression-free survival (PFS) after transplantation were 80.6% and 65.7%, respectively. Twenty-one cases of diffuse large B-cell lymphoma recurrence, for which there is proven usefulness of auto-PBSCT, showed good results after transplantation, with the 3-year OS and PFS after transplantation being 100% and 74.3%, respectively. CONCLUSION: The safety and efficacy of high-dose Ara-C MEAM therapy were demonstrated, but the expected therapeutic effect on central nervous system lesions could not be fully evaluated owing to the small number of cases.
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Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Transplante de Células-Tronco de Sangue Periférico , Humanos , Transplante de Células-Tronco de Sangue Periférico/métodos , Citarabina/efeitos adversos , Estudos Retrospectivos , Transplante Autólogo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Etoposídeo/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Melfalan/efeitos adversos , Condicionamento Pré-Transplante/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Accurate evaluation of hip instability is critical for the diagnosis and successful treatment of developmental dysplasia of the hip (DDH). However, dynamic evaluation of hip instability is not well established. This study aimed to use the lateral view from a radiograph to evaluate dynamic antero-posterior hip instability in patients with DDH. METHODS: Seventy-four patients (92 hips) with DDH (DDH group) and 46 patients (59 hips) without hip pain and DDH (Control group) were examined. A false profile view (FPV) according to Lequesne was taken at standard and 90° flexion with the hip of interest defined as functional FPV; the translation of the center of the femoral head (CFH) obtained from the functional FPV was measured. As a validation test, we measured the anterior translation of the CFH using ultrasonography (US). RESULTS: There was a significant difference between the two groups in the translation of the CFH (p < 0.01). The degree of CFH translation depended on the severity of DDH (lateral center edge angle, r = -0.56, p < 0.01; vertical center anterior margin angle, r = -0.57, p<0.01) and lateralization of the femoral head (head lateralization index, r = 0.54, p < 0.01). There was a significant correlation between functional FPV and US measurements (r = 0.71, p < 0.01). CONCLUSION: The present study confirmed that antero-posterior hip instability in DDH patients can be detected using functional FPV. Our novel measurement, as a new method for assessing hip instability, may be useful for evaluating hip dynamic instability in diagnosing the etiology, and determining and evaluating the treatment for DDH at lower cost and improved accessibility.
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Luxação Congênita de Quadril , Humanos , Luxação Congênita de Quadril/diagnóstico por imagem , Articulação do Quadril/diagnóstico por imagem , Radiografia , Artralgia , Cabeça do Fêmur/diagnóstico por imagem , Estudos Retrospectivos , AcetábuloRESUMO
A novel anionic tridentate borate ligand with a 6-methylpyridyl donor, TpyMe, has been synthesized. Comparison of the molecular structures and reactivities of nickel(II)-bromido complexes with tris(azolyl)borate ligands composed of pyridyl, pyrazolyl, or oxazolinyl donors indicates the characteristic sterically demanding nature and strong electron donating ability of TpyMe.
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Recent studies have reported that measurable residual disease (MRD) analysis using NPM1 mutations helps determine whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) is indicated in acute myeloid leukemia (AML) patients. However, the optimal timing and cutoff value for measuring MRD using genomic DNA remain undetermined. This study aimed to investigate the optimal timing and cutoff value to ascertain the value of NPM1 mutation in MRD assessment. NPM1-mutated MRD was quantified by real-time polymerase chain reaction of bone marrow samples from 56 patients with NPM1-positive AML who achieved hematological remission. The area under the receiver-operating characteristic curve was greatest when MRD was assessed after two courses of post-remission therapy with a cutoff value of 0.010% (specificity, 68.4%; sensitivity, 87.0%). Patients whose MRD was below the cutoff value throughout the course of treatment had significantly better overall survival and relapse-free survival rates. Of the 33 patients who did not undergo transplantation during the first remission, all of the 11 who were never MRD-negative at any point experienced a relapse. Evaluating MRD with a cutoff value of 0.010% after two courses of post-remission therapy helps predict prognosis and determine the indication for allo-HSCT.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutação , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Nucleofosmina , Prognóstico , RecidivaRESUMO
Mutations of CCAAT/enhancer-binding protein alpha (CEBPAmu) are found in 10% to 15% of de novo acute myeloid leukemia (AML) cases. Double-mutated CEBPA (CEBPAdm) is associated with a favorable prognosis; however, single-mutated CEBPA (CEBPAsm) does not seem to improve prognosis. We investigated CEBPAmu for prognosis in 1028 patients with AML, registered in the Multi-center Collaborative Program for Gene Sequencing of Japanese AML. It was found that CEBPAmu in the basic leucine zipper domain (bZIP) was strongly associated with a favorable prognosis, but CEBPAmu out of the bZIP domain was not. The presence of CEBPAmu in bZIP was a strong indicator of a higher chance of achieving complete remission (P < .001), better overall survival (OS; P < .001) and a lower risk of relapse (P < .001). The prognostic significance of CEBPAmu in bZIP was also observed in the subgroup with CEBPAsm (all patients: OS, P = .008; the cumulative incidence of relapse, P = .063; patients aged ≤70 years and with intermediate-risk karyotype: OS, P = .008; cumulative incidence of relapse, P = .026). Multivariate analysis of 744 patients aged ≤70 years showed that CEBPAmu in bZIP was the most potent predictor of OS (hazard ratio, 0.3287; P < .001). CEBPAdm was validated as a cofounding factor, which was overlapping with CEBPAmu in bZIP. In summary, these findings indicate that CEBPAmu in bZIP is a potent marker for AML prognosis. It holds potential in the refinement of treatment stratification and the development of targeted therapeutic approaches in CEBPA-mutated AML.
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Proteínas Estimuladoras de Ligação a CCAAT , Leucemia Mieloide Aguda , Idoso , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Humanos , Cariótipo , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Mutação , PrognósticoRESUMO
AIMS: Rotational acetabular osteotomy (RAO) has been reported to be effective in improving symptoms and preventing osteoarthritis (OA) progression in patients with mild to severe develomental dysplasia of the hip (DDH). However, some patients develop secondary OA even when the preoperative joint space is normal; determining who will progress to OA is difficult. We evaluated whether the preoperative cartilage condition may predict OA progression following surgery using T2 mapping MRI. METHODS: We reviewed 61 hips with early-stage OA in 61 patients who underwent RAO for DDH. They underwent preoperative and five-year postoperative radiological analysis of the hip. Those with a joint space narrowing of more than 1 mm were considered to have 'OA progression'. Preoperative assessment of articular cartilage was also performed using 3T MRI with the T2 mapping technique. The region of interest was defined as the weightbearing portion of the acetabulum and femoral head. RESULTS: There were 16 patients with postoperative OA progression. The T2 values of the centre to the anterolateral region of the acetabulum and femoral head in the OA progression cases were significantly higher than those in patients without OA progression. The preoperative T2 values in those regions were positively correlated with the narrowed joint space width. The receiver operating characteristic analysis revealed that the T2 value of the central portion in the acetabulum provided excellent discrimination, with OA progression patients having an area under the curve of 0.858. Furthermore, logistic regression analysis showed T2 values of the centre to the acetabulum's anterolateral portion as independent predictors of subsequent OA progression (p < 0.001). CONCLUSION: This was the first study to evaluate the relationship between intra-articular degeneration using T2 mapping MRI and postoperative OA progression. Our findings suggest that preoperative T2 values of the hip can be better prognostic factors for OA progression than radiological measures following RAO. Cite this article: Bone Joint J 2021;103-B(9):1472-1478.
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Cartilagem Articular/diagnóstico por imagem , Luxação Congênita de Quadril/diagnóstico por imagem , Luxação Congênita de Quadril/cirurgia , Osteoartrite/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Adolescente , Adulto , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Osteoartrite/prevenção & controle , Osteotomia/métodos , Complicações Pós-Operatórias/prevenção & controle , Período Pós-Operatório , Valor Preditivo dos TestesRESUMO
BACKGROUND/AIM: Combination cancer therapy is currently under investigation. This study examined the effect of cancer combination therapy using the E3 and C1 (E3C1) domains of developmental endothelial locus-1 (Del1) and cisplatin (CDDP) in murine transplanted tumors. MATERIALS AND METHODS: Mice with transplanted tumors (A431, SCCKN or SCC-4 cells) were injected intraperitoneally with CDDP and injected locally with nonviral plasmid vectors encoding E3C1. Histochemical analysis of the transplanted tumors was then performed to assess the effects on prognosis. RESULTS: The CDDP+E3C1 injected group had reduced tumor growth and longer survival compared to the CDDP injected group. In addition, cell death was observed in the tumor of the CDDP+E3C1 group.. Furthermore, angiogenesis and increased blood vessels were observed together with stromal development. CONCLUSION: The CDDP+E3C1 treatment resulted in improved survival and poor tumor stromal development in mice with transplanted tumors.
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Antineoplásicos , Neoplasias , Animais , Antineoplásicos/farmacologia , Cisplatino , Terapia Combinada , Vetores Genéticos , Camundongos , Neovascularização Patológica/genéticaRESUMO
ABSTRACT Background: Cancer gene therapy using a nonviral vector is expected to be repeatable, safe, and inexpensive, and to have long-term effectiveness. Gene therapy using the E3 and C1 (E3C1) domain of developmental endothelial locus-1 (Del1) has been shown to improve prognosis in a mouse transplanted tumor model. Objective: In this study, we examined how this treatment affects angiogenesis in mouse transplanted tumors. Materials and methods: Mouse transplanted tumors (SCCKN human squamous carcinoma cell line) were injected locally with a nonviral plasmid vector encoding E3C1 weekly. Histochemical analysis of the transplanted tumors was then performed to assess the effects of E3C1 on prognosis. Results: All mice in the control group had died or reached an endpoint within 39 days. In contrast, one of ten mice in the E3C1 group had died by day 39, and eight of ten had died or reached an endpoint by day 120 (p < 0.01). Enhanced apoptosis in tumor stroma was seen on histochemical analyses, as was inhibited tumor angiogenesis in E3C1-treated mice. In addition, western blot analysis showed decreases in active Notch and HEY1 proteins. Conclusion: These findings indicate that cancer gene therapy using a nonviral vector encoding E3C1 significantly improved life-span by inhibiting tumor angiogenesis. (REV INVEST CLIN. 2021;73(1):39-51)
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Animais , Coelhos , Proteínas de Ligação ao Cálcio/uso terapêutico , Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/terapia , Moléculas de Adesão Celular/uso terapêutico , Fator de Crescimento Epidérmico/uso terapêutico , Domínio Discoidina/genética , Proteínas de Ligação ao Cálcio/genética , Células Tumorais Cultivadas , Terapia Genética , Moléculas de Adesão Celular/genética , Motivos de Aminoácidos , Fator de Crescimento Epidérmico/genética , Camundongos Nus , Transplante de Neoplasias , Neovascularização Patológica/terapiaRESUMO
BACKGROUND: Because peripheral blood stem cell (PBSC) collection places a burden on the patient and should ideally be completed in a single procedure, a convenient clinical predictive factor is needed. METHODS: This retrospective study included 72 patients who underwent autologous PBSC collection. A median volume of 3.9 × 106 CD34-positive cells/kg (range: 0.3-47.4 × 106 cells/kg) was collected on the first day. We defined failure as inability to collect 2.0 × 106 cells/kg on the first day. PBSC collection was classified as failed (n = 25, 34.7%) and successful (n = 47, 65.3%), and patient clinical characteristics were analyzed. RESULTS: The success group had significantly more cases in which a differential white blood cell count in peripheral blood on the day of PBSC collection detected promyelocytes (n = 34 [72.3%] vs. n = 11 [44.0%] in the failure group; P = 0.008). Sixty-two patients underwent autologous PBSC transplantation (median number of transplanted cells, 5.6 × 106/µL; range: 1.60-47.4 × 106 cells/µL). Among transplanted patients, the success and failure groups did not significantly differ in relation to the interval until neutrophil, platelet, or red blood cell engraftment. CONCLUSION: The presence of promyelocytes in peripheral blood may be a useful indicator of the optimal timing for single-step PBSC collection.
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Células Precursoras de Granulócitos , Transplante de Células-Tronco de Sangue Periférico/métodos , Células-Tronco de Sangue Periférico , Coleta de Tecidos e Órgãos/métodos , Transplante Autólogo/métodos , Adolescente , Adulto , Idoso , Antígenos CD34 , Feminino , Humanos , Leucemia Promielocítica Aguda/terapia , Contagem de Leucócitos , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Cancer gene therapy using a nonviral vector is expected to be repeatable, safe, and inexpensive, and to have longterm effectiveness. Gene therapy using the E3 and C1 (E3C1) domain of developmental endothelial locus-1 (Del1) has been shown to improve prognosis in a mouse transplanted tumor model. OBJECTIVE: In this study, we examined how this treatment affects angiogenesis in mouse transplanted tumors. MATERIALS AND METHODS: Mouse transplanted tumors (SCCKN human squamous carcinoma cell line) were injected locally with a nonviral plasmid vector encoding E3C1 weekly. Histochemical analysis of the transplanted tumors was then performed to assess the effects of E3C1 on prognosis. RESULTS: All mice in the control group had died or reached an endpoint within 39 days. In contrast, one of ten mice in the E3C1 group had died by day 39, and eight of ten had died or reached an endpoint by day 120 (p < 0.01). Enhanced apoptosis in tumor stroma was seen on histochemical analyses, as was inhibited tumor angiogenesis in E3C1-treated mice. In addition, western blot analysis showed decreases in active Notch and HEY1 proteins. CONCLUSION: These findings indicate that cancer gene therapy using a nonviral vector encoding E3C1 significantly improved life-span by inhibiting tumor angiogenesis.
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Proteínas de Ligação ao Cálcio/uso terapêutico , Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/terapia , Moléculas de Adesão Celular/uso terapêutico , Domínio Discoidina , Fator de Crescimento Epidérmico/uso terapêutico , Terapia Genética , Neovascularização Patológica/terapia , Motivos de Aminoácidos , Animais , Proteínas de Ligação ao Cálcio/genética , Moléculas de Adesão Celular/genética , Domínio Discoidina/genética , Fator de Crescimento Epidérmico/genética , Camundongos , Camundongos Nus , Transplante de Neoplasias , Células Tumorais CultivadasRESUMO
This report discusses a case of a 75-year-old female patient with metachronous multicentric carcinomas in the oral cavity at 4 different sites. In this patient, there were no generally associated characteristics, such as drinking alcohol, chewing betel quid or smoking cigarettes. However, her elder sister died due to oral carcinoma. Although well-known risk factors for oral carcinoma were not detected, a previous family history was found. These findings suggest the potential for an unknown genetic anomaly associated with oral carcinoma. This is the first report to describe a female patient with oral multicentric carcinoma arising from four different sites.
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Carcinoma , Neoplasias Bucais , Idoso , Consumo de Bebidas Alcoólicas , Areca , Feminino , Humanos , Fatores de Risco , FumarRESUMO
Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is a key predictive factor for the prognosis of acute myeloid leukemia (AML). We compared the detection sensitivity of fragment analysis with that of PCR-electrophoresis using MV4-11 (FLT3-ITD) and NKM-1 (FLT3-wild type) cell lines. DNA of these cells was mixed at different ratios and subjected to PCR-electrophoresis or fragment analysis. PCR-electrophoresis was found to have an FLT3-ITD allelic ratio (AR) detection limit of 0.034-0.072. Visual inspection of the PCR-electrophoresis revealed a lower detection sensitivity than that of fragment analysis. Therefore, it is essential to conduct fragment analysis when screening for FLT3-ITD.
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BACKGROUND: Because the cause of liver dysfunction after allogeneic hematopoietic stem cell transplantation (HSCT) is difficult to identify in the early stages, treatment may be delayed. Therefore, early factors associated with unfavorable outcomes of liver dysfunction must be identified. The objective of this study was to identify unfavorable prognostic factors for liver dysfunction during the early period after transplantation. METHODS: We defined liver dysfunction as elevated liver or biliary enzyme levels (corresponding to Grade 2 in the Common Terminology Criteria for Adverse Events version 4.0) within 30 days of transplantation and retrospectively investigated data from 82 patients who had undergone allogeneic HSCT at our center. RESULTS: Elevated liver or biliary enzyme levels were observed in almost half of the patients studied (n=40, 48.7%). Elevated total bilirubin (T-Bil) level was the most frequently observed unfavorable prognostic factor and had the greatest effect on overall survival (OS), progression-free survival (PFS), and non-relapse mortality (NRM) (probability of unfavorable outcome in patients without and with elevated T-Bil level: OS, 58.9% vs. 15.4%, p < 0.001; PFS, 46.4% vs. 15.4%, p < 0.001; NRM, 10.7% vs. 53.8%, p < 0.001). Moreover, the probability of an unfavorable outcome increased in relation to the degree of T-Bil elevation and absence of improvement over time in T-Bil level. CONCLUSION: Elevated T-Bil level was an important marker of outcomes for liver dysfunction after allogeneic HSCT.
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Bilirrubina/sangue , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Adolescente , Adulto , Aloenxertos , Biomarcadores , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Acute kidney injury (AKI) and chronic kidney disease (CKD) are considered common complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). OBJECTIVES AND METHOD: In this study, 114 patients who had undergone allo-HSCT were retrospectively analyzed to investigate the risk factors for onset of posttransplant AKI and CKD as defined by the new Kidney Disease Improving Global Outcomes criteria. RESULTS: Seventy-four patients (64.9%) developed AKI and 25 (21.9%) developed CKD. The multivariate analysis showed that the risk factors for developing stage 1 or higher AKI were age ≥46 years at the time of transplant (p = 0.001) and use of ≥3 nephrotoxic drugs (p = 0.036). For CKD, the associated risk factors were disease status other than complete remission at the time of transplantation (p = 0.018) and onset of AKI after transplant (p = 0.035). The 5-year overall survival (OS) was significantly reduced by development of AKI (p < 0.001), but not CKD. Posttransplant AKI significantly increased the 5-year nonrelapse mortality (p < 0.001), whereas posttransplant CKD showed an increasing tendency, but the difference was not significant. CONCLUSIONS: Posttransplant AKI impacts OS, significantly increases the risk of CKD, and is significantly associated with disseminated intravascular coagulation and use of Ë3 nephrotoxic drugs.
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Injúria Renal Aguda/etiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Insuficiência Renal Crônica/etiologia , Injúria Renal Aguda/patologia , Adolescente , Adulto , Criança , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prognóstico , Indução de Remissão , Insuficiência Renal Crônica/patologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Adulto JovemRESUMO
BACKGROUND: Few reports have focused on chronic subdural hematoma (CSDH) in the very elderly, who have lived beyond average life expectancy. Our aim is to appraise treatment outcomes of burr-hole craniotomy for CSDH in the elderly, focusing on cure, recurrence, and complications. METHODS: Fifty patients ≤79 years of age (group A) and 73 patients ≥80 years of age (group B) were studied. Recurrence was defined as requiring reoperation for hematoma regrowth or symptomatic failure. A cure was regarded as having been achieved in the absence of hematoma on postoperative computed tomography. Complications were defined as any harmful event related to the treatment procedure for CSDH. RESULTS: Cure was documented in 31 patients in group A (63%) and 24 patients in group B (33%) (P = 0.0017). Median intervals to cure were 2.76 and 3.73 months, respectively (P = 0.06). Cumulative cure rates were 51%/76% and 36%/59%, respectively, at the sixth/twelfth postoperative months. Recurrence was documented in 2 patients (4%) and 11 patients (15%), respectively (P = 0.07). Median intervals to recurrence were 0.81 and 1.25 months, respectively (P = 0.049). Cumulative recurrence-free rates were 96%/92% and 87%/75%, respectively, at the third/sixth postoperative months. Complications were observed in 2 patients (4%) and 4 patients (5%), respectively (P = 1.00). CONCLUSIONS: With advancing age, CSDH might show a greater tendency to recur and a longer time is required to achieve a cure. However, complications developed only in high-risk patients. Thus, surgical treatment for CSDH in elderly patients, even those who have lived beyond life expectancy, might provide acceptably effective results.
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Hematoma Subdural Crônico/cirurgia , Trepanação/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Hematoma Subdural Crônico/mortalidade , Humanos , Estimativa de Kaplan-Meier , Expectativa de Vida , Masculino , Complicações Pós-Operatórias/epidemiologia , Recidiva , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Trepanação/mortalidadeRESUMO
The prognostic significance of FLT3-tyrosine kinase domain (TKD) mutations remains unknown. To investigate the prognostic impact of FLT3-TKD, 676 de novo acute myeloid leukemia (AML), we retrospectively analyzed cases and conducted a review of the literature. Of the 676 de novo AML cases, 34 (5.0%) were FLT3-TKD-positive; both FLT3-TKD and FLT3-ITD were noted in only two cases (0.3%). Although no significant differences in relapse-free survival (RFS) were noted, FLT3-TKD-positive cases showed better prognoses than FLT3-ITD-positive cases (FLT3-TKD versus FLT3-ITD, p = 0.152). For overall survival (OS), although FLT3-TKD-positive cases showed prognoses similar to those for FLT3-WT cases, their prognoses were significantly better than those of FLT3-ITD-positive cases (FLT3-TKD versus FLT3-ITD, p = 0.032). Moreover, the 5-year OS for FLT3-TKD-positive cases was 46.1%, indicating that this as an intermediate prognosis group. Although no reports from Asia have indicated a frequency of FLT3-TKD-positive cases > 10%, several reports from Europe and the United States have indicated frequencies > 10%. This suggests the possibility that FLT3-TKD-positive cases are less common in Asia than in Europe and the United States. We anticipate that in the future, the appearance of targeting agents, such as FLT3 inhibitors, will improve the prognosis of FLT3-TKD-positive AML relative to that of FLT3-WT AML.
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Leucemia Mieloide Aguda/diagnóstico , Mutação , Tirosina Quinase 3 Semelhante a fms/genética , Ásia , Europa (Continente) , Leucemia Mieloide Aguda/mortalidade , Prognóstico , Domínios Proteicos/genética , Proteínas Tirosina Quinases/genética , Estudos Retrospectivos , Análise de Sobrevida , Sequências de Repetição em Tandem , Estados UnidosRESUMO
INTRODUCTION: Acute myelogenous leukemia (AML) in elderly patients is associated with an increased incidence of complications and treatment-related toxicity because of the frequency of comorbid disease and age-related deterioration in organ function. Despite advances in AML treatment in recent years, elderly patients have experienced limited benefit, and their outcomes remain poor. This study aimed to perform a comprehensive gene mutation analysis in elderly AML patients and identify gene mutations that could serve as prognostic factors. METHODS: An analysis of gene mutations was performed for 281 AML patients, including 98 elderly patients aged 65 years or above. RESULTS: Compared to younger AML patients, elderly patients showed a higher frequency of the following gene mutations: TP53 (P = 0.026), PTPN11 (P = 0.006), RUNX1 (P = 0.024), TET2 (P = 0.002), and ASXL1 (P = 0.023). The complete remission rate was significantly lower in DNMT3A mutation-positive cases (4.26%, P = 0.011) and TP53 mutation-positive cases (2.13%, P = 0.031) than in negative cases. The overall survival rate was significantly poorer in cases with FLT3-ITD (P = 0.003), DNMT3A (P = 0.033), or TP53 mutation (P < 0.001). Conversely, cases with PTPN11 mutation (P = 0.014) had a significantly more favorable prognosis. In multivariate analysis, FLT3-ITD (P = 0.011) and TP53 mutation positivity (P = 0.002) were independent poor prognostic factors, as were a performance status of 3 or above (P < 0.001) and poor cytogenetic prognosis (P = 0.001). In contrast, PTPN11 mutation positivity (P = 0.023) was an independent favorable prognosis factor. CONCLUSION: Analysis of gene mutations in elderly AML patients is very important, not only for establishing prognosis, but also for introducing appropriate molecular-targeted treatments.
Assuntos
Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Mutação , Proteínas de Neoplasias/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Taxa de SobrevidaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso de 80 Anos ou mais , Biópsia , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/patologia , Dacriocistite/diagnóstico , Diagnóstico Diferencial , Erros de Diagnóstico , Face , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Segunda Neoplasia Primária/patologia , Sarcoidose/diagnóstico , Pele/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Resultado do TratamentoRESUMO
In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation (NPM1 mut)-positive acute myeloid leukemia (AML) with an fms-like kinase 3-internal tandem duplication (FLT3-ITD) allele ratio (AR) <0.5 (low AR) has a favorable prognosis, and allogeneic hematopoietic stem cell transplant (allo-HSCT) in the first complete remission (CR1) period is not actively recommended. We studied 147 patients with FLT3-ITD gene mutation-positive AML, dividing them into those with low AR and those with AR of ≥0.5 (high AR), and examined the prognostic impact according to allo-HSCT in CR1. Although FLT3-ITD AR and NPM1 mut are used in the prognostic stratification, we found that NPM1 mut-positive AML with FLT3-ITD low AR was not associated with favorable outcome (overall survival [OS], 41.3%). Moreover, patients in this group who underwent allo-HSCT in CR1 had a significantly more favorable outcome than those who did not (relapse-free survival [RFS] P = .013; OS P = .003). Multivariate analysis identified allo-HSCT in CR1 as the sole favorable prognostic factor (RFS P < .001; OS P < .001). The present study found that prognosis was unfavorable in NPM1 mut-positive AML with FLT3-ITD low AR when allo-HSCT was not carried out in CR1.