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OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.
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Infarto do Miocárdio , Humanos , Biomarcadores , Estudos Prospectivos , Infarto do Miocárdio/diagnóstico , Troponina I , Valor Preditivo dos Testes , Serviço Hospitalar de Emergência , Algoritmos , Troponina TRESUMO
The KamLAND-Zen experiment has provided stringent constraints on the neutrinoless double-beta (0νßß) decay half-life in ^{136}Xe using a xenon-loaded liquid scintillator. We report an improved search using an upgraded detector with almost double the amount of xenon and an ultralow radioactivity container, corresponding to an exposure of 970 kg yr of ^{136}Xe. These new data provide valuable insight into backgrounds, especially from cosmic muon spallation of xenon, and have required the use of novel background rejection techniques. We obtain a lower limit for the 0νßß decay half-life of T_{1/2}^{0ν}>2.3×10^{26} yr at 90% C.L., corresponding to upper limits on the effective Majorana neutrino mass of 36-156 meV using commonly adopted nuclear matrix element calculations.
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BACKGROUND: Although immunotherapy is thought to be a promising cancer treatment, most patients do not respond to immunotherapy. In this post hoc analysis of a phase 1/2 study, associations of programmed death ligand 1 (PD-L1), PD-L2, and HLA class I expressions with responses to dendritic cells (DCs)-based immunotherapy were investigated in patients with advanced sarcoma. METHODS: This study enrolled 35 patients with metastatic and/or recurrent sarcomas who underwent DC-based immunotherapy. The associations of PD-L1, PD-L2, and HLA class I expressions in tumor specimens, which were resected before immunotherapy, with immune responses (increases of IFN-γ and IL-12) and oncological outcomes were evaluated. RESULTS: Patients who were PD-L2 (+) showed lower increases of IFN-γ and IL-12 after DC-based immunotherapy than patients who were PD-L2 (-). The disease control (partial response or stable disease) rates of patients who were PD-L1 (+) and PD-L1 (-) were 0% and 22%, respectively. Disease control rates of patients who were PD-L2 (+) and PD-L2 (-) were 13% and 22%, respectively. Patients who were PD-L1 (+) tumors had significantly poorer overall survival compared with patients who were PD-L1 (-). No associations of HLA class I expression with the immune response or oncological outcomes were observed. CONCLUSIONS: This study suggests that PD-L1 and PD-L2 are promising biomarkers of DC-based immunotherapy, and that addition of immune checkpoint inhibitors to DC-based immunotherapy may improve the outcomes of DC-based immunotherapy.
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Antígeno B7-H1/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Imunoterapia , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Sarcoma/terapia , Adulto , Biomarcadores Tumorais/metabolismo , Células Dendríticas , Feminino , Humanos , Interferon gama/metabolismo , Interleucina-12/metabolismo , Masculino , Sarcoma/imunologia , Sarcoma/mortalidade , Sarcoma/patologia , Resultado do TratamentoRESUMO
This study investigated the utility of patent ductus arteriosus (PDA) closure with hemostatic clip by comparing with traditional PDA closure. Medical records of 51 dogs with surgical closure of PDA were reviewed and retrospective study was conducted. 29 dogs were treated by procedure with hemostatic clip (Group HC), and 22 dogs were treated by surgical ligation (Group SL). Data pertaining to breed, sex, age and body weight at the time of surgery, echocardiographic minimal ductal diameter, duration of surgery, hemostatic clip size, echocardiographic findings, hemor-rhage, residual ductal flow and recanalization were collected from records. The results showed that procedure with hemostatic clip had been selected in lighter dogs than traditional PDA closure. Duration of surgery performed only hemostatic clip technique was significantly shorter than that in group SL. Preoperative LVIDd, E-wave and FS were significantly lower than postoperative ones. As regard all parameters, the differences between pre- and postoperative periods were not significantly different between group HC and group SL. Hemorrhage, residual ductal flow, and recanalization were not significantly different in both groups. The present study showed that procedure with hemostatic clip is beneficial in that it is available in smaller dogs and can make shorter operation duration than traditional PDA closure. Moreover, the procedure is effective for the resolution of volume overload of the left atrium and ventricle in short-term outcome. Complications including hemorrhage, residual ductal flow and recanaliza-tion were not significantly different with both techniques.
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Doenças do Cão/cirurgia , Permeabilidade do Canal Arterial/veterinária , Instrumentos Cirúrgicos/veterinária , Animais , Cães , Permeabilidade do Canal Arterial/cirurgia , Feminino , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Localized-type tenosynovial giant cell tumor (TGCT) is a rare, neoplastic disease with only limited data supporting treatment protocols. We describe treatment protocols and evaluate their oncological outcome, complications, and functional results in a large multicenter cohort of patients. A secondary study aim was to identify factors associated with local recurrence after surgical treatment. METHODS: Patients with histologically proven localized TGCT of a large joint were included if they had been treated between 1990 and 2017 in 1 of 31 tertiary sarcoma centers. Of 941 patients with localized TGCT, 62% were female. The median age at initial treatment was 39 years, and the median duration of follow-up was 34 months. Sixty-seven percent of the tumors affected the knee, and the primary treatment at the tertiary center was 1-stage open resection in 73% of the patients. Proposed factors for predicting a first local recurrence after treatment in the tertiary center were tested in a univariate analysis, and those that demonstrated significance were subsequently included in a multivariate analysis. RESULTS: The localized TGCT recurred in 12% of all cases, with local-recurrence-free rates at 3, 5, and 10 years of 88%, 83%, and 79%, respectively. The strongest factor for predicting recurrent disease was a prior recurrence (p < 0.001). Surgical treatment decreased pain and swelling in 71% and 85% of the patients, respectively, and such treatment was associated with complications in 4% of the patients. Univariate and multivariate analyses of the patients who had not undergone therapy previously yielded positive associations between local recurrence and a tumor size of ≥5 cm versus <5 cm (hazard ratio [HR] = 2.50; 95% confidence interval [CI] = 1.32 to 4.74; p = 0.005). Arthroscopy (versus open surgery) was significantly associated with tumor recurrence in the univariate analysis (p = 0.04) but not in the multivariate analysis (p = 0.056). CONCLUSIONS: Factors associated with recurrence after resection of localized-type TGCT were larger tumor size and initial treatment with arthroscopy. Relatively low complication rates and good functional outcomes warrant an open approach with complete resection when possible to reduce recurrence rates in high-risk patients. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Tumor de Células Gigantes de Bainha Tendinosa/cirurgia , Artropatias/cirurgia , Sarcoma/cirurgia , Adulto , Artroscopia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Complicações Pós-OperatóriasRESUMO
We present a precision analysis of the ^{136}Xe two-neutrino ßß electron spectrum above 0.8 MeV, based on high-statistics data obtained with the KamLAND-Zen experiment. An improved formalism for the two-neutrino ßß rate allows us to measure the ratio of the leading and subleading 2νßß nuclear matrix elements (NMEs), ξ_{31}^{2ν}=-0.26_{-0.25}^{+0.31}. Theoretical predictions from the nuclear shell model and the majority of the quasiparticle random-phase approximation (QRPA) calculations are consistent with the experimental limit. However, part of the ξ_{31}^{2ν} range allowed by the QRPA is excluded by the present measurement at the 90% confidence level. Our analysis reveals that predicted ξ_{31}^{2ν} values are sensitive to the quenching of NMEs and the competing contributions from low- and high-energy states in the intermediate nucleus. Because these aspects are also at play in neutrinoless ßß decay, ξ_{31}^{2ν} provides new insights toward reliable neutrinoless ßß NMEs.
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Aims: The aims of this study were to evaluate the long-term outcome of surgery for bone or soft-tissue metastases from renal cell carcinoma (RCC) and to determine factors that affect prognosis. Patients and Methods: Between 1993 and 2014, 58 patients underwent surgery for bone or soft-tissue metastases from RCC at our hospital. There were 46 men and 12 women with a mean age of 60 years (25 to 84). The mean follow-up period was 52 months (1 to 257). The surgical sites included the spine (33 patients), appendicular skeleton (ten patients), pelvis (eight patients), thorax (four patients), and soft tissue (three patients). The surgical procedures were en bloc metastasectomy in 46 patients (including 33 patients of total en bloc spondylectomy (TES)) and intralesional curettage in 12 patients. These patients were retrospectively evaluated for factors associated with prognosis. Results: The one-, three-, five-, ten-, and 15-year overall survival (OS) rates were 89%, 75%, 62%, 48%, and 25%, respectively. The median survival time (MST) was 127 months for en bloc metastasectomy and 54 months for intralesional curettage and bone grafting. The median survival time was 127 months for the spine, 140 months for lesions of the appendicular skeleton, and 54 months for the pelvis. Multivariate analysis showed that non-clear cell type RCC and metastases to more than two sites were independent risk factors for a poor prognosis. Conclusion: Patients with bone or soft-tissue metastases from a RCC have a reasonable prognosis, making surgical resection a viable option even in patients in whom the metastases are advanced. Cite this article: Bone Joint J 2018;100-B:1241-8.
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Neoplasias Ósseas/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Neoplasias de Tecidos Moles/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Neoplasias Renais/mortalidade , Masculino , Metastasectomia/métodos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/secundário , Taxa de Sobrevida , Resultado do TratamentoRESUMO
We propose a differential interference contrast method for cells using hard x-ray Gabor holography and knife-edge filtering in the spatial frequency domain, without relying on beam shearing. A phase object is holographically recorded and reconstructed by computer. Interference between the wavefronts of zeroth order weighted by ejπ/2 in the positive frequency region produces a dark image. Similarly, interference between the wavefronts of the zeroth order weighted by ej3π/2 in the negative frequency region produces a bright image. By adding these two intensity distributions, good quality phase-contrast images of 8-µm-diameter polystyrene beads and human HeLa cells were obtained.
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Holografia/métodos , Interpretação de Imagem Assistida por Computador/métodos , Microscopia de Contraste de Fase/métodos , Microesferas , Células HeLa/patologia , Humanos , Poliestirenos , Raios XAssuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina/efeitos adversos , Toxidermias/etiologia , Eosinofilia/induzido quimicamente , Foliculite/induzido quimicamente , Dermatopatias Vesiculobolhosas/induzido quimicamente , Idoso , Eosinofilia/patologia , Foliculite/patologia , Humanos , Masculino , Dermatopatias Vesiculobolhosas/patologiaAssuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/imunologia , Linfócitos do Interstício Tumoral/imunologia , Pleurisia/imunologia , Neoplasias Torácicas/secundário , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Nivolumabe , Neoplasias Torácicas/tratamento farmacológico , Neoplasias Torácicas/imunologia , Parede Torácica/patologiaRESUMO
BACKGROUND: Atrial fibrillation is common after oesophageal surgery. The aim of this study was to evaluate whether landiolol hydrochloride was effective and safe in the prevention of atrial fibrillation after oesophagectomy, and to see whether a reduction in incidence of atrial fibrillation would reduce other postoperative complications. METHODS: This single-centre study enrolled patients scheduled for transthoracic oesophagectomy in a randomized, double-blind, placebo-controlled trial between March 2013 and January 2016. Enrolled patients were randomized with a 1 : 1 parallel allocation ratio to either landiolol prophylaxis or placebo. The primary endpoint was the occurrence of atrial fibrillation after oesophagectomy. Secondary endpoints were incidence of postoperative complications, and effects on haemodynamic and inflammatory indices. RESULTS: One hundred patients were enrolled, 50 in each group. Postoperative atrial fibrillation occurred in 15 patients (30 per cent) receiving placebo versus five (10 per cent) receiving landiolol (P = 0·012). The overall incidence of postoperative complications was significantly lower in the landiolol group (P = 0·046). In the landiolol group, postoperative heart rate was suppressed effectively, but the decrease in BP was not harmful. The interleukin 6 level was significantly lower on days 3 and 5 after surgery in the landiolol group (P = 0·001 and P = 0·002 respectively). CONCLUSION: Landiolol was effective and safe in preventing atrial fibrillation after oesophagectomy. Registration number: UMIN000010648 (http://www.umin.ac.jp/ctr/).
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Antiarrítmicos/uso terapêutico , Fibrilação Atrial/prevenção & controle , Esofagectomia/efeitos adversos , Morfolinas/uso terapêutico , Ureia/análogos & derivados , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Método Duplo-Cego , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Ureia/uso terapêuticoRESUMO
BACKGROUND: Antimelanoma differentiation-associated protein (anti-MDA)5 antibodies are associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis (CADM) or dermatomyositis (DM). OBJECTIVES: We aimed to evaluate the relevance of monitoring anti-MDA5 antibody levels for the management of RP-ILD in patients with CADM or DM. METHODS: Twelve patients with CADM (n = 10) or DM (n = 2) accompanied by RP-ILD were included. Baseline characteristics and outcomes were recorded. Serial measurements of anti-MDA5 antibody levels were measured. All patients were treated with corticosteroids, tacrolimus and intravenous cyclophosphamide. RESULTS: All patients achieved RP-ILD remission after combined immunosuppressive therapy for a mean of 6·8 months, with significant decreases noted in the mean anti-MDA5 antibody levels at remission. Six (50%) patients became anti-MDA5 antibody negative after therapy. After a mean follow-up of 31 months, RP-ILD relapse was observed in four (33%) patients in both the anti-MDA5 antibody sustained positive group and the negative conversion group. However, relapsed patients in the sustained positive group relapsed earlier than those in the negative conversion group. Thus, a decrease in anti-MDA5 antibody levels during remission was associated with longer remission. Relapses were associated with a reincrease of anti-MDA5 antibody levels in four of four (100%) patients. In contrast, none of the patients without reincrease in anti-MDA5 antibody exhibited symptoms of relapse during follow-up. Therefore, reincrease in anti-MDA5 antibody levels was associated with relapse. CONCLUSIONS: The anti-MDA5 antibody level is a novel parameter for monitoring and a good predictor of RP-ILD relapse in patients with CADM or DM.
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Dermatomiosite/imunologia , Doenças Pulmonares Intersticiais/imunologia , Corticosteroides/uso terapêutico , Autoanticorpos/metabolismo , Ciclofosfamida/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Dermatomiosite/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do TratamentoRESUMO
Background: Oxidative stress mitigated by antioxidant enzymes is thought to be involved in the progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT). This study investigated the association between genetic variations in antioxidant enzymes and the efficacy of ADT as well as its biological background. Patients and methods: The non-synonymous or promoter-locating polymorphisms of antioxidant enzymes were examined as well as the time to CRPC progression and overall survival in 104 and 92 patients treated with ADT for metastatic and non-metastatic prostate cancer, respectively. In addition, intracellular reactive oxygen species and expression levels of antioxidant enzymes were examined in castration-resistant and enzalutamide-resistant cells. Results: In metastatic prostate cancer, the AG/GG allele in GSTM3 rs7483 and CT/TT allele in CAT rs564250 were associated with a significantly lower risk of progression to CRPC and all-cause death compared with homozygotes of the major AA allele (hazard ratio [HR]; [95% confidence interval (CI)], 0.55 [0.34-0.86], P = 0.0086) and CC allele (HR; [95% CI], 0.48 [0.24-0.88], P = 0.016), respectively. On multivariate analyses, only GSTM3 rs7483 was associated with significant progression risk (AG/GG versus AA; HR; [95% CI], 0.45 [0.25-0.79], P = 0.0047) even after Bonferroni adjustment. In non-metastatic prostate cancer, the AG/GG allele in GSTM3 rs7483 was associated with a significantly lower risk of progression to CRPC (HR; [95% CI], 0.35 [0.10-0.93], P = 0.034) and all-cause death (HR; [95% CI], 0.26 [0.041-0.96], P = 0.043) compared with the AA allele. Intracellular reactive oxygen species levels were increased, accompanied with augmented GSTM3 expression in both castration-resistant and enzalutamide-resistant cells. Conclusions: Differential activity of antioxidant enzymes caused by the polymorphism in GSTM3 may contribute to resistance to hormonal therapy through oxidative stress. The GSTM3 rs7483 polymorphism may be a promising biomarker for prostate cancer patients treated with ADT.
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Glutationa Transferase/genética , Estresse Oxidativo/efeitos dos fármacos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Idoso , Alelos , Antagonistas de Androgênios/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Antioxidantes/administração & dosagem , Benzamidas , Catalase/genética , Progressão da Doença , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Estresse Oxidativo/genética , Feniltioidantoína/administração & dosagem , Feniltioidantoína/análogos & derivados , Modelos de Riscos Proporcionais , Neoplasias de Próstata Resistentes à Castração/patologiaRESUMO
Azathioprine (AZA) is increasingly being prescribed to rheumatoid arthritis (RA) patients. Following oral administration, AZA is converted into its active form. Inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) patients with low thiopurine (S)-methyltransferase (TPMT) activity tend to respond well to AZA therapy. In a previous study of Japanese SLE patients under low-dose AZA therapy, the group with the 94C>A mutation in inosine triphosphatase (ITPA) showed greater improvement in their disease activity index. However, it is not yet clear how genotypes relate to responsiveness to RA treatment. The genotypes ITPA 94C>A, TPMT*3C, NUDT15 595C>T, GST-M1, GST-T1 and MRP4/ABCC4 2269G>A of Japanese patients with RA were determined. The relationship between these genotypes and response to AZA therapy was evaluated using the Disease Activity Score 28 (DAS28) and various medical data. Of the 22 patients 15 had the ITPA 94C/C genotype, 7 had the ITPA 94C/A genotype, none had the TPMT*3C mutation, 4 had the NUDT15 595C>T mutation, 8 had the GST-M1 and T1 null genotypes and 9 had the MRP4/ABCC4 2269G>A mutation. Changes in DAS28 at 6 months after baseline were similar in both ITPA genotype groups. However, the maintenance dose of AZA was significantly lower in the C/A group than in the C/C group (0.85±0.30 mg/kg/day vs. 1.2±0.46 mg/kg/day, respectively; p = 0.043). The ITPA 94C/A group showed the same response to RA treatment as the C/C group, but at a lower dose. This demonstrates that RA patients with the ITPA 94C>A mutation are more responsive to AZA.
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Antirreumáticos/metabolismo , Artrite Reumatoide/enzimologia , Artrite Reumatoide/genética , Azatioprina/metabolismo , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Povo Asiático , Azatioprina/uso terapêutico , Feminino , Deleção de Genes , Frequência do Gene , Genótipo , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mutação/genética , Polimorfismo Genético , Estudos RetrospectivosRESUMO
BACKGROUND: Although testosterone suppression during androgen-deprivation therapy (ADT) and obesity have been reported to affect ADT efficacy, there are few comprehensive analyses on the impact on ADT outcome. Recently, we demonstrated that the SRD5A2 polymorphism was associated with metastatic prostate cancer prognosis. Therefore, in this study, we investigated the relationship between ADT serum testosterone levels or body mass index (BMI) and the prognosis among men treated with primary ADT for metastatic prostate cancer. In addition, we examined the association of serum testosterone levels during ADT with the SRD5A2 polymorphism. METHODS: This study included 96 Japanese patients with metastatic prostate cancer. The relationship between clinicopathological parameters, including serum testosterone levels during ADT and BMI, and progression-free survival, overall survival and survival from progression following primary ADT treatment for metastatic prostate cancer was examined. Additionally, the association between the SRD5A2 gene polymorphism (rs523349) and serum testosterone levels during ADT was examined in 86 cases. RESULTS: Among clinicopathological parameters, the lowest quartile of serum testosterone levels during ADT was a significant predictor of better overall survival as well as survival from castration resistance. However, BMI was not associated with prognosis. The CC allele in the SRD5A2 gene (rs523349), encoding the less active 5α-reductase, was associated with lower serum testosterone levels during ADT. CONCLUSIONS: Taken together, these findings revealed a dramatic suppression of serum testosterone by ADT was associated with better survival among men with metastatic prostate cancer that have undergone primary ADT, which may be affected by the SRD5A2 gene polymorphism.
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3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Proteínas de Membrana/genética , Polimorfismo Genético , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Testosterona/sangue , Idoso , Antagonistas de Androgênios/uso terapêutico , Progressão da Doença , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Análise de SobrevidaRESUMO
Analyses of nuclear emulsion detectors that can detect and identify charged particles or radiation as tracks have typically utilized optical microscope systems because the targets have lengths from several µm to more than 1000 µm. For recent new nuclear emulsion detectors that can detect tracks of submicron length or less, the current readout systems are insufficient due to their poor resolution. In this study, we developed a new system and method using an optical microscope system for rough candidate selection and the hard X-ray microscope system at SPring-8 for high-precision analysis with a resolution of better than 70 nm resolution. Furthermore, we demonstrated the analysis of submicron-length tracks with a matching efficiency of more than 99% and position accuracy of better than 5 µm. This system is now running semi-automatically.
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The aim of this study was to explore the biological functions of a tetraspanin family protein CD82 expressed aberrantly in chemotherapy-resistant CD34(+)/CD38(-) acute myelogenous leukemia (AML) cells. Microarray analysis of patient-isolated CD34(+)/CD38(-) AML cells revealed that the levels of anti-apoptotic protein BCL2L12 were downregulated after CD82 depletion by specific short hairpin RNA (shRNA). Western blot analysis indicated that BCL2L12 was aberrantly expressed in patient-isolated AML cells and AML cell lines. Furthermore, CD82 blockade by a specific antibody downregulated BCL2L12 in parallel with dephosphorylation of signal transducer and activator of transcription 5 (STAT5) and AKT, whereas pharmacological inhibition of STAT5 and AKT activation decreased BCL2L12 expression in leukemia cells. In addition, shRNA-mediated downregulation of BCL2L12 increased the levels of cleaved caspase-3 and suppressed proliferation of leukemia cells, impairing their engraftment in immunodeficient mice. Taken together, our results indicate that CD82 regulated BCL2L12 expression via STAT5A and AKT signaling and stimulated proliferation and engrafting of leukemia cells, suggesting that CD82 and BCL2L12 may be promising therapeutic targets in AML.
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Proteína Kangai-1/fisiologia , Leucemia Mieloide Aguda/patologia , Proteínas Musculares/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , Fator de Transcrição STAT5/fisiologia , Transdução de Sinais/fisiologia , Idoso , Idoso de 80 Anos ou mais , Apoptose , Feminino , Humanos , Proteína Kangai-1/análise , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , TranscriptomaRESUMO
Canine protein-losing enteropathy (PLE) is associated with severe gastrointestinal disorders and has a guarded to poor prognosis although little information is available regarding factors affecting prognosis. The purpose of this study was to identify the prognostic factors for survival of dogs with PLE. Ninety-two dogs diagnosed with PLE from 2006 to 2011 were included in a retrospective cohort study. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Variables recorded at the time of diagnosis were statistically analysed for possible prognostic factors in a univariate and multivariate Cox proportional hazard model. In the multivariate analysis, the predictors for mortality in dogs with PLE were more highly scored in terms of canine inflammatory bowel disease activity index (CIBDAI) (P = 0.0003), clonal rearrangement of lymphocyte antigen receptor genes (P = 0.003), and elevation of blood urea nitrogen (BUN) (P = 0.03). Using histopathological diagnosis, both small- and large-cell lymphomas were associated with significantly shorter survival times than chronic enteritis (CE) and intestinal lymphangiectasia (IL). Normalization of CIBDAI and plasma albumin concentration within 50 days of initial treatment was associated with a longer survival time. In conclusion, CIBDAI, clonal rearrangement of lymphocyte antigen receptor genes, histopathological diagnosis, and response to initial treatments would be valuable in separating the underlying causes and could be important in predicting prognosis in dogs with PLE.
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Doenças do Cão/fisiopatologia , Enteropatias Perdedoras de Proteínas/veterinária , Animais , Cães , Feminino , Masculino , Prognóstico , Enteropatias Perdedoras de Proteínas/fisiopatologia , Estudos Retrospectivos , Análise de SobrevidaRESUMO
In 1999, we developed a technique for biological reconstruction after excision of a bone tumour, which involved using autografts of the bone containing the tumour treated with liquid nitrogen. We have previously reported the use of this technique in 28 patients at a mean follow up of 27 months (10 to 54). In this study, we included 72 patients who underwent reconstruction using this technique. A total of 33 patients died and three were lost to follow-up, at a mean of 23 months (2 to 56) post-operatively, leaving 36 patients available for a assessment at a mean of 101 months 16 to 163) post-operatively. The methods of reconstruction included an osteo-articular graft in 16, an intercalary in 13 and, a composite graft with prosthesis in seven. Post-operative function was excellent in 26 patients (72.2%), good in seven (19.4%), and fair in three (8.3%) according to the functional evaluation system of Enneking. No recurrent tumour occurred within the grafts. The autografts survived in 29 patients (80.6%), and the rates of survival at five and ten years were 86.1% and 80.6 %, respectively. Seven of 16 osteo-articular grafts (44%) failed because of fracture or infection, but all the composite and intercalary grafts survived. The long-term outcomes of frozen autografting, particularly using composite and intercalary grafts, are satisfactory and thus represent a good method of treatment for patients with a sarcoma of bone or soft tissue.
Assuntos
Neoplasias Ósseas/cirurgia , Transplante Ósseo/métodos , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Adolescente , Adulto , Idoso , Transplante Ósseo/efeitos adversos , Criança , Feminino , Seguimentos , Congelamento , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Salvamento de Membro/métodos , Masculino , Pessoa de Meia-Idade , Nitrogênio , Osteossarcoma/cirurgia , Coleta de Tecidos e Órgãos/métodos , Transplante Autólogo/métodos , Resultado do TratamentoRESUMO
There have been a few reports of patients with a combination of lumbar and thoracic spinal stenosis. We describe six patients who suffered unexpected acute neurological deterioration at a mean of 7.8 days (6 to 10) after lumbar decompressive surgery. Five had progressive weakness and one had recurrent pain in the lower limbs. There was incomplete recovery following subsequent thoracic decompressive surgery. The neurological presentation can be confusing. Patients with compressive myelopathy due to lower thoracic lesions, especially epiconus lesions (T10 to T12/L1 disc level), present with similar symptoms to those with lumbar radiculopathy or cauda equina lesions. Despite the rarity of this condition we advise that patients who undergo lumbar decompressive surgery for stenosis should have sagittal whole spine MRI studies pre-operatively to exclude proximal neurological compression.