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We investigated the relationship between the prognostic importance of anatomic tumour burden and subtypes of breast cancer using data from the Korean Breast Cancer Registry Database. In HR+/HER2+ and HR-/HER2-tumours, an increase in T stage profoundly increased the hazard of death, while the presence of lymph node metastasis was more important in HR+/HER2+ and HR-/HER2+ tumours among 131,178 patients with stage I-III breast cancer. The patterns of increasing mortality risk and tumour growth (per centimetre) and metastatic nodes (per node) were examined in 67,038 patients with a tumour diameter ≤ 7 cm and < 8 metastatic nodes. HR+/HER2- and HR-/HER2- tumours showed a persistent increase in mortality risk with an increase in tumour diameter, while the effect was modest in HER2+ tumours. Conversely, an increased number of metastatic nodes was accompanied by a persistently increased risk in HR-/HER2+ tumours, while the effect was minimal for HR-/HER2- tumours with > 3 or 4 nodes. The interactions between the prognostic significance of anatomic tumour burden and subtypes were significant. The prognostic relevance of the anatomic tumour burden was non-linear and highly dependent on the subtypes of breast cancer.
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Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Carga Tumoral , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
Because of the poor prognosis and of oral mucosal melanoma, and patients' short survival, large, randomised, clinical studies are difficult. We have investigated its demographic characteristics and analysed the effect of treatment, resection margins, and metastases on survival. We recorded age, sex, site of primary tumour, and types of treatment, survival, and metastases in 74 patients treated at the Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital. Survival was analysed based on bony invasion, depth of invasion, and resection margins, and we found that it varied depending on the primary site (p=0.002), and declined with liver (p=0.001) or brain (p=0.033) metastases. The two-year survival according to the primary site was as follows: palate 85% (n=32), anterior maxillary gingiva 53% (n=13), mandible 58% (n=13), and posterior maxillary gingival 74% (n=10) and buccal mucosa 50% (n=4). The two-year survival was 34% (n=8) in patients with liver metastases and 23% (n=7) in patients with brain metastases. In cases of bony invasion (p=0.005), depth of invasion (p=0.042), unclear resection margin (p=0.023), or higher T stages (p=0.009), the survival declined considerably. Neck dissection did not affect survival (p=0.343). Survival of the patients given chemotherapy was significantly lower (p=0.013) and the two-year survival was 54.0%. The patients given radiotherapy showed no significant difference in survival compared with those not given radiotherapy (p=0.107). In conclusion, primary site, bony invasion, resection margins, depth of invasion and systemic metastases were critical to predict prognosis and selection of treatment of oral mucosal melanoma.
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Margens de Excisão , Melanoma , Humanos , Melanoma/cirurgia , Mucosa Bucal/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND AND PURPOSE: Flow-diverter treatment for previously stented aneurysms has been reported to be less effective and prone to complications. In this study, we evaluated the effectiveness and safety of flow diverters for recurrent aneurysms after stent-assisted coiling. MATERIALS AND METHODS: Patients who underwent flow-diverter placement for recurrent aneurysms after stent-assisted coiling between March 2015 and March 2019 were recruited. Clinical and radiographic characteristics and clinical and angiographic outcomes were retrospectively evaluated. RESULTS: Among 133 patients who underwent flow-diverter insertion, 17 (male/female ratio = 5:12; mean age, 53.8 years) were treated for recurrent aneurysms after stent placement with (n = 16) or without (n = 1) coiling. Eight patients initially presented with subarachnoid hemorrhage; 7, with headache; and 2, with visual field defects. Angiographic morphology included large/giant saccular in 12 patients, dissecting in 2, fusiform in 1, traumatic pseudoaneurysm in 1, and ruptured blood blister-like aneurysm in 1. The duration between the first treatment and flow-diverter placement ranged from 2 weeks to 15 months (median, 6 months). Flow-diverter placement was successful in all cases without any complications. All patients had favorable outcomes (mRS, 0-2), without any newly appearing symptoms. Aneurysms were followed up with conventional angiography at least once in 6-18 months. Sixteen aneurysms showed complete occlusion, and 1 aneurysm was enlarged. CONCLUSIONS: Results from this case series investigating flow-diverter placement for recurrent aneurysms after stent-assisted coiling suggested that the procedure is safe and effective. Further study in a larger population may be warranted.
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Prótese Vascular , Embolização Terapêutica/métodos , Procedimentos Endovasculares/instrumentação , Aneurisma Intracraniano/terapia , Reoperação/instrumentação , Adulto , Idoso , Embolização Terapêutica/instrumentação , Procedimentos Endovasculares/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Stents , Resultado do TratamentoRESUMO
AIM: To compare the diagnostic performance of total counts of metastatic lymph nodes (LN-sum) and conventional multidetector (MD) computed tomography (CT) staging in the nodal evaluation of advanced gastric cancer (AGC) patients. MATERIALS AND METHODS: In total, 127 consecutive patients who underwent preoperative MDCT and gastrectomy for AGC were identified. Metastatic LNs on MDCT were defined as LNs with a short axis ≥8 mm, marked or heterogeneous enhancement, and morphological features (central necrosis, round shape, clustering). The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the N-stage using LN-sum and conventional MDCT staging were generated and compared. In addition, metastatic LN counts between the MDCT and the histopathological examinations and correlation between LN-sum and histopathological nodal status were analysed. RESULTS: The total counts of metastatic LNs on MDCT was significantly smaller than those detected in histopathological assessments (p<0.0001). LN-sum showed significant correlation with the pathological N stage and the number of metastatic LNs (rho=0.69, 0.73, p<0.0001). The areas under the receiver operating characteristic curve were 0.896, and 0.835, for N stage ≥N2 and N3, with cut-off values of 12.5 and 23.5 mm, respectively. LN-sum provided better diagnostic performance than conventional MDCT staging for discriminating N0-2 versus N3; sensitivity, accuracy, PPV and NPV of LN-sum were significantly higher (80.4 versus 52.2%, 81.1 versus 68.5%, 71.2 versus 57.1%, and 88 versus 74.1%). CONCLUSION: LN-sum may be sufficiently useful in assessing the N3 stage of AGC and may help to plan appropriate therapy for AGC patients.
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Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND: The association between psoriasis and risk of malignancy has not been thoroughly evaluated in a large longitudinal cohort of Asian population. OBJECTIVE: To determine the long-term risk of malignancy in Korean adult patients with psoriasis. METHODS: We conducted a nationwide population-based prospective cohort study with a 15-year observational period. During the baseline period (1997-2000), total 1 773 786 Korean subjects who received health insurance from the National Health Insurance System were enrolled and 5788 subjects were defined as a psoriasis group. The number of new-onset malignancy was collected during the observational period (2001-2015). RESULTS: Patients with psoriasis had a higher adjusted hazard ratio (aHR) for development of overall malignancy [aHR 1.08, 95% confidence interval (CI) 1.00-1.18] and gastric cancer (aHR 1.31, 95% CI 1.08-1.58) compared to controls. The risks of non-Hodgkin lymphoma and non-melanoma skin cancer were significantly increased only in patients with psoriasis who received systemic treatments (aHR 2.86, 95% CI 1.07-7.61 and aHR 3.93, 95% CI 1.47-10.47, respectively). CONCLUSION: Psoriasis is associated with long-term risk for overall malignancy in Koreans, which was primarily driven by the increased risk of gastric cancer.
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Psoríase/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Estudos Prospectivos , Psoríase/epidemiologia , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
We report the case of a breast cancer patient in whom a two-phase 18F-sodium-fluoride (18F-NaF) bone PET/CT was useful for detecting hidden bone metastases and assessing treatment response. The patient underwent a two-phase bone PET/CT to evaluate a newly developed lesion found on bone scintigraphy following surgery. In the perfusion and bone phase PET/CT images, focally increased perfusion and bony uptake were found in the sacrum and L5 vertebra, suggesting bone metastases of breast cancer. Therefore, the patient subsequently underwent palliative treatment. In another twoPET/CT studies (each including two-phase bone images) performed after 3and 6months of follow-up, the perfusion phase images showed an improvement of the lesion uptake more clearly than in the bone phase images in the visual and semi-quantitative analyses, and thus the perfusion phase images were more useful for clarifying the treatment response earlier than the bone phase images. This is the first case showing the clinical usefulness of 18F-NaF bone PET/CT with the perfusion imaging technique for evaluating bone metastases and the therapeutic response of metastatic bone lesions.
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Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Vértebras Lombares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Sacro/diagnóstico por imagem , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Remodelação Óssea , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/terapia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Radioisótopos de Flúor , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Osteoblastos/metabolismo , Cuidados Paliativos , Compostos Radiofarmacêuticos , Radioterapia Adjuvante , Fluoreto de SódioRESUMO
AIM: To investigate the prognostic significance of computed tomography (CT) attenuation and 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) uptake in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) for predicting overall survival (OS) in patients with pancreatic adenocarcinoma. MATERIALS AND METHODS: Data were collected retrospectively from 66 patients with pancreatic adenocarcinoma who had undergone pretreatment combined FDG positron-emission tomography (PET)/CT imaging and subsequent curative or palliative treatment. Metabolic parameters of primary tumour including total lesion glycolysis (TLG) and heterogeneity factor were measured. Volume, CT attenuation (attenuation), and FDG uptake of SAT and VAT were derived from PET/CT acquisitions. Survival analysis using Cox proportional hazard modelling was performed to assess the relationship between both attenuation and FDG uptake of fat tissue and OS. RESULTS: During follow-up, 33 patients (50%) died and the median OS was 12 months. There were significant positive correlations between attenuation and mean standardised uptake values of both SAT (p<0.001, r=0.697) and VAT (p<0.001, r=0.742). Attenuation and FDG uptake of adipose tissue were significantly associated with heterogeneity factor and T stage. Patients with high FDG uptake and attenuation of SAT and VAT had significantly worse OS than those with low values. On multivariate analysis, attenuation of SAT (p=0.047) and VAT (p=0.021), and FDG uptake of VAT (p=0.005) were correlated significantly with OS after adjusting for age, sex, body mass index, TNM stage, and TLG. CONCLUSIONS: CT attenuation of SAT and VAT, and FDG uptake of VAT significantly correlated with OS in patients with pancreatic adenocarcinoma, independent of TNM staging and TLG.
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Adenocarcinoma/diagnóstico por imagem , Tecido Adiposo/metabolismo , Fluordesoxiglucose F18/farmacocinética , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos/farmacocinética , Tomografia Computadorizada por Raios X , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Carga TumoralRESUMO
AIM: To evaluate the prevalence, clinical relevance, and magnetic resonance imaging (MRI) features of extra-capsular ganglia at the gastrocnemius origin and to assess their association with internal derangement and osteoarthritis of the knee. MATERIALS AND METHODS: One hundred consecutive knee MRI examinations, obtained within a 6-month period from patients with no history of recent knee trauma, recent injections, inflammatory arthritis, infection, or tumours, were evaluated retrospectively for the presence of ganglia at the gastrocnemius origin. The lesions were divided into two groups: an intra-capsular and an extra-capsular group. Cyst morphology (size, shape, and internal septa), internal derangement of the knee (cartilage lesion, cruciate ligament injury, meniscal tear, and corner injury on MRI, and osteoarthritis of the knee on radiographs) were evaluated. The chi-square, Fisher's exact, and t-tests were used to compare the two groups, in addition to multivariate stepwise logistic regression analysis. RESULTS: Thirty-nine ganglia with an extra-capsular location were identified on 100 knee MRI (39 %). Rounded shape and internal septa were more common in the extra-capsular than in the intra-capsular group (p<0.001). Frequencies of high-grade cartilage, meniscal tear, and high-grade osteoarthritis significantly differed between the groups (p≤0.038). In multivariate analysis, the only significant association was between high-grade osteoarthritis and the extra-capsular group. CONCLUSION: Extra-capsular ganglia at the gastrocnemius origin were not uncommon on knee MRI and had features typical of ganglia found at other sites. High-grade osteoarthritis was significantly associated with extra-capsular ganglia.
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Gânglios/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Músculo Esquelético/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The use of calcium phosphate bone cement has been described to allow for retention of reduction. Therefore, we evaluated whether augmentation with resorbable calcium phosphate could improve fracture stability in osteoporotic hip fractures. The results showed that augmentation with calcium phosphate cement significantly improved the stability of intertrochanteric fractures. INTRODUCTION: The aim with this study was to measure whether augmentation with resorbable calcium phosphate cement could improve fracture stability in osteoporotic hip fractures. METHODS: We retrospectively reviewed 82 patients who underwent closed reduction and internal fixation with proximal femoral nail (PFN) for unstable intertrochanteric fractures between 2014 and 2017. In 42 of 82 patients, patients were treated with a PFN alone (group I). These patients were compared with 40 patients for whom the same device combined with calcium phosphate cement for augmentation was used (group II). Questionnaire surveys or telephone interviews were conducted and patients completed a self-report Harris hip score (HHS) and visual analog scale (VAS) scores. Radiographic outcomes including mean sliding distance of screw, femoral shortening, and varus collapse were compared. Postoperative complications were compared. RESULTS: Clinical outcomes at 6 months after surgery were equivalent in both groups. Screw sliding, femoral shortening, and varus collapse were all significantly reduced in the cemented group at the last follow-up (p < 0.001, p = 0.005, p < 0.001, respectively). A total of 9 (21%) complications occurred in group I. In contrast, 2 (5%) complications were seen in group II (p = 0.029). CONCLUSIONS: Augmentation with calcium phosphate cement significantly improved the stability of intertrochanteric fractures fixed with a PFN and reduced overall failure rates. We believe augmentation with resorbable calcium phosphate cement for osteoporotic hip fractures is a reasonable option in selected patients.
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Cimentos Ósseos/uso terapêutico , Fosfatos de Cálcio/uso terapêutico , Fixação Interna de Fraturas/métodos , Fraturas do Quadril/cirurgia , Fraturas por Osteoporose/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Fixação Interna de Fraturas/efeitos adversos , Consolidação da Fratura , Fraturas do Quadril/diagnóstico por imagem , Humanos , Masculino , Variações Dependentes do Observador , Fraturas por Osteoporose/diagnóstico por imagem , Complicações Pós-Operatórias , Radiografia , Estudos RetrospectivosRESUMO
Aims: Identifying predictors of compartment syndrome in the foot after a fracture of the calcaneus may lead to earlier diagnosis and treatment. The aim of our study was to identify any such predictors. Patients and Methods: We retrospectively reviewed 303 patients (313 fractures) with a fracture of the calcaneus who presented to us between October 2008 and September 2016. The presence of compartment syndrome and potential predictors were identified by reviewing their medical records. Potential predictors included age, gender, concomitant foot injury, mechanism of injury, fracture classification, time from injury to admission, underlying illness, use of anticoagulant/antiplatelet agents, smoking status and occupation. Associations with predictors were analyzed using logistic regression analysis. Results: Of the 313 fractures of the calcaneus, 12 (3.8%) developed a compartment syndrome. A Sanders type IV fracture was the only strongly associated factor (odds ratio 21.67, p = 0.007). Other variables did not reach statistical significance. Conclusion: A Sanders type IV fracture is the best predictor of compartment syndrome after a fracture of the calcaneus. Cite this article: Bone Joint J 2018;100-B:303-8.
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Calcâneo/lesões , Síndromes Compartimentais/etiologia , Traumatismos do Pé/complicações , Fraturas Ósseas/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Traumatismos do Pé/cirurgia , Fixação de Fratura/métodos , Fraturas Ósseas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND AND PURPOSE: Longitudinally extensive transverse myelitis is a well-documented spinal manifestation of neuromyelitis optica spectrum disorders, however, other forms of nontumorous myelopathy can also manifest as longitudinally extensive transverse myelitis. Our aim was to evaluate the MR imaging features of aquaporin-4 antibody-positive longitudinally extensive transverse myelitis, which is strongly associated with neuromyelitis optica spectrum disorders. MATERIALS AND METHODS: We evaluated cervicomedullary junction involvement, cord expansion ratios, bright spotty lesions, the number of involved segments, skipped lesions, enhancement patterns, and axial distribution patterns using spinal MR imaging of 41 patients with longitudinally extensive transverse myelitis who underwent aquaporin-4 antibody testing. Univariate logistic regression analysis was performed to identify factors associated with aquaporin-4 antibody seropositivity, which were then used to develop a scoring system for diagnosing aquaporin-4 antibody-positive longitudinally extensive transverse myelitis. Interrater reliability for cord expansion ratio measurement and bright spotty lesions was determined using intraclass correlation coefficients and κ values, respectively. RESULTS: Fifteen patients with longitudinally extensive transverse myelitis were aquaporin-4 antibody-positive. Sex (female), cervicomedullary junction involvement, a cord expansion ratio of >1.4, and bright spotty lesions were significantly associated with aquaporin-4 antibody seropositivity. The sensitivity and specificity of the scoring system were 73.3% and 96.2%, respectively. The interclass correlation value for the cord expansion ratio was 0.78, and the κ value for bright spotty lesions was 0.61. CONCLUSIONS: Our scoring system, based on cervicomedullary junction involvement, higher cord expansion ratio, bright spotty lesions, and female sex, can facilitate the timely diagnosis of neuromyelitis optica spectrum disorders.
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Aquaporina 4/imunologia , Autoanticorpos/imunologia , Mielite Transversa/diagnóstico por imagem , Mielite Transversa/imunologia , Mielite Transversa/patologia , Adolescente , Adulto , Idoso , Aquaporina 4/sangue , Autoanticorpos/sangue , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/imunologia , Neuromielite Óptica/patologia , Reprodutibilidade dos Testes , Adulto JovemRESUMO
The discovery of a two-dimensional electron gas (2DEG) at the LaAlO3/SrTiO3 interface 1 has resulted in the observation of many properties2-5 not present in conventional semiconductor heterostructures, and so become a focal point for device applications6-8. Its counterpart, the two-dimensional hole gas (2DHG), is expected to complement the 2DEG. However, although the 2DEG has been widely observed 9 , the 2DHG has proved elusive. Herein we demonstrate a highly mobile 2DHG in epitaxially grown SrTiO3/LaAlO3/SrTiO3 heterostructures. Using electrical transport measurements and in-line electron holography, we provide direct evidence of a 2DHG that coexists with a 2DEG at complementary heterointerfaces in the same structure. First-principles calculations, coherent Bragg rod analysis and depth-resolved cathodoluminescence spectroscopy consistently support our finding that to eliminate ionic point defects is key to realizing a 2DHG. The coexistence of a 2DEG and a 2DHG in a single oxide heterostructure provides a platform for the exciting physics of confined electron-hole systems and for developing applications.
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This study evaluated the effects of proximal segment rotation and the extent of mandibular setback on post-sagittal split ramus osteotomy (SSRO) relapse using three-dimensional (3D) analysis. Thirty-one patients diagnosed with a skeletal class III malocclusion who underwent SSRO alone were enrolled in this study. The movements of the mandibular condyles were assessed using cone beam computed tomography (CBCT) and a 3D imaging program at ≤1 month before the operation (T0), 1 week after the operation (T1), and 6 months (T2) and 1year (T3) postoperative. Yaw and roll were increased at T1 as compared to T0. However, the proximal segments reverted to their original positions between T2 and T3. There was a positive correlation between the extent of the posterior movement of the mandible and relapse at 6 months and 1year postoperative. Although the proximal bone segments showed displacement in three dimensions at T1, they reverted to their original positions over time. In addition, although there was a positive correlation between the extent of the posterior movement of the mandible and the occurrence of post-surgical relapse at 6 months and 1year post-surgery, the rotation of the proximal bone segment during surgery had no relationship with postoperative relapse.
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Tomografia Computadorizada de Feixe Cônico , Imageamento Tridimensional , Má Oclusão Classe III de Angle/diagnóstico por imagem , Má Oclusão Classe III de Angle/cirurgia , Osteotomia Sagital do Ramo Mandibular/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Estudos Prospectivos , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: Cixutumumab is a fully human IgG1 monoclonal antibody to the insulin-like growth factor type I receptor that can potentially reverse resistance and enhance the efficacy of chemotherapy. METHODS: Bevacizumab-eligible patients with stage IV or recurrent non-squamous, non-small-cell lung cancer and good performance status were randomized to receive standard doses of paclitaxel, carboplatin, and bevacizumab to a maximum of six cycles followed by bevacizumab maintenance (CPB) until progression (arm A) or CPB plus cixutumumab 6 mg/kg i.v. weekly (arm B). RESULTS: Of 175 patients randomized, 153 were eligible and treated (78 in arm A; 75 in arm B). The median progression-free survival was 5.8 months (95% CI 5.4-7.1) in arm A versus 7 months (95% CI 5.7-7.6) in arm B (P = 0.33); hazard ratio 0.92 (95% CI 0.65-1.31). Objective response was 46.2% versus 58.7% in arm A versus arm B (P = 0.15). The median overall survival was 16.2 months in arm A versus 16.1 months in arm B (P = 0.95). Grade 3/4 neutropenia and febrile neutropenia, thrombocytopenia, fatigue, and hyperglycemia were increased with cixutumumab. CONCLUSIONS: The addition of cixutumumab to CPB increased toxicity without improving efficacy and is not recommended for further development in non-small-cell lung cancer. Both treatment groups had longer OS than historical controls which may be attributed to several factors, and emphasizes the value of a comparator arm in phase II trials. CLINICALTRIALS.GOV IDENTIFIER: NCT00955305.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Masculino , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Taxa de SobrevidaRESUMO
The restriction (R)-point decision is fundamental to normal differentiation and the G1-S transition, and the decision-making machinery is perturbed in nearly all cancer cells. The mechanisms underlying the cellular context-dependent R-point decision remain poorly understood. We found that the R-point was dysregulated in Runx3-/-mouse embryonic fibroblasts (MEFs), which formed tumors in nude mice. Ectopic expression of Runx3 restored the R-point and abolished the tumorigenicity of Runx3-/-MEFs and K-Ras-activated Runx3-/-MEFs (Runx3-/-;K-RasG12D/+). During the R-point, Runx3 transiently formed a complex with pRb and Brd2 and induced Cdkn1a (p21Waf1/Cip1/Sdi1; p21), a key regulator of the R-point transition. Cyclin D-CDK4/6 promoted dissociation of the pRb-Runx3-Brd2 complex, thus turning off p21 expression. However, cells harboring oncogenic K-Ras maintained the pRb-Runx3-Brd2 complex and p21 expression even after introduction of Cyclin D1. Thus, Runx3 plays a critical role in R-point regulation and defense against cellular transformation.
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Transformação Celular Neoplásica , Subunidade alfa 3 de Fator de Ligação ao Core/fisiologia , Animais , Carcinogênese , Inibidor de Quinase Dependente de Ciclina p21/genética , Genes ras , Células HEK293 , Humanos , Camundongos , Proteínas Serina-Treonina Quinases/fisiologia , Proteína do Retinoblastoma/fisiologia , Fatores de TranscriçãoAssuntos
Ceratodermia Palmar e Plantar/radioterapia , Lasers de Gás , Idoso , Dióxido de Carbono , Feminino , Mãos , Humanos , Resultado do TratamentoRESUMO
Objectives We analyzed the clinical follow-up results of 88 lupus nephritis patients to find prognostic factors for the development of chronic kidney disease in ethnically homogeneous Korean patients with biopsy-proven lupus nephritis. Methods Sociodemographic, clinical, laboratory, and treatment-related data at the time of kidney biopsy and during follow-up were obtained. Renal biopsy specimens were reclassified according to the International Society of Pathology/Renal Pathology Society classification, separately, by two renal pathologists blinded to the previous classification. Univariate and multivariate analyses were performed using the Cox proportional hazard regression model to identify independent risk factors for chronic kidney disease in lupus nephritis patients. Results Eighteen of 88 patients (20.5%) developed chronic kidney disease during a mean follow-up of 47.6 months (range: 12-96 months). Patients who developed chronic kidney disease were older at onset of lupus nephritis, had less education, and were more likely to have hypertension; they had lower serum albumin levels, lower platelet levels, higher serum creatinine levels, lower estimated glomerular filtration rate, higher chronicity index, and lower frequency of anti-ribosomal P antibodies, and they were less likely to be in complete remission in the first year. In stepwise multivariable analyses, hypertension, lower glomerular filtration rate, and failure to achieve complete remission in the first year of treatment were significant predictors of the development of chronic kidney disease in lupus nephritis patients. Conclusions These findings suggest that patients with hypertension and decreased kidney function at the onset of lupus nephritis and showing a poor response to immunosuppressive drugs in the first year should be monitored carefully and managed aggressively to avoid deterioration of kidney function.
Assuntos
Nefrite Lúpica/complicações , Insuficiência Renal Crônica/etiologia , Adulto , Biomarcadores/sangue , Biópsia , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/complicações , Imunossupressores/uso terapêutico , Rim/fisiopatologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Sistema de Registros , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , República da Coreia , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) have multiple immunomodulatory properties and hold therapeutic potential for inflammatory diseases. However, the therapeutic and immunologic effects of human umbilical cord blood-derived MSCs (huMSCs) remain largely unexamined for asthma. OBJECTIVE: This study was to investigate the immunomodulatory properties of huMSCs in an ovalbumin (OVA)-induced murine asthma model. METHODS: Mice were injected intraperitoneally with OVA and an aluminium hydroxide adjuvant. huMSCs were administered via the tail vein (5×105 cells/100 uL) to female BALB/c mice prior to the initial OVA challenge. The effects of huMSCs were assessed by investigating airway hyperresponsiveness, histological changes, inflammatory cell numbers, serum allergen-specific antibodies, cytokine production in spleen, lung tissue, and bronchoalveolar lavage (BAL) fluid as well as expansion of regulatory T cells. RESULTS: Administration of huMSCs significantly reduced methacholine bronchial hyperresponsiveness and eosinophil counts in BAL cells. Similarly, there was a significant decrease in serum OVA-specific IgE and IgG1 levels along with Th2 cytokine production (IL-4, IL-5, and IL-13) in the lung and spleen tissues, whereas increased percentage of regulatory T cells was observed after treatment with huMSCs. CONCLUSIONS: Our results suggest that huMSC treatment reduces OVA-induced allergic inflammation, which could be mediated by regulatory T cells.