RESUMO
CD73 is a cell-surface ectoenzyme that hydrolyzes the conversion of extracellular adenosine monophosphate to adenosine, which in turn can promote resistance to immune checkpoint blockade therapy. Immune response may therefore be improved by targeting tumor CD73, and this possibility underlines the need to non-invasively assess tumor CD73 level. In this study, we developed a cysteine site-specific 89Zr-labeled anti-CD73 (89Zr-CD73) IgG immuno-PET technique that can image tumor CD73 expression in living bodies. Anti-CD73 IgG was reduced with tris(2-carboxyethyl)phosphine, underwent sulfohydryl moiety-specific conjugation with deferoxamine-maleimide, and was radiolabeled with 89Zr. CT26 mouse colon cancer cells, CT26/CD73 cells engineered to constitutively overexpress CD73, and 4T1.2 mouse breast cancer cells underwent cell binding assays and western blotting. Balb/c nude mice bearing tumors underwent 89Zr-CD73 IgG PET imaging and biodistribution studies. 89Zr-CD73 IgG showed 20-fold higher binding to overexpressing CT26/CD73 cells compared to low-expressing CT26 cells, and moderate expressing 4T1.2 cells showed uptake that was 38.9 ± 1.51% of CT26/CD73 cells. Uptake was dramatically suppressed by excess unlabeled antibody. CD73 content proportionately increased in CT26 and CT26/CD73 cell mixtures was associated with linear increases in 89Zr-CD73 IgG uptake. 89Zr-CD73 IgG PET/CT displayed clear accumulation in CT26/CD73 tumors with greater uptake compared to CT26 tumors (3.13 ± 1.70%ID/g vs. 1.27 ± 0.31%ID/g at 8 days; P = 0.04). Specificity was further supported by low CT26/CD73 tumor-to-blood ratio of 89Zr-isotype-IgG compared to 89Zr-CD73 IgG (0.48 ± 0.08 vs. 2.68 ± 0.52 at 4 days and 0.53 ± 0.07 vs. 4.81 ± 1.02 at 8 days; both P < 0.001). Immunoblotting and immunohistochemistry confirmed strong CD73 expression in CT26/CD73 tumors and low expression in CT26 tumors. 4T1.2 tumor mice also showed clear 89Zr-CD73 IgG accumulation at 8 days (3.75 ± 0.70%ID/g) with high tumor-to-blood ratio compared to 89Zr-isotype-IgG (4.91 ± 1.74 vs. 1.20 ± 0.28; P < 0.005). 89Zr-CD73 IgG specifically targeted CD73 on high expressing cancer cells in vitro and tumors in vivo. Thus, 89Zr-CD73 IgG immuno-PET may be useful for the non-invasive monitoring of CD73 expression in tumors of living subjects.
Assuntos
5'-Nucleotidase , Neoplasias do Colo , Cisteína , Tomografia por Emissão de Pósitrons , Zircônio , Animais , 5'-Nucleotidase/metabolismo , Zircônio/química , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/metabolismo , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Camundongos , Linhagem Celular Tumoral , Tomografia por Emissão de Pósitrons/métodos , Cisteína/metabolismo , Humanos , Radioisótopos , Feminino , Camundongos Endogâmicos BALB C , Distribuição Tecidual , Camundongos Nus , Proteínas Ligadas por GPI/metabolismo , Proteínas Ligadas por GPI/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismoRESUMO
OBJECTIVE: Segmenting the aorta into zones based on anatomical landmarks is a current trend to better understand interventions for aortic dissection or aneurysm. However, comprehensive reference values for aortic zones are lacking. The aim of this study was to establish reference values for aortic size using a fully automated deep learning based segmentation method. METHODS: This retrospective study included 704 healthy adults (mean age 50.6 ± 7.5 years; 407;57.8%] males) who underwent contrast enhanced chest computed tomography (CT) for health screening. A convolutional neural network (CNN) was trained and applied on 3D CT images for automatic segmentation of the aorta based on the Society for Vascular Surgery and Society of Thoracic Surgeons classification. The CNN generated masks were reviewed and corrected by expert cardiac radiologists. RESULTS: Aortic size was significantly larger in males than in females across all zones (zones 0 - 8, all p < .001). The aortic size in each zone increased with age, by approximately 1 mm per 10 years of age, e.g., 25.4, 26.7, 27.5, 28.8, and 29.8 mm at zone 2 in men in the age ranges of 30 - 39, 40 - 49, 50 - 59, 60 - 69, and ≥ 70 years, respectively (all p < .001). CONCLUSION: The deep learning algorithm provided reliable values for aortic size in each zone, with automatic masks comparable to manually corrected ones. Aortic size was larger in males and increased with age. These findings have clinical implications for the detection of aortic aneurysms and other aortic diseases.
RESUMO
OBJECTIVE: Residual aortic dissection (AD) following DeBakey type I AD repair is associated with a high rate of adverse events that need additional intervention or surgery. This study aimed to identify clinical and early post-operative computed tomography angiography (CTA) imaging factors associated with adverse events in patients with type I AD after ascending aorta replacement. METHODS: This single centre, retrospective cohort study included consecutive patients with type I AD who underwent ascending aorta replacement from January 2011 to December 2017 and post-operative CTA within three months. The primary outcome was AD related adverse events, defined as AD related death and re-operation due to aortic aneurysm or impending rupture. The location and size of the primary intimal tears, aortic diameter, and false lumen status were evaluated. Regression analyses were performed to identify factors associated with AD related adverse events. A decision tree model was used to classify patients as high or low risk. RESULTS: Of 103 participants (55.43 ± 13.94 years; 49.5% male), 24 (23.3%) experienced AD related adverse events. In multivariable Cox regression analysis, connective tissue disease (hazard ratio [HR] 15.33; p < .001), maximum aortic diameter ≥ 40 mm (HR 4.90; p < .001), and multiple (three or more) intimal tears (HR 7.12; p < .001) were associated with AD related adverse events. The three year cumulative survival free from AD related events was lower in the high risk group with aortic diameter ≥ 40 mm and multiple intimal tears (41.7% vs. 90.9%; p < .001). CONCLUSION: Early post-operative CTA findings indicating a maximum aortic diameter ≥ 40 mm and multiple intimal tears may predict a higher risk of adverse events. These findings suggest the need for careful monitoring and more vigilant management approaches in these cases.
Assuntos
Dissecção Aórtica , Angiografia por Tomografia Computadorizada , Humanos , Masculino , Feminino , Dissecção Aórtica/cirurgia , Dissecção Aórtica/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Fatores de Risco , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Resultado do Tratamento , Medição de Risco , Aneurisma Aórtico/cirurgia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/mortalidade , Fatores de Tempo , Reoperação/estatística & dados numéricosRESUMO
Very late antigen-4 (VLA4; CD49d) is a promising immune therapy target in treatment-resistant leukemia and multiple myeloma, and there is growing interest in repurposing the humanized monoclonal antibody (Ab), natalizumab, for this purpose. Positron emission tomography with radiolabeled Abs (immuno-PET) could facilitate this effort by providing information on natalizumab's in vivo pharmacokinetic and target delivery properties. In this study, we labeled natalizumab with 89Zr specifically on sulfhydryl moieties via maleimide-deferoxamine conjugation. High VLA4-expressing MOLT4 human T cell acute lymphoblastic leukemia cells showed specific 89Zr-natalizumab binding that was markedly blocked by excess Ab. In nude mice bearing MOLT4 tumors, 89Zr-natalizumab PET showed high-contrast tumor uptake at 7 days postinjection. Biodistribution studies confirmed that uptake was the highest in MOLT4 tumors (2.22 ± 0.41%ID/g) and the liver (2.33 ± 0.76%ID/g), followed by the spleen (1.51 ± 0.42%ID/g), while blood activity was lower at 1.12 ± 0.21%ID/g. VLA4-specific targeting in vivo was confirmed by a 58.1% suppression of tumor uptake (0.93 ± 0.15%ID/g) when excess Ab was injected 1 h earlier. In cultured MOLT4 cells, short-term 3 day exposure to the proteasome inhibitor bortezomib (BTZ) did not affect the α4 integrin level, but BTZ-resistant cells that survived the treatment showed increased α4 integrin expression. When the effects of BTZ treatment were tested in mice, there was no change of the α4 integrin level or 89Zr-natalizumab uptake in MOLT4 leukemia tumors, which underscores the complexity of tumor VLA4 regulation in vivo. In conclusion, 89Zr-natalizumab PET may be useful for noninvasive monitoring of tumor VLA4 and may assist in a more rational application of Ab-based therapies for hematologic malignancies.
Assuntos
Integrina alfa4beta1 , Leucemia , Humanos , Animais , Camundongos , Natalizumab/uso terapêutico , Cisteína , Integrina alfa4 , Camundongos Nus , Distribuição Tecidual , Linhagem Celular Tumoral , Tomografia por Emissão de Pósitrons/métodos , Zircônio/químicaRESUMO
BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major obstacle limiting long-term graft survival. Effective noninvasive surveillance modalities reflecting both coronary artery and microvascular components of CAV are needed. OBJECTIVES: The authors evaluated the diagnostic performance of dynamic computed tomography-myocardial perfusion imaging (CT-MPI) and coronary computed tomography angiography (CCTA) for CAV. METHODS: A total of 63 heart transplantation patients underwent combined CT-MPI and CCTA plus invasive coronary angiography (ICA) with intravascular ultrasonography (IVUS) between December 2018 and October 2021. The median interval between CT-MPI and heart transplantation was 4.3 years. Peak myocardial blood flow (MBF) of the whole myocardium (MBFglobal) and minimum MBF (MBFmin) among the 16 segments according to the American Heart Association model, except the left ventricular apex, were calculated from CT-MPI. CCTA was assessed qualitatively, and the degree of coronary artery stenosis was recorded. CAV was diagnosed based on both ICA (ISHLT criteria) and IVUS. Patients were followed up for a median time of 2.3 years after CT-MPI and a median time of 5.7 years after transplantation. RESULTS: Among the 63 recipients, 35 (55.6%) had diagnoses of CAV. The median MBFglobal and MBFmin were significantly lower in patients with CAV (128.7 vs 150.4 mL/100 mL/min; P = 0.014; and 96.9 vs 122.8 mL/100 mL/min; P < 0.001, respectively). The combined use of coronary artery stenosis on CCTA and MBFmin showed the highest diagnostic performance with an area under the curve of 0.886 (sensitivity: 74.3%, specificity: 96.4%, positive predictive value: 96.3%, and negative predictive value: 75.0%). CONCLUSIONS: The combination of CT-MPI and CCTA demonstrated excellent diagnostic performance for the detection of CAV. One-stop evaluation of the coronary artery and microvascular components involved in CAV using combined CCTA and CT-MPI may be a potent noninvasive screening method for early detection of CAV.
Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Imagem de Perfusão do Miocárdio , Humanos , Angiografia Coronária/métodos , Angiografia por Tomografia Computadorizada/métodos , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X/métodos , Miocárdio , Aloenxertos , Perfusão , Doença da Artéria Coronariana/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodosRESUMO
BACKGROUND: Primary cardiac sarcomas are rare and their clinicopathologic features are heterogeneous. Among them, particularly intimal sarcoma is a diagnostic challenge due to nonspecific histologic features. Recently, MDM2 amplification reported to be a characteristic genetic event in the intimal sarcoma. In this study, we aimed to identify the types and incidence of primary cardiac sarcomas that occurred over 25 years in tertiary medical institutions, and to find clinicopatholgical significance through reclassification of diagnoses using additional immunohistochemistry (IHC). METHODS: We reviewed the primary cardiac sarcoma cases between January 1993 and June 2018 at Asan Medical Center, South Korea, with their clinicopathologic findings, and reclassified the subtypes, especially using IHC for MDM2 and then, analyzed the significance of prognosis. RESULTS: Forty-eight (6.8%) cases of a primary cardiac sarcoma were retrieved. The tumors most frequently involved the right atrium (n = 25, 52.1%), and the most frequent tumor subtype was angiosarcoma (n = 23, 47.9%). Seven cases (53.8%) were newly reclassified as an intimal sarcoma by IHC for MDM2. Twenty-nine (60.4%) patients died of disease (mean, 19.8 months). Four patients underwent a heart transplantation and had a median survival of 26.8 months. This transplantation group tended to show good clinical outcomes in the earlier stages, but this was not statistically significant (p = 0.318). MDM2 positive intimal sarcoma showed the better overall survival (p = 0.003) than undifferentiated pleomorphic sarcoma. Adjuvant treatment is beneficial for patient survival (p < 0.001), particularly in angiosarcoma (p < 0.001), but not in intimal sarcoma (p = 0.154). CONCLUSION: Our study supports the use of adjuvant treatment in primary cardiac sarcoma, as it was associated with a significantly better overall survival rate. Further consideration of tumor histology may be important in determining the optimal use of adjuvant treatment for different types of sarcomas. Therefore, accurate diagnosis by MDM2 test is important condsidering patient's prognosis and treatment.
Assuntos
Neoplasias Cardíacas , Hemangiossarcoma , Sarcoma , Humanos , Terapia Combinada , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/genética , Neoplasias Cardíacas/terapia , Hemangiossarcoma/genética , Hemangiossarcoma/terapia , Prognóstico , Proteínas Proto-Oncogênicas c-mdm2/genética , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/terapiaRESUMO
Background: To determine the role of dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) in the management of postoperative chylothorax after lung cancer surgery. Methods and Results: Between July 2017 and November 2021, patients who developed postoperative chylothorax following pulmonary resection and mediastinal lymph node dissection were assessed and those who underwent DCMRL for the evaluation of chyle leak were evaluated. The findings of DCMRL and conventional lymphangiography were compared. The incidence of postoperative chylothorax was 0.9% (50/5587). Among the patients with chylothorax, a total of 22 patients (44.0% [22/50]; mean age, 67.6 ± 7.9 years; 15 men) underwent DCMRL. Treatment outcomes were compared between patients with conservative management (n = 10) and those with intervention (n = 12). The patients demonstrated unilateral pleural effusion, ipsilateral to the operation site, and showed right-sided dominance. The most frequent site of thoracic duct injury showing contrast media leakage was visualized at the subcarinal level. No DCMRL-related complication occurred. DCMRL showed comparable performance to conventional lymphangiography in visualizing the central lymphatics, including cisterna chyli (DCMRL vs. conventional lymphangiography, 72.7% vs. 45.5%, p = 0.25) and thoracic duct (90.9% vs. 54.5%, p = 0.13), and in localizing thoracic duct injury (90.9% vs. 54.5%, p = 0.13). On follow-up, the amount of chest tube drainage after lymphatic intervention showed a significant difference over time from that after medical treatment only (p = 0.02). Conclusion: DCMRL can provide detailed information about the leak site and the central lymphatic anatomy in patients with chylothorax after lung cancer surgery. The findings of DCMRL can guide subsequent treatment planning for optimal outcomes.
Assuntos
Quilotórax , Neoplasias Pulmonares , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Quilotórax/diagnóstico por imagem , Quilotórax/etiologia , Quilotórax/terapia , Linfografia/métodos , Imageamento por Ressonância Magnética/métodos , Ducto Torácico/cirurgia , Espectroscopia de Ressonância Magnética/efeitos adversos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/complicaçõesRESUMO
OBJECTIVE: To investigate the prognostic value of preoperative cardiac magnetic resonance imaging (MRI) for long-term major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing tricuspid valve (TV) surgery for functional tricuspid regurgitation (TR). MATERIALS AND METHODS: The preoperative cardiac MR images, New York Heart Association functional class, comorbidities, and clinical events of 78 patients (median [interquartile range], 59 [51-66.3] years, 28.2% male) who underwent TV surgery for functional TR were comprehensively reviewed. Cox proportional hazards analyses were performed to assess the associations of clinical and imaging parameters with MACCEs and all-cause mortality. RESULTS: For the median follow-up duration of 5.4 years (interquartile range, 1.2-6.6), MACCEs and all-cause mortality were 51.3% and 23.1%, respectively. The right ventricular (RV) end-systolic volume index (ESVI) and the systolic RV mass index (RVMI) were higher in patients with MACCEs than those without them (77 vs. 68 mL/m², p = 0.048; 23.5 vs. 18.0%, p = 0.011, respectively). A high RV ESVI was associated with all-cause mortality (hazard ratio [HR] per value of 10 higher ESVI = 1.10, p = 0.03). A high RVMI was also associated with all-cause mortality (HR per increase of 5 mL/m² RVMI = 1.75, p < 0.001). After adjusting for age and sex, only RVMI remained a significant predictor of MACCEs and all-cause mortality (p < 0.05 for both). After adjusting for multiple clinical variables, RVMI remained significantly associated with all-cause mortality (p = 0.005). CONCLUSION: RVMI measured on preoperative cardiac MRI was an independent predictor of long-term outcomes in patients who underwent TV surgery for functional TR.
Assuntos
Insuficiência da Valva Tricúspide , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Resultado do Tratamento , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/cirurgiaRESUMO
OBJECTIVE: We implemented a novel resectable myocardial model for mock myectomy using a hybrid method of three-dimensional (3D) printing and silicone molding for patients with apical hypertrophic cardiomyopathy (ApHCM). MATERIALS AND METHODS: From January 2019 through May 2020, 3D models from three patients with ApHCM were generated using the end-diastolic cardiac CT phase image. After computer-aided designing of measures to prevent structural deformation during silicone injection into molding, 3D printing was performed to reproduce anatomic details and molds for the left ventricular (LV) myocardial mass. We compared the myocardial thickness of each cardiac segment and the LV myocardial mass and cavity volumes between the myocardial model images and cardiac CT images. The surgeon performed mock surgery, and we compared the volume and weight of the resected silicone and myocardium. RESULTS: During the mock surgery, the surgeon could determine an ideal site for the incision and the optimal extent of myocardial resection. The mean differences in the measured myocardial thickness of the model (0.3, 1.0, 6.9, and 7.3 mm in the basal, midventricular, apical segments, and apex, respectively) and volume of the LV myocardial mass and chamber (36.9 mL and 14.8 mL, 2.9 mL and -9.4 mL, and 6.0 mL and -3.0 mL in basal, mid-ventricular and apical segments, respectively) were consistent with cardiac CT. The volume and weight of the resected silicone were similar to those of the resected myocardium (6 mL [6.2 g] of silicone and 5 mL [5.3 g] of the myocardium in patient 2; 12 mL [12.5 g] of silicone and 11.2 mL [11.8 g] of the myocardium in patient 3). CONCLUSION: Our 3D model created using hybrid 3D printing and silicone molding may be useful for determining the extent of surgery and planning surgery guided by a rehearsal platform for ApHCM.
Assuntos
Cardiomiopatia Hipertrófica , Silicones , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Humanos , Miocárdio , Impressão TridimensionalRESUMO
Disease progression (DP) in interstitial lung disease (ILD) is variable and difficult to predict. In previous reports, serum Krebs von den Lungen-6 (KL-6) was suggested to be useful in diagnosing and predicting survival in ILD. The aim of our study was to investigate the usefulness of serum KL-6 as a predictor of DP in ILD. Clinical data of 199 patients with ILD (idiopathic pulmonary fibrosis: 22.8%) were prospectively collected and serum KL-6 levels were measured. DP was defined as a relative decline in forced vital capacity (FVC) ≥ 10%, acute exacerbation, or death during follow-up. The median follow-up period was 11.1 months. The mean age of the subjects was 62.2 years, and 59.8% were male. DP occurred in 21.6% of patients. The progressed group showed lower FVC, lower diffusing capacity for carbon monoxide, lower the minimum oxygen saturation during the 6-minute walk test, higher fibrosis scores on high-resolution computed tomography, and higher KL-6 levels (826.3 vs. 629.0 U/mL; p < 0.001) than those of the non-progressed group. In receiver operating characteristic curve analysis, serum KL-6 levels were a significant predictor of DP in ILD (area under the curve = 0.629, p = 0.009, and the optimal cut-off level was 811 U/mL). In multivariable Cox analysis, high serum KL-6 levels (≥ 800 U/mL) were only independently associated with DP in ILD (HR 2.689, 95% CI 1.445-5.004, P = 0.002). Serum KL-6 levels might be useful to predict DP in patients with ILD.
Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Mucina-1/sangue , Tomografia Computadorizada por Raios X , Idoso , Biomarcadores/sangue , Intervalo Livre de Doença , Feminino , Humanos , Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/fisiopatologia , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Taxa de Sobrevida , Capacidade VitalRESUMO
Reports on lymphatic intervention for chylothorax complicating thoracic aortic surgery are limited. We aimed to evaluate technical and clinical outcomes of lymphangiography and thoracic duct embolization (TDE) for chylothorax complicating thoracic aortic surgery.Nine patients (mean age, 38.9 years) who underwent chylothorax interventions after thoracic aortic surgery (aorta replacement [nâ=â7] with [nâ=â2] or without [nâ=â5] lung resection, and vascular ring repair [nâ=â2]) were reviewed retrospectively. Magnetic resonance (MR) lymphangiograms were obtained in 5 patients. The median interval between surgery and conventional lymphangiography was 9 days (range, 4-28 days). TDE clinical success was defined as lymphatic leakage resolution with chest tube removal within 2 weeks.MR lymphangiograms revealed contrast leakage from the thoracic duct (nâ=â4) or no definite leakage (nâ=â1), which correlated well with conventional lymphangiogram findings. The technical success rate of conventional lymphangiography was 88.9% (8/9); 8 patients showed contrast leakage, while the patient without definite leakage on MR lymphangiography had small inguinal lymph nodes, and thoracic duct visualization by conventional lymphangiography failed. The technical success rates of antegrade and retrograde TDE via pleural access were 75% (6/8) and 100% (3/3), respectively. Clinical outcomes after embolization, as judged by the tube-removal day, were similar between low- (<500âmL/day) and high-output (≥500âmL/day) chylothorax patients. The drainage amount decreased significantly after lymphangiography/TDE, from 710.0âmL/day to 109.7âmL/day (pâ<â.05). The clinical success rate of TDE was 87.8% (7/8).Conventional lymphangiography and TDE yielded high technical success rates and demonstrated encouraging clinical outcomes for chylothorax complicating thoracic aortic surgery.
Assuntos
Aorta Torácica/cirurgia , Quilotórax/terapia , Embolização Terapêutica/métodos , Linfografia/métodos , Complicações Pós-Operatórias/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Quilotórax/diagnóstico por imagem , Quilotórax/etiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Obtaining adequate effective orifice area (EOA) in surgical aortic valve replacement (SAVR) is important to minimize pressure gradients across the prosthetic aortic valve (AV) and improve clinical outcomes. However, the predictors of EOA are unclear. METHODS: From July 2011 to March 2016, patients undergoing SAVR who were preoperatively evaluated using a computed tomography (CT) on the aortic root were enrolled. Indexed EOA (iEOA) was used as an indicator of prosthetic AV opening area. The aortic root parameters investigated were the annular diameter (max and min), annular perimeter, annular area, and maximal dimensions of the proximal ascending aorta. These variables were evaluated as predictors of EOA, and an individual surgeon was incorporated in analysis for verifying surgeon dependent factors. RESULTS: Among the 710 patients included in this study [age: 64.9±10.8 years; females: n=285 (40.1%)], 370 (52.1%) were implanted with bio-prosthesis. Mean prosthetic iEOA was 1.1±0.3 cm2/m2. Univariable linear regression analysis showed that all indexed aortic root parameters (maximal and minimal annular diameters, annular perimeter, annular area, and sinus dimensions) were significantly associated with iEOA (P<0.001). Multivariable analysis showed that indexed aortic annular area, indexed maximal diameter of the Valsalva sinus, female sex, and bio-prosthesis, supra-annular type prosthesis and surgeon were significant and independent determinants of iEOA (adjusted R2=0.513, P<0.001). CONCLUSIONS: Aortic annular area and Valsalva sinus diameter are independent determinants for iEOA measured by preoperative CT; surgeon-dependent factors are also significant determinants in SAVR.
RESUMO
It was previously reported that tetraiodothyroacetic acid (tetrac) inhibits angiogenesis by binding to the cell surface receptor for thyroid hormone on integrin αVß3. Therefore, we synthesized and evaluated two 64Cu-labeled tetrac derivatives and a Cy5.5-labeled tetrac derivative for tumor angiogenesis imaging. Tetrac was structurally modified to conjugate with 1,4,7,10-tetraazacyclododecane-N,N',Nâ³,Nâ³'-tetraacetic acid (DOTA) via its hydroxy or carboxylic acid end, and the resulting DOTA-conjugated tetrac derivatives were then labeled with 64Cu. Tetrac was also conjugated with Cy5.5 via its carboxylic acid end. All three tetrac derivatives (1-3) exhibited greater inhibitory activity than tetrac against endothelial cell tube formation. The U87MG cell binding of [64Cu]2 showed a time-dependent increase over 24â¯h and it was inhibited by 38% at 4â¯h in the presence of tetrac, indicating specificity of [64Cu]2 to the thyroid hormone receptor site on integrin αVß3. Positron emission tomography (PET) images of U87MG tumor-bearing mice injected with [64Cu]1 and [64Cu]2 revealed that high radioactivity accumulated in the tumors, and that the tumor uptake and tumor-to-nontarget uptake ratio were higher in small tumors than in large tumors. In addition, the Cy5.5-labeled tetrac derivative (3) displayed a strong near-infrared (NIR) signal in the tumors. Taken together, these results suggest that these ligands hold promise as imaging agents for visualization of tumor angiogenesis.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Carbocianinas/química , Neovascularização Patológica/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tiroxina/análogos & derivados , Animais , Células Cultivadas , Radioisótopos de Cobre , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/diagnóstico por imagem , Tiroxina/síntese química , Tiroxina/químicaRESUMO
Current advances in CT techniques allow thorough evaluation of the beating heart. The strengths of cardiac CT relative to echocardiography and magnetic resonance imaging are its high availability in most institutions, rapid production of high-quality images, and outstanding delineation of the anatomy. For many normal variants and pathologic conditions, such as thrombi, masses, and congenital abnormalities of the left atrium, CT findings are sufficient to make a presumptive diagnosis. Assessments of the left atrium and left atrial appendage are particularly important for the management of atrial fibrillation, as various catheter-based procedures are aimed at the mechanical and electrical isolation of these structures. CT offers information crucial to a successful catheter-based procedure or surgery. Therefore, a comprehensive review of the geometry (shape, size, and relative position), along with various CT imaging features of pathologic states, should be provided in radiology reports to be of clinical value.
RESUMO
BACKGROUND: Hemoptysis is one of the most important complications associated with fungus ball. However, the association of the primary size of the fungus ball and its change with the incidence of hemoptysis was not fully established. This study aims to determine the clinical risk factors of severe hemoptysis and natural course of fungus ball. METHODS: A retrospective study on patients with fungus ball was performed. Patients with severe hemoptysis-related events were compared to those without events, and the predictors for severe hemoptysis were investigated by Cox regression analysis. Three subgroups (decreased, stable, and increased) were classified according to the long-term size change, and the severe hemoptysis-free survival duration was analyzed by the Kaplan-Meier survival curve. RESULTS: Among 173 patients, 50 (28.9%) experienced severe hemoptysis-related events. Risk-adjusted analysis revealed that age [hazard ratio (HR), 0.964; 95% confidence interval (CI), 0.939-0.989], blood-tinged sputum [HR, 2.717; 95% CI, 1.513-4.879], and thick wall cavitary fungus balls [HR, 2.332; 95% CI, 1.290-4.215] were significant predictors of severe hemoptysis-related events in patients with fungus ball. However, the baseline size of the fungus ball and its change rate were not independent risk factors for severe hemoptysis-related events. Besides, the decreased group did not have a favorable outcome in severe hemoptysis related to fungus ball. CONCLUSIONS: In a tertiary hospital, the incidence of severe hemoptysis-related events in patients with fungus ball was not low and reached 28.9%. Young patients, those with thick wall cavitary fungus ball, and those with complaints of blood-tinged sputum should be considered for early surgical treatment to prevent severe hemoptysis.
RESUMO
The aim of the present study was to investigate the detoxifying effects of aloe polysaccharide (APS), propolis, and the mixture of APS and propolis on the urinary excretion of major human tobacco carcinogens, BaP and an addictive stimulant alkaloid, nicotine. Smokers (≥20 cigarettes/day) were randomly classified into four subgroups (10 people/group) and were given 600â¯mg/day of APS, 600â¯mg/day of propolis, or 600â¯mg/day of the mixture of APS (420â¯mg/day) and propolis (180â¯mg/day) for four weeks. Urinary excretion of BaP and cotinine (a metabolite of nicotine) increased in a time-dependent manner increased after supplementation with APS (BaP, 2.23-fold; cotinine, 2.64-fold), propolis (BaP, 1.30-fold; cotinine, 2.08-fold), and the mixture (BaP, 2.33-fold; cotinine, 2.28-fold) compared with smoker control. Creatinine, glucose, and total bilirubin levels significantly decreased in a time-dependent manner after supplementation with APS (creatinine, 15.24%; glucose, 40.22%; total bilirubin, 48.82%), propolis (creatinine, 16.83%; glucose, 36.25%; total bilirubin, 52.59%), and the mixture (creatinine, 16.36%; glucose, 46.37%; total bilirubin, 39.20%) (pâ¯<â¯0.05). These results suggest that supplementation with APS, propolis, or the mixture could reduce the risk of cancer or other diseases associated with tobacco smoking by enhancing urinary excretion of BaP and nicotine.
Assuntos
Aloe/química , Cotinina/urina , Nicotina/metabolismo , Polissacarídeos/farmacologia , Própole/farmacologia , Fumar/urina , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Nicotina/farmacocinética , Nicotina/urina , Polissacarídeos/administração & dosagem , Polissacarídeos/química , Própole/administração & dosagem , Própole/química , Adulto JovemRESUMO
PURPOSE: Cigarette smoking (CS) is one of the major risk factors of cerebral atherosclerotic disease, however, its level of contribution to extracranial and intracranial atherosclerotic stenosis (ECAS and ICAS) was not fully revealed yet. The purpose of our study was to assess the association of CS to cerebral atherosclerosis along with other risk factors. MATERIALS AND METHODS: All consecutive patients who were angiographically confirmed with severe symptomatic cerebral atherosclerotic disease between January 2002 and December 2012 were included in this study. Multivariate logistic regression analyses were performed to identify risk factors for ECAS and ICAS. Thereafter, CS group were compared to non-CS group in the entire study population and in a propensity-score matched population with two different age-subgroups. RESULTS: Of 1709 enrolled patients, 794 (46.5%) had extracranial (EC) lesions and the other 915 (53.5%) had intracranial (IC) lesions. CS group had more EC lesions (55.8% vs. 35.3%, P<0.001) whereas young age group (<50 years) had more IC lesion (84.5% vs. 47.6%, P<0.001). In multivariate analysis, seven variables including CS, male, old age, coronary heart disease, higher erythrocyte sedimentation rate, multiple lesions, and anterior lesion were independently associated with ECAS. In the propensity-score matched CS group had significant more EC lesion compared to non-CS group (65.7% vs. 47.9%) only in the old age subgroup. CONCLUSION: In contrast to a significant association between CS and severe symptomatic ECAS shown in old population, young patients did not show this association and showed relatively higher preference of ICAS.
RESUMO
BACKGROUND: Lung cancer screening with low-dose computed tomography reduced mortality in selected high risk patients. However, the use of chest radiography for lung cancer screening in Asian populations is still controversial. We investigated the effectiveness of chest radiographic surveillance using a nationwide health service data in South Korea. METHODS: Data from the Korean National Health Insurance Service examinee cohort of 2004 to 2013 were examined, and 63,228 patients with lung cancer were identified, 38,494 (57%) of whom underwent chest radiography screening. The others did not undergo lung cancer screening and were considered as a control group. Clinical data including age, smoking, screening intervals, lung cancer stages, treatments, and survival were collected. Survival gain from surveillance after adjustment for lead-time bias based on the sojourn time was calculated. Cox-proportional hazard analyses were performed to evaluate the effectiveness of screening and to determine the appropriate screening interval for chest radiography surveillance. RESULTS: Early lung cancer was found in 38% of patients receiving chest radiography versus 26% of those without surveillance. A patient age of more than 65 years (hazard ratio [HR], 1.53; 95% confidence limits [CL], 1.50-1.56), male (HR, 1.66; 95% CL, 1.62-1.70), and high lung cancer stages at the time of diagnosis were independent factors associated with mortality (each, P < 0.001). Chest radiography surveillance was a factor for decreasing mortality in female (HR, 0.81; 95% CL, 0.77-0.84, P < 0.001), with mortality reduction of 10% at the 3- and 5-year survival time-points. In female patients, chest radiography surveillance at intervals of less than 3 years was an independent predictor of improved survival. CONCLUSIONS: Surveillance chest radiography increased survival in a female screened population in South Korea. Chest radiography intervals of less than 3 years may help to detect lung cancer in female patients.
Assuntos
Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Radiografia Torácica , Idoso , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Vigilância da População , Modelos de Riscos Proporcionais , Sistema de Registros , República da Coreia/epidemiologiaRESUMO
Clinical features of human metapneumovirus (HMPV) infection have not been well documented for adults. We investigated clinical and radiologic features of HMPV infection in 849 adults in a tertiary hospital in South Korea. We classified patients into groups on the basis of underlying diseases: immunocompetent patients, solid tumor patients, solid organ transplantation recipients, hematopoietic stem cell transplant recipients, hematologic malignancy patients, and patients receiving long-term steroid treatment. Of 849 HMPV-infected patients, 756 had community-acquired infections, 579 had pneumonia, and 203 had infections with other pathogens. Mortality rates were highest in hematopoietic stem cell transplantation recipients (22% at 30 days). Older age, current smoking, and underlying disease were associated with HMPV pneumonia. Body mass index and an immunocompromised state were associated with 30-day mortality rates in HMPV-infected patients. Bronchial wall thickening, ground-glass opacity, and ill-defined centrilobular nodules were common computed tomography findings for HMPV pneumonia. Macronodules and consolidation were observed in <50% of patients.
Assuntos
Infecções Comunitárias Adquiridas/diagnóstico por imagem , Metapneumovirus/fisiologia , Infecções por Paramyxoviridae/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Idoso , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/virologia , Feminino , Neoplasias Hematológicas/diagnóstico por imagem , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , Infecções por Paramyxoviridae/mortalidade , Infecções por Paramyxoviridae/virologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , República da Coreia/epidemiologia , Centros de Atenção Terciária , Tomografia Computadorizada por Raios XRESUMO
Primary osteoporosis is a disease related to excessive bone resorption due to estrogen insufficiency that occurs postmenopause. Protocatechuic acid (PCA), or 3,4-dihydroxybenzoic acid, is a common compound present in numerous plants. Although numerous biological activities of PCA have been identified, its antiosteoporotic function has not been well established. In this study, the antiosteoporotic activity of PCA supplementation was determined in ovariectomized (OVX) female ICR mice at 12 weeks after OVX. The biomechanical properties of a bone were evaluated by microcomputed tomography. The signaling molecules associated with osteoclast differentiation were determined in bone marrow cells through immunoblot or RT-PCR. Oral supplementation with PCA (20 mg/kg/day) significantly ameliorated the OVX-mediated stimulation of osteoclast activity based on decreases in serum levels of receptor activator of nuclear factor κB ligand (RANKL), osteocalcin, and bone alkaline phosphatase and increase in serum osteoprotegerin (each group, n = 6; p < 0.05). In addition, the OVX-induced decreases in mRNA expression levels of cathepsin K, calcitonin receptor, nuclear factor of activated T cell cytoplasmic 1 (NFATc1), and tumor necrosis factor (TNF) receptor-associated factor-6 (TRAF6) in bone marrow cells were significantly attenuated (each group, n = 6; p < 0.05). Finally, the loss of trabecular bone and changes in biomechanical properties of a bone were significantly improved by supplementation with 20 mg/kg PCA (each group, n = 6; p < 0.05). Collectively, our results show that PCA supplement suppressed trabecular bone loss in OVX mice and therefore might be an effective alternative approach for preventing the progression of postmenopausal osteoporosis.