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OBJECTIVE: To investigate the usefulness of pre- and post-treatment metabolic tumor volume (MTV) obtained from positron emission tomography (PET) in predicting prognosis and evaluating recurrence in patients with hypopharyngeal cancer (HPC). MATERIALS AND METHODS: Forty-three consecutive HPC patients treated with chemoradiotherapy were retrospectively analyzed. Maximum standard uptake value (SUVmax) and MTV of tumor (T) and lymph node (N) were analyzed. RESULTS: On multivariate analysis using pre-treatment parameters, MTV-T (p = 0.049) and MTV-TN (p = 0.043) were significantly associated with local control (LC), and MTV-N (p = 0.049) was significantly associated with disease-specific survival (DSS). Post-treatment MTV-TN was also significantly associated with prognosis (p < 0.001 in LC; p = 0.002 in DSS) and recurrence (area under curve 0.95). Neither pre- nor post-treatment SUVmax was significantly associated with prognosis. CONCLUSION: Pre- and post-treatment MTV appears useful for predicting prognosis and evaluating recurrence.
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OBJECTIVE: Aortic dissection (AD) is a fatal disease that occurs suddenly without preceding clinical signs or symptoms. Although high salt intake is a proposed risk factor for cardiovascular diseases, the relationship between AD and high salt intake has not been clarified. We examined the effect of high-salt challenge on a mouse AD model. Approach and Results: AD was induced in male mice by continuous infusion of ß-aminopropionitrile and Ang II (angiotensin II). High-salt challenge exacerbated aortic wall destruction in AD. Deletion of Il17a (IL-17KO [IL (interleukin)-17A knockout]) did not affect the AD phenotype at baseline, but it abolished the high salt-induced worsening of the aortic destruction. Unexpectedly, aortas of IL-17KO mice exhibited global changes in ECM (extracellular matrix)-related genes without alteration of proinflammatory genes, altered architecture of collagen fibers, and reduced stiffness before AD induction. The aortas of IL-17KO mice were less sensitive to AD-inducing stimuli, as shown by the induction of phenotypic modulation markers SMemb and vimentin, suggesting a reduced stress response. The aortas of IL-17KO mice had a higher population of smooth muscle cells with nuclear-localized phosphorylated Smad2, indicative of TGFß (transforming growth factor-beta) signal activation. Consistently, pretreatment of smooth muscle cells in culture with IL-17A blunted the activation of Smad2 by TGFß1. CONCLUSIONS: These findings indicate that high salt intake has a worsening effect on AD in the context of high aortic wall stiffness, which is under the control of IL-17A through ECM metabolism. Therefore, salt restriction may represent a low-cost and practical way to reduce AD risk.
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Aneurisma da Aorta Torácica/genética , Dissecção Aórtica/genética , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica , Interleucina-17/genética , Músculo Liso Vascular/metabolismo , Sódio na Dieta/efeitos adversos , Dissecção Aórtica/metabolismo , Dissecção Aórtica/patologia , Animais , Aneurisma da Aorta Torácica/metabolismo , Aneurisma da Aorta Torácica/patologia , Células Cultivadas , Modelos Animais de Doenças , Progressão da Doença , Matriz Extracelular/patologia , Interleucina-17/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/patologia , RNA/genética , Transdução de SinaisRESUMO
Aortic dissection (AD) is a serious clinical condition that is unpredictable and frequently results in fatal outcome. Although rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR), has been reported to be effective in preventing aortopathies in mouse models, its mode of action has yet to be clarified. A mouse AD model that was created by the simultaneous administration of ß-aminopropionitrile (BAPN) and angiotensin II (AngII) for 14 days. Rapamycin treatment was started either at day 1 or at day 7 of BAPN+AngII challenge, and continued throughout the observational period. Rapamycin was effective both in preventing AD development and in suppressing AD progression. On the other hand, gefitinib, an inhibitor of growth factor signaling, did not show such a beneficial effect, even though both rapamycin and gefitinib suppressed cell cycle activation in AD. Rapamycin suppressed cell cycle-related genes and induced muscle development-related genes in an AD-related gene expression network without a major impact on inflammation-related genes. Rapamycin augmented the activation of Akt1, Akt2, and Stat3, and maintained the contractile phenotype of aortic smooth muscle cells. These findings indicate that rapamycin was effective both in preventing the development and in suppressing the progression of AD, indicating the importance of the mTOR pathway in AD pathogenesis.
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Dissecção Aórtica/tratamento farmacológico , Dissecção Aórtica/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Sirolimo/farmacologia , Aminopropionitrilo/toxicidade , Dissecção Aórtica/induzido quimicamente , Dissecção Aórtica/prevenção & controle , Angiotensina II/toxicidade , Animais , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular , Modelos Animais de Doenças , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Ontologia Genética , Masculino , Camundongos , Músculo Liso Vascular/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/metabolismoRESUMO
A 75-year-old woman presented to our hospital with a history of fever, cervical lymphadenopathy, and fatigue. Computed tomography(CT)revealed systemic lymphadenopathy with prominent splenomegaly. Axillary lymph node biopsy results revealed diffuse proliferation of atypical lymphoid cells with arborizing high endothelial venules. Immunohistochemical staining was positive for CD3, CD5, and CD10, but negative for CD20 and CD79a. Given these findings, a diagnosis of angioimmunoblastic T-cell lymphoma(AITL)was made. Due to the extremely high tumor burden, pre-therapy with corticosteroids was initiated. However, the patient suddenly went into hemorrhagic shock. Contrast-enhanced CT revealed abdominal bleeding due to splenic rupture. Bleeding was rapidly controlled using transcatheter arterial embolization(TAE). Five days after TAE, mini-CHOP therapy was initiated. Splenomegaly is common in hematologic disease. Owing to the lethality of the condition, in cases of progressive anemia with splenomegaly in patients with hematologic disease, the possibility of splenic rupture should be considered. Since TAE carries no risk of post-splenectomy infection and allows timely resumption of chemotherapy, it could be considered as one of the preferred treatment choices for splenic rupture in hemodynamically unstable patients.
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Embolização Terapêutica , Linfoma de Células T , Neoplasias Esplênicas/complicações , Ruptura Esplênica , Idoso , Feminino , Hemorragia , Humanos , Linfoma de Células T/complicações , Ruptura Espontânea , Esplenectomia , Ruptura Esplênica/etiologiaRESUMO
PURPOSE: To evaluate 90-day outcomes after balloon-occluded retrograde transvenous obliteration (BRTO) with ethanolamine oleate (EO) in patients with gastric varices (GVs). MATERIALS AND METHODS: An 8-site prospective single-arm clinical trial was conducted. Patients who had endoscopically confirmed GVs with a gastrorenal shunt were eligible for the study. Overnight BRTO was performed, and efficacy was evaluated by endoscopy and contrast-enhanced computed tomography (CT). RESULTS: Forty-five patients (26 men and 19 women; mean age, 67.8 y) were enrolled. The complete regression rate of GVs based on endoscopic images on day 90 was 79.5% (35 of 44 patients; 95% confidence interval, 64.7%-90.2%). The rate of complete thrombosis of GVs based on contrast-enhanced CT on day 90 was 93.0% (40 of 43 patients; 95% confidence interval, 80.9%-98.5%). One patient experienced 2 events of bleeding from GVs, which was different from the GVs treated with BRTO. Appearance of new esophageal varices (EVs) or worsening of existing EVs occurred in 16 of 45 patients (35.6%). Forty-four of 45 patients (97.8%) experienced adverse events (AEs) related to EO, which included fever in 24 (53.3%), hematuria in 23 (51.1%), hemolysis in 16 (35.6%), back pain in 16 (35.6%), and abdominal pain in 10 (22.2%). One case of moderate to severe ascites (2.3%) was observed on day 90. One case of sepsis was the only serious AE observed in relation to EO. CONCLUSIONS: The present study demonstrates that BRTO with EO for the treatment of GVs is a clinically effective procedure with many mild to moderate AEs.
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Oclusão com Balão/métodos , Varizes Esofágicas e Gástricas/terapia , Ácidos Oleicos/uso terapêutico , Soluções Esclerosantes/uso terapêutico , Idoso , Oclusão com Balão/efeitos adversos , Meios de Contraste , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Feminino , Gastroscopia , Humanos , Japão , Masculino , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
PURPOSE: To investigate predictive factors and cutoff value of transient elastography (TE) measurements for assessing improvement in liver function after balloon-occluded retrograde transvenous obliteration (BRTO) for gastric varices (GV). MATERIALS AND METHODS: Retrospective analysis was performed of 50 consecutive patients followed for > 3 months after BRTO, who had undergone TE before BRTO between January 2011 and February 2015. The correlation between change in liver function (total bilirubin, albumin, and prothrombin time) and baseline liver function values and liver stiffness measurement (LSM) by TE was evaluated by Pearson correlation test. Receiver operating characteristic curves were used to determine cutoff values for discriminating between patients who had improved liver function and patients who did not. The time interval from BRTO to aggravation of esophageal varices (EV) (worsening morphology, development of new varices, or variceal rupture) grouped by cutoff values was also analyzed. RESULTS: Serum albumin was significantly improved at 3 months after BRTO (3.57 g/dL vs 3.74 g/dL, P < .001). There was a significant negative correlation between change in albumin and baseline LSM (r = -0.50, P < .001). The best cutoff point for LSM was ≤ 22.9 kPa, with sensitivity and specificity of 78.4% and 69.2%, respectively, for predicting which patients would have improved albumin after BRTO. Among 33 patients, 29 (88%) patients had improved albumin. The 1-year progression rate of EV after BRTO was 13.6% in patients with LSM ≤ 22.9 kPa. CONCLUSIONS: The predictive factor for improvement in albumin after BRTO was lower LSM (≤ 22.9 kPa) using TE.
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Oclusão com Balão , Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas/terapia , Circulação Hepática , Cirrose Hepática/diagnóstico por imagem , Testes de Função Hepática , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Oclusão com Balão/efeitos adversos , Bilirrubina/sangue , Biomarcadores/sangue , Progressão da Doença , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/fisiopatologia , Feminino , Humanos , Fígado/metabolismo , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Tempo de Protrombina , Curva ROC , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/metabolismo , Albumina Sérica Humana , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: This single-arm, multicenter, phase-II trial evaluated the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) using fine-powder cisplatin and iodized-oil suspension in patients with intermediate- and advanced-stage [Barcelona Clinic Liver Cancer (BCLC) stage-B and stage-C] hepatocellular carcinomas (HCCs). METHODS: The Institutional Review Board approved this study and patients provided written informed consent. Thirty-five patients (24 men and 11 women, mean 74 ± 6 years [range 60-87 years]) with BCLC stage-B (57 %, 20/35) or stage-C (43 %, 15/35) HCCs who were not candidates for other locoregional treatments were enrolled. HAIC was performed using a suspension of fine-powder cisplatin with a maximum dose of 65 mg/m(2) and iodized oil on demand. The primary endpoint was the response rate evaluated based on Response Evaluation Criteria in Solid Tumor (RECIST) and modified RECIST (mRECIST). Secondary endpoints were overall survival, progression-free survival, and safety. RESULTS: The initial and best overall response rates at 4 weeks and 3 months, respectively, were 14 and 17 % based on RECIST, and 57 and 23 % based on mRECIST. The median overall and progression-free survival times were 18 and 4 months, respectively. The most frequent grade-3 or grade-4 adverse events were elevation of serum alanine (23 %) and aspartate aminotransferase (20 %), and thrombocytopenia (17 %). CONCLUSION: This HAIC provides promising therapeutic effects with acceptable safety to patients with intermediate-stage and advanced-stage HCCs.
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Carcinoma Hepatocelular/tratamento farmacológico , Cisplatino/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Feminino , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Óleo Iodado/administração & dosagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pós , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: To evaluate the feasibility of gastric variceal (GV) volumetry using computed tomography (CT) images taken before balloon-occluded retrograde transvenous obliteration (B-RTO) and to assess its correlation with the actual amount of 5% ethanolamine oleate and iodinated contrast medium (EOI) injected in B-RTO. METHODOLOGY: Forty-seven consecutive patients with GV underwent B-RTO of the gastrorenal shunt. GV volume was measured with preoperative CT images by three radiologists. Statistical significance was examined by intraclass correlation coefficient (ICC) for concordance among three radiologists and by Pearson correlation test for correlation between GV volume and the amount of 5% EOI injected. RESULTS: GV volumes measured by three radiologists significantly correlated with each other (ICC=0.959). Combining all patients and all measurements, the mean GV volume and the mean amount of 5% EOI were 27.02±16.67cm3 and 28.72±17.72mL, respectively. There was a significant correlation between GV volume, calculated as a mean of the three values measured by the three radiologists, and the amount of EOI (r2=0.706, p<0.001). CONCLUSIONS: GV volume measured on CT showed a significant correlation with the amount of 5% EOI injected. CT volumetry of GV has the potential to determine an amount of the sclerosing agent to be injected in B-RTO.
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Oclusão com Balão , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Varizes Esofágicas e Gástricas/terapia , Tomografia Computadorizada Multidetectores , Escleroterapia , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Ácidos Oleicos/administração & dosagem , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Soluções Esclerosantes/administração & dosagem , Resultado do TratamentoRESUMO
PURPOSE: To evaluate whether antitumor immunity is enhanced systemically by combining radiofrequency ablation (RFA) and local injection of an immunostimulant, OK-432. MATERIALS AND METHODS: Experiments were approved by the institutional animal care committee. Experimental Japanese rabbits inoculated with VX2 tumors in the lung and the auricle were randomized into four groups of eight: control (supportive care), RFA (RFA of lung tumor), OK-432 (direct injection of OK-432 into lung tumor), and combination therapy (lung RFA and direct OK-432 injection into lung tumor). All procedures were performed 1 week after implantation of VX2 tumors (week 1). In addition, a VX2 tumor rechallenge test was performed in the RFA and combination therapy groups. Survival time was evaluated by means of the Kaplan-Meier method and by using the log-rank test for intergroup comparison. Mean auricle tumor volumes were calculated every week. Specific growth rates (SGRs) were calculated and compared by using the Mann-Whitney test. RESULTS: The median survival times of the control, RFA, OK-432, and combination therapy groups were 23, 36.5, 46.5, and 105 days, respectively. Survival was significantly prolonged in the combination therapy group when compared with the other three groups (P <.05). The mean auricle tumor volume decreased only in the combination therapy group. The mean auricle tumor volumes of the combination therapy group from week 1 to week 7 were 205, 339, 264, 227, 143, 127, and 115 mm(3). SGR in the combination therapy group became significantly smaller than those in the other three groups (P < .05). In the rechallenge test, the volume of all reimplanted tumors decreased. CONCLUSION: Combining RFA with local injection of immunostimulant OK-432 may lead to indirectly activation of systemic antitumor immunity.
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Ablação por Cateter , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Picibanil/farmacologia , Animais , Linhagem Celular Tumoral , Terapia Combinada , Injeções Intralesionais , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Picibanil/administração & dosagem , Modelos de Riscos Proporcionais , Coelhos , Distribuição Aleatória , Estatísticas não Paramétricas , Taxa de SobrevidaRESUMO
A 74-year-old patient presented with hematochezia and a history of liver cirrhosis with repeated bleeding from esophageal and rectal varices. Endoscopic examination revealed multiple rectal varices with positive red color signs. Ascites, severe portosystemic thrombosis and a splenorenal shunt were diagnosed on a contrast-enhanced dynamic computed tomography examination. From a transjugular approach, we circumvented thrombosed regions by maneuvering double balloon catheters through the shunt and dilated left colic marginal vein. We managed to successfully obliterate the varices.
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PURPOSE: Portal venous system thrombosis is a complication of partial splenic artery embolization, and pre-treatment risk assessment is thus important. The purpose of this study was to identify the risk factors for portal venous system thrombosis after partial splenic artery embolization. MATERIALS AND METHODS: We retrospectively analyzed 67 consecutive patients who underwent contrast-enhanced computed tomography before and after first partial splenic artery embolization between July 2007 and October 2018. As risk factors, we investigated age, sex, hematological data, liver function, steroid use, heparin use, and findings from pre- and post-treatment computed tomography. Uni- and multivariate analyses were performed to evaluate the relationship between thrombus appearance or growth and these factors. Values of p < 0.05 were considered significant. RESULTS: Partial splenic artery embolization was technically successful in all 67 patients. Nine patients showed appearance or growth of thrombus. Univariate analysis showed maximum diameter of the splenic vein before treatment (p = 0.0076), percentage of infarcted spleen (p = 0.017), and volume of infarcted spleen (p = 0.022) as significant risk factors. Multivariate analysis showed significant differences in maximum diameter of the splenic vein before treatment (p = 0.041) and percentage of infarcted spleen (p = 0.023). According to receiver operating characteristic analysis, cutoffs for maximum diameter of the splenic vein and percentage of infarcted spleen for distinguishing the appearance or growth of thrombus were 17 mm and 58.2%. CONCLUSION: Large maximum diameter of the splenic vein before partial splenic artery embolization and high percentage of infarcted spleen after partial splenic artery embolization were identified as risk factors for portal venous system thrombosis. LEVEL OF EVIDENCE: Level 4, Case Series.
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Embolização Terapêutica/efeitos adversos , Veia Porta/fisiopatologia , Artéria Esplênica/fisiopatologia , Veia Esplênica/anatomia & histologia , Tomografia Computadorizada por Raios X/métodos , Trombose Venosa/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Embolização Terapêutica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombose Venosa/fisiopatologia , Adulto JovemRESUMO
A 62-year-old woman was referred for cough and lower abdominal pain. F-FDG PET/CT showed strong uptake not only in the left lung mass and hilar and mediastinal lymph nodes, but also a huge lower abdominal mass. All lesions were initially thought to be multiple metastases because bronchial biopsy of the lung mass showed poorly differentiated adenocarcinoma. However, the abdominal mass was found to be malignant peritoneal mesothelioma after surgical resection. It was difficult to diagnose this case correctly before resection because localized malignant peritoneal mesothelioma is rare.
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Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Mesotelioma/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Feminino , Humanos , Mesotelioma Maligno , Pessoa de Meia-IdadeRESUMO
Aortic dissection (AD) is the acute destruction of aortic wall and is reportedly induced by inflammatory response. Here we investigated the role of smooth muscle Socs3 (a negative regulator of Janus kinases/signal transducer and activator of transcription signaling) in AD pathogenesis using a mouse model generated via ß-aminopropionitrile and angiotensin II infusion. Socs3 deletion specifically in smooth muscle cells yielded a chronic inflammatory response of the aortic wall, which was associated with increased fibroblasts, reinforced aortic tensile strength, and less-severe tissue destruction. Although an acute inflammatory response is detrimental in AD, smooth muscle-regulated inflammatory response seemed protective against AD.
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OBJECTIVE: To determine the utility of low-dose gelatin sponge particles and 5% ethanolamine oleate iopamidol (EOI) mixture in retrograde transvenous obliteration (GERTO) for gastric varices (GV). METHODS: 57 consecutive patients who underwent balloon-occluded retrograde transvenous obliteration (B-RTO) for GV were divided into three groups with Hirota's grade by balloon-occluded retrograde transvenous venography. Hirota's Grade 1 patients were assigned to G1 group and underwent treatment with 5% EOI. Grade ≥ 2 patients prior to August 2015 were G ≥ 2 group treated with 5% EOI, and those treated thereafter were GERTO group. The amount of EOI used per unit GV volume (EOI/GV ratio), the times to embolization and recurrence rate of GV were evaluated. RESULTS: The EOI/GV ratio was 0.66 ± 0.19 in G1, 1.5 ± 0.8 in G ≥ 2, and 0.58 ± 0.23 in GERTO (G ≥ 2 vs GERTO, p < 0.0001). The times to embolization were 26.5 ± 10.5 min for G1, 39.2 ± 26.8 for G ≥ 2, and 21.4 ± 9.4 for GERTO (G ≥ 2 vs GERTO, p = 0.005). The recurrence rate was not significantly different in any of the groups. CONCLUSION: GERTO was performed in lower amount of sclerosants and in less time compared to conventional B-RTO in Hirota's grade ≥2. ADVANCES IN KNOWLEDGE: Feasibility of low-dose gelatin sponge particles and 5% EOI mixture as sclerosants for GV.
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Oclusão com Balão/métodos , Varizes Esofágicas e Gástricas/terapia , Gelatina/administração & dosagem , Iopamidol/administração & dosagem , Ácidos Oleicos/administração & dosagem , Soluções Esclerosantes/administração & dosagem , Idoso , Oclusão com Balão/efeitos adversos , Combinação de Medicamentos , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Flebografia/métodosRESUMO
Aortic dissection (AD) is a major cause of acute aortic syndrome with high mortality due to the destruction of aortic walls. Although recent studies indicate the critical role of inflammation in the disease mechanism of AD, it is unclear how inflammatory response is initiated. Here, we demonstrate that myocardin-related transcription factor A (MRTF-A), a signal transducer of humoral and mechanical stress, plays an important role in pathogenesis of AD in a mouse model. A mouse model of AD was created by continuous infusion of angiotensin II (AngII) that induced MRTF-A expression and caused AD in 4 days. Systemic deletion of Mrtfa gene resulted in a marked suppression of AD development. Transcriptome and gene annotation enrichment analyses revealed that AngII infusion for 1 day caused pro-inflammatory and pro-apoptotic responses before AD development, which were suppressed by Mrtfa deletion. AngII infusion for 1 day induced pro-inflammatory response, as demonstrated by expressions of Il6, Tnf, and Ccl2, and apoptosis of aortic wall cells, as detected by TUNEL staining, in an MRTF-A-dependent manner. Pharmacological inhibition of MRTF-A by CCG-203971 during AngII infusion partially suppressed AD phenotype, indicating that acute suppression of MRTF-A is effective in preventing the aortic wall destruction. These results indicate that MRTF-A transduces the stress of AngII challenge to the pro-inflammatory and pro-apoptotic responses, ultimately leading to AD development. Intervening this pathway may represent a potential therapeutic strategy.
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Dissecção Aórtica/genética , Inflamação/genética , Transativadores/genética , Transcriptoma/genética , Dissecção Aórtica/induzido quimicamente , Dissecção Aórtica/patologia , Angiotensina II/toxicidade , Animais , Apoptose/efeitos dos fármacos , Quimiocina CCL2/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-6/genética , Camundongos , Estresse Mecânico , Fator de Necrose Tumoral alfa/genéticaRESUMO
Optimal blood pressure (BP) targets for hypertension have been an important clinical issue but have been elusive. The Systolic Blood Pressure Intervention Trial (SPRINT) showed significant benefits of intensive BP-lowering treatment with a target systolic BP level of < 120 mm Hg on major cardiovascular (CV) events and mortality, whereas there was a modest increase in renal events related to BP-lowering treatment. We searched the PubMed, Cochrane CENTRAL, and ICHUSHI databases for randomized trials that assigned participants to intensive versus usual BP-lowering treatment with different BP targets. The outcomes were major CV events, all-cause death, myocardial infarction, stroke, heart failure, renal events, and adverse events. Nineteen trials that enrolled a total of 55,529 participants with a mean follow-up duration ranging from 1.6 to 12.2 years were included in the present analysis. There was a significant reduction in major CV events, myocardial infarction, and stroke and a trend toward a reduction in heart failure associated with intensive BP-lowering treatment, but no differences in the risks of all-cause death, renal events, or adverse events were observed between the randomized groups. Subgroup analyses indicated that intensive BP-lowering treatment with a target of < 130/80 mm Hg and/or achievement of BP < 130/80 mm Hg were associated with a significant reduction in major CV events compared with the usual group. In conclusion, intensive BP-lowering treatment reduces the risk of CV events. A target BP level of < 130/80 mm Hg appears to be optimal for CV protection in patients with hypertension.
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Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Determinação da Pressão Arterial , Objetivos , HumanosRESUMO
Aortic dissection is a life-threatening condition, which is characterised by separation of the constituent layers of the aortic wall. We have recently shown that monocyte/macrophage infiltration into the aortic wall is a pathogenic mechanism of the condition. In the present study, we investigated whether the anti-inflammatory agent, indomethacin, could inhibit monocyte/macrophage accumulation in the aortic wall and ensuing dissection. Indomethacin was administered (from 3 days prior with daily oral administration) to mice in which aortic dissection was induced using beta-aminopropionitrile (BAPN) and angiotensin II (Ang II) infusion (2 weeks). Indomethacin prevented death from abdominal aortic dissection and decreased incidence of aortic dissection by as high as 40%. Histological and flow cytometry analyses showed that indomethacin administration resulted in inhibition of monocyte transendothelial migration and monocyte/macrophage accumulation in the aortic wall. These results indicate that indomethacin administration reduces rate of onset of aortic dissection in a murine model of the condition.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Aneurisma da Aorta Abdominal/tratamento farmacológico , Dissecção Aórtica/prevenção & controle , Ruptura Aórtica/prevenção & controle , Indometacina/uso terapêutico , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Animais , Aorta Abdominal/efeitos dos fármacos , Aorta Abdominal/patologia , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Objective Balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices (GV) is associated with drawbacks including a postoperative increase in portal pressure and the risk of subsequent worsening of esophageal varices (EV). Selective B-RTO that embolizes only the varices may have the potential to minimize such risks. The aim of this study is to retrospectively compare the postoperative course of patients after selective B-RTO (Group S) and conventional B-RTO (Group B). Methods One hundred four patients treated from January 2007 to April 2012 were classified into Groups S (n=5) and B (n=99). In the univariate analysis, the volume of 5% ethanolamine oleate iopamiodol (EOI) administered at baseline and the GV blood flow on endoscopic ultrasound after B-RTO were considered as covariates. The rates of GV recurrence and EV aggravation was also compared between Groups B and S. Results In Group S, the volume of 5% EOI was significantly lower (Group S vs. Group B: 14.6±5.5 vs. 28.5±16.4 mL; p=0.0012) and the rate of EV aggravation was lower in comparison to Group B (p=0.045). However, in Group S, the rate of complete eradication of GV blood flow was significantly lower (Group S vs. Group B: 0% vs. 89.9%; p<0.001) and the rate of re-treatment for GV was higher in comparison to Group B (Group S vs. Group B: 60% vs. 1.0%; p<0.001). Conclusion Selective B-RTO for GV could minimize the risk of a worsening of EV or reduce the amount of sclerosants; however, the rate of recurrence was high in comparison to conventional B-RTO.
Assuntos
Oclusão com Balão/métodos , Embolização Terapêutica/métodos , Varizes Esofágicas e Gástricas/cirurgia , Idoso , Endossonografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Peripartum cardiomyopathy (PPCM) is rare but life-threatening. We herein report the case of a 48-year-old woman with PPCM after oocyte donation and delivery of twins. Two weeks after delivery, she suffered from severe symptoms of heart failure [orthopnea, New York Heart Association (NYHA) class IV, pulmonary edema and a reduced left ventricular ejection fraction of 18%]. Although standard heart failure therapy was effective for diminishing the congestion, it was not sufficient to improve her symptoms or left ventricular systolic dysfunction. During admission, we added bromocriptine. A year later after the onset, she was in a good state with an improved left ventricular systolic function.
Assuntos
Bromocriptina/administração & dosagem , Bromocriptina/uso terapêutico , Cardiomiopatias/tratamento farmacológico , Doação de Oócitos/métodos , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Cardiomiopatias/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Período Periparto , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnósticoRESUMO
Objective Therapeutic predictors derived from the venous pressure before therapy have not been identified for Budd-Chiari syndrome (BCS). The aim of this study was to determine whether or not measuring the distal pressure or pressure gradient was useful for predicting treatment efficacy in BCS. Methods We retrospectively analyzed seven consecutive patients diagnosed with symptomatic BCS at our hospital between 2008 and 2017. Distal and proximal venous pressures at occlusion sites of BCS were measured before treatment in all cases. The pressure gradient was defined as the difference between distal and proximal venous pressures. A receiver operating characteristics (ROC) analysis was performed for venous pressures. Results Percutaneous old balloon angioplasty (POBA) was performed in seven cases, with technical success achieved in all cases (100%). No complications were encountered. The median primary patency was 574 (interquartile range, 439.5-1,056.5) days. The 1-year primary patency rate was 71.73%. Six cases (85.7%) showed resolution of symptoms, representing clinical success. The ROC analysis revealed a high distal pressure (area under the ROC curve = 0.83, cut-off=12 mmHg) as a predictor of treatment efficacy of POBA for symptomatic BCS. In addition, the pressure gradient was considered significant from a clinical perspective, because the 6 successful cases with resolution of symptoms showed a large pressure gradient (range, 8-21 mmHg) before treatment, whereas the failed case showed a relatively small pressure gradient (7 mmHg). Conclusion High distal pressure and a large pressure gradient might predict the treatment efficacy of balloon angioplasty for symptomatic BCS.