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ApoA-I amyloidosis is an extremely rare form of systemic amyloidosis that commonly involves the heart, kidneys, and liver. ApoA-I amyloidosis is caused by amyloidogenic variants of APOA1 that are inherited in an autosomal dominant manner. Here, we report a 69-year-old man with sporadic cardiac amyloidosis who was born to consanguineous parents and carried a homozygous variant of p.Leu202Arg in APOA1.
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Neurofibromatosis type 1 (NF1) is an autosomal dominant multi-organ disease. The clinical manifestations include not only skin lesions and malignant tumors but also lung complications, including pulmonary arterial hypertension (PAH). However, the association between gene mutations in NF1 and the occurrence of PAH has not yet been elucidated. We herein report a case of isolated PAH in a 67-year-old woman with NF1, presumably caused by a novel heterozygous mutation, c.4485_4486delinsAT (p.Lys1496Ter), in the NF1 gene.
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INTRODUCTION: It remains unclear whether increased perirenal fat (PRF) accumulation is equally related to renal involvement in patients with and without diabetes mellitus (DM). We evaluated the association between PRF volume (PRFV) and low glomerular filtration rate (GFR) and proteinuria in people with or without type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We performed a cross-sectional analysis of 473 individuals without T2DM (non-DM, n=202) and with T2DM (DM, n=271). PRFV (cm3), obtained from non-contrast CT, was indexed as PRF index (PRFV/body surface area, cm3/m2). Multivariate-adjusted models were used to determine the ORs of PRFV and PRFV index for detecting estimated GFR (eGFR) decrease of <60 mL/min/1.73 m2 proteinuria onset, or both. RESULTS: Although body mass index (BMI), visceral fat area, and waist circumference were comparable between the non-DM and DM groups, kidney volume, PRFV, and PRFV index were higher in individuals with T2DM than in those without T2DM. In the multivariate analysis, after adjusting for age, sex, BMI, hypertension, smoking history, and visceral fat area ≥100 cm2, the cut-off values of PRFV index were associated with an eGFR<60 in individuals with DM (OR 6.01, 95% CI 2.20 to 16.4, p<0.001) but not in those without DM. CONCLUSIONS: PRFV is associated with low eGFR in patients with T2DM but not in those without T2DM. This suggests that PRF accumulation is more closely related to the onset and progression of diabetic kidney disease (DKD) than non-DKD. Clarifying the mechanisms through which PRF influences DKD development could pave the way for novel prevention and treatment strategies.
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Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Humanos , Estudos Transversais , Adiposidade , Diabetes Mellitus Tipo 2/complicações , Japão , Insuficiência Renal Crônica/complicações , Obesidade/complicações , Proteinúria/complicaçõesRESUMO
BACKGROUND: The role of the angiotensin receptor neprilysin inhibitor (ARNI) in cardiac function, particularly its impact on pulmonary circulation, remains underexplored. Recent studies have described abnormal mean pulmonary artery pressure (mPAP)-cardiac output (CO) responses as having the potential to assess the disease state. The aim of this study was to assess the effects of ARNI on pulmonary circulation in heart failure. We measured echocardiographic parameters post 6-min walk (6 MW) and compared the changes with baseline and follow-up. Our hypothesis was that pulmonary pressure-flow relationship of the pulmonary circulation obtained by 6 MW stress echocardiography would be improved with treatment. METHODS: We prospectively enrolled 39 heart failure patients and conducted the 6 MW test indoors. Post-6 MW echocardiography measured echocardiographic variables, and CO was derived from electric cardiometry. Individualized ARNI doses were optimized, with follow-up echocardiographic evaluations after 1 year. RESULTS: Left ventricular (LV) volume were significantly reduced (160.7 ± 49.6 mL vs 136.0 ± 54.3 mL, P < 0.001), and LV ejection fraction was significantly improved (37.6 ± 11.3% vs 44.9 ± 11.5%, P < 0.001). Among the 31 patients who underwent 6 MW stress echocardiographic study at baseline and 1 year later, 6 MW distance increased after treatment (380 m vs 430 m, P = 0.003). The ΔmPAP/ΔCO by 6 MW stress decreased with treatment (6.9 mmHg/L/min vs 2.8 mmHg/L/min, P = 0.002). The left atrial volume index was associated with the response group receiving ARNI treatment for pulmonary circulation. CONCLUSIONS: Initiation of ARNI was associated with improvement of left ventricular size and LVEF. Additionally, the 6 MW distance increased and the ΔmPAP/ΔCO was improved to within normal range with treatment.
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Insuficiência Cardíaca , Neprilisina , Humanos , Valsartana , Tetrazóis/farmacologia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico , Receptores de Angiotensina , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Combinação de Medicamentos , Aminobutiratos/uso terapêutico , Aminobutiratos/farmacologiaRESUMO
BACKGROUND: Cancer therapeutics-related cardiac dysfunction (CTRCD) affect the prognosis of patients with breast cancer. Echocardiographic surveillance of patients treated with anti-human epidermal growth factor receptor type 2 (HER2) antibodies has been recommended, but few reports have provided evidence on patients with breast cancer only. We aimed to evaluate the effectiveness of echocardiographic surveillance for breast cancer patients. METHODS: We identified 250 patients with breast cancer who were treated with anti-HER2 antibodies from July 2007 to September 2021. We divided 48 patients with echocardiographic surveillance every 3â¯months into the surveillance group and 202 patients without echocardiographic surveillance into the non-surveillance group. In the surveillance group, patients with a considerable reduction in global longitudinal strain of 15â¯% were considered for the initiation of cardioprotective drugs. The composite outcome of CTRCD and acute heart failure was the study endpoint. RESULTS: The mean age was 59⯱â¯12â¯years. During the follow-up period of 15â¯months (12-17â¯months), 12 patients reached the endpoint. The surveillance group had significantly lower incidence of the composite outcome (2.1â¯% vs. 5.5â¯%, adjusted odds ratio: 0.28, 95â¯% confidential intervals: 0.09-0.94; pâ¯=â¯0.039) and higher rates of prescriptions of cardioprotective drugs than the non-surveillance group. CONCLUSIONS: The incidence of cardiac complications was significantly lower in the surveillance group than the non-surveillance group, which supports the effectiveness of echocardiographic surveillance in patients with breast cancer.
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Antineoplásicos , Neoplasias da Mama , Cardiopatias , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Neoplasias da Mama/tratamento farmacológico , Antineoplásicos/efeitos adversos , Cardiotoxicidade/etiologia , Fatores de Risco , EcocardiografiaRESUMO
The Mediterranean diet, which is characterized by high consumption of olive oil, prevents cardiovascular disease. Meanwhile, olive mill wastewater (OMWW), which is obtained as a byproduct during olive oil production, contains various promising bioactive components such as water-soluble polyphenols. Hydroxytyrosol (HT), the major polyphenol in OMWW, has anti-oxidative and anti-inflammatory properties; however, the atheroprotective effects of OMWW and HT remain to be fully understood. Here, we investigated the effect of OMWW and HT on atherogenesis. Male 8-week-old apolipoprotein E-deficient mice were fed a western-type diet supplemented with OMWW (0.30%w/w) or HT (0.02%w/w) for 20 weeks. The control group was fed a non-supplemented diet. OMWW and HT attenuated the development of atherosclerosis in the aortic arch as determined by Sudan IV staining (P < 0.01, respectively) without alteration of body weight, plasma lipid levels, and blood pressure. OMWW and HT also decreased the production of oxidative stress (P < 0.01, respectively) and the expression of NADPH oxidase subunits (e.g., NOX2 and p22phox) and inflammatory molecules (e.g. IL-1ß and MCP-1) in the aorta. The results of in vitro experiments demonstrated that HT inhibited the expression of these molecules that were stimulated with LPS in RAW264.7 cells, murine macrophage-like cells. OMWW and HT similarly attenuated atherogenesis. HT is a major component of water-soluble polyphenols in OMWW, and it inhibited inflammatory activation of macrophages. Therefore, our results suggest that the atheroprotective effects of OMWW are at least partially attributable to the anti-inflammatory effects of HT.
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Aterosclerose , Olea , Camundongos , Masculino , Animais , Águas Residuárias , Olea/química , Azeite de Oliva/farmacologia , Azeite de Oliva/química , Aterosclerose/prevenção & controle , Anti-Inflamatórios/farmacologia , Polifenóis/farmacologia , Polifenóis/química , Água , ApolipoproteínasRESUMO
BACKGROUND: We sought to compare the outcomes of patients receiving combination therapy of diuretics and neurohormonal blockers, with a matched cohort with monotherapy of loop diuretics, using real-world big data. METHODS: This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). After exclusion criteria, we identified 78,685 patients who were first hospitalized with heart failure (HF) between April 2015 and March 2017. Propensity score (PS) was estimated with logistic regression model, with neurohormonal blockers (angiotensin-converting enzyme inhibitor : ACEi or angiotensin receptor blocker : ARB, ?-blockers and mineralocorticoid receptor antagonists : MRA) as the dependent variable and 24 clinically relevant covariates to compare the in-hospital mortality between monotherapy of loop diuretics and combination therapies. RESULTS: On PS-matched analysis, patients with ACEi?/?ARB, ?-blockers, and MRA had lower total in-hospital mortality and in-hospital mortality within 7 days, 14 days and 30 days. In the sub-group analysis, regardless of clinical characteristics including elderly people and cancer, patients treated with a combination of loop diuretics and neurohormonal blockers had significantly lower in-hospital mortality than matched patients. CONCLUSIONS: Our data indicate the benefits of guideline-directed medical therapy to loop diuretics in the management of HF. J. Med. Invest. 70 : 41-53, February, 2023.
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Inibidores da Enzima Conversora de Angiotensina , Insuficiência Cardíaca , Humanos , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêuticoRESUMO
BACKGROUND: Mechanical stress on the heart, such as high blood pressure, initiates inflammation and causes hypertrophic heart disease. However, the regulatory mechanism of inflammation and its role in the stressed heart remain unclear. IL-1ß (interleukin-1ß) is a proinflammatory cytokine that causes cardiac hypertrophy and heart failure. Here, we show that neural signals activate the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3) inflammasome for IL-1ß production to induce adaptive hypertrophy in the stressed heart. METHODS: C57BL/6 mice, knockout mouse strains for NLRP3 and P2RX7 (P2X purinoceptor 7), and adrenergic neuron-specific knockout mice for SLC17A9, a secretory vesicle protein responsible for the storage and release of ATP, were used for analysis. Pressure overload was induced by transverse aortic constriction. Various animal models were used, including pharmacological treatment with apyrase, lipopolysaccharide, 2'(3')-O-(4-benzoylbenzoyl)-ATP, MCC950, anti-IL-1ß antibodies, clonidine, pseudoephedrine, isoproterenol, and bisoprolol, left stellate ganglionectomy, and ablation of cardiac afferent nerves with capsaicin. Cardiac function and morphology, gene expression, myocardial IL-1ß and caspase-1 activity, and extracellular ATP level were assessed. In vitro experiments were performed using primary cardiomyocytes and fibroblasts from rat neonates and human microvascular endothelial cell line. Cell surface area and proliferation were assessed. RESULTS: Genetic disruption of NLRP3 resulted in significant loss of IL-1ß production, cardiac hypertrophy, and contractile function during pressure overload. A bone marrow transplantation experiment revealed an essential role of NLRP3 in cardiac nonimmune cells in myocardial IL-1ß production and cardiac phenotype. Pharmacological depletion of extracellular ATP or genetic disruption of the P2X7 receptor suppressed myocardial NLRP3 inflammasome activity during pressure overload, indicating an important role of ATP/P2X7 axis in cardiac inflammation and hypertrophy. Extracellular ATP induced hypertrophic changes of cardiac cells in an NLRP3- and IL-1ß-dependent manner in vitro. Manipulation of the sympathetic nervous system suggested sympathetic efferent nerves as the main source of extracellular ATP. Depletion of ATP release from sympathetic efferent nerves, ablation of cardiac afferent nerves, or a lipophilic ß-blocker reduced cardiac extracellular ATP level, and inhibited NLRP3 inflammasome activation, IL-1ß production, and adaptive cardiac hypertrophy during pressure overload. CONCLUSIONS: Cardiac inflammation and hypertrophy are regulated by heart-brain interaction. Controlling neural signals might be important for the treatment of hypertensive heart disease.
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Inflamassomos , Proteínas de Transporte de Nucleotídeos , Camundongos , Ratos , Humanos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Inflamação , Arritmias Cardíacas , Encéfalo/metabolismo , Cardiomegalia , Trifosfato de Adenosina/metabolismo , Interleucina-1beta/metabolismo , Proteínas de Transporte de Nucleotídeos/metabolismoRESUMO
PURPOSE: Amyloid light chain (AL) and transthyretin (ATTR) are the major subtypes of cardiac amyloidosis (CA). 99mTc-pyrophosphate (PYP) scintigraphy is used to differentiate ATTR from other CA subtypes. We adapted the standardized uptake value (SUV) for 99mTc-PYP and proposed two quantitative indices, amyloid deposition volume (AmyDV) and total amyloid uptake (TAU). This study aimed to evaluate the utility of these quantitative indices in differentiating ATTR from non-ATTRs. MATERIALS AND METHODS: Before the SUV measurement, the Becquerel calibration factor (BCF) of 99mTc was obtained by a phantom experiment. Thirty-two patients who had undergone hybrid SPECT/CT imaging 3 h after injection of 99mTc-PYP (370 MBq) were studied. CT attenuation correction for image reconstruction was applied in all. We calculated SUV, AmyDV, and TAU using a quantitative analysis software program for bone SPECT (GI-BONE) and analyzed AmyDV using two methods: threshold method (set 40%); and constant value method (average SUVmax of ribs). We assessed the diagnostic ability of heart-to-contralateral lung (H/CL) ratio, SUV, AmyDV, and TAU to differentiate ATTR from non-ATTR using receiver operating characteristic (ROC) analysis. RESULTS: Statistically significant differences in all quantitative indices were observed between ATTR and non-ATTR. The area under the curve of each quantitative index for discriminating between ATTR and non-ATTR were as follows: H/CL, 0.997; SUVmax, 0.953; SUVmean (M1), 0.964; SUVmean (M2), 0.969; AmyDV (M1), 0.875; AmyDV (M2), 0.974; and TAU, 0.974. The AmyDV (M2) had higher diagnostic ability than AmyDV (M1). Thus, TAU was calculated as AmyDV (M2) × SUVmean (M2). In the ROC curve, SUV, AmyDV, and TAU had almost the same diagnostic ability as H/CL in distinguishing ATTR from non-ATTRs. CONCLUSIONS: We propose two novel 3D-based quantitative parameters (AmyDV and TAU) that have almost equal ability to discriminate ATTR from non-ATTR.
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Amiloidose , Cardiomiopatias , Humanos , Difosfatos , Pirofosfato de Tecnécio Tc 99m , Cardiomiopatias/diagnóstico por imagem , Amiloidose/diagnóstico por imagem , Cintilografia , AmiloideRESUMO
Transthyretin amyloidosis (ATTR) variant is a life-threatening hereditary disease predominantly affecting the peripheral nervous system and heart. Tafamidis, which prevents the deposition of amyloid by stabilizing transthyretin, is available for the treatment of neuropathy and cardiomyopathy of ATTR. However, whether tafamidis could eliminate established amyloid deposits and improve cardiac function remains unknown. We reported a case of regression of left ventricular hypertrophy after tafamidis therapy in a patient with an ATTR variant. J. Med. Invest. 69 : 320-322, August, 2022.
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Neuropatias Amiloides Familiares , Pré-Albumina , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/tratamento farmacológico , Benzoxazóis , Humanos , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/etiologia , Pré-Albumina/genéticaRESUMO
In lifestyle-related diseases, such as cardiovascular, metabolic, respiratory, and kidney diseases, chronic inflammation plays a causal role in their pathogenesis; however, underlying mechanisms of sterile chronic inflammation are not well-understood. Previous studies have confirmed the damage of cells in these organs in the presence of various risk factors such as diabetes, dyslipidemia, and cigarette smoking, releasing various endogenous ligands for pattern recognition receptors. These studies suggested that nucleic acids released from damaged tissues accumulate in these tissues, acting as an endogenous ligand. Undamaged DNA is an integral factor for the sustenance of life, whereas, DNA fragments, especially those from pathogens, are potent activators of the inflammatory response. Recent studies have indicated that inflammatory responses such as the production of type I interferon (IFN) induced by DNA-sensing mechanisms which contributes to self-defense system in innate immunity participates in the progression of inflammatory diseases by the recognition of nucleic acids derived from the host, including mitochondrial DNA (mtDNA). The body possesses several types of DNA sensors. Toll-like receptor 9 (TLR9) recognizes DNA fragments in the endosomes. In addition, the binding of DNA fragments in the cytosol activates cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS), resulting in the synthesis of the second messenger cyclic GMP-AMP (cGAMP). The binding of cGAMP to stimulator of interferon genes (STING) activates NF-κB and TBK-1 signaling and consequently the production of many inflammatory cytokines including IFNs. Numerous previous studies have demonstrated the role of DNA sensors in self-defense through the recognition of DNA fragments derived from pathogens. Beyond the canonical role of TLR9 and cGAS-STING, this review describes the role of these DNA-sensing mechanism in the inflammatory responses caused by endogenous DNA fragments, and in the pathogenesis of lifestyle-related diseases.
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Background: Stress echocardiography is an emerging tool used to detect exercise-induced pulmonary hypertension (EIPH). However, facilities that can perform stress echocardiography are limited by issues such as cost and equipment. Objective: We evaluated the usefulness of a deep learning (DL) approach based on a chest X-ray (CXR) to predict EIPH in 6-min walk stress echocardiography. Methods: The study enrolled 142 patients with scleroderma or mixed connective tissue disease with scleroderma features who performed a 6-min walk stress echocardiographic test. EIPH was defined by abnormal cardiac output (CO) responses that involved an increase in mean pulmonary artery pressure (mPAP). We used the previously developed AI model to predict PH and calculated PH probability in this cohort. Results: EIPH defined as ΔmPAP/ΔCO >3.3 and exercise mPAP >25 mmHg was observed in 52 patients, while non-EIPH was observed in 90 patients. The patients with EIPH had a higher mPAP at rest than those without EIPH. The probability of PH based on the DL model was significantly higher in patients with EIPH than in those without EIPH. Multivariate analysis showed that gender, mean PAP at rest, and the probability of PH based on the DL model were independent predictors of EIPH. A model based on baseline parameters (age, gender, and mPAP at rest) was improved by adding the probability of PH predicted by the DL model (AUC: from 0.65 to 0.74; p = 0.046). Conclusion: Applying the DL model based on a CXR may have a potential for detection of EIPH in the clinical setting.
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A 66-year-old Japanese man receiving systemic chemotherapy for advanced gastric cancer presented with exertional dyspnea. D-dimer was elevated in the blood. Echocardiography revealed pulmonary hypertension, and a ventilation-perfusion scan indicated decreased perfusion in the bilateral lungs. Cardiac catheterization showed no evidence of pulmonary artery embolization and revealed cytologically confirmed adenocarcinoma. Thus, pulmonary tumor thrombotic microangiopathy (PTTM) was diagnosed. The patient died of respiratory failure on the 17th hospitalization day despite systemic chemotherapy. Retrospective serological testing revealed increased vascular endothelial growth factor in the pulmonary artery blood. This is a rare case with antemortem cytologically proven PTTM mediated by VEGF.
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Neoplasias Pulmonares , Células Neoplásicas Circulantes , Neoplasias Gástricas , Microangiopatias Trombóticas , Idoso , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Masculino , Células Neoplásicas Circulantes/patologia , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Estudos Retrospectivos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Tomografia Computadorizada por Raios X , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Despite recent advances in imaging for myocardial deformation, left ventricular ejection fraction (LVEF) is still the most important index for systolic function in daily practice. Its role in multiple fields (e.g., valvular heart disease, myocardial infarction, cancer therapy-related cardiac dysfunction) has been a mainstay in guidelines. In addition, assessment of LVEF is vital to clinical decision-making in patients with heart failure. However, notable limitations to LVEF include poor inter-observer reproducibility dependent on observer skill, poor acoustic windows, and variations in measurement techniques. To solve these problems, methods for standardization of LVEF by sharing reference images among observers and artificial intelligence for accurate measurements have been developed. In this review, we focus on the standardization of LVEF using reference images and automated LVEF using artificial intelligence.
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Inteligência Artificial , Disfunção Ventricular Esquerda , Ventrículos do Coração/diagnóstico por imagem , Humanos , Reprodutibilidade dos Testes , Volume Sistólico , Função Ventricular EsquerdaRESUMO
BACKGROUND: Cardiovascular diseases are the second most common cause of mortality among cancer survivors, after death from cancer. We sought to assess the impact of cancer on the short-term outcomes of acute myocardial infarction (AMI), by analysing data obtained from a large-scale database. METHODS: This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination. We identified patients who were hospitalised for primary AMI between April 2012 and March 2017. Propensity Score (PS) was estimated with logistic regression model, with cancer as the dependent variable and 21 clinically relevant covariates. The main outcome was in-hospital mortality. RESULTS: We split 1 52 208 patients into two groups with or without cancer. Patients with cancer tended to be older (cancer group 73±11 years vs non-cancer group 68±13 years) and had smaller body mass index (cancer group 22.8±3.6 vs non-cancer 23.9±4.3). More patients in the non-cancer group had hypertension or dyslipidaemia than their cancer group counterparts. The non-cancer group also had a higher rate of percutaneous coronary intervention (cancer 92.6% vs non-cancer 95.2%). Patients with cancer had a higher 30-day mortality (cancer 6.0% vs non-cancer 5.3%) and total mortality (cancer 8.1% vs non-cancer 6.1%) rate, but this was statistically insignificant after PS matching. CONCLUSION: Cancer did not significantly impact short-term in-hospital mortality rates after hospitalisation for primary AMI.
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Infarto do Miocárdio/complicações , Neoplasias/mortalidade , Pontuação de Propensão , Sistema de Registros , Medição de Risco/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Neoplasias/complicações , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Background The prognosis of patients with cancer-venous thromboembolism (VTE) is not well known because of a lack of registry data. Moreover, there is also no knowledge on how specific types are related to prognosis. We sought to evaluate the clinical characteristics and outcomes of patients with cancer-associated VTE, compared with a matched cohort without cancer using real-world registry data of VTE. Methods and Results This study was based on the Diagnosis Procedure Combination database in the JROAD-DPC (Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination). Of 5 106 151 total patients included in JROAD-DPC, we identified 49 580 patients who were first hospitalized with VTE from April 2012 to March 2017. Propensity score was estimated with a logistic regression model, with cancer as the dependent variable and 18 clinically relevant covariates. After propensity matching, there were 25 148 patients with VTE with or without cancer. On propensity score-matched analysis with 25 148 patients with VTE, patients with cancer had higher total in-hospital mortality within 7 days (1.3% versus 1.1%, odds ratio [OR], 1.66; 95% CI, 1.31-2.11; P<0.0001), 14 days (2.5% versus 1.5%, OR, 2.07; 95% CI, 1.72-2.49; P<0.0001), and 30 days (4.8% versus 2.0%, OR, 2.85; 95% CI, 2.45-3.31; P<0.0001). On analysis for each type of cancer, in-hospital mortality in 11 types of cancer was significantly high, especially pancreas (OR, 12.96; 95% CI, 6.41-26.20), biliary tract (OR, 8.67; 95% CI, 3.00-25.03), and liver (OR, 7.31; 95% CI, 3.05-17.50). Conclusions Patients with cancer had a higher in-hospital acute mortality for VTE than those without cancer, especially in pancreatic, biliary tract, and liver cancers.
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Neoplasias/complicações , Pontuação de Propensão , Sistema de Registros , Tromboembolia Venosa/mortalidade , Idoso , Idoso de 80 Anos ou mais , Causas de Morte/tendências , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Hospitalização/tendências , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND: Sirt7 is a recently identified sirtuin and has important roles in various pathological conditions, including cancer progression and metabolic disorders. It has previously been reported that Sirt7 is a key molecule in acute myocardial wound healing and pressure overload-induced cardiac hypertrophy. In this study, the role of Sirt7 in neointimal formation after vascular injury is investigated.MethodsâandâResults:Systemic (Sirt7-/-) and smooth muscle cell-specific Sirt7-deficient mice were subjected to femoral artery wire injury. Primary vascular smooth muscle cells (VSMCs) were isolated from the aorta of wild type (WT) and Sirt7-/-mice and their capacity for cell proliferation and migration was compared. Sirt7 expression was increased in vascular tissue at the sites of injury. Sirt7-/-mice demonstrated significant reduction in neointimal formation compared to WT mice. In vitro, Sirt7 deficiency attenuated the proliferation of serum-induced VSMCs. Serum stimulation-induced upregulation of cyclins and cyclin-dependent-kinase 2 (CDK2) was significantly attenuated in VSMCs of Sirt7-/-compared with WT mice. These changes were accompanied by enhanced expression of the microRNA 290-295 cluster, the translational negative regulator of CDK2, in VSMCs of Sirt7-/-mice. It was confirmed that smooth muscle cell-specific Sirt7-deficient mice showed significant reduction in neointima compared with control mice. CONCLUSIONS: Sirt7 deficiency attenuates neointimal formation after vascular injury. Given the predominant role in vascular neointimal formation, Sirt7 is a potentially suitable target for treatment of vascular diseases.