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BACKGROUND AND AIM: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare form of idiopathic interstitial pneumonias; its physical characteristics include a slender build with platythorax and progressive weight loss. However, the clinical significance of body mass index (BMI) and weight loss remains unclear in patients with IPPFE. Therefore, we aimed to clarify the association between baseline BMI, weight loss after diagnosis, and the prognosis of patients with IPPFE. METHODS: This retrospective study included 71 patients diagnosed with IPPFE at our institution between 2005-2021. BMI at diagnosis was classified into three: underweight (<18.5 kg/m2), normal weight (≥18.5 to <25.0 kg/m2), or overweight (≥25.0 kg/m2). An annual rate of weight change after the diagnosis was evaluated, and ≥5% per year decrease was defined as a significant weight loss. We investigated clinical features and prognosis based on baseline BMI and weight loss. RESULTS: Of the 71 patients, 48 (67.6%) and 23 (32.4%) were classified as underweight and normal weight, respectively, and none were overweight. Significant weight loss occurred in 24 (33.8%) patients, and they tended to have more cases of dyspnea and had significantly older age, lower BMI, higher rates of co-existence of lower-lobe interstitial lung disease, lower pulmonary function test results and higher incidence of pneumothorax after the diagnosis than those without weight loss. Patients with BMI <18.5 kg/m2 and those with weight loss had a significantly worse prognosis than those with BMI ≥18.5 kg/m2 or those without weight loss, respectively (p=0.005, p<0.001). Multivariate analysis revealed that low BMI and weight loss were independent poor prognostic factors. CONCLUSIONS: Low BMI and weight loss are associated with poor prognosis in patients with IPPFE.
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BACKGROUND: Although clinical guidelines recommend self-care assessment for patients with chronic heart failure (CHF), its prognostic significance remains controversial. This study aimed to compare the prognostic significance of self-care behavior on mortality between patients with and without a history of recent hospitalization for heart failure (HF). METHODS: We analyzed consecutive 1907 CHF patients from a Japanese multicenter registry (January 2020-June 2023) using the 9-item European Heart Failure Self-care Behavior Scale (EHFScBS-9) at enrolment. Suboptimal self-care behavior was defined as a scoreâ¯<â¯70 on the EHFScBS-9. Patients were divided into recent (within 30â¯days post-discharge, nâ¯=â¯664) and no recent hospitalization for HF groups (nâ¯=â¯1263), respectively. The primary outcome was a composite of all-cause death and rehospitalization for HF. RESULTS: During a median follow-up period of 427 (interquartile range 273-630) days, the primary outcome occurred in 100 patients. Patients with suboptimal self-care behavior exhibited a higher incidence of the primary outcome in the recent hospitalization for HF group (pâ¯=â¯0.020) but not in the no recent hospitalization for HF group (Pâ¯=â¯0.16). Multivariable regressions showed suboptimal self-care behavior was independently associated with the primary outcome in the recent hospitalization for HF group with a significant interaction (Pâ¯=â¯0.029). CONCLUSION: In patients recently hospitalized for HF, but not in those without a recent hospitalization history for HF, suboptimal self-care behavior was associated with adverse events. This indicates the importance of self-care education for these patients.
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Aims: Although frailty assessment is recommended for guiding treatment strategies and outcome prediction in elderly patients with heart failure (HF), most frailty scales are subjective, and the scores vary among raters. We sought to develop a machine learning-based automatic rating method/system/model of the clinical frailty scale (CFS) for patients with HF. Methods and results: We prospectively examined 417 elderly (≥75 years) with symptomatic chronic HF patients from 7 centres between January 2019 and October 2023. The patients were divided into derivation (n = 194) and validation (n = 223) cohorts. We obtained body-tracking motion data using a deep learning-based pose estimation library, on a smartphone camera. Predicted CFS was calculated from 128 key features, including gait parameters, using the light gradient boosting machine (LightGBM) model. To evaluate the performance of this model, we calculated Cohen's weighted kappa (CWK) and intraclass correlation coefficient (ICC) between the predicted and actual CFSs. In the derivation and validation datasets, the LightGBM models showed excellent agreements between the actual and predicted CFSs [CWK 0.866, 95% confidence interval (CI) 0.807-0.911; ICC 0.866, 95% CI 0.827-0.898; CWK 0.812, 95% CI 0.752-0.868; ICC 0.813, 95% CI 0.761-0.854, respectively]. During a median follow-up period of 391 (inter-quartile range 273-617) days, the higher predicted CFS was independently associated with a higher risk of all-cause death (hazard ratio 1.60, 95% CI 1.02-2.50) after adjusting for significant prognostic covariates. Conclusion: Machine learning-based algorithms of automatically CFS rating are feasible, and the predicted CFS is associated with the risk of all-cause death in elderly patients with HF.
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AIMS: Iron deficiency (ID) is a common co-morbidity in patients with heart failure (HF). A recent study showed that ID defined by the current guideline criteria was not associated with worse clinical outcomes, and new ID criteria was proposed in patients with HF. However, the external applicability of the new proposed criteria is unclear. We sought to investigate the applicability of the proposed ID criteria in Japanese patients with HF. METHODS AND RESULTS: We prospectively examined 763 patients with chronic HF from a Japanese multicentre registry. The proposed ID criteria were transferrin saturation (TSAT) < 20% and serum iron ≤13 mmol/L and the guideline ID criteria were serum ferritin <100 ng/mL or, when ferritin was 100-299 ng/mL, TSAT <20%. Among all patients (456 male, mean age 71 ± 13 years), 213 (28%) and 444 (58%) met the proposed and guideline ID criteria, respectively. During a median follow-up period of 436 days (interquartile range 297-565), the primary outcome of all-cause mortality occurred in 56 (7%) patients. There was no significant difference in the primary outcome between the patients with and without guideline ID criteria (P = 0.32), whereas patients with serum iron ≤10 µmol/L showed higher mortality (P = 0.002). In multivariable Cox regressions, the proposed ID criteria, but not guideline ID criteria, were independently associated with the risk of all-cause mortality (HR 2.01, 95% CI 1.16-3.51 and HR 1.32, 95% CI 0.76-2.28, respectively), even after adjustment for covariates. CONCLUSIONS: When defined by the proposed criteria and not the guideline criteria, ID was associated with higher mortality in patients with chronic HF, suggesting that the proposed ID criteria is applicable to the Japanese population.
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Anemia Ferropriva , Insuficiência Cardíaca , Deficiências de Ferro , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/complicações , Anemia Ferropriva/epidemiologia , População do Leste Asiático , Prognóstico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Ferritinas , Doença Crônica , Ferro/metabolismoRESUMO
Compounds with 3,4-fused tricyclic indole (FTI) frameworks are attractive scaffolds for drug discovery. We synthesized FTI-6D, a compound with this framework, which was cytotoxic in several human cancer cell lines. FTI-6D induced apoptosis via activation of the p53 downstream mitochondria-related apoptotic pathway, characterized by an increased ratio of pro-apoptotic Bcl-2 family members to anti-apoptotic members. This change was followed by caspase-9 and caspase-3 cleavage and activation in two cancer cell lines, RKO and AGS. The anti-proliferating effect of FTI-6D was remarkably detected in eight cancer cells with wild-type TP53 (TP53_wt), including RKO and AGS, but not in seven cancer cells with mutated TP53 (TP53_mut). Additionally, p53 protein levels increased after FTI-6D treatment in TP53_wt cancer cells, and the cytotoxic effect of FTI-6D was decreased by TP53 knockdown. Accordingly, the expression of p53 downstream genes involved in apoptotic signaling pathways, such as BBC3 and TP53INP1, and those involved in cell growth inhibition, such as CDKN1A, was upregulated in TP53_wt cancer cells. These results suggest that the anti-proliferative and apoptosis-inducing activities of FTI-6D rely on p53 and the corresponding signaling processes. This study demonstrated that FTI-6D shows anti-cancer activity against TP53_wt cancer cells. FTI-6D may have potential as a prototype compound for a new drug to utilize a functional p53 pathway in TP53_wt cancer cells.
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Neoplasias , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Genes p53 , Apoptose , Linhagem Celular Tumoral , Células HCT116 , Neoplasias/genética , Proteínas de Transporte/genética , Proteínas de Choque Térmico/metabolismoRESUMO
The interventricular septum curvature, measured in images of electrocardiogram-gated 320-slice multidetector computed tomography, is reportedly useful and less invasive than right heart catheterization, as it could provide clues regarding pulmonary arterial pressure in patients with chronic thromboembolic pulmonary hypertension. Although pulmonary endarterectomy is an efficient treatment for chronic thromboembolic pulmonary hypertension, the interventricular septum curvature in patients who have received pulmonary endarterectomy has not been evaluated. We evaluated whether the interventricular septum curvature on electrocardiogram-gated 320-slice multidetector computed tomography can predict pulmonary hemodynamics in chronic thromboembolic pulmonary hypertension even after pulmonary endarterectomy. We studied 40 patients with chronic thromboembolic pulmonary hypertension (60.5 ± 9.7 years; 30 females), who underwent pulmonary endarterectomy at Chiba University Hospital between December 2010 and July 2018. To measure the interventricular septum curvature, we prepared left ventricular short-axis tomographic images from 4D images of electrocardiogram-gated 320-slice multidetector computed tomography. We calculated the radius of interventricular septum and determined the interventricular septum curvature in both the systolic and diastolic phases. We compared the interventricular septum curvature with pulmonary hemodynamics measured by right heart catheterization before and after pulmonary endarterectomy. After pulmonary endarterectomy, the correlations of the interventricular septum curvature with mean pulmonary arterial pressure, systolic pulmonary arterial pressure, and pulmonary vascular resistance disappeared, although the interventricular septum curvature was correlated with these pulmonary hemodynamic parameters before pulmonary endarterectomy. Changes in systolic interventricular septum curvature revealed significant correlations with changes in mean pulmonary arterial pressure, systolic pulmonary arterial pressure and pulmonary vascular resistance. Diastolic interventricular septum curvature also showed significant correlations with preoperative pulmonary hemodynamics, but not with postoperative pulmonary hemodynamics. Changes in the interventricular septum curvature after pulmonary endarterectomy could estimate the efficacy of pulmonary endarterectomy, although the interventricular septum curvature after pulmonary endarterectomy showed no significant correlations with pulmonary hemodynamics. Additionally, our findings confirmed that the interventricular septum curvature before pulmonary endarterectomy could be used to evaluate the severity of disease.
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Hepatopulmonary syndrome (HPS) and pulmonary arteriovenous malformation (PAVM) are hypoxemic diseases caused by right-to-left shunting but are rarely concomitant with pulmonary hypertension (PH). A 66-year-old woman with chronic hepatitis C was scheduled to undergo liver transplantation. She was referred to our department for hypoxia and an abnormal shadow in the right lung found on a preoperative examination. She was diagnosed with HPS and a PAVM in the right middle lobe. After liver transplantation, PH temporarily developed, but the pulmonary arterial pressure normalized after coil embolization. Combined HPS and PAVM may cause unique changes in pulmonary hemodynamics during treatment.
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Malformações Arteriovenosas/complicações , Síndrome Hepatopulmonar/complicações , Hipertensão Pulmonar/complicações , Idoso , Embolização Terapêutica/métodos , Feminino , Hemodinâmica , Hepatite C Crônica/complicações , Hepatite C Crônica/cirurgia , Humanos , Hipertensão Pulmonar/terapia , Hipóxia/etiologia , Transplante de Fígado/métodosAssuntos
Antagonistas Muscarínicos/efeitos adversos , Quinuclidinas/efeitos adversos , Síncope/induzido quimicamente , Tetra-Hidroisoquinolinas/efeitos adversos , Torsades de Pointes/induzido quimicamente , Bexiga Urinária Hiperativa/tratamento farmacológico , Idoso de 80 Anos ou mais , Eletrocardiografia , Feminino , Humanos , Succinato de Solifenacina , Resultado do TratamentoRESUMO
Anomalous right coronary artery arising from the left sinus of Valsalva is a rare congenital abnormality. Percutaneous coronary intervention of the anomalous-origin right coronary artery can be challenging. Iatrogenic aorto-coronary dissection is a rare and life-threatening complication. We present a case of aortocoronary dissection that occurred during angioplasty of the anomalous-origin right coronary artery.
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Angioplastia Coronária com Balão/efeitos adversos , Anomalias dos Vasos Coronários , Vasos Coronários/lesões , Erros Médicos , Seio Aórtico/anormalidades , Seio Aórtico/lesões , Idoso , Aortografia , Angiografia Coronária , Estenose Coronária/terapia , Anomalias dos Vasos Coronários/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Humanos , Masculino , Seio Aórtico/diagnóstico por imagem , Stents , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
Left main coronary artery atresia is an extremely rare disease. Differential diagnosis of left main coronary artery atresia from atherosclerotic occlusion of left main coronary artery is difficult even if performing invasive coronary angiography. We present a case of a 48-year-old male with left main coronary artery atresia. Echocardiography showed left ventricular dysfunction. Invasive coronary angiography showed absence of left main coronary artery. A multidetector computed tomography showed a string-like structure at the site of left main coronary artery. A diagnosis of left main coronary artery atresia was made, and he underwent coronary artery bypass grafting. At the operation, a thin and not-sclerotic left main coronary artery was observed. Echocardiography, performed after the surgery, showed normalization of the left ventricular systolic function. Multidetector computed tomography might be a useful method to diagnose left main coronary artery atresia.
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Angiografia Coronária , Anomalias dos Vasos Coronários/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Ponte de Artéria Coronária , Anomalias dos Vasos Coronários/cirurgia , Ecocardiografia , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular Esquerda/cirurgiaRESUMO
We report a case of internal mammary artery graft dissection. Cardiac catheterization showed a spiral dissection in the anastomotic site of internal mammary artery graft with TIMI 3 flow. Percutaneous stenting for native coronary artery lesions was performed. Cardiac catheterization, performed 2 years after the stenting, showed no change in the internal mammary artery dissection. This is the first case of unhealed chronic dissection of internal mammary artery graft.
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Dissecção Aórtica/diagnóstico , Artéria Torácica Interna/patologia , Transplantes , Dissecção Aórtica/cirurgia , Doença Crônica , Feminino , Humanos , Artéria Torácica Interna/cirurgia , Pessoa de Meia-Idade , Transplantes/efeitos adversosRESUMO
Mechanical stress by pressure overload due to hypertension or valvular heart disease such as aortic valve stenosis induces cardiac hypertrophy. It has been well established that the mechanical stretch of cardiac myocytes in vitro induces hypertrophic responses such as the expression of immediate early response genes including c-fos. However, it remains uncertain whether the mechanical forces due to pure atmospheric pressure can induce similar responses in cardiac myocytes. We thus cultured rat neonatal cardiac myocytes in an atmospheric pressure chamber apparatus and determined the effects of pure pressure stress on c-fos gene expression. Pressures greater than 80 mmHg enhanced c-fos mRNA after 30 minutes. These results suggest that pure atmospheric pressure overload can also induce early hypertrophic responses in cardiac myocytes.
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Cardiomegalia/genética , Regulação da Expressão Gênica no Desenvolvimento , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , RNA Mensageiro/genética , Animais , Animais Recém-Nascidos , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Células Cultivadas , Modelos Animais de Doenças , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-fos/biossíntese , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: There are few biological markers, which strictly show the severity of congestive heart failure (CHF). METHODS AND RESULTS: Lymphocyte G-protein coupled receptor kinase (GRK) mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction in 15 CHF patients: 5 patients classified as New York Heart Association class-II treated with angiotensin converting enzyme inhibitor (ACEI) (IIA), 5 patients in class-II without ACEI (IIC), and 5 patients in class-III treated with ACEI (IIIA). GRK mRNA level in IIIA was significantly higher than those in IIA (p<0.05). GRK mRNA level in IIA were significantly lower than those in IIC (p<0.05). CONCLUSIONS: The expression level of lymphocyte GRK might show the severity of CHF, and ACEI treatment could reduce the level of GRK in CHF patients.
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Inibidores da Enzima Conversora de Angiotensina/farmacologia , Receptor Quinase 1 Acoplada a Proteína G/genética , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Insuficiência Cardíaca/enzimologia , Insuficiência Cardíaca/genética , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Biomarcadores/sangue , Feminino , Receptor Quinase 1 Acoplada a Proteína G/análise , Receptor Quinase 1 Acoplada a Proteína G/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Linfócitos/química , Linfócitos/enzimologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/análise , RNA Mensageiro/genética , Receptores Adrenérgicos beta/efeitos dos fármacos , Receptores Adrenérgicos beta/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Enhanced expression of G protein-coupled receptor kinase (GRK) has been reported in failing hearts and in the present study the stability of enhanced GRK mRNA expression, and the correlation between the expression level of GRK mRNA in peripheral lymphocytes and in the heart were both evaluated. METHODS AND RESULTS: Isoproterenol was injected into rats for 2 weeks, and then GRK5 mRNA was assessed by quantitative reverse transcriptase-palymerase chain reaction. An enhanced expression of cardiac GRK5 mRNA was observed even after 4 weeks of recovery. The isoproterenol-induced increased expression of GRK2 and GRK5 mRNA was equally observed in the heart and lymphocytes, and there was a close correlation between the heart and lymphocytes in the level of expression of each GRK mRNA. CONCLUSIONS: The GRK mRNA level is maintained at a high level for a long period without continuous beta-adrenergic receptor stimulation. The level in circulating lymphocytes could be used as a surrogate marker to estimate the level of cardiac GRK expression and, presumably, the beta-adrenergic receptor function of cardiomyocytes.
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Agonistas Adrenérgicos beta/administração & dosagem , Proteínas Quinases Dependentes de AMP Cíclico/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Isoproterenol/administração & dosagem , Linfócitos/metabolismo , Miocárdio/metabolismo , Proteínas Serina-Treonina Quinases/biossíntese , Animais , Proteínas Quinases Dependentes de AMP Cíclico/genética , Quinase 5 de Receptor Acoplado a Proteína G , Masculino , Miócitos Cardíacos/metabolismo , Proteínas Serina-Treonina Quinases/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Receptores Adrenérgicos beta/metabolismo , Quinases de Receptores Adrenérgicos betaRESUMO
Immature vascular smooth muscle cells (VSMCs) proliferate responding to extrinsic mitogens and accumulate in neointima after arterial injuries. Cell proliferation is positively regulated by cyclin/cyclin-dependent kinase (CDK) complex and negatively controlled by CDK inhibitors; CKIs such as p27(kip1) and p57(kip2). In this study, embryonic rat thoracic aorta VSMCs; A10 were G0/G1 arrested by serum starvation, re-stimulated with serum, and harvested every four hours. Both CKIs co-expressed in quiescent VSMCs and rapidly diminished by stimulation. Protein level of p27(kip1) was regulated by both transcription and post-transcription, but that of p57(kip2) was mainly by post-transcription. Supplemental overexpression of p57(kip2) inhibited the activations of G1 cyclin/CDKs and subsequent hyperphosphorylations of all three retinoblastoma pocket proteins as well as G1/S transition of cell cycle. Our findings suggest that the downregulations of not only p27(kip1), but also p57(kip2) responding to mitogenic stimulation, play key roles in the cell cycle progression of VSMCs.
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Ciclo Celular/fisiologia , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Regulação para Baixo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Animais , Células Cultivadas , Ciclina G , Ciclina G1 , Inibidor de Quinase Dependente de Ciclina p57/genética , Ciclinas/metabolismo , Regulação Enzimológica da Expressão Gênica , Ligação Proteica , RNA Mensageiro/genética , Ratos , SoroRESUMO
BACKGROUND: Animal models are indispensable in order to investigate the mechanism of various diseases and to explore the counter measures for those disease states. Although there are several animal models of ischemic heart diseases, surgical interventions required to create myocardial ischemia sometimes give rise to a problem in the yield of model. This study describes a new technique for inducing myocardial ischemia in rats. METHODS AND RESULTS: A 0.014-inch guidewire was introduced via the carotid artery and selectively advanced into the coronary arteries under fluoroscopy. Transmural myocardial ischemia was confirmed by ST-segment elevation and by the appearance of left ventricular wall motion abnormalities on the echocardiogram. Reversibility of the wire-induced myocardial ischemia was demonstrated by complete resolution of both ST-segment elevation and wall motion abnormalities after removing the wire. CONCLUSION: Wire-induced myocardial ischemia was reproducible and is less invasive than conventional ischemic models in rats. This method is a powerful and useful tool for the investigation of ischemic heart disease in small animals.