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1.
Lancet ; 404(10450): 377-392, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39067905

RESUMO

First described more than 350 years ago, infective endocarditis represents a global health concern characterised by infections affecting the native or prosthetic heart valves, the mural endocardium, a septal defect, or an indwelling cardiac device. Over recent decades, shifts in causation and epidemiology have been observed. Echocardiography remains pivotal in the diagnosis of infective endocarditis, with alternative imaging modalities gaining significance. Multidisciplinary management requiring expertise of cardiologists, cardiovascular surgeons, infectious disease specialists, microbiologists, radiologists and neurologists, is imperative. Current recommendations for clinical management often rely on observational studies, given the limited number of well conducted randomised controlled trials studying infective endocarditis due to the rarity of the disease. In this Seminar, we provide a comprehensive overview of optimal clinical practices in infective endocarditis, highlighting key aspects of pathophysiology, pathogens, diagnosis, management, prevention, and multidisciplinary approaches, providing updates on recent research findings and addressing remaining controversies in diagnostic accuracy, prevention strategies, and optimal treatment.


Assuntos
Endocardite , Humanos , Endocardite/diagnóstico , Endocardite/terapia , Endocardite/epidemiologia , Ecocardiografia , Antibacterianos/uso terapêutico
2.
Clin Transplant ; 38(4): e15304, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38591111

RESUMO

INTRODUCTION: This study aimed to compare postoperative outcomes after cardiac surgery in solid-organ transplant recipients and nontransplant patients. METHODS: We performed a retrospective analysis of 78 consecutive transplant recipients who underwent cardiac surgery at Asan Medical Center between 2000 and 2022 and were matched with 312 nontransplant patients who underwent cardiac surgery at a 1:4 ratio. The outcomes included 30-day mortality, all-cause death, cardiac death, readmission, and cardiac readmission. RESULTS: There was no significant difference in baseline characteristics between the two groups. The most common type of cardiac surgery performed in solid organ transplant recipients was isolated valve surgery, followed by isolated CABG. The 30-day mortality was not significantly different between transplant recipients and nontransplant patients (3.9% vs. 3.5%; P > .99). Solid organ transplant recipients showed a higher all-cause mortality compared to nontransplant patients (29.1% vs. 14.3% at 5 years; P = .001); however, there was no significant difference in cardiac death between the two groups (2.6% vs. 3.2% at 5 years; P = .80). In addition, the readmission and cardiac readmission rates showed comparable findings to that of mortality. CONCLUSION: Cardiac surgery can be performed safely in solid organ transplant recipients, with postoperative cardiovascular outcomes comparable to those observed in nontransplant patients.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Transplante de Órgãos , Humanos , Estudos Retrospectivos , Transplantados , Análise por Pareamento , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Transplante de Órgãos/efeitos adversos
3.
Artigo em Inglês | MEDLINE | ID: mdl-38719137

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 (CT) 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 CT 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 CT 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.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38442916

RESUMO

BACKGROUND: As redo surgical aortic valve replacement (AVR) is relatively high risk, valve-in-valve transcatheter AVR has emerged as an alternative for failed prostheses. However, the majority of studies are outdated. This study assessed the current clinical outcomes of redo AVR. METHODS AND RESULTS: This study enrolled 324 patients who underwent redo AVR due to prosthetic valve failure from 2010 to 2021 in four tertiary centers. The primary outcome was operative mortality. The secondary outcomes were overall survival, cardiac death, and aortic valve-related events. Logistic regression analysis, clustered Cox proportional hazards models, and competing risk analysis were used to evaluate the independent risk factors. Redo AVR was performed in 242 patients without endocarditis and 82 patients with endocarditis. Overall operative mortality was 4.6% (15 deaths). Excluding patients with endocarditis, the operative mortality of redo AVR decreased to 2.5%. Multivariate analyses demonstrated that endocarditis (hazard ratio [HR]: 3.990, p = 0.014), longer cardiopulmonary bypass time (HR: 1.006, p = 0.037), and lower left ventricular ejection fraction (LVEF) (HR: 0.956, p = 0.034) were risk factors of operative mortality. Endocarditis and lower LVEF were independent predictors of overall survival. CONCLUSION: The relatively high risk of redo AVR was due to reoperation for prosthetic valve endocarditis. The outcomes of redo AVR for nonendocarditis are excellent. Our findings suggest that patients without endocarditis, especially with acceptable LVEF, can be treated safely with redo AVR.

5.
Molecules ; 29(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38257395

RESUMO

Autophagy is a pivotal biological process responsible for maintaining the homeostasis of intracellular organelles. Yet the molecular intricacies of peroxisomal autophagy (pexophagy) remain largely elusive. From a ubiquitin-related chemical library for screening, we identified several inhibitors of the Von Hippel-Lindau (VHL) E3 ligase, including VH298, thereby serving as potent inducers of pexophagy. In this study, we observed that VH298 stimulates peroxisomal degradation by ATG5 dependently and escalates the ubiquitination of the peroxisomal membrane protein ABCD3. Interestingly, the ablation of NBR1 is similar to the curtailed peroxisomal degradation in VH298-treated cells. We also found that the pexophagy induced by VH298 is impeded upon the suppression of gene expression by the translation inhibitor cycloheximide. Beyond VHL inhibition, we discovered that roxadustat, a direct inhibitor of HIF-α prolyl hydroxylase, is also a potent inducer of pexophagy. Furthermore, we found that VH298-mediated pexophagy is blocked by silencing HIF-1α. In conclusion, our findings suggest that VH298 promotes pexophagy by modulating VHL-mediated HIF-α transcriptional activity.


Assuntos
Autofagia , Ciclopropanos , Macroautofagia , Pirrolidinas , Tiazóis , Humanos , Células HeLa , Homeostase , Proteína Supressora de Tumor Von Hippel-Lindau/genética
6.
J Surg Res ; 285: 236-242, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36709542

RESUMO

BACKGROUND: As life span increases, in patients having a bioprosthetic valve, the development of hemodynamic valve deterioration (HVD) is an important concern. We evaluated the association of developing HVD to survival in patients undergoing surgical aortic valve replacement (SAVR). METHODS: The individuals undergoing isolated SAVR and serial echocardiography exams (interval >30 d) were included in this study. HVD was defined as mean pressure gradient ≥ 20 mmHg, mean pressure gradient ≥10 mmHg higher than in the baseline exam, or more than moderate regurgitation on Doppler echocardiography (moderate and severe grade). A time-dependent Cox proportional hazard model was used for this study. RESULTS: A total of 631 patients were included. The mean age was 71.8 ± 6.1 y old (female: 53.6%). HVD was found in 259 patients (41%) during echocardiographic follow-up (mean 3.3 ± 3.0 y). Patient-prosthetic mismatch was found in 174 patients. One hundred and twenty-six patients died during follow-up (median 62.1 mo, interquartile range 31.1-96.8). The development of HVD was an independent risk factor for death during follow-up (P = 0.038, hazard ratio 1.46, 95% confidential interval: 1.02-2.08). CONCLUSIONS: HVD was common after bioprosthetic SAVR during mid-term follow-up. Developing HVD, including moderate and severe grades, was associated with a poor survival rate compared with patients without HVD.


Assuntos
Estenose da Valva Aórtica , Bioprótese , Implante de Prótese de Valva Cardíaca , Humanos , Feminino , Idoso , Valva Aórtica/cirurgia , Resultado do Tratamento , Hemodinâmica , Desenho de Prótese
7.
Biochem Biophys Res Commun ; 545: 69-74, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33545634

RESUMO

Peroxisomes play an essential role in cellular homeostasis by regulating lipid metabolism and the conversion of reactive oxygen species (ROS). Several peroxisomal proteins, known as peroxins (PEXs), control peroxisome biogenesis and degradation. Various mutations in the PEX genes are genetic causes for the development of inheritable peroxisomal-biogenesis disorders, such as Zellweger syndrome. Among the peroxins, PEX1 defects are the most common mutations in Zellweger syndrome. PEX1 is an AAA-ATPase that regulates the recycling of PEX5, which is essential for importing peroxisome matrix proteins. However, the post-transcriptional regulation of PEX1 is largely unknown. Here, we showed that heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) controls PEX1 expression. In addition, we found that depletion of HNRNPA1 induces autophagic degradation of peroxisome, which is blocked in ATG5-knockout cells. In addition, depletion of HNRNPA1 increased peroxisomal ROS levels. Inhibition of the generation of peroxisomal ROS by treatment with NAC significantly suppressed pexophagy in HNRNPA1-deficient cells. Taken together, our results suggest that depletion of HNRNPA1 increases peroxisomal ROS and pexophagy by downregulating PEX1 expression.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/metabolismo , Ribonucleoproteína Nuclear Heterogênea A1/metabolismo , Macroautofagia/fisiologia , Proteínas de Membrana/metabolismo , Peroxissomos/metabolismo , ATPases Associadas a Diversas Atividades Celulares/genética , Proteína 5 Relacionada à Autofagia/antagonistas & inibidores , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Células Cultivadas , Regulação para Baixo , Técnicas de Inativação de Genes , Células HCT116 , Células HeLa , Ribonucleoproteína Nuclear Heterogênea A1/deficiência , Ribonucleoproteína Nuclear Heterogênea A1/genética , Humanos , Macroautofagia/genética , Proteínas de Membrana/genética , Processamento Pós-Transcricional do RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Síndrome de Zellweger/genética , Síndrome de Zellweger/metabolismo
8.
J Korean Med Sci ; 36(9): e57, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686809

RESUMO

BACKGROUND: We compared early and 2-year clinical outcomes of sutureless aortic valve replacement (SAVR) with conventional aortic valve replacement (CAVR) in a nationwide study based on claims data. METHODS: From December 2016 to November 2018, 3,173 patients underwent bioprosthetic aortic valve replacements. SAVR and CAVR were performed in 641 and 2,532 patients, respectively. Propensity score-matched analysis was performed in 640 patient pairs. RESULTS: Operative mortality rate was 2.8% without significant differences between the SAVR (3.4%) and CAVR (2.3%) groups (P = 0.324). There were no significant differences in postoperative morbidities between the groups except for permanent pacemaker (PPM) implantation. PPM implantation rate was significantly higher in the SAVR (3.8%) than in the CAVR group (0.9%) (P < 0.001). One- and two-year overall survival was 89.1% and 87.5%, respectively, without significant differences between the groups (SAVR group vs. CAVR grouP = 89.9% and 90.5% vs. 87.2% and 88.7%, respectively; P = 0.475). There were no significant differences in the cumulative incidence of cardiac death, stroke, aortic valve reoperation and infective endocarditis between the groups. Cumulative PPM implantation incidence at 6 months in the CAVR was 1.1%, and no patient required PPM implantation after 6 months. In the SAVR, the cumulative PPM implantation incidence at 0.5, one, and two years was 3.9%, 5.0% and 5.6%, respectively. The cumulative PPM implantation rate was higher in the SAVR group than in the CAVR group (P < 0.001). CONCLUSION: Early and 2-year clinical outcomes between SAVR and CAVR were not different except for a high rate of permanent pacemaker implantation in the SAVR group.


Assuntos
Valvopatia Aórtica/cirurgia , Próteses Valvulares Cardíacas/estatística & dados numéricos , Procedimentos Cirúrgicos sem Sutura/métodos , Idoso , Idoso de 80 Anos ou mais , Valvopatia Aórtica/mortalidade , Bioprótese/estatística & dados numéricos , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Marca-Passo Artificial/estatística & dados numéricos , Complicações Pós-Operatórias , Pontuação de Propensão , República da Coreia , Taxa de Sobrevida , Resultado do Tratamento
9.
J Card Surg ; 36(10): 3711-3718, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34310744

RESUMO

BACKGROUND AND AIM OF THE STUDY: Although dopamine and norepinephrine are recommended as first-line agents in the treatment of shock, it is unclear which is the optimal vasoactive inotropic agent (VIA) to manage postcardiotomy circulatory shock. This single-center, randomized clinical trial aimed to investigate the efficacy and safety of dopamine versus norepinephrine in postcardiotomy circulatory shock. METHODS: We randomly assigned the patients with postcardiotomy circulatory shock to receive either dopamine or norepinephrine. When shock persisted despite the dose of 20 µg/kg/min of dopamine or the dose of 0.2 µg/kg/min of norepinephrine, epinephrine or vasopressin could be added. The primary endpoint was new-onset tachyarrhythmic event during drug infusion. Secondary endpoints included requirement of additional VIAs, postoperative complications, and all-cause mortality within 30 days of drug initiation. RESULTS: At the planned interim analysis of 100 patients, the boundary for the benefit of norepinephrine has been crossed, and the study was stopped early. Excluding two patients withdrawing a consent, 48 patients were assigned to dopamine and 50 patients to norepinephrine. New-onset tachyarrhythmic event occurred in 12 (25%) patients in the dopamine and one (2%) patient in the norepinephrine group (p = .009). The requirement for additional VIAs was more common in the dopamine group (p < .001). Other secondary endpoints were similar between groups. CONCLUSIONS: Despite the limited study subjects with early determination, in patients with postcardiotomy circulatory shock, dopamine as a first-line vasopressor was associated with higher tachyarrhythmic events and greater need for additional VIAs compared with norepinephrine.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Choque Séptico , Choque , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Dopamina , Humanos , Norepinefrina , Choque/tratamento farmacológico , Choque/etiologia , Choque Séptico/tratamento farmacológico , Vasoconstritores , Vasopressinas
10.
Int J Mol Sci ; 22(20)2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34681602

RESUMO

Particulate matters (PMs) increase oxidative stress and inflammatory response in different tissues. PMs disrupt the formation of primary cilia in various skin cells, including keratinocytes and melanocytes. In this study, we found that 2-isopropylmalic acid (2-IPMA) promoted primary ciliogenesis and restored the PM2.5-induced dysgenesis of primary cilia in dermal fibroblasts. Moreover, 2-IPMA inhibited the generation of excessive reactive oxygen species and the activation of stress kinase in PM2.5-treated dermal fibroblasts. Further, 2-IPMA inhibited the production of pro-inflammatory cytokines, including IL-6 and TNF-α, which were upregulated by PM2.5. However, the inhibition of primary ciliogenesis by IFT88 depletion reversed the downregulated cytokines by 2-IPMA. Moreover, we found that PM2.5 treatment increased the MMP-1 expression in dermal fibroblasts and a human 3-D-skin model. The reduced MMP-1 expression by 2-IPMA was further reversed by IFT88 depletion in PM2.5-treated dermal fibroblasts. These findings suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in dermal fibroblasts.


Assuntos
Citocinas/metabolismo , Ativação Enzimática/efeitos dos fármacos , Malatos/farmacologia , Metaloproteinase 1 da Matriz/metabolismo , Técnicas de Cultura de Células , Linhagem Celular , Cílios/metabolismo , Cílios/patologia , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Interleucina-6/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Metaloproteinase 1 da Matriz/genética , Modelos Biológicos , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/toxicidade , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Regulação para Cima/efeitos dos fármacos
11.
Molecules ; 26(17)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34500843

RESUMO

Primary cilia mediate the interactions between cells and external stresses. Thus, dysregulation of primary cilia is implicated in various ciliopathies, e.g., degeneration of the retina caused by dysregulation of the photoreceptor primary cilium. Particulate matter (PM) can cause epithelium injury and endothelial dysfunction by increasing oxidative stress and inflammatory responses. Previously, we showed that PM disrupts the formation of primary cilia in retinal pigment epithelium (RPE) cells. In the present study, we identified 2-isopropylmalic acid (2-IPMA) as a novel inducer of primary ciliogenesis from a metabolite library screening. Both ciliated cells and primary cilium length were increased in 2-IPMA-treated RPE cells. Notably, 2-IPMA strongly promoted primary ciliogenesis and restored PM2.5-induced dysgenesis of primary cilia in RPE cells. Both excessive reactive oxygen species (ROS) generation and activation of a stress kinase, JNK, by PM2.5 were reduced by 2-IPMA. Moreover, 2-IPMA inhibited proinflammatory cytokine production, i.e., IL-6 and TNF-α, induced by PM2.5 in RPE cells. Taken together, our data suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in RPE cells.


Assuntos
Inflamação/metabolismo , Material Particulado/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Cílios/metabolismo , Cílios/ultraestrutura , Citocinas/metabolismo , Ativação Enzimática , Técnicas de Silenciamento de Genes , Humanos , MAP Quinase Quinase 4/metabolismo , Malatos/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Retina
12.
J Vasc Surg ; 72(4): 1288-1297, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32723689

RESUMO

BACKGROUND: Patients presenting with descending aortic aneurysms developing after aortic dissection often undergo continued aortic expansion which may require operative interventions to address the risk of aortic rupture. In light of the current advances in various treatment options, including endovascular approaches, we analyzed our experience with open surgical repair (OSR) of aneurysms of the descending aorta following aortic dissection. METHODS: Patients who underwent open repair for aneurysmal changes of the descending aorta after chronic dissection were retrospectively studied. The 30-day operative mortality rate, midterm survival, and major complications were analyzed. Patients were divided into two categories; primary chronic type B aortic dissection and remnant repaired type A aortic dissection (RTAAD). RESULTS: There were 149 patients with enlargement of the descending thoracic aorta developing after aortic dissection. Of these, 49 patients had medical management, while the remaining 100 patients received OSR. These patients were included in the present analysis. The 30-day mortality and permanent paraplegia rates were 9% and 4%, respectively. The 1-, 3-, and 5-year survival rates were 83%, 80.9%, and 76.1%, respectively. The 1- and 5-year survival rates between the primary chronic type B aortic dissection and remnant RTAAD groups showed no significant between-group differences at 86.7% and 84.3%, and 80% and 71.3%, respectively (P = .289). The overall outcomes of other complications such as renal injury, bleeding reoperation, and extracorporeal membrane oxygenation support showed no significant between-group differences, including an insignificantly higher neurologic complication rate in the remnant RTAAD group. The survival rate in patients with Marfan syndrome was significantly higher than in the patients without Marfan syndrome (P = .033). CONCLUSIONS: OSR for descending aortic aneurysms developing after chronic aortic dissection showed good early and mid- to long-term outcomes, with acceptably low complication rates. OSR for descending aortic aneurysm after chronic aortic dissection associated with Marfan syndrome also showed good early and mid- to long-term outcomes.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Síndrome de Marfan/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Dissecção Aórtica/etiologia , Dissecção Aórtica/mortalidade , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/mortalidade , Implante de Prótese Vascular/métodos , Doença Crônica/mortalidade , Doença Crônica/terapia , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Síndrome de Marfan/complicações , Síndrome de Marfan/mortalidade , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
13.
Eur Heart J ; 40(32): 2727-2736, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31220232

RESUMO

AIMS: To evaluate the acute and long-term prognosis of acute aortic syndrome (AAS) according to the disease entity [intramural haematoma (IMH) vs. aortic dissection (AD)] and the anatomical location (type A vs. B). METHODS AND RESULTS: A total of 1012 patients [672 with AD and 340 with IMH (33.6%)] were enrolled between 1993 and 2015. Compared with AD patients, IMH patients were older and had higher frequency of female sex and distal aorta involvement. The overall crude in-hospital mortality of AAS was 8.6%; type A AD [15.0%; adjusted hazard ratio (aHR) 30.4; 95% confidence interval (CI) 8.62-107.3; P < 0.001], type A IMH (8.0%; aHR 4.85; 95% CI 1.29-18.2; P = 0.019), type B AD (5.0%; aHR 3.51; 95% CI 1.00-12.4; P = 0.051), and type B IMH [1.5%; aHR 1.00 (reference)]. During a median follow-up duration of 8.5 years (interquartile range: 4.0-13.5 years), AD (aHR 2.78; 95% CI 1.87-4.14; P < 0.001) and type A (aHR 2.28; 95% CI 1.45-3.58; P < 0.001) was associated with a higher risk of aortic death. After 90 days, a risk of aortic death was no longer associated with anatomical location (aHR 0.74; 95% CI 0.40-1.36; P = 0.33), but remained associated with disease entity (aHR 1.83; 95% CI 1.10-3.04; P = 0.02). CONCLUSION: The clinical features, response to treatment strategy, and outcomes of IMH patients were distinct from those of AD patients. Both early and late survival was better for IMH than for AD. In addition to the anatomical location of AAS, the disease entity is an independent factor associated with both acute and long-term mortality in patients with AAS. Further investigation is necessary to confirm the prognostic implication of disease entity in different patient populations.


Assuntos
Doenças da Aorta , Dissecção Aórtica , Hematoma , Idoso , Dissecção Aórtica/classificação , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/mortalidade , Doenças da Aorta/classificação , Doenças da Aorta/diagnóstico , Doenças da Aorta/mortalidade , Feminino , Hematoma/classificação , Hematoma/diagnóstico , Hematoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
14.
Clin Anat ; 33(1): 117-123, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31576608

RESUMO

Current knowledge of the aortic root geometric anatomy and its surgical implications remain limited. We analyzed multiple predefined parameters of the aortic root to increase our understanding of the geometric changes that occur in normal and aneurysmal transformations. Between November 2003 and September 2015, the aortic roots of 107 healthy subjects (control group) and 105 annuloaortic ectasia (AAE) patients (AAE group) were analyzed using multiplanar reformatted computed tomographic images. The intercommissural distance (ICD), sinus width (SW), and sinus volume (SV) of the left (LCS), right (RCS), and noncoronary sinuses (NCS) of Valsalva were adopted as study parameters. In the control group, all study parameters of the LCS were smaller than those of the RCS and the NCS. In the AAE group, all parameters of the LCS were significantly smaller than those of the RCS or NCS, but the RCS and NCS parameters were similar. Proportionately less LCS enlargement relative to either the RCS or NCS was observed in root aneurysm(AAE group) than in the control group. We observed a distinct aortic root geometric pattern which was characterized by the LCS being smaller than either the RCS or NCS, while the latter were similar. This geometric configuration was significantly accentuated in AAE patients due to the greater disproportionate disparity in the LCS relative to either the RCS or NCS than in the roots of normal control subjects. Clin. Anat. 32:117-123, 2019. © 2019 Wiley Periodicals, Inc.


Assuntos
Aneurisma da Aorta Torácica/diagnóstico por imagem , Valva Aórtica/diagnóstico por imagem , Seio Aórtico/diagnóstico por imagem , Adulto , Idoso , Valva Aórtica/anatomia & histologia , Estudos de Casos e Controles , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador , Seio Aórtico/anatomia & histologia , Tomografia Computadorizada por Raios X
15.
Biochem Biophys Res Commun ; 516(3): 713-718, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31253394

RESUMO

Mitochondria are essential for providing the energy necessary for neuronal function. Dysregulation of mitochondrial dynamics has been linked with the pathogenesis of many neurodegenerative diseases. Dynamin related protein 1 (Drp1) participates in fission activity in the mitochondria, and post-translational modifications to Drp1 modulate complex mitochondrial dynamics. However, the regulation of Drp1 at the post-transcriptional level remains poorly understood. In this study, we found that the RNA-binding protein Hu antigen R (HuR) post-transcriptionally regulates Drp1 expression. HuR interacts with Drp1 mRNA at its 3' untranslated region. Depletion of HuR reduces Drp1 expression, which leads to mitochondrial elongation in SH-SY5Y neuroblastoma cells. In contrast, ectopic expression of HuR enhances Drp1 expression, which promotes mitochondrial fragmentation in response to treatment with the mitochondrial complex 1 inhibitor MPP+. In addition, depletion of HuR suppressed the generation of mitochondrial ROS and cytotoxicity in MPP+ treated cells. Taken together, these findings suggest that HuR controls mitochondrial morphology via regulation of Drp1.


Assuntos
Dinaminas/genética , Proteína Semelhante a ELAV 1/genética , Regulação Neoplásica da Expressão Gênica , Mitocôndrias/genética , Dinâmica Mitocondrial/genética , Proteínas de Ligação a RNA/genética , 1-Metil-4-fenilpiridínio/farmacologia , Regiões 3' não Traduzidas/genética , Linhagem Celular Tumoral , Dinaminas/metabolismo , Proteína Semelhante a ELAV 1/metabolismo , Herbicidas/farmacologia , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Ligação Proteica , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo
16.
Circ J ; 81(6): 806-814, 2017 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-28344200

RESUMO

BACKGROUND: New-onset diabetes mellitus (DM) can occur as a serious complication after heart transplantation, but the comparative data on its clinical impact on survival and on transplant-related adverse events are limited.Methods and Results:We reviewed a total of consecutive 391 patients aged ≥17 years undergoing isolated orthotopic heart transplantation at the present institution from 1992 to 2013. The entire cohort was divided into 3 groups: (1) no diabetes (n=257); (2) pre-existing DM (n=46); and (3) new-onset DM (n=88). Early and long-term clinical outcomes were compared across the 3 groups. Early death occurred in 8 patients (2.0%). Of the 345 non-diabetic patients before transplantation, 88 (25.5%) developed new-onset DM postoperatively. During follow-up, 83 (21.2%) died. On time-varying Cox analysis, new-onset DM was associated with increased risk for overall death (HR, 2.11; 95% CI: 1.26-3.55) and tended to have a greater risk for severe chronic kidney disease (HR, 1.77; 95% CI: 0.94-3.44). Compared with the no-diabetes group, the new-onset DM group had a worse survival rate (P=0.035), but a similar survival rate to that of the pre-existing DM group (P=0.364). CONCLUSIONS: New-onset DM has a negative effect on long-term survival and kidney function after heart transplantation. Further studies are warranted to evaluate the relevance of early diagnosis and timely control of new-onset DM to improve long-term survival.


Assuntos
Diabetes Mellitus/etiologia , Diabetes Mellitus/mortalidade , Transplante de Coração , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/mortalidade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
17.
Circulation ; 132(17): 1620-9, 2015 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-26338955

RESUMO

BACKGROUND: Current practice guidelines recommend surgical repair of large thoracic aortic aneurysms to prevent fatal aortic dissection or rupture, but limited natural history data exist to support clinical criteria for timely intervention. METHODS AND RESULTS: Of 3247 patients with thoracic aortic aneurysm registered in our institutional Thoracic Aortic Center Database, we identified and reviewed 257 nonsyndromic patients (age, 72.4±10.5 years; 143 female) with descending thoracic or thoracoabdominal aortic aneurysm without a history of aortic dissection in whom surgical intervention was not undertaken. The primary end point was a composite of aortic dissection/rupture and sudden death. Baseline mean maximal aortic diameter was 52.4±10.8 mm, with 103 patients having diameters ≥55 mm. During a median follow-up of 25.1 months (quartiles 1-3, 8.3-56.4 months), definite and possible aortic events occurred in 19 (7.4%) and 31 (12.1%) patients, respectively. On multivariable analyses, maximal aortic diameter at baseline emerged as the only significant predictor of aortic events (hazard ratio=1.12; 95% confidence interval, 1.08-1.15). Estimated rates of definite aortic events within 1 year were 5.5%, 7.2%, and 9.3% for aortic diameters of 50, 55, and 60 mm, respectively. Receiver-operating characteristic curves for discriminating aortic events were higher for indexed aortic sizes referenced by body size (area under the curve=0.832-0.889) but not significantly different from absolute maximal aortic diameter (area under the curve=0.805). CONCLUSIONS: Aortic size was the principal factor related to aortic events in unrepaired descending thoracic or thoracoabdominal aortic aneurysm. Although the risk of aortic events started to increase with a diameter >5.0 to 5.5 cm, it is uncertain whether repair of thoracic aortic aneurysms in this range leads to overall benefit, and the threshold for repair requires further evaluation.


Assuntos
Aorta Torácica/ultraestrutura , Aneurisma da Aorta Torácica/epidemiologia , Dissecção Aórtica/epidemiologia , Ruptura Aórtica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/patologia , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/patologia , Aneurisma da Aorta Torácica/cirurgia , Doenças da Aorta/epidemiologia , Ruptura Aórtica/patologia , Ruptura Aórtica/cirurgia , Aterosclerose/epidemiologia , Bases de Dados Factuais , Morte Súbita/epidemiologia , Morte Súbita/etiologia , Diabetes Mellitus/epidemiologia , Dilatação Patológica/epidemiologia , Feminino , Seguimentos , Humanos , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Curva ROC , Risco , Fumar/epidemiologia
18.
Circulation ; 130(11 Suppl 1): S39-44, 2014 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-25200054

RESUMO

BACKGROUND: Optimal management strategy of acute aortic dissection (AD) with retrograde extension from entry tear in the descending aorta into the ascending aorta remains undetermined. METHODS AND RESULTS: Of the 538 patients who were diagnosed as having acute AD from 1999 through 2011, 49 patients (37 men; 52.5±13.1 years) were identified as having entry tear in the descending aorta with retrograde extension of AD into the ascending aorta. Sixteen patients who were clinically stable with thrombosed false lumen in the ascending aorta were treated medically (MED group), whereas 33 patients underwent aortic replacement (SURG group) on an intention-to-treat basis. In the MED group, 1 patient was converted to urgent aortic surgery and 2 patients underwent endovascular stent grafting in the descending aorta during the initial hospitalization. The early (30-day or in-hospital) mortality rates were 0% and 9.1% in the MED and SURG group, respectively (P=0.54). Follow-up was complete in all patients (median, 61.4 months; Q1-Q3, 28.2-99.1 months). The 5-year 100% survival rate in the MED group was higher than that in the SURG group (81.2±7.0%; P=0.080), in the surgically treated patients with antegrade type A AD (74.5±2.8%; P=0.038), and in the patients with type B AD (75.3±3.3%; P=0.045). Aortic event-free survival at 5 years was 52.7±14.8% and 69.6±8.0% in the MED and SURG groups, respectively (P=0.98). CONCLUSIONS: Patients with acute retrograde type A AD showed a more favorable prognosis than patients with antegrade AD. In selected patients with retrograde type A AD, excellent outcomes could be achieved with initial medical management combined with timely interventions.


Assuntos
Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Ruptura Aórtica/cirurgia , Doença Aguda , Adulto , Idoso , Aorta/patologia , Doenças da Aorta/etiologia , Implante de Prótese Vascular , Procedimentos Cirúrgicos Cardíacos , Ponte Cardiopulmonar , Causas de Morte , Intervalo Livre de Doença , Emergências , Procedimentos Endovasculares , Feminino , Seguimentos , Mortalidade Hospitalar , Humanos , Hipotermia Induzida , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Stents , Trombose/etiologia , Resultado do Tratamento
19.
Radiology ; 276(3): 724-31, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25902187

RESUMO

PURPOSE: To investigate the cardiac computed tomographic (CT) findings and clinical implications of subprosthetic pannus in patients who have undergone aortic valve replacement. MATERIALS AND METHODS: The institutional review board approved this retrospective study, and the need to obtain written informed consent was waived. From April 2011 to March 2012, 88 patients (mean age, 63 years; 45 men) with a prosthetic aortic valve who underwent cardiac CT were retrospectively selected. Dynamic cardiac CT images were analyzed by using a multiplanar reformatted technique. The presence or absence of subprosthetic pannus and its extent were evaluated at cardiac CT. The geometric orifice area and the effective orifice area of each prosthetic valve were measured to enable analysis of the pannus encroachment ratio in the systolic phase. Hemodynamic parameters at echocardiography, including mean transprosthetic pressure gradient (MTPG), were compared between patients with and those without pannus. The encroachment ratio and the MTPG were correlated by using the Spearman test to evaluate the relationship between the two variables. RESULTS: Seventeen patients (19%) had subprosthetic pannus at cardiac CT. In patients with subprosthetic pannus, MTPG, peak pressure gradient, transvalvular peak velocity, and left ventricular ejection fraction (LVEF) were significantly higher than in patients without pannus (MTPG: 28.1 mm Hg ± 19.8 [standard deviation] vs 14.0 mm Hg ± 6.5, P = .004; peak pressure gradient: 53.1 mm Hg ± 38.4 vs 26.1 mm Hg ± 11.4, P = .004; transvalvular peak velocity: 3.3 m/sec ± 1.3 vs 2.5 m/sec ± 0.5; and LVEF: 64.7% ± 7.4 vs 56.8% ± 10.5, P = .004). A high MTPG (≥40 mm Hg) was observed in four patients at echocardiography, and subprosthetic panni were identified at CT in all four patients. In patients with increased MTPGs, the encroachment ratio by subprosthetic pannus at CT was significantly higher than that in patients with MTPGs of less than 40 mm Hg (42.7 ± 13.3 vs 7.6 ± 3, P = .012). CONCLUSION: Cardiac CT revealed subprosthetic pannus to be a cause of the hemodynamic changes in patients who had undergone aortic valve replacement. By helping quantify the encroachment ratio by pannus, cardiac CT may help differentiate which subprosthetic panni might lead to substantial flow limitation over the prosthetic aortic valve.


Assuntos
Valva Aórtica/cirurgia , Técnicas de Imagem Cardíaca , Cardiopatias/diagnóstico por imagem , Cardiopatias/etiologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Cardiopatias/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Eur Radiol ; 25(6): 1614-22, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25519977

RESUMO

OBJECTIVES: We aimed to evaluate the role of preoperative cardiac computed tomography (CT) for adults with congenital cardiac septal defect (CSD). METHODS: Sixty-five consecutive patients who underwent preoperative CT and surgery for CSD were included. The diagnostic accuracy of CT and the concordance rate of the subtype classification of CSD were evaluated using surgical findings as the reference standard. Sixty-five patients without CSD who underwent cardiac valve surgery were used as a control group. An incremental value of CT over echocardiography was described retrospectively. RESULTS: Sensitivity and specificity of CT for diagnosis of CSD were 95 % and 100 %, respectively. The concordance rate of subtype classification was 91 % in CT and 92 % in echocardiography. The maximum size of the defect measured by CT correlated well with surgical measurement (r = 0.82), and the limit of agreement was -0.9 ± 7.42 mm. In comparison with echocardiography, CT was able to detect combined abnormalities in three cases, and exclusively provided correct subtype classification or clarified suspected abnormal findings found on echocardiography in seven cases. CONCLUSIONS: Cardiac CT can accurately demonstrates CSD in preoperative adult patients. CT may have an incremental role in preoperative planning, particularly in those with more complex anatomy. KEY POINTS: • Cardiac CT can demonstrate cardiac septal defect accurately in preoperative planning. • Cardiac CT can demonstrate combined abnormalities of cardiac septal defect. • Cardiac CT may have an incremental role over echocardiography in complex anatomy.


Assuntos
Defeitos dos Septos Cardíacos/diagnóstico por imagem , Coração/diagnóstico por imagem , Cuidados Pré-Operatórios/métodos , Tomografia Computadorizada por Raios X/métodos , Procedimentos Cirúrgicos Cardíacos , Ecocardiografia , Feminino , Defeitos dos Septos Cardíacos/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
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