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1.
Arterioscler Thromb Vasc Biol ; 43(6): 979-994, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37078290

RESUMO

BACKGROUND: Genetic variants at the TRIB1 gene locus are strongly associated with plasma lipid traits and the risk of coronary artery disease in humans. Here, we analyzed the consequences of Trib1 deficiency on lipid metabolism and atherosclerotic lesion formation in atherosclerosis-susceptible Ldlr-/- mice. METHODS: Trib1-/- mice were crossed onto the Ldlr-/- background to generate double-knockout mice (Trib1-/-Ldlr-/-) and fed a semisynthetic, modified AIN76 diet (0.02% cholesterol and 4.3% fat) until 20 weeks of age. RESULTS: Trib1-/-Ldlr-/- mice had profoundly larger (5.8-fold) and more advanced atherosclerotic lesions at the aortic root as compared with Trib1+/+Ldlr-/- controls. Further, we observed significantly elevated plasma total cholesterol and triglyceride levels in Trib1-/-Ldlr-/- mice, resulting from higher VLDL (very-low-density lipoprotein) secretion. Lipidomics analysis revealed that loss of Trib1 altered hepatic lipid composition, including the accumulation of cholesterol and proinflammatory ceramide species, which was accompanied by signs of hepatic inflammation and injury. Concomitantly, we detected higher plasma levels of IL (interleukin)-6 and LCN2 (lipocalin 2), suggesting increased systemic inflammation in Trib1-/-Ldlr-/- mice. Hepatic transcriptome analysis demonstrated significant upregulation of key genes controlling lipid metabolism and inflammation in Trib1-/-Ldlr-/- mice. Further experiments suggested that these effects may be mediated through pathways involving a C/EPB (CCAAT/enhancer binding protein)-PPARγ (peroxisome proliferator-activated receptor γ) axis and JNK (c-Jun N-terminal kinase) signaling. CONCLUSIONS: We provide experimental evidence that Trib1 deficiency promotes atherosclerotic lesion formation in a complex manner that includes the modulation of lipid metabolism and inflammation.


Assuntos
Aterosclerose , Hipercolesterolemia , Hiperlipidemias , Animais , Camundongos , Aterosclerose/patologia , Colesterol/metabolismo , Hipercolesterolemia/genética , Inflamação/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de LDL
2.
Am J Nephrol ; 51(7): 511-519, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32659755

RESUMO

BACKGROUND: Arteriovenous (AV) fistulas are considered the gold standard for ensuring safe and long-term vascular access in patients with haemodialysis-dependent end-stage renal disease. However, previous studies demonstrated that high-flow AV fistulas might add additional cardiovascular burden in the post-transplant setting, leading to frequent fistula closure in this population. Currently, there is no consensus regarding management of high-flow fistulas in post-transplant patients with stable kidney function. The present randomized controlled trial examines the effect of prophylactic AV fistula closure on high-output heart failure. METHODS: Twenty-eight kidney transplant patients with stable graft function, absence of pre-existing severe cardiac failure, and brachial arterial flow rate of at least 1,500 mL/min were recruited and randomized in a 1:1 ratio to an intervention and control group, respectively. The intervention group was subject to immediate fistula ligature. Patients within the control group were referred to fistula ligature only if the main study endpoint high-output heart failure was reached. The latter was defined by the presence of at least 1 clinical sign (i.e., worsening NYHA score) and at least 2 of the following echocardiographic parameters: diameter of right atrium (major) >53 mm, right atrium (minor) >44 mm, inferior vena cava ≥21 mm, right pulmonary artery >20 mm, TAPSE <16 mm, systolic pulmonal artery pressure >40 mm Hg, and/or left ventricular eccentricity index <1. During a 24-month follow-up period, quarterly measurements of kidney function, NT-proBNP, and lactate dehydrogenase as well as a biannual echocardiographic check-up were performed. RESULTS: High-output heart failure attributable to high-flow fistula was reported in 5 of 13 control patients (38.5%), whereas no patient in the intervention group presented with clinical and echocardiographic signs of high-output heart failure during the follow-up period. Thus, prophylactic ligature of high-flow fistulas avoided high-output heart failure in our patient population (p = 0.013). Three patients in the control group, however, had to undergo fistula ligature due to aneurysm formation (n = 2) and steal phenomenon (n = 1). Median NT-proBNP levels decreased from 317 ng/L pre-ligature to 223 ng/L post-ligature (p = 0.003). Serum creatinine levels did not significantly differ before and after AV fistula ligature (1.69 vs. 1.60 mg/dL, respectively, p = 0.059). Improvement of echocardiographic findings (e.g., a decrease in systolic pulmonary arterial pressure) was found in 7 of 8 ligature patients but did not reach statistical significance. CONCLUSION: Prophylactic ligature of high-flow AV fistulas after kidney transplantation can avoid high-output heart failure, and a more liberal approach to close AV fistulas might be justified.


Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Insuficiência Cardíaca/epidemiologia , Transplante de Rim/efeitos adversos , Ligadura/métodos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Profiláticos/métodos , Adolescente , Adulto , Idoso , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Falência Renal Crônica/terapia , Ligadura/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Profiláticos/estatística & dados numéricos , Estudos Prospectivos , Fluxo Sanguíneo Regional , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Tempo para o Tratamento/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem
3.
Eur Radiol ; 30(1): 663-671, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31428825

RESUMO

OBJECTIVES: The comparability of left ventricular ejection fraction (LVEF) measurements by cardiac magnetic resonance (CMR) and 2D echocardiography (2DE) early after ST-elevation myocardial infarction (STEMI) remains unclear. METHODS: In this study, LVEF measured by CMR and 2DE (Simpson's method) were compared in 221 patients after STEMI treated by primary percutaneous coronary intervention. 2DE image quality was systematically assessed and studies reported by an accredited examiner. Intermodality agreement was assessed by the Bland-Altman method. Major adverse cardiac events (MACE) were defined as the composite of death, myocardial infarction or hospitalisation for heart failure. Patients were followed up for a median of 40.9 months (IQR 28.1-56). RESULTS: After non-anterior STEMI, LVEF measurements by 2DE (single and biplane) were consistently underestimated in comparison to CMR (CMR 55.7 ± 9.5% vs. 2DE-4CV 49 ± 8.2% (p = 0.06), 2DE-2CV 52 ± 8% (p < 0.001), 2DE-biplane 53.5 ± 7.1% (p = 0.01)). After anterior STEMI, there was no significant difference in LVEF measurements by 2DE and CMR with acceptable limits of agreement (CMR 49 ± 11% vs. 2DE-4CV 49 ± 8.2% (p = 0.8), 2DE-2CV 49 ± 9.2% (p = 0.9), 2DE-biplane 49.6 ± 8% (p = 0.5)). In total, 15% of patients experienced a MACE during follow-up. In multivariate Cox regression analysis, reduced LVEF (< 52%) as assessed by either 2DE or CMR was predictive of MACE (2DE HR = 2.57 (95% CI 1.1-6.2), p = 0.036; CMR HR = 2.51 (95% CI 1.1-5.7), p = 0.028). CONCLUSIONS: At baseline after non-anterior STEMI, 2D echocardiography significantly underestimated LVEF in comparison to CMR, whereas after anterior infarction, measurements were within acceptable limits of agreement. Both imaging modalities offered similar prognostic values when a reduced LVEF < 52% was applied. KEY POINTS: • After non-anterior STEMI, 2D-echocardiography significantly underestimated LVEF compared with cardiac MRI • An ejection fraction of < 52% in the acute post-infarct period by both 2D echocardiography and CMR offered similar prognostic values.


Assuntos
Ecocardiografia/métodos , Imageamento por Ressonância Magnética/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Volume Sistólico , Disfunção Ventricular Esquerda/complicações
4.
Eur Heart J Suppl ; 22(Suppl M): M19-M25, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33664636

RESUMO

A therapeutic dilemma arises when infective endocarditis (IE) is complicated by a neurologic event. Postponement of surgery up to 4 weeks is recommended by the guidelines, however, this negatively impacts outcomes in many patients with an urgent indication for surgery due to uncontrolled infection, disease progression, or haemodynamic deterioration. The current literature is ambiguous regarding the safety of cardiopulmonary bypass in patients with recent neurologic injury. Nevertheless, most publications demonstrate a lower risk for secondary haemorrhagic conversion of uncomplicated ischaemic lesions than the risk for recurrent embolism under antibiotic treatment. Here, we discuss the current literature regarding neurologic stroke complicating IE with an indication for surgery.

5.
J Biol Chem ; 293(29): 11527-11536, 2018 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-29899113

RESUMO

Macrophages are essential for innate immunity and inflammatory responses and differentiate into various functional phenotypes. Tribbles homolog 1 (Trib1), a member of the mammalian Tribbles homolog pseudokinase family, has been implicated in regulation of cell differentiation, proliferation, and metabolism, but its role in macrophage biology has not been fully elucidated. Here, we investigated the consequences of Trib1 deficiency on macrophage functions and M1/M2 polarization. Bone marrow-derived macrophages (BMDMs) from Trib1-deficient (Trib1-/-) mice exhibited elevated phagocytic capacity, correlating with up-regulation of several scavenger receptors. Concomitantly, uptake of modified low-density lipoprotein was increased in Trib1-/- BMDMs. Trib1-/- macrophages also exhibited diminished migration in the presence of the chemokine MCP-1, associated with reduced expression of the MCP-1 receptor Ccr2 Furthermore, Trib1 deficiency attenuated the response of BMDMs to both M1 and M2 stimuli; induction of the M1-marker genes Il6, Il1b, and Nos2 upon LPS/IFNγ stimulation and of the M2-marker genes Cd206, Fizz1, and Arg1 upon IL-4 stimulation was reduced. Functionally, Trib1 deficiency decreased secretion of proinflammatory cytokines (IL-6, TNFα, IL-1ß, and CXCL1) and reduced nitric oxide and reactive oxygen species production in M1-polarized macrophages. Supporting the attenuated M2 phenotype, IL-4-stimulated Trib1-/- macrophages secreted less IL-10 and TGFß. Mechanistically, Trib1-/- BMDMs displayed lower levels of Janus kinase 1 (JAK1), resulting in reduced activation of LPS/IFNγ-mediated STAT1 signaling. Likewise, decreased levels of JAK1 along with lower activation of STAT6 and STAT3 were observed in M2-polarized Trib1-/- BMDMs. Our findings suggest that Trib1 extensively controls macrophage M1/M2 polarization via the JAK/STAT signaling pathway.


Assuntos
Movimento Celular , Polaridade Celular , Deleção de Genes , Peptídeos e Proteínas de Sinalização Intracelular/genética , Macrófagos/citologia , Fagocitose , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Animais , Células da Medula Óssea/citologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Janus Quinase 1/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais
6.
Eur Heart J ; 39(15): 1246-1254, 2018 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-28329105

RESUMO

Advanced percutaneous and surgical procedures in structural and congenital heart disease require precise pre-procedural planning and continuous quality control. Although current imaging modalities and post-processing software assists with peri-procedural guidance, their capabilities for spatial conceptualization remain limited in two- and three-dimensional representations. In contrast, 3D printing offers not only improved visualization for procedural planning, but provides substantial information on the accuracy of surgical reconstruction and device implantations. Peri-procedural 3D printing has the potential to set standards of quality assurance and individualized healthcare in cardiovascular medicine and surgery. Nowadays, a variety of clinical applications are available showing how accurate 3D computer reformatting and physical 3D printouts of native anatomy, embedded pathology, and implants are and how they may assist in the development of innovative therapies. Accurate imaging of pathology including target region for intervention, its anatomic features and spatial relation to the surrounding structures is critical for selecting optimal approach and evaluation of procedural results. This review describes clinical applications of 3D printing, outlines current limitations, and highlights future implications for quality control, advanced medical education and training.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Cardiologia/normas , Cardiopatias Congênitas/diagnóstico por imagem , Impressão Tridimensional/instrumentação , Procedimentos Cirúrgicos Cardíacos/normas , Cardiopatias Congênitas/cirurgia , Humanos , Modelos Anatômicos , Período Perioperatório/normas , Próteses e Implantes/normas , Garantia da Qualidade dos Cuidados de Saúde , Software
7.
Eur Radiol ; 28(12): 5129-5136, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29869175

RESUMO

OBJECTIVES: To evaluate right ventricle (RV) function by coronary computed tomography angiography (CTA) using a novel automated three-dimensional (3D) RV volume segmentation tool in comparison with clinical reference modalities. METHODS: Twenty-six patients with severe end-stage heart failure [left ventricle (LV) ejection fraction (EF) <35%] referred to CTA were enrolled. A specific individually tailored biphasic contrast agent injection protocol was designed (80%/20% high/low flow) was designed. Measurement of RV function [EF, end-diastolic volume (EDV), end-systolic volume (ESV)] by CTA was compared with tricuspid annular plane systolic excursion (TAPSE) by transthoracic echocardiography (TTE) and right heart invasive catheterisation (IC). RESULTS: Automated 3D RV volume segmentation was successful in 26 (100%) patients. Read-out time was 3 min 33 s (range, 1 min 50s-4 min 33s). RV EF by CTA was stronger correlated with right atrial pressure (RAP) by IC (r = -0.595; p = 0.006) but weaker with TAPSE (r = 0.366, p = 0.94). When comparing TAPSE with RAP by IC (r = -0.317, p = 0.231), a weak-to-moderate non-significant inverse correlation was found. Interobserver correlation was high with r = 0.96 (p < 0.001), r = 0.86 (p < 0.001) and r = 0.72 (p = 0.001) for RV EDV, ESV and EF, respectively. CT attenuation of the right atrium (RA) and right ventricle (RV) was 196.9 ± 75.3 and 217.5 ± 76.1 HU, respectively. CONCLUSIONS: Measurement of RV function by CTA using a novel 3D volumetric segmentation tool is fast and reliable by applying a dedicated biphasic injection protocol. The RV EF from CTA is a closer surrogate of RAP than TAPSE by TTE. KEY POINTS: • Evaluation of RV function by cardiac CTA by using a novel 3D volume segmentation tool is fast and reliable. • A biphasic contrast agent injection protocol ensures homogenous RV contrast attenuation. • Cardiac CT is a valuable alternative modality to CMR for the evaluation of RV function.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Insuficiência Cardíaca/diagnóstico por imagem , Função Ventricular Direita/fisiologia , Adulto , Idoso , Técnicas de Imagem Cardíaca/métodos , Ecocardiografia/métodos , Feminino , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Imageamento Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Volume Sistólico/fisiologia , Tomografia Computadorizada por Raios X/métodos , Função Ventricular Esquerda/fisiologia
8.
Biochim Biophys Acta Mol Basis Dis ; 1863(7): 1709-1717, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28501567

RESUMO

Differentiation of adipocytes is a highly regulated process modulated by multiple transcriptional co-activators and co-repressors. JMJD1C belongs to the family of jumonji C (jmjC) domain-containing histone demethylases and was originally described as a ligand-dependent co-activator of thyroid hormone and androgen receptors. Here, we explored the potential role of Jmjd1c in white adipocyte differentiation. To investigate the relevance of Jmjd1c in adipogenesis, murine 3T3-L1 preadipocyte cells with transient knock-down of Jmjd1c (3T3_Jmjd1c) were generated. Depletion of Jmjd1c led to the formation of smaller lipid droplets, reduced accumulation of triglycerides and maintenance of a more fibroblast-like morphology after adipocyte differentiation. Concomitantly, insulin stimulated uptake of glucose and fatty acids was significantly reduced in 3T3_Jmjd1c adipocytes. In line with these observations we detected lower expression of key genes associated with lipid droplet formation (Plin1, Plin4, Cidea) and uptake of glucose and fatty acids (Glut4, Fatp1, Fatp4, Aqp7) respectively. Finally, we demonstrate that depletion of Jmjd1c interferes with mitotic clonal expansion (MCE), increases levels of H3K9me2 (dimethylation of lysine 9 of histone H3) at promotor regions of adipogenic transcription factors (C/EBPs and PPARγ) and leads to reduced induction of these key regulators. In conclusion, we have identified Jmjd1c as a modulator of adipogenesis. Our data suggest that Jmjd1c may participate in MCE and the activation of the adipogenic transcription program during the induction phase of adipocyte differentiation in 3T3-L1 cells.


Assuntos
Adipócitos/metabolismo , Adipogenia , Diferenciação Celular , Fibroblastos/metabolismo , Histona Desmetilases com o Domínio Jumonji/deficiência , Gotículas Lipídicas/metabolismo , Células 3T3-L1 , Adipócitos/citologia , Animais , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Fibroblastos/citologia , Glucose/genética , Glucose/metabolismo , Histonas/genética , Histonas/metabolismo , Camundongos , Mitose , PPAR gama/genética , PPAR gama/metabolismo , Regiões Promotoras Genéticas
9.
Eur Radiol ; 26(7): 1999-2008, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26385805

RESUMO

OBJECTIVES: Phase-contrast CMR (PC-CMR) might provide a fast and robust non-invasive determination of left ventricular function in patients after ST-segment elevation myocardial infarction (STEMI). METHODS: Cine sequences in the left-ventricular (LV) short-axis and free-breathing, retrospectively gated PC-CMR were performed in 90 patients with first acute STEMI and 15 healthy volunteers. Inter- and intra-observer agreement was determined. The correlations of clinical variables (age, gender, ejection fraction, NT pro-brain natriuretic peptide [NT-proBNP] with cardiac index (CI) were calculated. RESULTS: For CI, there was a strong agreement of cine CMR with PC-CMR in healthy volunteers (r: 0.82, mean difference: -0.14 l/min/m(2), error ± 23 %). Agreement was lower in STEMI patients (r: 0.61, mean difference: -0.17 l/min/m(2), error ± 32 %). In STEMI patients, CI measured with PC-CMR showed lower intra-observer (1 % vs. 9 %) and similar inter-observer variability (9 % vs. 12 %) compared to cine CMR. CI was significantly correlated with age, ejection fraction and NT-proBNP values in STEMI patients. DISCUSSION: The agreement of PC-CMR and cine CMR for the determination of CI is lower in STEMI patients than in healthy volunteers. After acute STEMI, CI measured with PC-CMR decreases with age, LV ejection fraction and higher NT-proBNP. KEY POINTS: • Cine CMR and PC-CMR correlate well in healthy volunteers. • Agreement is lower in STEMI patients. • Cardiac Output should be measured with one method longitudinally. • Cardiac output decreases with age after myocardial infarction.


Assuntos
Débito Cardíaco/fisiologia , Imagem Cinética por Ressonância Magnética/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Adulto , Idoso , Aorta/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Meios de Contraste/administração & dosagem , Circulação Coronária/fisiologia , Feminino , Seguimentos , Frequência Cardíaca/fisiologia , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Função Ventricular Esquerda/fisiologia
13.
Eur Heart J ; 35(2): 69-76, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24144789

RESUMO

Current interventional procedures in structural heart disease and cardiac arrhythmias require peri-interventional echocardiographic monitoring and guidance to become as safe, expedient, and well-tolerated for patients as possible. Intracardiac echocardiography (ICE) complements and has in part replaced transoesophageal echocardiography (TEE), including real-time three-dimensional (RT-3D) imaging. The latter is still widely accepted as a method to prepare for and to guide interventional treatments. In contrast to TEE, ICE represents a purely intraprocedural guiding and imaging tool unsuitable for diagnostic purposes. Patients tolerate ICE much better, and the method does not require general anaesthesia. Accurate imaging of the particular pathology, its anatomic features, and spatial relation to the surrounding structures is critical for catheter and wire positioning, device deployment, evaluation of the result, and for ruling out complications. This review describes the peri-interventional role of ICE, outlines current limitations, and points out future implications. Two-dimensional ICE has become a suitable guiding tool for a variety of percutaneous treatments in patients who are conscious or under monitored anaesthesia care, whereas RT-3DICE is still undergoing clinical testing. Continuous TEE monitoring under general anaesthesia remains a widely accepted alternative.


Assuntos
Ecocardiografia/métodos , Cardiopatias/diagnóstico por imagem , Apêndice Atrial/cirurgia , Cateterismo Cardíaco/economia , Cateterismo Cardíaco/métodos , Cardiologia/educação , Análise Custo-Benefício , Ecocardiografia/economia , Europa (Continente) , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Cuidados Intraoperatórios/métodos , Anuloplastia da Valva Mitral/métodos , Dispositivo para Oclusão Septal , Ultrassonografia de Intervenção/economia , Ultrassonografia de Intervenção/métodos , Estados Unidos , Técnicas de Fechamento de Ferimentos
14.
J Clin Med ; 13(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38999259

RESUMO

Background: Despite being the most commonly performed valvular intervention, risk prediction for aortic valve replacement in patients with severe aortic stenosis by currently used risk scores remains challenging. The study aim was to develop a biomarker-based risk score by means of a neuronal network. Methods: In this multicenter study, 3595 patients were divided into test and validation cohorts (70% to 30%) by random allocation. Input variables to develop the ABC-AS score were age, the cardiac biomarker high-sensitivity troponin T, and a patient history of cardiac decompensation. The validation cohort was used to verify the scores' value and for comparison with the Society of Thoracic Surgery Predictive Risk of Operative Mortality score. Results: Receiver operating curves demonstrated an improvement in prediction by using the ABC-AS score compared to the Society of Thoracic Surgery Predictive Risk of Operative Mortality (STS prom) score. Although the difference in predicting cardiovascular mortality was most notable at 30-day follow-up (area under the curve of 0.922 versus 0.678), ABC-AS also performed better in overall follow-up (0.839 versus 0.699). Furthermore, univariate analysis of ABC-AS tertiles yielded highly significant differences for all-cause (p < 0.0001) and cardiovascular mortality (p < 0.0001). Head-to-head comparison between both risk scores in a multivariable cox regression model underlined the potential of the ABC-AS score (HR per z-unit 2.633 (95% CI 2.156-3.216), p < 0.0001), while the STS prom score failed to reach statistical significance (p = 0.226). Conclusions: The newly developed ABC-AS score is an improved risk stratification tool to predict cardiovascular outcomes for patients undergoing aortic valve intervention.

15.
Catheter Cardiovasc Interv ; 81(4): 651-3, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22753272

RESUMO

A 67-year-old male presented with a left ventricular ejection fraction of 21% and an atrial septal defect (ASD), the closure of which carries a risk of worsening the patients' clinical situation. The ASD contributed significantly to heart failure according to NYHA class III to IV, on the other hand. Preconditioning, echocardiographic testing, and test closure were carried out in order to minimize the risk and to finally close the defect successfully in behoof of the patient.


Assuntos
Cateterismo Cardíaco , Cardiomiopatias/etiologia , Comunicação Interatrial/terapia , Isquemia Miocárdica/complicações , Idoso , Cateterismo Cardíaco/instrumentação , Cardiomiopatias/diagnóstico , Cardiomiopatias/fisiopatologia , Ecocardiografia Transesofagiana , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Comunicação Interatrial/complicações , Comunicação Interatrial/diagnóstico , Comunicação Interatrial/diagnóstico por imagem , Comunicação Interatrial/fisiopatologia , Humanos , Masculino , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatologia , Valor Preditivo dos Testes , Dispositivo para Oclusão Septal , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda
16.
Front Cardiovasc Med ; 10: 1256112, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38028449

RESUMO

Introduction: Previous analyses have reported the outcomes of transcatheter aortic valve replacement (TAVR) for patients with low-flow, low-gradient (LFLG) aortic stenosis (AS), without stratifying according to the route of access. Differences in mortality rates among access routes have been established for high-gradient (HG) patients and hypothesized to be even more pronounced in LFLG AS patients. This study aims to compare the outcomes of patients with LFLG or HG AS following transfemoral (TF) or transapical (TA) TAVR. Methods: A total of 910 patients, who underwent either TF or TA TAVR with a median follow-up of 2.22 (IQR: 1.22-4.03) years, were included in this multicenter cohort study. In total, 146 patients (16.04%) suffered from LFLG AS. The patients with HG and LFLG AS were stratified according to the route of access and compared statistically. Results: The operative mortality rates of patients with HG and LFLG were found to be comparable following TF access. The operative mortality rate was significantly increased for patients who underwent TA access [odds ratio (OR): 2.91 (1.54-5.48), p = 0.001] and patients with LFLG AS [OR: 2.27 (1.13-4.56), p = 0.02], which could be corroborated in a propensity score-matched subanalysis. The observed increase in the risk of operative mortality demonstrated an additive effect [OR for TA LFLG: 5.45 (2.35-12.62), p < 0.001]. LFLG patients who underwent TA access had significantly higher operative mortality rates (17.78%) compared with TF LFLG (3.96%, p = 0.016) and TA HG patients (6.36%, p = 0.024). Conclusions: HG patients experienced a twofold increase in operative mortality rates following TA compared with TF access, while LFLG patients had a fivefold increase in operative mortality rates. TA TAVR appears suboptimal for patients with LFLG AS. Prospective studies should be conducted to evaluate alternative options in cases where TF is not possible.

17.
Cell Metab ; 35(12): 2136-2152.e9, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-37989315

RESUMO

The peripheral nervous system harbors a remarkable potential to regenerate after acute nerve trauma. Full functional recovery, however, is rare and critically depends on peripheral nerve Schwann cells that orchestrate breakdown and resynthesis of myelin and, at the same time, support axonal regrowth. How Schwann cells meet the high metabolic demand required for nerve repair remains poorly understood. We here report that nerve injury induces adipocyte to glial signaling and identify the adipokine leptin as an upstream regulator of glial metabolic adaptation in regeneration. Signal integration by leptin receptors in Schwann cells ensures efficient peripheral nerve repair by adjusting injury-specific catabolic processes in regenerating nerves, including myelin autophagy and mitochondrial respiration. Our findings propose a model according to which acute nerve injury triggers a therapeutically targetable intercellular crosstalk that modulates glial metabolism to provide sufficient energy for successful nerve repair.


Assuntos
Bainha de Mielina , Nervos Periféricos , Bainha de Mielina/metabolismo , Neuroglia , Células de Schwann/metabolismo , Regeneração Nervosa/fisiologia
18.
Cells ; 11(9)2022 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-35563883

RESUMO

Regeneration of articular cartilage remains challenging. The aim of this study was to increase the stability of pure bioactive glass (BG) scaffolds by means of solvent phase polymer infiltration and to maintain cell adherence on the glass struts. Therefore, BG scaffolds either pure or enhanced with three different amounts of poly(D-L-lactide-co-glycolide) (PLGA) were characterized in detail. Scaffolds were seeded with primary porcine articular chondrocytes (pACs) and human mesenchymal stem cells (hMSCs) in a dynamic long-term culture (35 days). Light microscopy evaluations showed that PLGA was detectable in every region of the scaffold. Porosity was greater than 70%. The biomechanical stability was increased by polymer infiltration. PLGA infiltration did not result in a decrease in viability of both cell types, but increased DNA and sulfated glycosaminoglycan (sGAG) contents of hMSCs-colonized scaffolds. Successful chondrogenesis of hMSC-colonized scaffolds was demonstrated by immunocytochemical staining of collagen type II, cartilage proteoglycans and the transcription factor SOX9. PLGA-infiltrated scaffolds showed a higher relative expression of cartilage related genes not only of pAC-, but also of hMSC-colonized scaffolds in comparison to the pure BG. Based on the novel data, our recommendation is BG scaffolds with single infiltrated PLGA for cartilage tissue engineering.


Assuntos
Cartilagem Articular , Células-Tronco Mesenquimais , Animais , Cartilagem Articular/metabolismo , Condrogênese , Colágeno Tipo II/metabolismo , Dioxanos , Células-Tronco Mesenquimais/metabolismo , Suínos , Engenharia Tecidual , Alicerces Teciduais/química
19.
J Biomed Biotechnol ; 2011: 185683, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21151667

RESUMO

To perform cardiac imaging in mice without having to invest in expensive dedicated equipment, we adapted a clinical 1.5 Tesla (T) magnetic resonance imaging (MRI) scanner for use in a murine ischemia/reperfusion model. Phase-sensitive inversion recovery (PSIR) sequence facilitated the determination of infarct sizes in vivo by late gadolinium enhancement. Results were compared to histological infarct areas in mice after ischemia/reperfusion procedure with a good correlation (r = 0.807, P < .001). In addition, fractional area change (FAC) was assessed with single slice cine MRI and was matched to infarct size (r = -0.837) and fractional shortening (FS) measured with echocardiography (r = 0.860); both P < .001. Here, we demonstrate the use of clinical 1.5 MRI scanners as a feasible method for basic phenotyping in mice. These widely available scanners are capable of investigating in vivo infarct dimensions as well as assessment of cardiac functional parameters in mice with reasonable throughput.


Assuntos
Técnicas de Imagem Cardíaca/instrumentação , Imageamento por Ressonância Magnética/instrumentação , Traumatismo por Reperfusão/patologia , Análise de Variância , Animais , Técnicas de Imagem Cardíaca/métodos , Modelos Animais de Doenças , Ecocardiografia , Ventrículos do Coração/patologia , Compostos Heterocíclicos , Imageamento por Ressonância Magnética/métodos , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/patologia , Compostos Organometálicos , Fenótipo
20.
J Sleep Res ; 20(4): 598-605, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21707809

RESUMO

Reliable, valid and cost-effective methods for the assessment of infant sleep and sleep problems are of major importance. In this study, the first aim was to assess the agreement of an electronic diary as well as a paper diary with actigraphy for measuring infant sleep patterns in a community sample. The second aim was to assess the feasibility and acceptance of, and compliance with, the electronic diary and the paper diary. Ninety parents reported infant sleep behavior in a paper diary in their home environments for a total of 6 days, 95 in an electronic diary, within two consecutive weeks while actigraphic data were obtained simultaneously. We found moderate to good agreement between electronic diaries and actigraphy (r = 0.41-0.65, P < 0.01), and paper diaries and actigraphy (r = 0.47-0.70, P < 0.01). In addition, this study also found good agreement between both diaries and also between both diaries and actigraphy for sleep percentage over 24 h (electronic diaries and actigraphy: 54.1 ± 0.7%, 52.5 ± 0.7%, P < 0.05; paper diaries and actigraphy: 55.1 ± 0.5%, 52.2 ± 0.6%, P < 0.01) and for daytime (electronic diaries and actigraphy: 27.3 ± 0.9%, 23.5 ± 1.2%, P < 0.01; paper diaries and actigraphy: 27.3 ± 0.8%, 23.2 ± 1.0%, P < 0.01), with the exception that less daytime sleep was recorded on actigraphy than on either diary. In conclusion, the electronic diary and the paper diary are valid and well-accepted methods for the assessment of infant sleep. Parents preferred the electronic diary but, conversely, they were less compliant in completing it.


Assuntos
Prontuários Médicos , Pais , Sono , Actigrafia , Adulto , Fatores Etários , Feminino , Humanos , Lactente , Masculino , Reprodutibilidade dos Testes
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