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1.
Cell Mol Life Sci ; 81(1): 206, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38709307

RESUMEN

The epithelial-mesenchymal transformation (EMT) process of alveolar epithelial cells is recognized as involved in the development of pulmonary fibrosis. Recent evidence has shown that lipopolysaccharide (LPS)-induced aerobic glycolysis of lung tissue and elevated lactate concentration are associated with the pathogenesis of sepsis-associated pulmonary fibrosis. However, it is uncertain whether LPS promotes the development of sepsis-associated pulmonary fibrosis by promoting lactate accumulation in lung tissue, thereby initiating EMT process. We hypothesized that monocarboxylate transporter-1 (MCT1), as the main protein for lactate transport, may be crucial in the pathogenic process of sepsis-associated pulmonary fibrosis. We found that high concentrations of lactate induced EMT while moderate concentrations did not. Besides, we demonstrated that MCT1 inhibition enhanced EMT process in MLE-12 cells, while MCT1 upregulation could reverse lactate-induced EMT. LPS could promote EMT in MLE-12 cells through MCT1 inhibition and lactate accumulation, while this could be alleviated by upregulating the expression of MCT1. In addition, the overexpression of MCT1 prevented LPS-induced EMT and pulmonary fibrosis in vivo. Altogether, this study revealed that LPS could inhibit the expression of MCT1 in mouse alveolar epithelial cells and cause lactate transport disorder, which leads to lactate accumulation, and ultimately promotes the process of EMT and lung fibrosis.


Asunto(s)
Transición Epitelial-Mesenquimal , Ácido Láctico , Lipopolisacáridos , Transportadores de Ácidos Monocarboxílicos , Fibrosis Pulmonar , Simportadores , Transportadores de Ácidos Monocarboxílicos/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/antagonistas & inhibidores , Animales , Transición Epitelial-Mesenquimal/efectos de los fármacos , Lipopolisacáridos/farmacología , Simportadores/metabolismo , Simportadores/genética , Simportadores/antagonistas & inhibidores , Ratones , Ácido Láctico/metabolismo , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/inducido químicamente , Ratones Endogámicos C57BL , Línea Celular , Masculino , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Células Epiteliales Alveolares/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos
2.
Artículo en Inglés | MEDLINE | ID: mdl-39075656

RESUMEN

INTRODUCTION: The anterior and lateral position of the anterolateral papillary muscle (ALPM) has found to be reached with better catheter stability and less mechanical bumping via the transseptal (TS) compared to the retrograde aortic (RA) approach. The aim of this study is to compare the TS and RA approaches on mapping and ablation of ventricular arrhythmias (VAs) arising from ALPMs. METHODS: Thirty-two patients with ALPM-VAs undergoing mapping and ablation via the TS approach were included and compared with 31 patients via the RA approach within the same period. Acute success was compared, as well as other outcomes including misinterpreted mapping results due to bumping, radiofrequency (RF) attempts, procedural time and success rate at 12-month follow-up. RESULTS: Acute success was achieved in more cases in the TS group (96.4% vs. 72.0%, p = .020). During activation mapping, bump-provoked premature ventricular complexes (PVCs) misinterpreted as clinical PVCs were more common in the RA group (30.0% vs. 58.3%, p = .036), leading to more RF attempts (3.5 ± 2.7 vs. 7.2 ± 6.8, p = .006). Suppression of VAs were finally achieved in the unsuccessful cases by changing to the alternative approach, but the procedural time was significantly less in the TS group (90.0 ± 33.0 vs. 113.7 ± 41.1 min, p = .027) with less need to change the approach, although follow-up success rates were similar (75.0% vs. 71.0%, p = .718). CONCLUSION: A TS rather than RA approach as the initial approach appears to facilitate mapping and ablation of ALPM-VAs, specifically by decreasing the possibility of misleading mapping results caused by bump-provoked PVC, and increase the acute success rate thereby.

3.
BMC Cardiovasc Disord ; 24(1): 398, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39085776

RESUMEN

BACKGROUND: Stroke and thromboembolism in nonvalvular atrial fibrillation (NVAF) primarily arise from thrombi or sludge in the left atrial appendage (LAA). Comprehensive insight into the characteristics of these formations is essential for effective risk assessment and management. METHODS: We conducted a single-center retrospective observational of 176 consecutive NVAF patients with confirmed atrial/appendage thrombus or sludge determined by a pre-ablation transesophageal echocardiogram (TEE) from December 2017 to April 2019. We obtained clinical and echocardiographic characteristics, including left atrial appendage emptying velocity (LAAeV) and filling velocity (LAAfV). Data analysis focused on identifying the morphology and location of thrombus or sludge. Patients were divided into the solid thrombus and sludge groups, and the correlation between clinical and echocardiographic variables and thrombotic status was analyzed. RESULTS: Morphological classification: In total, thrombi were identified in 78 patients, including 71 (40.3%) mass and 7 (4.0%) lamellar, while sludge was noted in 98 (55.7%). Location classification: 92.3% (72/78) of patients had thrombus confined to the LAA; 3.8% (3/78) had both LA and LAA involvement; 2.7% (2/78) had LA, LAA and RAA extended into the RA, the remained 1.2%(1/78) was isolated to RAA. 98.0% (96/98) of patients had sludge confined to the LAA; the remaining 2.0% (2/98) were present in the atrial septal aneurysm, which protrusion of interatrial septum into the RA. The thrombus and sludge groups showed low LAAeV (19.43 ± 9.59 cm/s) or LAAfV (17.40 ± 10.09 cm/s). Only LA dimension ≥ 40 mm was independently associated with the thrombus state in the multivariable model. CONCLUSION: This cohort study identified rare thrombus morphology and systematically summarized the classification of thrombus morphology. The distribution of thrombus and sludge outside limited to LAA was updated, including bilateral atrial and appendage involvement and rare atrial septal aneurysm sludge. LAAeV and LAAfV were of limited value in distinguishing solid thrombus from sludge. CLINICAL TRIAL NUMBER: ChiCTR-OCH-13,003,729.


Asunto(s)
Apéndice Atrial , Fibrilación Atrial , Ecocardiografía Transesofágica , Trombosis , Humanos , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/diagnóstico , Estudios Retrospectivos , Masculino , Femenino , Trombosis/diagnóstico por imagen , Trombosis/etiología , Anciano , Persona de Mediana Edad , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/fisiopatología , Factores de Riesgo , Valor Predictivo de las Pruebas , Función del Atrio Izquierdo , Cardiopatías/diagnóstico por imagen , Cardiopatías/fisiopatología , Tromboembolia/etiología , Tromboembolia/diagnóstico por imagen , Tromboembolia/diagnóstico
4.
Pacing Clin Electrophysiol ; 47(4): 518-524, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38407374

RESUMEN

BACKGROUND: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long-term outcomes of patients with AF and LBBB after catheter ablation. METHODS: Forty-two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non-LBBB group. Late recurrence and a composite endpoint of stroke, all-cause mortality, and cardiovascular hospitalization were compared between the two groups. RESULTS: Late recurrence rate was significantly higher in the LBBB group than that in the non-LBBB group (54.8% vs. 31.5%, p = .034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.40, p = .031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64-9.64, p = .002). CONCLUSIONS: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Accidente Cerebrovascular , Humanos , Bloqueo de Rama/etiología , Factores de Riesgo , Accidente Cerebrovascular/etiología , Ablación por Catéter/efectos adversos , Resultado del Tratamiento , Recurrencia
5.
Lab Invest ; 103(1): 100021, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36748196

RESUMEN

Mechanical ventilation (MV) has become a clinical first-line treatment option for patients with respiratory failure. However, it was unclear whether MV further aggravates the process of sepsis-associated pulmonary fibrosis and eventually leads to sepsis and mechanical ventilation-associated pulmonary fibrosis (S-MVPF). This study aimed to explore the mechanism of S-MVPF concerning integrin ß3 activation in glycometabolic reprogramming of lung fibroblasts. We found that MV exacerbated sepsis-associated pulmonary fibrosis induced by lipopolysaccharide, which was accompanied by proliferation of lung fibroblasts, increased deposition of collagen in lung tissue, and increased procollagen type I carboxy-terminal propeptide in the bronchoalveolar lavage fluid. A large number of integrin ß3- and pyruvate kinase M2-positive fibroblasts were detected in lung tissue after stimulation with lipopolysaccharide and MV, with an increase in lactate dehydrogenase A expression and lactate levels. S-MVPF was primarily attenuated in integrin ß3-knockout mice, which also resulted in a decrease in the levels of pyruvate kinase M2, lactate dehydrogenase A, and lactate. In conclusion, MV aggravated sepsis-associated pulmonary fibrosis, with glycometabolic reprogramming mediated by integrin ß3 activation. Thus, integrin ß3-mediated glycometabolic reprogramming might be a potential therapeutic target for S-MVPF.


Asunto(s)
Fibrosis Pulmonar , Sepsis , Ratones , Animales , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/metabolismo , Integrina beta3/metabolismo , Respiración Artificial , Lipopolisacáridos , Lactato Deshidrogenasa 5 , Piruvato Quinasa , Sepsis/complicaciones
6.
Am Heart J ; 260: 34-43, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36813122

RESUMEN

BACKGROUND: In randomized studies, the strategy of pulmonary vein antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion. OBJECTIVE: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for the ablation of PeAF. STUDY DESIGN: The PROMPT-AF study (clinicaltrials.gov 04497376) is a prospective, multicenter, open-label, randomized trial using a 1:1 parallel-control approach. Patients (n = 498) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI, and 3 linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The follow-up duration is 12 months. The primary end point is freedom from atrial arrhythmias of >30 seconds, without antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months). CONCLUSIONS: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Humanos , Fibrilación Atrial/cirugía , Venas Pulmonares/cirugía , Estudios Prospectivos , Atrios Cardíacos/cirugía , Etanol , Ablación por Catéter/métodos , Resultado del Tratamiento , Recurrencia
7.
Semin Thromb Hemost ; 49(7): 673-678, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36108652

RESUMEN

BACKGROUND: Left ventricular thrombus (LVT) is a common complication of dilated cardiomyopathy (DCM), causing morbidity and mortality. METHODS: This study retrospectively analyzed patients with DCM from January 2002 to August 2020 in Beijing Anzhen Hospital. Clinical characteristics were compared between the LVT group and the age and sex 1:4 matched with the LVT absent group. The receiver operator characteristic (ROC) curve was plotted to evaluate the diagnostic value of D-dimer predicting LVT occurrence in DCM. RESULTS: A total of 3,134 patients were screened, and LVT was detected in 72 (2.3%) patients on echocardiography. The patients with LVT had higher D-dimer, fibrinogen, and lower systolic blood pressure than those without LVT. The ejection fraction (EF) was lower and left ventricular end-systolic diameter was larger in the LVT group. Severe mitral regurgitation (MR) was more common in the LVT absent groups. The prevalence of atrial fibrillation was lower in the LVT group. The ROC curve analysis yielded an optimal cut-off value of 444 ng/mL DDU (D-dimer units) for D-dimer to predict the presence of LVT. Multivariable binary logistic regression analysis revealed that EF (OR = 0.90, 95% CI = 0.86-0.95), severe MR (OR = 0.19, 95% CI = 0.08-0.48), and D-dimer level (OR = 15.4, 95% CI = 7.58-31.4) were independently associated with LVT formation. CONCLUSION: This study suggested that elevated D-dimer levels (>444 ng/mL DDU) and reduced EF were independently associated with increased risk of LVT formation. Severe MR could decrease the incidence of LVT.


Asunto(s)
Cardiomiopatía Dilatada , Trombosis , Humanos , Estudios Retrospectivos , Cardiomiopatía Dilatada/complicaciones , Factores de Riesgo
8.
Europace ; 25(3): 1000-1007, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-36514946

RESUMEN

AIMS: Fascicular ventricle tachycardia (FVT) arising from the proximal aspect of left His-Purkinje system (HPS) has not been specially addressed. Current study was to investigate its clinical, electrocardiographic, and electrophysiological characteristics. METHODS AND RESULTS: Eighteen patients who were identified as this rare FVT were consecutively enrolled, and their scalar electrocardiogram and electrophysiological data were collected and analysed. The ventricular tachycardia (VT) morphology was similar to sinus rhythm (SR) in eight patients, left bundle branch block type in one patient, right bundle branch block type in seven patients, and both narrow and wide QRS type in two patients. During VT, right-sided His potential preceded the QRS with His-ventricle (H-V) interval of 36.3 ± 12.4 ms, which was shorter than that during SR (-51.4 ± 8.6 ms) (P = 0.002). The earliest Purkinje potentials (PPs) were recorded within 7 ± 3 mm of left-side His and preceded the QRS by 49.1 ± 14.0 ms. Mapping along the left anterior fascicle and left posterior fascicle revealed an antegrade activation sequence in all with no P1 potentials recorded. In the two patients with two VT morphologies, the earliest PP was documented at the same site, and the activation sequence of HPS remained antegrade. Ablation at the earliest PP successfully eliminated the tachycardia, except one patient who developed complete atrial-ventricular block and two patients who abandoned ablations. After at least 12 months follow-up, 15 patients were free from any recurrences. CONCLUSIONS: Fascicular ventricle tachycardia arising from the proximal aspect of left HPS was featured by recording slightly shorter H-V interval and absence of P1 potentials. Termination of VT requires ablation at the left-sided His or its adjacent region.


Asunto(s)
Ablación por Catéter , Taquicardia Ventricular , Humanos , Ramos Subendocárdicos/cirugía , Ablación por Catéter/métodos , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiología , Taquicardia Ventricular/cirugía , Fascículo Atrioventricular/cirugía , Electrocardiografía , Bloqueo de Rama/diagnóstico , Bloqueo de Rama/cirugía
9.
Europace ; 25(10)2023 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-37712716

RESUMEN

AIMS: The clinical correlates and outcomes of asymptomatic atrial fibrillation (AF) in hospitalized patients are largely unknown. We aimed to investigate the clinical correlates and in-hospital outcomes of asymptomatic AF in hospitalized Chinese patients. METHODS AND RESULTS: We conducted a cross-sectional registry study of inpatients with AF enrolled in the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation Project between February 2015 and December 2019. We investigated the clinical characteristics of asymptomatic AF and the association between the clinical correlates and the in-hospital outcomes of asymptomatic AF. Asymptomatic and symptomatic AF were defined according to the European Heart Rhythm Association score. Asymptomatic patients were more commonly males (56.3%) and had more comorbidities such as hypertension (57.4%), diabetes mellitus (18.6%), peripheral artery disease (PAD; 2.3%), coronary artery disease (55.5%), previous history of stroke/transient ischaemic attack (TIA; 17.9%), and myocardial infarction (MI; 5.4%); however, they had less prevalent heart failure (9.6%) or left ventricular ejection fractions ≤40% (7.3%). Asymptomatic patients were more often hospitalized with a non-AF diagnosis as the main diagnosis and were more commonly first diagnosed with AF (23.9%) and long-standing persistent/permanent AF (17.0%). The independent determinants of asymptomatic presentation were male sex, long-standing persistent AF/permanent AF, previous history of stroke/TIA, MI, PAD, and previous treatment with anti-platelet drugs. The incidence of in-hospital clinical events such as all-cause death, ischaemic stroke/TIA, and acute coronary syndrome (ACS) was higher in asymptomatic patients than in symptomatic patients, and asymptomatic clinical status was an independent risk factor for in-hospital all-cause death, ischaemic stroke/TIA, and ACS. CONCLUSION: Asymptomatic AF is common among hospitalized patients with AF. Asymptomatic clinical status is associated with male sex, comorbidities, and a higher risk of in-hospital outcomes. The adoption of effective management strategies for patients with AF should not be solely based on clinical symptoms.


Asunto(s)
Fibrilación Atrial , Isquemia Encefálica , Enfermedades Cardiovasculares , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/terapia , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/terapia , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/complicaciones , Ataque Isquémico Transitorio/epidemiología , Estudios Transversales , Mejoramiento de la Calidad , Pronóstico , Factores de Riesgo
10.
Pacing Clin Electrophysiol ; 46(11): 1412-1418, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37736872

RESUMEN

BACKGROUND: Despite undergoing a single ablation, many patients with paroxysmal atrial fibrillation (PAF) experience a gradually increasing recurrence rate. This study aims to examine the relationship between left atrial appendage emptying velocity (LAAeV) and filling velocity (LAAfV) profiles and 3-year recurrence of AF after ablation. METHODS: We conducted a prospective study of 658 consecutive PAF patients who underwent their first ablation between January 2018 and December 2019. We collected the clinical and echocardiographic characteristics of the patients. LAAeV and LAAfV were obtained from a transesophageal echocardiogram (TEE) before catheter ablation. Patients were followed at regular intervals to monitor for the primary outcome of AF recurrence. RESULTS: After a median follow-up period of 35.3 months (range, 10.7-36.3), 288 patients (43.8%) experienced AF recurrence after catheter ablation. Patients who experienced AF recurrence had decreased LAAeV and LAAfV (LAAeV: 56.5 ± 21.2 vs. 59.6 ± 20.7 cm/s, p = .052; LAAfV: 47.5 ± 17.9 vs. 51.7 ± 18.2, p = .003). Kaplan-Meier analysis showed that patients in the low LAAeV (<55 cm/s) group had a poorer event-free survival rate than those in the high LAAeV (≥55 cm/s) group (log-rank p = .012). Patients with LAAfV <48 cm/s had a significantly higher risk of AF recurrence than those with LAAfV ≥48 cm/s (log-rank p = .003). In the multivariable model, low LAAfV pre-ablation in TEE-guided was significantly independently associated with 3-year recurrence after single radiofrequency ablation in patients with PAF, along with LA dimension and duration of AF. CONCLUSION: This study found an independent association between low LAAfV pre-ablation in TEE-guided and 3-year recurrence after single radiofrequency ablation in patients with PAF.


Asunto(s)
Apéndice Atrial , Fibrilación Atrial , Ablación por Catéter , Humanos , Fibrilación Atrial/cirugía , Estudios Prospectivos , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/cirugía , Ecocardiografía/métodos , Ablación por Catéter/métodos , Recurrencia , Resultado del Tratamiento
11.
Pacing Clin Electrophysiol ; 46(1): 20-30, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36401609

RESUMEN

BACKGROUND: Perimitral atrial tachycardia (PMAT) is the most frequent type of iatrogenic atrial tachycardia (AT) after atrial fibrillation (AF) ablation. Vein of Marshall ethanol infusion (EIVOM) is a promising technique in mitral isthmus (MI) ablation. METHODS: A total of 165 patients with PMAT were divided into three groups according to ablation strategies, including RF only group (n = 89), RF-EIVOM group (initial RF ablation with adjunctive EIVOM, n = 28), and EIVOM-RF group (first-step EIVOM with touch-up RF ablation, n = 48). Acute and follow-up procedure outcomes were evaluated. RESULTS: PMAT terminated in 89.9%, 89.3%, and 93.7% of patients in RF only, RF-EIVOM and EIVOM-RF groups, respectively (p = .715), with complete MI block achieved in 80.9%, 89.3%, and 95.8% of patients (EIVOM-RF vs. RF only, p = .012). First-step utilization of EIVOM was associated with a significant shortening of RF ablation time at MI (EIVOM-RF 2.1 ± 1.3 min, RF only 7.9 ± 5.9 min, RF-EIVOM 6.8 ± 5.8 min; p < .001) and a decrease in the proportion of patients need ablation within coronary sinus (CS, EIVOM-RF 14.6%, RF only 61.8%, RF-EIVOM 64.3%; p < .001). After a mean follow-up of 12.1 ± 6.2 months, AF/AT recurred in 39 (43.8%), 6 (21.4%), and 12 (25.0%) patients in RF only, RF-EIVOM, and EIVOM-RF group (RF-EIVOM vs. RF only, p = .026; EIVOM-RF vs. RF only, p = .022). CONCLUSIONS: EIVOM was associated with an enhanced acute MI block rate as well as reduced AF/AT recurrence. First-step utilization of EIVOM promises to significantly simplify the RF ablation process. CONDENSED ABSTRACT: PMAT is the most common type of iatrogenic AT after AF ablation procedures. EIVOM contributed to a higher acute MI block rate and lower arrhythmia recurrence risk during follow-up. First-step utilization of EIVOM significantly reduced the need for radiofrequency ablation at MI and inside CS with the advantage of creating a homogenous, transmural lesion and eliminating epicardial connections.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Taquicardia Supraventricular , Humanos , Etanol , Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Enfermedad Iatrogénica , Resultado del Tratamiento , Recurrencia
12.
Neurochem Res ; 47(10): 3192-3201, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35895152

RESUMEN

Parkinson's disease (PD) is a common neurodegenerative disease. Previously we identified tetranectin (TN) as a differentially expressed protein in the cerebrospinal fluid of PD patients, and we were surprised to find that TN knockout mice developed PD features. However, the specific role of TN in PD has not been clarified. In this study, we aimed to determine the effect of exogenous TN on cellular PD models and elucidate the underlying mechanisms. We found that exogenous TN could alleviate pre-formed-fibrils (PFFs)-induced synucleinopathies in SH-SY5Y cells and reduce the cell-to-cell transmission of α-synuclein (SYN). We also found that TN can promote the degradation of SYN by plasmin, which may account for its effect on cellular PD models. Moreover, administration of SYN/PFFs decreased the expression of TN and increased the expression of plasminogen activator inhibitor-1 (PAI-1) in SH-SY5Y cells, thereby reducing plasmin activity. Our findings depict a possible SYN-TN-plasmin interaction in which elevated levels of extracellular SYN monomers and aggregates in PD diminish the production of TN and PAI-1. Such changes lead to a reduced plasmin activity, which in turn reduces the degradation of extracellular SYN, thus forming a vicious cycle.


Asunto(s)
Neuroblastoma , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Sinucleinopatías , Animales , Fibrinolisina , Humanos , Lectinas Tipo C , Ratones , Enfermedades Neurodegenerativas/metabolismo , Enfermedad de Parkinson/metabolismo , Plasminógeno , Inhibidor 1 de Activador Plasminogénico , alfa-Sinucleína/metabolismo
13.
Semin Dial ; 35(1): 40-49, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34816483

RESUMEN

BACKGROUND: Dialysis unit blood pressure (BP) pattern showed superiority in prognostic evaluation and interdialytic BP burden assessment. However previous studies mainly focused on the recurrent BP pattern within a session (intradialytic BP change or intradialytic BP slope), the clinical value of the weekly pattern of dialysis unit BP is unknown. METHODS: We performed a prospective cohort study in adult end stage renal disease (ESRD) patients on thrice weekly hemodialysis (HD). The slope and the change of the postdialysis systolic BP (SBP) in the course of a week (post-SBP slope and post-SBP change) were used to characterize the weekly pattern of dialysis unit BP. Outcomes included all-cause mortality, cardiovascular mortality, and first cardiovascular event. We also measured the home BP in our cohort. RESULTS: One hundred and twenty-nine subjects were followed over a median of 31 months. Higher post-SBP slope (≥0.185) was independently associated with increased risk of all-cause mortality, cardiovascular mortality, and first cardiovascular event. Results were similar for increased post-SBP change. HD patients with a higher post-SBP slope or an increased post-SBP change also had significant increased interdialytic BP burden measured by home SBP on both dialysis days and non-dialysis days. CONCLUSIONS: Post-SBP slope and post-SBP change might be promising dialysis unit BP markers for prognostic evaluation and interdialytic BP burden assessment.


Asunto(s)
Hipertensión , Fallo Renal Crónico , Adulto , Presión Sanguínea/fisiología , Femenino , Humanos , Hipertensión/etiología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/terapia , Masculino , Pronóstico , Estudios Prospectivos , Diálisis Renal/efectos adversos
14.
Pacing Clin Electrophysiol ; 45(9): 1032-1041, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35866663

RESUMEN

BACKGROUND: Atrial fibrillation (AF) and stable coronary artery disease (SCAD) frequently coexist. This study aimed to assess the long-term outcome of catheter ablation in patients with paroxysmal AF and SCAD. METHODS: In total, 12,104 patients with paroxysmal AF underwent catheter ablation in the Chinese Atrial Fibrillation Registry between 2011 and 2019 were screened. A total of 441 patients with SCAD were matched with patients without SCAD in a 1:4 ratio. The primary endpoint was AF recurrence after single ablation. The composite secondary endpoints were thromboembolism, coronary events, major bleeding, all-cause death. RESULTS: Over a mean follow-up of 46.0 ± 18.9 months, the recurrence rate in patients with SCAD was significantly higher after a single ablation (49.0% vs. 41.9%, p = .03). The very late recurrence rate of AF in the SCAD group was also significantly higher than that in the control group (38.9% vs. 31.2%;p = .04). In multivariate analysis, adjusted with the female, smoking, duration of AF, previous thromboembolism, COPD, and statins, SCAD was independently associated with AF recurrence (adjusted HR, 1.19 [1.02-1.40], p = .03). The composite secondary endpoints were significantly higher in the SCAD group (12.70% vs. 8.54%, p = .02), mainly due to thromboembolism events (8.16% vs. 4.41%, p < .01). CONCLUSIONS: SCAD significantly increased the risk of recurrence after catheter ablation of paroxysmal AF. The incidence of thromboembolic events after catheter ablation of paroxysmal AF in the patients with SCAD was significantly higher than that in those without SCAD.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Enfermedad de la Arteria Coronaria , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Tromboembolia , Ablación por Catéter/efectos adversos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/cirugía , Femenino , Humanos , Recurrencia , Tromboembolia/epidemiología , Tromboembolia/etiología , Resultado del Tratamiento
15.
Pacing Clin Electrophysiol ; 45(12): 1349-1356, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36112388

RESUMEN

BACKGROUND: Debates exist in the repeat ablation strategy for patients with recurrence presenting as persistent atrial fibrillation (AF) after initial persistent AF ablation. OBJECTIVE: To compare the outcome between the "2C3L" and "extensive ablation" approach in patients undergoing repeat procedures for recurrent persistent AF. METHODS: Propensity-score matching was performed in 196 patients with AF recurrence undergoing repeat ablation, and 79 patients treated with "2C3L" strategy were matched to 79 patients treated with "extensive ablation" strategy. The "2C3L" approach included pulmonary vein isolation, mitral isthmus, left atrial roof, and cavotricuspid isthmus ablation, while the "extensive ablation" strategy included extensive ablation of a variety of other targets aiming to terminate the AF. The primary outcome was freedom from any atrial tachyarrhythmia after 24-h ambulatory monitoring follow-up for 12 months. RESULTS: No statistically significant difference was found between the primary outcome between the "2C3L" and the "extensive ablation" group [70.9% vs. 69.6%, p = .862; 95% confidence interval (CI) -12.8 to 15.3], although the "extensive ablation" group had a significantly high proportion of AF termination (19.0% for "2C3L" vs. 41.8% for "extensive ablation" group, p = .002; 95% CI 8.5-35.9). And AF termination was not related to the primary outcome in multifactorial regression. At 40 ± 22 months after the repeat procedure, the primary outcome was also comparable (57.0 % for "2C3L" vs. 48.1% for "extensive ablation" group, p = .265; 95% CI -6.6 to 23.7). CONCLUSION: The outcome between the "2C3L" and "extensive ablation" approaches was comparable in patients undergoing repeat procedures for recurrent persistent AF.


Asunto(s)
Fibrilación Atrial , Humanos , Fibrilación Atrial/cirugía
16.
J Thromb Thrombolysis ; 53(4): 868-877, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34677727

RESUMEN

This study aimed to explore antithrombotic strategy and its relationship with outcomes in patients with atrial fibrillation (AF) at high risk for stroke and chronic coronary syndrome (CCS) in real-world clinical practice. Patients with AF at high risk for stroke complicated with CCS from China Atrial Fibrillation Registry (CAFR) were enrolled. The patients were divided into non-antithrombotic (Non-AT) group, oral anticoagulants (OAC) group, antiplatelet therapy (APT) group (aspirin or clopidogrel), and dual antiplatelet therapy (DAPT) group (aspirin + clopidogrel) according to their antithrombotic strategies at baseline. The patients with OAC + single antiplatelet drug (14 cases) and OAC + dual antiplatelet therapy (7 cases) were excluded for the small sample size. The primary effectiveness outcome was the composite outcome of coronary events, thromboembolism, and all-cause mortality. The primary safety outcome was major bleeding events. From 2011 to 2018, 25,512 patients were included in the CARF study, 769 patients with AF at high risk for stroke and CCS were enrolled in this study. After a follow-up of 47.4 ± 25.3 months, the incidences of primary effectiveness outcome were 44.6%, 25.7%, 43.6%, and 29.1% in the four groups, respectively (P < 0.001). The incidences of primary effectiveness and all-cause mortality were both significantly lower in the OAC group than in the Non-AT group, (25.7% vs. 44.6%, HR 0.53, 95% CI 0.39-0.73, P < 0.001) and (14.6% vs. 38.5%, HR 0.36, 95%CI 0.25-0.52, P < 0.001). In multivariate analysis, age (HR 1.03, 95%CI 1.01-1.05, P = 0.015), heart failure (HR 1.67, 95%CI 1.20-2.33, P = 0.002) and OAC (HR 0.66, 95%CI 0.47-0.91, P = 0.012) were independent factors for the composite outcome. There was no significant difference in major bleeding events between the four groups. OAC monotherapy significantly reduced the primary effectiveness composite outcome and all-cause mortality in the patients with AF at high risk for stroke complicated with CCS. However, there was no significant difference in major bleeding among the different antithrombotic strategies.Trial Registration www.chictr.org.cn (No. ChiCTR-OCH-13003729).


Asunto(s)
Fibrilación Atrial , Enfermedad Coronaria , Fibrinolíticos , Anticoagulantes/efectos adversos , Aspirina/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Clopidogrel/efectos adversos , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/tratamiento farmacológico , Fibrinolíticos/efectos adversos , Hemorragia/epidemiología , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Resultado del Tratamiento
17.
Med Sci Monit ; 28: e934747, 2022 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-35418552

RESUMEN

BACKGROUND Low-density lipoprotein cholesterol (LDL-C) reduction improves cardiovascular outcomes. This study investigates the relationship between lipid levels and outcomes in patients with nonvalvular atrial fibrillation by LDL-C quarters. MATERIAL AND METHODS Patients with atrial fibrillation were enrolled from 31 typical hospitals in China. Of 19 515 patients, 6775 with nonvalvular atrial fibrillation (NVAF) were followed for 5 years or until an event occurred. RESULTS Hyperlipidemia was not an independent risk factor for stroke/thromboembolism and cardiovascular mortality among patients with NVAF (hazard ratio 0.82, 95% CI 0.7-0.96, P=0.82). When patients were divided into quartiles according to LDL-C levels at the time of enrollment (Q1, <1.95; Q2, 1.95-2.51; Q3, 2.52-3.09; and Q4, >3.09 mmol/L), as LDL-C increased, events tapered off according to Kaplan-Meier curves for patients who were without oral anticoagulants and off statins (non-OAC; log-rank=8.3494, P=0.0393) and for those with oral anticoagulants (OAC; log-rank=6.7668 P=0.0797). This relationship was stronger for patients who were without OAC treatment and off statins than for those with OAC treatment. The relationship was not significant in patients with or without OAC and on statins (log-rank=2.5080, P=0.4738). This relationship also existed in patients with CHA2DS2-VASc scores <2 (log-rank=5.893, P=0.1167). For those with CHA2DS2-VASc scores ≥2 (log-rank=6.6163, P=0.0852), the relationship was stronger. CONCLUSIONS In patients with NVAF using standard or no lipid-lowering medication, low plasma LDL-C levels were related to an increased risk of stroke/thromboembolism and cardiovascular mortality.


Asunto(s)
Fibrilación Atrial , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Accidente Cerebrovascular , Tromboembolia , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , LDL-Colesterol , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Sistema de Registros , Factores de Riesgo , Accidente Cerebrovascular/complicaciones
18.
J Med Internet Res ; 24(11): e42185, 2022 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-36449345

RESUMEN

BACKGROUND: Interest in critical care-related artificial intelligence (AI) research is growing rapidly. However, the literature is still lacking in comprehensive bibliometric studies that measure and analyze scientific publications globally. OBJECTIVE: The objective of this study was to assess the global research trends in AI in intensive care medicine based on publication outputs, citations, coauthorships between nations, and co-occurrences of author keywords. METHODS: A total of 3619 documents published until March 2022 were retrieved from the Scopus database. After selecting the document type as articles, the titles and abstracts were checked for eligibility. In the final bibliometric study using VOSviewer, 1198 papers were included. The growth rate of publications, preferred journals, leading research countries, international collaborations, and top institutions were computed. RESULTS: The number of publications increased steeply between 2018 and 2022, accounting for 72.53% (869/1198) of all the included papers. The United States and China contributed to approximately 55.17% (661/1198) of the total publications. Of the 15 most productive institutions, 9 were among the top 100 universities worldwide. Detecting clinical deterioration, monitoring, predicting disease progression, mortality, prognosis, and classifying disease phenotypes or subtypes were some of the research hot spots for AI in patients who are critically ill. Neural networks, decision support systems, machine learning, and deep learning were all commonly used AI technologies. CONCLUSIONS: This study highlights popular areas in AI research aimed at improving health care in intensive care units, offers a comprehensive look at the research trend in AI application in the intensive care unit, and provides an insight into potential collaboration and prospects for future research. The 30 articles that received the most citations were listed in detail. For AI-based clinical research to be sufficiently convincing for routine critical care practice, collaborative research efforts are needed to increase the maturity and robustness of AI-driven models.


Asunto(s)
Inteligencia Artificial , Medicina , Humanos , Cuidados Críticos , Bibliometría , Unidades de Cuidados Intensivos
19.
J Transl Med ; 19(1): 355, 2021 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-34404433

RESUMEN

BACKGROUND: Diabetic nephropathy (DN) is a leading cause of renal failure, whereas the effective and early diagnostic biomarkers are still lacking. METHODS: Fourteen cytokines and chemokines mRNA were detected in urinary extracellular vesicles (EVs) from the screening cohort including 4 healthy controls (HC), 4 diabetes mellitus (DM) and 4 biopsy-proven DN patients, and was validated in another 16 HC and 15 DM and 28 DN patients. Correlation analysis was performed between the candidate biomarkers and clinic parameters as well as kidney histological changes. The findings were also confirmed in DN rat model with single injection of STZ. RESULTS: The number of small EVs secreted in urine was increased in DN patients compared to DM patients and healthy controls, with expression of AQP1 (a marker of proximal tubules) and AQP2 (a marker of distal/collecting tubules). Small EVs derived CCL21 mRNA increased significantly in DN patients and correlated with level of proteinuria and eGFR. Interestingly, elevated CCL21 mRNA from urine small EVs was observed in DN patients with normal renal function and could discriminate early DN patients from DM more efficiently compared to eGFR and proteinuria. CCL21 also showed an accurate diagnostic ability in distinguishing incipient from overt DN. Histologically, CCL21 mRNA expression increased progressively with the deterioration of tubulointerstitial inflammation and showed the highest level in nodular sclerosis group (class III) in DN patients. Remarkable infiltration of CD3 positive T cells including both CD4 and CD8 positive T cell population were observed in DN patients with high-CCL21 expression. Besides, accumulation of CD3 positive T cells correlated with level of urinary small EVs derived CCL21 and co-localized with CCL21 in the tubulointerstitium in DN patients. Finally, the correlation of CCL21 expression in renal cortex and urinary small EVs was confirmed in STZ-induced DN rat model. CONCLUSIONS: Urinary small EVs derived CCL21 mRNA may serve as early biomarker for identifying DN linked with pathogenesis. CCL21 mRNA mediated T cell infiltration may constitute the key mechanism of chronic inflammation in DN.


Asunto(s)
Quimiocina CCL21 , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Vesículas Extracelulares , Animales , Acuaporina 2 , Biomarcadores , Quimiocina CCL21/genética , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/genética , Humanos , ARN Mensajero/genética , Ratas
20.
J Surg Res ; 266: 353-360, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34087618

RESUMEN

BACKGROUND: The aim of this study was to investigate the secretion patterns of brain natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP) after traumatic brain injury (TBI) and to analyze the source of them in cerebrospinal fluid (CSF). MATERIALS AND METHODS: We synchronously measured BNP and NT-proBNP concentrations in paired CSF and plasma samples from 22 moderate to severe TBI patients and 40 healthy control patients. The CSF and/or plasma ratio of albumin (QAlbumin) was calculated daily. The BNP and NT-proBNP levels of CSF and plasma were compared between TBI patients and control patients. RESULTS: CSF BNP and NT-proBNP levels peaked on day 3 after injury, as did the plasma BNP and NT-proBNP levels. The CSF BNP and NT-proBNP levels in TBI patients were elevated from day 1, which was significantly higher than control group (P < 0.05 and P < 0.01, respectively). However, in plasma, only NT-proBNP levels were significantly higher than in the control group from day 2 (P < 0.05). In addition, QBNP, defined as CSF BNP concentration and/or plasma BNP concentration, was significantly higher in TBI patients than in the control group (P < 0.01). However, QAlbumin remained within ranges of a mild to moderate dysfunction of blood-brain-barrier in TBI patients. CONCLUSIONS: CSF BNP concentrations are elevated and peak on day 3 after moderate to severe TBI. CSF BNP may originate from the brain and may be a potential biomarker of TBI.


Asunto(s)
Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/líquido cefalorraquídeo , Péptido Natriurético Encefálico/sangre , Péptido Natriurético Encefálico/líquido cefalorraquídeo , Fragmentos de Péptidos/sangre , Fragmentos de Péptidos/líquido cefalorraquídeo , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad
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