RESUMO
We aimed to identify serum exosomal microRNAs (miRNAs) associated with the transition from atrial fibrillation (AF) to sinus rhythm (SR) and investigate their potential as biomarkers for the early recurrence of AF within three months post-treatment. We collected blood samples from eight AF patients at Chang Gung Memorial Hospital in Taiwan both immediately before and within 14 days following rhythm control treatment. Exosomes were isolated from these samples, and small RNA sequencing was performed. Using DESeq2 analysis, we identified nine miRNAs (16-2-3p, 22-3p, 23a-3p, 23b-3p, 125a-5p, 328-3p, 423-5p, 504-5p, and 582-3p) associated with restoration to SR. Further analysis using the DIABLO model revealed a correlation between the decreased expression of miR-125a-5p and miR-328-3p and the early recurrence of AF. Furthermore, early recurrence is associated with a longer duration of AF, presumably indicating a more extensive state of underlying cardiac remodeling. In addition, the reads were mapped to mRNA sequences, leading to the identification of 14 mRNAs (AC005041.1, ARHGEF12, AMT, ANO8, BCL11A, DIO3OS, EIF4ENIF1, G2E3-AS1, HERC3, LARS, NT5E, PITX1, SLC16A12, and ZBTB21) associated with restoration to SR. Monitoring these serum exosomal miRNA and mRNA expression patterns may be beneficial for optimizing treatment outcomes in AF patients.
Assuntos
Fibrilação Atrial , Exossomos , MicroRNAs , Humanos , Fibrilação Atrial/genética , MicroRNAs/genética , Coração , Exossomos/genética , RNA Mensageiro , AnoctaminasRESUMO
The loss of semaphorin 3A (Sema3A), which is related to endothelial-to-mesenchymal transition (EndMT) in atrial fibrosis, is implicated in the pathogenesis of atrial fibrillation (AF). To explore the mechanisms by which EndMT affects atrial fibrosis and assess the potential of a Sema3A activator (naringin) to prevent atrial fibrosis by targeting transforming growth factor-beta (TGF-ß)-induced EndMT, we used human atria, isolated human atrial endocardial endothelial cells (AEECs), and used transgenic mice expressing TGF-ß specifically in cardiac tissues (TGF-ß transgenic mice). We evaluated an EndMT marker (Twist), a proliferation marker (proliferating cell nuclear antigen; PCNA), and an endothelial cell (EC) marker (CD31) through triple immunohistochemistry and confirmed that both EndMT and EC proliferation contribute to atrial endocardial fibrosis during AF in TGF-ß transgenic mice and AF patient tissue sections. Additionally, we investigated the impact of naringin on EndMT and EC proliferation in AEECs and atrial fibroblasts. Naringin exhibited an antiproliferative effect, to which AEECs were more responsive. Subsequently, we downregulated Sema3A in AEECs using small interfering RNA to clarify a correlation between the reduction in Sema3A and the elevation of EndMT markers. Naringin treatment induced the expression of Sema3A and a concurrent decrease in EndMT markers. Furthermore, naringin administration ameliorated AF and endocardial fibrosis in TGF-ß transgenic mice by stimulating Sema3A expression, inhibiting EndMT markers, reducing atrial fibrosis, and lowering AF vulnerability. This suggests therapeutic potential for naringin in AF treatment.
Assuntos
Fibrilação Atrial , Proliferação de Células , Células Endoteliais , Transição Epitelial-Mesenquimal , Flavanonas , Átrios do Coração , Semaforina-3A , Fator de Crescimento Transformador beta , Animais , Humanos , Masculino , Camundongos , Fibrilação Atrial/metabolismo , Fibrilação Atrial/patologia , Fibrilação Atrial/genética , Fibrilação Atrial/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose , Flavanonas/farmacologia , Átrios do Coração/metabolismo , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/patologia , Camundongos Transgênicos , Semaforina-3A/metabolismo , Semaforina-3A/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: Sustained, chronic activation of ß-adrenergic receptor (ß-AR) signaling leads to cardiac arrhythmias, with exchange proteins directly activated by cAMP (Epac1 and Epac2) as key mediators. This study aimed to evaluate whether CD44, a transmembrane receptor mediating various cellular responses, participates in Epac-dependent arrhythmias. METHODS: The heart tissue from CD44 knockout (CD44-/-) mice, cultured HL-1 myocytes and the tissue of human ventricle were used for western blot, co-immunoprecipitaiton and confocal studies. Line-scanning confocal imaging was used for the study of cellular Ca2+ sparks on myocytes. Optical mapping and intra-cardiac pacing were applied for arrhythmia studies on mice's hearts. RESULTS: In mice, isoproterenol, a ß-AR agonist, upregulated CD44 and Epac1 and increased the association between CD44 and Epac1. Isoproterenol upregulated the expression of phospho-CaMKII (p-CaMKII), phospho-ryanodine receptor (p-RyR), and phospho-phospholamban (p-PLN) in mice and cultured myocytes; these effects were attenuated in CD44-/- mice compared with wild-type controls. In vitro, isoproterenol, 8-CPT-cAMP (an Epac agonist), and osteopontin (a ligand of CD44) significantly upregulated the expression of p-CaMKII, p-RyR, and p-PLN; this effect was attenuated by CD44 small interfering RNA (siRNA). In myocytes, resting Ca2+ sparks were induced by isoproterenol and overexpressed CD44, which were prevented by inhibiting CD44. Ex vivo optical mapping and in vivo intra-cardiac pacing studies showed isoproterenol-induced triggered events and arrhythmias in ventricles were prevented in CD44-/- mice. The inducibility of ventricular arrhythmias (VAs) was attenuated in CD44-/- HF mice compared with wild-type HF controls. In patients, CD44 were upregulated, and the association between CD44 and Epac1 were increased in ventricles with reduced contractility. CONCLUSION: CD44 regulates ß-AR- and Epac1-mediated Ca2+-handling abnormalities and VAs. Inhibition of CD44 is effective in reducing VAs in HF, which is potentially a novel therapeutic target for preventing the arrhythmias and sudden cardiac death in patients with diseased hearts.
Assuntos
Fatores de Troca do Nucleotídeo Guanina , Receptores Adrenérgicos beta , Humanos , Camundongos , Animais , Receptores Adrenérgicos beta/genética , Receptores Adrenérgicos beta/metabolismo , Isoproterenol/farmacologia , Isoproterenol/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/farmacologia , Miócitos Cardíacos/metabolismo , Cálcio/metabolismo , Arritmias Cardíacas/genética , Arritmias Cardíacas/metabolismo , Sinalização do Cálcio , Adrenérgicos/metabolismo , Adrenérgicos/farmacologia , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismoRESUMO
BACKGROUND: The sutureless valve has gained popularity for degenerative aortic valve stenosis but not congenital bicuspid aortic valve (BAV) due to anatomical challenges. We reviewed our modified implant techniques for patients with BAV. METHODS: From June 2015 to June 2019, 66 patients with aortic valve stenosis were treated with the Perceval sutureless valve, 20 of whom had BAV. The demographics, type of BAV (the Sievers classification), and associated pathologies, surgical outcomes, and midterm hemodynamics were recorded. RESULTS: The median age was 64 (range: 49-81) years and the Society of Thoracic Surgeons score was 2.186 (range: 0.407-6.384). Annular plication was performed in 9 (75%) of 12 type 0 and 3 (37.5%) of 8 type I, with implanted valve sizes of M, L, and XL in 6, 10, 4 cases, respectively. Three patients, all type 0 in the initial learning periods, required intraoperative redeployment due to malposition of the valve. The final implant was successful in all without conversion to traditional prosthesis. The median extubation time was 4 hours and the durations of intensive care unit and hospital stay were 1 and 6 days. At a median follow-up of 46 (23-72) months, there was one late mortality due to hemorrhagic stroke sequel. The last echo revealed none had more than mild paravalvular leakage and the mean transvalvular pressure gradient remained stable at 9.70 (range: 6.94-15.0) mm Hg. CONCLUSION: The sutureless valve can achieve satisfactory outcomes in BAV without paravalvular leakage and excellent hemodynamics. It may serve as the benchmark for transcatheter aortic valve implantation in this unique population.
Assuntos
Estenose da Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Doenças das Valvas Cardíacas , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Humanos , Pessoa de Meia-Idade , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/cirurgia , Doenças das Valvas Cardíacas/complicações , Doença da Válvula Aórtica Bicúspide/cirurgia , Resultado do Tratamento , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodosRESUMO
BACKGROUND: Perioperative coagulopathy and intractable bleeding are severe complications in acute type A aortic dissection (ATAAD) repair surgery. Mediastinal packing with delayed sternal closure (DSC) is a commonly adapted technique to stabilize the hemorrhagic tendency. This retrospective study aims to investigate the early and late outcomes and risk factors in patients who underwent DSC procedure during ATAAD repair surgery. METHODS: This study investigated 704 consecutive patients who underwent ATAAD repair at this institution between January 2007 and September 2020. These patients were dichotomized into the DSC (n = 109; 15.5%) and primary sternal closure (PSC) groups (n = 595; 84.5%). The clinical features, surgical information, postoperative complications, 5-years cumulative survival, and freedom from reoperation rates were compared. A multivariate logistic regression analysis was used to identify the independent risk factors for patients who underwent DSC. RESULTS: The DSC group showed a higher rate of hemopericardium and preoperative malperfusion, and was associated with longer cardiopulmonary bypass and aortic clamping times and a higher rate of intraoperative extracorporeal membrane oxygenation (ECMO) support. The DSC group showed higher blood transfusion volumes and rate of reexploration for bleeding after surgery. However, the in-hospital mortality rates (17.4% vs. 13.3%; P = 0.249), 5-year survival rates (66.9% vs. 68.2%; P = 0.635), and freedom from reoperation rates (89.1% vs. 82.5%; P = 0.344) were comparable between the DSC and PSC groups. Multivariate analysis revealed that hemopericardium, preoperative malperfusion, and intraoperative ECMO support were risk factors for implementing DSC. CONCLUSIONS: DSC is an efficient life-saving technique to stabilize patients with intractable bleeding after undergoing ATAAD repair surgery, which leads to acceptable short- and long-term outcomes. Patients who were at risk for intractable bleeding should have early decision-making for implementing DSC.
Assuntos
Dissecção Aórtica , Derrame Pericárdico , Dissecção Aórtica/cirurgia , Humanos , Estudos Retrospectivos , Fatores de Risco , Esterno/cirurgia , Resultado do TratamentoRESUMO
Atrial fibrosis is an essential contributor to atrial fibrillation (AF). It remains unclear whether atrial endocardial endothelial cells (AEECs) that undergo endothelial-mesenchymal transition (EndMT) are among the sources of atrial fibroblasts. We studied human atria, TGF-ß-treated human AEECs, cardiac-specific TGF-ß-transgenic mice, and heart failure rabbits to identify the underlying mechanism of EndMT in atrial fibrosis. Using isolated AEECs, we found that miR-181b was induced in TGF-ß-treated AEECs, which decreased semaphorin 3A (Sema3A) and increased EndMT markers, and these effects could be reversed by a miR-181b antagomir. Experiments in which Sema3A was increased by a peptide or decreased by a siRNA in AEECs revealed a mechanistic link between Sema3A and LIM-kinase 1/phosphorylated cofilin (LIMK/p-cofilin) signaling and suggested that Sema3A is upstream of LIMK in regulating actin remodeling through p-cofilin. Administration of the miR-181b antagomir or recombinant Sema3A to TGF-ß-transgenic mice evoked increased Sema3A, reduced EndMT markers, and significantly decreased atrial fibrosis and AF vulnerability. Our study provides a mechanistic link between the induction of EndMT by TGF-ß via miR-181b/Sema3A/LIMK/p-cofilin signaling to atrial fibrosis. Blocking miR-181b and increasing Sema3A are potential strategies for AF therapeutic intervention.
Assuntos
Fibrilação Atrial , MicroRNAs , Semaforina-3A , Fatores de Despolimerização de Actina , Animais , Antagomirs , Fibrilação Atrial/genética , Fibrilação Atrial/metabolismo , Fibrilação Atrial/patologia , Células Endoteliais , Transição Epitelial-Mesenquimal , Fibrose , Átrios do Coração , Camundongos , Camundongos Transgênicos , MicroRNAs/genética , MicroRNAs/metabolismo , Coelhos , Semaforina-3A/genética , Semaforina-3A/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
Extracorporeal membrane oxygenation (ECMO) is one of the common invasive treatments for the care of critically ill patients with heart failure, respiratory failure, or both. There are two modes of ECMO, namely, veno-venous (VV) and veno-arterial (VA), which have different indications, survival rates, and incidences of complications. This study's aim was to examine whether depression status differed between patients who had received VV-ECMO or VA-ECMO and had been discharged from the hospital. This was a descriptive, cross-sectional, and correlational study of patients who had been discharged from the hospital at least one month after receiving ECMO at a medical center in northern Taiwan from June 2006 to June 2020 (N = 142). Participants were recruited via convenience and quota sampling. Data were collected in the cardiovascular outpatient department between October 2015-October 2016 (n = 52) and September 2019-August 2020 (n = 90). Participants completed the Hospital Anxiety and Depression Scale-Depression (HADS-D) as a measure of depression status. Post-discharge depression scores for patients who received VV-ECMO (n = 67) was significantly higher (p = 0.018) compared with participants who received VA-ECMO (n = 75). In addition, the mode of ECMO was a predictor of post-discharge depression (p = 0.008) for participants who received VV-ECMO. This study concluded that patients who received VV-ECMO may require greater mental health support. Healthcare professionals should establish a psychological clinical care pathway evaluated by multiple healthcare professionals.
Assuntos
Oxigenação por Membrana Extracorpórea , Assistência ao Convalescente , Estudos Transversais , Depressão/epidemiologia , Depressão/terapia , Oxigenação por Membrana Extracorpórea/efeitos adversos , Humanos , Alta do Paciente , Estudos Retrospectivos , SobreviventesRESUMO
BACKGROUND: Patients with critical illness may face challenges after hospital discharge; therapeutic outcomes of extracorporeal membrane oxygenation (ECMO) are typically measured by survival rate. However, ECMO is an integral part of treatment in critical care medicine, which requires an outcome measure beyond survival. Post-discharge health-related quality of life (HRQoL) is such an indicator. OBJECTIVES: To measure HRQoL in adult patients who had previously undergone ECMO and explore influential factors related to HRQoL. METHODS: This cross-sectional descriptive study used a convenience sample of patients discharged between April 2006-April 2016 after at least one month following ECMO. The study was conducted from October 2015 to October 2016, which included data collected from structured questionnaires: the Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised and Short-Form Survey-36-v2. Stepwise linear regression determined predictor variables of physical and mental HRQoL. RESULTS: Age of participants (N = 144) ranged from 24 to 81 years; long-term survival rate was 28.6% after a median follow-up of 1060 days (range = 44-3150 days). Mean scores for physical and mental components of HRQoL were 46.32 and 50.39, respectively. Level of HRQoL was low to moderate. Employment affected all physical components of HRQoL; depression was the main predictor for physical and mental components. Self-perceived health status and anxiety were also factors that influenced HRQoL. CONCLUSIONS: Variables of employment, self-perceived health status and mental health influenced HRQoL. Early assessment of these factors by healthcare professionals can allow integration of multidimensional interventions following hospital discharge, which could improve HRQoL for patients weaned from ECMO.
Assuntos
Oxigenação por Membrana Extracorpórea , Adulto , Assistência ao Convalescente , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Pessoa de Meia-Idade , Alta do Paciente , Qualidade de Vida , Adulto JovemRESUMO
BACKGROUND: Postoperative stroke is a severe and potentially disabling complication following surgical intervention for acute type A aortic dissection (ATAAD). This retrospective study aims to compare the early and late outcomes between patients who had hemorrhagic and ischemic stroke after undergoing ATAAD repair surgery. METHODS: Between January 2007 and June 2020, a total of 685 consecutive patients underwent ATAAD repair at our institution. Patients who had a preoperative stroke or were unconscious at presentation were excluded from this study. Of the 656 included for analysis, 102 (15.5%) patients had a postoperative stroke confirmed by computed tomography angiography. The strokes were classified into the ischemia group (n = 83, 12.7%) and hemorrhage group (n = 19, 2.9%). Clinical features, surgical information, postoperative complications, modified Rankin Scale (mRS) scores after discharge, and 5-year cumulative survival rates were compared. RESULTS: Demographics, comorbidities, and presentations of ATAAD were similar between the two groups, except a higher rate of preoperative antithrombotic medication was found in the hemorrhage group. The hemorrhage group was associated with a higher complexity of aortic arch replacement, longer cardiopulmonary bypass, and aortic clamping times than the ischemia group. A higher in-hospital mortality rate (42.1% versus 20.5%; p = 0.048) and a higher median mRS score at the 3-month follow-up after discharge (6[3-6] versus 4[2-6]; p = 0.027) were found in the hemorrhage group. The hemorrhage group showed a lower 5-year cumulative survival rate (23.4% versus 57.8%; p = 0.003) compared with the ischemia group. CONCLUSIONS: Postoperative hemorrhagic stroke was associated with poorer neurological outcomes and lower survival rates than those with ischemic stroke. Patients who have complex arch replacement, long cardiopulmonary bypass and aortic clamping times are at risk for postoperative hemorrhagic stroke and should have intensive neurological surveillance for early diagnosis and treatment after ATAAD repair surgery.
Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Acidente Vascular Cerebral , Doença Aguda , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Hemorragia , Humanos , Isquemia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
Extracorporeal membrane oxygenation (ECMO) is considered a salvage therapy in cases of severe acute respiratory distress syndrome (ARDS) with profound hypoxemia. However, the need for high-volume fluid resuscitation and blood transfusions after ECMO initiation introduces a risk of fluid overload. Positive fluid balance is associated with mortality in critically ill patients, and conservative fluid management for ARDS patients has been shown to shorten both the duration of mechanical ventilation and time spent in intensive care, albeit without a significant effect on survival. Nonetheless, few studies have addressed the influence of fluid balance on clinical outcomes in severe ARDS patients undergoing ECMO. In the current retrospective study, we examined the impact of cumulative fluid balance (CFB) on hospital mortality in 152 cases of severe ARDS treated using ECMO. Overall hospital mortality was 53.3%, and we observed a stepwise positive correlation between CFB and the risk of death. Cox regression models revealed that CFB during the first 3 days of ECMO was independently associated with higher hospital mortality (adjusted hazard ratio 1.110 [95% CI 1.027-1.201]; p = 0.009). Our findings indicate the benefits of a conservative treatment approach to avoid fluid overload during the early phase of ECMO when dealing with severe ARDS patients.
RESUMO
Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome caused by direct (local damage to lung parenchyma) or indirect lung injury (insults from extrapulmonary sites with acute systemic inflammatory response), the clinical and biological complexity can have a profound effect on clinical outcomes. We performed a retrospective analysis of 152 severe ARDS patients receiving extracorporeal membrane oxygenation (ECMO). Our objective was to assess the differences in clinical characteristics and outcomes of direct and indirect ARDS patients receiving ECMO. Overall hospital mortality was 53.3%. A total of 118 patients were assigned to the direct ARDS group, and 34 patients were assigned to the indirect ARDS group. The 28-, 60-, and 90-day hospital mortality rates were significantly higher among indirect ARDS patients (all p < 0.05). Cox regression models demonstrated that among direct ARDS patients, diabetes mellitus, immunocompromised status, ARDS duration before ECMO, and SOFA score during the first 3 days of ECMO were independently associated with mortality. In indirect ARDS patients, SOFA score and dynamic compliance during the first 3 days of ECMO were independently associated with mortality. Our findings revealed that among patients receiving ECMO, direct and indirect subphenotypes of ARDS have distinct clinical outcomes and different predictors for mortality.
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Urinary liver-type fatty acid binding protein (L-FABP) is a novel biomarker with promising performance in detecting kidney injury. Previous studies reported that L-FABP showed moderate discrimination in patients that underwent cardiac surgery, and other studies revealed that longer duration of cardiopulmonary bypass (CPB) was associated with a higher risk of postoperative acute kidney injury (AKI). This study aims to examine assessing CPB duration first, then examining L-FABP can improve the discriminatory ability of L-FABP in postoperative AKI. A total of 144 patients who received cardiovascular surgery were enrolled. Urinary L-FABP levels were examined at 4 to 6 and 16 to 18 h postoperatively. In the whole study population, the AUROC of urinary L-FABP in predicting postoperative AKI within 7 days was 0.720 at 16 to 18 h postoperatively. By assessing patients according to CPB duration, the urinary L-FABP at 16 to 18 h showed more favorable discriminating ability with AUROC of 0.742. Urinary L-FABP exhibited good performance in discriminating the onset of AKI within 7 days after cardiovascular surgery. Assessing postoperative risk of AKI through CPB duration first and then using urinary L-FABP examination can provide more accurate and satisfactory performance in predicting postoperative AKI.
RESUMO
BACKGROUND: The DeBakey classification divides Stanford acute type A aortic dissection (ATAAD) into DeBakey type I (D1) and type II (D2) according to the extent of acute aortic dissection (AAD). This retrospective study aimed to compare the early and late outcomes of D1-AAD and D2-AAD through a propensity score-matched analysis. METHODS: Between January 2009 and April 2020, 599 consecutive patients underwent ATAAD repair at our institution, and were dichotomized into D1 (n = 543; 90.7%) and D2 (n = 56; 9.3%) groups. Propensity scoring was performed with a 1:1 ratio, resulting in a matched cohort of 56 patients per group. The clinical features, postoperative complications, 5-year cumulative survival and freedom from reoperation rates were compared. RESULTS: In the overall cohort, the D1 group had a lower rate of preoperative shock and more aortic arch replacement with longer cardiopulmonary bypass time. The D1 group had a higher in-hospital mortality rate than the D2 group in overall (15.8% vs 5.4%; P = 0.036) and matched cohorts (19.6% vs 5.4%; P = 0.022). For patients that survived to discharge, the D1 and D2 groups demonstrated similar 5-year survival rates in overall (77.0% vs 85.2%; P = 0.378) and matched cohorts (79.1% vs 85.2%; P = 0.425). The 5-year freedom from reoperation rates for D1 and D2 groups were 80.0% and 97.1% in overall cohort (P = 0.011), and 93.6% and 97.1% in matched cohort (P = 0.474), respectively. CONCLUSIONS: Patients with D1-AAD had a higher risk of in-hospital mortality than those with D2-AAD. However, for patients who survived to discharge, the 5-year survival rates were comparable between both groups.
Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Doença Aguda , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Feminino , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The high mortality rate of patients with severe acute respiratory distress syndrome (ARDS) warrants aggressive clinical intervention. Extracorporeal membrane oxygenation (ECMO) is a salvage therapy for life-threatening hypoxemia. Randomized controlled trials of ECMO for severe ARDS comprise a number of ethical and methodological issues. Therefore, indications and optimal timing for implementation of ECMO, and predictive risk factors for outcomes have not been adequately investigated. We performed propensity score matching to match ECMO-supported and non-ECMO-supported patients at 48 h after ARDS onset for comparisons based on clinical outcomes and hospital mortality. A total of 280 severe ARDS patients were included, and propensity score matching of 87 matched pairs revealed that the 90-d hospital mortality rate was 56.3% in the ECMO group and 74.7% in the non-ECMO group (p = 0.028). Subgroup analysis revealed that greater severity of ARDS, higher airway pressure, or a higher Sequential Organ Failure Assessment score tended to benefit from ECMO treatment in terms of survival. Multivariate logistic regression revealed that hospital mortality was significantly lower among patients who received ECMO than among those who did not. Our findings suggested that early initiation of ECMO (within 48 h) may increase the likelihood of survival for patients with severe ARDS.
RESUMO
Patients with primary mitral regurgitation (MR) may remain asymptomatic for many years. For unknown reasons, some shift from a compensated to a decompensated state and progress to fatal heart failure. To elucidate the genetic determinants of this process, we recruited 28 patients who underwent mitral valve surgery and stratified them into control, compensated MR, and decompensated MR groups. Tissue biopsies were obtained from the patients' left ventricular (LV) lateral wall for a transcriptome-wide profiling of 64,769 probes to identify differentially expressed genes (DEGs). Using cutoff values at the 1% FDR significance level and sex- and age-adjusted regression models, we identified 12 significant DEGs (CTGF, MAP1B, SERPINE1, MYH9, MICAL2, MYO1D, CRY1, AQP7P3, HTRA1, PRSS23, IGFBP2, and FN1). The most significant gene was CTGF (adjusted R2 = 0.74, p = 1.80 × 10-8). We found that the majority of genes expressed in the more advanced decompensated MR group were pro-fibrotic genes associated with cardiac fibrosis. In particular, six pro-fibrotic genes (CTGF, SERPINE1, MYH9, HTRA1, PRSS23, and FN1) were overexpressed and enriched in pathways involved in ECM (extracellular matrix) protein remodeling. Therapeutic interventions that antagonize these six genes may slow the progression toward decompensated MR.
Assuntos
Ventrículos do Coração/metabolismo , Insuficiência da Valva Mitral/metabolismo , Insuficiência da Valva Mitral/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Biópsia , Matriz Extracelular/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/patologia , Insuficiência da Valva Mitral/complicações , Análise de Sequência com Séries de Oligonucleotídeos , Análise de Regressão , Volume Sistólico , Transcriptoma , Disfunção Ventricular Esquerda/complicações , Função Ventricular Esquerda , Remodelação Ventricular/genéticaRESUMO
The Perceval sutureless valve has gained in popularity for treating degenerative aortic valve stenosis but not for congenital type 0 bicuspid aortic valve owing to anatomic challenges. We modified implant techniques following the four principles of ECHO-an acronym for elasticity, circularity, height, and orientation-to prevent paravalvular leakage and malposition.
Assuntos
Implante de Prótese de Valva Cardíaca/métodos , Próteses Valvulares Cardíacas , Estenose da Valva Mitral/cirurgia , Valva Mitral/anormalidades , Procedimentos Cirúrgicos sem Sutura/métodos , Humanos , Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/congênito , Estenose da Valva Mitral/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP referenced to predicted body weight (PBW) or respiratory system compliance have better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO). METHODS: We performed a retrospective analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded. RESULTS: A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3%. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that mean MP alone, MP referenced to PBW, and MP referenced to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP referenced to compliance (HR 2.289 [95% CI 1.214-4.314], p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 [95% CI 1.018-1.104], p = 0.005) or MP referenced to PBW (HR 1.004 [95% CI 1.002-1.007], p < 0.001). The 90-day hospital mortality of patients with high MP (> 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (⦠14.4 J/min) (70.7% vs. 46.8%, p = 0.004), and the 90-day hospital mortality of patients with high MP referenced to compliance (> 0.53 J/min/ml/cm H2O) during the first 3 days of ECMO was significantly higher than that of patients with low MP referenced to compliance (⦠0.53 J/min/ml/cm H2O) (63.6% vs. 29.7%, p < 0.001). CONCLUSIONS: MP during the first 3 days of ECMO was the only ventilatory variable independently associated with 90-day hospital mortality, and MP referenced to compliance during ECMO was more predictive for mortality than was MP alone.
Assuntos
Oxigenação por Membrana Extracorpórea/classificação , Mortalidade Hospitalar/tendências , Fenômenos Mecânicos , Síndrome do Desconforto Respiratório/mortalidade , Adulto , Idoso , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/epidemiologia , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , Estatísticas não Paramétricas , Taiwan/epidemiologiaRESUMO
BACKGROUND/PURPOSE: Understanding of the three-dimensional airway space in three skeletal patterns is important in orthodontic treatment. This study investigated differences between the volume of pharyngeal airway sections and the smallest cross-sectional area in three skeletal patterns by using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: The 90 patients were collected to measure total pharyngeal airway volume (TP), velopharyngeal airway volume (VP), glossopharyngeal airway volume (GP), oropharyngeal airway volume (OP), hypopharyngeal airway volume (HP), and the smallest cross-sectional areas (SCA) of the upper respiratory tract as well as other relevant anatomical structures. The mean values differences between classes were analyzed using ANOVA. Pearson's test was used to compare classes in terms of the correlations between different factors. RESULTS: Patients in skeletal classes I and III exhibited significantly higher SCA values (322.6 mm2and 344.5â¯mm2 respectively) than those in skeletal class II (240.8â¯mm2). Subjects from skeletal classes I and III exhibited significantly higher values of VP, HP, and OP than those in skeletal class II. Skeletal classes I and III exhibited significantly higher TP values (31190.1â¯mm3 and 30696.2â¯mm3, respectively) than those in skeletal class II (22386.0â¯mm3). Non-significant relationships were discovered between pharyngeal airway and skeletal pattern. Conversely, significant relationships were found between TP and gender, ANB, SNB, hyoid and pogonion positions. CONCLUSION: The skeletal class II has smaller airway volume than those in skeletal class I and III. The pharyngeal airway volumes could serve as a guide in differentiating the different skeletal classes in clinical settings.
RESUMO
Aldehyde dehydrogenase 2 (ALDH2) is an enzyme that detoxifies reactive oxygen species (ROS)-generated aldehyde adducts such as 4-hydroxy-trans-2-nonenal (4-HNE). Previous meta-analyses have shown an increase in the risk of atrial fibrillation (AF) in patients with chronic alcohol consumption. ALDH2*2, a common dysfunctional polymorphism in the ALDH2 gene, has been linked to an increased risk of cancer and heart disease. We tested the effect of ALDH2 deficiency on alcohol-induced AF in a murine model of chronic-binge ethanol feeding, with ALDH2*2 knock-in (KI) mice generated by a CRISPR/CAS9 system. In addition, right atrial appendages were obtained from eight patients with AF undergoing open heart surgery. The results showed that burst atrial pacing induced a greater susceptibility to AF in ALDH2*2 KI mice exposed to chronic ethanol intoxication than in wild-type mice, resulting from a higher degree of 4-HNE accumulation and collagen deposition in their atria. Alda-1 attenuated transforming growth factor beta 1 (TGF-ß1) expression and collagen deposition in the atria and reduced AF inducibility. Patients with AF and the ALDH2*2 allele exhibited greater oxidative stress and substrate remodeling in their atria than non-carriers. In conclusion, ALDH2 deficiency may increase the risk of chronic alcohol and tachypacing-induced AF through the accumulation of 4-HNE and increased ROS production.