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BACKGROUND: Atrial fibrillation surgical radiofrequency ablation (AFSA) during mitral valve surgery (MVS) has almost completely superseded the Cox-Maze procedure for the treatment of atrial fibrillation. METHODS: We retrospectively analyzed 100 patients who underwent MVS + AFSA in our institution from January 2008 to June 2017. We compared the effectiveness of AFSA in patients who underwent LAA exclusion to those who did not. Moreover, we analyzed the role of preoperative AF duration (≤ or >1 year) and medial-lateral left atrial dimensions (ML-LAD) (≤ or >6 cm). The efficacy endpoint was freedom from AF at discharge and at 2-year follow-up. The safety endpoints were need of a permanent pacemaker (PMK), surgical re-exploration, occurrence of stroke, and left circumflex artery or esophageal lesions. RESULTS: Overall, the rate of AF freedom was 69% at discharge and 80% at 2-year follow-up. LAA exclusion did not influence AF freedom at 2-year follow-up, and 84.6% of patients who underwent LAA exclusion were in the sinus rythm (SR) at 2 year compared to 75% of those who did not receive LAA exclusion free from AF as well (p=0.230). AF duration ≤1 or >1 year did not influence sinus rhythm (SR) maintenance (85.7% vs. 75.8%; p=0.224), and in these two groups, LAA exclusion did not change the efficacy of AFSA. ML-LAD ≤ 6 cm was associated with better results in terms of SR maintenance. A statistically significant association between LAA exclusion and SR maintenance at 2-year follow-up (p=0.017) was found among patients with ML-LAD ≤ 6 cm. Complications included 7 cases of PMK implantation, 2 cases of surgical re-exploration, and 1 case of stroke. No circumflex artery or esophageal lesions occurred after surgical procedures. CONCLUSIONS: In our experience, AFSA during isolated MVS resulted in good outcomes in terms of SR maintenance and incidence of complications. AF duration ≤ 1 year did not influence results, while patients with ML-LAD ≤ 6 cm had significantly better results regarding SR at follow-up. In patients with ML-LAD ≤ 6 cm, LAA exclusion significantly increased the success rate of SR maintenance at 2-year follow-up.
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Respiratory diseases represent a major healthcare burden worldwide. Lung transplantation (LTx) is the "gold standard" for end-stage patients, strongly limited by shortage of available/suitable donor lungs. Normothermic ex vivo lung perfusion (EVLP) has significantly increased the number of lungs suitable for transplantation. Steen solution is used for EVLP, but the mechanisms involved in its beneficial properties remain to be clarified. We investigated the effects of Steen solution in an in vitro protocol of cold starvation and normothermic recovery on human lung spheroids, named pneumospheres (PSs), containing epithelial/basal cells, and on endothelial human umbilical vein endothelial cells (HUVEC). Steen solution significantly preserved the viability of PSs, reduced reactive oxygen species (ROS) release by PSs and HUVECs, decreased NADPH-oxidase (NOX) activity in PSs, and reduced inflammatory cytokines expression levels in HUVECs. Steen solution was able to specifically reduce NADPH oxidase 2 (NOX2) isoform activation, particularly in PSs, as detected by soluble-NOX2 peptide and p47-phosphorylation. Interestingly, a specific NOX2 inhibitor could partly mimic the pro-survival effect of Steen on PSs. We provide the first evidence that Steen solution can preserve lung epithelial/progenitor cells viability partially through NOX2 downregulation, and exert antioxidant effects on parenchymal cells, with consequent ROS reduction. These results suggest that NOX2 inhibition might be an additional strategy to reduce cellular damage during LTx procedures.
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Antioxidantes/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Soluciones Isotónicas/farmacología , Pulmón/efectos de los fármacos , Soluciones Preservantes de Órganos/farmacología , Preservación de Órganos/métodos , Esferoides Celulares/efectos de los fármacos , Adolescente , Adulto , Células Cultivadas , Citoprotección , Femenino , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Pulmón/metabolismo , Masculino , NADPH Oxidasa 2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/prevención & control , Esferoides Celulares/metabolismo , Adulto JovenRESUMEN
PURPOSE: Ventricular-arterial (V-A) decoupling decreases myocardial efficiency and is exacerbated by tachycardia that increases static arterial elastance (Ea). We thus investigated the effects of heart rate (HR) reduction on Ea in septic shock patients using the beta-blocker esmolol. We hypothesized that esmolol improves Ea by positively affecting the tone of arterial vessels and their responsiveness to HR-related changes in stroke volume (SV). METHODS: After at least 24 h of hemodynamic optimization, 45 septic shock patients, with an HR ≥95 bpm and requiring norepinephrine to maintain mean arterial pressure (MAP) ≥65 mmHg, received a titrated esmolol infusion to maintain HR between 80 and 94 bpm. Ea was calculated as MAP/SV. All measurements, including data from right heart catheterization, echocardiography, arterial waveform analysis, and norepinephrine requirements, were obtained at baseline and at 4 h after commencing esmolol. RESULTS: Esmolol reduced HR in all patients and this was associated with a decrease in Ea (2.19 ± 0.77 vs. 1.72 ± 0.52 mmHg l(-1)), arterial dP/dt max (1.08 ± 0.32 vs. 0.89 ± 0.29 mmHg ms(-1)), and a parallel increase in SV (48 ± 14 vs. 59 ± 18 ml), all p < 0.05. Cardiac output and ejection fraction remained unchanged, whereas norepinephrine requirements were reduced (0.7 ± 0.7 to 0.58 ± 0.5 µg kg(-1) min(-1), p < 0.05). CONCLUSIONS: HR reduction with esmolol effectively improved Ea while allowing adequate systemic perfusion in patients with severe septic shock who remained tachycardic despite standard volume resuscitation. As Ea is a major determinant of V-A coupling, its reduction may contribute to improving cardiovascular efficiency in septic shock.
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Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Propanolaminas/administración & dosificación , Arteria Pulmonar/fisiopatología , Choque Séptico/fisiopatología , Adulto , Anciano , Ecocardiografía , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Norepinefrina/uso terapéutico , Estudios Prospectivos , Volumen Sistólico/efectos de los fármacos , Vasoconstrictores/uso terapéuticoRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial pneumonia of unknown etiology, which is associated with the histopathologic pattern of usual interstitial pneumonia (UIP) and leads to a progressive decrease of respiratory function. The present article describes a case of a 62-year-old ex-smoker referred to our hospital because of IPF. After 2 years of follow-up, the subject experienced a significant worsening of pulmonary function and was enrolled in a lung transplantation program. Afterward, a pharmacological treatment with pirfenidone was started, achieving a stabilization of respiratory function. The patient underwent a single lung transplantation by means of a normothermic ex vivo lung perfusion (EVLP) approach according to the Toronto model. At 20-month evaluation the subject's respiratory function was significantly improved, and quality of life was considerably ameliorated. We believe that an integrated multidisciplinary approach should be considered a key option for the treatment of individuals with IPF.
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Antiinflamatorios no Esteroideos/uso terapéutico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/cirugía , Trasplante de Pulmón , Piridonas/uso terapéutico , Terapia Combinada , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Fibrosis Pulmonar/terapia , Calidad de VidaRESUMEN
Subjects carrying the T2238C ANP gene variant have a higher risk to suffer a stroke or myocardial infarction. The mechanisms through which T2238C/αANP exerts detrimental vascular effects need to be fully clarified. In the present work we aimed at exploring the impact of C2238/αANP (mutant form) on atherosclerosis-related pathways. As a first step, an atherosclerosis gene expression macroarray analysis was performed in vascular smooth muscle cells (VSMCs) exposed to either T2238/αANP (wild type) or C2238/αANP. The major finding was that apolipoprotein E (ApoE) gene expression was significantly downregulated by C2238/αANP and it was upregulated by T2238/αANP. We subsequently found that C2238/αANP induces ApoE downregulation through type C natriuretic peptide receptor (NPR-C)-dependent mechanisms involving the upregulation of miR199a-3p and miR199a-5p and the downregulation of DNAJA4. In fact, NPR-C knockdown rescued ApoE level. Upregulation of miR199a by NPR-C was mediated by a reactive oxygen species-dependent increase of the early growth response protein-1 (Egr-1) transcription factor. In fact, Egr-1 knockdown abolished the impact of C2238/αANP on ApoE and miR199a. Of note, downregulation of ApoE by C2238/αANP was associated with a significant increase in inflammation, apoptosis and necrosis that was completely rescued by the exogenous administration of recombinant ApoE. In conclusion, our study dissected a novel mechanism of vascular damage exerted by C2238/αANP that is mediated by ApoE downregulation. We provide the first demonstration that C2238/αANP downregulates ApoE in VSMCs through NPR-C-dependent activation of Egr-1 and the consequent upregulation of miR199a. Restoring ApoE levels could represent a potential therapeutic strategy to counteract the harmful effects of C2238/αANP.
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Apolipoproteínas E/metabolismo , Factor Natriurético Atrial/genética , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , MicroARNs/metabolismo , Músculo Liso Vascular/citología , Mutación/genética , Miocitos del Músculo Liso/metabolismo , Apolipoproteínas E/genética , Apoptosis , Aterosclerosis/genética , Aterosclerosis/patología , Biomarcadores/metabolismo , Supervivencia Celular , Vasos Coronarios/citología , Humanos , Inflamación/patología , MicroARNs/genética , Modelos Biológicos , Necrosis , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores del Factor Natriurético Atrial/metabolismo , Venas Umbilicales/citología , Regulación hacia ArribaRESUMEN
We studied the usefulness of preoperative resistance index to select patients who will benefit most from renal stenting. Sixty-two patients underwent renal stenting. All had chronic renal insufficiency with serum creatinine values ranging from 1.5 to 2.5 mg/dL and blood urea nitrogen between 80 and 107 mg/dL. All treated renal artery stenosis were >70%. Reduction in blood pressure in the early stages was observed in 39 (62.9%) patients; 31 (79.4%) patients returned to preoperative values within 12 months. A progressive reduction in creatinine values and blood urea nitrogen was reached in 43 (69.4%) patients, 12 (19.4%) patients remained unchanged, and the remaining 7 (11.2%) patients worsened. The best improvement in renal function was obtained in patients with a resistance index of ≤0.75 A preoperative resistance index up to 0.75 could be used as an indicator to predict which candidates will have improved renal function after stenting.
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Procedimientos Endovasculares/instrumentación , Riñón/fisiopatología , Obstrucción de la Arteria Renal/terapia , Insuficiencia Renal Crónica/fisiopatología , Stents , Anciano , Biomarcadores/sangre , Presión Sanguínea , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Recuperación de la Función , Obstrucción de la Arteria Renal/complicaciones , Obstrucción de la Arteria Renal/diagnóstico , Obstrucción de la Arteria Renal/fisiopatología , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular , Resistencia VascularRESUMEN
INTRODUCTION: Surgical replacement for aortic stenosis is fraught with complications in high-risk patients. Transcatheter techniques may offer a minimally invasive solution, but their comparative effectiveness and safety is uncertain. We performed a network meta-analysis on this topic. METHODS: Randomized trials on transcatheter aortic valve replacement vs surgery were searched. The primary outcome was all cause death. Risk estimates were obtained with Bayesian network meta-analytic methods. RESULTS: Four trials with 1,805 patients were included. After a median of 8 months, risk of death and myocardial infarction was not different when comparing surgery versus transcatheter procedures, irrespective of device or access. Conversely, surgery was associated with higher rates of major bleeding (odds ratio vs CoreValve=3.03 [95% credible interval: 2.23-4.17]; odds ratio vs transfemoral Sapien =1.82 [1.21-2.70]; odds ratio vs transapical Sapien =2.08 [1.20-3.70]), and acute kidney injury (odds ratio vs CoreValve =2.08 [1.33-3.32]; odds ratio vs transapical Sapien =2.78 [2.21-99.80]), but lower rates of pacemaker implantation (odds ratio vs CoreValve =0.41 [0.28-0.59]), and moderate or severe aortic regurgitation (odds ratio vs CoreValve =0.06 [0.02-0.27]; odds ratio vs Sapien=0.17 [0.02-0.76]). Strokes were less frequent with CoreValve than with transfemoral Sapien (odds ratio =0.32 [0.13-0.73]) or transapical Sapien (odds ratio =0.33 [0.10-0.93]), whereas pacemaker implantation was more common with CoreValve (odds ratio vs surgery =2.46 [1.69-3.61]; odds ratio vs transfemoral Sapien =2.22 [1.27-3.85]). CONCLUSIONS: Survival after transcatheter or surgical aortic valve replacement is similar, but there might be differences in the individual safety and effectiveness profile between the treatment strategies and the individual devices used in transcatheter aortic valve implantation.
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AIM: Autologous pericardium annuloplasty (APA) is an alternative to prosthetic ring implantation for mitral valve (MV) repair, avoiding the use of foreign material and preserving the mitral annulus' physiological motion. However, data on durability are questionable. Therefore, we analyzed long-term outcomes of treating degenerative mitral regurgitation (MR) with APA. METHODS: Four hundred ninety patients (mean age, 54.3±11.3 years, [15-77 years]; N.=360 men [74.1%]) who had undergone APA and neochordae implantation between July 1988 and December 2006 were retrospectively studied. RESULTS: MR was purely degenerative in 434 (89.3%) patients; endocarditis was present in 44 (9.1%) patients; an anterior, posterior, or bileaflet prolapse was present in 32 (6.6%), 241 (49.6%), and 213 (43.8%) patients, respectively. Clinical follow-up was 100% complete at a median of 6.5 years (5th percentile, 0.9; 95th percentile, 14.9) with an echocardiographic study in 92% of patients. In-hospital mortality was 1% (5 deaths); overall and late cardiac mortality were 7.6% and 3.9% (37 and 19 deaths), respectively. Kaplan-Meier curves for overall survival, late cardiac survival, and freedom from reoperation at 15 years (20 cases) were 86% (95%CI 80-91), 93% (95%CI 88-96), and 93% (95%CI 88-96), respectively. At 15 years, freedom from recurrent MR (28 patients) and endocarditis (6 events) were 86% (95%CI 76-91) and 97% (95%CI 92-99). Dehiscence, significant calcification of APA, and hemolysis never occurred. At reoperations, annular pericardium appeared covered by a smooth layer of tissue. CONCLUSION: APA is feasible, safe, and cost-effective, providing long-term durability, high survival, and a low rate of valve-related complications.
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Implantación de Prótesis de Válvulas Cardíacas , Anuloplastia de la Válvula Mitral/métodos , Insuficiencia de la Válvula Mitral/cirugía , Válvula Mitral/cirugía , Pericardio/trasplante , Adolescente , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Mortalidad Hospitalaria , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Válvula Mitral/fisiopatología , Anuloplastia de la Válvula Mitral/efectos adversos , Anuloplastia de la Válvula Mitral/mortalidad , Insuficiencia de la Válvula Mitral/diagnóstico , Insuficiencia de la Válvula Mitral/mortalidad , Insuficiencia de la Válvula Mitral/fisiopatología , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/cirugía , Recurrencia , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Platelet activation contributes to the alteration of endothelial function, a critical initial step in atherogenesis through the production and release of prooxidant mediators. There is uncertainty about the precise role of polyphenols in interaction between platelets and endothelial cells (ECs). We aimed to investigate whether polyphenols are able to reduce endothelial activation induced by activated platelets. First, we compared platelet activation and flow-mediated dilation (FMD) in 10 healthy subjects (HS) and 10 patients with peripheral artery disease (PAD). Then, we evaluated the effect of epicatechin plus catechin on platelet-HUVEC interaction by measuring soluble cell adhesion molecules (CAMs), NOx production, and eNOS phosphorylation (p-eNOS) in HUVEC. Compared to HS, PAD patients had enhanced platelet activation. Conversely, PAD patients had lower FMD than HS. Supernatant of activated platelets from PAD patients induced an increase of sCAMs release and a decrease of p-eNOS and nitric oxide (NO) bioavailability compared to unstimulated HUVEC. Coincubation of HUVEC, with supernatant of PAD platelets patients, pretreated with a scalar dose of the polyphenols, resulted in a decrease of sCAMs release and in an increase of p-eNOS and NO bioavailability. This study demonstrates that epicatechin plus catechin reduces endothelial activation induced by activated platelets.
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Plaquetas/efectos de los fármacos , Catequina/farmacología , Enfermedad Arterial Periférica/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Plaquetas/metabolismo , Moléculas de Adhesión Celular/metabolismo , Estudios Transversales , Femenino , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo III/metabolismo , Óxidos de Nitrógeno/metabolismo , Enfermedad Arterial Periférica/metabolismo , Enfermedad Arterial Periférica/patología , Fosforilación/efectos de los fármacos , Activación Plaquetaria/efectos de los fármacosRESUMEN
INTRODUCTION: Uncertainty persists on the clinical impact of impedance threshold devices in out-of-hospital cardiac arrest. We conducted an updated systematic review on impedance threshold devices. METHODS: Several databases were searched for studies testing the effectiveness of impedance threshold devices in patients with cardiac arrest. The primary endpoint was long-term survival. RESULTS: Seven trials (11,254 patients) were included. In 4 studies (2,284 patients) impedance threshold devices were used with active compression-decompression-cardiopulmonary resuscitation, and in the others alone. Overall, impedance threshold devices did not impact on the rate of return of spontaneous circulation (odds ratio=1.17 [0.96-1.43], p=0.114), favorable neurologic outcome (odds ratio=1.56 [0.97-2.50], p=0.065), or long-term survival (odds ratio=1.22 [0.94-1.58], p=0.127). These analyses were fraught with heterogeneity (respectively, p=0.055, p=0.236, and p=0.011) and inconsistency (respectively, I-squared=51% , I-squared=27% , and I-squared=67%). Exploratory analysis showed that combined use of impedance threshold devices with active compression-decompression significantly increased the likelihood of return of spontaneous circulation (odds ratio=1.19 [1.00-1.40], p=0.045), favorable neurologic outcome (odds ratio=1.60 [1.14-2.25], p=0.006), and long-term survival (odds ratio=1.52 [1.11-2.08], p=0.009). The favorable impact of the interaction between impedance threshold devices and active compression-decompression was also confirmed at meta-regression analysis (respectively, b=0.195 [0.004-0.387], p=0.045, b=0.500 [0.079-0.841], p=0.018, b=0.413 [0.063-0.764], p=0.021). CONCLUSIONS: The evidence base on impedance threshold devices is apparently inconclusive, with a neutral impact on clinically relevant outcomes. However, exploratory analysis focusing on the combined use of impedance threshold devices with active compression-decompression suggests that this combo treatment may be useful to improve patient prognosis.
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Lung transplantation (OLT) is a viable option for end-stage pulmonary diseases in selected patients with satisfactory long-term results. However, the paucity of available donors engenders a prolonged stay on the waiting list with progressive decline of lung function. In cases of sudden respiratory failure, admission to an intensive care unit with institution of extracorporeal membrane oxygenation (ECMO) may be an option while a waiting an emergency OLT. In 12 OLT candidates we started ECMO because of acute decline of lung function. Eleven patients had cystic fibrosis and the other subject, histiocytosis X. In 7 patients bilateral OLT was performed after a mean waiting time of 6 days from ECMO institution; 5 patients died on ECMO at a mean time of 11.6 days. After OLT 2 patients required reoperation for hemothorax; renal failure and acute leg ischemia occurred in 2 patients. The mean weaning time from ECMO after OLT was 2.14 days. No patient died in the perioperative period and 1-year survival was 85.7%. ECMO represents a valid option as a bridge to urgent OLT for selected candidates.
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Oxigenación por Membrana Extracorpórea , Trasplante de Pulmón , HumanosRESUMEN
INTRODUCTION: Novel oral anticoagulants have been tested against warfarin for atrial fibrillation, yet no direct comparison is available. We thus aimed to perform pair-wise (direct) and warfarin-adjusted network (i.e. indirect) meta-analyses of novel oral anticoagulants for atrial fibrillation. METHODS: Databases were searched for randomized warfarin-controlled trials of novel anticoagulants for non-valvular atrial fibrillation. The primary end-point was long-term stroke/systemic embolism. Odds ratios (95% intervals) were computed with RevMan and WinBUGS. RESULTS: Seven trials (52701 patients) were included, focusing on apixaban, dabigatran, edoxaban and rivaroxaban. Pair-wise meta-analysis showed that after a weighted average of 23 months these novel anticoagulants lead to significant reductions in the risk of stroke/systemic embolism (odds ratio=0.81 [0.71-0.92], I2=23%) and all cause death (odds ratio=0.88 [0.82-0.95], I2=0%) in comparison to warfarin. Network meta-analysis showed that apixaban and dabigatran proved similarly superior to warfarin in preventing stroke/systemic embolism (odds ratio=0.78 [0.62-0.96] for apixaban vs warfarin; odds ratio=0.66 [0.52-0.84] for high-dose dabigatran vs warfarin; odds ratio for apixaban vs high-dose dabigatran=1.17 [0.85-1.63]), but apixaban was associated with fewer major bleedings (odds ratio=0.73 [0.57-0.93]) and drug discontinuations (odds ratio=0.64 [0.52-0.78]) than dabigatran. Rivaroxaban did not reduce stroke/systemic embolism (odds ratio=0.87 [0.71-1.07]) or major bleedings in comparison to warfarin (odds ratio=0.87 [0.71-1.07]) and was associated with more major bleedings in comparison to apixaban (odds ratio=1.52 [1.19-1.92]). Data for edoxaban were inconclusive. CONCLUSIONS: Novel oral anticoagulants appear as a very promising treatment option for atrial fibrillation.
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Bilateral sequential lung transplantation (BSLT) is nowadays considered a valid therapeutic option for patients with end stage cystic fibrosis. We report our experience with 104 BSLTs in 101 patients. The overall survivals at 1, 3, 5, 10 years were 79%, 65%, 58%, and 42%, respectively. Perioperative mortality was 14.8% (n = 15). The leading causes of perioperative mortality were primary graft dysfunction and sepsis. Three patients were retransplanted owing to obliterative bronchiolitis. In 70 cases (69%), patients displayed ≥ 1 additional risk factors: previous lung resections, colonization by Burkholderia cepacia, diabetes, pneumothorax, or noninvasive ventilatory support. The mean preoperative 1-second forced expiratory volume of 0.69 ± 0.2 L (22%) increased to 85% at 1 year after the operation. The mean time on the waiting list was 12 ± 5 months. The 5 patients treated with extracorporeal membrane oxygenation before urgent transplantation were operated after 3, 5, 6, 30, and 3 days respectively. During the procedure, cardiopulmonary bypass was required in 33 patients (32%). Lung transplantation represents a unique opportunity to ameliorate the quality and improve the survival of patients affected by cystic fibrosis. Timing of referral and patient selection remain crucial for success.
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Fibrosis Quística/cirugía , Trasplante de Pulmón/métodos , Adolescente , Adulto , Oxigenación por Membrana Extracorpórea , Femenino , Volumen Espiratorio Forzado , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Factores de Riesgo , Resultado del Tratamiento , Listas de Espera , Adulto JovenRESUMEN
Many studies demonstrated that human adult cardiac progenitor cells in the form of cardiospheres (CSps) could represent a powerful candidate for cardiac cell therapy. To achieve the clinical translation of this biotechnological product, the development of well-defined culture conditions is required to optimize their proliferation and differentiation. Thrombin, a serine protease acting through the protease-activated receptor 1 (PAR-1) signalling to modulate many cellular functions such as proliferation and differentiation in several cell types, is one of the factors included in the CSps medium. Therefore, the assessment of the effective dependence of the thrombin related cellular effects from PAR-signalling is strategic both for understanding the biological potential of these cells and for the GMP translation of the medium formulation, using synthesised analogs. In this study the effects of thrombin on human CSps and their potential relationship with the specific proteolytic activation of PAR-1 have been investigated in different culture conditions, including thrombin inhibitor hirudin and PAR-1 agonist/ antagonist peptides TFLLR and MUMB2. In this study we show that, in the presence of thrombin and TFLLR, CSps, in which PAR-1 expression was evidenced by immunofluorescence and western blot analysis, increase their proliferation activity (BrdU assay). Such increased proliferative rate was consistently associated with a higher phosphorylation level of the cell cycle inhibitor GSK3. Concerning the assessment of the potential effects of thrombin and its agonist on differentiation, both western blot and real-time PCR analysis for stemness, cardiac and vascular markers (such as cKit, cx43 and KDR) showed that CSps commitment was substantially unaffected, except for GATA4 mRNA, whose transcription was down-regulated in the presence of the natural protease, but not after treatment with TFLLR. In conclusion, activation of PAR-1-dependent signalling is important to support CSps proliferative potential, keeping unaltered or at best stable their differentiation properties. The availability of thrombin agonists, such as TFLLR, able to guarantee the required growth effect without affecting CSps lineage commitment, could represent a technological improvement for cost-effective, easy-to-handle and GMPtranslatable synthetic media.
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Proliferación Celular/efectos de los fármacos , Hemostáticos/farmacología , Miocardio/metabolismo , Oligopéptidos/farmacología , Esferoides Celulares/metabolismo , Células Madre/metabolismo , Trombina/farmacología , Antígenos de Diferenciación/biosíntesis , Células Cultivadas , Fibrinolíticos/farmacología , Hirudinas/farmacología , Humanos , Miocardio/citología , Receptor PAR-1/agonistas , Receptor PAR-1/antagonistas & inhibidores , Receptor PAR-1/metabolismo , Esferoides Celulares/citología , Células Madre/citologíaRESUMEN
Primary adult cardiac tumors are rare entities with a low indices. In 90% of cases are benign. Among malignant tumors angiosarcomas are the most common. In 80% of cases they arises in the right atrium, more often in younger males as compared to benign tumors. The majority of them manifests as locally already advanced disease, precluding macroscopically complete surgical resection. Moreover, the presence of macro- and micrometastasis makes the prognosis always prohibitive. The duration of symptoms is in the order of months and the median survival ranges from 6 to 11 months. Death cause is usually a complication of locally recurrent disease: tamponade, hemopericardium are common. Treatment is multidisciplinary. The combination of chemo- and radiotherapy with surgery aims to increase survival. In the management of unresectable tumors, due to anatomic reason or Iocoregional spread, an important role is played by pre-operatory chemotherapy or chemo-radiation to increase short term survival.
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Neoplasias Cardíacas/complicaciones , Síndrome de la Vena Cava Superior/etiología , Adulto , Terapia Combinada , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/terapia , Humanos , MasculinoRESUMEN
The aim of cardiac cell therapy is to restore at least in part the functionality of the diseased or injured myocardium by the use of stem/progenitor cells. Recent clinical trials have shown the safety of cardiac cell therapy and encouraging efficacy results. A surprisingly wide range of non-myogenic cell types improves ventricular function, suggesting that benefits may result in part from mechanisms that are distinct from true myocardial regeneration. While clinical trials explore cells derived from skeletal muscle and bone marrow, basic researchers are investigating sources of new cardiomyogenic cells, such as resident myocardial progenitors and embryonic stem cells. In this commentary we briefly review the evolution of cell-based cardiac repair, some progress that has been made toward this goal, and future perspectives in the regeneration of cardiac tissue.
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Cardiopatías/terapia , Animales , Separación Celular , Ensayos Clínicos como Asunto , Cardiopatías/metabolismo , Cardiopatías/patología , Humanos , Mioblastos Cardíacos/citología , Regeneración , Ingeniería de TejidosRESUMEN
Carnitine is a physiological cellular constituent that favors intracellular fatty acid transport, whose role on platelet function and O(2) free radicals has not been fully investigated. The aim of this study was to seek whether carnitine interferes with arachidonic acid metabolism and platelet function. Carnitine (10-50 microM) was able to dose dependently inhibit arachidonic acid incorporation into platelet phospholipids and agonist-induced arachidonic acid release. Incubation of platelets with carnitine dose dependently inhibited collagen-induced platelet aggregation, thromboxane A(2) formation, and Ca(2+) mobilization, without affecting phospholipase A(2) activation. Furthermore, carnitine inhibited platelet superoxide anion (O(2)(-)) formation elicited by arachidonic acid and collagen. To explore the underlying mechanism, arachidonic acid-stimulated platelets were incubated with NADPH. This study showed an enhanced platelet O(2)(-) formation, suggesting a role for NADPH oxidase in arachidonic acid-mediated platelet O(2)(-) production. Incubation of platelets with carnitine significantly reduced arachidonic acid-mediated NADPH oxidase activation. Moreover, the activation of protein kinase C was inhibited by 50 microM carnitine. This study shows that carnitine inhibits arachidonic acid accumulation into platelet phospholipids and in turn platelet function and arachidonic acid release elicited by platelet agonists.
Asunto(s)
Ácido Araquidónico/metabolismo , Plaquetas/fisiología , Carnitina/farmacología , Estrés Oxidativo/fisiología , Plaquetas/metabolismo , Proteínas Sanguíneas/metabolismo , Calcio/metabolismo , Humanos , Membranas Intracelulares/metabolismo , Concentración Osmolar , Fosfolípidos/metabolismo , Fosforilación , Agregación Plaquetaria/fisiología , Especies Reactivas de Oxígeno/metabolismo , Tromboxano A2/biosíntesisRESUMEN
Accessory mitral valve leaflet is a very rare cause of left ventricular outflow tract obstruction. We report a patient presenting this cardiac abnormality who undergone cardiac surgery. A 60-year-old man, presented coronary artery disease and moderate left ventricular tract obstruction due to accessory mitral valve leaflet. The accessory mitral valve leaflet had the typical morphology of a parachute-shaped attached partially to the anterior mitral valve leaflet, with chordae tendinae attached to: 1) an accessory papillary muscle inserted at the free-wall closed to the apex; 2) interconnected with the chordae tendinae of the anterior mitral valve leaflet; 3) a second accessory papillary muscle inserted to the interventricular septum. He underwent successful coronary revascularization of 2 vessels and accessory leaflet excision. A review of 21 cases with accessory mitral valve leaflet is reported.
Asunto(s)
Puente de Arteria Coronaria/métodos , Enfermedad Coronaria/diagnóstico , Cardiopatías Congénitas/diagnóstico , Válvula Mitral/anomalías , Obstrucción del Flujo Ventricular Externo/diagnóstico , Cateterismo Cardíaco , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/cirugía , Ecocardiografía Transesofágica , Estudios de Seguimiento , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Resultado del Tratamiento , Obstrucción del Flujo Ventricular Externo/complicaciones , Obstrucción del Flujo Ventricular Externo/cirugíaRESUMEN
BACKGROUND: The exact incidence of associated aortic valve incompetence (AVI) and abdominal aortic aneurysm (AAA) in the general population is not known. In recent years, we have observed this association with increasing frequency. This observation is probably due to the extensive preoperative screening of the cardiac and vascular status of patients who are candidates for surgical procedures. The choice of the optimal surgical strategy is needed to achieve low operative morbidity and mortality. The present study reviews our experience with a subset of patients suffering the association of AVI and large AAA. Surgical strategy, clinical management and outcome are presented. METHODS: Between January 1982 and May 2000, 76 patients with the association of AAA and AVI have been evaluated in our institution. Forty-four patients have been treated for both AAA and aortic valve (AV) regurgitation. These patients have been divided into three groups on the basis of the surgical strategy adopted. Group 1: combined procedure (16 patients); group 2: AAA repair prior to AV surgery (nine patients); group 3: AV surgery prior to aneurysm repair (19 patients). RESULTS: Hospital mortality was 4.5% (two patients); overall mortality was 6.8% (three patients). CONCLUSIONS: In patients with AAA and AVI, an accurate and complete preoperative evaluation is essential. Surgical strategy should be individualized on the basis of the cardiac preoperative status.