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BACKGROUND AND METHODS: Heart transplant recipients (HTr) have a higher probability of suffer from severe coronavirus disease-2019 (COVID-19) in comparison to general population, but their risk has changed over the course of the pandemic in relation to various factors. We conducted a prospective study including all HTr at risk of COVID-19 in a tertiary center between February 2020 and October 2022. The aim was to analyze how the prognosis (incidence of pneumonia and mortality) of COVID-19 in HTr has evolved over time, contextualizing variants, vaccination, and other treatments. RESULTS: Of 308 HTr included, 124 got the infection (39.2%). COVID and non-COVID HTr had similar baseline characteristics. COVID-19 patients with pneumonia had a poorer prognosis than those with less severe presentations, with a higher rate of hospitalization (93.3 vs. 14.1%, p < .001) and death (41.0 vs. 1.2%, p < .001). Multivariate analysis identified age ≥60 years (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.16-11.49, p = .027), and chronic kidney disease ≥3a (OR 4.95, 95% CI 1.39-17.54, p = .014) as predictors of pneumonia. Two-dose vaccination (OR 0.20, CI 95% 0.05-0.72, p = .02) and early remdesivir administration (OR 0.17, CI 0.03-0.90, p = .037) were protective factors. Over the course of the pandemic considering three periods in the follow-up (prevaccination February-December 2020, postvaccination January-December 2021, and post early remdesivir indication January-October 2022), we observed a reduction in pneumonia incidence from 62% to 19% (p < .001); and mortality (from 23% to 4%, p < .001). CONCLUSIONS: The prognosis of COVID-19 in HTr has improved over time, likely due to vaccination and early administration of remdesivir.
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COVID-19 , Trasplante de Corazón , Humanos , Persona de Mediana Edad , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias , SARS-CoV-2 , Estudios Prospectivos , Trasplante de Corazón/efectos adversos , Receptores de TrasplantesRESUMEN
Antibodies directed against donor-specific human leukocyte antigens (HLAs) can be detected de novo after heart transplantation and play a key role in long-term survival. De novo donor-specific antibodies (dnDSAs) have been associated with cardiac allograft vasculopathy, antibody-mediated rejection, and mortality. Advances in detection methods and international guideline recommendations have encouraged the adoption of screening protocols among heart transplant units. However, there is still a lack of consensus about the correct course of action after dnDSA detection. Treatment is usually started when antibody-mediated rejection is present; however, some dnDSAs appear years before graft failure is detected, and at this point, damage may be irreversible. In particular, class II, anti-HLA-DQ, complement binding, and persistent dnDSAs have been associated with worse outcomes. Growing evidence points towards a more aggressive management of dnDSA. For that purpose, better diagnostic tools are needed in order to identify subclinical graft injury. Cardiac magnetic resonance, strain techniques, or coronary physiology parameters could provide valuable information to identify patients at risk. Treatment of dnDSA usually involves plasmapheresis, intravenous immunoglobulin, immunoadsorption, and ritxumab, but the benefit of these therapies is still controversial. Future efforts should focus on establishing effective treatment protocols in order to improve long-term survival of heart transplant recipients.
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Background: Chronic use of Angiotensin-converting enzyme (ACE) inhibitors (ACEi) and aldosterone-receptor blockers (ARB) is not associated with worse outcomes in patients with COVID-19. However, evidence on the impact of their discontinuation during hospital admission is scarce. Our aim was to determine whether withdrawal of ACEi, ARB and mineralocorticoid receptor antagonists (MRA) is associated with all-cause mortality in a real-life large cohort of patients with SARS-CoV-2 infection. Methods: Observational cohort study from a large referral center from 1 March 2020 to 20 April 2020. Withdrawal of renin-angiotensin-aldosterone system inhibitors was defined as the absence of any received dose during hospital admission in patients receiving chronic treatment. Prescriptions during admission were confirmed by data from the central pharmacy computerized system. Results: A total of 2042 patients (mean age 68.4±17.6, 57.1% male) with confirmed COVID-19 were included. During a median follow-up of 57 (21-55) days, 583 (28.6%) died. Prior to hospital admission 468 (22.9%), 343 (16.8%) and 83 (4.1%) patients were receiving ACEi, ARB and MRA respectively. During the study period, 216 (46.2%), 193 (56.3%) and 41 (49.4%) were withdrawn from the corresponding drug. After adjusting for age, cardiovascular risk factors, baseline comorbidities and in-hospital COVID-19 dedicated treatment, withdrawal of ACE inhibitors (hazard ration [HR] 1.48 [95% confidence interval -CI- 1.16-1.89]) and MRA (HR 2.01 [95% CI 1.30-3.10]) were shown to be independent predictors of all-cause mortality. No independent relationship between ARB withdrawal and mortality was observed. Conclusion: ACEi and MRA withdrawal were associated with higher mortality. Strong consideration should be given to not discontinuing these medications during hospital admission.
Introdução: O uso crónico de inibidores da ECA (IECA) e de antagonistas dos recetores de aldosterona (ARA) não está associado a resultados piores em doentes com Covid-19. No entanto, a evidência relativa ao impacto da sua retirada durante a admissão hospitalar é escassa. O nosso objetivo foi determinar se a retirada do IECA, ARA e antagonistas dos recetores dos mineralocorticóides (ARM) está associada à mortalidade por todas as causas numa grande coorte real de doentes com infeção por SRA-CoV-2. Métodos: Estudo coorte observacional a partir de um grande centro de referência de 1 de março de 2020 a 20 de abril de 2020. A retirada dos inibidores do sistema RAAS foi definida como a ausência de qualquer dose recebida durante a admissão hospitalar em doentes que recebem tratamento prolongado. As prescrições durante a admissão foram confirmadas por dados do sistema informático da farmácia central. Resultados: Um total de 2042 doentes (idade média de 68,4 ±17,6, 57,1% do sexo masculino) com COVID-19 confirmado foram incluídos. Durante um acompanhamento médio de 57 (21-55) dias, 583 (28,6%) morreram. Conclusão: A retirada do IECA e do ARM foi associada a uma mortalidade mais elevada. Deve ser dada grande atenção para não interromper estes medicamentos durante a admissão hospitalar.
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Tratamiento Farmacológico de COVID-19 , Anciano , Anciano de 80 o más Años , Aldosterona , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Angiotensinas , Antihipertensivos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Renina , Estudios Retrospectivos , SARS-CoV-2RESUMEN
An abnormal visual experience early in life, caused by strabismus, unequal refractive power of the eyes, or eye occlusion, is a major cause of amblyopia (lazy eye), a highly diffused neurodevelopmental disorder severely affecting visual acuity and stereopsis abilities. Current treatments for amblyopia, based on a penalization of the fellow eye, are only effective when applied during the juvenile critical period of primary visual cortex plasticity, resulting mostly ineffective at older ages. Here, we developed a new paradigm of operant visual perceptual learning performed under conditions of conventional (binocular) vision in adult amblyopic rats. We report that visual perceptual learning induced a marked and long-lasting recovery of visual acuity, visual depth perception abilities and binocular matching of orientation preference, and we provide a link between the last two parameters.
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BACKGROUND: Physical activity has been recently shown to enhance adult visual cortical plasticity, both in human subjects and animal models. While physical activity activates mitochondrial oxidative metabolism leading to a transient production of reactive oxygen species, it remains unknown whether this process is involved in the plasticizing effects elicited at the visual cortical level. RESULTS: Here, we investigated whether counteracting oxidative stress through a dietary intervention with antioxidants (vitamins E and C) interferes with the impact of physical exercise on visual cortex plasticity in adult rats. Antioxidant supplementation beyond the closure of the critical period blocked ocular dominance plasticity in response to eye deprivation induced by physical activity in adult rats. CONCLUSIONS: Antioxidants exerted their action through a mithormetic effect that involved dampening of oxidative stress and insulin-like growth factor 1 (IGF-1) signaling in the brain.
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Condicionamiento Físico Animal , Corteza Visual , Adulto , Humanos , Ratas , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Estrés Oxidativo , Mitocondrias/metabolismo , Corteza Visual/fisiologíaRESUMEN
In the last decades, the effects of sedentary lifestyles have emerged as a critical aspect of modern society. Interestingly, recent evidence demonstrated that physical exercise plays an important role not only in maintaining peripheral health but also in the regulation of central nervous system function. Many studies have shown that physical exercise promotes the release of molecules, involved in neuronal survival, differentiation, plasticity and neurogenesis, from several peripheral organs. Thus, aerobic exercise has emerged as an intriguing tool that, on one hand, could serve as a therapeutic protocol for diseases of the nervous system, and on the other hand, could help to unravel potential molecular targets for pharmacological approaches. In the present review, we will summarize the cellular interactions that mediate the effects of physical exercise on brain health, starting from the factors released in myocytes during muscle contraction to the cellular pathways that regulate higher cognitive functions, in both health and disease.
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BACKGROUND: Myocardial injury has been identified as a common complication in patients with COVID-19. However, recent research has serious limitations, such as non-guideline definition of myocardial injury, heterogenicity of troponin sampling or very short-term follow-up. Using data from a large European cohort, we aimed to overcome these pitfalls and adequately characterize myocardial damage in COVID-19. METHODS: Consecutive patients with confirmed SARS-CoV-2 infection and available high-sensitive troponin I (hs-TnI), from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. RESULTS: A total of 918 patients (mean age 63.2 ± 15.5 years, 60.1% male) with a median follow-up of 57 (49-63) days were included. Of these, 190 (20.7%) fulfilled strict criteria for myocardial injury (21.1% chronic, 76.8% acute non-ischemic, 2.1% acute ischemic). Time from onset of symptoms to maximum hs-TnI was 11 (7-18) days. Thrombotic and bleeding events, arrhythmias, heart failure, need for mechanical ventilation and death were significantly more prevalent in patients with higher hs-TnI concentrations, even without fulfilling criteria for myocardial injury. hs-TnI was identified as an independent predictor of mortality [HR 2.52 (1.57-4.04) per 5-logarithmic units increment] after adjusting for multiple relevant covariates. CONCLUSION: Elevated hs-TnI is highly prevalent among patients with SARS-CoV-2 infection. Even mild elevations well below the 99th URL were significantly associated with higher rates of cardiac and non-cardiac complications, and higher mortality. Future research should address the role of serial hs-TnI assessment to improve COVID-19 prognostic stratification and clinical outcomes.
ANTECEDENTES: El daño miocárdico parece una complicación frecuente en pacientes con COVID-19. Sin embargo, la literatura al respecto presenta serias limitaciones, como definiciones incorrectas, heterogeneidad de las determinaciones de troponina o seguimientos cortos. Utilizando datos de una cohorte amplia, el objetivo del trabajo fue caracterizar adecuadamente el daño miocárdico en pacientes con COVID-19 utilizando una metodología adecuada. MÉTODOS: Se estudió a pacientes consecutivos con infección confirmada y determinaciones disponibles de troponina I de alta sensibilidad (hs-TnI), desde el 1 de marzo hasta el 20 de abril del 2020, que hubieran completado al menos un mes de seguimiento o fallecieran durante el periodo de estudio. RESULTADOS: Se incluyó a 918 pacientes (edad 63,2 ± 15,5 años, 60,1% varones) con un seguimiento mediano de 57 (49-63) días. De estos, 190 (20,7%) cumplían criterios estrictos de lesión miocárdica (21,1% crónica, 76,8% aguda no isquémica, 2,1% aguda isquémica). El tiempo desde el inicio de los síntomas hasta la hs-TnI máxima fue de 11 (7-18) días. Los eventos trombóticos y hemorrágicos, las arritmias, la insuficiencia cardíaca, la necesidad de ventilación mecánica y la muerte fueron significativamente más frecuentes en pacientes con concentraciones elevadas de hs-TnI, incluso por debajo del nivel de lesión miocárdica. La hs-TnI resultó un predictor independiente de mortalidad (HR 2,52 [(1,57-4,04] por cada 5 unidades logarítmicas). CONCLUSIÓN: La hs-TnI elevada es altamente prevalente entre los pacientes con COVID-19. Elevaciones leves muy por debajo del límite para definir lesión miocárdica se asociaron con más complicaciones y mayor mortalidad. La determinación protocolizada de hs-TnI en estos enfermos podría mejorar su estratificación pronóstica y los resultados clínicos.
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Background: Myocardial injury has been identified as a common complication in patients with COVID-19. However, recent research has serious limitations, such as non-guideline definition of myocardial injury, heterogenicity of troponin sampling or very short-term follow-up. Using data from a large European cohort, we aimed to overcome these pitfalls and adequately characterize myocardial damage in COVID-19.MethodsConsecutive patients with confirmed SARS-CoV-2 infection and available high-sensitive troponin I (hs-TnI), from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied.ResultsA total of 918 patients (mean age 63.2±15.5 years, 60.1% male) with a median follow-up of 57 (4963) days were included. Of these, 190 (20.7%) fulfilled strict criteria for myocardial injury (21.1% chronic, 76.8% acute non-ischemic, 2.1% acute ischemic). Time from onset of symptoms to maximum hs-TnI was 11 (718) days. Thrombotic and bleeding events, arrhythmias, heart failure, need for mechanical ventilation and death were significantly more prevalent in patients with higher hs-TnI concentrations, even without fulfilling criteria for myocardial injury. hs-TnI was identified as an independent predictor of mortality [HR 2.52 (1.574.04) per 5-logarithmic units increment] after adjusting for multiple relevant covariates.ConclusionElevated hs-TnI is highly prevalent among patients with SARS-CoV-2 infection. Even mild elevations well below the 99th URL were significantly associated with higher rates of cardiac and non-cardiac complications, and higher mortality. Future research should address the role of serial hs-TnI assessment to improve COVID-19 prognostic stratification and clinical outcomes. (AU)
Antecedentes: El daño miocárdico parece una complicación frecuente en pacientes con COVID-19. Sin embargo, la literatura al respecto presenta serias limitaciones, como definiciones incorrectas, heterogeneidad de las determinaciones de troponina o seguimientos cortos. Utilizando datos de una cohorte amplia, el objetivo del trabajo fue caracterizar adecuadamente el daño miocárdico en pacientes con COVID-19 utilizando una metodología adecuada.MétodosSe estudió a pacientes consecutivos con infección confirmada y determinaciones disponibles de troponina I de alta sensibilidad (hs-TnI), desde el 1 de marzo hasta el 20 de abril del 2020, que hubieran completado al menos un mes de seguimiento o fallecieran durante el periodo de estudio.ResultadosSe incluyó a 918 pacientes (edad 63,2±15,5 años, 60,1% varones) con un seguimiento mediano de 57 (49-63) días. De estos, 190 (20,7%) cumplían criterios estrictos de lesión miocárdica (21,1% crónica, 76,8% aguda no isquémica, 2,1% aguda isquémica). El tiempo desde el inicio de los síntomas hasta la hs-TnI máxima fue de 11 (7-18) días. Los eventos trombóticos y hemorrágicos, las arritmias, la insuficiencia cardíaca, la necesidad de ventilación mecánica y la muerte fueron significativamente más frecuentes en pacientes con concentraciones elevadas de hs-TnI, incluso por debajo del nivel de lesión miocárdica. La hs-TnI resultó un predictor independiente de mortalidad (HR 2,52 [(1,57-4,04] por cada 5 unidades logarítmicas).ConclusiónLa hs-TnI elevada es altamente prevalente entre los pacientes con COVID-19. Elevaciones leves muy por debajo del límite para definir lesión miocárdica se asociaron con más complicaciones y mayor mortalidad. La determinación protocolizada de hs-TnI en estos enfermos podría mejorar su estratificación pronóstica y los resultados clínicos. (AU)
Asunto(s)
Humanos , Biomarcadores , Insuficiencia Cardíaca , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Infecciones por Coronavirus/epidemiología , Troponina I , Pronóstico , MortalidadRESUMEN
BACKGROUND: Myocardial injury has been identified as a common complication in patients with COVID-19. However, recent research has serious limitations, such as non-guideline definition of myocardial injury, heterogenicity of troponin sampling or very short-term follow-up. Using data from a large European cohort, we aimed to overcome these pitfalls and adequately characterize myocardial damage in COVID-19. METHODS: Consecutive patients with confirmed SARS-CoV-2 infection and available high-sensitive troponin I (hs-TnI), from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. RESULTS: A total of 918 patients (mean age 63.2±15.5 years, 60.1% male) with a median follow-up of 57 (49-63) days were included. Of these, 190 (20.7%) fulfilled strict criteria for myocardial injury (21.1% chronic, 76.8% acute non-ischemic, 2.1% acute ischemic). Time from onset of symptoms to maximum hs-TnI was 11 (7-18) days. Thrombotic and bleeding events, arrhythmias, heart failure, need for mechanical ventilation and death were significantly more prevalent in patients with higher hs-TnI concentrations, even without fulfilling criteria for myocardial injury. hs-TnI was identified as an independent predictor of mortality [HR 2.52 (1.57-4.04) per 5-logarithmic units increment] after adjusting for multiple relevant covariates. CONCLUSION: Elevated hs-TnI is highly prevalent among patients with SARS-CoV-2 infection. Even mild elevations well below the 99th URL were significantly associated with higher rates of cardiac and non-cardiac complications, and higher mortality. Future research should address the role of serial hs-TnI assessment to improve COVID-19 prognostic stratification and clinical outcomes.
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COVID-19 , Insuficiencia Cardíaca , Anciano , Biomarcadores , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , SARS-CoV-2 , Troponina IRESUMEN
AIMS: Age, sex, and cardiovascular disease have been linked to thromboembolic complications and poorer outcomes in COVID-19. We hypothesize that CHADS2 and CHA2DS2-VASc scores may predict thromboembolic events and mortality in COVID-19. METHODS AND RESULTS: COVID-19 hospitalized patients with confirmed SARS-CoV-2 infection from 1 March to 20 April 2020 who completed at least 1-month follow-up or died were studied. CHADS2 and CHA2DS2-VASc scores were calculated. Given the worse prognosis of male patients in COVID-19, a modified CHA2DS2-VASc score (CHA2DS2-VASc-M) in which 1 point was given to male instead of female was also calculated. The associations of these scores with laboratory results, thromboembolic events, and death were analysed. A total of 3042 patients (mean age 62.3 ± 20.3 years, 54.9% male) were studied and 115 (3.8%) and 626 (20.6%) presented a definite thromboembolic event or died, respectively, during the study period [median follow 59 (50-66) days]. Higher score values were associated with more marked abnormalities of inflammatory and cardiac biomarkers. Mortality was significantly higher with increasing scores for CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M (P < 0.001 for trend). The CHA2DS2-VASc-M showed the best predictive value for mortality [area under the receiver operating characteristic curve (AUC) 0.820, P < 0.001 for comparisons]. All scores had poor predictive value for thromboembolic events (AUC 0.497, 0.490, and 0.541, respectively). CONCLUSION: The CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M scores are significantly associated with all-cause mortality but not with thromboembolism in COVID-19 patients. They are simple scoring systems in everyday use that may facilitate initial 'quick' prognostic stratification in COVID-19.
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Fibrilación Atrial , COVID-19 , Accidente Cerebrovascular , Tromboembolia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , SARS-CoV-2 , Tromboembolia/diagnóstico , Tromboembolia/epidemiologíaRESUMEN
AIMS: Extensive research regarding the association of troponin and prognosis in coronavirus disease 2019 (COVID-19) has been performed. However, data regarding natriuretic peptides are scarce. N-terminal pro B-type natriuretic peptide (NT-proBNP) reflects haemodynamic stress and has proven useful for risk stratification in heart failure (HF) and other conditions such as pulmonary embolism and pneumonia. We aimed to adequately characterize NT-proBNP concentrations using a large cohort of patients with COVID-19, and to investigate its association with prognosis. METHODS AND RESULTS: Consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and available NT-proBNP determinations, from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. Of 3080 screened patients, a total of 396 (mean age 71.8 ± 14.6 years, 61.1% male) fulfilled all the selection criteria and were finally included, with a median follow-up of 53 (18-62) days. Of those, 192 (48.5%) presented NT-proBNP levels above the recommended cut-off for the identification of HF. However, only 47 fulfilled the clinical criteria for the diagnosis of HF. Patients with higher NT-proBNP during admission experienced more frequent bleeding, arrhythmias and HF decompensations. NT-proBNP was associated with mortality both in the whole study population and after excluding patients with HF. A multivariable Cox model confirmed that NT-proBNP was independently associated with mortality after adjusting for all relevant confounders (hazard ratio 1.28, 95% confidence interval 1.13-1.44, per logarithmic unit). CONCLUSION: NT-proBNP is frequently elevated in COVID-19. It is strongly and independently associated with mortality after adjusting for relevant confounders, including chronic HF and acute HF. Therefore, its use may improve early prognostic stratification in this condition.
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COVID-19 , Insuficiencia Cardíaca , Anciano , Anciano de 80 o más Años , Biomarcadores , Femenino , Insuficiencia Cardíaca/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Pronóstico , SARS-CoV-2RESUMEN
AIMS: To evaluate the burden of tricuspid regurgitation (TR) in a large cohort, determine the right ventricle involvement of patients with TR and determine the characteristics of isolated TR. METHODS AND RESULTS: Prospective study where consecutive patients undergoing an echocardiographic study in 10 centres were included. All studies with significant TR (at least moderate) were selected. We considered that patients with one of pulmonary systolic hypertension >50 mmHg, left ventricular ejection fraction <35%, New York Heart Association III-IV, or older than 85 years, had a high surgical risk. A total of 35 088 echocardiograms were performed. Significant TR was detected in 6% of studies. Moderate TR was found in 69.6%, severe in 25.5%, massive in 3.9%, and torrential in 1.0% of patients. Right ventricle was dilated in 81.7% of patients with massive/torrential TR, in 55.9% with severe TR, and in 29.3% with moderate TR (P < 0.001). Primary TR was present in 7.4% of patients whereas secondary TR was present in 92.6%. Mitral or aortic valve disease was the most common aetiology (54.6%), following by isolated TR (16%). Up to 51.9% of patients with severe, massive, or torrential primary TR and 57% of patients with severe, massive, or torrential secondary TR had a high surgical risk. CONCLUSION: Significant TR is a prevalent condition and a high proportion of these patients have an indication for valve intervention. More than a half of patients with severe, massive, or torrential TR had a high surgical risk. Massive/torrential TR may have implications regarding selection and monitoring patients for percutaneous treatment.
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Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Tricúspide , Estudios de Cohortes , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Volumen Sistólico , Resultado del Tratamiento , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagen , Insuficiencia de la Válvula Tricúspide/epidemiología , Insuficiencia de la Válvula Tricúspide/cirugía , Función Ventricular IzquierdaAsunto(s)
Cardiomiopatías/diagnóstico por imagen , Ecocardiografía Transesofágica/métodos , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Músculos Papilares/diagnóstico por imagen , Anciano , Cardiomiopatías/complicaciones , Cardiomiopatías/patología , Resultado Fatal , Femenino , Humanos , Imagenología Tridimensional , Insuficiencia de la Válvula Mitral/etiología , Músculos Papilares/patología , Rotura EspontáneaRESUMEN
The natural history of pediatric nonalcoholic steatohepatitis is still unknown; however, there are differences between adult and pediatric presentation. Apoptosis may play an important role in pathophysiologic pathways involved in liver damage and progression. Our aim was to detect early apoptosis markers, activated caspase-3 and cleaved cytokeratin-18, in hepatocytes and to correlate their presence with clinical, serologic, and histologic characteristics in pediatric nonalcoholic steatohepatitis. Twenty-five pediatric nonalcoholic steatohepatitis liver biopsies were evaluated by immunohistochemistry for presence of activated caspase-3 and cleaved cytokeratin-18. Biopsy specimens were semiquantitatively graded for activity (steatosis, inflammation, and ballooning) and fibrosis. Records were reviewed for serum aspartate aminotransferase, alanine aminotransferase, cholesterol, triglycerides, and body mass index, which was elevated in 92% of cases. Serum aspartate aminotransferase and alanine aminotransferase were elevated in 32% and 68% of cases, respectively. Sixty percent of biopsies exhibited lobular steatosis grade 3, 84% lobular inflammatory activity grade 1, 72% ballooning grade 1, and 76% fibrosis stage 3. Cleaved cytokeratin-18 was associated with milder fibrosis (P = .02) and inflammation (P = .07), although there was no association with steatosis grade. Activated caspase-3 detection was also associated with low inflammatory grade (P = .03) but not with fibrosis and steatosis. This study reveals interesting differential features concerning nonalcoholic steatohepatitis histologic characteristics and apoptosis markers compared with adult cases. Because, in this pediatric series, apoptosis seemed to be an early event in the cascade of liver injury steps, it would be useful to consider caspase inhibitors as potential therapeutic strategies to prevent liver damage progression.
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Apoptosis , Caspasa 3/metabolismo , Hígado Graso/patología , Hepatocitos/patología , Queratina-18/metabolismo , Hígado/patología , Adolescente , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Biomarcadores/metabolismo , Biopsia , Niño , Preescolar , Hígado Graso/clasificación , Hígado Graso/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente Directa , Hepatocitos/metabolismo , Humanos , Lactante , Hígado/metabolismo , Pruebas de Función Hepática , MasculinoRESUMEN
Se describe un caso de anomalía vascular asociado a atresia biliar extrahepática. La paciente de dos meses de edad presentaba desde el nacimiento, signos clínicos de colangiopatía obstructiva. En el acto quirúrgico se confirma AVBEH y mediante ileoportografía se advierte vena preduodenal que ingresa al hígado dando ramas independientes para los lóbulos derecho e izquierdo del hígado. La niña fallece. La anatomía patológica confirmó los hallazgos quirúrgicos y además otras anomalías (AU)
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Recién Nacido , Humanos , Colestasis Extrahepática/cirugíaRESUMEN
Se describe un caso de anomalía vascular asociado a atresia biliar extrahepática. La paciente de dos meses de edad presentaba desde el nacimiento, signos clínicos de colangiopatía obstructiva. En el acto quirúrgico se confirma AVBEH y mediante ileoportografía se advierte vena preduodenal que ingresa al hígado dando ramas independientes para los lóbulos derecho e izquierdo del hígado. La niña fallece. La anatomía patológica confirmó los hallazgos quirúrgicos y además otras anomalías