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Síndrome del Corazón Izquierdo Hipoplásico , Procedimientos de Norwood , Humanos , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/cirugía , Ventrículos Cardíacos/fisiopatología , Síndrome del Corazón Izquierdo Hipoplásico/diagnóstico por imagen , Síndrome del Corazón Izquierdo Hipoplásico/cirugía , Función Ventricular , Válvulas Cardíacas/fisiopatologíaRESUMEN
OBJECTIVE: This study compared the mortality, left atrioventricular valve-related reoperation, and left atrioventricular valve competence in symptomatic neonates and small infants who underwent staged repair incorporating pulmonary artery banding or primary repair for complete atrioventricular septal defect. METHODS: Patients weighing less than 4.0 kg at the time of undergoing staged (n = 37) or primary (n = 23) repair for balanced complete atrioventricular septal defect between 1999 and 2022 were reviewed. The mean follow-up period was 9.1 years. Freedom from moderate or greater left atrioventricular valve regurgitation was estimated with the Kaplan-Meier method. RESULTS: The staged group included smaller children (median weight, 2.9 vs 3.7 kg) and a higher proportion of neonates (41% vs 4%). All patients in the staged group survived pulmonary artery banding and underwent intracardiac repair (median weight, 6.8 kg). After pulmonary artery banding, the severity of left atrioventricular valve regurgitation improved in 10 of 12 patients (83%) without left atrioventricular valve anomaly who had mild or greater left atrioventricular valve regurgitation and a left atrioventricular valve Z score greater than 0. Although survival and freedom from left atrioventricular valve-related reoperation at 15 years (P = .195 and .602, respectively) were comparable between the groups, freedom from moderate or greater left atrioventricular valve regurgitation at 15 years was higher in the staged group (P = .026). CONCLUSIONS: Compared with primary repair, staged repair for complete atrioventricular septal defect in children weighing less than 4.0 kg resulted in comparable survival and reoperation rates and better left atrioventricular valve competence. Pulmonary artery banding may mitigate secondary left atrioventricular valve regurgitation unless a structural valve abnormality exists. Selective deferred intracardiac repair beyond the neonatal and small-infancy period may still play an important role in low-weight patients.
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Procedimientos Quirúrgicos Cardíacos , Defectos de los Tabiques Cardíacos , Insuficiencia de la Válvula Mitral , Lactante , Niño , Recién Nacido , Humanos , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/cirugía , Válvula Mitral , Reoperación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We herein elucidate the function of SARS-CoV-2derived 5'UTR in the human cells. 5'UTR bound host cellular RNAs were immunoprecipitated by gRNA-dCas13 (targeting luciferase RNA fused to SARS-CoV-2 5'UTR) in HEK293T and A549 cells. The 5'UTR bound RNA extractions were predominantly enriched for regulating lipid metabolism. Overexpression of SARS-CoV-2 5'UTR RNA altered the expression of factors involved in the process of the human Mevalonate pathway. In addition, we found that HMG-CoA reductase inhibitors were shown to suppress SARS-CoV-2 5'UTR-mediated translation activities. In conclusion, we deduce the array of host RNAs interacting with SARS-CoV-2 5'UTR that drives SARS-CoV-2 translation and influences host metabolic pathways.
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COVID-19 , SARS-CoV-2 , Humanos , Regiones no Traducidas 5' , SARS-CoV-2/genética , Metabolismo de los Lípidos , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Células HEK293 , COVID-19/genética , Biosíntesis de ProteínasRESUMEN
Although systemic treatment for hepatocellular carcinoma has advanced after the development of tyrosine kinase inhibitors such as sorafenib and lenvatinib, the effectiveness of a single tyrosine kinase inhibitor in survival extension of unresectable hepatocellular carcinoma is limited to a few months. Therefore, novel treatment options are required for unresectable hepatocellular carcinomas, including those with multiple lung metastases. This case report describes a hepatocellular carcinoma patient with a recurrence of multiple lung metastases, which was successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. A 79-year-old man underwent right hepatectomy for hepatocellular carcinoma, along with removal of the tumor thrombus in the inferior vena cava. Multiple lung metastases were detected 4 months after hepatectomy. Treatment with tyrosine kinase inhibitors, mainly lenvatinib, resulted in complete remission of the lung metastases, except for one lesion in segment 3 of the right lung which gradually enlarged. Twenty-three months after hepatectomy, partial resection of the right lung was performed using video-assisted thoracic surgery for this residual lesion in the right lung. The patient remained disease-free for 11 months after conversion pneumonectomy, without any adjuvant therapies. This is the first case report of multiple lung metastases originating from hepatocellular carcinoma which were successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. Conversion pneumonectomy after systemic therapy with tyrosine kinase inhibitors should be considered as a treatment strategy for patients with unresectable multiple lung metastases from hepatocellular carcinomas.
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OBJECTIVES: We compared 2-patch repair (TP) with modified single-patch repair (MSP) for complete atrioventricular septal defects and evaluated their effect on the left atrioventricular valve (LAVV) competence. We also identified risk factors for unfavorable functional outcomes. METHODS: This retrospective study included 118 patients with complete atrioventricular septal defects who underwent intracardiac repair from 1998 to 2020 (MSP: 69; TP: 49). The median follow-up period was 10.4 years. The functional outcome of freedom from moderate or greater LAVV regurgitation (LAVVR) was estimated using the Kaplan-Meier method. RESULTS: The hospital mortality was 1.7% (2/118) and late mortality was 0.8% (1/118). Eight patients required LAVV-related reoperation (MSP: 4; TP: 4) and none required left ventricular outflow tract-related reoperation. In the MSP group without LAVV anomaly, the receiver operating characteristic curve analysis revealed that the ventricular septal defect (VSD) depth was strongly associated with moderate or greater postoperative LAVVR, with the best cutoff at 10.9 mm. When stratified according to the combination of intracardiac repair type and VSD depth, the MSP-deep VSD (VSD depth >11 mm) group showed the worst LAVV competence among the 4 groups (P = .002). According to multivariate analysis, weight <4.0 kg, LAVV anomaly, and moderate or greater preoperative LAVVR were independent risk factors for moderate or greater postoperative LAVVR, whereas MSP was not a risk factor. CONCLUSIONS: Postoperative LAVVR remains an obstacle to improved functional outcomes. MSP provides LAVV competence similar to TP unless deep VSD is present. The surgical approach should be selected on the basis of anatomical variations, specifically VSD depth.
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Defectos del Tabique Interventricular , Defectos de los Tabiques Cardíacos , Humanos , Lactante , Estudios Retrospectivos , Defectos del Tabique Interventricular/diagnóstico por imagen , Defectos del Tabique Interventricular/cirugía , Reoperación , Resultado del TratamientoRESUMEN
The disadvantage of right ventricle-to-pulmonary artery (RV-PA) shunt is the need for more unplanned interventions to address stenosis in the shunt or branch pulmonary arteries, as compared to the modified Blalock-Taussig shunt group. Ring-enforced RV-PA PTFE conduit and dunk technique minimized these complications and right ventricle (RV) damage. Aortic arch obstruction increases afterload and leads to ventricular dysfunction and tricuspid regurgitation; therefore, most surgeons prefer to use homograft, autologous pericardium, or bovine pericardium to reconstruct the neoaorta. Artificial materials decrease the elastic properties, increase wall stiffness, and decrease the distensibility of the aorta; and as a result, RV function gradually deteriorates. This inelastic reconstructed aorta may be one of the reasons why long-term outcomes after the Fontan procedure are worse in hypoplastic left heart syndrome (HLHS) patients, in comparison to non-HLHS. Reconstruction of the neoaorta without any patch materials, or at least techniques that largely minimize the use of non-autologous materials, will offer a further refinement of our ability to optimize ventriculoarterial coupling and thereby long-term RV function.
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Procedimiento de Blalock-Taussing , Procedimiento de Fontan , Síndrome del Corazón Izquierdo Hipoplásico , Procedimientos de Norwood , Animales , Aorta Torácica/cirugía , Bovinos , Procedimiento de Fontan/métodos , Ventrículos Cardíacos/cirugía , Humanos , Síndrome del Corazón Izquierdo Hipoplásico/cirugía , Procedimientos de Norwood/métodos , Arteria Pulmonar/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: This study evaluated the impact of a staged surgical strategy incorporating a modified Blalock-Taussig shunt (BTS) for tetralogy of Fallot on pulmonary valve annulus growth, the rate of valve-sparing repair at the time of intracardiac repair, and long-term functional outcomes. METHODS: This retrospective study involved 330 patients with tetralogy of Fallot who underwent intracardiac repair between 1991 and 2019 and included 57 patients (17%) who underwent BTS. The mean follow-up period was 15.0 ± 7.3 years. We compared the data of patients who underwent BTS and patients who did not undergo BTS before intracardiac repair. RESULTS: The median age before BTS was 71 days (range, 28 to 199) and the median body weight was 4.3 kg (range, 3.3 to 6.8 kg). There were no inhospital or interstage deaths after BTS. The pulmonary valve annulus Z scores of patients with BTS revealed significant growth after BTS (from -4.2 ± 1.8 to -3.0 ± 1.7, P < .001). Valve-sparing repair was eventually performed in 207 patients (63%), including 26 (46%) who underwent staged repair. The overall freedom from pulmonary regurgitation-related reintervention was 99.7%, 99.1%, and 95.8% at 1, 5, and 20 years, respectively. CONCLUSIONS: A staged surgical strategy incorporating BTS as the first palliation for symptomatic patients resulted in no mortality. Blalock-Taussig shunt may have contributed to the avoidance of primary transannular patch repair and facilitated pulmonary valve annulus growth; therefore, approximately half of the symptomatic neonates and infants were recruited for valve-sparing repair. Staged repair may have led to functionally reliable delayed transannular patch repair, thereby resulting in fewer surgical reinterventions.
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Insuficiencia de la Válvula Pulmonar , Válvula Pulmonar , Tetralogía de Fallot , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Tetralogía de Fallot/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVE: Permanent loss of cardiomyocytes after myocardial infarction results in irreversible damage to cardiac function. The present study aims to enhance the cardiomyogenic efficiency of cardiosphere-derived cells (CDCs) to develop into large populations of cardiomyocytes by intrinsic activation of cardio-specific differentiation factors (Gata4, Mef2c, Nkx2-5, Hand2, and Tnnt2) by a CRISPR/dCas9 assisted transcriptional enhancement system. METHODS: Exhaustive screening was performed to identify the specific sequences in endogenous regulatory regions (enhancers and promoters) responsible for transcriptional activation of the target genes, via a CRISPR/dCas9 system fused with transcriptional activator VP64 (CRISPR-dCas9-VP64). In a rat model of acute myocardial infarction, we compared the regenerative potential and functional benefits of CDCs with or without transcriptional activation. RESULTS: We identified a panel of specific CRISPR RNA targeting the enhancers and promoters, which demonstrated significantly higher expression of differentiation factors of Gata4, Hand2, and Tnnt2. The group of CDCs with transcriptional activator VP64 (CDC with VP64) showed significant improvement in the left ventricular ejection fraction (61.9% vs 52.5% and 44.1% in the CDC without transcriptional activation group and control) and decreased scar area in the heart. CONCLUSIONS: We have identified endogenous regulatory regions responsible for an intrinsic activation of cardio-specific differentiation factors assisted via a CRISPR/dCas9 gene transcriptional system. The CRISPR/dCas9 system may provide an efficient and effective means of regulating Tnnt2 gene activation within stem cells. Subsequently, this system can be used to enhance transplanted CDCs differentiation potential within ischemic myocardia to better therapeutic outcomes of patients with ischemic heart disease.
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Proteína 9 Asociada a CRISPR , Edición Génica/métodos , Infarto del Miocardio/terapia , Miocitos Cardíacos/citología , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Modelos Animales de Enfermedad , Elementos de Facilitación Genéticos , Factor de Transcripción GATA4 , Ratas Sprague-Dawley , Volumen Sistólico , Activación Transcripcional , Troponina TAsunto(s)
Cardiopatías , Corazón/fisiología , Inmunidad/fisiología , Miocitos Cardíacos/fisiología , Regeneración , Trasplante de Células Madre/métodos , Células Madre/fisiología , Adulto , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Ensayos Clínicos como Asunto , Cardiopatías/clasificación , Cardiopatías/congénito , Cardiopatías/terapia , Humanos , Recién Nacido , Regeneración/inmunología , Regeneración/fisiologíaRESUMEN
OBJECTIVES: This study aimed to evaluate whether recoarctation of the aorta (reCoA) after the Norwood procedure for hypoplastic left heart syndrome correlates with pre- and postoperative anatomic factors. METHODS: This retrospective study included 48 patients who underwent Norwood procedure with right ventricle-to-pulmonary artery conduit between 2009 and 2017. Anatomical factors such as preoperative length, diameter of the main pulmonary artery (MPA), and postoperative neoaortic arch angle stratified by arch reconstruction technique were analysed using the receiver operating characteristic analysis. RESULTS: Eleven patients needed surgical intervention for reCoA at stage 2. Out of the 30 patients who underwent direct anastomosis during arch reconstruction, 7 developed reCoA. Seven patients received the full patch augmentation (patch augmentation for both lesser and greater curvatures) and were all spared from reCoA. Among the patients who had direct anastomosis, the preoperative MPA length was correlated with the postoperative arch angle (P = 0.021) and was associated with the occurrence of reCoA (P = 0.002) and the best cutoff value for MPA length was 10 mm. The postoperative arch angle was also correlated with the incidence of reCoA (P < 0.001) and was larger in patients who underwent the full patch augmentation than in patients who had direct anastomosis (126° vs 112°, P = 0.005) despite comparable MPA length. CONCLUSIONS: ReCoA after the Norwood procedure correlates with MPA length when a direct anastomosis was used. Direct anastomosis can be considered in patients with a longer preoperative MPA. In other cases, the full patch augmentation should be considered for obtaining a large and smooth neoaortic arch.
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Síndrome del Corazón Izquierdo Hipoplásico , Procedimientos de Norwood , Aorta , Humanos , Síndrome del Corazón Izquierdo Hipoplásico/diagnóstico por imagen , Síndrome del Corazón Izquierdo Hipoplásico/cirugía , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: This study aimed to determine the factors related to reintervention, especially for pulmonary stenosis (PS), in patients with Taussig-Bing anomaly (TBA) after the arterial switch operation. METHODS: This retrospective study included 34 patients with TBA who underwent the arterial switch operation between 1993 and 2018. Preoperative anatomic and physiologic differences and long-term outcomes were determined using a case-matched control with transposition of the great arteries with ventricular septal defect and TBA with an anterior and rightward aorta. RESULTS: At arterial switch operation, median age was 43 days (range, 16 to 102) and median body weight was 3.6 kg (range, 2.8 to 3.8 kg). Aortic arch obstruction and coronary anomalies were present in 64% and 41% of patients, respectively. The hospital mortality rate was 11%, including one cardiac death, and the late mortality rate was 2.9%. Furthermore, 41% patients underwent 26 reinterventions for PS. Patients undergoing PS-related reintervention had a significantly larger native pulmonary artery to aortic annulus size ratio than patients not receiving reintervention (1.69 vs 1.41, P = .02). This ratio was the only predictor of PS-related reintervention; it was significantly higher in the TBA group than in the transposition of great arteries/ventricular septal defect group. The PS-related reintervention was required more in the TBA group than in the transposition of great arteries/ventricular septal defect group. CONCLUSIONS: Regardless of complex coronary anatomy and associated anomalies, early and late survival were acceptable. Postoperative PS was strongly associated with having a larger native pulmonary valve, suggesting that an optimal surgical reconstruction was required for achieving an appropriate aortopulmonary anatomic relationship during the arterial switch operation.
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Operación de Switch Arterial/efectos adversos , Ventrículo Derecho con Doble Salida/cirugía , Arteria Pulmonar/anatomía & histología , Reoperación , Operación de Switch Arterial/métodos , Ventrículo Derecho con Doble Salida/patología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Modelos de Riesgos Proporcionales , Estenosis de la Válvula Pulmonar/etiología , Estenosis de la Válvula Pulmonar/cirugía , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Southwestern Japan suffered its worst rains in 2018 causing floods and mudslides, claiming 225 lives and forcing millions for evacuations. Referred as "Heisei san-ju-nenshichi-gatsugou", the disaster was the result of incessant precipitation caused by the interaction of typhoon "Prapiroon" with the seasonal rain front "Baiu". The present epidemiological study aims to investigate disaster-induced health issues in 728 residents of Innoshima island in the Hiroshima Prefecture by comparing their clinical data in pre-disaster (2017) and disaster-hit (2018) years which was obtained from annual health screening. Comparison of data showed a significant increase in the urine protein concentration in victims following the disaster. Probing further into the household conditions, showed that a total of 59,844 households were affected with water outage during the heavy rains, which was accompanied by severe damage of sewerage pipelines with complete recovery process taking two weeks. This two weeks of the crisis forced victims to refrain from using restrooms which in turn led to infrequent urination, thereby explaining the increased urine protein concentration in victims following the disaster. The present study addresses the acute health implications caused by the water crisis and serves as a precautionary measure for disaster management council to provide enhanced aftercare services in victims in further events of natural disasters.
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Significant achievements in paediatric cardiology, surgical treatment and intensive care of congenital heart disease have drastically changed clinical outcomes for paediatric patients. Nevertheless, late-onset heart failure in children after staged surgeries still remains a serious concern in the medical community. Heart transplantation is an option for treatment; however, the shortage of available organs is a persistent problem in many developed countries. In order to resolve these issues, advanced technologies, such as innovative mechanical circulatory support devices and regenerative therapies, are strongly desired. Accumulated evidence regarding cell-based cardiac regenerative therapies has suggested their safety and efficacy in treating adult heart failure. Given that young children seem to have a higher regenerative capacity than adults, stem cell-based therapies appear a promising treatment option for paediatric heart failure as well. Based on the findings from past trials and studies, we present the potential of various different types of stem cells, ranging from bone marrow mononuclear cells to cardiosphere-derived stem cells for use in paediatric cell-based therapies. Here, we assess both the current challenges associated with cell-based therapies and novel strategies that may be implemented in the future to advance stem cell therapy in the paediatric population.
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Cardiopatías Congénitas , Insuficiencia Cardíaca , Trasplante de Corazón , Tratamiento Basado en Trasplante de Células y Tejidos , Niño , Cardiopatías Congénitas/cirugía , Insuficiencia Cardíaca/terapia , Humanos , Trasplante de Células MadreRESUMEN
Heart diseases are one of the major causes of morbidity and mortality worldwide. Despite major advances in drug and interventional therapies, surgical procedures, and organ transplantation, further research into new therapeutic options is still necessary. Stem cell therapy has emerged as one option for the treatment of a variety of heart diseases. Although a large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach, the results obtained from these clinical studies are inconsistent, and stem cell-based improvements of heart performance and cardiac remodeling were found to be quite limited. Since the precise mechanisms underlying the therapeutic actions of stem cells are still under debate, researchers have developed a variety of strategies to improve and boost the potency of stem cells in repair. In this Reviews, we summarize both the current therapeutic strategies using stem cells and future directions for enhancing stem cell potency.