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A 14-year-old girl was scheduled for pulmonary valve replacement. A computed tomography scan showed an enlarged cardiac silhouette with an aneurysmal pulmonary artery. A less-invasive approach through the left axilla with peripheral cannulation was selected. The patient was draped in the decubitus position, with a roll under the left shoulder and the left arm over the head. The anatomical landmarks were the left nipple and the tip of the scapula. A 5-cm vertical incision in the mid-axillary line was performed, and the thorax was entered through the fourth intercostal space. Peripheral cannulation for cardiopulmonary bypass was achieved by a right groin dissection. Partial bypass was instituted and, on an unloaded heart, the ascending aorta plus the right appendage and the pulmonary artery were further cannulated. With the heart beating, the pulmonary artery was opened, and a 25-mm biological Carpentier Perimount-Magna valve was chosen. A second stitch was used to close the arteriotomy with large bites in a double row to reduce the perimeter of the trunk. Cardiopulmonary bypass was discontinued (after 64 minutes), and the cannulas were removed sequentially. Echocardiography showed a good result, with proper valve function and a reduced pulmonary artery. The patient was discharged on postoperative day 12 on antiplatelet therapy.
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Procedimentos Cirúrgicos Cardíacos , Valva Pulmonar , Feminino , Humanos , Adolescente , Axila/cirurgia , Valva Pulmonar/cirurgia , Reimplante , AortaRESUMO
Due to their suppressive capacity, regulatory T cells (Tregs) have attracted growing interest as an adoptive cellular therapy for the prevention of allograft rejection, but limited Treg recovery and lower quality of adult-derived Tregs could represent an obstacle to success. To address this challenge, we developed a new approach that provides large quantities of Tregs with high purity and excellent features, sourced from thymic tissue routinely removed during pediatric cardiac surgeries (thyTregs). We report on a 2-year follow-up of the first patient treated worldwide with thyTregs, included in a phase I/II clinical trial evaluating the administration of autologous thyTreg in infants undergoing heart transplantation. In addition to observing no adverse effects that could be attributed to thyTreg administration, we report that the Treg frequency in the periphery was preserved during the 2-year follow-up period. These initial results are consistent with the trial objective, which is to confirm safety of the autologous thyTreg administration and its capacity to restore the Treg pool.
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Transplante de Coração , Linfócitos T Reguladores , Adulto , Humanos , Lactente , Rejeição de Enxerto , Transplante HomólogoAssuntos
Transplante de Coração , Doadores de Tecidos , Humanos , Criança , Espanha , Perfusão , MorteRESUMO
OBJECTIVES: To describe the use of ventricular assist devices (VAD) in children in Spain and to identify variables related to survival. METHODS: This is an observational cohort study of all children younger than 18 years of age who underwent an initial implantation of a VAD at any of the 6 paediatric heart transplant centres from May 2006 to December 2020. Subjects were identified retrospectively from each hospital's database. RESULTS: Paracorporeal VADs were implanted in 118 children [pulsatile (63%), continuous (30.5%) or both types (5.9%)]. Small children (<0.7 m2 of body surface area) comprised the majority of this cohort (63.3%). Overall, 67% survived to VAD explantation, and 64.9% survived to hospital discharge. Non-central nervous system haemorrhage (39%) and stroke (38.1%) were the most common complications. Body weight <5 kg, congenital heart disease, pre-implantation bilirubin >34 µmol/l and bridge to decision strategy were associated with a higher mortality at hospital discharge and in the long-term. Interagency registry for mechanically assisted circulatory support (INTERMACS) status 1 and cardiac arrest prior to VAD implantation were related to long-term mortality, whereas pre-implantation renal replacement therapy and extracorporeal membrane oxygenation were not related to mortality. CONCLUSIONS: In Spain, 67% of the VAD-supported children have been bridged to heart transplantation or to recovery. Body weight lower than 5 kg, congenital heart disease diagnosis, cholestatic liver dysfunction, bridge to decision as VAD strategy, INTERMACS-1 status and cardiac arrest were pre-implantation variables related to mortality, whereas pre-implantation renal replacement therapy and extracorporeal membrane oxygenation were not.
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Parada Cardíaca , Cardiopatias Congênitas , Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Criança , Humanos , Insuficiência Cardíaca/terapia , Estudos Retrospectivos , Espanha , Resultado do TratamentoRESUMO
The aim of this study was to analyze patients diagnosed with chylothorax after congenital heart disease surgery among a cohort of neonatal patients, comparing the evolution, complications, and prognosis after surgery of patients who were and were not diagnosed with chylothorax, and to analyze possible risk factors that may predict the appearance of chylothorax in this population. Retrospective and observational study included all neonates (less than 30 days since birth) who underwent congenital heart disease surgery in a level III neonatal intensive care department. We included infants born between January 2014 and December 2019. We excluded those infants who were born before 34 weeks of gestational age or whose birth weight was less than 1800 g. We also excluded catheter lab procedures and patent ductus arteriosus closure surgeries. Included patients were divided into two groups depending on whether they were diagnosed with chylothorax or not after surgery, and both groups were compared in terms of perinatal-obstetrical information, surgical data, and NICU course after surgery. We included 149 neonates with congenital heart disease surgery. Thirty-one patients (20.8%) developed chylothorax, and in ten patients (32.3%), it was considered large volume chylothorax. Regarding the evolution of these patients, 22 infants responded to general dietetic measures, a catheter procedure was performed in 9, and 5 of them finally required pleurodesis. Cardiopulmonary bypass, median sternotomy, and delayed sternal closure were the surgical variables associated with higher risks of chylothorax. Patients with chylothorax had a longer duration of inotropic support and mechanical ventilation and took longer to reach full enteral feeds. As complications, they had higher rates of cholestasis, catheter-related sepsis, and venous thrombosis. Although there were no differences in neonatal mortality, patients with chylothorax had a higher rate of mortality after the neonatal period. In a multiple linear regression model, thrombosis and cardiopulmonary bypass multiplied by 10.0 and 5.1, respectively, the risk of chylothorax and have an umbilical vein catheter decreases risk. CONCLUSION: We have found a high incidence of chylothorax after neonatal cardiac surgery, which prolongs the average stay and causes significant morbidity and mortality. We suggested that chylothorax could be an underestimated complication of congenital heart disease surgery during the neonatal period. WHAT IS KNOWN: ⢠Acquired chylothorax in the neonatal period usually appears as a complication of congenital heart disease surgery, being the incidence quite variable among the different patient series (2.5-16.8%). The appearance of chylothorax as a complication of a cardiac surgery increases both mortality and morbidity in these patients, which makes it a quality improvement target in the postsurgical management of this population. WHAT IS NEW: â¢Most of the published studies include pediatric patients of all ages, from newborns to teenagers, and there is a lack of studies focusing on neonatal populations. The main strength of our study is that it reports, to the best of our knowledge, one of the largest series of neonatal patients receiving surgery for congenital heart disease in the first 30 days after birth. We have found a high incidence of chylothorax after cardiac surgery during the neonatal period compared to other studies. We suggested that chylothorax could be an underestimated complication of congenital heart disease surgery during this period of life.
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Procedimentos Cirúrgicos Cardíacos , Quilotórax , Cardiopatias Congênitas , Lactente , Adolescente , Humanos , Criança , Recém-Nascido , Estudos Retrospectivos , Quilotórax/epidemiologia , Quilotórax/etiologia , Quilotórax/terapia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/diagnóstico , Fatores de RiscoRESUMO
Due to their suppressive capacity, the adoptive transfer of regulatory T cells (Treg) has acquired a growing interest in controlling exacerbated inflammatory responses. Limited Treg recovery and reduced quality remain the main obstacles in most current protocols where differentiated Treg are obtained from adult peripheral blood. An alternate Treg source is umbilical cord blood, a promising source of Treg cells due to the higher frequency of naïve Treg and lower frequency of memory T cells present in the fetus' blood. However, the Treg number isolated from cord blood remains limiting. Human thymuses routinely discarded during pediatric cardiac surgeries to access the retrosternal operative field has been recently proposed as a novel source of Treg for cellular therapy. This strategy overcomes the main limitations of current Treg sources, allowing the obtention of very high numbers of undifferentiated Treg. We have developed a novel good manufacturing practice (GMP) protocol to obtain large Treg amounts, with very high purity and suppressive capacity, from the pediatric thymus (named hereafter thyTreg). The total amount of thyTreg obtained at the end of the procedure, after a short-term culture of 7 days, reach an average of 1,757 x106 (range 50 x 106 - 13,649 x 106) cells from a single thymus. The thyTreg product obtained with our protocol shows very high viability (mean 93.25%; range 83.35% - 97.97%), very high purity (mean 92.89%; range 70.10% - 98.41% of CD25+FOXP3+ cells), stability under proinflammatory conditions and a very high suppressive capacity (inhibiting in more than 75% the proliferation of activated CD4+ and CD8+ T cells in vitro at a thyTreg:responder cells ratio of 1:1). Our thyTreg product has been approved by the Spanish Drug Agency (AEMPS) to be administered as cell therapy. We are recruiting patients in the first-in-human phase I/II clinical trial worldwide that evaluates the safety, feasibility, and efficacy of autologous thyTreg administration in children undergoing heart transplantation (NCT04924491). The high quality and amount of thyTreg and the differential features of the final product obtained with our protocol allow preparing hundreds of doses from a single thymus with improved therapeutic properties, which can be cryopreserved and could open the possibility of an "off-the-shelf" allogeneic use in another individual.
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Fatores de Transcrição Forkhead , Linfócitos T Reguladores , Transferência Adotiva , Adulto , Linfócitos T CD8-Positivos , Terapia Baseada em Transplante de Células e Tecidos , Criança , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , HumanosRESUMO
BACKGROUND: Donation after Circulatory death is gaining worldwide acceptance. Most protocols regard their first cases to be performed with donor and recipient in the same institution. Few records of children or distant procurement have been published. METHODS: Our institution was offered a heart from a 3-day-old, 3.4-kg child, blood group A, suffering irreversible encephalopathy. Parents accepted withdrawal of life-sustaining therapy and agreed to donation. The donor hospital was located 340 km away. Concomitantly, a 2-month-old, 3.1 kg, blood group type B and with non-compaction ventricles was awaiting for the heart transplant in our unit. RESULTS: Thirty-seven minutes after withdrawal of life-sustaining therapy, the heart arrested. Five minutes afterwards, a sternotomy was performed. The supra-aortic vessels were clamped altogether. Aorta and right appendage were cannulated and connected to heart-lung machine. The innominate artery above the clamp was severed. The heart resumed spontaneous rhythm in less than 1 min. Ventilation was restored and extracorporeal circulation was maintained for 32 min. Upon cardiologic arrest, the graft was harvested as routinely. The heart was cold-stored and transported by plane to our Hospital. An orthotopic bicaval transplant was performed. Overall cold ischaemia was 245 min. Ten weeks later, the child was discharged home in good condition. CONCLUSION: Donation in circulatory death could increase the pool in neonates. Extracorporeal circulation proves successful for procurement in neonates. Distant procurement plus cold storage for donation in circulatory death is feasible. Donation in circulatory death and ABO non-compatible strategies are complementary to each other.
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Antígenos de Grupos Sanguíneos , Transplante de Coração , Obtenção de Tecidos e Órgãos , Transplantes , Humanos , Criança , Recém-Nascido , Lactente , Doadores de Tecidos , Isquemia Fria , MorteRESUMO
Background: Collaboration between cardiac surgeons and cardiologists can offer interventions that each specialist may not be able to offer on their own. This type of collaboration has been demonstrated with the hybrid Stage I in patients with hypoplastic heart syndrome. Since that time, a hybrid approach to cardiac interventions has been expanded to an incredible variety of potential indications. Methods: Seventy-one patients were scheduled for a hybrid procedure along 8 years. This was defined as close collaboration between surgeon and cardiologist working together in the same room, either cath-lab (27 patients) or theater (44 patients). Results: Six groups were arbitrarily defined. A: vascular cut-down in the cath-lab (27 neonates); B: bilateral banding (plus ductal stent) in hypoplastic left heart syndrome or alike (15 children); C: perventricular closure of muscular ventricular septal defect (10 cases); D: balloon/stenting of pulmonary branches along with major surgical procedure (12 kids); E: surgical implantation of Melody valve (six patients) and others (F, one case). Two complications were recorded: left ventricular free wall puncture and previous conduit tearing. Both drawbacks were successfully sort out under cardiopulmonary by-pass. Conclusion: Surgeon and cardiologist partnership can succeed where their isolated endeavors are not enough. Hybrid procedures keep on spreading, overcoming initial expectations. As a bridge to biventricular repair or transplant, bilateral banding plus ductal stent sounds interesting. Novel indications can be classified into different groups. Hybrid procedures are not complication-free.
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Regulatory T cells (Tregs), which are characterized by the expression of the transcription factor forkhead box P3 (FOXP3), are the main immune cells that induce tolerance and are regulators of immune homeostasis. Natural Treg cells (nTregs), described as CD4+CD25+FOXP3+, are generated in the thymus via activation and cytokine signaling. Transforming growth factor beta type 1 (TGF-ß1) is pivotal to the generation of the nTreg lineage, its maintenance in the thymus, and to generating induced Treg cells (iTregs) in the periphery or in vitro arising from conventional T cells (Tconvs). Here, we tested whether TGF-ß1 treatment, associated with interleukin-2 (IL-2) and CD3/CD28 stimulation, could generate functional Treg-like cells from human thymocytes in vitro, as it does from Tconvs. Additionally, we genetically manipulated the cells for ectopic FOXP3 expression, along with the TGF-ß1 treatment. We demonstrated that TGF-ß1 and ectopic FOXP3, combined with IL-2 and through CD3/CD28 activation, transformed human thymocytes into cells that expressed high levels of Treg-associated markers. However, these cells also presented a lack of homogeneous suppressive function and an unstable proinflammatory cytokine profile. Therefore, thymocyte-derived cells, activated with the same stimuli as Tconvs, were not an appropriate alternative for inducing cells with a Treg-like phenotype and function.
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CD25, the alpha chain of the IL-2 receptor, is expressed on activated effector T cells that mediate immune graft damage. Induction immunosuppression is commonly used in solid organ transplantation and can include antibodies blocking CD25. However, regulatory T cells (Tregs) also rely on CD25 for their proliferation, survival, and regulatory function. Therefore, CD25-blockade may compromise Treg protective role against rejection. We analysed in vitro the effect of basiliximab (BXM) on the viability, phenotype, proliferation and cytokine production of Treg cells. We also evaluated in vivo the effect of BXM on Treg in thymectomized heart transplant children receiving BXM in comparison to patients not receiving induction therapy. Our results show that BXM reduces Treg counts and function in vitro by affecting their proliferation, Foxp3 expression, and IL-10 secretion capacity. In pediatric heart-transplant patients, we observed decreased Treg counts and a diminished Treg/Teff ratio in BXM-treated patients up to 6-month after treatment, recovering baseline values at the end of the 12-month follow up period. These results reveal that the use of BXM could produce detrimental effects on Tregs, and support the evidence suggesting that BXM induction could impair the protective role of Tregs in the period of highest incidence of acute graft rejection.
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Basiliximab/efeitos adversos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Rejeição de Enxerto/induzido quimicamente , Rejeição de Enxerto/imunologia , Transplante de Coração , Subunidade alfa de Receptor de Interleucina-2/antagonistas & inibidores , Linfócitos T Reguladores/imunologia , Basiliximab/administração & dosagem , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Criança , Pré-Escolar , Citocinas/sangue , Feminino , Fatores de Transcrição Forkhead/metabolismo , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Lactente , Leucócitos Mononucleares , Masculino , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismoRESUMO
INTRODUCTION: Heart transplant after Fontan completion poses a unique surgical challenge. Twenty patients are presented, stressing the technical hints performed in the five anastomoses to match the graft in the recipient. METHODS: Data are collected from 20 Fontan patients between 2013 and 2019. Age (13 years), weight (37 kg.), and time interval between Fontan and transplant (7 years) are presented as median. Extracardiac conduit (size 18/20) was implanted in 15 patients, whereas atrio-pulmonary connection was performed in 4 and lateral tunnel in 1. Six patients developed protein-losing enteropathy. Seventeen stents had been previously deployed. RESULTS: The five anastomoses underwent some changes. Left atrium once, aorta 9 times, superior vena cava 7 times, pulmonary branches 15 times, and inferior vena cava 12 times. Follow-up was complete for a median of 42 months (range 6-84). Two patients died. ECMO was needed in six cases for pulmonary hypertension. Four patients had collateral vessels occluded in the cath lab, and stents were placed in superior vena cava (1) and aorta (1) post-transplant. Protein-losing enteropathy was resolved in five patients. Interestingly, one patient was on a systemic assist device before transplant (Levitronix) and right assistance (ECMO) afterwards. CONCLUSIONS: Transplant in Fontan patients is actually challenging. Hints in every of the five proposed anastomoses must be anticipated, including stents removal. Extra tissue from the donor (innominate vein, aortic arch, and pericardium) is strongly advisable. ECMO for right ventricular dysfunction was needed in nearly one-third of the cases. Overall results can match other transplant cohorts.
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Técnica de Fontan , Cardiopatias Congênitas , Enteropatias Perdedoras de Proteínas , Adolescente , Átrios do Coração/cirurgia , Cardiopatias Congênitas/cirurgia , Humanos , Enteropatias Perdedoras de Proteínas/etiologia , Artéria Pulmonar/cirurgia , Veia Cava Inferior/cirurgia , Veia Cava Superior/cirurgiaRESUMO
No disponible
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Humanos , Masculino , Feminino , Lactente , Criança , Adolescente , Adulto Jovem , Insuficiência da Valva Aórtica/cirurgia , Transposição das Grandes Artérias/efeitos adversos , Insuficiência da Valva Aórtica/etiologia , Complicações Pós-Operatórias/cirurgia , Transposição dos Grandes Vasos/complicações , Dispositivos de Acesso VascularRESUMO
No disponible
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Humanos , Cardiopatias Congênitas/cirurgia , Intervenção Coronária Percutânea/métodos , Stents , Coração Auxiliar , Hemodinâmica , Espanha/epidemiologiaRESUMO
OBJECTIVES: We sought to determine the indications, type, and outcomes of reoperations on the aortic root after repair of tetralogy of Fallot (TOF). METHODS: Eleven centers belonging to the European Congenital Heart Surgeons Association contributed to the data collection process. We included 36 patients who underwent surgical procedures on the aortic root, including surgery on the aortic valve and ascending aorta, between January 1975 and December 2017. Original diagnoses included TOF-pulmonary stenosis (n = 18) and TOF-pulmonary atresia (n = 18). The main indications for reoperation were aortic insufficiency (n = 19, 53%), aortic insufficiency and dilatation of the ascending aorta (n = 10, 28%), aortic root dilatation (n = 4, 11%), and ascending aorta dilatation (n = 3, 8%). RESULTS: The median age at reoperation was 30.4 years (interquartile range 20.3-45.3 years), and mechanical aortic valve replacement was the most common procedure performed. Five patients died early after reoperation (14%), and larger ascending aorta diameters were associated with early mortality (P = .04). The median age at the last follow-up was 41.4 years (interquartile range 24.5-51.6 years). Late death occurred in five patients (5/31, 16%). Most survivors (15/26, 58%) were asymptomatic at the last clinical examination (New York Heart Association, NYHA class I). The remaining patients were NYHA class II (n = 7) and III (n = 3). The most common symptoms were fatigue (n = 5), dyspnea (n = 4), and exercise intolerance (n = 3). CONCLUSIONS: Reoperations on the aortic root are infrequent but may become necessary late after TOF repair. The main indications for reoperation are aortic insufficiency, either isolated or associated with a dilatation of the ascending aorta. The surgical risk at reoperation was high and the presence of ascending aorta dilation is related to higher mortality.
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Aorta/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca , Tetralogia de Fallot/cirurgia , Adulto , Aorta/patologia , Criança , Pré-Escolar , Dilatação Patológica , Feminino , Seguimentos , Humanos , Masculino , Reoperação , Fatores de Tempo , Resultado do TratamentoRESUMO
Background: Congenital heart disease (CHD) is one of the main causes of morbidity and mortality in children. Microcirculatory changes in CHD patients have previously been investigated using a variety of techniques. Handheld videomicroscopy enables non-invasive direct visualization of the microcirculatory bed. The aim of our study was to determine if there are microcirculatory differences among CHD patients based on age and the presence of cyanosis. Methods: A prospective observational study was carried out. Patients with CHD undergoing corrective surgery were evaluated after anesthetic induction prior to surgery. Microcirculation was evaluated using sidestream dark field (SDF) imaging. Hemodynamics and respiratory, biochemical, and tissue perfusion parameters were analyzed. Results: A total of 30 patients were included, of whom 14 were classified as cyanotic and 16 as non-cyanotic. Cyanotic patients had a higher total vessel density (TVD) (p = 0.016), small vessel density (p = 0.004), and perfused small vessel density (p = 0.013), while their microvascular flow index (MFI) was lower (p = 0.013). After adjustment for age and PaO2, cyanotic patients showed increased TVD (p = 0.023), and small vessel density (p = 0.025) compared to non-cyanotic patients but there were no differences on the MFI. Age was directly correlated with total MFI (spearman's rho = 0.499, p = 0.005) and small vessel MFI (spearman's rho = 0.420, p = 0.021). After adjustment for the type of CHD (cyanotic vs. non-cyanotic) patients with MFI and small MFI vessels <3 were younger than those with values ≥3 (p = 0.033 and p = 0.037). Conclusions: SDF-based evaluation of microcirculation in CHD patients showed that patients with cyanotic defects had higher vascular density, as compared to patients with non-cyanotic defects. Younger patients were more likely to have a low MFI regardless of their type of CHD.
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We report a case of an 18-year-old woman who presented with infective endocarditis (IE), in two conduits percutaneously delivered in the right ventricle outflow tract ("double-barrel endocarditis"). The patient's clinical presentation, echocardiogram findings, infectious agent, clinical management, surgical approach, and follow-up assessment are described. Percutaneous pulmonary valve implantation has emerged as a viable therapy for conduit dysfunction in the right ventricular outflow tract. Although the percutaneous approach has several advantages, this strategy and the valves used are not complication-free. IE after transcatheter valve deployment has evoked the growing concern, as there is a higher incidence in these patients compared with patients with surgically repaired pulmonary valves. As a result, this type of surgical treatment is especially important.
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Endocardite Bacteriana/diagnóstico , Infecções por Bactérias Gram-Negativas/diagnóstico , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Próteses Valvulares Cardíacas/efeitos adversos , Infecções Relacionadas à Prótese/diagnóstico , Valva Pulmonar/cirurgia , Adolescente , Antibacterianos/uso terapêutico , Cateterismo Cardíaco , Cardiobacterium/genética , DNA Bacteriano/análise , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/terapia , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/terapia , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/terapia , Radiografia Torácica , ReoperaçãoRESUMO
This report describes a simple way to deal with time-consuming adhesions and cannula handling in patients with a paracorporeal assist device who are undergoing heart transplantation. By connecting the extrathoracic lines to the heart-lung machine, chest reentry becomes a straightforward issue.
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Cardiopatias Congênitas/cirurgia , Transplante de Coração/métodos , Ventrículos do Coração/cirurgia , Coração Auxiliar , Máquina Coração-Pulmão , Oxigenação por Membrana Extracorpórea/métodos , HumanosRESUMO
Pulmonary valve repair in an adolescent through upper ministernotomy is reported. Several tips to enhance proper display of the valve in the surgical field are depicted.