RESUMEN
BACKGROUND: The supported Ross is used to mitigate the neoaortic root dilation that has been described with the unsupported Ross. There is limited literature assessing the efficacy of the supported Ross in young patients. In this study, the fate of the neoaortic root was compared in the supported and unsupported Ross procedure in adolescent patients. METHODS: A retrospective review was performed of patients who underwent the Ross procedure between 1996 and 2019. An analysis was conducted of patients aged 10 to 18 years who underwent the supported and unsupported Ross operation, without a Konno enlargement, to assess for longitudinal echocardiographic changes. Given differences in follow-up time, both regression analysis and Mann-Whitney nonparametric tests were used to correct for time from discharge to most recent follow-up. RESULTS: The median follow-up time for supported and unsupported Ross patients without a Konno enlargement was 2.90 years (0.21-13.03 years) and 12.13 years (2.63-19.47 years), respectively. Unsupported Ross patients experienced a higher rate of change per year in the aortic annulus (P = .003 and P = .014) and aortic sinus (P = .002 and P = .002) diameters, respectively. There was no significant difference in the rate of change of end-diastolic left ventricular internal diameter (P = .703 and P = .92) and aortic insufficiency (P = .687 and P = .215) between the supported and unsupported Ross patients. CONCLUSIONS: Progressive dilation of the neoaortic root in unsupported Ross patients is significantly mitigated with the supported Ross with excellent stability. The supported Ross is safe and effective and may play an increasing role in the management of children with aortic disease.
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Insuficiencia de la Válvula Aórtica , Estenosis de la Válvula Aórtica , Procedimientos Quirúrgicos Cardíacos , Implantación de Prótesis de Válvulas Cardíacas , Válvula Pulmonar , Adolescente , Niño , Humanos , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Procedimientos Quirúrgicos Cardíacos/métodos , Insuficiencia de la Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Estudios Retrospectivos , Función Ventricular , Dilatación Patológica/cirugía , Estudios de Seguimiento , Estenosis de la Válvula Aórtica/cirugía , Válvula Pulmonar/cirugíaRESUMEN
AIMS: This study aimed to describe haemodynamic features of patients with advanced heart failure with preserved ejection fraction (HFpEF) as defined by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). METHODS AND RESULTS: We used pooled data from two dedicated HFpEF studies with invasive exercise haemodynamic protocols, the REDUCE LAP-HF (Reduce Elevated Left Atrial Pressure in Patients with Heart Failure) trial and the REDUCE LAP-HF I trial, and categorized patients according to advanced heart failure (AdHF) criteria. The well-characterized HFpEF patients were considered advanced if they had persistent New York Heart Association classification of III-IV and heart failure (HF) hospitalization < 12 months and a 6 min walk test distance < 300 m. Twenty-four (22%) out of 108 patients met the AdHF criteria. On evaluation, clinical characteristics and resting haemodynamics were not different in the two groups. Patients with AdHF had lower work capacity compared with non-advanced patients (35 ± 16 vs. 45 ± 18 W, P = 0.021). Workload-corrected pulmonary capillary wedge pressure normalized to body weight (PCWL) was higher in AdHF patients compared with non-advanced (112 ± 55 vs. 86 ± 49 mmHg/W/kg, P = 0.04). Further, AdHF patients had a smaller increase in cardiac index during exercise (1.1 ± 0.7 vs. 1.6 ± 0.9 L/min/m2 , P = 0.028). CONCLUSIONS: A significantly higher PCWL and lower cardiac index reserve during exercise were observed in AdHF patients compared with non-advanced. These differences were not apparent at rest. Therapies targeting the haemodynamic compromise associated with advanced HFpEF are needed.
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Insuficiencia Cardíaca , Presión Atrial , Insuficiencia Cardíaca/terapia , Hemodinámica , Humanos , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
CONTEXT: Therapy for snakebites relies on the application of antivenoms, which may be produced with different immunogenic mixtures of venom and possess different pharmaceutical characteristics. For these reasons, immunological cross-reactivity and heterologous neutralization were analyzed relative to the protein content of three antivenoms used in the Americas. METHODS: The antivenoms studied were composed of equine F(ab')2 fragments from animals immunized with Crotalinae venoms. The antivenoms were tested against venoms of seven pit viper species from Argentina, seven from Mexico, one from Costa Rica, and one from Colombia. RESULTS: Immunoblotting showed high cross-reactivity of all major protein bands with all the antivenoms tested. ELISA results also showed high cross-reactivity among the different venoms and antivenoms, and a high heterologous neutralization was observed. The results can be interpreted in different ways depending on whether the reactivity is considered in terms of the volume of antivenom used or by the amount of protein contained in this volume of antivenom. The antivenoms with high immunochemical reactivity and neutralizing capacity were those with higher protein content per vial; but when doses were adjusted by protein content, antivenoms of apparently lower neutralizing capacity and immunochemical reactivity showed at least similar potency and reactivity although volumetrically at higher doses. CONCLUSION: Protein content relative to neutralization potency of different products must be taken into account when antivenoms are compared, in addition to the volume required for therapeutic effect. These results show the importance of obtaining high-affinity and high-avidity antibodies to achieve good neutralization using low protein concentration and low-volume antivenoms.
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Antivenenos/inmunología , Animales , Antivenenos/química , Western Blotting , Bothrops , Reacciones Cruzadas/inmunología , Venenos de Crotálidos/inmunología , Ensayo de Inmunoadsorción Enzimática , Dosificación Letal Mediana , Ratones , Pruebas de Neutralización , Proteínas/análisisRESUMEN
INTRODUCTION: Vorinostat is a small molecule inhibitor of class I and II histone deacetylases with preclinical activity in melanoma. METHODS: We evaluated 32 patients with advanced primary cutaneous or ocular melanoma in a multi-institutional setting (PMH Phase II Consortium) with continuous daily oral vorinostat 400 mg. The primary endpoint was response rate by RECIST, with time to progression as a secondary endpoint. The study was designed to distinguish a response rate of 20 % from a RR of 5 % and to distinguish a 2 month median progression-free survival (PFS), from one of 3.1 months. The study proceeded to stage 2 following 2 of 16 responses.. We also assessed VEGF, FGF levels, P52 polymorphisms and chromatin-associated proteins as potential biomarkers. RESULTS: Therapy was associated with significant side effects, including fatigue, nausea, lymphopenia, and hyperglycemia. Eleven patients experienced at least one grade 3 or higher adverse event. There were two confirmed PRs in patients with cutaneous melanoma. Sixteen patients had stable disease and 14 patients had progressive disease for best response. In addition, two patients with cutaneous melanoma scored as stable disease had early unconfirmed partial responses with subsequent progression. Patients with stable disease or partial response (n = 18) had a median progression free survival of 5 months. (range 2-12 months). CONCLUSIONS: Vorinostat demonstrated some early responses and a high proportion of patients with stable disease, but did not meet its primary endpoint of response. Different schedules of this agent with BRAF mutation status and markers of histone acetylation could be explored in melanoma.
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Antineoplásicos/uso terapéutico , Inhibidores de Histona Desacetilasas/uso terapéutico , Ácidos Hidroxámicos/uso terapéutico , Melanoma/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Biomarcadores/sangre , Supervivencia sin Enfermedad , Femenino , Factores de Crecimiento de Fibroblastos/sangre , Inhibidores de Histona Desacetilasas/efectos adversos , Inhibidores de Histona Desacetilasas/farmacología , Histonas/metabolismo , Humanos , Ácidos Hidroxámicos/efectos adversos , Ácidos Hidroxámicos/farmacología , Masculino , Melanoma/genética , Melanoma/metabolismo , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Neoplasias Cutáneas , Proteína p53 Supresora de Tumor/genética , Factor A de Crecimiento Endotelial Vascular/sangre , Vorinostat , Melanoma Cutáneo MalignoRESUMEN
Aurora kinase A (AURKA) localizes to centrosomes and mitotic spindles where it mediates mitotic progression and chromosomal stability. Overexpression of AURKA is common in cancer, resulting in acquisition of alternate non-mitotic functions. In the current study, we identified a novel role for AURKA in regulating ovarian cancer cell dissemination and evaluated the efficacy of an AURKA-selective small molecule inhibitor, alisertib (MLN8237), as a single agent and combined with paclitaxel using an orthotopic xenograft model of epithelial ovarian cancer (EOC). Ovarian carcinoma cell lines were used to evaluate the effects of AURKA inhibition and overexpression on migration and adhesion. Pharmacological or RNA interference-mediated inhibition of AURKA significantly reduced ovarian carcinoma cell migration and adhesion and the activation-associated phosphorylation of the cytoskeletal regulatory protein SRC at tyrosine 416 (pSRC(Y416)). Conversely, enforced expression of AURKA resulted in increased migration, adhesion and activation of SRC in cultured cells. In vivo tumor growth and dissemination were inhibited by alisertib treatment as a single agent. Moreover, combination of alisertib with paclitaxel, an agent commonly used in treatment of EOC, resulted in more potent inhibition of tumor growth and dissemination compared with either drug alone. Taken together, these findings support a role for AURKA in EOC dissemination by regulating migration and adhesion. They also point to the potential utility of combining AURKA inhibitors with taxanes as a therapeutic strategy for the treatment of EOC patients.
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Aurora Quinasa A/metabolismo , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Animales , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Aurora Quinasa A/antagonistas & inhibidores , Aurora Quinasa A/genética , Azepinas/farmacología , Carcinoma Epitelial de Ovario , Adhesión Celular , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular , Femenino , Humanos , Ratones , Mitosis/efectos de los fármacos , Metástasis de la Neoplasia , Trasplante de Neoplasias , Neoplasias Glandulares y Epiteliales/enzimología , Neoplasias Ováricas/enzimología , Paclitaxel/farmacología , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología , Interferencia de ARN , ARN Interferente Pequeño/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Familia-src Quinasas/metabolismoRESUMEN
Aortic aneurysm formation after coarctation repair is a serious and life-threatening complication. Repairs using synthetic materials such as Dacron(®) may carry the highest risk of aneurysm formation and rupture. The authors sought to determine the prevalence of aneurysm formation in patients who previously underwent coarctation repair using Dacron(®) patch aortoplasty at their institution. Between 1977 and 1994, 63 patients underwent isolated coarctation repair using Dacron(®) patch aortoplasty. Aneurysms were defined as an aortic dimension 1.5 times that of the aorta at the level of the diaphragm as shown by angiography, computed tomography (CT) scan, or magnetic resonance imaging (MRI). Of 61 early survivors, 29 (47 %) experienced an aneurysm in the area of previous repair. Nine patients (31 %) had spontaneous rupture of the aneurysm, which caused death in seven cases. Elective or emergent aneurysm repair was performed for 20 patients without complication, and 2 patients are being monitored at this writing. The mean interval from patch placement to aneurysm repair was 15 years (range, 4-27 years). Overall freedom from the development of an aortic aneurysm was 97 % at 5 years, 90 % at 10 years, 69 % at 20 years, and 42 % at 25 years. After repair of coarctation using Dacron(®) patch aortoplasty, the risk for aneurysm formation in the area of repair and death from rupture is extremely high. Therefore, in accordance with the 2008 American Heart Association/American College of Cardiology (AHA/ACC) guidelines, all patients with repaired aortic coarctation should undergo either CT or MRI imaging at least every 5 years to assess for aortic aneurysm formation. More frequent imaging should be obtained for patients previously repaired with Dacron(®) patch aortoplasty.
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Aneurisma de la Aorta Torácica/epidemiología , Coartación Aórtica/cirugía , Prótesis Vascular/efectos adversos , Procedimientos de Cirugía Plástica/efectos adversos , Tereftalatos Polietilenos , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/etiología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Morbilidad/tendencias , Complicaciones Posoperatorias , Pronóstico , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de Tiempo , Tomografía Computarizada por Rayos X , Estados Unidos/epidemiologíaRESUMEN
Increased activity of SRC family kinases promotes tumor invasion and metastasis, and overexpression of the mitotic regulator Aurora kinase A (AURKA) drives tumor aneuploidy and chromosomal instability. These functions nominate SRC and AURKA as valuable therapeutic targets for cancer, and inhibitors for SRC and Aurora kinases are now being used in the clinic. In this study, we demonstrate potent synergy between multiple inhibitors of Aurora and SRC kinases in ovarian and colorectal cancer cell lines, but not in normal ovarian epithelial cell lines. Combination of Aurora and SRC inhibitors selectively killed cells that have undergone a preceding aberrant mitosis, and was associated with a postmitotic reattachment defect, and selective removal of aneuploid cell populations. Combined inhibition of Aurora kinase and SRC potentiated dasatinib-dependent loss of activated (Y(416)-phosphorylated) SRC. SRC and AURKA share a common interaction partner, NEDD9, which serves as a scaffolding protein with activities in cell attachment and mitotic control, suggesting SRC and AURKA might interact directly. In vitro, we observed physical interaction and mutual cross-phosphorylation between SRC and AURKA that enhanced SRC kinase activity. Together, these findings suggest that combination of SRC and Aurora-targeting inhibitors in the clinic may be a productive strategy.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Familia-src Quinasas/antagonistas & inhibidores , Aurora Quinasa A , Aurora Quinasas , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Dasatinib , Femenino , Humanos , Mitosis/efectos de los fármacos , Fosforilación , Proteínas Serina-Treonina Quinasas/fisiología , Pirazoles/farmacología , Pirimidinas/farmacología , Pirroles/farmacología , Tiazoles/farmacología , Familia-src Quinasas/fisiologíaRESUMEN
PURPOSE: Patients with advanced GIST following standard imatinib and sunitinib often have good performance status and need additional therapy. This study tested nilotinib, a second-generation tyrosine kinase inhibitor, in patients with advanced GIST refractory to standard therapies. METHODS: This single-center open-label phase II study has a primary objective to determine progression-free survival at 6 months. Using a novel statistical design, 17 patients were to be enrolled; if ≥ 10 were progression free (PF) at 2 months, 19 additional patients would be enrolled. The therapy was considered of benefit if ≥ 13 of 36 patients were PF at 6 months. All patients signed informed consent and entry criteria included normal cardiac function. Exploratory analyses correlating genotype with response were also performed. RESULTS: Thirteen patients were treated; 2 had received agents after imatinib and sunitinib. Treatment was well tolerated with one grade 4 anemia attributed to nilotinib. No measurable responses were observed; median time to progression was 2 months. One patient remained on study with stable disease for 12 months. Mutation testing is available from 10 primary tumors with 7 exon 11 mutations, 1 exon 9 mutation, and 2 without KIT/PDGFR mutations. Two samples from recurrent disease had 2 mutations, both primary exon 11 mutations with an additional exon 17 mutation, including the patient with prolonged stable disease. CONCLUSIONS: Nilotinib was well tolerated in these patients with advanced GIST. Accrual was halted due to insufficient clinical benefit. However, nilotinib may provide benefit to specific subsets of advanced GIST with exon 17 mutations.
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Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Anciano , Benzamidas , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Exones , Femenino , Tumores del Estroma Gastrointestinal/enzimología , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Humanos , Mesilato de Imatinib , Indoles/farmacología , Masculino , Persona de Mediana Edad , Mutación , Piperazinas/farmacología , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-kit/genética , Pirimidinas/efectos adversos , Pirimidinas/farmacología , Pirroles/farmacología , SunitinibRESUMEN
BACKGROUND: Limited and conflicting data exist on the diagnosis of cardiac allograft rejection with the use of echocardiography. The purpose of our study was to evaluate various systolic and diastolic indices, including newer tissue Doppler imaging techniques, in diagnosing cardiac allograft rejection. METHODS: We prospectively performed 426 echocardiography studies at the time of endomyocardial biopsy in 54 cardiac transplant patients. We measured left ventricular (LV) systolic and diastolic dimensions, mitral inflow pattern and annular velocities, and the myocardial performance index. Biopsies were assessed for cellular rejection and antibody-mediated rejection (AMR). RESULTS: Mild cellular rejection was diagnosed in 74 biopsy specimens and significant cellular rejection in 10 biopsy specimens. AMR was diagnosed in 30 biopsy specimens. In patients with mild or significant cellular rejection, no significant differences in echocardiographic parameters were observed. In patients with AMR, LV fractional shortening was significantly reduced compared with those with no AMR (mean±SD 31.8±8.9% vs 36.0±7.1%; P=.02). CONCLUSIONS: Although 1 echocardiographic parameter was statistically different in the setting of rejection, lack of consistency and overlap between nonrejection and rejection groups does not permit definitive noninvasive diagnosis of cardiac allograft rejection using this imaging modality.
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Ecocardiografía Doppler , Rechazo de Injerto/diagnóstico , Trasplante de Corazón/efectos adversos , Función Ventricular Izquierda , Biopsia , Diástole , Rechazo de Injerto/diagnóstico por imagen , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Rechazo de Injerto/fisiopatología , Humanos , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/fisiopatología , Miocardio/patología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Análisis de Regresión , Sístole , Trasplante Homólogo , Resultado del Tratamiento , UtahRESUMEN
Optimal timing for elective repair of total anomalous pulmonary venous return (TAPVR) in the case of an unobstructed anomalous pathway is unclear. All infants with a diagnosis of TAPVR as an isolated lesion who underwent surgical repair at Children's Hospital of Wisconsin from 1991 to 2007 were reviewed to assess location of drainage, presence of obstruction, age at presentation, age at surgery, death, need for extracorporeal membrane oxygenation (ECMO), length of hospital stay, length of mechanical ventilation (MV), and late pulmonary venous obstruction. A total of 65 patients were identified: 38 (59%) with supracardiac drainage, 10 (15%) with cardiac drainage, 11 (17%) with infracardiac drainage, and 6 (9%) with mixed drainage. For 39 (60%) of the 65 patients, obstruction was identified preoperatively. Three early and five late deaths occurred after surgery (12%), all involving patients with preoperative obstruction. Most of the late deaths (80%) involved patients who experienced recurrent obstruction. Of the 65 patients, 26 (40%) had no obstruction preoperatively, and none died, required ECMO support, or experienced late obstruction. For the 26 patients without obstruction, the timing of surgery was elective at the discretion of the supervising cardiologist. Among these 26 patients, 15 had surgery less than 10 days after presentation (median age, 18 days), and 53% of these 15 patients (8/15) had MV less than 5 days. In contrast, all 11 patients who had elective surgery more than 10 days after presentation (median age, 56 days) required MV for more than 5 days (p = 0.007). Isolated TAPVR appears to be at the highest risk for death and late postoperative obstruction when obstruction is present preoperatively. Patients with unobstructive TAPVR do very well, but potential morbidity related to prolonged MV appears to be significantly reduced by early elective surgery.
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Cardiopatías Congénitas/cirugía , Venas Pulmonares/anomalías , Venas Pulmonares/cirugía , Respiración Artificial , Distribución de Chi-Cuadrado , Oxigenación por Membrana Extracorpórea , Femenino , Cardiopatías Congénitas/mortalidad , Humanos , Lactante , Recién Nacido , Tiempo de Internación/estadística & datos numéricos , Masculino , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The purpose was to evaluate interfraction and intrafraction esophageal motion in the right-left (RL) and anterior-posterior (AP) directions using computed tomography (CT) in esophageal cancer patients. Eight patients underwent CT simulation and CT-on-rails imaging before and after radiotherapy. Interfraction displacement was defined as differences between pretreatment and simulation images. Intrafraction displacement was defined as differences between pretreatment and posttreatment images. Images were fused using bone registries, adjusted to the carina. The mean, average of the absolute, and range of esophageal motion were calculated in the RL and AP directions, above and below the carina. Thirty-one CT image sets were obtained. The incidence of esophageal interfraction motion > or =5 mm was 24% and > or =10 mm was 3%; intrafraction motion > or =5 mm was 13% and > or =10 mm was 4%. The average RL motion was 1.8 +/- 5.1 mm, favoring leftward movement, and the average AP motion was 0.6 +/- 4.8 mm, favoring posterior movement. Average absolute motion was 4.2 mm or less in the RL and AP directions. Motion was greatest in the RL direction above the carina. Coverage of 95% of esophageal mobility requires 12 mm left, 8 mm right, 10 mm posterior, and 9 mm anterior margins. In all directions, the average of the absolute interfraction and intrafraction displacement was 4.2 mm or less. These results support a 12 mm left, 8 mm right, 10 mm posterior, and 9 mm anterior margin for internal target volume (ITV) and can guide margins for future intensity modulated radiation therapy (IMRT) trials to account for organ motion and set up error in three-dimensional planning.
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Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/radioterapia , Esófago/diagnóstico por imagen , Movimiento , Planificación de la Radioterapia Asistida por Computador , Radioterapia Conformacional , Adulto , Anciano , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Planificación de la Radioterapia Asistida por Computador/métodos , Tomografía Computarizada por Rayos X , Carga TumoralRESUMEN
Hepatocyte turnover appears to be an important feature in the resolution of transient and progression of chronic hepadnavirus infections. Hepatocyte death, initiated through attack by antiviral cytotoxic T-lymphocytes (CTL), and compensatory hepatocyte proliferation, are both believed to be major contributing factors in the loss of virus DNA during immune resolution of transient infections. Noncytopathic curing of hepatocytes is also suggested to occur, though this mechanism does not prevent the death of large numbers of hepatocytes. Hepatocyte death, proliferation and curing are also important features of chronic infections, though the outcomes are different. In particular, immune selection due to persistent attack by antiviral CTL is thought to play a role in the emergence of hepatocytes infected with mutant strains of hepatitis B virus (HBV) (e.g. HBV e antigen-negative strains) and in the emergence of hepatocytes that appear refractory to HBV infection. In both instances, clonal expansion of subpopulations of hepatocytes may be inferred to have taken place. Interestingly, foci of altered hepatocytes and hepatocellular carcinomas (HCC) typically do no support virus replication. Thus, immune selection of hepatocytes by antiviral CTL, by inducing clonal expansion, may also play an important role in the progression to HCC. In this review, we discuss the evidence in support of roles for hepatocyte turnover in the resolution of transient and progression of chronic HBV infections.
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Hepatitis B Crónica/patología , Hepatocitos/patología , Animales , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Humanos , Linfocitos T Citotóxicos/inmunologíaRESUMEN
BACKGROUND: Staged palliation for hypoplastic left heart syndrome has been marked by high early mortality due to the limited cardiac output of the postischemic single right ventricle combined with the inefficiency and volatility of parallel circulation. METHODS: Since July 1996, we have performed stage 1 palliation (S1P) in 178 patients. Within this group is a consecutive cohort of 116 patients with true hypoplastic left heart syndrome that underwent S1P with a modified Blalock-Taussig shunt. A prospective database containing postoperative hemodynamic data was maintained on all patients. Studied were the incidence of organ failure, extracorporeal membrane oxygenation (ECMO), and mortality, as well as the relationship between these outcomes and postoperative hemodynamics. RESULTS: Hospital survival for this cohort was 93% (108/116). Patients who died after S1P had a lower superior vena cava oxygen saturation (SVO2) level compared with survivors (53.1% +/-10.6% versus 59.3% +/-9.2%, p = 0.034). Renal failure developed in 2 (1.7%) of the 116 patients, necrotizing enterocolitis developed in 1 (0.9%), and 5 (4.3%) had clinical seizures. ECMO support was instituted in 12 patients (10.3%). The SVO2 level was lower in patients requiring ECMO (54.0% +/- 9.7% versus 59.9% +/- 9.2%, p = 0.031). CONCLUSIONS: Goal-directed therapy with SVO2 as an indicator of systemic oxygen delivery is associated with excellent early survival and a low incidence of organ failure after S1P. Inability to optimize SVO2 in the early postoperative period is associated with an increased risk of organ failure, ECMO, and death.
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Causas de Muerte , Síndrome del Corazón Izquierdo Hipoplásico/mortalidad , Síndrome del Corazón Izquierdo Hipoplásico/cirugía , Consumo de Oxígeno/fisiología , Cuidados Paliativos/métodos , Procedimientos Quirúrgicos Cardíacos/métodos , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Masculino , Monitoreo Fisiológico/métodos , Análisis Multivariante , Oximetría , Cuidados Posoperatorios/métodos , Probabilidad , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Vena Cava SuperiorRESUMEN
This article is a review of our experience with the two-patch repair of complete atrioventricularis communis. From October 1988 through December 2005, 222 infants and children underwent surgery. There were six early (2.7%) and six late (2.7%) deaths. Reoperation was required in 22 patients (10%) for residual or recurrent mitral regurgitation or stenosis, subaortic stenosis, repair of a ventricular septal defect with or without pulmonary stenosis, placement of a right heart valved conduit, and/or placement of a permanent cardiac pacemaker. All patients survived second operations and no child required early or late mitral valve replacement. The two-patch repair is a reliable surgical technique resulting in low mortality and a low need for reoperation.
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Procedimientos Quirúrgicos Cardíacos/métodos , Defectos de la Almohadilla Endocárdica/cirugía , Defectos del Tabique Interatrial/cirugía , Defectos del Tabique Interventricular/cirugía , Estenosis de la Válvula Aórtica/etiología , Estenosis de la Válvula Aórtica/cirugía , Procedimientos Quirúrgicos Cardíacos/instrumentación , Puente Cardiopulmonar , Niño , Preescolar , Ecocardiografía , Defectos de la Almohadilla Endocárdica/complicaciones , Defectos de la Almohadilla Endocárdica/epidemiología , Estudios de Seguimiento , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/epidemiología , Defectos del Tabique Interventricular/complicaciones , Defectos del Tabique Interventricular/epidemiología , Humanos , Hipotermia Inducida , Lactante , Insuficiencia de la Válvula Mitral/etiología , Insuficiencia de la Válvula Mitral/cirugía , Estenosis de la Válvula Mitral/etiología , Estenosis de la Válvula Mitral/cirugía , Marcapaso Artificial , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estenosis de la Válvula Pulmonar/etiología , Estenosis de la Válvula Pulmonar/cirugía , Reoperación , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Complex forms of atrioventricular (AV) canal (C) such as; AVC with left ventricular outflow tract obstruction, tetralogy of Fallot with complete AVC, double orifice left AV valve, unbalanced complete AVC, and single ventricle patients with common AVC valve require careful preoperative planning and special techniques. This review will explore these technical modifications and outcomes for repair of complex variants of AVC. Optimal results will be achieved using an individually tailored approach that is guided by careful evaluation of the preoperative studies, precise operative technique, and intraoperative assessment of the reconstructed AV valve, as well as a willingness to re-intervene should the postoperative course not proceed as anticipated.
Asunto(s)
Cardiopatías Congénitas/patología , Cardiopatías Congénitas/cirugía , Procedimientos Quirúrgicos Cardíacos/métodos , Atrios Cardíacos/anomalías , Atrios Cardíacos/cirugía , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/diagnóstico por imagen , Válvulas Cardíacas/anomalías , Válvulas Cardíacas/cirugía , Ventrículos Cardíacos/anomalías , Ventrículos Cardíacos/cirugía , Humanos , Monitoreo Intraoperatorio , Arteria Pulmonar/cirugía , Reoperación , Tetralogía de Fallot/patología , Tetralogía de Fallot/cirugía , Ultrasonografía , Obstrucción del Flujo Ventricular Externo/etiología , Obstrucción del Flujo Ventricular Externo/patología , Obstrucción del Flujo Ventricular Externo/cirugíaRESUMEN
The fetal-placental unit is a semi-allograft and immunological recognition of pregnancy, together with the subsequent response of the maternal immune system, is necessary for a successful pregnancy. Dendritic cells (DC) show a biological plasticity that confers them special characteristics regulating both immunity and tolerance. Therapy employing DC proved to diminish the abortion in the DBA/2J-mated CBA/J females; however, the underlying mechanisms remain unknown. Here, we evaluated whether DC therapy influences the presence of immunoregulatory populations of cells at the fetal-maternal interface. To address this hypothesis, we analysed the pregnancy-protective CD8, gammadelta cell populations as well as transforming growth factor (TGF)-beta1 and progesterone-induced blocking factor (PIBF) expression at the fetal-maternal interface from abortion-prone female mice that had previously received adoptive transfer of syngeneic DC. Syngeneic DC therapy induced an increase in the number of CD8 and gammadelta cells. Additionally, an upregulation of TGF-beta1 and PIBF expression could be detected after DC transfer. We suggest that DC therapy differentially upregulates a regulatory/protective population of cells at the fetal-maternal interface. It is reasonable to assure that this mechanism would be responsible for the lower abortion rate.
Asunto(s)
Aborto Espontáneo/prevención & control , Células Dendríticas/trasplante , Preñez/inmunología , Aborto Habitual/inmunología , Aborto Habitual/prevención & control , Aborto Habitual/veterinaria , Aborto Inducido , Aborto Espontáneo/inmunología , Traslado Adoptivo , Animales , Antígenos CD8/metabolismo , Medios de Cultivo Condicionados , Células Dendríticas/inmunología , Células Dendríticas/fisiología , Femenino , Masculino , Ratones , Ratones Endogámicos DBA , Placenta/metabolismo , Embarazo , Proteínas Gestacionales/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Regulación hacia Arriba , Útero/anatomía & histologíaRESUMEN
BACKGROUND: Near infrared spectroscopy (NIRS) measures regional tissue oxygenation continuously and noninvasively and may allow assessment of changes in regional perfusion in real time. METHODS: We used NIRS monitoring to track real-time changes in regional oxygenation (rSO2) above and below the aortic cross-clamp in patients undergoing aortic coarctation repair and routinely stored these data in an operative electronic data base. This allowed us to analyze the changes in rSO2 during aortic coarctation repair for three pediatric age groups (neonates, infants <1 year, and children >1 year). Two site [cerebral (rSO2-C) and somatic thoracodorsal (rSO2-S)] rSO2 monitoring was performed in patients undergoing aortic coarctation repair. Data for rSO2 were analyzed across sites and age groups before, during and after cross-clamp. RESULTS: Twenty-six patients were available for analysis (11 neonates, 5 infants and 10 children). The regional oxygenation below the cross clamp (rSO2-S) declined significantly in all three age groups, but the decrease in neonates and infants <1 year of age was significantly greater than in the older children. CONCLUSIONS: Monitoring rSO2-S provides real-time trend information of regional oxygenation below the aortic cross-clamp. The decline in rSO2-S during aortic cross-clamp was rapid and large in most neonates and young infants <1 year which suggests impairment of regional perfusion presumably because of a lack of adequate collateral circulation to the monitored regional tissue. In contrast, the rSO2-S changed only to a minor degree in most infants and children >1 year, possibly because they had time to develop a more adequate collateral circulation around incomplete aortic obstruction.
Asunto(s)
Coartación Aórtica/cirugía , Espectroscopía Infrarroja Corta , Adolescente , Envejecimiento/fisiología , Anestesia General , Química Encefálica/fisiología , Niño , Circulación Colateral/fisiología , Constricción , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Monitoreo Intraoperatorio , Consumo de Oxígeno , Proyectos PilotoRESUMEN
Aortic valve replacement options are limited in children, and all of them have disadvantages. Aortic valve repair techniques have evolved slowly and have not gained wide acceptance; however, large series using a variety of techniques demonstrate that valve repair is possible with excellent early hemodynamics and satisfactory intermediate durability. The results of aortic valve repair at the Children's Hospital of Wisconsin are presented. Simple repairs (blunt valvotomy, commissurotomy, or commissurotomy with leaflet thinning) directed at congenital aortic stenosis resulted in 86% +/- 5% freedom from reintervention at 10 years. Repair of aortic insufficiency with ventricular septal defect (VSD) resulted in 93.3% +/- 6% freedom from reoperation at 10 years. Complex repairs included a combination of techniques and yielded 5-year freedom from reintervention of 83% +/- 7% compared with 73% +/- 11% for patients undergoing aortic valve replacement (P = .62). Aortic valve repair provides an alternative to aortic valve replacement in selected patients. The utility of aortic valve repair and aortic valve replacement must be measured not only in freedom from reintervention but also in regression of left ventricular mass and exercise testing. Improvement in outcome depends on better patient selection and suitable bioprosthetic materials.
Asunto(s)
Válvula Aórtica/cirugía , Procedimientos Quirúrgicos Cardíacos/métodos , Enfermedades de las Válvulas Cardíacas/cirugía , Adolescente , Adulto , Cateterismo , Niño , Preescolar , Estudios de Seguimiento , Enfermedades de las Válvulas Cardíacas/complicaciones , Humanos , Lactante , Recién Nacido , Selección de Paciente , Reoperación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: This study was undertaken to determine the utility of aortic valve repair in children. METHODS: A retrospective analysis was conducted on aortic valve surgery from 1973 to 2004 at Children's Hospital of Wisconsin. RESULTS: Procedures were classified as simple repairs (blunt valvotomy, commissurotomy with or without thinning, n = 147), repair of aortic insufficiency with ventricular septal defect (n = 22), complex repairs (any combination of additional procedures including suspension of prolapsed leaflets, leaflet extensions, repair of torn or perforated leaflets, annuloplasty, reduction of sinus of Valsalva plasty, and concomitant repair of supravalvular or subvalvular stenosis, n = 57), and replacements (n = 57, 20 mechanical, 2 porcine, and 35 human valves). Freedoms from reintervention for simple repairs and repair of aortic insufficiency with ventricular septal defect at 10 years were 86% +/- 5% and 93.3% +/- 6%, respectively. For complex valve repair, freedoms from reintervention at 1, 5, and 10 years were 94% +/- 3%, 85% +/- 6%, and 44% +/- 15%, versus 96% +/- 3%, 77% +/- 9%, and 77% +/- 9% for valve replacement ( P = .3). At intermediate follow-up, patients with complex valve repair had a residual gradient of 20 +/- 21 mm Hg, and 94% were free of severe aortic insufficiency. Residual aortic stenosis ( P < .05) but not the preoperative diagnosis of combined aortic stenosis and insufficiency predicted the need for reintervention. CONCLUSION: Freedom from reintervention after complex valve repairs was not different from that after valve replacement, with acceptable residual aortic stenosis and insufficiency. Simple repairs and repair of aortic insufficiency with ventricular septal defect yielded excellent long-term freedom from reintervention.
Asunto(s)
Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Procedimientos Quirúrgicos Cardíacos , Adolescente , Adulto , Niño , Preescolar , Defectos del Tabique Interventricular/cirugía , Humanos , Lactante , Recién Nacido , Reoperación , Estudios RetrospectivosRESUMEN
Sudden cardiac death (SCD) in children is the result of multiple etiologies and treatment (prophylaxis) must be tailored accordingly. In children who do not have congenital heart disease, surgical therapy of SCD typically consists of implantation of an internal defibrillator, with specific attention to the small size of the patient. In children who have unrepaired congenital heart disease, therapy of SCD is primarily repair of the congenital anomaly. In children or young adults who have previously undergone surgery for congenital heart disease, SCD therapy consists of repair of any residual or acquired structural defect, often in combination with antiarrhythmia surgery or defibrillator implantation.