RESUMEN
Nanoscale, localized corrosion underpins billions of dollars in damage and material costs each year; however, the processes responsible have remained elusive due to the complexity of studying degradative material behavior at nanoscale liquid-solid interfaces. Recent improvements to liquid cell scanning/transmission electron microscopy and associated techniques enable this first look at the nanogalvanic corrosion processes underlying this widespread damage. Nanogalvanic corrosion is observed to initiate at the near-surface ferrite/cementite phase interfaces that typify carbon steel. In minutes, the corrosion front delves deeper into the material, claiming a thin layer of ferrite around all exposed phase boundaries before progressing laterally, converting the ferrite to corrosion product normal to each buried cementite grain. Over the following few minutes, the corrosion product that lines each cementite grain undergoes a volumetric expansion, creating a lateral wedging force that mechanically ejects the cementite grains from their grooves and leaves behind percolation channels into the steel substructure.
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Compuestos Férricos , Acero , Carbono , Corrosión , Acero/químicaRESUMEN
As part of a clinical trial, this study examined the pharmacokinetics (PK) of oral treprostinil (TRE) in children with pulmonary arterial hypertension. The trial consisted of the following 3 cohorts: transition from parenteral (cohort 1) or inhaled (cohort 2) TRE, or de novo addition (cohort 3). Oral TRE was dosed 3 times daily. PK samples were obtained before an oral TRE dose, and at 2, 4, 6, and 8 hours thereafter. The PK parameters were calculated using noncompartmental analysis. Thirty-two children (n = 10 in cohorts 1 and 2, n = 12 in cohort 3) were enrolled; the median age was 12 years (range 7-17 years), and the median weight was 42.2 kg (range 19.3-78 kg). The median oral TRE dose for all subjects was 3.8 mg (5.9, 3.5, and 4.0 mg for cohorts 1, 2, and 3, respectively). The TRE concentration versus time profile demonstrated a peak concentration at a median of 3.8 hours with wide variability. In cohort 1, oral dosing led to higher peak (5.9 ng/mL) and lower trough (1 ng/mL) concentrations than parenteral (peak 5.4 ng/mL and trough 4.2 ng/mL), but a lower mean concentration (3.61 vs. 4.46 ng/mL), likely due to variable metabolism and noncomparable dosing. Both the area under the curve and average concentration were linearly correlated with oral TRE dose and dose normalized to body weight, but not with weight or age alone. In pediatric patients, an increased oral TRE dose or dose frequency may be required to minimize PK variability and achieve greater correlation with parenteral dosing.
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Antihipertensivos/administración & dosificación , Antihipertensivos/farmacocinética , Presión Arterial/efectos de los fármacos , Epoprostenol/análogos & derivados , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Arteria Pulmonar/efectos de los fármacos , Administración Oral , Adolescente , Factores de Edad , Antihipertensivos/sangre , Niño , Esquema de Medicación , Epoprostenol/administración & dosificación , Epoprostenol/sangre , Epoprostenol/farmacocinética , Femenino , Humanos , Masculino , Modelos Biológicos , Hipertensión Arterial Pulmonar/sangre , Hipertensión Arterial Pulmonar/fisiopatología , Arteria Pulmonar/fisiopatología , Resultado del Tratamiento , Estados UnidosRESUMEN
Rational control of nanoparticle (NP) size distribution during operation is crucial to improve catalytic performance and noble metal sustainability. Herein, we explore the Ostwald ripening (OR) of metal atoms on zeolite surfaces by a coupled theoretical-experimental approach. Zeolites with the same structure (ZSM-5) but different concentrations of aluminum doped into the matrix were observed to yield systematic differences in supported nanoparticle size distributions. Our first-principles simulations suggest that NP stability at high temperature is governed by both geometric constraints and the roughness of the energetic landscape. Calculated adatom migration paths across the zeolite surface and desorption paths from the supported NPs lend insight into the modified OR sintering processes with the emergence of different binding configurations as the aluminum concentration increases from pristine to heavily doped ZSM-5. These findings reveal the potential for the rational design of support structures to suppress OR sintering.
RESUMEN
This study evaluated the pharmacokinetics of intravenous (IV) and subcutaneous (SC) treprostinil in pediatric patients with pulmonary vascular disease, and compared them with existing adult data from a similar cohort. Blood samples were collected from pediatric patients receiving steady-state IV or SC treprostinil and were assessed for plasma treprostinil concentration using liquid chromatography and tandem mass spectrometry. Forty participants, 15 receiving IV and 25 receiving SC treprostinil, were included in the analysis. Age ranged from 0.1 to 15.6 years. The median dose of treprostinil was 45.5 ng·kg·min with a range of 8-146 ng·kg·min. There was a linear relationship between treprostinil dose and plasma concentration with an R of 0.57. On average, there were higher blood concentrations per given dose of IV treprostinil compared with those per given dose of SC, but the difference was not significant. Compared with adult data, the slope of the pediatric data was similar, but the y-intercept was significantly lower. Additionally, the concentration per dose ratio was significantly higher in adults compared with children. Pediatric patients have significantly lower average blood concentrations of treprostinil per given dose compared with adults, and higher, but not significantly so, blood concentrations when treprostinil is administered IV as compared with SC administration.
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Antihipertensivos/administración & dosificación , Antihipertensivos/farmacocinética , Epoprostenol/análogos & derivados , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Adolescente , Factores de Edad , Antihipertensivos/sangre , Niño , Preescolar , Cromatografía Liquida , Estudios Transversales , Monitoreo de Drogas , Epoprostenol/administración & dosificación , Epoprostenol/sangre , Epoprostenol/farmacocinética , Femenino , Humanos , Lactante , Infusiones Intravenosas , Infusiones Subcutáneas , Masculino , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/fisiopatología , Espectrometría de Masas en Tándem , Estados UnidosRESUMEN
Although elevated right ventricular pressure and left ventricular diastolic dysfunction measured by echocardiogram are independent predictors of death in adults with sickle cell disease (SCD), the utility of routine echocardiographic screening in the pediatric population is controversial. We performed a 3-year retrospective review of children ≥ 10 years of age with SCD who underwent an outpatient transthoracic echocardiogram as part of a screening program. Of 172 patients referred for screening, 105 (61%) had a measurable tricuspid regurgitation jet velocity (TRV): median 2.4 m/s (IQR 2.3-2.5). Elevated right ventricular (RV) pressure (TRV ≥ 2.5 m/s, 25 mmHg), documented in 30% (32/105), was significantly associated with chronic transfusion therapy and elevated lactate dehydrogenase. Left ventricle (LV) dilation, documented in 25% (44/172), was significantly associated with lower hemoglobin, and higher reticulocyte count, lactate dehydrogenase level, and bilirubin level. There was no association between elevated right ventricular pressure or left ventricle dilation and indices of biventricular systolic or diastolic function. The one death in the cohort during the study period had normal echocardiographic findings. In conclusion, mild RV pressure elevation and LV dilation in children with SCD is associated with abnormal laboratory markers of disease severity, but not with ventricular dysfunction over the 3-year study period.
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Anemia de Células Falciformes/fisiopatología , Función Ventricular Izquierda/fisiología , Función Ventricular Derecha/fisiología , Adolescente , Anemia de Células Falciformes/complicaciones , Niño , Progresión de la Enfermedad , Ecocardiografía , Femenino , Humanos , Masculino , Estudios Retrospectivos , Medición de RiesgoRESUMEN
PURPOSE: To develop a fast and automated volume-of-interest (VOI) prescription pipeline (AutoVOI) for single-voxel MRS that removes the need for manual VOI placement, allows flexible VOI planning in any brain region, and enables high inter- and intra-subject consistency of VOI prescription. METHODS: AutoVOI was designed to transfer pre-defined VOIs from an atlas to the 3D anatomical data of the subject during the scan. The AutoVOI pipeline was optimized for consistency in VOI placement (precision), enhanced coverage of the targeted tissue (accuracy), and fast computation speed. The tool was evaluated against manual VOI placement using existing T1 -weighted data sets and corresponding VOI prescriptions. Finally, it was implemented on 2 scanner platforms to acquire MRS data from clinically relevant VOIs that span the cerebrum, cerebellum, and the brainstem. RESULTS: The AutoVOI pipeline includes skull stripping, non-linear registration of the atlas to the subject's brain, and computation of the VOI coordinates and angulations using a minimum oriented bounding box algorithm. When compared against manual prescription, AutoVOI showed higher intra- and inter-subject spatial consistency, as quantified by generalized Dice coefficients (GDC), lower intra- and inter-subject variability in tissue composition (gray matter, white matter, and cerebrospinal fluid) and higher or equal accuracy, as quantified by GDC of prescribed VOI with targeted tissues. High quality spectra were obtained on Siemens and Philips 3T systems from 6 automatically prescribed VOIs by the tool. CONCLUSION: Robust automatic VOI prescription is feasible and can help facilitate clinical adoption of MRS by avoiding operator dependence of manual selection.
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Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Adulto , Algoritmos , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
While pulmonary hypertension (PH) is a potentially life threatening complication of many inflammatory conditions, an association between Aicardi Goutières syndrome (AGS), a rare genetic cause of interferon (IFN) overproduction, and the development of PH has not been characterized to date. We analyzed the cardiac function of individuals with AGS enrolled in the Myelin Disorders Bioregistry Project using retrospective chart review (nâ¯=â¯61). Additional prospective echocardiograms were obtained when possible (nâ¯=â¯22). An IFN signature score, a marker of systemic inflammation, was calculated through the measurement of mRNA transcripts of type I IFN-inducible genes (interferon signaling genes or ISG). Pathologic analysis was performed as available from autopsy samples. Within our cohort, four individuals were identified to be affected by PH: three with pathogenic gain-of-function mutations in the IFIH1 gene and one with heterozygous TREX1 mutations. All studied individuals with AGS were noted to have elevated IFN signature scores (Mann-Whitney pâ¯<â¯.001), with the highest levels in individuals with IFIH1 mutations (Mann-Whitney pâ¯<â¯.0001). We present clinical and histologic evidence of PH in a series of four individuals with AGS, a rare interferonopathy. Importantly, IFIH1 and TREX1 may represent a novel cause of PH. Furthermore, these findings underscore the importance of screening all individuals with AGS for PH.
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Enfermedades Autoinmunes del Sistema Nervioso/complicaciones , Exodesoxirribonucleasas/genética , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/patología , Helicasa Inducida por Interferón IFIH1/genética , Mutación , Malformaciones del Sistema Nervioso/complicaciones , Fosfoproteínas/genética , Adolescente , Niño , Humanos , Lactante , Recién Nacido , Masculino , Pronóstico , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
OBJECTIVE: To evaluate the effect of continuous treprostinil in infants with severe pulmonary hypertension associated with congenital diaphragmatic hernia (CDH) on specific markers of pulmonary hypertension severity and to report the safety and tolerability of treprostinil. STUDY DESIGN: We conducted a retrospective cohort study of infants with CDH-associated pulmonary hypertension treated with treprostinil from January 2011 to September 2016. Severity of pulmonary hypertension was assessed by echocardiogram and serum B-type natriuretic peptide (BNP) by using time points before initiation and 24 hours, 1 week, and 1 month after treprostinil initiation. Fisher exact tests, Wilcoxon-rank sum tests, and mixed-effects models were used for analysis. RESULTS: Seventeen patients were treated with treprostinil for a median of 54.5 days (IQR 44.3-110 days). Compared with the concurrent CDH population (n = 147), infants treated with treprostinil were more likely to require extracorporeal support (76.5% vs 25.2%, P < .0001), to have a longer hospital stay (144 vs 60 days, P < .0001), and to need longer mechanical ventilator support (76.5 vs 30.9 days, P < .0001). Following treprostinil initiation, there was a significant reduction in BNP at 1 week (1439 vs 393 pg/mL, P < .01) and 1 month (1439 vs 242 pg/mL, P = .01). Severity of pulmonary hypertension by echocardiogram improved at 1 month (OR 0.14, CI 95% 0.04-0.48, P = .002). Despite these improvements, overall mortality remained high (35%). There were no adverse events related to treprostinil, including no hypotension, hypoxia, or thrombocytopenia. CONCLUSIONS: In this cohort, treprostinil use was associated with improved severity of pulmonary hypertension assessed by echocardiogram and decreased BNP, with no significant side effects.
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Epoprostenol/análogos & derivados , Hernias Diafragmáticas Congénitas/complicaciones , Hipertensión Pulmonar/tratamiento farmacológico , Presión Esfenoidal Pulmonar/efectos de los fármacos , Sistema de Registros , Antihipertensivos/administración & dosificación , Relación Dosis-Respuesta a Droga , Epoprostenol/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/fisiopatología , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Hypertrophic cardiomyopathy has a range of clinical severity in children. Treatment options are limited, mainly on account of small patient size. Disopyramide is a sodium channel blocker with negative inotropic properties that effectively reduces left ventricular outflow tract gradients in adults with hypertrophic cardiomyopathy, but its efficacy in children is uncertain. A retrospective chart review of patients ⩽21 years of age with hypertrophic cardiomyopathy at our institution and treated with disopyramide was performed. Left ventricular outflow tract Doppler gradients before and after disopyramide initiation were compared as the primary outcome measure. Nine patients received disopyramide, with a median age of 5.6 years (range 6 days-12.9 years). The median left ventricular outflow tract Doppler gradient before initiation of disopyramide was 81 mmHg (range 30-132 mmHg); eight patients had post-initiation echocardiograms, in which the median lowest recorded Doppler gradient was 43 mmHg (range 15-100 mmHg), for a median % reduction of 58.2% (p=0.002). With median follow-up of 2.5 years, eight of nine patients were still alive, although disopyramide had been discontinued in six of the nine patients. Reasons for discontinuation included septal myomectomy (four patients), heart transplantation (one patient), and side effects (one patient). Disopyramide was effective for the relief of left ventricular outflow tract obstruction in children with hypertrophic cardiomyopathy, although longer-term data suggest that its efficacy is not sustained. In general, it was well tolerated. Further study in larger patient populations is warranted.
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Cardiomiopatía Hipertrófica/tratamiento farmacológico , Disopiramida/administración & dosificación , Ventrículos Cardíacos/diagnóstico por imagen , Función Ventricular Izquierda/fisiología , Adolescente , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/fisiopatología , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Ecocardiografía Doppler , Electrocardiografía , Femenino , Ventrículos Cardíacos/fisiopatología , Humanos , Lactante , Recién Nacido , Masculino , Pronóstico , Estudios Retrospectivos , Bloqueadores del Canal de Sodio Activado por Voltaje/administración & dosificación , Adulto JovenRESUMEN
Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, and older children and contributes to significant morbidity and mortality. However, current approaches to caring for pediatric patients with pulmonary hypertension have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a panel of experienced clinicians and clinician-scientists was assembled to review the current literature and to make recommendations on the diagnosis, evaluation, and treatment of pediatric pulmonary hypertension. This publication presents the results of extensive literature reviews, discussions, and formal scoring of recommendations for the care of children with pulmonary hypertension.
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Hipertensión Pulmonar/terapia , Fármacos Cardiovasculares/uso terapéutico , Niño , Preescolar , Terapia Combinada , Diagnóstico por Imagen/métodos , Manejo de la Enfermedad , Oxigenación por Membrana Extracorpórea , Asesoramiento Genético , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/terapia , Hernias Diafragmáticas Congénitas/complicaciones , Hernias Diafragmáticas Congénitas/terapia , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/genética , Lactante , Recién Nacido , Pulmón/embriología , Trasplante de Pulmón , Óxido Nítrico/administración & dosificación , Óxido Nítrico/uso terapéutico , Terapia por Inhalación de Oxígeno , Síndrome de Circulación Fetal Persistente/diagnóstico , Síndrome de Circulación Fetal Persistente/terapia , Complicaciones Posoperatorias/terapia , Respiración Artificial/efectos adversos , Respiración Artificial/métodos , Lesión Pulmonar Inducida por Ventilación Mecánica/prevención & controlRESUMEN
Pulmonary hypertension (PH) does not refer to a specific disease but rather a clinical manifestation emanating from a decrease in functional pulmonary vasculature resulting in progressively elevated right ventricle pressure and ultimately right heart failure. It is an uncommon disease process, but because of advancements in treatment, improved survival, and increasing prevalence, there is a greater likelihood that the emergency clinician will have to care for a child with PH. This review article, intended for emergency medical providers for children, is aimed at familiarizing clinicians with pediatric PH including the pathophysiology, clinical presentation and initial diagnostic strategies, basic chronic management, and management of a pulmonary hypertensive crisis.
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Servicios Médicos de Urgencia/métodos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Pediatría/métodosRESUMEN
The performance of multichannel transmit coil layouts and parallel transmission (pTx) RF pulse design was evaluated with respect to transmit B1 (B1 (+)) homogeneity and specific absorption rate (SAR) at 3 T for a whole body coil. Five specific coils were modeled and compared: a 32-rung birdcage body coil (driven either in a fixed quadrature mode or a two-channel transmit mode), two single-ring stripline arrays (with either 8 or 16 elements), and two multi-ring stripline arrays (with two or three identical rings, stacked in the z axis and each comprising eight azimuthally distributed elements). Three anatomical targets were considered, each defined by a 3D volume representative of a meaningful region of interest (ROI) in routine clinical applications. For a given anatomical target, global or local SAR controlled pTx pulses were designed to homogenize RF excitation within the ROI. At the B1 (+) homogeneity achieved by the quadrature driven birdcage design, pTx pulses with multichannel transmit coils achieved up to about eightfold reduction in local and global SAR. When used for imaging head and cervical spine or imaging thoracic spine, the double-ring array outperformed all coils, including the single-ring arrays. While the advantage of the double-ring array became much less pronounced for pelvic imaging, with a substantially larger ROI, the pTx approach still provided significant gains over the quadrature birdcage coil. For all design scenarios, using the three-ring array did not necessarily improve the RF performance. Our results suggest that pTx pulses with multichannel transmit coils can reduce local and global SAR substantially for body coils while attaining improved B1 (+) homogeneity, particularly for a "z-stacked" double-ring design with coil elements arranged on two transaxial rings.
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Imagen por Resonancia Magnética/instrumentación , Algoritmos , Simulación por Computador , Diseño de Equipo , Humanos , Modelos Teóricos , Programas InformáticosRESUMEN
Pulmonary arterial hypertension (PAH) contributes to disability and death in children with diverse cardiac, pulmonary, or systemic diseases, and therapeutic options are currently limited. Data from adult studies provide the basis for most PAH-specific therapies; however, many of these medications are commonly used in children on an off-label basis due to the life-threatening nature of PAH. Although currently approved for use in adult PAH, sildenafil is used extensively off-label for the treatment of neonates, infants, and children with PAH. Past studies have generally suggested favorable effects and outcomes in infants and young children with PAH, but these reports are generally uncontrolled observations, except for one single-center trial for persistent pulmonary hypertension of the newborn. Despite extensive clinical experience with sildenafil therapy in children and approval by the European Medicines Agency for its pediatric use in Europe, the U.S. Food and Drug Administration recently issued a warning against the use of sildenafil for pediatric PAH between 1 and 17 years of age due to an apparent increase in mortality during long-term therapy. Although these data are extremely limited, this U.S. Food and Drug Administration review challenges the pediatric PAH community to further assess the efficacy and safety of sildenafil, especially with chronic treatment. Although low doses of sildenafil are likely safe in pediatric PAH, further studies should carefully examine its role in the long-term therapy of children, especially with diverse causes of PAH. Pediatric patients with PAH require close surveillance and frequent monitoring, and persistent sildenafil monotherapy is likely insufficient with disease progression.
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Hipertensión Pulmonar/tratamiento farmacológico , Piperazinas/efectos adversos , Sulfonas/efectos adversos , Vasodilatadores/efectos adversos , Progresión de la Enfermedad , Monitoreo de Drogas , Humanos , Hipertensión Pulmonar/mortalidad , Piperazinas/administración & dosificación , Piperazinas/uso terapéutico , Vigilancia de Productos Comercializados , Purinas/administración & dosificación , Purinas/efectos adversos , Purinas/uso terapéutico , Citrato de Sildenafil , Sulfonas/administración & dosificación , Sulfonas/uso terapéutico , Estados Unidos , United States Food and Drug Administration , Vasodilatadores/administración & dosificación , Vasodilatadores/uso terapéuticoRESUMEN
Radiation exposure from pediatric cardiac catheterization may be substantial, although published estimates vary. We sought to report patient radiation dose across a range of diagnostic and interventional cases in a modern, high-volume pediatric catheterization laboratory. We retrospectively reviewed diagnostic and interventional cases performed in our pediatric catheterization laboratory from 1 April 2009 to 30 September 2011 for which radiation usage data were available as reported by the Artis Zee(®) (Siemens Medical Solutions) system. Electrophysiology cases were excluded. Radiation dose was quantified as air kerma dose (mGy) and dose-area product (DAP; µGy m(2)). The DAP was converted to an effective dose millisievert (mSv) using the Monte Carlo method. Radiation usage data were available from 2,265 diagnostic and interventional cases with an overall median air kerma dose of 135 mGy [interquartile range (IQR) 59-433], median DAP of 760 µGy m(2) (IQR 281-2,810), of which 75 % (IQR 59-90 %) was derived from fluoroscopy, and median effective dose of 6.2 mSv (IQR 2.7-14.1). Air kerma dose from a single camera >2,000 mGy occurred in 1.8 % of cases. Significant differences in all measures of radiation exposure existed based on procedural and interventional types (p = 0.0001), with interventional cases associated with the highest effective dose after adjusting for patient weight category (p < 0.001). Patient weight, age, fluoroscopy time, and proportional use of digital acquisition were independent predictors of exposure (p ≤ 0.001; R (2) = 0.59-0.64). In a modern, large-volume pediatric catheterization laboratory, the median effective dose is 6.2 mSv with a wide range of exposure based on patient- and procedure-specific factors. Radiation monitoring is an important component of a pediatric laboratory and further dose reduction strategies are warranted.
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Cateterismo Cardíaco/estadística & datos numéricos , Fluoroscopía/estadística & datos numéricos , Dosis de Radiación , Radiografía Intervencional/estadística & datos numéricos , Medición de Riesgo/métodos , Niño , Preescolar , Humanos , Lactante , Pediatría , Philadelphia , Estudios Retrospectivos , Factores de RiesgoAsunto(s)
Ventrículos Cardíacos/fisiopatología , Hernias Diafragmáticas Congénitas/complicaciones , Hipertensión Pulmonar/etiología , Disfunción Ventricular Izquierda/etiología , Ecocardiografía , Feto , Hernias Diafragmáticas Congénitas/terapia , Humanos , Hipertensión Pulmonar/terapia , Recién Nacido , Disfunción Ventricular Izquierda/terapiaRESUMEN
OBJECTIVES: To describe the prevalence of and identify risk factors for acute occlusive arterial injury (AOAI) in a large volume pediatric cardiac catheterization laboratory. BACKGROUND: AOAI is a known complication after pediatric cardiac catheterization. Prevalence and risk factors in the modern era are incompletely described. METHODS: A retrospective cohort study including all cardiac catheterization procedures performed between January 1, 2005 and June 30, 2010 was performed. Case status was defined by ≥1 of the following: exam consistent with occlusive arterial injury, use of an anticoagulant within 48 hr of catheterization to restore or maintain patency of the artery, or documented occlusive arterial injury by radiologic study. RESULTS: 3,254 patients had 5,715 catheterization procedures, which included 3,859 arterial access events. 167 cases of AOAI were identified for an overall prevalence of 4.3% among arterial access events. Multiple logistic regression identified independent risk factors: weight category [<4 kg: odds ratio (OR) 4.5 (95% CI: 2.6-7.7), P < 0.001; 4-6 kg: OR 2.1 (1.3-3.5), P = 0.002, compared to 6-8 kg referent group]; largest catheter outer diameter French size [OR 1.6 (1.3-1.9), P < 0.001]; final activated clotting time (ACT) <250 sec [OR 1.9 (1.4-2.7), P < 0.001]; and need for arterial catheter exchange [OR 1.8 (1.02-3.2), P = 0.04]. CONCLUSIONS: AOAI occurred in 4.3% of pediatric cardiac catheterizations, and was most likely in smaller children and those with larger arterial catheters. Risk was also independently increased by arterial catheter exchange and having a final ACT <250 sec. These data act as an important benchmark and identify areas for intervention for future studies.
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Arteriopatías Oclusivas/epidemiología , Cateterismo Cardíaco/efectos adversos , Lesiones del Sistema Vascular/epidemiología , Enfermedad Aguda , Adolescente , Adulto , Factores de Edad , Anciano , Anticoagulantes/uso terapéutico , Arteriopatías Oclusivas/diagnóstico , Arteriopatías Oclusivas/tratamiento farmacológico , Arteriopatías Oclusivas/fisiopatología , Peso Corporal , Cateterismo Cardíaco/instrumentación , Catéteres Cardíacos , Distribución de Chi-Cuadrado , Niño , Preescolar , Diseño de Equipo , Femenino , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Philadelphia/epidemiología , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular , Lesiones del Sistema Vascular/diagnóstico , Lesiones del Sistema Vascular/tratamiento farmacológico , Lesiones del Sistema Vascular/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Children and young adults with single-ventricle physiology have abnormal exercise capacity after the Fontan operation. A medication capable of decreasing pulmonary vascular resistance should allow improved cardiac filling and improved exercise capacity. METHODS AND RESULTS: This study was a double-blind, placebo-controlled, crossover trial conducted in children and young adults after Fontan. Subjects were randomized to receive placebo or sildenafil (20 mg three times daily) for 6 weeks. After a 6-week washout, subjects crossed over for an additional 6 weeks. Each subject underwent an exercise stress test at the start and finish of each phase. After taking sildenafil, subjects had a significantly decreased respiratory rate and decreased minute ventilation at peak exercise. At the anaerobic threshold, subjects had significantly decreased ventilatory equivalents of carbon dioxide. There was no change in oxygen consumption during peak exercise, although there was a suggestion of improved oxygen consumption at the anaerobic threshold. Improvement at the anaerobic threshold was limited to the subgroup with single left or mixed ventricular morphology and to the subgroup with baseline serum brain natriuretic peptide levels ≥100 pg/mL. CONCLUSIONS: In this cohort, sildenafil significantly improved ventilatory efficiency during peak and submaximal exercise. There was also a suggestion of improved oxygen consumption at the anaerobic threshold in 2 subgroups. These findings suggest that sildenafil may be an important agent for improving exercise performance in children and young adults with single-ventricle physiology after the Fontan operation. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00507819.
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Ejercicio Físico , Procedimiento de Fontan , Cardiopatías Congénitas/cirugía , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Piperazinas/uso terapéutico , Sulfonas/uso terapéutico , Administración Oral , Adolescente , Adulto , Niño , Estudios Cruzados , Método Doble Ciego , Femenino , Cardiopatías Congénitas/fisiopatología , Humanos , Masculino , Péptido Natriurético Encefálico/sangre , Consumo de Oxígeno/efectos de los fármacos , Piperazinas/efectos adversos , Purinas/efectos adversos , Purinas/uso terapéutico , Citrato de Sildenafil , Sulfonas/efectos adversos , Adulto JovenAsunto(s)
Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/terapia , Manejo de la Enfermedad , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , Recién Nacido de muy Bajo Peso , Displasia Broncopulmonar/epidemiología , Preescolar , Terapia Combinada , Progresión de la Enfermedad , Femenino , Humanos , Hipertensión Pulmonar/epidemiología , Lactante , Recién Nacido , Masculino , Guías de Práctica Clínica como Asunto , Pronóstico , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tasa de SupervivenciaRESUMEN
The objective of this study was describe the impact of sildenafil on echocardiographic measures of myocardial performance in children and young adults with a functional single-ventricle physiology late after Fontan surgery. A double-blind, placebo-controlled, crossover trial was conducted in children and young adults after the Fontan operation at a single pediatric center. Subjects were randomized to receive placebo or sildenafil (20 mg tid) for 6 weeks. After a 6-week washout period, subjects were crossed for an additional 6 weeks. Each subject underwent an echocardiogram at the start and finish of each phase. A total of 27 subjects completed study testing at a mean age of 14.9 years and a mean time from Fontan surgery of 11.3 years. After sildenafil, subjects demonstrated improvement in their myocardial performance index (MPI; -0.051; 95% CI -0.095, -0.0077; p 0.02) and in the product of the velocity time integral (VTI) of the dominant outflow tract and the heart rate (HR; 110 cm × bpm; 95% CI 7.5, 220; p = 0.04). Measures of diastolic performance, including inflow velocities, myocardial velocities, and the ratio of blood pool velocity to myocardial velocity during passive inflow, did not change. In this cohort, there were significant improvements in both the MPI and the product of the VTI × HR after 6 weeks of treatment with sildenafil. These findings suggest that sildenafil may be a useful therapy to improve or maintain ventricular performance in select patients after the Fontan operation.