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High-frequency oscillatory activity in cognition-related neural circuits during wakefulness consistently induces the growth of dendritic spines and axonal terminals. Although these structural changes are essential for cognitive functions, it is hypothesized that if these newly expanded structures fail to establish functional connections, they may become superfluous. Sleep is believed to facilitate the reduction of such redundant structures to maintain neural homeostasis. However, the mechanisms underlying this pruning process during sleep remain poorly understood. In this study, that melatonin type 3 receptors (MT3Rs) are selectively expressed in the stellate neurons of the medial entorhinal cortex (MEC) is demonstrated, an area where high melatonin levels are detected during sleep. Activation of MT3Rs during sleep initiates the shrinkage of dendritic spines in stellate neurons by downregulating neural network activity and dephosphorylating synaptic proteins in the MEC. This process is disrupted when MT3R expression is knocked down or when MT3Rs are blocked during sleep. Notably, interference with MT3Rs in the MEC during sleep impairs the acquisition of spatial memory but does not affect object memory acquisition following sleep. These findings reveal novel molecular mechanisms involving melatonin and MT3Rs in the regulation of dendritic spine shrinkage during sleep, which is crucial for the acquisition and consolidation of spatial memory.
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BACKGROUND: The interstage period after discharge from stage 1 palliation carries high morbidity and mortality. The impact of social determinants of health on interstage outcomes is not well characterized. We assessed the relationship between childhood opportunity and acute interstage outcomes. METHODS: Infants discharged home after stage 1 palliation in the National Pediatric Quality Improvement Collaborative Phase II registry (2016-2022) were retrospectively reviewed. Zip code-level Childhood Opportunity Index (COI), a composite metric of 29 indicators across education, health and environment, and socioeconomic domains, was used to classify patients into 5 COI levels. Acute interstage outcomes included death or transplant listing, unplanned readmission, intensive care unit admission, unplanned catheterization, and reoperation. The association between COI level and acute interstage outcomes was assessed using logistic regression with sequential adjustment for potential confounders. RESULTS: The analysis cohort included 1837 patients from 69 centers. Birth weight (P<0.001) and proximity to a surgical center at birth (P=0.02) increased with COI level. Stage 1 length of stay decreased (P=0.001), and exclusive oral feeding rate at discharge increased (P<0.001), with higher COI level. More than 98% of patients in all COI levels were enrolled in home monitoring. Death or transplant listing occurred in 101 (5%) patients with unplanned readmission in 987 (53%), intensive care unit admission in 448 (24%), catheterization in 345 (19%), and reoperation in 83 (5%). There was no difference in the incidence or time to occurrence of any acute interstage outcome among COI levels in unadjusted or adjusted analysis. There was no interaction between race and ethnicity and childhood opportunity in acute interstage outcomes. CONCLUSIONS: Zip code COI level is associated with differences in preoperative risk factors and stage 1 palliation hospitalization characteristics. Acute interstage outcomes, although common across the spectrum of childhood opportunity, are not associated with COI level in an era of highly prevalent home monitoring programs. The role of home monitoring in mitigating disparities during the interstage period merits further investigation.
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Mejoramiento de la Calidad , Humanos , Masculino , Femenino , Recién Nacido , Lactante , Estudios Retrospectivos , Sistema de Registros , Cuidados Paliativos/normas , Resultado del Tratamiento , Estados Unidos/epidemiología , Determinantes Sociales de la Salud , Readmisión del Paciente , Alta del PacienteRESUMEN
Background: FAV is offered to fetuses with severe aortic valve stenosis and evolving hypoplastic left heart syndrome. An inferential analysis of TS and SAE in a large series has not been reported. Objectives: The purpose of this study was to determine factors associated with fetal aortic valvuloplasty (FAV) technical success (TS) and serious adverse events (SAEs). Methods: Retrospective, single-center, cohort analysis of attempted FAV from March 1, 2000, to December 31, 2020. The primary outcome was the TS of FAV, and the secondary outcome was the presence of an SAE. Results: A total of 165 FAVs were attempted in 163 patients with a median gestational age of 24.6 weeks (IQR: 22.9-27.1 weeks). FAV TS was 85% (141/165) and was higher in the 2010 to 2020 era (94% [85/90] vs 75% [56/75]; P < 0.001). Pre-FAV echocardiographic left ventricle (LV) long axis dimension z-score >-0.10 (P < 0.001) and higher LV ejection fraction (P = 0.037) were independently associated with a higher odds of TS. There were 117 SAEs in 67 attempted FAVs (41%), 13 of which were fetal deaths (7.9%). By classification and regression tree analysis, gestational age <21 weeks or in older fetuses, a procedure time of ≥39.6 minutes was associated with higher SAE rate. In the multivariable logistic regression model correcting for gestational age, fetuses with an LV end-diastolic volume <4.09 mL had an age-adjusted OR of 4.71 (95% CI: 1.67-13.29; P = 0.004) for experiencing an SAE. Conclusions: TS of FAV has improved over time, and failure is associated with smaller fetal left heart sizes. SAEs are common and are associated with smaller left hearts and longer procedure times.
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Background: For infants with single ventricle heart disease, the time after stage 2 procedure (S2P) is believed to be a lower risk period compared with the interstage period; however, significant morbidity and mortality still occur. Objectives: This study aimed to identify risk factors for mortality or transplantation referral between S2P surgery and the first birthday. Methods: Retrospective cohort analysis of infants in the National Pediatric Cardiology Quality Improvement Collaborative who underwent staged single ventricle palliation from 2016 to 2022 and survived to S2P. Multivariable logistic regression and classification and regression trees were performed to identify risk factors for mortality and transplantation referral after S2P. Results: Of the 1,455 patients in the cohort who survived to S2P, 5.2% died and 2.3% were referred for transplant. Overall event rates at 30 and 100 days after S2P were 2% and 5%, respectively. Independent risk factors for mortality and transplantation referral included the presence of a known genetic syndrome, shunt type at stage 1 procedure (S1P), tricuspid valve repair at S1P, longer time to extubation and reintubation after S1P, ≥ moderate tricuspid regurgitation prior to S2P, younger age at S2P, and the risk groups identified in the classification and regression tree analysis (extracorporeal membrane oxygenation after S1P and longer S2P cardiopulmonary bypass time without extracorporeal membrane oxygenation). Conclusions: Mortality and transplantation referral rates after S2P to 1 year of age remain high â¼7%. Many of the identified risk factors after S2P are similar to those established for interstage factors around the S1P, whereas others may be unique to the period after S2P.
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BACKGROUND: Robust risk assessment is crucial for the growing repaired tetralogy of Fallot population at risk of major adverse clinical outcomes; however, current tools are hindered by lack of validation. This study aims to develop and validate a risk prediction model for death in the repaired tetralogy of Fallot population. METHODS AND RESULTS: Patients with repaired tetralogy of Fallot enrolled in the INDICATOR (International Multicenter Tetralogy of Fallot Registry) cohort with clinical, arrhythmia, cardiac magnetic resonance, and outcome data were included. Patients from London, Amsterdam, and Boston sites were placed in the development cohort; patients from the Toronto site were used for external validation. Multivariable Cox regression was used to evaluate factors associated with time from cardiac magnetic resonance until the primary outcome: all-cause death. Of 1552 eligible patients (n=1221 in development, n=331 in validation; median age at cardiac magnetic resonance 23.4 [interquartile range, 15.6-35.6] years; median follow up 9.5 years), 102 (6.6%) experienced the primary outcome. The multivariable Cox model performed similarly during development (concordance index, 0.83 [95% CI, 0.78-0.88]) and external validation (concordance index, 0.80 [95% CI, 0.71-0.90]) and identified older age at cardiac magnetic resonance, obesity, type of tetralogy of Fallot repair, higher right ventricular end-systolic volume index, and lower biventricular global function index as independent predictors of death. A risk-scoring algorithm dividing patients into low-risk (score ≤4) versus high-risk (score >4) groups was validated to effectively discriminate risk of death (15-year survival of 95% versus 74%, respectively; P<0.001). CONCLUSIONS: This externally validated mortality risk prediction algorithm can help identify vulnerable patients with repaired tetralogy of Fallot who may benefit from targeted interventions.
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Sistema de Registros , Tetralogía de Fallot , Humanos , Tetralogía de Fallot/cirugía , Tetralogía de Fallot/mortalidad , Masculino , Femenino , Medición de Riesgo/métodos , Adulto , Adolescente , Adulto Joven , Factores de Riesgo , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/mortalidad , Reproducibilidad de los Resultados , Factores de Tiempo , Valor Predictivo de las Pruebas , Causas de MuerteRESUMEN
Calcium oscillations are induced by different stresses. Calcium-dependent protein kinases (CDPKs/CPKs) are one major group of the plant calcium decoders that are involved in various processes including drought response. Some CPKs are calcium-independent. Here, we identified ZmCPK2 as a negative regulator of drought resistance by screening an overexpression transgenic maize pool. We found that ZmCPK2 does not bind calcium, and its activity is mainly inhibited during short term abscisic acid (ABA) treatment, and dynamically changed in prolonged treatment. Interestingly, ZmCPK2 interacts with and is inhibited by calcium-dependent ZmCPK17, a positive regulator of drought resistance, which is activated by ABA. ZmCPK17 could prevent the nuclear localization of ZmCPK2 through phosphorylation of ZmCPK2T60. ZmCPK2 interacts with and phosphorylates and activates ZmYAB15, a negative transcriptional factor for drought resistance. Our results suggest that drought stress-induced Ca2+ can be decoded directly by ZmCPK17 that inhibits ZmCPK2, thereby promoting plant adaptation to water deficit.
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Ácido Abscísico , Calcio , Sequías , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Proteínas Quinasas , Zea mays , Zea mays/efectos de los fármacos , Zea mays/metabolismo , Zea mays/genética , Zea mays/fisiología , Calcio/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Fosforilación , Proteínas Quinasas/metabolismo , Plantas Modificadas Genéticamente , Estrés Fisiológico/efectos de los fármacos , Unión Proteica/efectos de los fármacosRESUMEN
Although recent evidence indicated significant phenol and alkylamide interaction in aqueous solutions, the gastrointestinal digestion influence of the combination remains unclear. This study aims to investigate phenol and alkylamide interaction during in vitro digestion, focusing on bioaccessibility and bioactivity, including α-glucosidase inhibition and cellular antioxidant activity. Additionally, the structural mechanism of phenol and alkylamide interaction during in vitro digestion was explored. The results indicated that the presence of phenols and alkylamides significantly increased or decreased their respective bioaccessibility, depending on the Zanthoxylum varieties. Furthermore, although antagonistic phenol/alkylamide interaction was evident during α-glucosidase inhibition, cellular oxidative stress alleviation, and antioxidant gene transcription upregulation, this effect weakened gradually as digestion progressed. Glycoside bond cleavage and the methylation of phenols as well as alkylamide isomerization and addition were observed during digestion, modifying the hydrogen bonding sites and interaction behavior. This study provided insights into the phenol/alkylamide interaction in the gastrointestinal tract.
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Amidas , Antioxidantes , Digestión , Inhibidores de Glicósido Hidrolasas , Extractos Vegetales , Zanthoxylum , alfa-Glucosidasas , Zanthoxylum/química , Zanthoxylum/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/metabolismo , Inhibidores de Glicósido Hidrolasas/farmacología , alfa-Glucosidasas/metabolismo , alfa-Glucosidasas/química , alfa-Glucosidasas/genética , Humanos , Amidas/química , Amidas/metabolismo , Amidas/farmacología , Extractos Vegetales/química , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , Fenoles/química , Fenoles/metabolismo , Modelos Biológicos , Fenol/metabolismo , Fenol/químicaRESUMEN
BACKGROUND: Previous reports reveal inconsistent findings of right ventricular (RV) changes following pregnancy in subjects with repaired tetralogy of Fallot (rTOF). METHODS: A two-center, retrospective cohort study which included women with rTOF who completed pregnancy that were matched to nulliparous women with rTOF by age at the time of baseline cardiac magnetic resonance (CMR), RV ejection fraction (RVEF), and indexed RV end-diastolic volume (RVEDVi). Pre-pregnancy and postpartum cardiac magnetic resonance (CMR) were analyzed and compared to sequential CMR of nulliparous subjects with rTOF. RESULTS: Thirty-six women with rTOF who completed pregnancy were matched to 72 nulliparous women with rTOF. Over a mean period of 3.1 years for the pregnancy group and 2.7 years for the comparison group, there was no significant change in the RVEDVi, RVEF, RV mass, pulmonary regurgitation severity, left ventricular (LV) volumes, LV ejection fraction (LVEF), or LV mass when comparing the baseline CMR and the follow-up CMR in either of the groups. There was a slight increase in RV indexed end-systolic volume (RVESVi) when comparing the baseline CMR and the follow-up CMR in the pregnancy group (68.93, SD 23.34 ml/m2 at baseline vs. 72.97, SD 25.24 mL/m2 at follow-up, P = .028). Using a mixed effects model for CMR parameters change over time; when adjusted for time between baseline and follow-up CMR there was no significant difference in rate of change between the pregnancy and comparison groups. CONCLUSIONS: Most ventricular remodeling parameters measured by CMR did not significantly change in subjects with rTOF who completed pregnancy or in nulliparous subjects with rTOF. In the pregnancy group, RVESVi is larger in those individuals who have undergone pregnancy without a significant change in ventricular function. These patients should be followed longitudinally to determine the long-term ventricular and clinical effects of pregnancy.
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Imagen por Resonancia Cinemagnética , Volumen Sistólico , Tetralogía de Fallot , Humanos , Femenino , Tetralogía de Fallot/cirugía , Tetralogía de Fallot/fisiopatología , Embarazo , Estudios Retrospectivos , Adulto , Volumen Sistólico/fisiología , Imagen por Resonancia Cinemagnética/métodos , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Complicaciones Cardiovasculares del Embarazo/diagnóstico por imagen , Función Ventricular Derecha/fisiología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Procedimientos Quirúrgicos Cardíacos/métodos , Estudios de Seguimiento , Adulto JovenRESUMEN
OBJECTIVES: Parachute left atrioventricular valve (LAVV) complicates atrioventricular septal defect (AVSD) repair. We evaluate outcomes of AVSD patients with parachute LAVV and identify risk factors for adverse outcomes. METHODS: We evaluated all patients undergoing repair of AVSD with parachute LAVV from 2012 to 2021. The primary outcome was a composite of time-to-death, LAVV reintervention and development of greater than or equal to moderate LAVV dysfunction (greater than or equal to moderate LAVV stenosis and/or LAVV regurgitation). Event-free survival for the composite outcome was estimated using Kaplan-Meier methodology and competing risks analysis. Cox proportional hazards regression was used to identify predictors of the primary outcome. RESULTS: A total of 36 patients were included with a median age at repair of 4 months (interquartile range 2.3-5.5 months). Over a median follow-up of 2.6 years (interquartile range 1.0-5.6 years), 6 (17%) patients underwent LAVV reintervention. All 6 patients who underwent LAVV reintervention had right-dominant AVSD. Sixteen patients (44%) met the composite outcome, and all did so within 2 years of initial repair. Transitional AVSD (versus complete), prior single-ventricle palliation, leaving the cleft completely open and greater than or equal to moderate preoperative LAVV regurgitation were associated with a higher risk of LAVV reintervention in univariate analysis. In multivariate analysis, leaving the cleft completely open was associated with the composite outcome. CONCLUSIONS: Repair of AVSD with parachute LAVV remains a challenge with a significant burden of LAVV reintervention and dysfunction in medium-term follow-up. Unbalanced, right-dominant AVSDs are at higher risk for LAVV reintervention. Leaving the cleft completely open might independently predict poor overall outcomes and should be avoided when possible. CLINICAL TRIAL REGISTRATION NUMBER: IRB-P00041642.
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BACKGROUND: Identification of risk factors for biventricular (BiV) repair in children with hypoplastic left ventricles (HLV) has been challenging. We sought to identify preoperative cardiovascular magnetic resonance (CMR) predictors of outcome in patients with HLVs who underwent BiV repair, with a focus on the mitral valve (MV). METHODS: Single-center retrospective analysis of preoperative CMRs on patients with HLV (≤50 mL/m2) and no endocardial fibroelastosis who underwent BiV repair from 2005-2022. CMR measurements included MV orifice area in diastole. The primary composite outcome included time to death, transplant, BiV takedown, heart failure admission, left atrial decompression, or unexpected reoperation; and the secondary outcome included more than or equal to moderate mitral stenosis and/or regurgitation. RESULTS: Median follow-up was 0.7 (interquartile range 0.1, 2.2) years. Of 122 patients [59 atrioventricular canal (AVC) and 63 non-AVC] age 3 ± 2.8 years at the time of BiV repair, freedom from the primary outcome at 2 years was 53% for AVC and 69% for non-AVC (log rank p = 0.12), and freedom from the secondary outcome at 2 years was 49% for AVC and 79% for non-AVC (log rank p < 0.01). Independent predictors of primary outcome for AVC patients included MV orifice area z-score <-2 and transitional AVC; for non-AVC patients, predictors included MV orifice area z-score <-2, abnormal MV anatomy, and conal-septal ventricular septal defect. Independent predictors of secondary outcome for AVC patients included older age at surgery, transitional AVC, and transposition of the great arteries. CONCLUSION: In children with HLV, low MV orifice area and pre-existing MV pathology are risk factors for adverse outcome after BiV repair.
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Procedimientos Quirúrgicos Cardíacos , Síndrome del Corazón Izquierdo Hipoplásico , Válvula Mitral , Valor Predictivo de las Pruebas , Humanos , Estudios Retrospectivos , Femenino , Masculino , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Válvula Mitral/fisiopatología , Válvula Mitral/anomalías , Síndrome del Corazón Izquierdo Hipoplásico/cirugía , Síndrome del Corazón Izquierdo Hipoplásico/diagnóstico por imagen , Síndrome del Corazón Izquierdo Hipoplásico/fisiopatología , Factores de Riesgo , Preescolar , Factores de Tiempo , Lactante , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Medición de Riesgo , Resultado del Tratamiento , Niño , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/fisiopatología , Función Ventricular IzquierdaRESUMEN
The development of an analytical method for assessing pungency intensity and determining geographical origins is crucial for evaluating the quality of visually similar Zanthoxylum bungeanum pericarp (PZB). This study analyzed 210 PZB samples from 14 origins across China, focusing on origin adulteration identification and pungency intensity using a combination of differential pulse voltammetry (DPV) and machine learning algorithms. The artificial neural network (ANN) and K-nearest neighbor (KNN) algorithms provided the highest accuracy in origin identification (100 %) and adulteration detection (97.9 %) respectively. Moreover, the ANN excelled in predicting pungency intensity (R2 = 0.918). Assessment via feature importance analysis of DPV features revealed that segments of polyphenols (0.34-0.52 V and 1.0-1.2 V) and alkylamides (1.0-1.2 V) contributed significantly to the PZB pungency intensity. These findings highlight the potential of DPV as a reliable method for assessing the quality of PZB, and offer a promising solution for ensuring the geographical authenticity of this important crop.
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Capsicum , Zanthoxylum , Algoritmos , Redes Neurales de la Computación , Aprendizaje AutomáticoRESUMEN
The hypocretin (Hcrt) (also known as orexin) neuropeptidic wakefulness-promoting system is implicated in the regulation of spatial memory, but its specific role and mechanisms remain poorly understood. In this study, we revealed the innervation of the medial entorhinal cortex (MEC) by Hcrt neurons in mice. Using the genetically encoded G-protein-coupled receptor activation-based Hcrt sensor, we observed a significant increase in Hcrt levels in the MEC during novel object-place exploration. We identified the function of Hcrt at presynaptic glutamatergic terminals, where it recruits fast-spiking parvalbumin-positive neurons and promotes gamma oscillations. Bidirectional manipulations of Hcrt neurons' projections from the lateral hypothalamus (LHHcrt) to MEC revealed the essential role of this pathway in regulating object-place memory encoding, but not recall, through the modulation of gamma oscillations. Our findings highlight the significance of the LHHcrt-MEC circuitry in supporting spatial memory and reveal a unique neural basis for the hypothalamic regulation of spatial memory.
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Hipotálamo , Memoria Espacial , Ratones , Animales , Orexinas/metabolismo , Hipotálamo/metabolismo , Neuronas/fisiología , Área Hipotalámica Lateral/fisiologíaRESUMEN
AIMS: To synthesize the published studies on medication adherence trajectories among patients with chronic diseases and identify the influencing factors. DESIGN: Systematic review. DATA SOURCES: Medline (Ovid), Embase (Ovid) and Web of Science core collection were searched from database inception to 1 July 2022. REVIEW METHODS: Potentially eligible articles were independently screened by three reviewers using set inclusion and exclusion criteria. The Joanna Briggs Institute critical appraisal checklist for cohort studies was used to appraise the quality of the included articles. Three reviewers independently evaluated the quality, extracted data and resolved differences by consensus. Results were presented using descriptive synthesis, and the prevalence of recategorised medication adherence trajectories was calculated from the published data. RESULTS: Fifty studies were included. Medication adherence trajectories among patients with chronic diseases were synthesized into six categories: adherence, non-adherence, decreasing adherence, increasing adherence, fluctuating adherence and moderate adherence. Low and moderate evidence showed that (1) patient-related factors, including age, sex, race, marital status and mental status; (2) healthcare team and system-related factors, including healthcare utilization, insurance and primary prescriber specialty; (3) socioeconomic factors including education, income and employment status; (4) condition-related factors including complications and comorbidities and (5) therapy-related factors including the number of medications, use of other medications, and prior medication adherence behaviours were factors influencing the medication adherence trajectory. Marital status and prior medication adherence behaviour were the only influencing factors with moderate evidence of an effect. CONCLUSION: The medication adherence trajectory among patients with chronic diseases varied widely. Further studies are warranted to determine contributory factors. IMPLICATIONS FOR THE PROFESSION: Healthcare providers should be aware that patients' medication adherence has different trajectories and should take appropriate measures to improve patients' medication adherence patterns. PATIENT OR PUBLIC CONTRIBUTION: None. As a systematic review, patients and the public were not involved.
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Cumplimiento de la Medicación , Humanos , Enfermedad Crónica , Estudios de CohortesRESUMEN
BACKGROUND: CHD is a lifelong condition with a significant burden of disease to patients and families. With increased survival, attention has shifted to longer-term outcomes, with a focus on social determinants of health. Among children with CHD, socioeconomic status is associated with disparities in outcomes. Household material hardship is a concrete measure of poverty and may serve as an intervenable measure of socioeconomic status. METHODS: A longitudinal survey study was conducted at multiple time points (at acute hospitalisation, then 12-24 months later in the chronic phase) to determine the prevalence of household material hardship among parents of children with advanced heart disease and quality of life during long-term follow-up. RESULTS: The analytic cohort was 160 children with a median patient age of 1 year (IQR 1,4) with 54% of patients <2 years. During acute hospitalisation, over one-third of families reported household material hardship (37%), with significantly lower household material hardship in the chronic phase at 16% (N = 9 of 52). For parents reporting household material hardship during acute hospitalisation, 50% had resolution of household material hardship by the chronic phase. Household material hardship-exposed children were significantly more likely to be publicly insured (56% versus 20%, p = 0.03) with lower quality of life than those without household material hardship (64% versus 82%, p = 0.013). CONCLUSION: The burden of heart disease during the chronic phase of illness is high. Household material hardship may serve as a target to ensure equity in the care and outcomes of CHD patients and their families.
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BACKGROUND: Phosphodiesterase inhibitors are known to relieve symptoms in the setting of heart failure, although their effects in restrictive ventricular physiology have been poorly characterized. We explored the association between the use of milrinone and volume administration during the first 72 hours following surgical repair of tetralogy of Fallot (TOF). METHODS: We reviewed all cases of primary surgical repair of TOF with pulmonary stenosis or atresia at Boston Children's Hospital between 2011 and 2020. To adjust for baseline differences between patients who did and did not receive milrinone, we matched patients with similar propensity scores in a 1:1 ratio (use of milrinone versus not). We then compared the need for volume administration during the first 72 hours postoperatively, vital signs, and measures of cardiac output between the matched cohorts. Additionally, in the group of patients receiving milrinone, linear regression modeling was used to explore the relationship between total dose of milrinone and total volume administration. RESULTS: Among 351 included patients, 134 received perioperative milrinone. A total of 212 patients (106 per group) were matched based on anatomic and surgical risks using a propensity score. After propensity matching, compared with nonmilrinone-treated patients, milrinone-treated patients were given postoperative volume more frequently (66% vs 52%; difference 14% [95% confidence interval, CI, 1%-27%]; P = .036). Milrinone-treated patients had a slower recovery of tachycardia during the first 12 hours (difference in slope 0.30 [95% CI, 0.14-0.47] beats per minute [BPM]/h; P < .001), and the intergroup difference peaked at 12 hours postoperatively (8 [95% CI, 5-12] BPM). Milrinone administration was not associated with improved cardiac output, including arteriovenous oxyhemoglobin saturation difference. In propensity-matched patients receiving milrinone, the total volume administered during the first 72 postoperative hours was significantly associated with the cumulative dose of postoperative milrinone ( r = 0.20; 95% CI, 0.01-0.38; P = .036). Based on the slope of the regression line, for every 1000 µg/kg of milrinone (equivalent to ~0.25 µg/kg/min for 72 hours) administered in the first 72 postoperative hours, an estimated 11.0 (95% CI, 0.6-21.4) mL/kg additional volume was administered. CONCLUSIONS: The use of milrinone within the first 72 hours following TOF repair is associated with more frequent administration of volume, a positive association between a higher total dose of postoperative milrinone and the amount of postoperative volume administered, a higher heart rate, and a lower blood pressure, but is not associated with improved cardiac output.
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Background: The right ventricle (RV) has complex geometry and function, with motion along three separate axes-longitudinal, radial, and anteroposterior. Quantitative assessment of RV function by two-dimension echocardiography (2DE) has been limited as a consequence of this complexity, whereas newer three dimensional (3D) analysis offers the potential for more comprehensive assessment of the contributors to RV function. The aims of this study were to quantify the longitudinal, radial and anteroposterior components of global RV function using 3D echocardiography in a cohort of healthy children and to examine maturational changes in these parameters. Methods: Three-dimensional contours of the RV were generated from a cohort of healthy pediatric patients with structurally normal hearts at two centers. Traditional 2D and 3D echo characteristics were recorded. Using offline analysis of 3D datasets, RV motion was decomposed into three components, and ejection fractions (EF) were calculated (longitudinal-LEF; radial-REF; and anteroposterior-AEF). The individual decomposed EF values were indexed against the global RVEF. Strain values were calculated as well. Results: Data from 166 subjects were included in the analysis; median age was 13.5 years (range 0 to 17.4 years). Overall, AEF was greater than REF and LEF (29.2 ± 6.2% vs. 25.1 ± 7.2% and 25.7 ± 6.0%, respectively; p < 0.001). This remained true when indexed to overall EF (49.8 ± 8.7% vs. 43.3 ± 11.6% and 44.4 ± 10%, respectively; p < 0.001). Age-related differences were present for global RVEF, REF, and all components of RV strain. Conclusions: In healthy children, anteroposterior shortening is the dominant component of RV contraction. Evaluation of 3D parameters of the RV in children is feasible and enhances the overall understanding of RV function, which may allow improvements in recognition of dysfunction and assessment of treatment effects in the future.
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INTRODUCTION: Dexmedetomidine (DEX) is frequently used as an adjunct agent for prolonged sedation in the intensive care unit (ICU), though its effect on concomitant opioids or benzodiazepines infusions is unclear. We explored the impact of DEX on concomitant analgosedation in a cohort of ventilated pediatric patients in a cardiac ICU, with stratification of patients according to duration of ventilation (< 5 versus ≥ 5 days) following DEX initiation. METHODS: We conducted a retrospective analysis on ventilated patients receiving a DEX infusion ≥ 24 h and at least one other sedative/analgesic infusion (January 2011-June 2021). We evaluated trends of daily doses of opioids and benzodiazepines from 24 h before to 72 h following DEX initiation, stratifying patients based on ventilation duration after DEX initiation (< 5 versus ≥ 5 days). RESULTS: After excluding 1146 patients receiving DEX only, 1073 patients were included [median age 234 days (interquartile range 90, 879)]. DEX was associated with an opioid infusion in 99% of patients and a benzodiazepine infusion in 62%. Among patients ventilated for < 5 days (N = 761), opioids increased in the first 24 h following DEX initiation [+ 1.12 mg/kg/day (95% CI 0.96, 1.23), P < 0.001], then decreased [- 0.90 mg/kg/day (95% CI - 0.89, - 0.71), P < 0.001]; benzodiazepines slowly decreased [- 0.20 mg/kg/day (95% CI - 0.21, - 0.19), P < 0.001]. Among patients ventilated for ≥ 5 days (N = 312), opioid administration doubled [+ 2.09 mg/kg/day (95% CI 1.82, 2.36), P < 0.001] in the first 24 h, then diminished minimally [- 0.18 mg/kg/day (95% CI - 0.32, - 0.04), P = 0.015] without returning to baseline; benzodiazepine administration decreased minimally [- 0.03 mg/kg/day (95% CI - 0.05, - 0.01), P = 0.010]. Similar trends were confirmed when adjusting for age, gender, surgical complexity, recent major invasive procedures, duration of mechanical ventilation before DEX initiation, extubation within 72 h following DEX initiation, mean hourly DEX dose, and use of neuromuscular blocking infusion. CONCLUSION: While in patients ventilated < 5 days opioids initially increased and then quickly decreased in the 72 h following DEX initiation, among patients ventilated ≥ 5 days opioids doubled, then decreased only minimally; benzodiazepines decreased minimally in both groups, although more slowly in the long-ventilation cohort. These findings may inform decision-making on timing of DEX initiation in ventilated patients already being treated with opioid or benzodiazepine infusions.
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Analgésicos Opioides , Dexmedetomidina , Humanos , Niño , Analgésicos Opioides/uso terapéutico , Benzodiazepinas/uso terapéutico , Dexmedetomidina/efectos adversos , Estudios Retrospectivos , Hipnóticos y Sedantes/uso terapéutico , Unidades de Cuidados Intensivos , Respiración ArtificialRESUMEN
BACKGROUND: Lymphatic complications are common in patients with Fontan circulation. Three-dimensional balanced steady-state free precession (3D bSSFP) angiography by cardiovascular magnetic resonance (CMR) is widely used for cardiovascular anatomical assessment. We sought to determine the frequency of thoracic duct (TD) visualization using 3D bSSFP images and assess whether TD characteristics are associated with clinical outcomes. METHODS: This was a retrospective, single-center study of patients with Fontan circulation who underwent CMR. Frequency matching of age at CMR was used to construct a comparison group of patients with repaired tetralogy of Fallot (rTOF). TD characteristics included maximum diameter and a qualitative assessment of tortuosity. Clinical outcomes included protein-losing enteropathy (PLE), plastic bronchitis, listing for heart transplantation, and death. A composite outcome was defined as presence of any of these events. RESULTS: The study included 189 Fontan patients (median age 16.1 years, IQR 11.0-23.2 years) and 36 rTOF patients (median age 15.7 years, IQR 11.1-23.7 years). The TD diameter was larger (median 2.50 vs. 1.95 mm, p = 0.002) and more often well visualized (65% vs. 22%, p < 0.001) in Fontan patients vs. rTOF patients. TD dimension increased mildly with age in Fontan patients, R = 0.19, p = 0.01. In Fontan patients, the TD diameter was larger in those with PLE vs. without PLE (age-adjusted mean 4.11 vs. 2.72, p = 0.005), and was more tortuous in those with NYHA class ≥ II vs. class I (moderate or greater tortuosity 75% vs. 28.5%, p = 0.02). Larger TD diameter was associated with a lower ventricular ejection fraction that was independent of age (partial correlation = - 0.22, p = 0.02). More tortuous TDs had a higher end-systolic volume (mean 70.0 mL/m2 vs. 57.3 mL/m2, p = 0.03), lower creatinine (mean 0.61 mg/dL vs. 0.70 mg/dL, p = 0.04), and a higher absolute lymphocyte count (mean 1.80 K cells/µL vs. 0.76 K cells/µL, p = 0.003). The composite outcome was present in 6% of Fontan patients and was not associated with TD diameter (p = 0.50) or tortuosity (p = 0.09). CONCLUSIONS: The TD is well visualized in two-thirds of patients with Fontan circulation on 3D-bSSFP images. Larger TD diameter is associated with PLE and increased TD tortuosity is associated with an NYHA class ≥ II.
Asunto(s)
Procedimiento de Fontan , Tetralogía de Fallot , Humanos , Adolescente , Conducto Torácico/diagnóstico por imagen , Procedimiento de Fontan/efectos adversos , Estudios Retrospectivos , Valor Predictivo de las Pruebas , Espectroscopía de Resonancia MagnéticaRESUMEN
Optimal reverse remodeling of the right ventricle (RV), a sentinel goal of pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot, is not fully predicted by volume-based pre-PVR parameters. Our objectives were to characterize novel geometric RV parameters in patients receiving PVR and in controls, and to identify associations between these parameters and chamber remodeling post-PVR. Secondary analysis was performed on cardiac magnetic resonance (CMR) data from 60 patients enrolled in a randomized trial of PVR with and without surgical RV remodeling. 20 healthy age-matched subjects served as controls. The primary outcome was optimal post-PVR RV remodeling (end-diastolic volume index (EDVi) ≤ 114 ml/m2 and ejection fraction (EF) ≥ 48%) vs. suboptimal remodeling (EDVi ≥ 120 ml/m2 and EF ≤ 45%). RV geometry was markedly different at baseline in PVR patients compared with controls, with lower systolic surface area-to-volume ratio (SAVR) (1.16 ± 0.26 vs.1.44 ± 0.21 cm2/mL, p < 0.001) and lower systolic circumferential curvature (0.87 ± 0.27 vs. 1.07 ± 0.30 cm- 1, p = 0.007) but similar longitudinal curvature. In the PVR cohort, higher systolic SAVR was associated with higher RVEF both pre- and post-PVR (p < 0.001). Among PVR patients, 15 had optimal and 19 had suboptimal remodeling post-PVR. Multivariable modeling showed that among the geometric parameters, higher systolic SAVR (OR 1.68 per 0.1 cm2/mL increase; p = 0.049) and shorter systolic RV long-axis length (OR 0.92 per 0.1 cm increase; p = 0.035) were independently associated with optimal remodeling. Compared with controls, PVR patients have lower SAVR and lower circumferential but not longitudinal curvature. Higher pre-PVR systolic SAVR is associated with optimal remodeling post-PVR.
Asunto(s)
Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Pulmonar , Válvula Pulmonar , Tetralogía de Fallot , Humanos , Válvula Pulmonar/diagnóstico por imagen , Válvula Pulmonar/cirugía , Insuficiencia de la Válvula Pulmonar/diagnóstico por imagen , Insuficiencia de la Válvula Pulmonar/cirugía , Insuficiencia de la Válvula Pulmonar/complicaciones , Resultado del Tratamiento , Función Ventricular Derecha , Remodelación VentricularRESUMEN
Background: Accurate measurement of ventricular volumes is an important clinical imaging goal. Three-dimensional echocardiography (3DEcho) is used increasingly as it is more available and less costly than cardiac magnetic resonance (CMR). For the right ventricle (RV), the current practice is to acquire 3DEcho volumes from the apical view. However, in some patients the RV may be better seen from the subcostal view. Therefore, this study compared RV volume measurements from the apical vs. the subcostal view, using CMR as a reference standard. Methods: Patients <18 years old undergoing a clinical CMR examination were prospectively enrolled. 3DEcho was performed on the day of the CMR. 3DEcho images were acquired with Philips Epic 7 ultrasound system from apical and subcostal views. Offline analysis was performed with TomTec 4DRV Function for 3DEcho images and cvi42 for CMR ones. RV end-diastolic volume and end-systolic volume were collected. Agreement between 3DEcho and CMR was assessed with Bland-Altman analysis and the intraclass correlation coefficient (ICC). Percentage (%) error was calculated using CMR as the reference standard. Results: Forty-seven patients were included in the analysis (age range 10 months to 16 years). The ICC was moderate to excellent for all volume comparisons to CMR (subcostal vs. CMR: end-diastolic volume 0.93, end-systolic volume 0.81; apical vs. CMR: end-diastolic volume 0.94, end-systolic volume 0.74).The 3DEcho mean % error vs. CMR for end-systolic volume was 25% for subcostal and 31% for apical; for end-diastolic volume it was 15% for subcostal and 16% for apical. The % error was not significantly different between apical vs. subcostal views for end-systolic and end-diastolic volume measurements. Conclusions: For apical and subcostal views, 3DEcho-derived ventricular volumes agree well with CMR. Neither echo view has a consistently smaller error when compared to CMR volumes. Accordingly, the subcostal view can be used as an alternative to the apical view when acquiring 3DEcho volumes in pediatric patients, particularly when the image quality from this window is superior.