RESUMEN
We used a nationally representative database of the US, which included 1995 myocarditis cases, among whom 620 children had COVID-19. While the risk of in-hospital mortality was not higher, illness severity and length of hospital stay were higher in patients with myocarditis and COVID-19 than those without COVID-19.
Asunto(s)
COVID-19 , Miocarditis , Humanos , Niño , Miocarditis/terapia , Tiempo de InternaciónRESUMEN
BACKGROUND: COVID-19 infection is generally regarded as an acute self-limiting illness in children, but it can cause significant morbidity and mortality in both healthy and high-risk children. There are limited data on the outcomes of children with congenital heart disease (CHD) and COVID-19. This study aimed to examine the risks of mortality, in-hospital cardiovascular and non-cardiovascular complications in this patient population. METHODS: We analyzed data from hospitalized pediatric patients from 2020 using the nationally representative National Inpatient Sample (NIS). Children hospitalized for COVID-19 were included, and weighted data were used to compare in-hospital mortality and morbidities between children with and without CHD. RESULTS: Out of 36,690 children admitted with a diagnosis of COVID-19 infection(ICD-10 code:U07.1 and B97.29) during calendar year 2020, 1240 (3.4%) had CHD. The risk of mortality in children with CHD was not significantly higher than those without CHD(1.2% vs. 0.8%, p = 0.50), with adjusted OR (aOR) of 1.7 (95% CI: 0.6-5.3). Tachyarrhythmias and heart block were more likely in CHD children with an aOR of 4.2 (95% CI: 1.8-9.9) and aOR of 5.0 (95% CI: 2.4-10.8), respectively. Similarly, respiratory failure [aOR = 2.0 (1.5-2.8)], respiratory failure requiring non-invasive mechanical ventilation [aOR = 2.7 (1.4-5.2)] and invasive mechanical ventilation [aOR = 2.6 (1.6-4.0)], and acute kidney injury [aOR = 3.4 (2.2-5.4)] were all significantly higher among patients with CHD. Median length of hospital stay in children with CHD was longer than those without CHD [5 days (IQR: 2-11) vs. 3 days (IQR: 2-5), p = < 0.001]. CONCLUSIONS: Children with CHD hospitalized with COVID-19 infection were at increased risk of serious cardiovascular and non-cardiovascular adverse clinical outcomes. They also had increased length of hospital stay and utilization of healthcare resources.
Asunto(s)
COVID-19 , Cardiopatías Congénitas , Insuficiencia Respiratoria , Niño , Humanos , COVID-19/terapia , COVID-19/complicaciones , Hospitalización , Tiempo de Internación , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/epidemiología , Insuficiencia Respiratoria/complicacionesRESUMEN
BACKGROUND: The new bronchopulmonary dysplasia (BPD) grading system was developed based on its correlation with long-term respiratory and neurodevelopmental outcomes and may provide better personalized prognostication. Identifying early-life predictors for accurate BPD grade prediction may allow interventions to be tailored to individual needs. This study aimed to assess whether oxygenation index (OI) dynamics in the first three weeks of life are a predictor of BPD grade. METHODS: A single-center retrospective study was performed. Generalized additive mixed modeling was used to model OI trajectories for each BPD grade subgroup. A multinomial regression model was then developed to quantify the association between OI dynamics and BPD grade. RESULTS: Two hundred fifty-four infants were identified for inclusion in the trajectory modeling. A total of 6,243 OI data points were available for modeling. OI trajectory estimates showed distinct patterns in the three groups, most prominent during the third week of life. The average daily OI change was -0.33 ± 0.52 (n = 85) in the No-BPD group, -0.04 ± 0.75 (n = 82) in the Low-Grade BPD group, and 0.22 ± 0.65 (n = 75) in the High-Grade BPD group (p < 0.001). A multinomial regression analysis showed the initial OI value and the average daily OI change both independently correlated with BPD grade outcomes after adjusting for birth gestation, birth weight z-score, sex, and the duration of invasive ventilation. CONCLUSION: Early-life OI dynamics may be a useful independent marker for BPD grade prediction. Prospective studies may be warranted to further validate the findings.
Asunto(s)
Displasia Broncopulmonar , Enfermedades del Prematuro , Lactante , Recién Nacido , Humanos , Displasia Broncopulmonar/diagnóstico , Recien Nacido Prematuro , Estudios Retrospectivos , Estudios Prospectivos , Edad GestacionalRESUMEN
BACKGROUND: Bronchopulmonary dysplasia (BPD) is one of the most common and serious sequelae of prematurity. Prompt diagnosis using prediction tools is crucial for early intervention and prevention of further adverse effects. This study aims to develop a BPD-free survival prediction tool based on the concept of the developmental origin of BPD with machine learning. METHODS: Datasets comprising perinatal factors and early postnatal respiratory support were used for initial model development, followed by combining the two models into a final ensemble model using logistic regression. Simulation of clinical scenarios was performed. RESULTS: Data from 689 infants were included in the study. We randomly selected data from 80% of infants for model development and used the remaining 20% for validation. The performance of the final model was assessed by receiver operating characteristics which showed 0.921 (95% CI: 0.899-0.943) and 0.899 (95% CI: 0.848-0.949) for the training and the validation datasets, respectively. Simulation data suggests that extubating to CPAP is superior to NIPPV in BPD-free survival. Additionally, successful extubation may be defined as no reintubation for 9 days following initial extubation. CONCLUSIONS: Machine learning-based BPD prediction based on perinatal features and respiratory data may have clinical applicability to promote early targeted intervention in high-risk infants.
Asunto(s)
Displasia Broncopulmonar , Enfermedades del Prematuro , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/prevención & control , Femenino , Retardo del Crecimiento Fetal , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Aprendizaje AutomáticoRESUMEN
BACKGROUND: Pediatric myocarditis is a rare disease with substantial mortality. Little is known regarding its prognostic factors. We hypothesize that certain comorbidities and procedural needs may increase risks of poor outcomes. This study aims to identify prognostic factors for pediatric myocarditis. METHODS: The national Kids' Inpatient Database was used in the study. A random forests algorithm was implemented for mortality prediction based on comorbidities and procedures. Linear regression analysis was then performed to quantify their associations with mortality and length of stay. RESULTS: The prevalence of pediatric myocarditis among all pediatric hospitalizations doubled from 2003 to 2016. The mortality rate peaked in 2006 (6.7%) and declined steadily thereafter, with a rate of 3.2% in 2016. Brain injury (including encephalopathy, cerebral edema, and intracranial hemorrhage), acute kidney injury, dysrhythmias, coagulopathy, sepsis, and ECMO use were all independent prognostic factors associated with increased mortality and prolonged hospital stay. CONCLUSION: Prognostic factor identification may not be straightforward in rare diseases such as pediatric myocarditis due to small cohort size in each treating facility. Findings from this report provide insights into the prognostic factors for pediatric myocarditis, and may allow clinicians to be better prepared when informing patients and their families regarding disease outcomes. IMPACT: The rate of hospitalization due to pediatric myocarditis was increasing but the mortality rate was declining over the past decade. End organ damage, including the brain and the kidney, was associated with mortality and prolonged hospital stay in pediatric myocarditis. Tachyarrhythmias and cardiac function compromise requiring ECMO were also associated with mortality and prolonged hospital stay. A data science approach combining machine learning algorithms and conventional regression modeling using a large dataset may facilitate risk factor identification and outcome correlation in rare diseases, as illustrated in this study.
Asunto(s)
Aprendizaje Automático , Miocarditis/epidemiología , Edad de Inicio , Comorbilidad , Minería de Datos , Bases de Datos Factuales , Humanos , Tiempo de Internación , Miocarditis/diagnóstico , Miocarditis/mortalidad , Miocarditis/terapia , Prevalencia , Pronóstico , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Young children and those with chronic medical conditions are at risk for complications of influenza including cardiopulmonary compromise. Here we aim to examine risks of mortality, clinical complications in children with congenital heart disease (CHD) hospitalized for influenza. METHODS: We analyzed data from in-hospital pediatric patients from 2003, 2006, 2009, 2012 and 2016 using the nationally representative Kids Inpatient Database (KID). We included children 1 year and older and used weighted data to compare the incidence of in-hospital mortality and rates of complications such as respiratory failure, acute kidney injury, need for mechanical ventilation, arrhythmias and myocarditis. RESULTS: Data from the KID estimated 125,470 children who were admitted with a diagnosis of influenza infection. Out of those, 2174(1.73%) patients had discharge diagnosis of CHD. Children with CHD who required hospitalization for influenza had higher in-hospital mortality (2.0% vs 0.5%), with an adjusted OR (aOR) of 2.8 (95% CI: 1.7-4.5). Additionally, acute respiratory failure and acute kidney failure were more likely among patients with CHD, with aOR of 1.8 (95% CI: 1.5-2.2) and aOR of 2.2 (95% CI: 1.5-3.1), respectively. Similarly, the rate of mechanical ventilatory support was higher in patients with CHD compared to those without, 14.1% vs 5.6%, aOR of 1.9 (95% CI: 1.6-2.3). Median length of hospital stay in children with CHD was longer than those without CHD [4 (IQR: 2-8) days vs. 2 (IQR: 2-4) days]. Outcomes were similar between those with severe vs non-severe CHD. CONCLUSIONS: Children with CHD who require hospital admission for influenza are at significantly increased risk for in-hospital mortality, morbidities, emphasizing the need to reinforce preventative measures (e.g. vaccination, personal hygiene) in this particularly vulnerable population.
Asunto(s)
Cardiopatías Congénitas , Gripe Humana , Niño , Preescolar , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/epidemiología , Mortalidad Hospitalaria , Hospitalización , Humanos , Lactante , Gripe Humana/complicaciones , Gripe Humana/epidemiología , Tiempo de InternaciónRESUMEN
The polarity and organization of radial glial cells (RGCs), which serve as both stem cells and scaffolds for neuronal migration, are crucial for cortical development. However, the cytoskeletal mechanisms that drive radial glial outgrowth and maintain RGC polarity remain poorly understood. Here, we show that the Arp2/3 complex - the unique actin nucleator that produces branched actin networks - plays essential roles in RGC polarity and morphogenesis. Disruption of the Arp2/3 complex in murine RGCs retards process outgrowth toward the basal surface and impairs apical polarity and adherens junctions. Whereas the former is correlated with an abnormal actin-based leading edge, the latter is consistent with blockage in membrane trafficking. These defects result in altered cell fate, disrupted cortical lamination and abnormal angiogenesis. In addition, we present evidence that the Arp2/3 complex is a cell-autonomous regulator of neuronal migration. Our data suggest that Arp2/3-mediated actin assembly might be particularly important for neuronal cell motility in a soft or poorly adhesive matrix environment.
Asunto(s)
Complejo 2-3 Proteico Relacionado con la Actina/metabolismo , Células Ependimogliales/citología , Complejo 2-3 Proteico Relacionado con la Actina/genética , Animales , Apoptosis/genética , Apoptosis/fisiología , Movimiento Celular/genética , Movimiento Celular/fisiología , Polaridad Celular/genética , Polaridad Celular/fisiología , Proliferación Celular/genética , Proliferación Celular/fisiología , Células Ependimogliales/metabolismo , Ratones , Morfogénesis/genética , Morfogénesis/fisiología , Neurogénesis/genética , Neurogénesis/fisiología , Neuronas/citología , Neuronas/metabolismoRESUMEN
Originating from ectodermal epithelium, radial glial cells (RGCs) retain apico-basolateral polarity and comprise a pseudostratified epithelial layer in the developing cerebral cortex. The apical endfeet of the RGCs faces the fluid-filled ventricles, while the basal processes extend across the entire cortical span towards the pial surface. RGC functions are largely dependent on this polarized structure and the molecular components that define it. In this review, we will dissect existing molecular evidence on RGC polarity establishment and during cerebral cortex development and provide our perspective on the remaining key questions.
Asunto(s)
Polaridad Celular , Corteza Cerebral/metabolismo , Ectodermo/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas del Tejido Nervioso/genética , Neuroglía/metabolismo , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/ultraestructura , Uniones Adherentes/metabolismo , Uniones Adherentes/ultraestructura , Animales , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Corteza Cerebral/citología , Corteza Cerebral/crecimiento & desarrollo , Ventrículos Cerebrales/citología , Ventrículos Cerebrales/crecimiento & desarrollo , Ventrículos Cerebrales/metabolismo , Ectodermo/citología , Ectodermo/crecimiento & desarrollo , Embrión de Mamíferos , Epitelio/crecimiento & desarrollo , Epitelio/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/ultraestructura , Humanos , Proteínas del Tejido Nervioso/metabolismo , Neuroglía/citología , Piamadre/citología , Piamadre/crecimiento & desarrollo , Piamadre/metabolismoRESUMEN
Left axis deviation (LAD) in children is rare but may be associated with structural heart disease. The aim of this study is to systematically assess the significance of LAD in the pediatric population. We included studies listed in PubMed, EMBASE, Web of Science, Cochrane databases, and Google Scholar before May 31, 2018 and their reference lists. Nine selected studies were grouped into two categories: (1) prevalence of heart diseases in children with LAD on ECG and (2) prevalence of LAD in children with healthy hearts. Two authors independently extracted data using a standardized data extraction form. We identified nine studies including 7514 subjects. Among children with LAD, 66.3% (95% CI 36.9-86.9%) had heart disease. There was heterogeneity amongst studies with Q-value of 142.5 and I2 of 97.2%. The mean LAD rate was 1.6% in children with healthy hearts with 95% CI (0.4-2.2%) with Q-value of 11.8, I2 66.3% and T 0.34 with p value of 0.018. The limitation of study is that the included studies spanned 7 decades from the 1950s to 2018. Primary diagnostic modalities have evolved over time and the definition of LAD also varied among studies. In conclusion, LAD is associated with children with heart diseases, but may also be observed in healthy children. The degree of LAD axis correlated with the likelihood of congenital heart disease (CHD). Physical examination is crucial for identifying CHD in individuals with LAD.
Asunto(s)
Electrocardiografía , Cardiopatías/diagnóstico , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Cardiopatías/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Prevalencia , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUND: Kawasaki disease is an acute vasculitis of childhood and is the leading cause of acquired heart disease in the developed countries. METHODS: Data from hospital discharge records were obtained from the National Kids Inpatient Database for years 2009 and 2012. Hospitalisations by months, hospital regions, timing of admission, insurance types, and ethnicity were analysed. Length of stay and total charges were also analysed. RESULTS: There were 10,486 cases of Kawasaki disease from 12,678,005 children hospitalisation. Kawasaki disease was more common between 0 and 5 years old, in male, and in Asian. The January-March quarter had the highest rate compared to the lowest in the July-September quarter (OR=1.62, p < 0.001). Admissions on the weekend had longer length of stay [4.1 days (95 % CI: 3.97-4.31)] as compared to admissions on a weekday [3.72 days (95 % CI: 3.64-3.80), p < 0.001]. Blacks had the longest length of stay and whites had the shortest [4.33 days (95 % CI: 4.12-4.54 days) versus 3.60 days (95 % CI: 3.48-3.72 days), p < 0.001]. Coronary artery aneurysm was identified in 2.7 % of all patients with Kawasaki disease. Children with coronary artery aneurysm were hospitalised longer and had higher hospital charge. Age, admission during weekend, and the presence of coronary artery aneurysm had significant effect on the length of stay. CONCLUSIONS: This report provides the most updated epidemiological information on Kawasaki disease hospitalisation. Age, admissions during weekend, and the presence of coronary artery aneurysm are significant contributors to the length of stay.
Asunto(s)
Costo de Enfermedad , Tiempo de Internación/tendencias , Síndrome Mucocutáneo Linfonodular/epidemiología , Preescolar , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria/tendencias , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Síndrome Mucocutáneo Linfonodular/economía , Síndrome Mucocutáneo Linfonodular/terapia , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Junctional ectopic tachycardia is a serious tachyarrhythmic complication following pediatric cardiac surgery. It is difficult to manage and is associated with significant morbidity and mortality. Conventional nonpharmacological and pharmacological measures have shown limited effects. Dexmedetomidine is an α2 agonist which has recently been shown in multiple studies to be effective. AIMS: The aim of this systematic review with meta-analysis was to evaluate the efficacy of prophylactic dexmedetomidine administration in the prevention of junctional ectopic tachycardia in pediatric patients following cardiac surgeries. METHODS: We searched MEDLINE, EMBASE, Cochrane, Web of Science, and relevant references published in English before December 20, 2017 and performed meta-analysis on the selected studies, with one group receiving prophylactic perioperative dexmedetomidine administration and another group receiving placebo. The primary outcome was the incidence of junctional ectopic tachycardia, secondary outcomes included bradycardia, hypotension, intensive care unit stay, total hospital stay, inotropic scores, and total mechanical ventilation time. Odds ratio or mean difference with 95% confidence intervals were calculated using a random effect model. RESULTS: Seven studies (5 prospective randomized studies and 2 retrospective case-controlled studies) with a total of 1616 patients were analyzed. The incidence of junctional ectopic tachycardia in the dexmedetomidine group was significantly reduced compared to placebo. Similarly, intensive care unit stay, inotropic scores, and total mechanical ventilation time were also significantly decreased in the dexmedetomidine group. No significant increases in adverse events were found. Mortality was low in both groups. CONCLUSION: Prophylactic dexmedetomidine is effective in reducing the incidence of postoperative junctional ectopic tachycardia without significant increases in adverse events in pediatric patients undergoing surgery for congenital heart diseases.
Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Procedimientos Quirúrgicos Cardíacos , Dexmedetomidina/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Taquicardia Ectópica de Unión/prevención & control , Niño , Preescolar , Humanos , Lactante , Pediatría/métodos , Resultado del TratamientoRESUMEN
As acute myeloid leukemia (AML) xenograft models improve, the potential for using them to evaluate novel therapeutic strategies becomes more appealing. Currently, there is little information on using standard chemotherapy regimens in AML xenografts. Here we have characterized the immunodeficient mouse response to combined Ara-C (cytarabine) and doxorubicin treatment. We observed significant toxicity associated with doxorubicin that required optimization of the route of injection as well as the maximum-tolerated dose for immunodeficient strains. Mice treated with an optimized 5-day induction protocol showed transient weight loss, short-term reduction of peripheral blood cell and platelet counts, and slight anemia. Considerable cytotoxicity was observed in the bone marrow (BM), with primitive LSK cells having a significant survival advantage relative to more mature cells, consistent with the idea of chemotherapy targeting actively growing cells. Treated leukemic mice demonstrated reduced disease burden and increased survival, demonstrating efficacy. AML cells showed significantly increased sensitivity to doxorubicin-containing therapy compared with murine BM cells. Although early treatment could result in some cures, mice with significant leukemia grafts were not cured by using induction therapy alone. Overall, the data show that this model system is useful for the evaluation of novel chemotherapies in combination with standard induction therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Leucemia Mieloide Aguda/tratamiento farmacológico , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Línea Celular Tumoral , Citarabina/administración & dosificación , Doxorrubicina/administración & dosificación , Vías de Administración de Medicamentos , Resistencia a Antineoplásicos/fisiología , Hematopoyesis/efectos de los fármacos , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/patología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones SCID , Ratones Transgénicos , Resultado del TratamientoRESUMEN
AML1-ETO (AE) is a fusion product of translocation (8;21) that accounts for 40% of M2 type acute myeloid leukemia (AML). In addition to its role in promoting preleukemic hematopoietic cell self-renewal, AE represses DNA repair genes, which leads to DNA damage and increased mutation frequency. Although this latter function may promote leukemogenesis, concurrent p53 activation also leads to an increased baseline apoptotic rate. It is unclear how AE expression is able to counterbalance this intrinsic apoptotic conditioning by p53 to promote survival and self-renewal. In this report, we show that Bcl-xL is up-regulated in AE cells and plays an essential role in their survival and self-renewal. Further investigation revealed that Bcl-xL expression is regulated by thrombopoietin (THPO)/MPL-signaling induced by AE expression. THPO/MPL-signaling also controls cell cycle reentry and mediates AE-induced self-renewal. Analysis of primary AML patient samples revealed a correlation between MPL and Bcl-xL expression specifically in t(8;21) blasts. Taken together, we propose that survival signaling through Bcl-xL is a critical and intrinsic component of a broader self-renewal signaling pathway downstream of AML1-ETO-induced MPL.
Asunto(s)
Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Leucemia Mieloide Aguda/patología , Proteínas de Fusión Oncogénica/metabolismo , Preleucemia/metabolismo , Preleucemia/patología , Receptores de Trombopoyetina/metabolismo , Trombopoyetina/metabolismo , Proteína bcl-X/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Western Blotting , Ciclo Celular , Diferenciación Celular , Proliferación Celular , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Sangre Fetal/citología , Sangre Fetal/metabolismo , Feto/citología , Feto/metabolismo , Citometría de Flujo , Perfilación de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Hígado/citología , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones SCID , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas de Fusión Oncogénica/genética , ARN Mensajero/genética , Proteína 1 Compañera de Translocación de RUNX1 , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Trombopoyetina/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Trombopoyetina/genética , Proteína bcl-X/genéticaRESUMEN
OBJECTIVE: To assess the association between antenatal corticosteroids exposure and postnatal growth in infants born at 23-29 weeks' gestation. STUDY DESIGN: This retrospective study used data from the Pediatrix Clinical Data Warehouse. Maternal-infant dyads from 2018 to 2020 were included. Inverse propensity weighting (IPW) was applied to balance pre-treatment confounders. Primary outcomes included postnatal weight, length, and head circumference growth trajectory percentiles. RESULT: The unadjusted cohort consisted of 11,912 dyads. After IPW adjustment, there were 23,231 dyads. Exposed infants showed higher postnatal trajectory percentiles for weight (by 3.4%), length (by 1.8%), and head circumference (by 2.5%) when compared to non-exposed infants. The positive association between antenatal corticosteroids and postnatal growth was only observed in infants not exposed to preeclampsia/eclampsia/HELLP syndrome or without fetal growth restriction. CONCLUSION: Antenatal corticosteroids exposure is associated with better postnatal growth. The study is limited by its retrospective nature.
Asunto(s)
Corticoesteroides , Efectos Tardíos de la Exposición Prenatal , Lactante , Embarazo , Humanos , Femenino , Estudios Retrospectivos , Corticoesteroides/efectos adversos , Edad Gestacional , CefalometríaRESUMEN
BACKGROUND: Patient reviews (PRs) have emerged as a method to assess patient experiences with healthcare in order to improve the quality of care. Both institutional and third-party organizations collect quantitative data and comments from these patient surveys, usually accessible to the public for review. Our study examined dermatologists' perceptions of PRs and assessed their impact on dermatologists. METHODS: A survey was sent to the Association of Professors of Dermatology listserv (response rate 30%). RESULTS: Most respondents disagreed with the statements that PRs are good for doctors (63%), good for patients (58%), helpful for doctors (58%), or that high PRs indicate being a good doctor (65%). The majority disagreed that PRs should be available publicly (60%). Respondents agreed that PRs contribute to depersonalization (60%), energy depletion or exhaustion (55%), added stress at work (70%), negativism/cynicism about work (60%), and diminished professional efficacy (29%). Self-identified female respondents were more likely to agree that PRs added stress to work compared to self-identified males (66% vs. 42%, P < 0.05). CONCLUSIONS: Overall, these findings suggest that PRs may negatively impact dermatologists' well-being and perceived stress levels.
Asunto(s)
Dermatólogos , Dermatología , Masculino , Humanos , Femenino , Encuestas y Cuestionarios , Atención a la Salud , OrganizacionesRESUMEN
OBJECTIVES: The impact of exclusive human milk diet (EHMD) on postnatal growth remains controversial. This study aims to investigate the association between EHMD and short-term growth. METHODS: This multicenter retrospective study aims to compare growth between the EHMD and non-EHMD groups among infants <32 weeks of gestation. Primary outcomes include weight, length, and head circumference growth trajectories between birth and 34 weeks postmenstrual age. Sensitivity and subgroup analyses were performed. RESULTS: An EHMD was independently associated with poorer length growth, especially in infants born at ≥28 weeks' gestation or those exposed to hypertensive disorders of pregnancy. While initiating fortification at <26 kcal/oz on an EHMD showed inferior growth, initiating fortification at ≥26 kcal/oz was associated with improved weight growth, and similar length and head circumference growth when compared to the non-EHMD group. CONCLUSIONS: An EHMD with initial fortification at ≥26 kcal/oz may be implemented to avoid bovine milk exposure while sustaining comparable growth.
RESUMEN
AML1-ETO (AE) is a fusion product of t(8;21) observed in 40% French-American-British M2 type of acute myeloid leukemia (AML). Clinical data suggest that Ras mutation is a frequent cooperating event in t(8;21) AML. Whether constitutively active Ras promotes leukemogenesis on the t(8;21) background has not been demonstrated experimentally. Here, we retrovirally expressed N-Ras(G12D) in AE-expressing human hematopoietic cells to investigate cooperativity. The AE/N-Ras(G12D) cultures were cytokine-independent, enriched for CD34 positivity, and possessed increased colony-forming and replating abilities. N-Ras(G12D) expression led to Bcl-2 up-regulation and reduced apoptosis. Ectopic Bcl-2 expression also resulted in enhanced colony-forming and replating abilities but was insufficient to sustain cytokine independence. AE/N-Ras(G12D) cells were more sensitive to Bcl-2 inhibition with ABT-737 than parent AE cells. Enhanced engraftment of AE/N-Ras(G12D) cells was observed on intrafemoral injection into immunodeficient mice, presumably because of improved survival in the bone marrow microenvironment. N-Ras(G12D) promotes progression toward transformation in AE-expressing cells, partially through up-regulating Bcl-2.
Asunto(s)
Transformación Celular Neoplásica/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Sangre Fetal/citología , Sangre Fetal/metabolismo , Genes ras , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Mutación , Proteínas de Fusión Oncogénica/genética , Animales , Diferenciación Celular/genética , Supervivencia Celular/genética , Cocarcinogénesis , Humanos , Leucemia Mieloide Aguda/etiología , Ratones , Modelos Genéticos , Trasplante de Neoplasias , Preleucemia/etiología , Preleucemia/genética , Preleucemia/patología , Proteína 1 Compañera de Translocación de RUNX1 , Transducción Genética , Trasplante HeterólogoRESUMEN
The Rac family of small Rho GTPases coordinates diverse cellular functions in hematopoietic cells including adhesion, migration, cytoskeleton rearrangements, gene transcription, proliferation, and survival. The integrity of Rac signaling has also been found to critically regulate cellular functions in the initiation and maintenance of hematopoietic malignancies. Using an in vivo gene targeting approach, we demonstrate that Rac2, but not Rac1, is critical to the initiation of acute myeloid leukemia in a retroviral expression model of MLL-AF9 leukemogenesis. However, loss of either Rac1 or Rac2 is sufficient to impair survival and growth of the transformed MLL-AF9 leukemia. Rac2 is known to positively regulate expression of Bcl-2 family proteins toward a prosurvival balance. We demonstrate that disruption of downstream survival signaling through antiapoptotic Bcl-2 proteins is implicated in mediating the effects of Rac2 deficiency in MLL-AF9 leukemia. Indeed, overexpression of Bcl-xL is able to rescue the effects of Rac2 deficiency and MLL-AF9 cells are exquisitely sensitive to direct inhibition of Bcl-2 family proteins by the BH3-mimetic, ABT-737. Furthermore, concurrent exposure to NSC23766, a small-molecule inhibitor of Rac activation, increases the apoptotic effect of ABT-737, indicating the Rac/Bcl-2 survival pathway may be targeted synergistically.
Asunto(s)
Leucemia Bifenotípica Aguda/tratamiento farmacológico , Leucemia Bifenotípica Aguda/metabolismo , Neuropéptidos/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas de Unión al GTP rac/antagonistas & inhibidores , Aminoquinolinas/farmacología , Animales , Compuestos de Bifenilo/farmacología , Línea Celular Tumoral , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Leucemia Bifenotípica Aguda/genética , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Ratones Transgénicos , Neuropéptidos/deficiencia , Neuropéptidos/genética , Nitrofenoles/farmacología , Piperazinas/farmacología , Pirimidinas/farmacología , Transducción de Señal , Sulfonamidas/farmacología , Trasplante Heterólogo , Proteína bcl-X/genética , Proteínas de Unión al GTP rac/deficiencia , Proteínas de Unión al GTP rac/genética , Proteína de Unión al GTP rac1 , Proteína RCA2 de Unión a GTPRESUMEN
Most growth references for very preterm infants were developed using measurements taken at birth, and were thought to represent intrauterine growth. However, it remains unclear whether the goal of approximating an intrauterine growth rate as stated by the American Academy of Pediatrics is attainable by very preterm infants. Using real-world measurement data from very preterm infants born between 2010 through 2020, we develop models to characterize the patterns of postnatal growth, and compare them to intrauterine growth. By assessing the weight growth rate, we show three phases of postnatal growth not evident in intrauterine growth. Furthermore, postnatal length and head circumference growth exhibit a slow rate after birth, followed by an acceleration. Collectively, postnatal and intrauterine growth are distinctly different. Although postnatal growth models do not represent optimal growth of very preterm infants, they can serve as a practical tool for clinical assessment of growth and for nutrition research.