Breast Milk-Derived Antibodies Impair Vaccine Immunity in Suckling Mice.

Breast milk confers multiple benefits to the neonate, including passive immunity against multiple microorganisms via Abs. However, it remains unclear whether breast milk-derived Abs affect vaccine-induced immunity in the neonate. We evaluated in C57BL/6 and BALB/c mice whether breastfeeding from an mRNA-SARS-CoV-2-vaccinated dam affects vaccine-induced immunity in neonate mice. Using an experimental model that allows the distinction of maternal Abs and neonate Abs based on their allotype, we show that breastfeeding from an immune dam is associated with reduced vaccine immunity in the neonate. Importantly, mice that breastfed from an immune dam showed reduced numbers of plasma cells after vaccination, relative to mice that breastfed from a naive dam. Our subsequent studies using an mRNA-luciferase reporter system show that passive transfer of Abs through breastfeeding accelerates the clearance of vaccine Ag in suckling mice, resulting in reduced Ag availability. Altogether, maternal Abs transferred through breast milk can protect against infectious microorganisms, but they may also interfere with the neonate's response to vaccination by accelerating the clearance of vaccine Ag. These findings are important for understanding the effects of maternal Abs on the neonate's response to vaccines and may provide insights for improving neonatal vaccines.

Time-dependent enhancement of mRNA vaccines by 4-1BB costimulation.

mRNA vaccines have demonstrated efficacy against COVID-19. However, concerns regarding waning immunity and breakthrough infections have motivated the development of next-generation vaccines with enhanced efficacy. In this study, we investigated the impact of 4-1BB costimulation on immune responses elicited by mRNA vaccines in mice. We first vaccinated mice with an mRNA vaccine encoding the SARS-CoV-2 spike antigen like the Moderna and Pfizer-BioNTech vaccines, followed by administration of 4-1BB costimulatory antibodies at various times post-vaccination. Administering 4-1BB costimulatory antibodies during the priming phase did not enhance immune responses. However, administering 4-1BB costimulatory antibodies after 96 hours elicited a significant improvement in CD8 T cell responses, leading to enhanced protection against breakthrough infections. A similar improvement in immune responses was observed with multiple mRNA vaccines, including vaccines against common cold coronavirus, human immunodeficiency virus (HIV), and arenavirus. These findings demonstrate a time-dependent effect by 4-1BB costimulation and provide insights for developing improved mRNA vaccines.

Pre-existing immunity modulates responses to mRNA boosters.

mRNA vaccines are effective in preventing severe COVID-19, but breakthrough infections, emerging variants, and waning immunity warrant the use of boosters. Although mRNA boosters are being implemented, the extent to which pre-existing immunity influences the efficacy of boosters remains unclear. In a cohort of individuals primed with the mRNA-1273 or BNT162b2 vaccines, we report that lower antibody levels before boost are associated with higher fold-increase in antibody levels after boost, suggesting that pre-existing antibody modulates the immunogenicity of mRNA vaccines. Our studies in mice show that pre-existing antibodies accelerate the clearance of vaccine antigen via Fc-dependent mechanisms, limiting the amount of antigen available to prime B cell responses after mRNA boosters. These data demonstrate a "tug of war" between pre-existing antibody responses and de novo B cell responses following mRNA vaccination, and they suggest that transient downmodulation of antibody effector function may improve the efficacy of mRNA boosters.

Improved control of SARS-CoV-2 by treatment with a nucleocapsid-specific monoclonal antibody.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main antigen in all approved COVID-19 vaccines and is also the only target for monoclonal antibody (mAb) therapies. Immune responses to other viral antigens are generated after SARS-CoV-2 infection, but their contribution to the antiviral response remains unclear. Here, we interrogated whether nucleocapsid-specific antibodies can improve protection against SARS-CoV-2. We first immunized mice with a nucleocapsid-based vaccine and then transferred sera from these mice into naive mice, followed by challenge with SARS-CoV-2. We show that mice that received nucleocapsid-specific sera or a nucleocapsid-specific mAb exhibited enhanced control of SARS-CoV-2. Nucleocapsid-specific antibodies elicited NK-mediated, antibody-dependent cellular cytotoxicity (ADCC) against infected cells. To our knowledge, these findings provide the first demonstration in the coronavirus literature that antibody responses specific to the nucleocapsid protein can improve viral clearance, providing a rationale for the clinical evaluation of nucleocapsid-based mAb therapies to treat COVID-19.

Adoptive B cell therapy for chronic viral infection.

T cell-based therapies have been widely explored for the treatment of cancer and chronic infection, but B cell-based therapies have remained largely unexplored. To study the effect of B cell therapy, we adoptively transferred virus-specific B cells into mice that were chronically infected with lymphocytic choriomeningitis virus (LCMV). Adoptive transfer of virus-specific B cells resulted in increase in antibody titers and reduction of viral loads. Importantly, the efficacy of B cell therapy was partly dependent on antibody effector functions, and was improved by co-transferring virus-specific CD4 T cells. These findings provide a proof-of-concept that adoptive B cell therapy can be effective for the treatment of chronic infections, but provision of virus-specific CD4 T cells may be critical for optimal virus neutralization.

Pre-existing immunity modulates responses to mRNA boosters.

mRNA vaccines have shown high efficacy in preventing severe COVID-19, but breakthrough infections, emerging variants and waning antibody levels have warranted the use of boosters. Although mRNA boosters have been widely implemented, the extent to which pre-existing immunity influences the efficacy of boosters remains unclear. In a cohort of individuals primed with the mRNA-1273 or BNT162b2 vaccines, we observed that lower antibody levels before boost were associated with higher fold-increase in antibody levels after boost, suggesting that pre-existing antibody modulates the boosting capacity of mRNA vaccines. Mechanistic studies in mice show that pre-existing antibodies significantly limit antigen expression and priming of B cell responses after mRNA vaccination. Furthermore, we demonstrate that the relative superiority of an updated Omicron vaccine over the original vaccine is critically dependent on the serostatus of the host. These data demonstrate that pre-existing immunity dictates responses to mRNA vaccination, elucidating specific circumstances when updated SARS-CoV-2 vaccines confer superior protection to original vaccines.

Fractionating a COVID-19 Ad5-vectored vaccine improves virus-specific immunity.

SARS-CoV-2 has caused a global pandemic that has infected more than 250 million people worldwide. Although several vaccine candidates have received emergency use authorization, there is still limited knowledge on how vaccine dosing affects immune responses. We performed mechanistic studies in mice to understand how the priming dose of an adenovirus-based SARS-CoV-2 vaccine affects long-term immunity to SARS-CoV-2. We first primed C57BL/6 mice with an adenovirus serotype 5 vaccine encoding the SARS-CoV-2 spike protein, similar to that used in the CanSino and Sputnik V vaccines. The vaccine prime was administered at either a standard dose or 1000-fold lower dose, followed by a boost with the standard dose 4 weeks later. Initially, the low dose prime induced lower immune responses relative to the standard dose prime. However, the low dose prime elicited immune responses that were qualitatively superior and, upon boosting, exhibited substantially more potent recall and functional capacity. We also report similar effects with a simian immunodeficiency virus (SIV) vaccine. These findings show an unexpected advantage of fractionating vaccine prime doses, warranting a reevaluation of vaccine trial protocols for SARS-CoV-2 and other pathogens.

Cross-protective immunity following coronavirus vaccination and coronavirus infection.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have shown efficacy against SARS-CoV-2, it is unknown if coronavirus vaccines can also protect against other coronaviruses that may infect humans in the future. Here, we show that coronavirus vaccines elicited cross-protective immune responses against heterologous coronaviruses. In particular, we show that a severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) vaccine developed in 2004 and known to protect against SARS-CoV-1 conferred robust heterologous protection against SARS-CoV-2 in mice. Similarly, prior coronavirus infections conferred heterologous protection against distinct coronaviruses. Cross-reactive immunity was also reported in patients with coronavirus disease 2019 (COVID-19) and in individuals who received SARS-CoV-2 vaccines, and transfer of plasma from these individuals into mice improved protection against coronavirus challenges. These findings provide the first demonstration to our knowledge that coronavirus vaccines (and prior coronavirus infections) can confer broad protection against heterologous coronaviruses and establish a rationale for universal coronavirus vaccines.

Limiting the priming dose of a SARS CoV-2 vaccine improves virus-specific immunity.

Since late 2019, SARS-CoV-2 has caused a global pandemic that has infected 128 million people worldwide. Although several vaccine candidates have received emergency use authorization (EUA), there are still a limited number of vaccine doses available. To increase the number of vaccinated individuals, there are ongoing discussions about administering partial vaccine doses, but there is still a paucity of data on how vaccine fractionation affects vaccine-elicited immunity. We performed studies in mice to understand how the priming dose of a SARS CoV-2 vaccine affects long-term immunity to SARS CoV-2. We first primed C57BL/6 mice with an adenovirus-based vaccine encoding SARS CoV-2 spike protein (Ad5-SARS-2 spike), similar to that used in the CanSino and Sputnik V vaccines. This prime was administered either at a low dose (LD) of 10 6 PFU or at a standard dose (SD) of 10 9 PFU, followed by a SD boost in all mice four weeks later. As expected, the LD prime induced lower immune responses relative to the SD prime. However, the LD prime elicited immune responses that were qualitatively superior, and upon boosting, mice that were initially primed with a LD exhibited significantly more potent immune responses. Overall, these data demonstrate that limiting the priming dose of a SARS CoV-2 vaccine may confer unexpected benefits. These findings may be useful for improving vaccine availability and for rational vaccine design.

Impact of outpatient SARS-CoV-2 infections in minority children.

ABSTRACT: Data regarding COVID-19 in the adult population and hospitalized children is rapidly evolving, but little is known about children infected with severe acute respiratory syndrome coronavirus 2 who do not require hospitalization.In an observational, retrospective study we analyzed risk factors, demographics and clinical course of non-hospitalized patients ≤ 21 years of age with COVID-19 infection.Of the 1,796 patients evaluated, 170 were infected, and 40 participated in a telephone survey. Children older >10 years of age (OR: 2.19), Hispanic ethnicity (OR: 3) and residing in counties with higher rates of poverty (OR: 1.5) were associated with higher risk of infection, while older girls were more likely to experience prolonged duration of symptoms (median: 32 days). Consistent with prior reports, fever and cough were present in most of our patients. Shortness of breath, diarrhea, anosmia, and ageusia were more common in our outpatient population than previously reported.Larger studies addressing the clinical and psychosocial impact of CoVID-19 infection in children living in high-risk environments are warranted.

Novel Electrospun Pullulan Fibers Incorporating Hydroxypropyl-ß-Cyclodextrin: Morphology and Relation with Rheological Properties.

Fibers produced by electrospinning from biocompatible, biodegradable and naturally occurring polymers have potential advantages in drug delivery and biomedical applications because of their unique functionalities. Here, electrospun submicron fibers were produced from mixtures containing an exopolysaccharide (pullulan) and a small molecule with hosting abilities, hydroxypropyl-ß-cyclodextrin (HP-ß-CD), thus serving as multi-functional blend. The procedure used water as sole solvent and excluded synthetic polymers. Rheological characterization was performed to evaluate the impact of HP-ß-CD on pullulan entanglement concentration (CE); the relationship with electrospinnability and fiber morphology was investigated. Neat pullulan solutions required three times CE (~20% w/v pullulan) for effective electrospinning and formation of bead-free nanofibers. HP-ß-CD (30% w/v) facilitated electrospinning, leading to the production of continuous, beadless fibers (average diameters: 853-1019 nm) at lower polymer concentrations than those required in neat pullulan systems, without significantly shifting the polymer CE. Rheological, Differential Scanning Calorimetry (DSC) and Dynamic Light Scattering (DLS) measurements suggested that electrospinnability improvement was due to HP-ß-CD assisting in pullulan entanglement, probably acting as a crosslinker. Yet, the type of association was not clearly identified. This study shows that blending pullulan with HP-ß-CD offers a platform to exploit the inherent properties and advantages of both components in encapsulation applications.

Limitaciones en los profesores de Ciencias Médicas de Sancti Spirítus en el desarrollo de investigaciones educativas / Limitations of Medical Sciences professors in Sancti Spirítus in the development of educational research

RESUMEN Fundamento: Las Ciencias Médicas se caracterizan por estudios profesionales en relación a la salud pública y al proceso de salud enfermedad, pero presentan debilidades en la formación del profesional de la Medicina, en el conocimiento y desarrollo de sus habilidades investigativas. Objetivo: Determinar las limitaciones del docente de las Ciencias Médicas en la investigación educativa en el colectivo de primer año de la carrera de Medicina. Metodología: Se realizó un estudio descriptivo de corte transversal; la población estuvo conformada por 30 docentes del colectivo de año, 3 directivos de la facultad el resto profesores principales de las asignaturas. Se realizó el análisis de documentos, la entrevista a directivos, docentes y estudiantes, la encuesta a docentes, y la triangulación de datos en la carrera de Medicina durante el curso 2017-2018 de la Universidad de Ciencias Médicas de Sancti Spíritus. Resultados: Reflejan la formación de un docente concentrado en el contenido de la enseñanza del saber disciplinar, en detrimento de su implicación hacia la investigación educativa, donde el colectivo del año académico no evidencia su potencial formativo. Conclusiones: La actuación del docente de las ciencias médicas se concibe desde lo individual y grupal en el ejercicio docente. Reconociendo que la investigación científica forma parte de sus funciones, pero se inclinan a la materia que imparten y el colectivo de año no los estimula hacia la investigación de los problemas educativos.

ABSTRACT Background: Medical Sciences are characterized by professional studies related to public health and the disease health process, but they present weaknesses in the training of the medical professional, also in the knowledge and development of their research skills. Objective: To determine the limitations of the Medical Sciences professors in the educational research in the first academic year group of the Medicine career. Methodology: A descriptive cross-sectional study was carried out; the population consisted of 30 teachers from the teachers´ academic year group, 3 faculty directors, and the rest, some of the main professors of the subjects. The analysis of documents, the interview with managers, teachers and students, the survey of teachers, and the triangulation of data in the Medicine career during the course 2017-2018 at the Sancti Spíritus University of Medical Sciences were used. Results: The performance of teacher of medical sciences is conceived from both, the individual and the group in the teaching practice. Recognizing that the scientific research is part of their functions, but they are mainly interested into the subject they teach and the teachers´ academic year group does not encourage them to research about educational problems.

Limitaciones en los profesores de Ciencias Médicas de Sancti Spirítus en el desarrollo de investigaciones educativas / Limitations of Medical Sciences professors in Sancti Spirítus in the development of educational research

RESUMEN Fundamento: Las Ciencias Médicas se caracterizan por estudios profesionales en relación a la salud pública y al proceso de salud enfermedad, pero presentan debilidades en la formación del profesional de la Medicina, en el conocimiento y desarrollo de sus habilidades investigativas. Objetivo: Determinar las limitaciones del docente de las Ciencias Médicas en la investigación educativa en el colectivo de primer año de la carrera de Medicina. Metodología: Se realizó un estudio descriptivo de corte transversal; la población estuvo conformada por 30 docentes del colectivo de año, 3 directivos de la facultad el resto profesores principales de las asignaturas. Se realizó el análisis de documentos, la entrevista a directivos, docentes y estudiantes, la encuesta a docentes, y la triangulación de datos en la carrera de Medicina durante el curso 2017-2018 de la Universidad de Ciencias Médicas de Sancti Spíritus. Resultados: Reflejan la formación de un docente concentrado en el contenido de la enseñanza del saber disciplinar, en detrimento de su implicación hacia la investigación educativa, donde el colectivo del año académico no evidencia su potencial formativo. Conclusiones: La actuación del docente de las ciencias médicas se concibe desde lo individual y grupal en el ejercicio docente. Reconociendo que la investigación científica forma parte de sus funciones, pero se inclinan a la materia que imparten y el colectivo de año no los estimula hacia la investigación de los problemas educativos.

ABSTRACT Background: Medical Sciences are characterized by professional studies related to public health and the disease health process, but they present weaknesses in the training of the medical professional, also in the knowledge and development of their research skills. Objective: To determine the limitations of the Medical Sciences professors in the educational research in the first academic year group of the Medicine career. Methodology: A descriptive cross-sectional study was carried out; the population consisted of 30 teachers from the teachers´ academic year group, 3 faculty directors, and the rest, some of the main professors of the subjects. The analysis of documents, the interview with managers, teachers and students, the survey of teachers, and the triangulation of data in the Medicine career during the course 2017-2018 at the Sancti Spíritus University of Medical Sciences were used. Results: The performance of teacher of medical sciences is conceived from both, the individual and the group in the teaching practice. Recognizing that the scientific research is part of their functions, but they are mainly interested into the subject they teach and the teachers´ academic year group does not encourage them to research about educational problems.

Seizure Detection by Critical Care Providers Using Amplitude-Integrated Electroencephalography and Color Density Spectral Array in Pediatric Cardiac Arrest Patients.

OBJECTIVES: Determine the accuracy and confidence of critical care medicine providers to identify seizures using amplitude-integrated electroencephalography versus amplitude-integrated electroencephalography combined with color density spectral array electroencephalography (aEEG + CDSA). DESIGN: Tutorial and questionnaire. SETTING: PICU. SUBJECTS: Pediatric critical care providers (attendings, fellows, and nurses). INTERVENTIONS: A standardized powerpoint tutorial on amplitude-integrated electroencephalography and color density spectral array followed by classification of 100 amplitude-integrated electroencephalography images and 100 amplitude-integrated electroencephalography combined with color density spectral array as displaying seizures or not displaying seizures. MEASUREMENTS AND MAIN RESULTS: Electroencephalography tracings were obtained from children monitored with continuous electroencephalography after cardiac arrest. The gold standard for seizure identification was continuous electroencephalography interpretation by a pediatric electroencephalographer. The same electroencephalography tracings were used to generate images containing only amplitude-integrated electroencephalography or aEEG + CDSA. Twenty-three critical care medicine providers underwent a 30-minute tutorial on amplitude-integrated electroencephalography and color density spectral array interpretation. They were then asked to determine if there were seizures on 100 amplitude-integrated electroencephalography images and 100 aEEG + CDSA. Amplitude-integrated electroencephalography seizure detection sensitivity was 77% (95% CI, 73%-80%), specificity of 65% (95% CI, 62%-67%), negative predictive value of 88% (95% CI, 86%-90%), and positive predictive value of 46% (95% CI, 43%-49%). For aEEG + CDSA, sensitivity was 77% (95% CI, 74%-81%), specificity of 68% (95% CI, 66%-71%), negative predictive value of 89% (95% CI, 87%-90%), and positive predictive value of 49% (95% CI, 46%-52%). Sensitivity for status epilepticus detection was 77% (95% CI, 71%-82%) with amplitude-integrated electroencephalography and 75% (95% CI, 69%-81%) with aEEG + CDSA. The addition of color density spectral array to amplitude-integrated electroencephalography did not improve seizure detection. However, 87% of critical care medicine providers qualitatively felt that combining both modalities increased their ability to detect seizures. CONCLUSIONS: Amplitude-integrated electroencephalography and aEEG + CDSA offer reasonable sensitivity and negative predictive value for seizure detection by critical care medicine providers. aEEG + CDSA did not improve seizure detection over amplitude-integrated electroencephalography alone although critical care medicine providers felt more confident using both tools combined. Amplitude-integrated electroencephalography and color density spectral array require further evaluation as a tool for screening for seizures and should only be used in conjunction with professional continuous electroencephalography review.

Early Electroencephalographic Background Features Predict Outcomes in Children Resuscitated From Cardiac Arrest.

OBJECTIVES: To determine 1) whether early electroencephalographic background features were associated with survival and neurologic outcomes among children resuscitated from cardiac arrest and not treated with therapeutic hypothermia and 2) if addition of electroencephalographic background to commonly used clinical criteria is more predictive of outcome than clinical criteria alone. DESIGN: Retrospective study. SETTING: PICU and Cardiac ICUs of a tertiary children's hospital. PATIENTS: Patients resuscitated from in-hospital or out-of-hospital cardiac arrest who underwent clinically indicated electroencephalographic monitoring and were not treated with therapeutic hypothermia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred twenty-eight patients underwent electroencephalographic monitoring within 1 day of return of spontaneous circulation. Background category was normal in four subjects (3%), slow-disorganized in 58 subjects (45%), discontinuous-burst suppression in 24 subjects (19%) and attenuated-flat in 42 subjects (33%). Forty-six subjects (36%) had a reactive electroencephalography. Twenty subjects (15%) had a seizure during electroencephalographic monitoring. Absence of reactivity (p < 0.001) and seizures (p = 0.04) were associated with worse electroencephalographic background category. After controlling for covariates, for each incrementally worse background score, the odds of death was 3.63 (95% CI, 2.18-6.0; p < 0.001) and the odds of unfavorable neurologic outcome was 4.38 (95% CI, 2.51-7.17; p = 0.001). CONCLUSIONS: Worse electroencephalographic background early after resuscitation from both in-hospital and out-of-hospital cardiac arrest is associated with increased odds of death and unfavorable neurologic outcomes at hospital discharge. These electroencephalographic background patterns may be used in addition to clinical criteria to support prognostic decision making.

Strategies to Maximize Enrollment in a Prospective Study of Comatose Children in the PICU.

OBJECTIVES: To analyze barriers to recruitment encountered during a prospective study in the PICU and evaluate strategies implemented to improve recruitment. DESIGN: Prospective observational study of continuous electroencephalogram monitoring in comatose children. SETTING: PICUs at four North American institutions. PATIENTS: Patients with a Glasgow Coma Scale score of less than or equal to 8 for at least an hour. INTERVENTIONS: Four strategies to increase recruitment were sequentially implemented. MEASUREMENTS AND MAIN RESULTS: The baseline enrollment rate was 2.1 subjects/mo, which increased following the single-site introduction of real-time patient screening using an online dashboard (4.5 subjects/mo), deferred consenting (5.2 subjects/mo), and weekend screening (6.1 subjects/mo). However, the subsequent addition of three new study sites was the greatest accelerator of enrollment (21 subjects/mo), representing a 10-fold increase from baseline (p < 0.0001). CONCLUSIONS: Identifying barriers to recruitment and implementing creative strategies to increase recruitment can successfully increase enrollment rates in the challenging ICU environment.

[Child neurodevelopment: normal characteristics and warning signs in children under five years]. / Neurodesarrollo infantil: características normales y signos de alarma en el niño menor de cinco años.

The development of the nervous system is a complex process that results in the maturation of structures, the acquisition of skills and finally the formation of the individual as a unique person. This review contains information about the main characteristics of the processes of brain development, the characteristics of normal neurological development in different areas: gross and fine motor, language, sensory and socialization; and it is also accompanied by a description of the major changes in the development, identifiable in the daily clinical work of pediatricians. Our goal is to enhance knowledge in this key area of assessment of early childhood to detect problems sufficiently in advance for their timely intervention.

Neurodesarrollo infantil: características normales y signos de alarma en el niño menor de cinco años / Child neurodevelopment: normal characteristics and warning signs in children under five years

El desarrollo del sistema nervioso es un proceso complejo que tiene como resultado la maduración de las estructuras, la adquisición de habilidades y, finalmente, la formación del individuo como persona única. La presente revisión recoge información acerca de las principales características de los procesos de desarrollo cerebral, las características del desarrollo neurológico normal en las diferentes áreas: motora gruesa y fina, lenguaje, sensorial y socialización; se acompaña también de una descripción de las principales alteraciones en el desarrollo, identificables en la consulta diaria del pediatra. Nuestro objetivo es reforzar el conocimiento en esta área clave de la evaluación del niño menor de cinco años para detectar problemas con la debida antelación para su intervención oportuna...

The development of the nervous system is a complex process that results in the maturation of structures, the acquisition of skills and finally the formation of the individual as a unique person. This review contains information about the main characteristics of the processes of brain development, the characteristics of normal neurological development in different areas: gross and fine motor, language, sensory and socialization; and it is also accompanied by a description of the major changes in the development, identifiable in the daily clinical work of pediatricians. Our goal is to enhance knowledge in this key area of assessment of early childhood to detect problems sufficiently in advance for their timely intervention...

Electrographic status epilepticus and long-term outcome in critically ill children.

OBJECTIVE: Electrographic seizures (ES) and electrographic status epilepticus (ESE) are common in children in the pediatric intensive care unit (PICU) with acute neurologic conditions. We aimed to determine whether ES or ESE was associated with worse long-term outcomes. METHODS: Three hundred children with an acute neurologic condition and encephalopathy underwent clinically indicated EEG monitoring and were enrolled in a prospective observational study. We aimed to obtain follow-up data from 137 subjects who were neurodevelopmentally normal before PICU admission. RESULTS: Follow-up data were collected for 60 of 137 subjects (44%) at a median of 2.7 years. Subjects with and without follow-up data were similar in clinical characteristics during the PICU admission. Among subjects with follow-up data, ES occurred in 12 subjects (20%) and ESE occurred in 14 subjects (23%). Multivariable analysis indicated that ESE was associated with an increased risk of unfavorable Glasgow Outcome Scale (Extended Pediatric Version) category (odds ratio 6.36, p = 0.01) and lower Pediatric Quality of Life Inventory scores (23 points lower, p = 0.001). Among subjects without prior epilepsy diagnoses ESE was associated with an increased risk of subsequently diagnosed epilepsy (odds ratio 13.3, p = 0.002). ES were not associated with worse outcomes. CONCLUSIONS: Among children with acute neurologic disorders who were reported to be neurodevelopmentally normal before PICU admission, ESE but not ES was associated with an increased risk of unfavorable global outcome, lower health-related quality of life scores, and an increased risk of subsequently diagnosed epilepsy even after adjusting for neurologic disorder category, EEG background category, and age.

Electrographic seizures after convulsive status epilepticus in children and young adults: a retrospective multicenter study.

OBJECTIVE: To describe the prevalence, characteristics, and predictors of electrographic seizures after convulsive status epilepticus (CSE). STUDY DESIGN: This was a multicenter retrospective study in which we describe clinical and electroencephalographic (EEG) features of children (1 month to 21 years) with CSE who underwent continuous EEG monitoring. RESULTS: Ninety-eight children (53 males) with CSE (median age of 5 years) underwent subsequent continuous EEG monitoring after CSE. Electrographic seizures (with or without clinical correlate) were identified in 32 subjects (33%). Eleven subjects (34.4%) had electrographic-only seizures, 17 subjects (53.1%) had electroclinical seizures, and 4 subjects (12.5%) had an unknown clinical correlate. Of the 32 subjects with electrographic seizures, 15 subjects (46.9%) had electrographic status epilepticus. Factors associated with the occurrence of electrographic seizures after CSE were a previous diagnosis of epilepsy (P = .029) and the presence of interictal epileptiform discharges (P < .0005). The median (p25-p75) duration of stay in the pediatric intensive care unit was longer for children with electrographic seizures than for children without electrographic seizures (9.5 [3-22.5] vs 2 [2-5] days, Wilcoxon test, Z = 3.916, P = .0001). Four children (4.1%) died before leaving the hospital, and we could not identify a relationship between death and the presence or absence of electrographic seizures. CONCLUSIONS: After CSE, one-third of children who underwent EEG monitoring experienced electrographic seizures, and among these, one-third experienced entirely electrographic-only seizures. A previous diagnosis of epilepsy and the presence of interictal epileptiform discharges were risk factors for electrographic seizures.