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1.
medRxiv ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39371157

RESUMEN

Importance: Declining mortality in the field of pediatric critical care medicine has shifted practicing clinicians' attention to preserving patients' neurodevelopmental potential as a main objective. Earlier identification of critically ill children at risk for incurring neurologic morbidity would facilitate heightened surveillance that could lead to timelier clinical detection, earlier interventions, and preserved neurodevelopmental trajectory. Objective: Develop machine-learning models for identifying acquired neurologic morbidity while hospitalized with critical illness and assess correlation with contemporary serum-based, brain injury-derived biomarkers. Design: Retrospective cohort study. Setting: Two large, quaternary children's hospitals. Exposures: Critical illness. Main Outcomes and Measures: The outcome was neurologic morbidity, defined according to a computable, composite definition at the development site or an order for neurocritical care consultation at the validation site. Models were developed using varying time windows for temporal feature engineering and varying censored time horizons prior to identified neurologic morbidity. Optimal models were selected based on F1 scores, cohort sizes, calibration, and data availability for eventual deployment. A generalizable created at the development site was assessed at an external validation site and optimized with spline recalibration. Correlation was assessed between development site model predictions and measurements of brain biomarkers from a convenience cohort. Results: After exclusions there were 14,222-25,171 encounters from 2010-2022 in the development site cohorts and 6,280-6,373 from 2018-2021 in the validation site cohort. At the development site, an extreme gradient boosted model (XGBoost) with a 12-hour time horizon and 48-hour feature engineering window had an F1-score of 0.54, area under the receiver operating characteristics curve (AUROC) of 0.82, and a number needed to alert (NNA) of 2. A generalizable XGBoost model with a 24-hour time horizon and 48-hour feature engineering window demonstrated an F1-score of 0.37, AUROC of 0.81, AUPRC of 0.51, and NNA of 4 at the validation site. After recalibration at the validation site, the Brier score was 0.04. Serum levels of the brain injury biomarker glial fibrillary acidic protein measurements significantly correlated with model output (rs=0.34; P=0.007). Conclusions and Relevance: We demonstrate a well-performing ensemble of models for predicting neurologic morbidity in children with biomolecular corroboration. Prospective assessment and refinement of biomarker-coupled risk models in pediatric critical illness is warranted.

4.
JAMA Netw Open ; 7(6): e2414122, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38857050

RESUMEN

Importance: Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective: To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants: This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure: Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures: The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. Results: Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance: The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.


Asunto(s)
COVID-19 , Hospitalización , Enfermedades del Sistema Nervioso , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica , Humanos , COVID-19/complicaciones , COVID-19/epidemiología , Niño , Femenino , Masculino , Preescolar , Hospitalización/estadística & datos numéricos , Adolescente , Estudios Prospectivos , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/epidemiología , Lactante , Índice de Severidad de la Enfermedad
5.
Epilepsia ; 65(8): e148-e155, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38837761

RESUMEN

In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1-1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3-2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3-8.9)-particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3-21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5-20.1)-than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ = .519, p = .005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.


Asunto(s)
Dieta Cetogénica , Inmunoterapia , Estado Epiléptico , Humanos , Estado Epiléptico/terapia , Estado Epiléptico/tratamiento farmacológico , Masculino , Femenino , Dieta Cetogénica/métodos , Inmunoterapia/métodos , Inmunoterapia/tendencias , Adolescente , Adulto , Epilepsia Refractaria/terapia , Epilepsia Refractaria/dietoterapia , Niño , Anticuerpos Monoclonales Humanizados/uso terapéutico , Persona de Mediana Edad , Preescolar , Anticonvulsivantes/uso terapéutico , Adulto Joven , Rituximab/uso terapéutico , Manejo de la Enfermedad
6.
Childs Nerv Syst ; 40(9): 2829-2833, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38907117

RESUMEN

PURPOSE: Transcranial doppler based diagnostic criteria for cerebral vasospasm are not well established in the pediatric population because there is no published normative data to support the diagnosis. Studies have relied on expert consensus, but the definitions have not been validated in children diagnosed with angiographic evidence of vasospasm. Obtaining normative data is a prerequisite to defining pediatric cerebral vasospasm and the Lindegaard Ratio (LR). In this study, we obtained normative data and calculation of the normal LR from healthy children aged 10-16 years. METHODS: TCD and carotid ultrasonography was used to measure steady state velocities of both the middle cerebral artery (VMCA) and the extracranial internal cerebral artery (VEICA) in healthy children aged 10-16 years. Demographic information, hemodynamic characteristics and the calculated LR (VMCA/VEICA) was determined for each subject using descriptive statistics. RESULTS: Of the 26 healthy children, 13 were male and 13 were female. VMCA ranged between 53 and 93 cm/sec. LR ranged between 1 and 2.2 for the cohort. VMCA for both males and females were within 2 standard deviations (SD) of the normal mean flow velocity. As the VMCA velocities approached 2 SD above the mean, LR did not exceed 2.2. CONCLUSION: Our results help define a threshold for LR which can be used to establish radiographic criteria for cerebral vasospasm in children. Our data suggests that using VMCA criteria alone would overestimate cerebral vasospasm and raises question of whether an LR threshold other than 3 is more appropriate for the cut off between hyperemia versus vasospasm in children.


Asunto(s)
Ultrasonografía Doppler Transcraneal , Humanos , Niño , Femenino , Masculino , Adolescente , Ultrasonografía Doppler Transcraneal/métodos , Valores de Referencia , Arteria Cerebral Media/diagnóstico por imagen , Velocidad del Flujo Sanguíneo/fisiología , Vasoespasmo Intracraneal/diagnóstico por imagen , Circulación Cerebrovascular/fisiología
7.
Front Pediatr ; 12: 1340385, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38410766

RESUMEN

Introduction: Hospitalized children diagnosed with SARS-CoV-2-related conditions are at risk for new or persistent symptoms and functional impairments. Our objective was to analyze post-hospital symptoms, healthcare utilization, and outcomes of children previously hospitalized and diagnosed with acute SARS-CoV-2 infection or Multisystem Inflammatory Syndrome in Children (MIS-C). Methods: Prospective, multicenter electronic survey of parents of children <18 years of age surviving hospitalization from 12 U.S. centers between January 2020 and July 2021. The primary outcome was a parent report of child recovery status at the time of the survey (recovered vs. not recovered). Secondary outcomes included new or persistent symptoms, readmissions, and health-related quality of life. Multivariable backward stepwise logistic regression was performed for the association of patient, disease, laboratory, and treatment variables with recovered status. Results: The children [n = 79; 30 (38.0%) female] with acute SARS-CoV-2 (75.7%) or MIS-C (24.3%) had a median age of 6.5 years (interquartile range 2.0-13.0) and 51 (64.6%) had a preexisting condition. Fifty children (63.3%) required critical care. One-third [23/79 (29.1%)] were not recovered at follow-up [43 (31, 54) months post-discharge]. Admission C-reactive protein levels were higher in children not recovered vs. recovered [5.7 (1.3, 25.1) vs. 1.3 (0.4, 6.3) mg/dl, p = 0.02]. At follow-up, 67% overall had new or persistent symptoms. The most common symptoms were fatigue (37%), weakness (25%), and headache (24%), all with frequencies higher in children not recovered. Forty percent had at least one return emergency visit and 24% had a hospital readmission. Recovered status was associated with better total HRQOL [87 (77, 95) vs. 77 (51, 83), p = 0.01]. In multivariable analysis, lower admission C-reactive protein [odds ratio 0.90 (95% confidence interval 0.82, 0.99)] and higher admission lymphocyte count [1.001 (1.0002, 1.002)] were associated with recovered status. Conclusions: Children considered recovered by their parents following hospitalization with SARS-CoV-2-related conditions had less symptom frequency and better HRQOL than those reported as not recovered. Increased inflammation and lower lymphocyte count on hospital admission may help to identify children needing longitudinal, multidisciplinary care. Clinical Trial Registration: ClinicalTrials.gov (NCT04379089).

9.
Photochem Photobiol Sci ; 23(1): 23-29, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38095821

RESUMEN

The worsening problem of antimicrobial drug resistance requires a nuanced approach. Since the conventional drug pipeline is unlikely to be sufficient to avoid massive increases in mortality by the mid-twenty-first century, other methods of antisepsis will be required. These might be used either in place of (allowing conservation) or together with conventional agents. Of such approaches, locally applied protocols involving photo-antimicrobials suggest themselves, particularly as early intervention, e.g. in bacterial tonsillitis, would be curative without recourse to conventional drugs, and would thus prevent the development of more serious diseases such as pneumonia or meningitis. However, given the pharmaceutical industry's lack of investment in such approaches, support would be required from other areas of bioscience, such as the biomed or biotech sectors.


Asunto(s)
Antiinfecciosos , Infecciones Bacterianas , Humanos , Farmacorresistencia Microbiana , Antibacterianos/uso terapéutico
10.
J Periodontol ; 95(4): 360-371, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38112075

RESUMEN

BACKGROUND: The aim of this study was to evaluate the effect of active oxygen-releasing gel as an adjuvant, with and without antimicrobial photodynamic therapy (aPDT), in the treatment of residual pockets in periodontal patients with type 2 diabetes mellitus (DM2). METHODS: Patients with residual pockets with probing depth (PD) ≥4 mm and bleeding on probing (BOP) were divided into the following groups: SI (n = 17)-subgingival instrumentation in a single session; BM (n = 17)-SI followed by local application of active oxygen-releasing gel inside the periodontal pocket for 3 min; BM + aPDT (n = 17)-SI followed by application of BM for 3 min and pocket irrigation with methylene blue, and 660-nm diode laser irradiation at 100 mW for 50 s. The periodontal clinical parameters, serum levels of glycated hemoglobin, and immunological analysis of crevicular fluid were evaluated. All data were submitted to statistical analysis (α = 5%). RESULTS: A significant reduction in BOP was verified at 90 and 180 days in the BM + aPDT group. The percentage of sites with PD ≥ 4 mm was significantly reduced at 90 days in BM + aPDT and BM, whereas after 180 days only BM showed a significant reduction. In the BM + aPDT group, there was a significant reduction in tumor necrosis factor α levels at 90 days. There were no differences between the treatments. CONCLUSION: The use of adjuvant active oxygen-releasing gel, with or without aPDT, resulted in the same clinical benefits as SI in the treatment of residual pockets in poorly controlled DM2 patients.


Asunto(s)
Diabetes Mellitus Tipo 2 , Geles , Líquido del Surco Gingival , Hemoglobina Glucada , Láseres de Semiconductores , Azul de Metileno , Índice Periodontal , Bolsa Periodontal , Fotoquimioterapia , Fármacos Fotosensibilizantes , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fotoquimioterapia/métodos , Bolsa Periodontal/tratamiento farmacológico , Bolsa Periodontal/terapia , Masculino , Femenino , Persona de Mediana Edad , Líquido del Surco Gingival/química , Azul de Metileno/uso terapéutico , Hemoglobina Glucada/análisis , Láseres de Semiconductores/uso terapéutico , Fármacos Fotosensibilizantes/uso terapéutico , Factor de Necrosis Tumoral alfa , Anciano , Estudios de Seguimiento , Terapia Combinada , Adulto , Raspado Dental/métodos , Resultado del Tratamiento
11.
Neurocrit Care ; 39(3): 593-599, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37704934

RESUMEN

BACKGROUND: The implementation of multimodality monitoring in the clinical management of patients with disorders of consciousness (DoC) results in physiological measurements that can be collected in a continuous and regular fashion or even at waveform resolution. Such data are considered part of the "Big Data" available in intensive care units and are potentially suitable for health care-focused artificial intelligence research. Despite the richness in content of the physiological measurements, and the clinical implications shown by derived metrics based on those measurements, they have been largely neglected from previous attempts in harmonizing data collection and standardizing reporting of results as part of common data elements (CDEs) efforts. CDEs aim to provide a framework for unifying data in clinical research and help in implementing a systematic approach that can facilitate reliable comparison of results from clinical studies in DoC as well in international research collaborations. METHODS: To address this need, the Neurocritical Care Society's Curing Coma Campaign convened a multidisciplinary panel of DoC "Physiology and Big Data" experts to propose CDEs for data collection and reporting in this field. RESULTS: We report the recommendations of this CDE development panel and disseminate CDEs to be used in physiologic and big data studies of patients with DoC. CONCLUSIONS: These CDEs will support progress in the field of DoC physiologic and big data and facilitate international collaboration.


Asunto(s)
Investigación Biomédica , Elementos de Datos Comunes , Humanos , Inteligencia Artificial , Macrodatos , Trastornos de la Conciencia/diagnóstico , Trastornos de la Conciencia/terapia
12.
Crit Care Med ; 51(12): 1740-1753, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37607072

RESUMEN

OBJECTIVES: To address areas in which there is no consensus for the technologies, effort, and training necessary to integrate and interpret information from multimodality neuromonitoring (MNM). DESIGN: A three-round Delphi consensus process. SETTING: Electronic surveys and virtual meeting. SUBJECTS: Participants with broad MNM expertise from adult and pediatric intensive care backgrounds. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two rounds of surveys were completed followed by a virtual meeting to resolve areas without consensus and a final survey to conclude the Delphi process. With 35 participants consensus was achieved on 49% statements concerning MNM. Neurologic impairment and the potential for MNM to guide management were important clinical considerations. Experts reached consensus for the use of MNM-both invasive and noninvasive-for patients in coma with traumatic brain injury, aneurysmal subarachnoid hemorrhage, and intracranial hemorrhage. There was consensus that effort to integrate and interpret MNM requires time independent of daily clinical duties, along with specific skills and expertise. Consensus was reached that training and educational platforms are necessary to develop this expertise and to provide clinical correlation. CONCLUSIONS: We provide expert consensus in the clinical considerations, minimum necessary technologies, implementation, and training/education to provide practice standards for the use of MNM to individualize clinical care.


Asunto(s)
Competencia Clínica , Adulto , Niño , Humanos , Consenso , Técnica Delphi , Encuestas y Cuestionarios , Estándares de Referencia
14.
Seizure ; 111: 51-55, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37523933

RESUMEN

PURPOSE: Delayed treatment in status epilepticus (SE) is independently associated with increased treatment resistance, morbidity, and mortality. We describe the prehospital management pathway and Emergency Medical Services (EMS) timeliness in children who developed refractory convulsive status epilepticus (RCSE). METHODS: Retrospective multicenter study in the United States using prospectively collected observational data from June 2011 to March 2020. We selected pediatric patients (one month-21 years) with RCSE initiated outside the hospital and transported to the hospital by EMS. RESULTS: We included 91 patients with a median (percentile25-percentile75) age of 3.0 (1.5-7.3) years. The median time from seizure onset to hospital arrival was 45 (30-67) minutes, with a median time cared for by EMS of 24 (15-36) minutes. Considering treatment by caregivers and EMS before hospital arrival, 20 (22%) patients did not receive any anti-seizure medications (ASM) and 71 (78%) received one to five doses of benzodiazepines (BZD), without non-BZD ASM. We provided the prehospital treatment flow path of these patients through caregivers and EMS including relevant time points. Patients with a history of SE were more likely to receive the first BZD in the prehospital setting compared to patients without a history of SE (adjusted HR 3.25, 95% CI 1.72-6.12, p<0.001). CONCLUSION: In this multicenter study of pediatric RCSE, prehospital treatment may be streamlined further. Patients with a history of SE were more likely to receive prehospital rescue medication.

15.
Neurology ; 101(5): e546-e557, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37295955

RESUMEN

BACKGROUND AND OBJECTIVES: The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus (RSE) in children. METHODS: An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus [rESE]) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort. We explored clinical variables that could be acquired early after presentation to emergency medical services with univariate analysis of the raw data. Variables with p < 0.1 were retained for univariable and multivariable regression analyses. Multivariable logistic regression models were fit to age-matched and sex-matched data to obtain variables associated with RSE. RESULTS: We compared data from a total of 595 episodes of pediatric SE. Univariate analysis demonstrated no differences in time to the first BZD (RSE 16 minutes [IQR 5-45]; rESE 18 minutes [IQR 6-44], p = 0.068). Time to second-line ASM was shorter in patients with RSE (RSE 65 minutes; rESE 70 minutes; p = 0.021). Both univariable and multivariable regression analyses revealed a family history of seizures (OR 0.37; 95% CI 0.20-0.70, p = 0.0022) or a prescription for rectal diazepam (OR 0.21; 95% CI 0.078-0.53, p = 0.0012) was associated with decreased odds of RSE. DISCUSSION: Time to initial BZD or second-line ASM was not associated with progression to RSE in our cohort of patients with rESE. A family history of seizures and a prescription for rectal diazepam were associated with a decreased likelihood of progression to RSE. Early attainment of these variables may help care for pediatric rESE in a more patient-tailored manner. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patient and clinical factors may predict RSE in children with convulsive seizures.


Asunto(s)
Epilepsia Refractaria , Estado Epiléptico , Humanos , Niño , Anticonvulsivantes/uso terapéutico , Estudios de Casos y Controles , Estudios Retrospectivos , Estado Epiléptico/tratamiento farmacológico , Benzodiazepinas/uso terapéutico , Convulsiones/tratamiento farmacológico , Epilepsia Refractaria/tratamiento farmacológico , Diazepam/uso terapéutico
16.
Epilepsia ; 64(9): 2297-2309, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37287398

RESUMEN

OBJECTIVE: Seizures are common in critically ill children and neonates, and these patients would benefit from intravenous (IV) antiseizure medications with few adverse effects. We aimed to assess the safety profile of IV lacosamide (LCM) among children and neonates. METHODS: This retrospective multicenter cohort study examined the safety of IV LCM use in 686 children and 28 neonates who received care between January 2009 and February 2020. RESULTS: Adverse events (AEs) were attributed to LCM in only 1.5% (10 of 686) of children, including rash (n = 3, .4%), somnolence (n = 2, .3%), and bradycardia, prolonged QT interval, pancreatitis, vomiting, and nystagmus (n = 1, .1% each). There were no AEs attributed to LCM in the neonates. Across all 714 pediatric patients, treatment-emergent AEs occurring in >1% of patients included rash, bradycardia, somnolence, tachycardia, vomiting, feeling agitated, cardiac arrest, tachyarrhythmia, low blood pressure, hypertension, decreased appetite, diarrhea, delirium, and gait disturbance. There were no reports of PR interval prolongation or severe cutaneous adverse reactions. When comparing children who received a recommended versus a higher than recommended initial dose of IV LCM, there was a twofold increase in the risk of rash in the higher dose cohort (adjusted incidence rate ratio = 2.11, 95% confidence interval = 1.02-4.38). SIGNIFICANCE: This large observational study provides novel evidence demonstrating the tolerability of IV LCM in children and neonates.


Asunto(s)
Anticonvulsivantes , Niño Hospitalizado , Recién Nacido , Humanos , Niño , Lacosamida , Anticonvulsivantes/efectos adversos , Estudios de Cohortes , Bradicardia/inducido químicamente , Bradicardia/epidemiología , Somnolencia , Acetamidas/efectos adversos , Resultado del Tratamiento , Estudios Retrospectivos
17.
Sci Rep ; 13(1): 10203, 2023 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-37353536

RESUMEN

Assessing the in vitro toxicity of compounds on cell cultures is an important step during the screening of candidate molecules for diverse applications. Among the strategies employed to determine cytotoxicity, MTT, neutral red, and resazurin are commonly used. Methylene blue (MB), a phenothiazinium salt, has several uses, such as dye, redox indicator, and even as treatment for human disease and health conditions, such as malaria and methemoglobinemia. However, MB has only been sparsely used as a cellular toxicity indicator. As a viability indicator, MB is mostly applied to fixed cultures at high concentrations, especially when compared to MTT or neutral red. Here we show that MB and its related compounds new methylene blue (NMB), toluidine blue O (TBO), and dimethylmethylene blue (DMMB) can be used as cytotoxicity indicators in live (non-fixed) cells treated for 72 h with DMSO and cisplatin. We compared dye uptake between phenothiazinium dyes and neutral red by analyzing supernatant and cell content via visible spectra scanning and microscopy. All dyes showed a similar ability to assess cell toxicity compared to either MTT or neutral red. Our method represents a cost-effective alternative to in vitro cytotoxicity assays using cisplatin or DMSO, indicating the potential of phenothiazinium dyes for the screening of candidate drugs and other applications.


Asunto(s)
Colorantes , Fenotiazinas , Humanos , Fenotiazinas/farmacología , Cisplatino/farmacología , Rojo Neutro , Dimetilsulfóxido , Azul de Metileno
18.
Pediatr Neurol ; 146: 1-7, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37356227

RESUMEN

BACKGROUND: Pediatric neurocritical care (PNCC) has emerged as a field to care for children at the intersection of critical illness and neurological dysfunction. PNCC fellowship programs evolved over the past decade to train physicians to fill this clinical need. We aimed to characterize PNCC fellowship training infrastructure and curriculum in the United States and Canada. METHODS: Web-based survey of PNCC fellowship program leaders during November 2019 to January 2020. RESULTS: There were 14 self-identified PNCC fellowship programs. The programs were supported by Child Neurology and/or Pediatric Critical Care Medicine divisions at tertiary/quaternary care institutions. Most programs accepted trainees who were board-eligible or board-certified in child neurology or pediatric critical care medicine. Clinical training consisted mostly of rotations providing PNCC consultation (n = 13) or as a provider on the pediatric intensive care unit-based neurointensive care team (n = 2). PNCC-specific didactics were delivered at most institutions (n = 13). All institutions provided training in electroencephalography use in the intensive care unit and declaration of death by neurological criteria (n = 14). Scholarly activity was supported by most programs, including protected time for research (n = 10). CONCLUSIONS: We characterized PNCC fellowship training in the United States and Canada, which in this continuously evolving field, lays the foundation for exploring standardization of training going forward.


Asunto(s)
Cuidados Críticos , Becas , Niño , Humanos , Estados Unidos , Encuestas y Cuestionarios , América del Norte , Curriculum , Educación de Postgrado en Medicina
19.
J Child Neurol ; 38(3-4): 121-129, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36991568

RESUMEN

Clinical guidance on outpatient follow-up of children hospitalized with acute neurologic complications of SARS-CoV2 infection is needed. We describe the clinical infrastructure of our pediatric neurology post-Covid clinic, including our clinical evaluation and cognitive testing battery specific to this patient population, and a case series of our initial patient cohort. Our findings demonstrate cognitive sequelae in all 4 of our patients months following acute SARS-CoV2 infection with neurologic complications including acute disseminated encephalomyelitis, posterior reversible encephalopathy syndrome, viral encephalitis, and gait difficulties. Verbal and executive function domains were predominantly affected in our cohort, even in patients who did not endorse symptomatic or academic complaints at follow-up. Our recommendations include systematic clinical follow-up for children following hospitalization with SARS-CoV2 infection with a comprehensive cognitive battery to monitor for cognitive sequalae and to assist with developing an individualized education plan for the child as they return to school.


Asunto(s)
COVID-19 , Neurología , Síndrome de Leucoencefalopatía Posterior , Humanos , Niño , Estudios de Seguimiento , ARN Viral , COVID-19/complicaciones , SARS-CoV-2
20.
Pediatr Neurol ; 141: 1-8, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36731228

RESUMEN

BACKGROUND: Continuous electroencephalography (cEEG) is commonly used for neuromonitoring in pediatric intensive care units (PICU); however, there are barriers to real-time interpretation of EEG data. Quantitative EEG (qEEG) transforms the EEG signal into time-compressed graphs, which can be displayed at the bedside. A survey was designed to understand current PICU qEEG use. METHODS: An electronic survey was sent to the Pediatric Neurocritical Care Research Group and Pediatric Status Epilepticus Research Group, and intensivists in 16 Canadian PICUs. Questions addressed demographics, qEEG acquisition and storage, clinical use, and education. RESULTS: Fifty respondents from 39 institutions completed the survey (response rate 53% [39 of 74 institutions]), 76% (37 of 50) from the United States and 24% (12 of 50) from Canada. Over half of the institutions (22 of 39 [56%]) utilize qEEG in their ICUs. qEEG use was associated with having a neurocritical care (NCC) service, ≥200 NCC consults/year, ≥1500 ICU admissions/year, and ≥4 ICU EEGs/day (P < 0.05 for all). Nearly all users (92% [24 of 26]) endorsed that qEEG enhanced care of children with acute neurological injury. Lack of training in qEEG was identified as a common barrier [85% (22 of 26)]. Reviewing and reporting of qEEG was not standard at most institutions. Training was required by 14% (three of 22) of institutions, and 32% (seven of 22) had established curricula. CONCLUSIONS: ICU qEEG was used at more than half of the institutions surveyed, but review, reporting, and application of this tool remained highly variable. Although providers identify qEEG as a useful tool in patient management, further studies are needed to define clinically meaningful pediatric trends, standardize reporting, and enhance educate bedside providers.


Asunto(s)
Electroencefalografía , Unidades de Cuidado Intensivo Pediátrico , Humanos , Niño , Estudios Transversales , Canadá , América del Norte
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