Jacobs Institute of Women's Health
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Imaging Clusters of Pediatric Low-Grade Glioma are Associated with Distinct Molecular Characteristics
No full textBACKGROUND AND PURPOSE: Cancers show heterogeneity at various levels, from genome to radiological imaging. This study aimed to explore the interplay between genomic, transcriptomic, and radiophenotypic data in pediatric low-grade glioma (pLGG), the most common group of brain tumors in children. MATERIALS AND METHODS: We analyzed data from 201 pLGG patients in the Children\u27s Brain Tumor Network (CBTN), using principal component analysis and K-Means clustering on 881 radiomic features, along with clinical variables (age, sex, tumor location), to identify imaging clusters and examine their association with 2021 WHO pLGG classifications. To determine the transcriptome pathways linked to imaging clusters, we employed a supervised machine learning model with elastic net logistic regression based on the pathways identified through gene set enrichment and gene co-expression network analyses. RESULTS: Three imaging clusters with distinct radiomic characteristics were identified. BRAF V600E mutations were primarily found in imaging cluster 3, while KIAA1549::BRAF fusion occurred in subtype 1. The model\u27s predictive accuracy (AUC) was 0.77 for subtype 1, 0.78 for subtype 2, and 0.70 for subtype 3. Each imaging cluster exhibited unique molecular mechanisms: subtype 1 was linked to oxidative phosphorylation, PDGFRB, and interleukin signaling, whereas subtype 3 was associated with histone acetylation and DNA methylation pathways, related to BRAF V600E pLGGs. CONCLUSIONS: Our radiogenomics study indicates that the intrinsic molecular characteristics of tumors correlate with distinct imaging subgroups in pLGG, paving the way for future multi-modal investigations that may enhance understanding of disease progression and targetability. ABBREVIATIONS: WHO = World Health Organization; CBTN = Children\u27s Brain Tumor Network; pLGG = pediatric Low-Grade Glioma; EFS = Event-Free Survival; PC = Principal Component; CNS = Central Nervous System
Fetal Callosal Anomalies: A Narrative Review and Practical Recommendations for Pediatric Neurologists
No full textAgenesis of the corpus callosum is a common indication for fetal neurology consultation, increasingly identified through advances in fetal sonography and fetal magnetic resonance imaging. Despite improvements in diagnostic accuracy, prognostic counseling is challenging due to highly variable neurodevelopmental outcomes. Several factors contribute to neurodevelopmental outcome variability, including associated anomalies and etiologic considerations such as genetic, acquired, and environmental factors. This narrative review discusses existing literature on prenatal findings, postnatal outcomes, and comorbidities to provide practical guidelines for prenatal diagnosis, counseling, and postnatal management. Additionally, practice and research gaps are identified to advocate for guidelines to improve counseling, management, and optimization of outcomes for affected children and families
The Heterogeneous Clinical Manifestations of Atopic Dermatitis Across Diverse Patient Populations
No full textAtopic dermatitis (AD) presents with a wide range of clinical manifestations with variable distribution, morphology, chronicity, and severity that may differ across ethnic and racial groups. A scoping literature review was conducted and included all studies of the clinical manifestations of adult AD in diverse populations. Promoting awareness of the heterogeneous clinical manifestations of AD may benefit the diagnosis, treatment, and characterization of eczema
Improving the Quality of Pediatric Basic Life Support Cardiopulmonary Resuscitation With a Novel Method: The Maryland Hiccup
No full textPrehospital high-performance cardiopulmonary resuscitation (CPR) has demonstrated remarkable improvements in the survival of adult patients after out-of-hospital cardiac arrest (OHCA). With a goal to improve pediatric survival rates, Maryland Emergency Medical Services (EMS) for Children created a pediatric-specific high-performance CPR protocol to align with the existing state protocol for adult CPR. While prehospital CPR for adults has moved toward continuous compressions, prehospital CPR for children without an advanced airway continues to adhere to American Heart Association (AHA)/International Liaison Committee on Resuscitation (ILCOR) guidance for two ventilations for every 15 compressions. The Maryland Hiccup (MH) is a novel approach to pediatric CPR. The method combines the goal of continuous compressions with AHA/ILCOR guidance for a 15:2 compression-to-ventilation ratio. In contrast to the two- to four-second pause after compression 15 of the AHA/ILCOR style, the hiccup of the MH method describes two brief pauses for ventilation during the upstrokes of compressions 14 and 15. We compare basic CPR quality metrics for two-rescuer high-performance CPR using the standard AHA/ILCOR 15:2 style compared to the MH style. We enrolled 38 Maryland EMS clinicians in two-person teams to perform simulated CPR on a pediatric manikin. We recorded compression and ventilation data for 76 two-minute cycles of high-performance CPR. Compression fraction was significantly improved using the MH when compared to the standard AHA style for high-performance CPR (median 98% vs 80%, p\u3c0.001). When compressions per minute (CPM) were compared by 30-second epochs, 80% of epochs were out of range (\u3c100 CPM or \u3e120 CPM) using the AHA/ILCOR style, while only 32% of epochs were out of range for MH style. No significant differences were found between the two CPR styles in ventilation volume or compression depth. The MH is a novel method for pediatric basic life support two-provider CPR which improves CPR quality metrics among EMS clinicians regardless of their prior experience. The use of this method in simulation allows near-continuous compressions without the placement of an advanced airway. Future research is needed to explore whether the CPR quality improvements translate to improved patient outcomes in real-world use
Willingness to Take Long-Acting Injectable Preexposure Prophylaxis (PrEP) and Preference for PrEP Modalities Among People Who Inject Drugs in Washington, DC
No full textBACKGROUND: People who inject drugs (PWID) face multilevel barriers to adhering to daily oral preexposure prophylaxis (PrEP). Long-acting injectable (LAI) PrEP may help overcome some of these barriers. Understanding willingness among PWID to take LAI PrEP and preferences for PrEP modality is important to promote LAI PrEP when it becomes available to them. METHODS: We analyzed data from the 2018 National HIV Behavioral Surveillance PWID data collection cycle in Washington, DC. Respondent-driven sampling weighted proportions and correlates of willingness to take LAI PrEP and preference for LAI PrEP versus daily oral PrEP were reported, overall and stratified by gender. RESULTS: Of 402 PWID, 69.1% reported being extremely likely/likely to take LAI PrEP; 52.4% preferred LAI PrEP over daily oral PrEP. Being female and uninsured were associated with higher odds of willingness to take LAI PrEP. Having no/low income and past-year sexual violence were associated with preferring LAI PrEP over daily oral PrEP. Men who inject drugs who were aware of PrEP had higher odds to prefer LAI PrEP over daily oral PrEP. Women who inject drugs (WWID) reporting no/low income, sexual violence, and receptive needle sharing were more likely to prefer LAI PrEP over daily oral PrEP. CONCLUSIONS: PWID in Washington, DC reported high willingness to take LAI PrEP; half reported preferring LAI PrEP. Improving education about PrEP is important for healthcare providers and PWID. Subgroups of WWID experiencing sexual violence may benefit from LAI PrEP. Human immunodeficiency virus prevention programs for PWID should consider gender differences when implementing LAI PrEP
Cerebral malaria
No full textCerebral malaria is the most lethal form of Plasmodium falciparum infection. The disease is defined clinically as an otherwise unexplained coma in someone with malaria parasitemia. One in 6 children with cerebral malaria dies and many survivors are left with neurologic, cognitive, or behavioral sequelae. Acute seizures are common and increasing numbers of them during the index illness are associated with a greater likelihood of adverse outcomes. Optimal treatment pathways for children with cerebral malaria have been standardized but the search for an adjunctive therapy that decreases cerebral malaria mortality or morbidity has, so far, remained elusive. After hospital discharge, care gaps for survivors continue in the diagnosis and management of educational challenges, behavioral abnormalities, and epilepsy, especially in the rural settings where malaria incidence is highest. In the past decade, science has elucidated much about cerebral malaria pathogenesis. Observational studies using magnetic resonance imaging, electroencephalogram, and transcranial doppler have all provided insight on the pathway from the initial infection transmitted by a mosquito, to death. Findings from each of these high technology modalities are also associated with outcomes in children with cerebral malaria. We review the epidemiology, clinical features, diagnostic considerations, optimal clinical care pathways, neurological sequalae, and existing care gaps in the management of cerebral malaria and its complications
Applying the Nova food classification to food product databases using discriminative ingredients: a methodological proposal
No full textBACKGROUND: Growing interest in the Nova food classification system surged among various stakeholders, driven primarily by compelling evidence linking the consumption of ultra-processed foods (UPFs) to negative health outcomes. This growing interest underscores the potential value of identifying clear markers to classify UPFs, particularly to support research and regulatory efforts. OBJECTIVE: To propose replicable methods to identify UPFs, by testing the sensitivity and specificity of these methods using a large sample of packaged foods from the 2017 Brazilian Food Labels Database. METHODS: We created five scenarios to identify UPFs using substances of rare culinary use and food additives typically found in UPFs and compared them with the Nova food classification process based on the product name and food categories, considered the classic method to identify UPFs. We estimated the proportion of foods and beverages identified as UPFs using the different scenarios based on the presence of discriminative ingredients. We used a diagnostic test and a receiver operating characteristic (ROC) to understand which of the five scenarios performed better compared to the classic method to identify UPFs. Finally, we conducted a sensitivity analysis to test the role of vitamins and minerals in identifying UPFs. RESULTS: We found variations in UPFs prevalence from 47 to 72% across the five scenarios, compared to 70% using the classic method to identify UPFs in Brazilian packaged foods. The scenario using food additives of a sole cosmetic function and substances of rare culinary use (scenario 3) identified a 65% UPF, while maintaining reasonable sensitivity and specificity, and the best-performing ROC curve. There was no significant difference in identifying UPFs when comparing the addition of vitamins and minerals to the food additives with sole cosmetic function. CONCLUSION: This study shows that using ingredient-based criteria, specifically cosmetic additives and substances of rare culinary use, can reliably identify UPFs, offering reproducibility, and supporting its use in research and policy applications
The gateway effect of cigarette, e-cigarette, cigar, and alcohol use vs. Cannabis use
No full textBACKGROUND: While the gateway hypothesis suggests that using tobacco and alcohol increases likelihood of initiating cannabis, cannabis use may precede and increase other substance use. We examined gateway effects of cigarettes, e-cigarettes, cigars, and alcohol on cannabis use, and reverse associations. METHODS: We analyzed 2023 survey data from 4,031 US young adults (M = 26.29, 60 % female, 19 % Hispanic, 14 % Black, 14 % Asian). Discrete-time survival analysis assessed hazards of initiating cannabis based on self-reported age of initiating other substances, and vice versa. Time(age)-lagged predictors indicated whether participants had initiated the other substances by one year younger, accounting for sociodemographics; state non-medical cannabis laws; lifetime depression, anxiety, or attention deficit disorder [ADD]) diagnoses; and personality characteristics. RESULTS: Lifetime use was: 68 % for cannabis, 45 % cigarettes, 49 % e-cigarettes, 31 % cigars, and 85 % alcohol. Past-year cigarette, e-cigarette, cigar, and alcohol initiation increased hazards of initiating cannabis (adjusted Hazard Ratio, aHR = 3.78, 95 %CI = 3.39-4.22; aHR = 2.17, 95 %CI = 1.86-2.53; aHR = 2.90, 95 %CI = 2.45-3.43; aHR = 3.41, 95 %CI = 3.11-3.75, respectively). Past-year cannabis initiation increased hazards of other substance initiation (cigarettes: aHR = 3.51, 95 %CI = 3.11-3.96; e-cigarettes: aHR = 3.73, 95 %CI = 3.34-4.17; cigars: aHR = 3.66, 95 %CI = 3.20-4.18; alcohol: aHR = 3.07, 95 %CI = 2.73-3.45). Associations were generally stronger when initiation occurred at ages 5-18 vs. \u3e 18. Depression predicted cannabis initiation; anxiety and ADD predicted e-cigarette initiation. Certain personality characteristics were protective against initiation (agreeableness and conscientiousness for each, openness for cigarettes and cigars, emotional stability for cannabis, cigarettes, and cigars); extraversion increased hazards of initiating cannabis and e-cigarettes. CONCLUSIONS: Interventions should target underlying mechanisms influencing the use of various substances, such as mental health and personality characteristics, especially among adolescents
