Current opinion in pediatrics最新文献

Purpose of review: Antimicrobial resistance is an escalating public health threat in Africa, and an awareness of the devastating impact on children is growing. This review highlights the prevalence and patterns of antimicrobial resistance among children in Africa, focusing on pathogens responsible for bloodstream infections, community-acquired pneumonia, bacterial meningitis, neonatal infections, diarrhea and malaria. Current strategies to tackle antimicrobial resistance in pediatric populations are discussed.

Recent findings: Bloodstream infections significantly contribute to child mortality, with high resistance observed in pathogens like Salmonella spp., Klebsiella spp., Escherichia coli , and Staphylococcus aureus . Additionally, rising resistance in pathogens causing community-acquired pneumonia, meningitis and bacterial diarrhea challenges the effectiveness of WHO-recommended therapies. Antibiotics used to treat neonatal infections, such as ampicillin, gentamicin and cefotaxime, are threatened by high resistance in Escherichia coli and Klebsiella spp , contributing to adverse neonatal outcomes. PfKelch 13 mutations linked to artemisinin resistance in parts of Africa raise public health concerns, as malaria remains a major cause of illness and death.

Summary: Stronger collaborative efforts are needed to enhance surveillance, improve diagnostic capabilities and update treatment protocols based on local pathogen sensitivities. More research is required on pediatric antimicrobial resistance in Africa.

Purpose of review: Applying discoveries from basic research to patients in the neonatal intensive care unit (NICU) is challenging given the difficulty of modeling this population in animal models, lack of translational relevance from animal models to humans, and scarcity of primary human tissue. Human cell-derived cerebral organoid models are an appealing way to address some of these gaps. In this review, we will touch on previous work to model neonatal conditions in cerebral organoids, some limitations of this approach, and recent strategies that have attempted to address these limitations.

Recent findings: While modeling of neurodevelopmental disorders has been an application of cerebral organoids since their initial description, recent studies have dramatically expanded the types of brain regions and disease models available. Additionally, work to increase the complexity of organoid models by including immune and vascular cells, as well as modeling human heterogeneity with mixed donor organoids will provide new opportunities to model neonatal pathologies.

Summary: Organoids are an attractive model to study human neurodevelopmental pathologies relevant to patients in the neonatal ICU. New technologies will broaden the applicability of these models to neonatal research and their usefulness as a drug screening platform.

Purpose of review: Climate change is no longer a distant threat but a present and accelerating force reshaping the epidemiology of infectious diseases in North America and elsewhere. Rising temperatures, shifting precipitation patterns, and extreme weather events are impacting the geographic distribution of pathogens and their vectors. Understanding these environmental influences on infectious diseases in children is essential for equipping healthcare providers to deliver competent care in the era of climate change.

Recent findings: The northward spread of vector-borne diseases, warming waters and soils, and disease outbreaks following extreme weather events highlight the complex and multifactorial ways through which the environment influences the spread of infectious diseases.

Summary: Continuing medical education and training on the evolving epidemiology of climate-sensitive diseases is critical for clinicians to address emerging health threats effectively. We advocate for more equitable funding and resource allocation to support innovative pediatric research on climate change and infectious diseases in the United States and other countries in North America.

Purpose of review: Precision medicine is based on the idea that treatment can be individualized for each patient in a given clinical environment. This review summarizes factors that should be considered when clinicians are creating individualized plans for intubation, specifically focusing on physiologically difficult airways. Recent literature identifying physiologic risk factors is summarized, and individual and system-level interventions that can potentially mitigate risk are reviewed.

Recent findings: Physiologic derangements, most notably hypoxia and hypotension, have been associated with increased incidence of severe adverse events during intubation attempts. Individualized peri-procedural efforts to improve physiologic parameters through optimal oxygen delivery, fluid resuscitation, vasopressor administration, and thoughtful choice in rapid sequence intubation (RSI) medications may improve patient outcomes. Systems of care are being built around airway bundles, cognitive aids, and collaborations with airway teams to optimize outcomes.

Summary: Providers should develop individualized care plans for their patients to optimize physiologic and anatomic parameters peri-intubation. The physiologically difficult airway affects the rate of first pass success and adverse events, therefore patients should be optimized prior to undergoing the procedure based on their clinical presentation and data.

Purpose of review: We provide an overview of the secular trend of earlier pubertal development, why there is a growing concern that environmental factors may be to blame, and how these factors may influence the developing reproductive axis.

Recent findings: We highlight recent work suggesting that, in addition to activating sex steroid receptors, environmental compounds may influence neuropeptide receptors and/or epigenetic regulators. We describe recent studies linking air pollution, metals, endocrine disrupting compounds (EDCs), short sleep duration, early life adversity, and stress to pubertal timing.

Summary: Pubertal timing is tightly controlled by genetic, epigenetic, and environmental factors. While animal and epidemiological studies have pointed to several potential environmental factors, additional work is necessary to identify the critical levels and developmental windows of exposure as well as the mechanistic underpinnings.

Purpose of review: Neonatal and infantile epilepsies represent a diverse group of disorders with significant neurodevelopmental impact, necessitating early diagnosis, and tailored treatment. Recent advancements in genetic research, phenotyping, and therapeutic development have reshaped the understanding and management of these conditions, making this review both timely and relevant.

Recent findings: Next-generation sequencing has emerged as a cornerstone for diagnosing neonatal and infantile epilepsies, offering high diagnostic yields and enabling identification of etiology-specific phenotypes. Precision therapies, including sodium channel blockers, ganaxolone, and mammalian target of rapamycin (mTOR) inhibitors, target specific molecular mechanisms. Early initiation of treatment in conditions with a high risk of progressing to epilepsy, like vigabatrin in tuberous sclerosis complex, lower the incidence of infantile spasms and improve developmental outcomes. Drug repurposing has also provided effective options, such as fenfluramine in Dravet syndrome, with promising outcomes. Gene-based therapies, including antisense oligonucleotides and gene replacement, represent the new frontier for addressing the root causes of these disorders.

Summary: The integration of genetic and molecular advancements is transforming the management of neonatal and infantile epilepsies, fostering precision-driven care. Continued research and innovation are essential to refine these strategies, optimize patient outcomes, and establish new standards of care.

Purpose of review: This paper reviews options for including community health accountability metrics for child healthcare systems, international and regional experience with such metrics, and some specific candidates for metric consideration.

Recent findings: The inclusion of community metrics in child health accountability systems requires expanded accountability frameworks and re-education of clinicians. Most of the experience with use of community metrics in accountability systems comes from international settings. Lessons learned in these settings include the importance of linking the metrics to various policy and practice implementation measures while balancing the incentives for such 'horizontal' or communitywide indicators with current incentives. The Accountable Communities for Health movement may be the best-known example of US community health indicators for accountability. Four new papers suggest specific child metrics for consideration as child metrics, but only infant mortality rates and high school graduation rates are sufficiently standardized and nationally reported to be useful for such efforts.

Summary: Healthcare accountability for child community health is an important next step, but the coordination with existing accountability systems, data collection systems, and financial incentives require more research to be effective in helping children. Infant mortality rates and high school graduation rates have the most potential as cross system accountability metrics.

Purpose of review: Adoptive immunotherapy brings hope to children and young adults diagnosed with high-risk solid tumors. Cellular (cell) therapies such as chimeric antigen receptor (CAR) T cell, CAR natural killer (NK) cell, and T cell receptor (TCR) T cell therapy are potential avenues of targeted therapy with limited long-term toxicities. However, development of cell therapies for solid tumors is in its nascent stages. Here, we will review the current clinical experience, barriers to efficacy, and strategies to improve clinical response and patient access.

Recent findings: Cell therapies are shown to be generally safe and well tolerated. Strategies to optimize antitumor activity have now moved into early-phase trials. The immunosuppressive tumor microenvironment remains a major barrier to efficacy, and efforts are underway to gain better understanding. This will inform future treatment strategies to enhance the antitumor activity of cell therapies.

Summary: Clinical experiences to date provide important insights on how to leverage cell therapies against solid tumors. Key factors in advancing the field include a better understanding of immune cell biology, tumor cell behavior, and the tumor microenvironment. Lastly, improving access to novel cell therapies remains an important consideration in the conduct of clinical trials and for future implementation into standard practice.

Purpose of review: To contextualize how pediatrics led the field in developing and implementing tools to screen for social determinants of health in clinical care as well as in creating innovative interventions to mitigate them, and to summarize where the evidence points as the next frontier.

Recent findings: The evidence showed that health-related social needs (HRSN), like food insecurity, energy insecurity, and housing instability, continue to drive poor health outcomes across the lifespan; patients and healthcare providers are open to discussing HRSN in clinical settings, though some providers feel ill-equipped to do so; to mitigate HRSN, healthcare plays a unique role in ensuring patients' HRSN are understood, referring to effective resources through building strong, lasting relationships with community partners, embedding services in the healthcare setting across all departments, and empowering patient families to participate in programs and services; and administrative burden hinders families from getting all the benefits to which they are entitled, which streamlined co-enrollment processes can address.

Summary: Pediatric providers can add a unique and credible voice to seeking changes to the safety-net, including co-enrollment, that could reduce administrative burden, address patients' HRSN, and improve health starting in the prenatal period through later adulthood.