Current opinion in pediatrics最新文献

Purpose of review: Describe why this review is timely and relevant.Undescended testis, or cryptorchidism, is a common diagnosis encountered by pediatricians that requires timely collaboration with pediatric surgical specialists to optimize outcomes for these patients. As this topic continues to be heavily researched, it is imperative to understand current recommendations and emerging management options including new surgical techniques, as well as common pitfalls in care highlighted in the literature.

Recent findings: Describe the main themes in the literature covered by the article.This review primarily examines current practice in management including delays in surgical referral, with unnecessary imaging being a key factor that delays time to surgery. This review briefly discusses the diagnosis of undescended testis and the various surgical techniques used including the more recently proposed laparoscopic staged traction orchiopexy (Shehata technique). The ineffectiveness of hormonal therapy is also addressed.

Summary: describe the implications of the findings for clinical practice or research.This review emphasizes prompt evaluation and diagnosis of undescended testis to facilitate appropriately timed surgical intervention, which plays a major role in outcomes for these patients. Identifying patients at risk of delayed referral is an area of focus for improvement, along with better resource utilization with fewer imaging. Familiarization of surgical options can also facilitate better patient education and provider understanding of risks/benefits.

Purpose of review: Primary immune regulatory disorders (PIRDs) are an increasing indication for hematopoietic stem cell transplant (HCT) in pediatric patients. Here, we provide an updated overview of HCT for PIRDs, and discuss future avenues for improvement in outcomes.

Recent findings: There are now more than 50 described monogenic PIRDs, which impact all aspects of immune tolerance, regulation, and suppression. Disease characteristics are highly variable, and HCT remains the only option for cure. We review advances in targeted therapies for individual PIRDs, which have significantly improved outcomes and the ability to safely bridge to transplant. Additionally, advances in GVHD prevention, graft manipulation, personalized conditioning regimens, and supportive care have all increased survival after HCT. The high inflammatory state increases the risk of nonengraftment, rejection, and autologous reconstitution. Therapy to reduce the inflammatory state may further improve outcomes. In addition, although younger patients with fewer comorbidities have better outcomes, the clinical courses of these diseases may be extremely variable thereby complicating the decision to proceed to HCT.

Summary: HCT for PIRDs is a growing consideration in cell therapy. Yet, there remain significant gaps in our understanding of which patients this curative therapy could benefit the most. Here, we review the current data supporting HCT for PIRDs as well as areas for future improvement.

Purpose of review: Allogeneic hematopoietic cell transplantation (HCT) is a curative option for many for inborn errors of immunity (IEI). This review highlights recent progress in the field of HCT for IEI.

Recent findings: Alternative donor transplantation continues to expand donor options for patients with IEI. Reduced intensity and reduced toxicity conditioning approaches are being investigated and optimized. Immunomodulatory bridging therapies are yielding impressive progress in outcomes for primary immune regulatory disorders (PIRD) but require further study in prospective trials. Single-institution, multicenter and consortium studies have improved our understanding of factors that affect overall outcomes in IEI and outcomes in Wiskott-Aldrich syndrome (WAS), chronic granulomatous disease (CGD) and PIRD in particular. Data show that second HCT offers a viable chance of cure to some IEI patients. Late effects in IEI HCT survivors are being better characterized. Preclinical studies of chemo(radiation)-free HCT strategies hold promise for decreasing HCT toxicity.

Summary: Improvements in our understanding of HCT donor choice, conditioning regimen, immunomodulatory bridging therapies, diagnostic and post-HCT surveillance testing and late effects continue to yield advancements in the field of HCT for IEI.

Purpose of review: This review aims to provide an overview of the current understanding of eosinophilic gastrointestinal disorders (EGIDs) and the role of the epithelium in influencing disease pathogenesis to inform and devise future therapeutic strategies.

Recent findings: Changes in epithelial cell structure, functions, and integrity are observed in EGIDs. In eosinophilic esophagitis (EoE), the esophageal epithelium has been shown to play key roles in perpetuating the inflammatory response in EoE through the expression of pro-inflammatory cytokines and immunological cell-surface proteins. Similar mechanisms appear to exist in the other EGIDs, including eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). Because of the increasing rarity of each non-EoE EGID, research focusing on how the epithelium is modulating disease in each lower gastrointestinal compartment is still in its rudimentary stages.

Summary: While there has been significant progress in understanding the role of the epithelium in EoE, further research is needed to obtain a better understanding of the mechanisms mediating epithelial-immune crosstalk in non-EoE EGIDs. Using EoE-epithelial cell research to inform future EGID investigations could lead to the development of new therapeutic interventions, such as targeted therapies to restore epithelial barrier function and reduce inflammation, to improve rare disease-patient quality of life.

Purpose of review: A growing number of gene therapies are getting FDA-approved for pediatric rare disorders to treat once incurable diseases. Opportunities for preventing lifetime illness and improving quality of life for these patients is now becoming a reality. Challenges exist in navigating the complexities of determining which patients will benefit from these new gene therapies and how to effectively deliver them as a standard of care.

Recent findings: Gene therapies have been approved for pediatric hematological, neuromuscular, cancer, and other disorders that have improved the quality of life for rare disease patients. FDA approval of these drugs has been on a case-by-case basis leading towards gaps in drug approval, physician and patient knowledge of new gene therapies, and ultimate delivery of these drugs. Identifying patients that would benefit from these drugs and other coordination of care issues have arisen with each unique gene therapy product. These gene therapies have unique requirements and patient indications that require a knowledgeable group of physicians and hospital administrators to incorporate their use as a standard of care. With more gene therapies on the near horizon for FDA approval, multidisciplinary teams may improve patient access to these drugs by streamlining approaches towards adapting gene therapies into clinical use.

Summary: The rapid increase in the number of FDA-approved gene therapies has not only created a number of challenges but also opportunities to improve the lives of pediatric patients with rare disorders. The adaptability of physicians, hospitals, and governmental regulatory boards is essential for delivering these new gene therapies safely and efficiently to these rare disease patients. Challenges still remain as to future requirements for additional gene therapy dosing and how to best manage financial burdens placed on the patient and providing institution.

Purpose of review: The national workforce shortage in genetics is being evaluated in order to identify a sustainable solution to the increasing demand for genomic services. An innovative solution to the short term needs is to integrate advanced practice providers (APPs) and embed genetic counselors into both outpatient and inpatient specialty care. Incorporating APPs into a genetic service is not unique in itself, but the method of implementation at Medical College of Wisconsin (MCW) was, at the time, unchartered.

Recent findings: There are >100 vacancies for board certified medical geneticists across the nation, training programs are not enrolling sufficient trainees to meet demand and more than a third of the current workforce plan to retire within the next 10 years.

Summary: The integration of advanced practice providers (nurse practitioners, midwives, physician assistants etc.) into both primary and specialty care has been an evolving practice since the mid-1900s and incorporating APPs into a genetic service was not unique in itself but the method of implementation was new at that time. This is a model to successfully develop a clinical practice model around a team-based structure incorporating nurse clinicians, advanced practice providers, genetic counselors, nutritionists, and physicians into an academic clinical genetics practice.

Purpose of review: Critically ill children are at risk of neurologic dysfunction and acquiring primary and secondary brain injury. Close monitoring of cerebral function is crucial to prevent, detect, and treat these complications.

Recent findings: A variety of neuromonitoring modalities are currently used in pediatric and neonatal ICUs. These include noninvasive modalities, such as electroencephalography, transcranial Doppler, and near-infrared spectroscopy, as well as invasive methods including intracranial pressure monitoring, brain tissue oxygen measurement, and cerebral microdialysis. Each modality offers unique insights into neurologic function, cerebral circulation, or metabolism to support individualized neurologic care based on a patient's own physiology. Utilization of these modalities in ICUs results in reduced neurologic injury and mortality and improved neurodevelopmental outcomes.

Summary: Monitoring of neurologic function can significantly improve care of critically ill children. Additional research is needed to establish normative values in pediatric patients and to standardize the use of these modalities.