Current opinion in pediatrics最新文献

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: To highlight the clinical presentation, diagnostic approach, and management of acquired inflammatory demyelinating syndromes in children.

Recent findings: The identification of myelin oligodendrocyte glycoprotein antibody-associated disease in 2017 and evolving evidence regarding best practices for management has had a significant impact on pediatric neuroimmunology, as has the shift in treatment of pediatric-onset multiple sclerosis, with the use of high-efficacy disease-modifying therapies early in the disease course.

Summary: With expanding awareness and growing interest in pediatric onset neuroinflammatory conditions, the number of children diagnosed with acquired demyelinating syndromes is rising. It is critical to refine our understanding of the underlying pathophysiological mechanisms in these disorders to provide the most effective care. Much of our practice continues to be modeled on adult care, and further large-scale pediatric studies are necessary to explore the natural history and assess the safety and efficacy of immunotherapies in childhood-onset demyelinating diseases.

Purpose of review: Patients with a functionally single ventricle (SV) are palliated with a series of procedures leading to a Fontan circulation. Over the life span, a substantial proportion of SV patients develop heart failure that can arise from circulatory or ventricular failure. Diastolic dysfunction (DD) is an important determinant of adverse outcomes in SV patients. However, assessment and categorization of DD in the SV remains elusive. We review recent literature and developments in assessment of DD in the SV and its relation to clinical outcomes.

Recent findings: DD is prevalent in the SV and associated with worse outcomes. Occult DD can be exposed with provocative testing by exercise or preload challenge during catheterization. Likewise, sensitivity to detect DD may be increased via assessment of atrial function and strain imaging. Recent studies revisiting previous concepts such as incoordinate diastolic wall motion show that these are associated with SV end-diastolic pressures and post-Fontan recovery, yielding accessible DD assessment. Emerging technologies such as ultrafast ultrasound (UFUS) can provide noninvasive assessment of myocardial stiffness, inefficient diastolic flow patterns and intraventricular pressure gradients, thereby yielding new tools and insights into diastolic myocardial and hemodynamic properties.

Summary: Characterizing DD in the SV continues to have substantial limitations, necessitating synthesis of multiple parameters into an overall assessment, accounting for their change over time, and in the context of the patient's clinical status. New and emerging techniques may help advance DD assessment and the ability to track response to treatment of new targets.

Purpose of review: To provide an updated review of novel and complementary treatment approaches for children and adolescents with attention-deficit/hyperactivity disorder.

Recent findings: The evidence for complementary attention-deficit/hyperactivity disorder treatments is often promising, but limited to small, unblinded studies. Recent evidence from larger, more rigorous studies reveals that most of these treatments have modest efficacy. Omega-3 polyunsaturated fatty acids, saffron, broad spectrum micronutrients, and physical exercise have potential benefits that seem to outweigh known risks. However, neurofeedback, cognitive training, and trigeminal nerve stimulation need further research to determine whether specific sub-groups of children/adolescents with attention-deficit/hyperactivity disorder would benefit long-term with their associated tolerable risks.

Summary: There is not sufficient evidence for complementary treatments to be recommended as substitutes for first-line pharmacological and psychosocial treatment options. Nonetheless, some adjuvant therapies to currently recommended attention-deficit/hyperactivity disorder treatments can be safe. Physicians should be familiar with existing and emerging complementary treatments to help guide families.

Purpose of review: Pulmonary hypertension (PH) is commonly observed in premature infants with bronchopulmonary dysplasia (BPD) and is associated with poor outcomes and increased mortality. This review explores the management of this intricate condition of the pulmonary vasculature, which exhibits heterogeneous effects and may involve both arterial and postcapillary components.

Recent findings: Current management of BPD-PH should focus on optimizing ventilatory support, which involves treatment of underlying lung disease, transitioning to a chronic phase ventilation strategy and evaluation of the airway. Data on management is limited to observational studies. Diuretics are considered a part of the initial management, particularly in infants with right ventricular dilation. In many cases, pulmonary vasodilator therapy is required to induce pulmonary arterial vasodilation, reduce right ventricular strain, and prevent coronary ischemia and heart failure. Echocardiography plays a pivotal role in guiding treatment decisions and monitoring disease progression.

Summary: BPD-PH confers a heightened risk of mortality and long-term cardio-respiratory adverse outcomes. Echocardiography has been advocated for screening, while catheterization allows for confirmation in select more complex cases. Successful management of BPD-PH requires a multidisciplinary approach, focusing on optimizing BPD treatment and addressing underlying pathologies.

Purpose of review: Speckle tracking echocardiography (STE)-derived measures of myocardial mechanics, referred to herewithin as strain measurements, directly assess myocardial contractility and provide a nuanced assessment of ventricular function. This review provides an overview of strain measurements and their current clinical value and utility in decision making in pediatric cardiology.

Recent findings: Strain measurements are advancing understanding of how cardiac dysfunction occurs in children with acquired and congenital heart disease (CHD). Global strain measurements can detect early changes in cardiac function and are reliable methods of serially monitoring systolic function in children. Global strain measurements are increasingly reported in echocardiographic assessment of ventricular function alongside ejection fraction. Research is increasingly focused on how strain measurements can help improve clinical management, risk stratification, and prognostic insight. Although more research is needed, preliminary studies provide hope that there will be clinical benefit for strain in pediatric cardiology management.

Summary: Strain measurements provide a more detailed assessment of ventricular function than conventional measures of echocardiographic functional assessment. Strain measurements are increasingly being used to advance understanding of normal and abnormal myocardial contractility, to increase sensitivity to detect early cardiac dysfunction, and to improve prognostic management in children with acquired and CHD.

Purpose of review: This article highlights the most recent advances in a review of the current literature in the field of pediatric heart failure and transplantation.

Recent findings: Diagnostically, the identification of new genetic factors has contributed to a deeper understanding of cardiomyopathy in children. Novel medications like sacubitril/valsartan and Sodium-Glucose cotransporter-2 (SGLT2) inhibitors, which are now standard in the adult population are being studied in pediatric population and offer new promise of pediatric heart failure treatment. Ventricular assist devices are more commonly used in cardiomyopathy patients and single ventricle patients as a bridge to transplant. Recent pediatric heart transplant society (PHTS) data demonstrated that waitlist survival improved significantly over the past decades (i) and new treatments such as daratumumab and eculizumab have been used in high-risk populations and demonstrate promising results. TEAMMATE trial is the first multicenter randomized clinical trial (RCT) in pediatric heart transplant (HT) to evaluate the safety and efficacy of everolimus (EVL) and low-dose tacrolimus (TAC) compared to standard-dose TAC and mycophenolate mofetil (MMF). It will provide valuable information about the safety and efficacy of EVL, TAC, and MMF (ii).Donor cell-free DNA has been used more in pediatric transplant recipients and has significantly decreased invasive EMB (iii).

Summary: This past 5 years have witness dramatic progress in the field of pediatric heart failure and transplantation including more use of mechanical support in heart failure patients with various underlying etiology, especially use of mechanical support in single ventricle patients and the use of sacubitril/valsartan and SGLT2 inhibitors in the pediatric population. The problem of the highly sensitized transplant recipient remains, although novel therapeutics have been added to our toolbox of options to maintain healthy allograft function. Ongoing research aims to further enhance our understanding and management of pediatric heart failure, emphasizing the need for continued innovation in this complex field.

Purpose of review: To highlight recent advances in pediatric cholestatic liver disease, including promising novel prognostic markers and new therapies.

Findings: Additional genetic variants associated with the progressive familial intrahepatic cholestasis (PFIC) phenotype and new genetic cholangiopathies, with an emerging role of ciliopathy genes, are increasingly being identified. Genotype severity predicts outcomes in bile salt export pump (BSEP) deficiency, and post-biliary diversion serum bile acid levels significantly affect native liver survival in BSEP and progressive familial intrahepatic cholestasis type 1 (FIC1 deficiency) patients. Heterozygous variants in the MDR3 gene have been associated with various cholestatic liver disease phenotypes in adults. Ileal bile acid transporter (IBAT) inhibitors, approved for pruritus in PFIC and Alagille Syndrome (ALGS), have been associated with improved long-term quality of life and event-free survival.

Summary: Next-generation sequencing (NGS) technologies have revolutionized diagnostic approaches, while discovery of new intracellular signaling pathways show promise in identifying therapeutic targets and personalized strategies. Bile acids may play a significant role in hepatic damage progression, suggesting their monitoring could guide cholestatic liver disease management. IBAT inhibitors should be incorporated early into routine management algorithms for pruritus. Data are emerging as to whether IBAT inhibitors are impacting disease biology and modifying the natural history of the cholestasis.