Advances in our understanding of genetic markers and targeted therapies for pediatric LCH.

INTRODUCTION: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm, encompassing a diverse clinical spectrum ranging from localized bone or skin lesions to a multisystemic life-threatening condition. Over the past decade, there has been an expansion in understanding the molecular biology of LCH, which translated into innovative targeted therapeutic approaches. AREAS COVERED: In this article, we will review the molecular alterations observed in pediatric LCH and the relationship between these molecular changes and the clinical phenotype, as well as targeted therapies in LCH. EXPERT OPINION: Mitogen-activated protein kinase (MAPK) pathway mutation is a hallmark of LCH and is identified in 80% of the cases. Notably, BRAFV600E mutation is seen in ~50-60% of the cases, ~30% has other MAPK pathway mutations, while 15-20% have no detected mutations. While the first line therapeutic approach is vinblastine and prednisone, targeted therapies - specifically BRAF/MEK inhibitors - emerged as a promising second-line salvage strategy, particularly when a mutation is identified. Most patients respond to BRAF/MEK inhibitors but at least 75% reactivate after stopping, however, most patients respond again when restarting inhibitors.

Do Children With an Allergic Transfusion Reaction Require Premedication For All Blood Products?

BACKGROUND: Children with a history of allergic transfusion reactions (ATRs) receive antihistamine premedication with or without hydrocortisone to prevent subsequent reactions. We aim to examine the frequency of developing ATRs to subsequent different blood product type transfusions. METHODS: A retrospective chart review of children who received blood product transfusions (packed red blood cells, platelets, frozen plasma, intravenous immunoglobin, albumin, and cryoprecipitate) and developed ATRs. Cases were identified through Transfusion Transmitted Injuries Surveillance System- Ontario database with a complementary chart review. Demographics and subsequent transfusions records were described. RESULTS: During this period, 35,925 blood products were transfused to 4153 patients. Thirty-eight ATRs were reported in 30 patients. All ATRs were minor except 1 anaphylaxis to albumin transfusion. Seven patients (23%) developed multiple ATRs, and all of them were of the same blood product type. A total of 60 subsequent different blood product types were transfused to the 7 patients who had multiple ATRs; none of those transfusions caused ATR. CONCLUSION: In children with a history of ATR, developing a reaction to a different blood product type is rare. Hence, premedicating those transfusions is not warranted.

Quality of Life and Glycemic Control in Saudi Children with Type 1 Diabetes at Different Developmental Age Groups.

BACKGROUND: Children with type 1 diabetes (T1D) at different stages of development have age-specific needs, which can influence their perception of quality of life (QoL). In our study, we aimed to emphasize these age-specific needs and assess the perception of QoL in Saudi children with T1D, as well as their parents correlating QoL scores with children's glycemic control. METHODS: This is a cross-sectional study in which children with T1D and their parents from 2 tertiary institutes in Saudi Arabia have answered a standard diabetes-specific QoL questionnaire (PedsQL™ 3.0 diabetes module, translated in Arabic). We also reported glycated hemoglobin (HbA1c) results for these children within a month of completing the questionnaire. The QoL total aggregate and domain scores for self (children) and proxy (parents') reports were compared and correlated with children's HbA1c. RESULTS: A sample was 288 self and proxy reports from 144 children with T1D of 3 age groups: 5 to 7 years (7%), 8 to 12 years (49%), and 13 to 18 years (44%), and their parents. QoL differed significantly between self and proxy reports in the total aggregate and domain scores (P-values range from .02 to <.001). The impact on QoL was significantly higher in female patients (P = .043). Insulin pump users had better HbA1c (P = .007), and HbA1c level was worse in those who intended to fast at Ramadan (P = .005). CONCLUSION: Children with T1D at different developmental age groups perceive QoL differently than their parents. Adjusting management as per age-specific challenges could potentially improve these children's QoL and glycemic control.

Management of Anticoagulation Therapy in Patients With Thromboembolism in the Context of Renal Dysfunction: Challenging Cases and Practical Algorithms.

BACKGROUND: Low-molecular-weight heparin is cleared through the kidneys and is commonly used for anticoagulation in the pediatric population. OBSERVATION: We present 3 challenging cases of children requiring anticoagulation in the context of acute kidney injury, nephrotic syndrome, and hemodialysis. CONCLUSIONS: A significant change in anti-factor Xa (anti-Xa) levels-used for drug monitoring-should prompt an assessment of renal function. In nephrotic syndrome, anti-Xa levels should be closely monitored when there is a change in the status of nephrotic disease activity. In hemodialysis patients, enoxaparin at once daily reduced dosing should be considered with trough and peak anti-Xa levels monitoring.