Background Spirometry is conventionally used to diagnose airway diseases in children with sickle cell disease (C‐SCD). However, spirometry is difficult for younger children to perform, is effort dependent, and it provides limited information on respiratory mechanics. Impulse oscillometry (IOS) is an effort‐independent pulmonary function test (PFT), which measures total airway resistance (R5Hz) and reactance (AX). IOS could be advantageous without certain limitations of spirometry. Aim To compare the accuracy of IOS vs spirometry in making the diagnosis of asthma and assessing age‐related pulmonary changes in C‐SCD. Study design Retrospective chart review. Subject selection Fifty‐six C‐SCD and thirty‐six controls (asthmatics without SCD) followed at Penn State with PFTs obtained during the initial pulmonary evaluation. Methodology We grouped C‐SCD into asthmatics and non‐asthmatics based on pre‐referral diagnosis and compared PFTs between two groups. Receiver operating characteristic (ROC) curve analyses and machine learning tools (XGBoost and artificial neural network) were used to rank the spirometry and IOS measures based on their ability to predict a diagnosis of asthma. Robust linear regression was used to analyze association among height/age with various PFT measures. Results Both ROC and XGBoost indicated that FEF25‐75%, forced expiratory volume in 1 second (FEV1)/forced vital capacity, and R5Hz(%) were the top three predictors for asthma diagnosis. R5Hz(%) and AX had superior bronchodilator response (BDR) than FEV1. IOS parameters had significant association with height/age in C‐SCD (possibly due to the stiff lungs) but not in controls. Conclusion IOS had advantages over spirometry in C‐SCD because it is feasible in early childhood, provides insights into the pulmonary mechanics, and is more sensitive to detect BDR.

A full-term newborn with kaposiform hemangioendothelioma (KHE) affecting the right thigh with thrombocytopenia due to Kasabach-Merritt phenomenon (KMP) was referred to our center. After biopsy, he rapidly evolved to severe thrombocytopenia and severe coagulopathy. Standard therapy was initiated with prednisolone and vincristine. His coagulopathy worsened to life-threatening hemorrhage necessitating aggressive blood products replacement. Sirolimus was added; he became transfusion independent with no further bleeding and reduction in tumor size. Addition of sirolimus to treatment of vascular anomalies with hemostatic complications should be considered as part of early treatment for patients with KMP/KHE.

Regulation of oncogenic gene expression by transcription factors that function as tumor suppressors is one of the major mechanisms that regulate leukemogenesis. Understanding this complex process is essential for explaining the pathogenesis of leukemia as well as developing targeted therapies. Here, we provide an overview of the role of Ikaros tumor suppressor and its role in regulation of gene transcription in acute leukemia. Ikaros (IKZF1) is a DNA-binding protein that functions as a master regulator of hematopoiesis and the immune system, as well as a tumor suppressor in acute lymphoblastic leukemia (ALL). Genetic alteration or functional inactivation of Ikaros results in the development of high-risk leukemia. Ikaros binds to the specific consensus binding motif at upstream regulatory elements of its target genes, recruits chromatin-remodeling complexes and activates or represses transcription via chromatin remodeling. Over the last twenty years, a large number of Ikaros target genes have been identified, and the role of Ikaros in the regulation of their expression provided insight into the mechanisms of Ikaros tumor suppressor function in leukemia. Here we summarize the role of Ikaros in the regulation of the expression of the genes whose function is critical for cellular proliferation, development, and progression of acute lymphoblastic leukemia.

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