Implementing a behavioral physical activity program in children and adolescent survivors of childhood cancer: a pilot randomized controlled trial.

Purpose We aimed to document the acceptability (enrollment rate) and feasibility (phone call delivery rate) of implementing a behavioral PA intervention over 12 weeks, in addition to documenting its effects on patient-reported outcomes and physical functioning. This study also describes the costs of carrying out a behavioral PA intervention. A total of 40 participants were randomized in a 1:1 ratio. The tailored behavioral PA intervention was developed based on the most recent PA guidelines in pediatric oncology and on the COM-B framework to enact PA behavior changes. The prescription (frequency, intensity, time and type (FITT)) was adjusted each week during the weekly support calls. The control group did not receive the intervention. 26 males and 14 females (13.6 years old on average and 2.9 years post-cancer treatment on average) participated in our study. The acceptability rate was 90.9% and the feasibility rate was > 85%. We found that 85% improved PA frequency, 80% improved PA intensity, 100% improved PA time, and 50.0% achieved the recommended PA guidelines. No adverse events were reported over the duration of the intervention. Physical function improved with longer 6-minute walk distances in the intervention group (465.8 ± 74.5 m) than in the control group (398.7 ± 92.9 m) (p = 0.016). PROs scores for all participants were within the limits of the normal range. The estimated cost per participant of carrying out this intervention was USD $126.57. Our 12-week behavioral PA intervention, based on the COM-B framework, was found to be acceptable, feasible and safe in childhood cancer survivors. This study is an important step in the right direction to make exercise standard practice in pediatric oncology.

Determinants of Decision Regret Regarding Fertility Preservation in Adolescent and Young Adult Cancer Survivors: A Systematic Review.

Given recent advances in cancer therapeutics, there is a growing population of adolescent and young adult (AYA) cancer survivors navigating the physical and psychological consequences of cancer treatment. Fertility preservation (FP) conversations are of increasing importance for these survivors. Decision regret (DR) is a measure of distress or remorse following a health care decision, and it is a useful tool to evaluate the impact of a treatment on quality of life. The aim of this systematic review is to culminate existing literature focused on determinants of FP DR among AYA cancer survivors and to propose future interventions to reduce DR among AYA cancer survivors. An electronic database search was performed using PubMed, Web of Science, and APA PsycINFO for articles published before December 2023 using the following search criteria: PubMed: "Fertility Preservation"[Mesh] AND decision regret, APA PsycINFO and Web of Science: Fertility Preservation AND decision regret. Articles were organized into five categories that emerged after initial review. Nineteen articles that focused on DR and FP in AYA cancer survivors aged ≤40 and ≥12 years were included. Article results were categorized into five categories pertaining to determinants of FP DR: Unmet Informational and Emotional Needs, Need for Developmentally Appropriate Conversations, Insufficiency of Provider Training, Quality and Timeliness of Fertility Preservation Discussions, and Societal Barriers. These results highlight the need for improved patient and provider education on FP, such as future longitudinal studies focused on standardization of FP-related protocols and the impact of their implementation on DR, especially for AYA cancer survivors.

Double and single mixed-lineage leukemia-rearranged subclones in pediatric acute myeloid leukemia: a case report.

BACKGROUND: Acute myeloid leukemia (AML) is a disease with a significant amount of cytogenetic heterogeneity including mixed-lineage leukemia (MLL) gene rearrangements. Pediatric AML commonly has genetic rearrangements which involve chromosome 11q23 in 15-20% of cases, and these genetic abnormalities have been associated with a poorer prognosis (Grimwade et al. in Blood 92:2322-2333, 1998; Raimondi et al. in Blood 94:3707-3716, 1999; Lie et al. in Br J Haematol 122: 217-225). MLL rearrangements in AML have been shown to have multiple different fusion partners (Meyer et al. in Leukemia 23:1490-1499). Heterogeneity of these cytogenetic abnormalities makes it difficult to determine how to approach patients from a treatment standpoint. This difficulty is further complicated when patients have more than a single MLL rearrangement. CASE PRESENTATION: A 10-year-old Caucasian girl presented with easy bruising and was found to have acute myeloid leukemia. Her cytogenetics showed two different MLL rearrangements, t(9;11)(p22;q23) and t(11;19)(q23;p13.3). At initial presentation she had no other cytogenetic findings. She responded well to initial therapy and achieved remission following the first induction cycle and completed four rounds of chemotherapy. She subsequently had a relapse of her AML, and her cytogenetics were consistent with a single MLL rearrangement, t(9;11)(p22;q23), in addition to monosomy 7. She was treated with reduction therapy and a haplo-identical bone marrow transplant but ultimately succumbed to her disease. CONCLUSION: MLL rearrangements are common in AML, but clinical significance continues to be elusive, and there is conflicting data on the prognostic significance. In the setting of multiple MLL rearrangements, there is concern for reduced survival, although treatment modifications are not currently done in this setting. This report details a case with multiple MLL rearrangements that initially responded to therapy but ultimately had disease progression with a selection of a leukemic clone containing a single MLL rearrangement.

Two novel deleterious variants of Angiotensin-I-converting Enzyme gene identified in a family with recurrent anhydramnios.

BACKGROUND: Anhydramnios results from the poor development of the placenta or problems with intrauterine development of the kidneys or urinary tract. Complete lack of amniotic fluid indicates a severe problem with the organs of the urinary system. The genes associated with anhydramnios show very diversity and are not yet well defined. METHODS: Whole-exome sequencing (WES) was used for an aborted male case around the 20th week of gestation diagnosed with anhydramnios. The resulted deleterious variants were verified by Sanger sequencing. Pathogenicity of deleterious variants was explored by in silico analysis. RESULTS: A maternally inherited deleterious frameshift variant, c.1454_1455insC, p.(S486Ffs29) in exon 9 and two paternally inherited missense variants c.1037C > G, p.(Ser346Trp) in exon 7 and c.1465A > G, p.(Asn489Asp) in exon 9 of Angiotensin-I-Converting Enzyme (ACE) gene were found and confirmed by Sanger sequencing. c.1454_1455insC, p.(S486Ffs29) and c.1037C > G, p.(Ser346Trp) were identified as two novel compound heterozygous deleterious variants. The pathogenicity of these deleterious variants was determined by in silico analysis and both the deleterious variants disrupt the structure of the ACE protein. CONCLUSION: Two novel compound heterozygous variants were identified in the case with anhydramnios, which may be associated with pathogenicity of anhydramnios. Our data also revealed that the WES approach may provide helpful information for genetic counseling of the families with anhydramnios.

Transcriptional Regulation of Genes by Ikaros Tumor Suppressor in Acute Lymphoblastic Leukemia.

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.

Pediatric-Oncology Simulation Training for Resident Education.

INTRODUCTION: We sought to evaluate pediatric oncology simulations intended to improve pediatric residents' skills and comfort in caring for children with cancer. METHOD: In a non-randomized trial, controls (the first three rotations) received a standard set of lectures, and the intervention arm received these lectures plus five simulation-training scenarios-fever/neutropenia, a new leukemia diagnosis, end-of-life care discussion, tumor lysis syndrome, and a mediastinal mass. All residents were tested after the rotation on the first three scenarios; management skills were evaluated independently by two raters. Before and after training, all residents completed an emotional-appraisal questionnaire evaluating each scenario as a perceived challenge or threat. Analysis of variance (ANOVA) measured differences by study arm in skills-checklist assessments and appraisals; repeated-measures ANOVA measured changes in emotional-appraisal scores. RESULTS: Forty-two residents (9 control, 33 intervention) participated. Inter-rater agreement for skills-checklist scores using average-measures intraclass correlation was high (0.847), and overall mean scores were significantly higher for the intervention than control group across both raters (P = 0.005). For all residents, perceived challenge increased in the end-of-life simulation, and perceived threat decreased in all three test scenarios. The intervention group, regardless of training year, evaluated the teaching scenarios favorably and felt that challenging oncology situations were addressed, skills were enhanced, and the simulations should be offered to other residents. CONCLUSIONS: It was feasible to introduce residents to difficult pediatric oncology scenarios using simulation. The intervention group performed more skills than controls when tested, and perceive threat declined in all residents after their pediatric oncology rotation.

Diagnostic value of spirometry vs impulse oscillometry: A comparative study in children with sickle cell disease.

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.

Kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon in an infant: Successful treatment with prednisolone, vincristine, and addition of sirolimus.

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.

Variability in State-Based Recommendations for Management of Alpha Thalassemia Trait and Silent Carrier Detected on the Newborn Screen.

We conducted an inventory of state-based recommendations for follow-up of alpha thalassemia silent carrier and trait identified on newborn screen. We found wide variability in the nature and timing of these recommendations. We recommend a standardized recommendation to guide pediatricians in evidenced-based care for this population.