Evaluation of venous thromboembolism risk factors reveals subtype heterogenicity in children with central venous catheters: a multicenter study from the Children's Hospital Acquired Thrombosis consortium.

Background: Acutely ill and medically complex children frequently rely on central venous catheters (CVCs) to provide life-sustaining treatment. Unfortunately, catheter-related thrombosis (CRT) is a serious and common complication. Little is known why some with a CVC develop CRT and others develop venous thromboembolism unrelated to the CVC (non-CRT).

Return emergency department visits for recurrent pulmonary embolism symptoms in children and adolescents.

Rates of pulmonary embolism (PE) in children have steadily increased over the past 2 decades. Patient outcomes after hospital discharge are poorly understood, and many patients experience recurrent or persistent chest pain or dyspnea, prompting a return to care. This retrospective cohort study of patients diagnosed with PE at a large children's hospital over a 9.

Astrocytes mediate cell non-autonomous correction of aberrant firing in human FXS neurons.

Pre-clinical studies of fragile X syndrome (FXS) have focused on neurons, with the role of glia remaining largely underexplored. We examined the astrocytic regulation of aberrant firing of FXS neurons derived from human pluripotent stem cells. Human FXS cortical neurons, co-cultured with human FXS astrocytes, fired frequent short-duration spontaneous bursts of action potentials compared with less frequent, longer-duration bursts of control neurons co-cultured with control astrocytes.

The ciliary gene INPP5E confers dorsal telencephalic identity to human cortical organoids by negatively regulating Sonic hedgehog signaling.

Defects in primary cilia, cellular antennas that control multiple intracellular signaling pathways, underlie several neurodevelopmental disorders, but it remains unknown how cilia control essential steps in human brain formation. Here, we show that cilia are present on the apical surface of radial glial cells in human fetal forebrain. Interfering with cilia signaling in human organoids by mutating the INPP5E gene leads to the formation of ventral telencephalic cell types instead of cortical progenitors and neurons.

The Histone Deacetylase 9 Stroke-Risk Variant Promotes Apoptosis and Inflammation in a Human iPSC-Derived Smooth Muscle Cells Model.

A common variant in the Histone Deacetylase 9 () gene is the strongest genetic risk for large-vessel stroke, and HDAC9 offers a novel target for therapeutic modulation. However, the mechanisms linking the variant with increased stroke risk is still unclear due to the lack of relevant models to study the underlying molecular mechanisms. We generated vascular smooth muscle cells using human induced pluripotent stem cells with the stroke risk variant to assess HDAC9-mediated phenotypic changes in a relevant cells model and test the efficacy of HDAC inhibitors for potential therapeutic strategies.

Symptomatic pulmonary embolus after catheter removal in children with catheter related thrombosis: A report from the CHAT Consortium.

Background: Appropriate timing of central venous catheter (CVC) removal, in relation to start of anticoagulation, in children after the diagnosis of a CVC-related thrombosis (CRT) is not well established.

Objectives: This retrospective cohort study evaluated the incidence of symptomatic pulmonary embolism (PE) after CVC removal using data from the multi-institutional Children's Hospital-Acquired Thrombosis (CHAT) Consortium Registry.

Patients/methods: The CHAT Registry consists of data from children aged 0-21 years with a hospital-acquired venous thromboembolism.

A New Risk Assessment Model for Hospital-Acquired Venous Thromboembolism in Critically Ill Children: A Report From the Children's Hospital-Acquired Thrombosis Consortium.

Objectives: To create a risk model for hospital-acquired venous thromboembolism in critically ill children upon admission to an ICU.

Design: Case-control study.

Setting: ICUs from eight children's hospitals throughout the United States.

Development of a Risk Model for Pediatric Hospital-Acquired Thrombosis: A Report from the Children's Hospital-Acquired Thrombosis Consortium.

Objective: To identify pertinent clinical variables discernible on the day of hospital admission that can be used to assess risk for hospital-acquired venous thromboembolism (HA-VTE) in children.

Study Design: The Children's Hospital-Acquired Thrombosis Registry is a multi-institutional registry for all hospitalized participants aged 0-21 years diagnosed with a HA-VTE and non-VTE controls. A risk assessment model (RAM) for the development of HA-VTE using demographic and clinical VTE risk factors present at hospital admission was derived using weighted logistic regression and the least absolute shrinkage and selection (Lasso) procedure.

Atypical Outcomes for Hepatitis-associated Acquired Aplastic Anemia: 2 Case Studies and Review of the Literature.

There is little data specifically dedicated to the long-term outcomes of the hepatitis-associated variant of aplastic anemia (HAAA). A majority of patients with nonsevere (moderate) aplastic anemia progress to severe aplastic anemia, and severe aplastic anemia typically results in death if left untreated. We present 2 unique cases of HAAA that contribute to our knowledge of the natural history of this disease variant.

Generation of twenty four induced pluripotent stem cell lines from twenty four members of the Lothian Birth Cohort 1936.

Cognitive decline is among the most feared aspects of ageing. We have generated induced pluripotent stem cells (iPSCs) from 24 people from the Lothian Birth Cohort 1936, whose cognitive ability was tested in childhood and in older age. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating oriP/EBNA1 backbone plasmids expressing six iPSC reprogramming factors (OCT3/4 (POU5F1), SOX2, KLF4, L-Myc, shp53, Lin28, SV40LT).

Conditional Gene Knockout in Human Cells with Inducible CRISPR/Cas9.

The advent of the easily programmable and efficient CRISPR/Cas9 nuclease system has revolutionized genetic engineering. While conventional gene knockout experiments using CRISPR/Cas9 are very valuable, these are not well suited to study stage-specific gene function in dynamic situations such as development or disease. Here we describe a CRISPR/Cas9-based OPTimized inducible gene KnockOut method (OPTiKO) for conditional loss-of-function studies in human cells.

Improving the Evaluation and Management of Abnormal Uterine Bleeding in Female Adolescents Presenting for Emergency Care.

Study Objective: We sought to improve emergency care for adolescents with abnormal uterine bleeding (AUB) by developing a clinical effectiveness guideline (CEG) and assessing its effect on quality of care.

Design, Setting, Participants, And Interventions: A stakeholder engagement group designed a CEG algorithm for emergency AUB management. Pediatric residents received CEG training and their knowledge and attitudes were assessed using pre- and post intervention surveys.

Response to treatment and adverse events associated with use of recombinant activated factor VII in children: a retrospective cohort study.

Background: Recombinant activated factor VII (rFVIIa) is United States (US) Food and Drug Administration (FDA)-approved for patients with hemophilia with inhibitors or congenital factor VII deficiency. Initial reports of off-label use highlighted its efficacy, though newer reports have not repeated these findings. In both types of publication, though, secondary thromboses have been seen in adult patients.

Venous thromboembolism in pediatric trauma patients: Ten-year experience and long-term follow-up in a tertiary care center.

Background: Pediatric trauma patients are at high risk for development of venous thromboembolism (VTE). Our objective is to describe incidence, risk factors, and timing of development of VTE, anticoagulation complications, and long-term VTE outcomes in a critically injured pediatric population.

Procedure: We did a retrospective review of pediatric (0-17 years) trauma admissions to intensive care unit from 2005 to 2014.

Optimized inducible shRNA and CRISPR/Cas9 platforms for in vitro studies of human development using hPSCs.

Inducible loss of gene function experiments are necessary to uncover mechanisms underlying development, physiology and disease. However, current methods are complex, lack robustness and do not work in multiple cell types. Here we address these limitations by developing single-step optimized inducible gene knockdown or knockout (sOPTiKD or sOPTiKO) platforms.

A Comparison of Extremity Thrombosis Rates in Adolescent and Young Adult Versus Younger Pediatric Oncology Patients at a Children's Hospital.

Purpose: To examine whether the rates of thrombosis in children (≤14 years of age) and adolescent/young adult (AYA) patients (15-22 years of age) with cancer is different.

Methods: We retrospectively studied the rates of thrombosis in children and AYA patients at the Children's Hospital of Pittsburgh during the years 2002-2010, using the tumor registry database. This list was then divided into two groups based on age at diagnosis.

Three cost-utility analyses of screening for intracranial hemorrhage in neonates with hemophilia.

Background: Intracranial hemorrhage (ICH) in the newborn period is a potential cause of serious morbidity and mortality in individuals with hemophilia. The incidence of ICH is estimated to be 2% to 4%; however, depending on the mode of delivery, it may be considerably higher. Considering the varying sensitivities and costs of various imaging modalities, there remains controversy surrounding universal cranial imaging.

The zebrafish reference genome sequence and its relationship to the human genome.

Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes.

A resource of vectors and ES cells for targeted deletion of microRNAs in mice.

The 21-23 nucleotide, single-stranded RNAs classified as microRNAs (miRNA) perform fundamental roles in diverse cellular and developmental processes. In contrast to the situation for protein-coding genes, no public resource of miRNA mouse mutant alleles exists. Here we describe a collection of 428 miRNA targeting vectors covering 476 of the miRNA genes annotated in the miRBase registry.

A cost-effectiveness analysis of coagulation testing prior to tonsillectomy and adenoidectomy in children.

Background: The American Society of Pediatric Otolaryngology recommends pre-operative coagulation testing only when indicated by history or physical exam. Nevertheless, many surgeons test all children scheduled for tonsillectomy and/or adenoidectomy (T&A). Studies of pre-operative screening have had conflicting results.