Retrospective study of haemophagocytic syndrome hospitalisations in children in the USA.

INTRODUCTION: The haemophagocytic syndrome (HS) is a rare condition that presents with uncontrolled inflammation leading to multiorgan failure and is associated with significant morbidity and mortality. Current national estimates of children hospitalised due to HS are unknown. Characterising and understanding the burden of HS-related hospitalisations at a national level is the initial step in optimising the overall care. METHODS: We performed a retrospective analysis of the Nationwide Inpatient Sample (NIS) from 2012 to 2014. The NIS is the largest all-payer inpatient care dataset in the USA that contains more than seven million hospital stays and its large sample size is ideal for developing national estimates of rare conditions. All patients aged up to 18 years who were primarily hospitalised due to HS were selected for our study. Descriptive statistics were used. A multitude of patient-level and hospital-level variables were assessed. Outcome variables included overall in-hospital mortality, hospital charges and the length of stay. RESULTS: A total of 840 patients aged up to 18 years were hospitalised primarily due to HS in the USA. Mean age was 5.7 years. 57.4% were males. Whites comprised 45%. 6.5% died in hospital. A vast majority (78%) were admitted on an emergency/urgent basis. The most frequent payers included Medicaid (50%) and private insurance (36.9%). Almost 80% of children had at least one comorbid condition. 96.3% of patients were treated in urban teaching hospitals. Southern regions accounted for 42.6% of all hospitalisations. The median length of stay in hospital was 9.6 days and the median hospitalisation charge was US$100 426. CONCLUSION: Nearly 1 in 15 children who were hospitalised due to HS died. The resource utilisation associated with HS-related hospitalisations is considerable. The majority of hospitalised children with HS had comorbid conditions.

Successful use of extracorporeal membrane oxygenation in a child with obstructive shock due to massive bilateral pulmonary embolism.

BACKGROUND: Acute massive pulmonary embolism (PE) is a very rare condition in children. We report the successful use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) as a lifesaving modality in a child with acute massive PE. CASE PRESENTATION: A nine-year-old female with spinal muscular atrophy type 1, chronic respiratory failure with tracheostomy and ventilator dependence presented with tachypnea and hypoxia. She had recent coiling of her pulmonary arterio-venous malformation. A chest computerized tomography scan showed massive bilateral PE. Urgent catheter-directed thrombolysis failed. She was placed on VA-ECMO with stabilization of hemodynamics. She underwent surgical thrombo-embolectomy followed by weaning of ECMO support. DISCUSSION: The use of VA ECMO supported the cardio-respiratory status and perfusion to facilitate surgical embolectomy.

The oncogenic membrane protein LMP1 sequesters TRAF3 in B-cell lymphoma cells to produce functional TRAF3 deficiency.

Loss-of-function mutations in genes encoding the signaling protein tumor necrosis factor receptor-associated factor 3 (TRAF3) are commonly found in human B-cell malignancies, especially multiple myeloma and B-cell lymphoma (BCL). B-cell TRAF3 deficiency results in enhanced cell survival, elevated activation receptor signaling, and increased activity of certain transcriptional pathways regulating expression of prosurvival proteins. A recent analysis of TRAF3 protein staining of ∼300 human BCL tissue samples revealed that a higher proportion of samples expressing the oncogenic Epstein-Barr virus-encoded protein latent membrane protein 1 (LMP1) showed low/negative TRAF3 staining than predicted. LMP1, a dysregulated mimic of the CD40 receptor, binds TRAF3 more effectively than CD40. We hypothesized that LMP1 may sequester TRAF3, reducing its availability to inhibit prosurvival signaling pathways in the B cell. This hypothesis was addressed via 2 complementary approaches: (1) comparison of TRAF3-regulated activation and survival-related events with relative LMP1 expression in human BCL lines and (2) analysis of the impact upon such events in matched pairs of mouse BCL lines, both parental cells and subclones transfected with inducible LMP1, either wild-type LMP1 or a mutant LMP1 with defective TRAF3 binding. Results from both approaches showed that LMP1-expressing B cells display a phenotype highly similar to that of B cells lacking TRAF3 genes, indicating that LMP1 can render B cells functionally TRAF3 deficient without TRAF3 gene mutations, a finding of significant relevance to selecting pathway-targeted therapies for B-cell malignancies.

Endothelial progenitor cell biology in disease and tissue regeneration.

Endothelial progenitor cells are increasingly being studied in various diseases ranging from ischemia, diabetic retinopathy, and in cancer. The discovery that these cells can be mobilized from their bone marrow niche to sites of inflammation and tumor to induce neovasculogenesis has afforded a novel opportunity to understand the tissue microenvironment and specific cell-cell interactive pathways. This review provides a comprehensive up-to-date understanding of the physiological function and therapeutic utility of these cells. The emphasis is on the systemic factors that modulate their differentiation/mobilization and survival and presents the challenges of its potential therapeutic clinical utility as a diagnostic and prognostic reagent.