TNFα facilitates clonal expansion of JAK2V617F positive cells in myeloproliferative neoplasms.

Proinflammatory cytokines such as TNFα are elevated in patients with myeloproliferative neoplasms (MPN), but their contribution to disease pathogenesis is unknown. Here we reveal a central role for TNFα in promoting clonal dominance of JAK2(V617F) expressing cells in MPN. We show that JAK2(V617F) kinase regulates TNFα expression in cell lines and primary MPN cells and TNFα expression is correlated with JAK2(V617F) allele burden. In clonogenic assays, normal controls show reduced colony formation in the presence of TNFα while colony formation by JAK2(V617F)-positive progenitor cells is resistant or stimulated by exposure to TNFα. Ectopic JAK2(V617F) expression confers TNFα resistance to normal murine progenitor cells and overcomes inherent TNFα hypersensitivity of Fanconi anemia complementation group C deficient progenitors. Lastly, absence of TNFα limits clonal expansion and attenuates disease in a murine model of JAK2(V617F)-positive MPN. Altogether our data are consistent with a model where JAK2(V617F) promotes clonal selection by conferring TNFα resistance to a preneoplastic TNFα sensitive cell, while simultaneously generating a TNFα-rich environment. Mutations that confer resistance to environmental stem cell stressors are a recognized mechanism of clonal selection and leukemogenesis in bone marrow failure syndromes and our data suggest that this mechanism is also critical to clonal selection in MPN.

Initial experience with novel mobile cardiac outpatient telemetry for children and adolescents with suspected arrhythmia.

OBJECTIVES: To report use of a novel mobile cardiac outpatient telemetry (MCOT) system for evaluation of children and adolescents with suspected cardiac arrhythmia. DESIGN: Prospective data collection and retrospective analysis. SETTING: All patients who received MCOT from The Children's Hospital at the Cleveland Clinic between 1/14/04 and 2/12/05 were screened. Patients older than 21 years and those with previously documented arrhythmia were excluded. PATIENTS: Fifty-nine consecutive MCOT studies were performed. Five patients met exclusion criteria leaving 54 subjects (mean age 12.4+/-4.5 years; range 3.2-19.7 years; 46% male) for inclusion. INTERVENTIONS: The MCOT system (CardioNet, USA) consists of a 3-electrode, 2-channel sensor that transmits wirelessly to a portable monitor. Monitors continuously store, analyze, and transmit the electrocardiogram through cellular and land telephone networks to a central station. MCOT was performed for 9-32 consecutive days (mean 24.5+/-7.4). Results. Twenty-one subjects (39%) did not experience symptoms during MCOT, yielding a diagnostic rate of 61% (N = 33). Of the 33 diagnostic studies, 9% (N = 3; mean age 16.9+/-0.6 years; range 16.2-17.3 years; 1 male) showed supraventricular tachycardia and 9% (N = 3; mean age 11.1+/-2.7 years; range 8.2-13.5 years; 1 male) showed supraventricular or ventricular ectopy. Minor skin irritation at sites of electrode placement was the only complication of MCOT (N = 5). CONCLUSIONS: MCOT is safe and useful for evaluation of children and adolescents with suspected arrhythmia, providing a diagnosis in 61% of subjects. The diagnostic yield of MCOT was superior to that expected from traditional event and Holter monitors in this pediatric population.

A novel approach to improve influenza vaccination rates among health care professionals: a prospective randomized controlled trial.

BACKGROUND: Although influenza is the leading infections cause of death in the United States, only 40% of health care workers (HCW) comply with Centers for Disease Control and Prevention recommendation for routine influenza vaccination. METHODS: This study investigated a novel approach for improving influenza vaccination rates among HCW. Eight hundred employees we selected, 200 each from the following 4 categories: professional staff, resident physicians, registered nurses, and licensed practical nurses. Subjects were randomly assigned to receive (1) no intervention, (2) a letter explaining the importance of influenza vaccine for HCW, (3) a ticket activated with influenza vaccine administration for a raffle of a free Caribbean vacation for 2, or (4) both the educational letter and the raffle ticket. We compared the proportion of employees receiving vaccination and participating in the raffle across groups. RESULTS: The influenza vaccination rate for all study subjects was 41%. The number of subjects receiving vaccine did not differ by occupation (P = .87) or intervention group (P = .66). CONCLUSIONS: This study provides no evidence to support the use of mailed educational letters or a single large raffle prize incentive as a means to boost hospital employee influenza vaccination rates.