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The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) share similar molecular characteristics in that they frequently harbor hotspot mutations in JAK2, CALR or MPL, leading to activated JAK/STAT signaling. However, these MPN have distinct symptoms, morphology, and natural histories, including different tendencies to progress to fibrosis. Although the role of inflammation in tissue fibrosis is well recognized, inflammatory gene expression in bone marrows involved by MPN has been understudied. We analyzed the expression of inflammatory genes by directly measuring RNA transcript abundance in bone marrow biopsies of 108 MPN patients. Unsupervised analyses identified gene expression patterns that distinguish prefibrotic (grade 1–2) MPN from overtly fibrotic (grade 2–3) MPN with high sensitivity and specificity in two independent cohorts. Furthermore, prefibrotic and overtly fibrotic MPN are separable into subsets with different activities in biological pathways linked to inflammation, including cytokines, chemokines, interferon response, and toll-like receptor signaling. In conclusion, this study demonstrates that MPN with overt fibrosis is associated with significant inflammatory gene upregulation in the bone marrow, revealing potential roles for multiple pro-inflammatory signaling networks in the development of myelofibrosis and suggesting potential therapeutic mechanisms to alleviate this process in the bone marrow microenvironment. [ABSTRACT FROM AUTHOR]

Objectives: The implementation of the Fetal and Infant Mortality Review (FIMR) process was examined as part of the evaluation of the national Healthy Start program, a federal program designed to reduce infant mortality in several communities. The implementation of the FIMR process over the 5-year funding period is described in terms of productivity, barriers and facilitators to implementation, and project expenditures. Methods. Data were derived from grant continuation applications and personal interviews with program staff to produce a qualitative description. Results: As of the summer of 1996, 14 of the 15 Healthy Start sites in the national evaluation had successfully implemented the FIMR process. Most sites had developed a two-tiered review process for examination of case data in which a review by health and social services professionals was followed by community review. In the period 1993 to 1995, the percentage of fetal and infant deaths reviewed had a median of 34% with a range of 4–79% across the sites at a cost of $600 to $3400 per death reviewed. Recommendations were variably implemented. Conclusions: The FIMR process provides an important opportunity to contribute to the knowledge base regarding infant mortality in these communities. The process, however, has important logistical requirements and may require substantial financial resources that may affect implementation of confidential inquiries into infant mortality and other health problems. [ABSTRACT FROM AUTHOR]