The GATA family of transcription factors, including the founding member, GATA-1, have an important role in gene regulation. GATA-1 is integral to successful hematopoiesis. A wide variety of mutations in GATA-1 affect its function, as well as its interaction with its cofactors (especially Friend of GATA) and the genes upon which GATA-1 acts. Here we review the known mutations, focusing on the specific alterations within the amino acid sequence, the resulting effect on hematopoietic development, and the clinical manifestations that result. Attention is also paid to the relationship between Trisomy 21, also known as Down syndrome, and the phenomenon of a truncated GATA-1, named GATA-1s. The evidence for specific interaction between GATA-1 and chromosome 21, which may explain the correlation between these two mutations, is briefly reviewed.
C-Mpl is the receptor for thrombopoietin (TPO), the main megakaryocyte (MK) growth factor, and c-Mpl is believed to be expressed on cells of the hematopoietic lineage. As MKs have been shown to enhance bone formation, it may be expected that mice in which c-Mpl was globally knocked out (c-Mpl−/− mice) would have decreased bone mass because they have fewer MKs. Instead, c-Mpl−/ − mice have a higher bone mass than WT controls. Using c-Mpl−/− mice we investigated the basis for this discrepancy and discovered that c-Mpl is expressed on both osteoblasts (OBs) and osteoclasts (OCs), an unexpected finding that prompted us to examine further how c-Mpl regulates bone. Static and dynamic bone histomorphometry parameters suggest that c-Mpl deficiency results in a high bone turnover state with a net gain in bone volume. In vitro, a higher percentage of c-Mpl −/− OBs were in active phases of the cell cycle, leading to an increased number of OBs. No difference in OB differentiation was observed in vitro as examined by real-time PCR and functional assays. In co-culture systems, which allow for the interaction between OBs and OC progenitors, c-Mpl−/− OBs enhanced osteoclastogenesis. Two of the major signaling pathways by which OBs regulate osteoclastogenesis, MCSF/OPG/RANKL and EphrinB2-EphB2/B4, were unaffected in c-Mpl−/− OBs. These data provide new findings for the role of MKs and c-Mpl expression in bone and may provide insight into the homeostatic regulation of bone mass as well as bone loss diseases such as osteoporosis.
Objective
Length of stay (LOS) includes time medically necessary in the hospital and time waiting for discharge (DC) afterward. This DC delay is determined in head and neck free flap patients. Reasons for and factors leading to DC delay, as well as associated adverse outcomes, are elucidated.
Methods
Retrospective chart review was performed for all head and neck free flap surgeries from 2012 to 2017. Data including demographics, comorbidities, and perioperative factors were collected. Regression analyses were performed to identify factors associated with DC delay.
Results
In total, 264 patients were included. Mean total LOS was 13.1 days. DC delay occurred in 65% of patients with a mean of 4.8 days. Factors associated with DC delay on univariate analysis included Medicaid/self-pay insurance, DC to a facility, and not having children (P < .05). Multivariate analysis showed prolonged medically necessary LOS and surgery on a Monday/Friday (P < .05) were associated with DC delay. Top reasons for DC delay included case management shortages, rejection by facility, and awaiting supplies. Eleven percent experienced complications during the DC delay.
Discussion
DC delay can add days and complications to the LOS. Prevention begins preoperatively with DC planning involving the patient’s closest family. Understanding limitations of the patient’s insurance may help plan DC destination. Optimizing hospital resources when available should be a focus.
Implications for Practice
Head and neck free flap patients require a team of teams unified in optimizing quality of care. DC delay is a novel quality metric reflecting the team’s overall performance. Through strategic DC planning and capitalizing on available resources, DC delay can be minimized.
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