Determination of oxygen saturation compared to a prescribed target range using continuous pulse oximetry in acutely unwell medical patients.

BACKGROUND: Both inadequate and excessive administration of oxygen to acutely unwell patients results in risk of harm. Guidelines recommend titration of oxygen to achieve a target oxygen saturation (SpO2) range. Information regarding whether this is being achieved is limited. METHODS: In this two-centre non-interventional study we used continuous pulse oximetry in acutely unwell medical patients over a 24-h period to determine the proportion of time spent with SpO2 within the prescribed target range and whether this is influenced by the target range, age, care in a high-dependency area and the number of oxygen adjustments. RESULTS: Eighty participants were included in the analysis. The mean (SD) proportion of time spent in target range was 55.6% (23.6), this was lower in those with a reduced hypercapnic target range (88-92% or below) compared to those with a range of 92-96%; difference - 13.1% (95% CI - 3.0 to - 23.2), P = 0.012. The proportion of time spent above range was 16.2% (22.9); this was higher in those with a reduced hypercapnic range; difference 21.6% (31.4 to 12), P < 0.001. The proportion of time below range was 28.4% (25.2); there was no difference between target ranges. The proportion of time spent in range was higher for those in a high dependency area in the multivariate model; difference 15.5% (95% CI 2.3 to 28.7), P = 0.02. CONCLUSIONS: Medical patients receiving oxygen in a ward setting spend significant periods of time with SpO2 both above and below the prescribed target range while receiving oxygen therapy.

Identification of novel Wilms' tumor suppressor gene target genes implicated in kidney development.

The Wilms' tumor suppressor gene (WT1) encodes a zinc finger transcription factor that is vital during development of several organs including metanephric kidneys. Despite the critical regulatory role of WT1, the pathways and mechanisms by which WT1 orchestrates development remain elusive. To identify WT1 target genes, we performed a genome-wide expression profiling analysis in cells expressing inducible WT1. We identified a number of direct WT1 target genes, including the epidermal growth factor (EGF)-family ligands epiregulin and HB-EGF, the chemokine CX3CL1, and the transcription factors SLUG and JUNB. The target genes were validated using quantitative reverse transcriptase-polymerase chain reaction, small interfering RNA knockdowns, chromatin immunoprecipitation, and luciferase reporter analyses. Immunohistochemistry of fetal kidneys confirmed that a number of the WT1 target genes had overlapping expression patterns with the highly restricted spatiotemporal expression of WT1. Finally, using an in vitro embryonic kidney culture assay, we found that the addition of recombinant epiregulin, amphiregulin, CX3CL1, and interleukin-11 significantly enhanced ureteric bud branching morphogenesis. Our genome-wide screen implicates WT1 in the transcriptional regulation of the EGF-family of growth factors as well as the CX3CL1 chemokine during nephrogenesis.