Heart Rate Variability, Clinical and Laboratory Measures to Predict Future Deterioration in Patients Presenting With Sepsis.

BACKGROUND: Risk stratification of patients presenting to the emergency department (ED) with sepsis can be challenging. We derived and evaluated performance of a predictive model containing clinical, laboratory, and heart rate variability (HRV) measures to quantify risk of deterioration in this population. METHODS: ED patients aged 21 and older satisfying the 1992 consensus conference criteria for sepsis and able to consent (directly or through a surrogate) were enrolled (n = 1,247). Patients had clinical, laboratory, and HRV data recorded within 1 h of ED presentation, and were followed to identify deterioration within 72 h. RESULTS: Eight hundred thirty-two patients had complete data, of whom 68 (8%) reached at least one endpoint. Optimal predictive performance was derived from a combination of laboratory values and HRV metrics with an area under the receiver-operating curve (AUROC) of 0.80 (95% CI, 0.65-0.92). This combination of variables was superior to clinical (AUROC = 0.69, 95% CI, 0.54-0.83), laboratory (AUROC = 0.77, 95% CI, 0.63-0.90), and HRV measures (AUROC = 0.76, 95% CI, 0.61-0.90) alone. The HRV+LAB model identified a high-risk cohort of patients (14% of all patients) with a 4.3-fold (95% CI, 3.2-5.4) increased risk of deterioration (incidence of deterioration: 35%), as well as a low-risk group (61% of all patients) with 0.2-fold (95% CI 0.1-0.4) risk of deterioration (incidence of deterioration: 2%). CONCLUSIONS: A model that combines HRV and laboratory values may help ED physicians evaluate risk of deterioration in patients with sepsis and merits validation and further evaluation.

Increased gp130 signaling in combination with inhibition of the MEK/ERK pathway facilitates embryonic stem cell isolation from normally refractory murine CBA blastocysts.

The standard method for isolation of ES cells from strain 129 mice does not give rise to ES lines of CBA origin. We investigated the effect of inhibition of MEK/ERK signaling in combination with increased stimulation of gp130 signaling on derivation of ES cells from CBA blastocysts. Inhibition of MEKI and MEKII using the drug U0126 and stimulation of gp130 signaling by elevating the level of LIF present gave rise to ES-like lines in 22.6% of explants. No lines arose when MEK was inhibited in the absence of additional LIF stimulation, nor when additional LIF stimulation occurred in the absence of MEK inhibition. Typically for ES cell lines, CBA-derived cells contributed to chimeric mice and differentiated broadly in vitro. Increased levels of gp130 signaling led to similar levels of STAT3 activation in strain 129 and CBA ES cells. We conclude that CBA ES cells have a requirement for additional STAT3 activation.