To understand the role of mitochondrial uncoupling protein (UCP) in regulating insulin signaling and glucose homeostasis, we created transgenicDrosophila lines with targeted UCP expression in insulin producing cells (IPCs). Increased UCP activity in IPCs results in decreased steady state Ca2+ levels in IPCs as well as decreased PI3K activity and increased FoxO nuclear localization in periphery. This reduced systemic insulin signaling is accompanied by a mild hyperglycemia and extended life span. To test the hypothesis that ATP-sensitive potassium (KATP) channels may link changes in metabolic activity (e.g., glucose mediated ATP production or UCP-mediated ATP reduction) with insulin secretion, we characterized the effects of glucose and a specific KATP channel blocker, glibenclamide on membrane potential in adult IPCs. Exposure to glucose depolarizes membrane potential of IPCs and this effect is mimicked with glibenclamide, suggesting that KATP channels contribute to the mechanism whereby IPCs sense changes in circulating sugar. Further, as demonstrated in mammalian β-pancreatic cells, high glucose initiates a robust Ca2+ influx in adult IPCs. The presence of functional KATP channels in adult IPCs is further substantiated by in situ hybridization detecting the transcript for the sulfonylurea receptor (Sur) subunit of the KATP channel in those cells. Quantitative expression analysis demon-strates a reduction in transcripts for both Sur and the inward rectifying potassium channel (Kir) subunits when IPCs are partially ablated. In summary, we have demonstrated a role for UCP in adult Drosophila IPCs in influencing systemic insulin signaling and longevity by a mechanism that may involve KATP channels.

ImportanceWhole-blood (WB) resuscitation has gained renewed interest among civilian trauma centers. However, there remains insufficient evidence that WB as an adjunct to component therapy–based massive transfusion protocol (WB-MTP) is associated with a survival advantage over MTP alone in adult civilian trauma patients presenting with severe hemorrhage.ObjectiveTo assess whether WB-MTP compared with MTP alone is associated with improved survival at 24 hours and 30 days among adult trauma patients presenting with severe hemorrhage.Design, Setting, and ParticipantsThis retrospective cohort study using the American College of Surgeons Trauma Quality Improvement Program databank from January 1, 2017, and December 31, 2018, included adult trauma patients with a systolic blood pressure less than 90 mm Hg and a shock index greater than 1 who received at least 4 units of red blood cells within the first hour of emergency department (ED) arrival at level I and level II US and Canadian adult civilian trauma centers. Patients with burns, death within 1 hour of ED arrival, and interfacility transfers were excluded. Data were analyzed from February 2022 to September 2022.ExposuresResuscitation with WB-MTP compared with MTP alone within 24 hours of ED presentation.Main Outcomes and MeasuresPrimary outcomes were survival at 24 hours and 30 days. Secondary outcomes selected a priori included major complications, hospital length of stay, and intensive care unit length of stay.ResultsA total of 2785 patients met inclusion criteria: 432 (15.5%) in the WB-MTP group (335 male [78%]; median age, 38 years [IQR, 27-57 years]) and 2353 (84.5%) in the MTP-only group (1822 male [77%]; median age, 38 years [IQR, 27-56 years]). Both groups included severely injured patients (median injury severity score, 28 [IQR, 17-34]; median difference, 1.29 [95% CI, −0.05 to 2.64]). A survival curve demonstrated separation within 5 hours of ED presentation. WB-MTP was associated with improved survival at 24 hours, demonstrating a 37% lower risk of mortality (hazard ratio, 0.63; 95% CI, 0.41-0.96; P = .03). Similarly, the survival benefit associated with WB-MTP remained consistent at 30 days (HR, 0.53; 95% CI, 0.31-0.93; P = .02).Conclusions and RelevanceIn this cohort study, receipt of WB-MTP was associated with improved survival in trauma patients presenting with severe hemorrhage, with a survival benefit found early after transfusion. The findings from this study are clinically important as this is an essential first step in prioritizing the selection of WB-MTP for trauma patients presenting with severe hemorrhage.

Background There is no evidence supporting intubation for a Glasgow Coma Scale (GCS) of 8. We investigated the effect of intubation in trauma patients with a GCS 6-8, with the hypothesis that intubation would increase mortality and length of stay. Methods We studied adult patients with GCS 6-8 from the 2016 National Trauma Data Bank. Intubated and non-intubated patients were compared using inverse probability weighted regression adjustment (IPWRA) to control for injury severity and patient characteristics. Outcomes were mortality, intensive care unit length of stay (ICU LOS), and total LOS. Stratified analysis was performed to investigate the effect in patients with and without head injuries. Results Among 6676 patients with a GCS between 6 and 84,078 were intubated within 1 h of arrival to the emergency department. The overall mortality rate was 15.1%. IPWRA revealed an increase in mortality associated with intubation (OR 1.05, 95% CI 1.03, 1.06). The results were similar in patients with head injuries (OR 1.04, 95% CI 1.02, 1.06) and without (OR 1.06, 95% CI 1.03, 1.10). Among the 5,742 patients admitted to the ICU, intubation was associated with a 14% increase in ICU LOS (95% CI 8-20%; 5.5 vs. 4.8 days; p < 0.001). The overall length of stay was 27% longer (95% CI 19.8-34.3%) among intubated patients (mean 7.7 vs 6.0 days; p < 0.001). Conclusion Among patients with GCS of 6 to 8, intubation on arrival was associated with an increase in mortality and with longer ICU and overall length of stay. The use of a strict threshold GCS to mandate intubation should be revisited.