Characterization of Postoperative Infection Risk in Cardiac Surgery Patients With Delayed Sternal Closure.

OBJECTIVES: To compare the incidence of postoperative infection in cardiac surgery patients who had delayed sternal closure (DSC) with those who had primary sternal closure (PSC) and evaluate the effectiveness of antibiotic prophylaxis in DSC patients. DESIGN: Retrospective, observational cohort study with propensity score matching. SETTING: Single academic medical center. PARTICIPANTS: Cardiothoracic surgery patients, excluding transplantation patients, from a single academic medical center who had DSC or PSC between November 2015 and November 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 2,685 patients who had cardiac surgery with cardiopulmonary bypass, 99 had DSC. Fifty-nine DSC patients met study inclusion criteria, and the final propensity score matched cohort included 57 patients with DSC and 57 patients with PSC. Propensity score matching reduced bias but was unable to balance all covariates. The most common indication for DSC was coagulopathy in 32 of the 57 patients. All patients in the PSC group received routine antibiotic prophylaxis for 48 hours after surgery. Patients in the DSC group received prolonged broadened prophylaxis until 48 hours after sternal closure. Despite prolonged broadened antibiotic prophylaxis, the DSC group had a higher rate of postoperative infection (31.6% v 3.5%; p < 0.005), mainly pneumonia (19.3% v 1.8%; p < 0.005), in the first 30 days after surgery. There was no difference in the incidence of sepsis (5.3% v 0%; p = 0.24), superficial skin and soft tissue infection (1.8% v 1.8%; p = 1), or mediastinitis/deep tissue infection (5.3% v 0%; p = 0.24) in patients with DSC. Seventy-seven percent of causative organisms for infection were Gram-negative bacteria in the matched cohort. CONCLUSION: The incidence of postoperative infection, particularly pneumonia, is high in cardiothoracic surgery patients with DSC, even with prolonged broadened antibiotic prophylaxis, but the rate of mediastinitis/deep tissue infection did not appear to be greater with DSC. Additional research is needed into optimal antibiotic prophylaxis in this high-risk group of patients.

Impact of ketamine versus fentanyl continuous infusion on opioid use in patients admitted to a surgical-trauma intensive care unit.

OBJECTIVE: Ketamine has been shown to decrease opioid utilization as an adjunct, but limited evidence is available on ketamine as a primary analgesic strategy. DESIGN: A retrospective chart review. PATIENTS AND PARTICIPANTS: Mechanically ventilated adult patients (≥18 years) in the surgery-trauma intensive care unit (STICU) with continuous infusion ketamine or fentanyl with concomitant propofol for at least 12 hours were screened for inclusion. The final analysis included 22 patients in the ketamine/propofol (KP) group and 24 patients in the fentanyl/propofol (FP) group. INTERVENTIONS: Patients in the STICU received KP or FP continuous infusions. MAIN OUTCOME MEASURES: The primary outcome compared opioid requirements between both groups during mechanical ventilation. RESULTS: The median opioid requirement during mechanical ventilation was significantly higher in the FP group compared to the KP group (median 1,392 milligrams of morphine equivalents (MMEs) [interquartile range (IQR) 709.5-2,292] versus 206.3 MME [IQR 87-510], p < 0.001). After extubation, there was no difference in opioid utilization. Patients in the KP group spent less time at goal Critical Care Pain Observation Tool compared to the FP group (median 77.6 percent, IQR [71.9-85.2] versus 88.9 percent, IQR [76.9-97.4], p = 0.003). The proportions of patients developing adverse effects were not significantly different between the two groups. CONCLUSIONS: Among critically ill mechanically ventilated patients in the STICU, continuous ketamine resulted in signifi-cantly less opioids during mechanical ventilation. Further studies with a larger sample size are needed to assess the ap-propriate dosing strategy for ketamine to produce adequate analgesia when used as a primary analgesic in mechanically ventilated patients.

The HMGB1 C-Terminal Tail Regulates DNA Bending.

High mobility group box protein 1 (HMGB1) is an architectural protein that facilitates the formation of protein-DNA assemblies involved in transcription, recombination, DNA repair, and chromatin remodeling. Important to its function is the ability of HMGB1 to bend DNA non-sequence specifically. HMGB1 contains two HMG boxes that bind and bend DNA (the A box and the B box) and a C-terminal acidic tail. We investigated how these domains contribute to DNA bending by HMGB1 using single-molecule fluorescence resonance energy transfer (FRET), which enabled us to resolve heterogeneous populations of bent and unbent DNA. We found that full-length (FL) HMGB1 bent DNA more than the individual A and B boxes. Removing the C-terminal tail resulted in a protein that bent DNA to a greater extent than the FL protein. These data suggest that the A and B boxes simultaneously bind DNA in the absence of the C-terminal tail, but the tail modulates DNA binding and bending by one of the HMG boxes in the FL protein. Indeed, a construct composed of the B box and the C-terminal tail only bent DNA at higher protein concentrations. Moreover, in the context of the FL protein, mutating the A box such that it could not bend DNA resulted in a protein that bent DNA similar to a single HMG box and only at higher protein concentrations. We propose a model in which the HMGB1 C-terminal tail serves as an intramolecular damper that modulates the interaction of the B box with DNA.