Anesthetic Management of Patients After Traumatic Injury With Resuscitative Endovascular Balloon Occlusion of the Aorta.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a temporizing maneuver for noncompressible torso hemorrhage. To our knowledge, this single-center brief report provides the most extensive anesthetic data published to date on patients who received REBOA. As anticipated, patients were critically ill, exhibiting lactic acidosis, hypotension, hyperglycemia, hypothermia, and coagulopathy. All patients received blood products during their index operations and received less inhaled anesthetic gas than normally required for healthy patients of the same age. This study serves as an important starting point for clinician education and research into anesthetic management of patients undergoing REBOA.

Asymmetric configurations in a reengineered homodimer reveal multiple subunit communication pathways in protein allostery.

Many allosteric proteins form homo-oligomeric complexes to regulate a biological function. In homo-oligomers, subunits establish communication pathways that are modulated by external stimuli like ligand binding. A challenge for dissecting the communication mechanisms in homo-oligomers is identifying intermediate liganded states, which are typically transiently populated. However, their identities provide the most mechanistic information on how ligand-induced signals propagate from bound to empty subunits. Here, we dissected the directionality and magnitude of subunit communication in a reengineered single-chain version of the homodimeric transcription factor cAMP receptor protein. By combining wild-type and mutant subunits in various asymmetric configurations, we revealed a linear relationship between the magnitude of cooperative effects and the number of mutant subunits. We found that a single mutation is sufficient to change the global allosteric behavior of the dimer even when one subunit was wild type. Dimers harboring two mutations with opposite cooperative effects had different allosteric properties depending on the arrangement of the mutations. When the two mutations were placed in the same subunit, the resulting cooperativity was neutral. In contrast, when placed in different subunits, the observed cooperativity was dominated by the mutation with strongest effects over cAMP affinity relative to wild type. These results highlight the distinct roles of intrasubunit interactions and intersubunit communication in allostery. Finally, dimers bound to either one or two cAMP molecules had similar DNA affinities, indicating that both asymmetric and symmetric liganded states activate DNA interactions. These studies have revealed the multiple communication pathways that homo-oligomers employ to transduce signals.

Identifying Prevalence and Potential Predictors of Do-Not-Attempt-Resuscitation Orders to Facilitate Preoperative Discussions on Code Status.

BACKGROUND: Do Not Attempt Resuscitation (DNAR) orders allow patients with life-threatening conditions to decline resuscitation efforts should the need arise. The American Society of Anesthesiologists (ASA) recommends discussions with patients on their code status to clarify and honor their goals of care perioperatively. This project sought to determine the prevalence of DNAR orders and to identify the demographics and potential clinical predictors of DNAR status at the beginning and end of admission, which would help anesthesiologists at our center facilitate these discussions. METHODS: Factors associated with DNAR status at beginning and at end of hospital stay were determined through univariate logistic regressions. For DNAR status at beginning and end of hospital admission, variables assessed were age at arrival, race, sex, palliative consult, use of palliative care service, length of stay in days, presence of surgery, presence of emergent surgery, care level, and medical service. RESULTS: Approximately 2.4 percent of the sample had an active DNAR order at the beginning of their hospital admission compared to 7.4 percent at the end of hospital admission. Factors significantly associated with DNAR status at the beginning of the hospital stay were consistent with prior literature (age, palliative care consult or service). However, factors significantly associated with DNAR status at the end of hospital stay that were notable included length of stay, undergoing emergent surgery, higher level of care, and being on the oncology service and medical respiratory intensive care unit. CONCLUSIONS: This retrospective study allows anesthesiologists at our institution to identify patients who may benefit from a more comprehensive perioperative discussion about code status based on certain clinical characteristics, which may improve quality of care by preventing unwanted resuscitative measures that do not align with a patient's goals of care.

Synthesis, Characterization, and Bioactivity of the Photoisomerizable Tubulin Polymerization Inhibitor azo-Combretastatin A4.

Combretastatin A4 is a stilbenoid tubulin binding mitotic inhibitor whose conformation greatly influences its potency, making it an excellent candidate for adaptation as a photoactivatable tool. Herein we report a novel synthesis, the facile isomerization with commercial grade equipment, and biological activity of azo-combretastatin A4 in vitro and in human cancer cells. Photoisomerized azo-combretestatin A4 is at least 200-fold more potent in cellular culture, making it a promising phototherapeutic and biomedical research tool.