Evaluation of Safety and Short-term Outcomes of Therapeutic Rigid Bronchoscopy Using Total Intravenous Anesthesia and Spontaneous Assisted Ventilation.

BACKGROUND: There is a paucity of published data regarding the optimal type of anesthesia and ventilation strategies during rigid bronchoscopy. OBJECTIVE: The aim of our study is to report the procedural and anesthesia-related complications with rigid bronchoscopy using total intravenous anesthesia and spontaneous assisted ventilation. METHODS: A retrospective review of patients undergoing therapeutic rigid bronchoscopy at the University of Chicago between October 2012 and December 2014 was performed. Data were recorded relating to patients' demographics, comorbidities, type of anesthesia, need for neuromuscular blockade (NMB), intraoperative hypoxemia, hypotension, perioperative adverse events, and mortality. RESULTS: Fifty-five patients underwent 79 rigid bronchoscopy procedures; 90% were performed for malignant disease and 90% of patients had an American Society of Anesthesiologists (ASA) class III or IV. The majority (76%) did not require use of NMB. The most common adverse events were intraoperative hypoxemia (67%) and hypotension (77%). Major bleeding and postoperative respiratory failure occurred in 3.8 and 5.1% of procedures, respectively. There was no intraoperative mortality or cardiac dysrhythmias. The 30-day mortality was 7.6% and was associated with older age, inpatient status, congestive heart failure, home oxygen use, and procedural duration. Intraoperative hypoxemia, hypotension, and ASA class were not associated with 30-day mortality. The majority (94%) of patients were discharged home. The use of NMB did not impact outcomes. CONCLUSIONS: This study suggests that therapeutic rigid bronchoscopy can be safely performed with total intravenous anesthesia and spontaneous assisted ventilation in patients with central airway obstruction, significant comorbidities, and a high ASA class. The only significant modifiable variable predicting the 30-day mortality was the duration of the procedure.

Systematically Mitigating the p38α Activity of Triazole-based BET Inhibitors.

The Bromodomain and Extra Terminal (BET) family of proteins recognize post-translational N-ε-acetylated lysine modifications, regulating transcription as "reader" proteins. Bromodomain inhibitors are interesting targets for the development of potential cancer, inflammation, and heart disease treatments. Several dual kinase-bromodomain inhibitors have been identified by screening kinase inhibitor libraries against BET proteins. Although potentially useful from a polypharmacology standpoint, multitarget binding complicates deciphering molecular mechanisms. This report describes a systematic approach to mitigating kinase activity in a dual kinase-bromodomain inhibitor based on a 1,2,3-triazole-pyrimidine core. By modifying the triazole substituent and altering the pyrimidine core, this structure-activity relationship study enhanced BET activity while reducing the p38α kinase activity >90,000-fold. A BRD4-D1 cocrystal structure indicates that the 1,2,3-triazole is acting as a N-ε-acetylated lysine mimic. A BRD4 sensitive cell line, MM.1S, was used to demonstrate activity in cells, which is further supported by reduced c-Myc expression.

Regiocontrolled Wacker Oxidation of Cinnamyl Azides.

A highly regioselective Wacker oxidation has been developed for the oxidation of cinnamyl azides. The catalytic oxidation tolerates the azide functionality, and more than 15 ß-azido ketones were isolated (25-92% yield). High regioselectivity for the aryl ketone is observed in all cases. A robustness screen was conducted to determine functional group tolerance. The products of the oxidaiton can be readily diversified.

An experimental investigation of possible memory biases affecting support for racial health care policy.

OBJECTIVES: We aimed to test the theory that estimates of racial disparities may be based on small recalled samples of specific individuals (Black vs White), a strategy likely to lead to underestimates of true racial disparities and a corresponding opposition to race-focused health care policies. METHODS: We asked a sample of White adults to list the first 5 Black and White individuals who came to mind, and then measured support for various race-focused health care policies. RESULTS: Analyses indicated that the Black individuals recalled by participants tended to be more famous and wealthy than their White counterparts. Furthermore, the tendency to list wealthier Black individuals predicted opposition to progressive racial health care programs. A follow-up study demonstrated that support for certain race-focused health care policies could be increased by informing Whites of potential memory biases. CONCLUSIONS: The survival and success of minority health care policies depend partially on public acceptance. Education regarding continuing racial disparities may help to increase support for race-focused health care policies.

Scope of attention, control of attention, and intelligence in children and adults.

Recent experimentation has shown that cognitive aptitude measures are predicted by tests of the scope of an individual's attention or capacity in simple working memory tasks and also by the ability to control attention. However, these experiments do not indicate how separate or related the scope and control of attention are. An experiment with 52 children (10 to 11 years old) and 52 college students included measures of the scope and control of attention, as well as verbal and nonverbal aptitude measures. The children showed little evidence of using sophisticated attentional control, but the scope of attention predicted intelligence in that group. In adults, both the scope and control of attention varied among individuals and accounted for considerable individual variance in intelligence. About one third that variance was shared between scope an d control, and the rest was unique to one or the other. Scope and control of attention appear to be related but distinct contributors to intelligence.