Postdischarge Opioid Use after Lower Extremity Bypass Surgery.

BACKGROUND: Opioid overprescription for acute postoperative pain is an inadvertent contributor to the opioid epidemic via pill diversion and misuse. In response, the surgical community advocates for evidence-based postoperative opioid prescribing guidelines. The objective of this study is to evaluate patient-reported opioid consumption after lower extremity bypass surgery. METHODS: We conducted a retrospective review of a prospectively maintained database of infrainguinal bypass operations from 2016 to 2019. For patients receiving an opioid prescription at discharge, a telephone survey was administered questioning the percentage of pills used. Exclusion criteria included chronic opioid use and reoperations or amputations within 30 days. The primary outcome was the difference in opioids prescribed versus opioids consumed. RESULTS: Forty-nine patients met inclusion criteria. Forty-one (84%) were prescribed opioids at discharge, and 27 (65.9%) completed the survey. The average age was 65.8 ± 7.7 years; 29.6% were women. Oxycodone immediate-release was most commonly prescribed (78%). On average, patients received 318 ± 156 morphine milligram equivalent. A total of 940 opioid pills were prescribed (36.0 ± 11.3 per patient), but only 37% were consumed. This difference resulted in 568 unused pills. CONCLUSIONS: This is the first study to specifically evaluate opioid use in a strictly lower extremity bypass population. Over 60% of pills were unused, which poses significant societal risk for misuse. Our findings contribute to knowledge of operation-specific opioid use, which may shape practice recommendations and reduce opioid overprescription after vascular surgery.

Architecture of the Mediator head module.

Mediator is a key regulator of eukaryotic transcription, connecting activators and repressors bound to regulatory DNA elements with RNA polymerase II (Pol II). In the yeast Saccharomyces cerevisiae, Mediator comprises 25 subunits with a total mass of more than one megadalton (refs 5, 6) and is organized into three modules, called head, middle/arm and tail. Our understanding of Mediator assembly and its role in regulating transcription has been impeded so far by limited structural information. Here we report the crystal structure of the essential Mediator head module (seven subunits, with a mass of 223 kilodaltons) at a resolution of 4.3 ångströms. Our structure reveals three distinct domains, with the integrity of the complex centred on a bundle of ten helices from five different head subunits. An intricate pattern of interactions within this helical bundle ensures the stable assembly of the head subunits and provides the binding sites for general transcription factors and Pol II. Our structural and functional data suggest that the head module juxtaposes transcription factor IIH and the carboxy-terminal domain of the largest subunit of Pol II, thereby facilitating phosphorylation of the carboxy-terminal domain of Pol II. Our results reveal architectural principles underlying the role of Mediator in the regulation of gene expression.

Mediator head module structure and functional interactions.

We used single-particle electron microscopy to characterize the structure and subunit organization of the Mediator Head module that controls Mediator-RNA polymerase II (RNAPII) and Mediator-promoter interactions. The Head module adopts several conformations differing in the position of a movable jaw formed by the Med18-Med20 subcomplex. We also characterized, by structural, biochemical and genetic means, the interactions of the Head module with TATA-binding protein (TBP) and RNAPII subunits Rpb4 and Rpb7. TBP binds near the Med18-Med20 attachment point and stabilizes an open conformation of the Head module. Rpb4 and Rpb7 bind between the Head jaws, establishing contacts essential for yeast-cell viability. These results, and consideration of the structure of the Mediator-RNAPII holoenzyme, shed light on the stabilization of the pre-initiation complex by Mediator and suggest how Mediator might influence initiation by modulating polymerase conformation and interaction with promoter DNA.

Synthesis of cyclic thioethers through tandem C(sp3)-S and C(sp2)-S bond formations from alpha,beta'-dichloro vinyl ketones.

The synthesis of 5- to 8-memebered cyclic thioethers 4 has been achieved through a simple two-step sequence. The present methodology utilizes the facile Friedel-Crafts acylation of terminal alkynes 1 with acid chlorides 2 followed by tandem C(sp(3))-S and C(sp(2))-S bond formations with NaSH.xH(2)O.