Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant).

Objective: The aim of this study was to determine preoperative patient characteristics associated with postoperative outpatient opioid use and assess the frequency of postoperative opioid overprescribing. Summary Background Data: Although characteristics associated with inpatient opioid use have been described, data regarding patient factors associated with opioid use after discharge are lacking. This hampers the development of individualized approaches to postoperative prescribing. Methods: We included opioid-naïve patients undergoing hysterectomy, thoracic surgery, and total knee and hip arthroplasty in a single-center prospective observational cohort study. Preoperative phenotyping included self-report measures to assess pain severity, fibromyalgia survey criteria score, pain catastrophizing, depression, anxiety, functional status, fatigue, and sleep disturbance. Our primary outcome measure was self-reported total opioid use in oral morphine equivalents. We constructed multivariable linear-regression models predicting opioids consumed in the first month following surgery. Results: We enrolled 1181 patients; 1001 had complete primary outcome data and 913 had complete phenotype data. Younger age, non-white race, lack of a college degree, higher anxiety, greater sleep disturbance, heavy alcohol use, current tobacco use, and larger initial opioid prescription size were significantly associated with increased opioid consumption. Median total oral morphine equivalents prescribed was 600 mg (equivalent to one hundred twenty 5-mg hydrocodone pills), whereas median opioid consumption was 188 mg (38 pills). Conclusions: In this prospective cohort of opioid-naïve patients undergoing major surgery, we found a number of characteristics associated with greater opioid use in the first month after surgery. Future studies should address the use of non-opioid medications and behavioral therapies in the perioperative period for these higher risk patients.

Initial opioid prescribing attributable to surgical and dental care is increasing relative to primary and chronic pain care. Evidence-based guideline development for surgical and dental prescribing is warranted in order to curb iatrogenic opioid morbidity and mortality.

This review summarizes current evidence related to perioperative opioid prescription fulfillment and use and discusses the role of personalized anesthesia care in mitigating opioid-related harms without compromising analgesia.

Microdialysis, an in vivo technique that permits collection and analysis of small molecular weight substances from the interstitial space, was developed more than 30 years ago and introduced into the clinical neurosciences in the 1990s. Today cerebral microdialysis is an established, commercially available clinical tool that is focused primarily on markers of cerebral energy metabolism (glucose, lactate, and pyruvate) and cell damage (glycerol), and neurotransmitters (glutamate). Although the brain comprises only 2% of body weight, it consumes 20% of total body energy. Consequently, the ability to monitor cerebral metabolism can provide significant insights during clinical care. Measurements of lactate, pyruvate, and glucose give information about the comparative contributions of aerobic and anaerobic metabolisms to brain energy. The lactate/pyruvate ratio reflects cytoplasmic redox state and thus provides information about tissue oxygenation. An elevated lactate pyruvate ratio (>40) frequently is interpreted as a sign of cerebral hypoxia or ischemia. However, several other factors may contribute to an elevated LPR. This article reviews potential non-hypoxic/ischemic causes of an increased LPR.