Identification of the specific molecular and functional signatures of pre-beta-HDL: relevance to cardiovascular disease.

While low concentrations of high-density lipoprotein-cholesterol (HDL-C) are widely accepted as an independent cardiovascular risk factor, HDL-C-rising therapies largely failed, suggesting the importance of both HDL functions and individual subspecies. Indeed HDL particles are highly heterogeneous, with small, dense pre-beta-HDLs being considered highly biologically active but remaining poorly studied, largely reflecting difficulties for their purification. We developed an original experimental approach allowing the isolation of sufficient amounts of human pre-beta-HDLs and revealing the specificity of their proteomic and lipidomic profiles and biological activities. Pre-beta-HDLs were enriched in highly poly-unsaturated species of phosphatidic acid and phosphatidylserine, and in an unexpectedly high number of proteins implicated in the inflammatory response, including serum paraoxonase/arylesterase-1, vitronectin and clusterin, as well as in complement regulation and immunity, including haptoglobin-related protein, complement proteins and those of the immunoglobulin class. Interestingly, amongst proteins associated with lipid metabolism, phospholipid transfer protein, cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase were strongly enriched in, or restricted to, pre-beta-HDL. Furthermore, pre-beta-HDL potently mediated cellular cholesterol efflux and displayed strong anti-inflammatory activities. A correlational network analysis between lipidome, proteome and biological activities highlighted 15 individual lipid and protein components of pre-beta-HDL relevant to cardiovascular disease, which may constitute novel diagnostic targets in a pathological context of altered lipoprotein metabolism.

Obturator nerve block does not provide analgesic benefits in total hip arthroplasty under multimodal analgesic regimen: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Although regional analgesia is considered an important component of optimal pain management, use of peripheral nerve blocks for total hip arthroplasty remains controversial. Since the obturator nerve innervates the anteromedial part of the joint capsule, we hypothesized that an obturator nerve block would decrease the opioid consumption after total hip arthroplasty. METHODS: In this single center, prospective, triple blinded study, we randomly allocated 60 patients undergoing total hip arthroplasty under opioid-sparing total intravenous general anesthesia to a preoperative obturator nerve block or a sham block (placebo group) using 20 mL of ropivacaine 0.2% or saline, respectively. All patients received a multimodal analgesic regimen with non-opioid analgesics including periarticular local infiltration analgesia. The primary outcome was the intravenous opioid consumption in the post-anesthesia care unit. RESULTS: Median (IQR) intravenous oxycodone consumption in the post-anesthesia care unit was 4 (2, 7.5) mg in the obturator nerve block group and 3 (0, 4) mg in the placebo group (p=0.05). There were no differences in pain scores between groups in the first 24 hours except at arrival on the surgical ward with significant higher pain scores in the placebo group (p=0.03). The ability to stand up and walk within 24 hours was comparable between groups as was the time to first walk (180 (90, 720) vs 240 (120, 780) min for the obturator nerve block and placebo groups, respectively; p=0.62). CONCLUSIONS: Obturator nerve block did not improve postoperative opioid consumption after total hip arthroplasty performed under general anesthesia with a multimodal analgesic regimen. TRIAL REGISTRATION NUMBER: NCT04085640.

Total knee arthroplasty under quadruple nerve block with ropivacaine 0.32%: effect of addition of intravenous dexmedetomidine to intravenous dexamethasone on analgesic duration.

BACKGROUND AND OBJECTIVES: Peripheral nerve blocks reduce postoperative pain and enhance recovery after total knee arthroplasty (TKA). This study aims to assess the benefits of addition of intravenous dexmedetomidine (DexM) to intravenous dexamethasone on the analgesic duration of quadruple nerve blocks. METHODS: This double-blind, randomized, controlled trial prospectively enrolled 90 patients scheduled for TKA under quadruple nerve blocks (sciatic, femoral, obturator, and lateral femoral cutaneous nerves blocks) with 70 mL, 0.32% ropivacaine. All patients received systemic dexamethasone 10 mg. Patients were randomized to receive DexM (2 µg/kg, intravenous) or placebo (1:1 ratio). The primary endpoint was the duration of analgesia defined as the time to first request for rescue analgesia (oxycodone). RESULTS: Kaplan-Meier curves for the first analgesic request were similar between groups (log-rank test; p=0.27). Median (IQR) duration of analgesia was similar between placebo (1575 min (1211-1952)) and DexM (1470 min (1263-1700)) groups (p=0.56). Cumulative consumption of oxycodone at the 48th hour was 20 mg (10-30) and 30 mg (20-40) in placebo and DexM groups, respectively (p=0.14). The day after surgery, 93% and 89% of patients were able to walk in placebo and DexM groups, respectively (p=0.46). Intravenous DexM was associated with bradycardia, hypotension and longer recovery room stay (p<0.05 for all comparisons). CONCLUSIONS: In a multimodal analgesic regimen, addition of systemic DexM (2 µg/kg) to systemic dexamethasone does not prolong the analgesic duration of quadruple nerve block with ropivacaine 0.32% after TKA. TRIAL REGISTRATION NUMBER: NCT03834129.