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International Journal of Surgery... Nov 2023A previous randomized controlled trial demonstrated that intermittent Pringle's maneuver (IPM) with a 25-min ischemic interval could be applied safely and efficiently in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
A previous randomized controlled trial demonstrated that intermittent Pringle's maneuver (IPM) with a 25-min ischemic interval could be applied safely and efficiently in hepatectomy for patients with hepatocellular carcinoma (HCC). But prolonging the hepatic inflow clamping time will inevitably aggravate the ischemia-reperfusion injury. Therefore, we aimed to evaluate the effect of prophylactic dexamethasone on alleviating surgical stress for HCC patients with a 25-min ischemic interval.
METHODS
From December 2022 to April 2023, patients who met the inclusion criteria were randomly assigned to the dexamethasone group or control group. Perioperative data and short-term survival outcomes between the two groups were recorded and compared, and subgroup analysis was performed.
RESULTS
Two hundred and seventy patients were allocated to the dexamethasone group ( n =135) and control group ( n =135). Patients in the dexamethasone group had lower area under the curve of serial alanine aminotransferase (AUC ALT ) ( P =0.043) and aspartate aminotransferase (AUC AST ) ( P =0.009), total bilirubin (TB) ( P =0.018), procalcitonin (PCT) ( P =0.012), interleukin-6 (IL-6) ( P =0.006), incidence of major complication ( P =0.031) and shorter postoperative hospital stay ( P =0.046) than those in the control group. Subgroup analysis showed that the dexamethasone group experienced milder hepatocellular injury than the control group for patients with cirrhosis, and for patients without cirrhosis, the dexamethasone group experienced milder inflammatory response. Moreover, the dexamethasone group preserved better liver function and experienced milder inflammatory response for patients undergoing major hepatectomy, although the hepatocellular injury was not significantly improved.
CONCLUSION
Preoperative dexamethasone administration can help improve perioperative outcomes for HCC patients when applying IPM with a 25-min ischemic interval in hepatectomy.
Topics: Humans; Carcinoma, Hepatocellular; Hepatectomy; Liver Neoplasms; Ischemia; Dexamethasone
PubMed: 37526089
DOI: 10.1097/JS9.0000000000000622 -
The New England Journal of Medicine Apr 2024
Topics: Humans; Multiple Myeloma; Bortezomib; Lenalidomide; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Antibodies, Monoclonal
PubMed: 38631009
DOI: 10.1056/NEJMc2402133 -
Journal of Critical Care Dec 2023The aim of this study is to design a population pharmacokinetic study to gain a deeper understanding of the pharmacokinetics of dexamethasone in critically ill COVID-19...
PURPOSE
The aim of this study is to design a population pharmacokinetic study to gain a deeper understanding of the pharmacokinetics of dexamethasone in critically ill COVID-19 patients in order to identify relevant covariates that can be used to personalize dosing regimens.
METHODS
Blood samples from critically ill patients receiving fixed-dose intravenous dexamethasone (6 mg/day) for the treatment of COVID-19 were sampled in a retrospective pilot study. The data were analyzed using Nonlinear Mixed Effects Modeling (NONMEM) software for population pharmacokinetic analysis and clinically relevant covariates were selected and evaluated.
RESULTS
A total of 51 dexamethasone samples from 18 patients were analyzed and a two-compartment model fit the data best. The mean population estimates were 2.85 L/h (inter-individual-variability 62.9%) for clearance, 15.4 L for the central volume of distribution, 12.3 L for the peripheral volume of distribution and 2.1 L/h for the inter-compartmental distribution clearance. The covariate analysis showed a significant negative correlation between dexamethasone clearance and CRP.
CONCLUSIONS
Dexamethasone PK parameters in ICU COVID patients were substantially different from those from non-ICU non-COVID patients, and inflammation may play an important role in dexamethasone exposure. This finding suggests that fixed-dose dexamethasone over several days may not be appropriate for ICU COVID patients.
Topics: Humans; Critical Illness; Retrospective Studies; Pilot Projects; COVID-19; COVID-19 Drug Treatment; Inflammation; Dexamethasone; Anti-Bacterial Agents
PubMed: 37542750
DOI: 10.1016/j.jcrc.2023.154395 -
Die Ophthalmologie Apr 2024
Topics: Dexamethasone; Glucocorticoids
PubMed: 38180488
DOI: 10.1007/s00347-023-01968-5 -
BMC Anesthesiology Sep 2023Dexamethasone (Dexa) has been recently found to exert an analgesic effect, whose action is closely related to IL-8. However, whether dexamethasone induces...
BACKGROUND
Dexamethasone (Dexa) has been recently found to exert an analgesic effect, whose action is closely related to IL-8. However, whether dexamethasone induces antinociception via glycolysis and mitochondria-related pathways is still unclear.
METHODS
Right hind paw inflammatory pain in mice was induced by intraplantar injection of Freund's Complete Adjuvant (FCA). Von Frey test was then used to measure the paw withdrawal threshold. The detection of glycolysis and mitochondrial pathway-related proteins and IL-8 were determined by Western blot and ELISA. The potential interaction between Dexa and fructose-1,6-bisphosphate (FBP, a PKM2 activator) was examined by simulation predictions using molecular docking.
RESULTS
Intrathecal administration of Dexa (20 µg/20 µL) had an obvious analgesic effect in FCA-treated mice, which was counteracted by the glycolysis inhibitor 2-deoxyglucose (2-DG, 5 mg/20 µL) or the mitochondria-related pathway inhibitor oligomycin complex (Oligo, 5 µg/20 µL). In the glycolysis pathway, Dexa decreased GLUT3 and had no impact on HIF-1α expression during FCA-induced inflammation. Additionally, Dexa further increased the PKM2 level, accompanied by the formation of hydrogen bonds between Dexa and the PKM2 activator fructose-1,6-bisphosphate (FBP). In the mitochondrial pathway, Dexa downregulated the expression of Mfn2 protein but not the PGC-1α and SIRT-1 levels in the spinal cord. Moreover, both 2-DG and Oligo decreased Mfn2 expression. Finally, IL-8 level was reduced by the single or combined administration of Dexa, 2-DG, and Oligo.
CONCLUSION
Dexa attenuated IL-8 expression via glycolysis and mitochondrial pathway-related proteins, thus mediating the analgesic effect during inflammatory pain.
Topics: Animals; Mice; Interleukin-8; Molecular Docking Simulation; Fructose; Glycolysis; Mitochondria; Dexamethasone; Analgesics
PubMed: 37723417
DOI: 10.1186/s12871-023-02277-9 -
Cardiovascular Drugs and Therapy Aug 2023Post-pericardiotomy syndrome (PPS) is a common complication of cardiac surgery. This systematic review aimed to investigate the efficacy of colchicine, indomethacin, and... (Review)
Review
PURPOSE
Post-pericardiotomy syndrome (PPS) is a common complication of cardiac surgery. This systematic review aimed to investigate the efficacy of colchicine, indomethacin, and dexamethasone in the treatment and prophylaxis of PPS.
METHODS
Literature research was carried out using PubMed. Studies investigating ≥ 10 patients with clinically PPS treated with colchicine, dexamethasone, and indomethacin and compared with placebo were included. Animal or in vitro experiments, studies on < 10 patients, case reports, congress reports, and review articles were excluded. Cochrane risk-of-bias tool for randomized trials (RoB2) was used for the quality assessment of studies.
RESULTS
Seven studies were included. Among studies with postoperative colchicine treatment, two of them demonstrated a significant reduction of PPS. In the single pre-surgery colchicine administration study, a decrease of PPS cases was registered. Indomethacin pre-surgery administration was linked to a reduction of PPS. No significant result emerged with preoperative dexamethasone intake.
CONCLUSION
Better outcomes have been registered when colchicine and indomethacin were administered as primary prophylactic agents in preventing PPS and PE. Further RCT studies are needed to confirm these results.
Topics: Humans; Pericardiectomy; Postpericardiotomy Syndrome; Cardiac Surgical Procedures; Colchicine; Indomethacin; Dexamethasone
PubMed: 34546452
DOI: 10.1007/s10557-021-07261-4 -
British Journal of Anaesthesia Jul 2024Reductionist thinking results in the bulk of anaesthesia trial designs being a single intervention to address what are in fact complex processes. The Perioperative...
Reductionist thinking results in the bulk of anaesthesia trial designs being a single intervention to address what are in fact complex processes. The Perioperative Administration of Dexamethasone and Infection (PADDI) trial assessed the safety of a single preoperative dose of dexamethasone. Surprising to most, in the original report, a single dose of dexamethasone increased the incidence of the secondary outcome chronic postsurgical pain. Was this a chance finding or does dexamethasone increase chronic postsurgical pain? In an attempt to address this question, the PADDI investigators have now analysed this prespecified secondary outcome in two ways: as a substudy published earlier in this Journal, and as a retrospective analysis of the ENIGMA-II chronic pain database in this issue of the Journal. The PADDI investigators have now presented enough data to convince us that indeed a single dose of dexamethasone is safe and effective. However, the increase in chronic postsurgical pain seen in the original PADDI publication highlights the complexities, and the possible immunologic mechanisms, behind the genesis of chronic postsurgical pain. These publications from the PADDI group raise questions about other anti-inflammatory agents we use regularly for long-term postoperative pain management, and highlights the need for well-designed clinical trials to address this critically important patient-centred adverse functional outcome.
Topics: Dexamethasone; Humans; Pain, Postoperative; Chronic Pain; Anti-Inflammatory Agents
PubMed: 38744550
DOI: 10.1016/j.bja.2024.04.011 -
Military Medicine Jan 2024This was an in vivo animal study designed to investigate the interaction between dexamethasone (Dex) and microRNA-204 (miR-204) in a mouse alkali burn-induced corneal...
INTRODUCTION
This was an in vivo animal study designed to investigate the interaction between dexamethasone (Dex) and microRNA-204 (miR-204) in a mouse alkali burn-induced corneal neovascularization (CNV) model. The function of miR-204 was then investigated in human mammary epithelial cells (HMECs) in vitro.
MATERIALS AND METHODS
The CNV model was induced by corneal alkali burn in BLAB/c mice. The mice were randomly divided into five groups: normal control (Ctrl), alkali burn-induced corneal injury (Alkali), alkali burn + Dex (Dex), alkali burn + negative control (NTC), and alkali burn + miR-204 agomir (miR-204). Subconjunctival injection of NTC, Dex, or miR-204 agomir was conducted at 0, 3, and 6 days, respectively, after alkali burn. The corneas were collected at day 7 after injury, and the CNV area was observed using immunofluorescence staining. The expression of miR-204 was analyzed with quantitative real time (qRT)-PCR. In HMECs, exogenous miR-204 agomir or antagomir was used to strengthen or inhibit the expression of miR-204. Migration assays and tube formation studies were conducted to evaluate the function of miR-204 on HMECs.
RESULTS
At 7 days post-alkali burn, CNV grew aggressively into the cornea. MicroRNA-204 expression was reduced in the Alkali group in contrast with the Ctrl group (P = .003). However, miR-204 was upregulated in the Dex group (vs. alkali group, P = .008). The CNV areas in the NTC and miR-204 groups were 59.30 ± 8.32% and 25.60 ± 2.30%, respectively (P = .002). In vitro, miR-204 agomir showed obvious inhibition on HMEC migration in contrast with NTC (P = .033) and miR-204 antagomir (P = .017). Compared with NTC, miR-204 agomir attenuated tube formation, while miR-204 antagomir accelerated HMEC tube formation (P < .05).
CONCLUSION
The role of Dex in attenuating CNV may be partly attributed to miR-204. MiR-204 may be a potential therapeutic target in alkali burn-induced CNV.
Topics: Animals; Humans; Mice; Alkalies; Antagomirs; Burns, Chemical; Cornea; Corneal Injuries; Corneal Neovascularization; Dexamethasone; Disease Models, Animal; Eye Burns; MicroRNAs
PubMed: 36043264
DOI: 10.1093/milmed/usac260 -
Toxicology and Applied Pharmacology Mar 2024The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly.
BACKGROUND
The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly.
OBJECTIVE
This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of Eucommia ulmoides, against dexamethasone-induced osteoporosis and chondrodysplasia.
METHODS
A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone. The impact of PDG on bone mineralization was assessed through alizarin red and calcein staining. Alkaline phosphatase activity was quantified to evaluate osteoblast function. The influence of PDG on chondrogenesis was estimated using alcian blue staining. Fluorescence imaging and motor behavior analysis were employed to assess the protective effect of PDG on the structure and function of dexamethasone-induced skeletal teratogenesis. qPCR determined the expression of osteogenesis and Wnt signaling-related genes. Molecular docking was used to assess the potential interactions between PDG and Wnt receptors.
RESULTS
PDG significantly increased bone mineralization and corrected spinal curvature and cartilage malformations in the zebrafish model. Furthermore, PDG enhanced swimming abilities compared to the model group. PDG mitigated dexamethasone-induced skeletal abnormalities in zebrafish by upregulating Wnt signaling, showing potential interaction with Wnt receptors FZD2 and FZD5.
CONCLUSION
PDG mitigates dexamethasone-induced osteoporosis and chondrodysplasia by promoting bone formation and activating Wnt signaling.
Topics: Humans; Animals; Aged; Zebrafish; Molecular Docking Simulation; Osteogenesis; Dexamethasone; Osteoporosis; Receptors, Wnt; Cell Differentiation; Lignans
PubMed: 38442791
DOI: 10.1016/j.taap.2024.116884 -
Redox Report : Communications in Free... Dec 2023Primary hepatocytes are widely used as a tool for studying metabolic function and regulation in the liver. However, the metabolic properties of primary hepatocytes are...
Primary hepatocytes are widely used as a tool for studying metabolic function and regulation in the liver. However, the metabolic properties of primary hepatocytes are gradually lost after isolation. Here, we illustrated that fatty acid metabolism is the major compromised metabolic process in isolated primary hepatocytes, along with drastically decreased GSH and ROS content, while lipid peroxidation is increased. Gain- and loss-of-function studies revealed that Slc7a11 expression is critical in maintaining fatty acid metabolism and facilitating hormone-induced fatty acid metabolic events, which is synergistic with dexamethasone treatment. Intriguingly, Slc7a11 expression and dexamethasone treatment cooperatively upregulated AKT and AMPK signaling and mitochondrial complex expression in primary hepatocytes. Furthermore, direct treatment with reduced GSH or inhibition of ferroptosis is sufficient to drive protective effects on fatty acid metabolism in primary hepatocytes. Our results demonstrate that Slc7a11 expression in isolated primary hepatocytes induces GSH production, which protects against ferroptosis, to increase fatty acid metabolic gene expression, AKT and AMPK signaling and mitochondrial function in synergy with dexamethasone treatment, thereby efficiently preserving primary hepatocyte metabolic signatures, thus providing a promising approach to better reserve primary hepatocyte metabolic activities after isolation to potentially improve the understanding of liver biological functions from studies using primary hepatocytes.
Topics: AMP-Activated Protein Kinases; Proto-Oncogene Proteins c-akt; Hepatocytes; Fatty Acids; Dexamethasone; Glutathione
PubMed: 37750478
DOI: 10.1080/13510002.2023.2260646