Opioid consumption for analgesia in burn patients is enormous. Non-opioid analgesics for burn pain management may result in opioid sparing, reducing opioid-related adverse reactions and drug tolerance or addiction. A dual-center, randomized controlled trial assessed Esketamine for the perioperative period in patients with severe [20-50 % total body surface area (TBSA)] and extensive (≥ 50 % TBSA) burns, comparing analgesia with standard anesthesia. Sixty patients were randomly allocated (1:1 ratio) to two arms. In the Treatment Arm, patients received intra-operative Esketamine and postoperative intravenous primary intelligent analgesia pump with Esketamine. Patients in the Control Arm received the same intervention as Treatment Arm without Esketamine. The primary endpoint was subjective analgesic efficacy (SAE) evaluated on Day 28 or the day before hospital discharge. Secondary outcomes included the postoperative Numeric Pain Rating (NPR) Scale at rest (NPRr) and during movement (NPRm) and opioid consumption. Gastrointestinal dysfunction Scores (GIDS) and serum markers of intestinal injury [intestinal fatty acid-binding protein 2 (iFabp2) and apolipoproteinA2 (ApoA2)] were measured in the 1st and 4th post-injury weeks. Depression and sleep quality were assessed by relevant questionnaires. Fifty-five patients were included in the analysis. Esketamine-treated Arm recorded a better analgesic efficacy than the Control Arm (proportion of patients with Grade 1 or 2 SAE scores, 67.9 % vs. 40.7 %, p = 0.022). Esketamine-treated patients had lower NPRm values (p = 0.033) and lower daily opioid consumption (p = 0.033) when compared with Controls. Esketamine-treated patients showed comparable gastrointestinal recovery to those in the Control Arm. The overall sleep quality might be improved in the Treatment Arm. Esketamine use is safe for perioperative primary intelligent analgesia of severe burns, resulting in improved resting pain control and lower opioid requirements. The trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn/) (ChiCTR2000034069).

Arterial stiffness is an emerging indicator of cardiovascular risk, but its causal relationship with a variety of age-related diseases is unclear. The objective is to assess the causal relationship between arterial stiffness index (ASI) and age-related diseases by Mendelian randomization (MR) analysis. We obtained instrumental variables associated with age-related diseases from genome-wide association studies (GWAS) of 484,598 European individuals, and data for ASI were obtained from the UK Biobank GWAS of 127,127 participants. We used the inverse variance-weighted as the primary analysis method. In addition, several sensitivity analyses including MR-Egger, weighted-median (WM), Mendelian randomization pleiotropy residual sum and outlier, and Cochran’s Q test were performed to test the robustness of the results. Reverse MR analysis was also performed to assess reverse causal relationships between age-related diseases and ASI. We verified the causal relationship between eight age-related diseases and ASI, of which cardiovascular disease ( β = 0.19), gallbladder disease ( β = 0.85), liver, biliary, or pancreas problem ( β = 1.02), hypertension ( β = 0.19), joint disorder ( β = 0.53), and esophageal disorder ( β = 2.10) elevated ASI. In contrast, hyperthyroidism or thyrotoxicosis ( β = −2.17) and bowel problems ( β = −1.83) may reduce ASI. This MR analysis reveals causal relationships between ASI and several age-related diseases. ASI is expected to be a potential indicator of health conditions for older populations.

Background: Elevated lactate levels are reliable biomarkers of tissue hypoperfusion and metabolic stress. However, their prognostic significance in extensive burn patients undergoing early excision and grafting (EEG) remains unclear. This study aimed to evaluate the prognostic value of perioperative lactate levels in predicting clinical deterioration following EEG in patients with extensive burns. Methods: In this retrospective cohort study, adult burn patients with ≥ 50% total burn surface area (TBSA) or ≥ 20% full-thickness burns treated between March 2021 and September 2023 were included. Patients were categorized into Deterioration and Non-Deterioration groups based on changes in Sequential Organ Failure Assessment (SOFA) scores. Statistical analyses included univariate and multivariate logistic regression, as well as receiver-operating characteristic (ROC) curve analysis. Results: Of 82 patients, 37.8% were classified into the Deterioration Group. Compared with the Non-Deterioration Group, these patients presented with a significantly higher burn index (BI), larger surgical area, and greater intraoperative blood transfusion volumes. Temporal trends in lactate levels appeared to differ between groups: lactate levels peaked on POD1 and returned to baseline by postoperative Day 3(POD3) in the Non-Deterioration Group, whereas they remained persistently elevated in the Deterioration Group. Among all perioperative time points, lactate levels on POD3 were significantly higher in the Deterioration Group (2.88 ± 0.65 mmol/L vs. 2.27 ± 0.68 mmol/L, p < 0.001) and were independently associated with clinical deterioration clinical deterioration (OR 2.97, 95% CI 1.18–8.71, p = 0.031). POD3 lactate levels demonstrated the highest discriminatory performance for identifying postoperative deterioration (AUC = 0.761, 95% CI 0.656–0.866). Conclusions: Among perioperative lactate levels in patients undergoing EEG for extensive burns, POD3 lactate levels were significantly associated with clinical deterioration and may serve as a useful marker to guide early risk assessment and supportive interventions.

Background: To investigate the effect of goal-directed hemodynamic treatment on perfusion and short-term prognosis in patients undergoing early Tangential excision and skin grafting for extensive burns.Methods: Ninety-five patients with extensive burns undergoing early Tangential excision and skin grafting were randomly divided into a standard hemodynamic management group (control group) and a goal-directed therapy group (GDHT group), with the control group guided by conventional parameters and the GDHT group guided by stroke volume (SV) based on Vigileo. The primary outcomes were cardiac complications, pulmonary complications, neurological disease, acute kidney injury, and pain within 7 days postoperatively. Secondary outcomes included microcirculatory perfusion metrics: The central venous-arterial carbon dioxide partial pressure difference (Pcv-aCO2), and blood lactate (Lac). investigators assessing outcomes were blinded to group allocation.Results: When analysing 47 subjects in the GDHT group and 48 subjects in the control group, fewer patients in the GDHT group had postoperative pulmonary complications [pneumonia (2:9, P=0.027); oxygenation index <300 (3:8, P=0.041)] and controls were more likely to have atrial fibrillation (4:12, P=0.032) Renal and neurological complications did not differ between groups. Pcv-aCO2 and Lac were higher in the Con group after the intervention compared to the control group, and there was no difference between the two groups postoperatively. In this study, Pcv-aCO2 and Lac were Key influencing factors for pulmonary complications within 7 days postoperatively (Beta=0.197, P=0.000; Beta=0.147, P=0.000).Conclusion: SV-guided GDHT improves microcirculatory perfusion and has fewer short-term postoperative complications compared with standard hemodynamic therapy.Trial registration: NCT05221788 (03/02/2022)

Background: Vascular calcification (VC) is a multifactorial process associated with adverse cardiovascular outcomes. The uric acid to high-density lipoprotein cholesterol ratio (UHR) has been proposed as a composite metabolic biomarker that reflects the balance between pro-oxidative and anti-inflammatory processes. However, its association with VC and the underlying mechanisms remain incompletely understood. Methods: This study integrated clinical association analysis, Mendelian randomization (MR), and network-based approaches. A retrospective cross-sectional analysis was conducted in 627 clinically stable cardiology inpatients, with aortic arch calcification (AoAC) assessed using chest radiographs. Multivariable logistic regression and restricted cubic spline analyses were used to examine the association between UHR and AoAC. Two-sample MR was performed to assess the potential causal effects of uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) on abdominal aortic calcification (AAC), a macrovascular calcification phenotype. Network-based analysis was conducted to explore potential molecular mechanisms. Results: Higher UHR levels were significantly associated with greater AoAC severity, which remained after adjusting for standard cardiovascular risk factors. MR analysis showed no significant genetic association between genetically predicted UA and AAC, whereas genetically predicted HDL-C showed an inverse association with AAC in the primary IVW analysis, but this was not consistently supported across sensitivity methods. Network-based analyses identified enrichment in inflammation- and remodeling-related pathways, including MAPK and PI3K–Akt signaling, with key hub targets such as TNF, AKT1, and EGFR. Conclusion: Higher UHR levels were associated with greater VC burden in clinically stable cardiology inpatients. The clinical, genetic, and network-based findings provide complementary evidence suggesting that UHR may reflect the combined influence of multiple metabolic and inflammatory processes associated with VC, rather than the direct effect of any single component.