Postoperative haemoglobin and anaemia-associated ischaemic events after major noncardiac surgery: A sex-stratified cohort study.

STUDY OBJECTIVE: To determine the sex-specific associations between postoperative haemoglobin and mortality or complications reflecting ischaemia or inadequate oxygen supply after major noncardiac surgery. DESIGN: A retrospective cohort study with prospective validation. SETTING: A large university hospital health system in China. PATIENTS: Men and women undergoing elective major noncardiac surgery. INTERVENTIONS AND MEASUREMENTS: The primary exposure was nadir haemoglobin within 48 h after surgery. The outcome of interest was a composite of postoperative mortality or ischaemic events including myocardial injury, acute kidney injury and stroke within hospitalisation. MAIN RESULTS: The study included 26,049 patients (15,757 men and 10,292 women). Low postoperative haemoglobin was a strong predictor of the composite outcome in both sexes, with the risk progressively increasing as the nadir haemoglobin concentration dropped below 130 g l-1 in men and 120 g l-1 in women (adjusted odds ratio [OR] 1.43, 95% CI 1.37-1.50 in men, and OR 1.45, 95% CI 1.35-1.55 in women, per 10 g l-1 decrease in postoperative nadir haemoglobin). Above these sex-specific thresholds, the change of nadir haemoglobin was no longer associated with odds of the composite outcome in either men or women. There was no significant interaction between patient sex and the association between postoperative haemoglobin and the composite outcome (Pinteraction = 0.673). Validation in an external prospective cohort (n = 2120) with systematic postoperative troponin and creatinine measurement confirmed our findings. CONCLUSIONS: Postoperative haemoglobin levels following major noncardiac surgery were nonlinearly associated with ischaemic complications or mortality, without any clinically important interaction with patient sex.

Use of dexmedetomidine to alleviate intestinal ischemia-reperfusion injury via intestinal microbiota modulation in mice.

Background: Intestinal ischemia-reperfusion (I/R) injury is a serious condition with unacceptable mortality rates. Our previous study revealed a protective effect of dexmedetomidine (DEX) on intestinal I/R injury, but its underlying mechanism remains unclear. Gut microbiota imbalance is associated with the progression of I/R injury. We hypothesized that DEX would attenuate intestinal I/R injury via modulating gut microbiota. Methods: An I/R injury model was established in C57BL/6 mice in the presence or absence of DEX preconditioning. Some mice were treated with antibiotics to deplete intestinal bacteria. Fecal microbiota transplantation (FMT) was performed by transplanting the feces of DEX-pretreated mice into a new batch of I/R mice. We analyzed the expression of Bacteroidetes and Firmicutes in feces, survival rate, and inflammatory cytokines. Results: DEX reversed I/R-induced bacterial abnormalities by increasing the ratio of Firmicutes to Bacteroidetes [DEX + I/R 3.02±0.36 vs. normal saline (NS) + I/R 0.82±0.15; 95% CI: 0.80-3.60; P<0.05] and was accompanied by increased 72-hour survival (0.40±0.16 vs. 0.10±0.09; P<0.05). The protective effect of DEX did not significantly differ from that of DEX + antibiotics. Furthermore, the bacteria of the DEX-pretreated mice decreased the release of inflammatory factors. Conclusions: This study revealed that DEX can alleviate intestinal I/R injury through a microbiota-related mechanism, providing a potential avenue for the management of intestinal I/R injury.

Peripheral interleukin-6-associated microglial QUIN elevation in basolateral amygdala contributed to cognitive dysfunction in a mouse model of postoperative delirium.

Background: Developing effective approaches for postoperative delirium has been hampered due to the lack of a pathophysiologically similar animal model to offer insights into the pathogenesis. The study, therefore, aimed to develop a delirium-like mouse model and explore the underlying mechanism. Methods: The three cycles of 10-min clamp following 5-min reopening of the superior mesenteric artery (SMA) were performed in adult male C57BL/6 mice to induce a delirium-like phenotype. Composite Z score calculated based on the results of Open Field, Y Maze and Buried Food Tests was employed to assess the delirium phenotype in mice. Microglia activities were monitored by immunofluorescence staining and comprehensive morphological analysis. Systemic administration of minocycline (MINO), IL-6 antibody or IL-6 neutralizing antibody, was applied to manipulate microglia. The expressions of Indoleamine 2,3-dioxygenase-1 (IDO-1) and quinolinic acid (QUIN) were examined by RT-PCR and High-Performance Liquid Chromatography/Mass Spectrometry, respectively. Cytokines were measured using fluorescence activated cell sorting method. Results: The repeated ischemia/reperfusion (I/R) surgery caused significant anxiety (P < 0.05) and cognition decline in working memory and orientation (P < 0.05) in mice at postoperative 24 h. The composite Z score, indicating an overall disturbance of brain function, fluctuated over 24 h after I/R surgery (P < 0.001). Immunofluorescent staining showed that the percentage of microglia in the basolateral amygdala (BLA) (P < 0.05) was reactivated after I/R surgery and was negatively correlated with dwell time at Y maze (R = -0.759, P = 0.035). Inhibiting microglia activities by MINO reduced QUIN productions (P < 0.01) that improved cognitive deficits (P < 0.05). The peripheral IL-6 might cause IL-6 elevation in the BLA. Systemic administration of IL-6 antibodies suppressed I/R-induced IL-6 elevations (P < 0.05), microglial reactivations (P < 0.05), IDO-1 expressions (P < 0.01), and neuroactive metabolite QUIN productions (P < 0.05) in the BLA, resulting in a recovery of cognitive deficits (P < 0.05). Injection of IL-6 exerted opposite effects. Conclusion: The repeated intestinal I/R surgery-induced mouse model is a simple and reproducible one of postoperative delirium. Peripheral IL-6-associated microglial QUIN elevations in the BLA contributed to cognitive dysfunction in the model of postoperative delirium.