Systemic chronic hypoxia is a feature of many diseases and may influence the communication between bone marrow (BM) and gut microbiota. Here we analyse patients with cyanotic congenital heart disease (CCHD) who are experiencing chronic hypoxia and characterize the association between bone marrow mesenchymal stem cells (BMSCs) and gut microbiome under systemic hypoxia. We observe premature senescence of BMSCs and abnormald-galactose accumulation in patients with CCHD. The hypoxia that these patients experience results in an altered diversity of gut microbial communities, with a remarkable decrease in the number ofLactobacilliand a noticeable reduction in the amount of enzyme-degradedd-galactose. Replenishing chronic hypoxic rats withLactobacillusreduced the accumulation ofd-galactose and restored the deficient BMSCs. Together, our findings show that chronic hypoxia predisposes BMSCs to premature senescence, which may be due to gut dysbiosis and thus inducedd-galactose accumulation.

Background: The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of remimazolam in clinical endoscopic procedure sedation.Methods: The authors searched the databases of PubMed, Embase, and Cochrane Library for studies published until January 2, 2021, that reported remimazolam sedation for endoscopic procedures. The sedative efficiency and the incidence of adverse events were assessed as outcomes. Cochrane Review Manager Software 5.3 was used to perform the statistical analyses.Results: Seven relevant studies involving a total of 1,996 patients were identified. We conducted a meta-analysis of the different controls used in the studies, that is, the placebo, midazolam, and propofol. The results demonstrated that remimazolam had a strong sedative effect, and its sedative efficiency was significantly higher than that of placebo [OR = 0.01, 95% CI: (0.00, 0.10), I² = 30%, p <0.00001]. The sedative efficiency of remimazolam was significantly higher than that of midazolam [OR = 0.12, 95% CI: (0.08, 0.21), I² = 0%, p < 0.00001] but lesser than that of propofol [OR = 12.22, 95% CI: (1.58, 94.47), I² = 0%, p = 0.02]. Regarding the adverse events, remimazolam is associated with a lower incidence of hypotension than placebo and midazolam. Similarly, remimazolam was associated with a lower incidence of hypotension and hypoxemia than propofol.Conclusions: Remimazolam is a safe and effective sedative for patients undergoing endoscopic procedures. The sedative efficiency of remimazolam was significantly higher than that of midazolam but slightly lower than that of propofol. However, the respiration and circulation inhibitory effects of remimazolam were weaker than those of midazolam and propofol.

Background: Cyanotic congenital heart disease (CCHD) is a complex pathophysiological condition involving systemic chronic hypoxia (CH). Some patients with CCHD are unoperated for various reasons and remain chronically hypoxic throughout their lives, which heightens the risk of heart failure as they age. Hypoxia activates cellular metabolic adaptation to balance energy demands by accumulating hypoxia-inducible factor 1-α (HIF-1α). This study aims to determine the effect of CH on cardiac metabolism and function in patients with CCHD and its association with age. The role of HIF-1α in this process was investigated, and potential therapeutic targets were explored. Methods: Patients with CCHD (n=25) were evaluated for cardiac metabolism and function with positron emission tomography/computed tomography and magnetic resonance imaging. Heart tissue samples were subjected to metabolomic and protein analyses. CH rodent models were generated to enable continuous observation of changes in cardiac metabolism and function. The role of HIF-1α in cardiac metabolic adaptation to CH was investigated with genetically modified animals and isotope-labeled metabolomic pathway tracing studies. Results: Prepubertal patients with CCHD had glucose-dominant cardiac metabolism and normal cardiac function. In comparison, among patients who had entered puberty, the levels of myocardial glucose uptake and glycolytic intermediates were significantly decreased, but fatty acids were significantly increased, along with decreased left ventricular ejection fraction. These clinical phenotypes were replicated in CH rodent models. In patients with CCHD and animals exposed to CH, myocardial HIF-1α was upregulated before puberty but was significantly downregulated during puberty. In cardiomyocyte-specific Hif-1α –knockout mice, CH failed to initiate the switch of myocardial substrates from fatty acids to glucose, thereby inhibiting ATP production and impairing cardiac function. Increased insulin resistance during puberty suppressed myocardial HIF-1α and was responsible for cardiac metabolic maladaptation in animals exposed to CH. Pioglitazone significantly reduced myocardial insulin resistance, restored glucose metabolism, and improved cardiac function in pubertal CH animals. Conclusions: In patients with CCHD, maladaptation of cardiac metabolism occurred during puberty, along with impaired cardiac function. HIF-1α was identified as the key regulator of cardiac metabolic adaptation in animals exposed to CH, and pubertal insulin resistance could suppress its expression. Pioglitazone administration during puberty might help improve cardiac function in patients with CCHD.

Oxidative stress may contribute to the development of acute kidney injury (AKI) after cardiac surgery. Acetaminophen can be considered an antioxidant because it inhibits hemoprotein-catalyzed lipid peroxidation. We hypothesized that perioperative acetaminophen administration is associated with reduced AKI after cardiac surgery. Retrospective observational cohort study. Patients aged≥18 years who had cardiac surgery were identified from 2 publicly available clinical registries: the Medical Information Mart for Intensive Care III (MIMIC-III) and the eICU Collaborative Research Database (eICU). Administration of acetaminophen in the first 48 hours after surgery. Severe AKI in the first 7 days after surgery, defined as stage 2 or stage 3 AKI according to KDIGO criteria. Multivariable cause-specific hazards regression analysis. We identified 5,791 patients from the MIMIC-III and 3,840 patients from the eICU registries. The overall incidence of severe AKI was 58% (3,390 patients) in the MIMIC-III cohort and 37% (1,431 patients) in the eICU cohort. Acetaminophen was administered in the early postoperative period to 4,185 patients (72%) and 2,737 patients (71%) in these 2 cohorts, respectively. In multivariable regression models, early postoperative use of acetaminophen was associated with a lower risk of severe AKI in both the MIMIC-III (adjusted hazard ratio [AHR], 0.86 [95% CI, 0.79-0.94]) and eICU (AHR, 0.84 [95% CI, 0.72-0.97]) cohorts. The benefit was consistent across sensitivity and subgroup analyses. No data on acetaminophen dose. Early postoperative acetaminophen administration was independently associated with a lower risk of severe AKI in adults recovering from cardiac surgery. Prospective trials are warranted to assess the extent to which the observed association is causal and estimate the extent to which acetaminophen administration might prevent or reduce the severity of AKI. There is uncertainty about whether antioxidant medications such as acetaminophen may protect against kidney injury. Therefore, we evaluated the associations between acetaminophen use and kidney outcomes in adults recovering from cardiac surgery in 2 large clinical registries. Acetaminophen treatment was significantly associated with a 14%-16% lower risk of severe and any-stage acute kidney injury but similar risks of kidney replacement therapy and in-hospital mortality. Our findings suggest that acetaminophen use may protect against kidney injury in adult patients recovering from cardiac surgery.

Aim: Determining whether intraoperative cerebral oximetry monitoring-guided intervention reduces the risk of postoperative cognitive dysfunction remains controversial. The objective of this study was to conduct an up-to-date meta-analysis to comprehensively assess the effects of regional cerebral oxygen saturation (rSO₂) monitoring-guided intervention on cognitive outcomes after cardiac surgery.Methods: PubMed, EMBASE, Ovid, and Cochrane Library databases were systematically searched using the related keywords for cardiac surgical randomized-controlled trials (RCTs) published from their inception to July 31, 2021. The primary outcome was postoperative delirium (POD). The secondary outcomes were postoperative cognitive decline (POCD) and other major postoperative outcomes. The odds ratio (OR) or weighted mean differences (WMDs) with 95% confidence interval (CI) were used to pool the data. The random-effect model was used for the potential clinical inconsistency. We performed meta-regression and subgroup analyses to assess the possible influence of rSO₂ monitoring-guided intervention on clinical outcomes.Results: In total, 12 RCTs with 1,868 cardiac surgical patients were included. Compared with controls, the incidences of POD (n = 6 trials; OR, 0.28; 95% CI, 0.09–0.84; p = 0.02; I² = 81%) and POCD (n = 5 trials; OR, 0.38; 95% CI, 0.16–0.93; p = 0.03; I² = 78%) were significantly lower in the intervention group. Cerebral oximetry desaturation also showed a positive association with the incidence of POD (n = 5 trials; OR, 2.02; 95% CI, 1.25–3.24; p = 0.004; I² = 81%). The duration of intensive care unit (ICU) stay was markedly shorter in the intervention group than in the control group (n = 10 trials; WMD, −0.22 days; 95% CI, −0.44 to −0.00; p = 0.05; I² = 74%). Univariate meta-regression analyses showed that the major sources of heterogeneity were age (p = 0.03), body mass index (BMI, p = 0.05), and the proportion of congenital heart disease (CHD, p = 0.02) for POD, age (p = 0.04) for POCD, diabetes mellitus (DM, p = 0.07), cerebrovascular accident (CVA, p = 0.02), and chronic obstructive pulmonary disease (COPD, p = 0.09) for ICU stay. Subsequent subgroup analyses also confirmed these results.Conclusion: Available evidence from the present study suggests that an intraoperative cerebral oximetry desaturation is associated with an increased POD risk, and the rSO₂ monitoring-guided intervention is correlated with a lower risk of POD and POCD, and a shorter ICU stay in adults undergoing cardiac surgery. These clinical benefits may be limited in patients with older age, diabetes status, high BMI, non-CHD, non-COPD, or a previous cardiovascular accident.Systematic Review Registration: [PROSPREO], identifier: [CRD42021252654].

Background: Post-cardiac surgery patients exhibit a higher incidence of postoperative delirium (PD) compared to non-cardiac surgery patients. Patients with various cardiac diseases suffer from preoperative sleep disorder (SPD) induced by anxiety, depression, breathing disorder, or other factors.Objective: To examine the effect of sleep disorder on delirium in post-cardiac surgery patients.Methods: We prospectively selected 186 patients undergoing selective cardiac valve surgery. Preoperative sleep quality and cognitive function of all eligible participants were assessed through the Pittsburgh Sleep Quality Index (PSQI) and the Montreal Cognitive Assessment, respectively. The Confusion Assessment Method for Intensive Care Unit was used to assess PD from the first to seventh day postoperatively. Patients were divided into two groups according to the PD diagnosis: (1) No PD group and (2) the PD group.Results: Of 186 eligible patients, 29 (15.6%) were diagnosed with PD. A univariate analysis showed that gender (p = 0.040), age (p = 0.009), SPD (p = 0.008), intraoperative infusion volume (p = 0.034), postoperative intubation time (p = 0.001), and intensive care unit stay time (p = 0.009) were associated with PD. A multivariate logistic regression analysis demonstrated that age (odds ratio (OR): 1.106; p = 0.001) and SPD (OR: 3.223; p = 0.047) were independently associated with PD. A receiver operating characteristic curve demonstrated that preoperative PSQI was predictive of PD (area under curve: 0.706; 95% confidence interval: 0.595–0.816). A binomial logistic regression analysis showed that there was a significant association between preoperative 6 and 21 PSQI scores and PD incidence (p = 0.009).Conclusions: Preoperative SPD was significantly associated with PD and a main predictor of PD.