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BackgroundResults from previous studies evaluating the effects of remote ischemic preconditioning (RIPC) on morbidity and mortality after cardiac surgery are inconsistent. This meta-analysis of randomized controlled trials (RCTs) aims to determine whether RIPC improves cardiac and renal outcomes in adults undergoing cardiac surgery.MethodsPubMed, EMBASE, and Cochrane Library were comprehensively searched to identify RCTs comparing RIPC with control in cardiac surgery. The coprimary outcomes were the incidence of postoperative myocardial infarction (MI) and the incidence of postoperative acute kidney injury (AKI). Meta-analyses were performed using a random-effect model. Subgroup analyses were conducted according to volatile only anesthesia versus propofol anesthesia with or without volatiles, high-risk patients versus non-high-risk patients, and Acute Kidney Injury Network (AKIN) or Kidney Disease Improving Global Outcomes (KDIGO) criteria versus other criteria for AKI diagnosis.ResultsA total of 79 RCTs with 10,814 patients were included. While the incidence of postoperative MI did not differ between the RIPC and control groups (8.2% vs 9.7%; risk ratio [RR] = 0.87, 95% confidence interval [CI], 0.76-1.01, P = .07, I2 = 0%), RIPC significantly reduced the incidence of postoperative AKI (22% vs 24.4%; RR = 0.86, 95% CI, 0.77-0.97, P = .01, I2 = 34%). The subgroup analyses showed that RIPC was associated with a reduced incidence of MI in non-high-risk patients, and that RIPC was associated with a reduced incidence of AKI in volatile only anesthesia, in non-high-risk patients, and in the studies using AKIN or KDIGO criteria for AKI diagnosis.ConclusionsThis meta-analysis demonstrates that RIPC reduces the incidence of AKI after cardiac surgery. This renoprotective effect of RIPC is mainly evident during volatile only anesthesia, in non-high-risk patients, and when AKIN or KDIGO criteria used for AKI diagnosis.

BackgroundDexmedetomidine sedation has been associated with favourable outcomes after surgery. We aimed to assess whether perioperative dexmedetomidine use is associated with improved survival after cardiac surgery.MethodsThis retrospective cohort study included 2068 patients undergoing on-pump coronary artery bypass grafting and/or valve surgery. Among them, 1029 patients received dexmedetomidine, and 1039 patients did not. Intravenous dexmedetomidine infusion of 0.007 μg kg-1 min-1 was initiated before or immediately after cardiopulmonary bypass and lasted for < 24 h. The primary outcome was 5-year survival after cardiac surgery. The propensity scores matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting approaches were used to minimise bias. Survival analyses were performed with Cox proportional-hazard models.ResultsThe median age was 63 yr old and the male to female ratio was 71:29 in both groups. Baseline covariates were balanced between groups after adjustment using PSM, IPTW, or overlap weighting. Patients receiving dexmedetomidine in cardiac surgical procedures had higher survival during postoperative 5 yr in unadjusted analysis (hazard ratio [HR]=0.63; 95% confidence interval [CI], 0.51-0.78; P

Coronavirus disease-2019 (COVID-19) has rapidly spread worldwide and causes high mortality of elderly patients. High-flow nasal cannula therapy (HFNC) is an oxygen delivery method for severely ill patients. We retrospectively analyzed the course of illness and outcomes in 110 elderly COVID-19 patients (≥65 years) treated with HFNC from 6 hospitals. 38 patients received HFNC (200 mmHg < PaO2/FiO2 ≤ 300 mmHg, early HFNC group), and 72 patients received HFNC (100 mmHg < PaO2/FiO2 ≤ 200 mmHg, late HFNC group). There were no significant differences of sequential organ failure assessment (SOFA) scores and APECH II scores between early and late HFNC group on admission. Compared with the late HFNC group, patients in the early HFNC group had a lower likelihood of developing severe acute respiratory distress syndrome (ARDS), longer time from illness onset to severe ARDS and shorter duration of viral shedding after illness onset, as well as shorter lengths of ICU and hospital stay. 24 patients died during hospitalization, of whom 22 deaths (30.6%) were in the late HFNC group and 2 (5.3%) in the early HFNC group. The present study suggested that the outcomes were better in severely ill elderly patients with COVID-19 receiving early compared to late HFNC.

Myocardial ischemia/reperfusion (I/R) injury leads to high mortality and morbidity due to the incomplete understanding of the underlying mechanism and the consequent lack of effective therapy. The present study revealed and validated key candidate genes in relation to inflammation and apoptosis pathways underlying myocardial I/R injury. Cathepsin S was identified as the top hub protein based on the protein-protein interaction analysis, and, thus, its role during myocardial I/R injury was further investigated. Myocardial I/R in mice resulted in significantly increased levels of myocardial injury biomarkers (cardiac troponin I, lactic dehydrogenase, and creatinine kinase-MB) and inflammatory cytokines (interleukin-1β [IL-1β], IL-6, and tumor necrosis factor-α), elevated apoptosis rate, and upregulated protein expression of cleaved caspase-8, cleaved caspase-3, and cleaved poly ADP-ribose polymerase. These abovementioned changes were blocked by two different selective cathepsin S inhibitors, LY3000328 or MIV-247. Moreover, Kaplan-Meier survival plot showed that cathepsin S inhibition improved 21-day survival rate following myocardial I/R injury. This study demonstrated that the inhibition of cathepsin S alleviated myocardial I/R-induced injury by suppressing inflammation and apoptosis, which may be used in clinical applications of cardioprotection.

AbstractCoronavirus disease-2019 (COVID-19) has rapidly spread worldwide. High-flow nasal cannula therapy (HFNC) is a major oxygen supporting therapy for severely ill patients, but information regarding the timing of HFNC application is scarce, especially in elderly patients. We retrospectively analyzed the clinical data of 110 elderly patients (≥65 years) who received HFNC from Renmin Hospital of Wuhan University, People’s Hospital of Xiantao City and Chinese Medicine Hospital of Shishou City in Hubei Province, China, and from Affiliated Hospital of Guangdong Medical University, People’s Hospital of Yangjiang City, People’s Hospital of Maoming City in Guangdong Province, China.Of the 110 patients, the median age was 71 years (IQR, 68-78) and 59.1% was male. Thirty-eight patients received HFNC when 200 mmHg < PO2/FiO2 ≤ 300 mmHg (early HFNC group), and 72 patients received HFNC treatment when 100 mmHg < PaO2/FiO2 ≤ 200 mmHg (late HFNC group). Compared with the late HFNC group, patients in the early HFNC group had a lower likelihood of developing severe ARDS, longer time from illness onset to severe ARDS and shorter duration of viral shedding after illness onset, as well as shorter lengths of ICU and hospital stay. Twenty-four patients died during hospitalization, of whom 22 deaths (30.6%) were in the late HFNC group and 2(5.3%) in the early HFNC group. It is concluded that the Prognosis was better in severely ill elderly patients with COVID-19 receiving early compared to late HFNC. This suggests HFNC could be considered early in this disease process.

Oxidative stress induced necroptosis is important in myocardial ischemia/reperfusion injury. Dexmedetomidine (Dex), an α2-adrenoceptor (α2-AR) agonist, has protective effect on oxidative stress induced cell apoptosis, but effects of Dex and Dex-mediated α2-AR activation on oxidant induced necroptosis was unclear. H9C2 cardiomyocytes were pre-treated with or without Dex and α2-AR antagonist yohimbine hydrochloride (YOH) before being exposed to H2O2 to induce oxidative cellular damage. Cell viability and lactate dehydrogenase (LDH) were detected by ELISA kits, protein expressions of Heme Oxygenase 1(HO-1), receptor interacting protein kinase 1 (RIPK1) and receptor interacting protein kinase 3 (RIPK3) were observed by WB, and TUNEL was used to detected cell apoptosis. H2O2 significantly decreased cell viability and increased LDH release and necroptotic and apoptotic cell deaths (all p  0.05). These findings indicated that Dex attenuates H2O2 induced cardiomyocyte necroptotic and apoptotic cell death respectively dependently and independently of α2-AR activation.

Allopurinol (ALP) attenuates oxidative stress and diabetic cardiomyopathy (DCM), but the mechanism is unclear. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) following the disassociation with its repressor Keap1 under oxidative stress can maintain inner redox homeostasis and attenuate DCM with concomitant attenuation of autophagy. We postulated that ALP treatment may activate Nrf2 to mitigate autophagy over-activation and consequently attenuate DCM. Streptozotocin-induced type 1 diabetic rats were untreated or treated with ALP (100 mg/kg/d) for 4 weeks and terminated after heart function measurements by echocardiography and pressure-volume conductance system. Cardiomyocyte H9C2 cells infected with Nrf2 siRNA or not were incubated with high glucose (HG, 25 mmol/L) concomitantly with ALP treatment. Cell viability, lactate dehydrogenase, 15-F2t-Isoprostane and superoxide dismutase (SOD) were measured with colorimetric enzyme-linked immunosorbent assays. ROS, apoptosis, was assessed by dihydroethidium staining and TUNEL, respectively. The Western blot and qRT-PCR were used to assess protein and mRNA variations. Diabetic rats showed significant reductions in heart rate (HR), left ventricular eject fraction (LVEF), stroke work (SW) and cardiac output (CO), left ventricular end-systolic volume (LVVs) as compared to non-diabetic control and ALP improved or normalized HR, LVEF, SW, CO and LVVs in diabetic rats (all P

Children with repeated inhalational anesthesia may develop cognitive disorders. This study aimed to investigate the transcriptome-wide response of hippocampus in young mice that had been exposed to multiple sevoflurane in the neonatal period. Mice received 3% sevoflurane for 2 h on postnatal day (PND) 6, 8, and 10, followed by arterial blood gas test on PND 10, behavioral experiments on PND 31-36, and RNA sequencing (RNA-seq) of hippocampus on PND 37. Functional annotation and protein-protein interaction analyses of differentially expressed genes (DEGs) and quantitative reverse transcription polymerase chain reaction (qPCR) were performed. Neonatal sevoflurane exposures induced cognitive and social behavior disorders in young mice. RNA-seq identified a total of 314 DEGs. Several enriched biological processes (ion channels, brain development, learning, and memory) and signaling pathways (oxytocin signaling pathway and glutamatergic, cholinergic, and GABAergic synapses) were highlighted. As hub-proteins, Pten was involved in nervous system development, synapse assembly, learning, memory, and behaviors, Nos3 and Pik3cd in oxytocin signaling pathway, and Cdk16 in exocytosis and phosphorylation. Some top DEGs were validated by qPCR. This study revealed a transcriptome-wide profile in mice hippocampus after multiple neonatal exposures to sevoflurane, promoting better understanding of underlying mechanisms and investigation of preventive strategies.

Objective: Neuropathic pain poses a persistent challenge in clinical management. Neuromodulation has emerged as a last‐resort therapy. Conventional spinal cord stimulation (Con SCS) often causes abnormal sensations and provides short analgesia, whereas high‐frequency spinal cord stimulation (HF SCS) is a newer therapy that effectively alleviates pain without paresthesia. However, the modes of action of 10kHz HF SCS (HF10 SCS) in pain relief remain unclear. To bridge this knowledge gap, we employed preclinical models that mimic certain features of clinical SCS to explore the underlying mechanisms of HF10 SCS. Addressing these issues would provide the scientific basis for improving and evaluating the effectiveness, reliability, and practicality of different frequency SCS in clinical settings. Methods: We established a preclinical SCS model to examine its effects in a neuropathic pain rat model. We conducted bulk and single‐cell RNA sequencing in the spinal dorsal horn (SDH) to examine cellular and molecular changes under different treatments. We employed genetic manipulations through intrathecal injection of a lentiviral system to explore the SCS‐mediated signaling axis in pain. Various behavioral tests were performed to evaluate pain conditions under different treatments. Results: We found that HF10 SCS significantly reduces immune responses in the SDH by inactivating the Kaiso‐P2X7R pathological axis in microglia, promoting long‐lasting pain relief. Targeting Kaiso‐P2X7R in microglia dramatically improved efficacy of Con SCS treatment, leading to reduced neuroinflammation and long‐lasting pain relief. Interpretation: HF10 SCS could improve the immunopathologic state in the SDH, extending its benefits beyond symptom relief. Targeting the Kaiso‐P2X7R axis may enhance Con SCS therapy and offer a new strategy for pain management. ANN NEUROL 2024;95:966–983 [ABSTRACT FROM AUTHOR]

Abnormalities in lipid metabolism induce myocardial structural and functional disorders, leading to the development of diabetic cardiomyopathy (DCM), which has become a hotspot in current DCM research. The transmembrane glycoprotein CD36 is a multifunctional membrane protein that facilitates fatty acid transport, which is involved in the regulation of cardiac lipid metabolism. CD36 signaling plays a key role in the pathogenesis of DCM mediated cardiac injuries. This article summarizes the structure of CD36 and its role in specific cell types, and further explores the pathophysiological role of CD36 in DCM, proposing that targeting CD36 may prove to be a potential pharmacological strategy in the prevention and treatment of DCM. [ABSTRACT FROM AUTHOR]