Dexmedetomidine Prevents Chronic Incisional Pain After Brain Tumor Resection: A Secondary Analysis of the Randomized Control Trial.

BACKGROUND: Dexmedetomidine was reported to reduce postoperative acute pain after neurosurgery. However, the efficacy of dexmedetomidine for preventing chronic incisional pain is uncertain. METHODS: This article is a secondary analysis of a randomized, double-blind, placebo-controlled trial. Eligible patients were randomly allocated to either the dexmedetomidine group or the placebo group. Patients assigned to the dexmedetomidine group were given a 0.6 µg kg -1 dexmedetomidine bolus followed by a 0.4 µg kg -1 h -1 maintenance dose until dural closure; placebo patients were given comparable amounts of normal saline. The primary end point was the incidence of incisional pain at 3 months after craniotomy evaluated by numerical rating scale scores and defined as any score >0. The secondary end points were postoperative acute pain scores, sleep quality, and Short-Form McGill Pain Questionnaire (SF-MPQ-2) at 3 months after craniotomy. RESULTS: From January 2021 to December 2021, a total of 252 patients were included in the final analysis: the dexmedetomidine group (n = 128) and the placebo group (n = 124). The incidence of chronic incisional pain was 23.4% (30 of 128) in the dexmedetomidine group versus 42.7% (53 of 124) in the placebo group (risk ratio, 0.55; 95% confidence interval, 0.38-0.80; P = .001). The overall severity of chronic incisional pain was mild in both groups. Patients in the dexmedetomidine group had lower acute pain severity on movement than those in the placebo group for the first 3 days after surgery (all adjusted P < .01). Sleep quality did not differ between groups. However, the SF-MPQ-2 total sensory ( P = .01) and neuropathic pain descriptor ( P = .023) scores in the dexmedetomidine group were lower than those in the placebo group. CONCLUSIONS: Prophylactic intraoperative dexmedetomidine infusion reduces the incidence of chronic incisional pain as well as acute pain score after elective brain tumor resections.

CircFOXN2 alleviates glucocorticoid- and tacrolimus-induced dyslipidemia by reducing FASN mRNA stability by binding to PTBP1 during liver transplantation.

We aimed to examine impacts and functional mechanism of circular RNA forkhead box N2 (FOXN2) in tacrolimus (TAC)- and dexamethasone (Dex)-induced lipid metabolism disorders. RNA level and protein contents in TAC, Dex, or combined TAC- plus Dex-treated patients and Huh-7 cells were measured utilizing quantitative real-time (qRT)-PCR and western blotting assays measured the formation of lipid droplet. Total cholesterol (TC) and triglyceride (TG) levels were determined using corresponding commercial kits and Oil red O staining. RNA immunoprecipitation and RNA pull-down verified the binding relationship among circFOXN2, polypyrimidine tract binding protein 1 (PTBP1) and fatty acid synthase (FASN). Male C57BL/6 mice were used to establish a dyslipidemia mouse model to validate the discoveries at the cellular level. Dex treatment significantly promoted TAC-mediated increase of TC and TG in serum samples and Huh-7 cells. Moreover, circFOXN2 was reduced but FASN was elevated in TAC-treated Huh-7 cells, and these expression trends were markedly enhanced by Dex cotreatment. Overexpression of circFOXN2 could reverse the accumulation of TC and TG and the upregulation of FASN and sterol regulatory element binding transcription factor 2 (SREBP2) mediated by Dex and TAC cotreatment. Mechanistically, circFOXN2 reduced FASN mRNA stability by recruiting PTBP1. The protective roles of circFOXN2 overexpression on lipid metabolism disorders were weakened by FASN overexpression. In vivo finding also disclosed that circFOXN2 greatly alleviated the dysregulation of lipid metabolism triggered by TAC plus Dex. CircFOXN2 alleviated the dysregulation of lipid metabolism induced by the combination of TAC and Dex by modulating the PTBP1/FASN axis.NEW & NOTEWORTHY Collectively, our experiments revealed for the first time that circFOXN2 alleviated the Dex- and TAC-induced dysregulation of lipid metabolism by regulating the PTBP1/FASN axis. These findings suggested that circFOXN2 and FASN might be candidate targets for the treatment of Dex- and TAC-induced metabolic disorders.

Rice co-expression network analysis identifies gene modules associated with agronomic traits.

Identifying trait-associated genes is critical for rice (Oryza sativa) improvement, which usually relies on map-based cloning, quantitative trait locus analysis, or genome-wide association studies. Here we show that trait-associated genes tend to form modules within rice gene co-expression networks, a feature that can be exploited to discover additional trait-associated genes using reverse genetics. We constructed a rice gene co-expression network based on the graphical Gaussian model using 8,456 RNA-seq transcriptomes, which assembled into 1,286 gene co-expression modules functioning in diverse pathways. A number of the modules were enriched with genes associated with agronomic traits, such as grain size, grain number, tiller number, grain quality, leaf angle, stem strength, and anthocyanin content, and these modules are considered to be trait-associated gene modules. These trait-associated gene modules can be used to dissect the genetic basis of rice agronomic traits and to facilitate the identification of trait genes. As an example, we identified a candidate gene, OCTOPUS-LIKE 1 (OsOPL1), a homolog of the Arabidopsis (Arabidopsis thaliana) OCTOPUS gene, from a grain size module and verified it as a regulator of grain size via functional studies. Thus, our network represents a valuable resource for studying trait-associated genes in rice.

Dexmedetomidine administration during brain tumour resection for prevention of postoperative delirium: a randomised trial.

BACKGROUND: Delirium is common, especially after neurosurgery. Dexmedetomidine might reduce delirium by improving postoperative analgesia and sleep quality. We tested the primary hypothesis that dexmedetomidine administration during intracerebral tumour resection reduces the incidence of postoperative delirium. METHODS: This randomised, double-blind, placebo-controlled trial was conducted in two tertiary-care hospitals in Beijing. We randomised 260 qualifying patients to either dexmedetomidine (n=130) or placebo (n=130). Subjects assigned to dexmedetomidine were given a loading dose of 0.6 µg kg-1 followed by continuous infusion at 0.4 µg kg-1 h-1 until dural closure; subjects in the placebo group were given comparable volumes of normal saline. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method twice daily during the initial 5 postoperative days. RESULTS: The average (standard deviation) age of participating patients was 45 (12) yr, duration of surgery was 4.2 (1.5) h, and patients assigned to dexmedetomidine were given an average of 126 (45) µg of dexmedetomidine. There was less delirium during the initial 5 postoperative days in patients assigned to dexmedetomidine (22%, 28 of 130 patients) than in those given placebo (46%, 60 of 130 patients) with a risk ratio of 0.51 (95% confidence interval: 0.36-0.74, P<0.001). Postoperative pain scores with movement, and recovery and sleep quality were improved by dexmedetomidine (P<0.001). The incidence of safety outcomes was similar in each group. CONCLUSIONS: Prophylactic intraoperative dexmedetomidine infusion reduced by half the incidence of delirium during the initial 5 postoperative days in patients recovering from elective brain tumour resection. CLINICAL TRIAL REGISTRATION: NCT04674241.

EXPLICIT-Kinase: A gene expression predictor for dissecting the functions of the Arabidopsis kinome.

Protein kinases regulate virtually all cellular processes, but it remains challenging to determine the functions of all protein kinases, collectively called the "kinome", in any species. We developed a computational approach called EXPLICIT-Kinase to predict the functions of the Arabidopsis kinome. Because the activities of many kinases can be regulated transcriptionally, their gene expression patterns provide clues to their functions. A universal gene expression predictor for Arabidopsis was constructed to predict the expression of 30,172 non-kinase genes based on the expression of 994 kinases. The model reconstituted highly accurate transcriptomes for diverse Arabidopsis samples. It identified the significant kinases as predictor kinases for predicting the expression of Arabidopsis genes and pathways. Strikingly, these predictor kinases were often regulators of related pathways, as exemplified by those involved in cytokinesis, tissue development, and stress responses. Comparative analyses revealed that portions of these predictor kinases are shared and conserved between Arabidopsis and maize. As an example, we identified a conserved predictor kinase, RAF6, from a stomatal movement module. We verified that RAF6 regulates stomatal closure. It can directly interact with SLAC1, a key anion channel for stomatal closure, and modulate its channel activity. Our approach enables a systematic dissection of the functions of the Arabidopsis kinome.

Assessment of the hydrochemistry, water quality, and human health risk of groundwater in the northwest of Nansi Lake Catchment, north China.

In this study, the formation mechanism and water quality of groundwater in the northwest of Nansi Lake Catchment (NNLC) were analyzed through mathematical statistics, hydrochemical analysis and entropy weighted water quality index (EWQI), and the human health risk of nitrate was also evaluated. To this end, 89 wells in the NNLC were sampled, and the groundwater samples were divided into three groups (I, II, and III) according to cluster analysis results and spatial distribution. The main results are as follows: Topographically, Groups I, II, and III correspond to the alluvial plains, apron plain, and low hills and its front margin, respectively. According to the Piper diagram, the hydrochemical types of Groups I and II groundwater are Na-SO4·Cl and Ca·Mg-HCO3, respectively, and that of Group III is more concentrated, mostly corresponding to the Ca-HCO3 type. Hydrochemical analysis indicated that the development of groundwater hydrochemistry is mainly attributable to water-rock interactions, with the primary process being the dissolution of minerals such as calcite, dolomite, gypsum, and albite. Evaporation exhibited an increasing trend from the northeast to the southwest. Groups I and III presented obvious effects of human activities, with Group I showing sulfate pollution and Group III mainly showing nitrate pollution. Analysis of the characteristics and causes of the groundwater hydrochemistry revealed the proposed approach has excellent performance for classification in areas with complex hydrogeological conditions. The results of EWQI showed that the overall water quality was good, following the order Group III > Group II > Group I. The overall human health risk of nitrate in groundwater was low, but the risk was slightly higher for children than for adults. Therefore, the effects of nitrate contamination should be considered when exploiting hilly and peri-urban groundwater for drinking water.

Transcriptome and DNA methylation analysis reveals molecular mechanisms underlying intrahepatic cholangiocarcinoma progression.

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy with increasing incidence. It has been suggested that DNA methylation drives cancer development. However, the molecular mechanisms underlying iCCA progression and the roles of DNA methylation still remain elusive. In this study, weighted correlation networks were constructed to identify gene modules and hub genes associated with the tumour stage. We identified 12 gene modules, two of which were significantly positively or negatively related to the tumour stage， respectively. Key hub genes SLC2A1, CDH3 and EFHD2 showed increased expression across the tumour stage and were correlated with poor survival, whereas decrease of FAM171A1, ONECUT1 and PHYHIPL was correlated with better survival. Pathway analysis revealed hedgehog pathway was activated in CDH3 up-regulated tumours, and chromosome separation was elevated in tumours expressing high EFHD2. JAK-STAT pathway was overrepresented in ONECUT1 down-regulated tumours, whereas Rho GTPases-formins signalling was activated in PHYHIPL down-regulated tumours. Finally, significant negative associations between expression of EFHD2, PHYHIPL and promoter DNA methylation were detected, and alterations of DNA methylation were correlated with tumour survival. In summary, we identified key genes and pathways that may participate in progression of iCCA and proposed putative roles of DNA methylation in iCCA.

Ketamine Alleviates Depressive Symptoms in Patients Undergoing Intracranial Tumor Resection: A Randomized Controlled Trial.

BACKGROUND: Depressive symptoms occur in over 40% of neurosurgical patients during the perioperative period. However, no measure has been suggested to have a rapid effect on depressive surgical patients during increasingly shorter stays in the hospital. This study aimed to determine whether ketamine could improve depressive symptoms rapidly and safely during the hospital stay. METHODS: This was a randomized, placebo-controlled, and double-blinded trial. Patients with moderate-to-severe depressive symptoms undergoing elective supratentorial brain tumor resection were randomized to intravenously receive either (1) 0.5 mg·kg-1 ketamine for 40 minutes or (2) an identical volume of normal saline. The primary outcome was treatment response on postoperative day 3, defined as a ≥50% reduction from the baseline depressive score. The secondary outcomes included the rate of remission and safety outcomes. The Montgomery-Åsberg Depression Rating Scale was applied by trained psychiatrists to evaluate depressive symptoms. RESULTS: A total of 84 neurosurgical patients were enrolled in the trial. The response rate was increased by the administration of ketamine (41.5% [17/41] vs 16.3% [7/43]; relative risk [RR]: 2.51, 95% confidence interval [CI], 1.18-5.50) relative to the administration of placebo at 3 days. Furthermore, the remission rate at discharge (29.3% [12/41] vs 7.0% [3/43]; RR: 4.20, 95% CI, 1.28-13.80) was also improved by ketamine. No psychotic symptoms or adverse events were reported to be substantially higher in the ketamine group. CONCLUSIONS: The trial indicates that the intraoperative administration of ketamine could alleviate moderate-to-severe depressive symptoms in neurosurgical patients without worsening safety.

A characterization of groundwater fluoride, influencing factors and risk to human health in the southwest plain of Shandong Province, North China.

This study investigated 324 groundwater samples collected from the southwest plain of Shandong Province during the dry and wet seasons. Groundwater fluoride in the study area and the influencing factors were characterized and discussed using statistical analysis, ion ratios, Piper diagrams, the saturation index (SI) and ArcGIS software. In addition, the risk posed by groundwater fluoride to human health was assessed. The results showed that groundwater in the study area had elevated fluoride concentrations, with average dry and wet season concentrations of 1.15 mg·L-1 and 1.08 mg·L-1, respectively. Groundwater fluoride showed consistent spatial variations during the dry and wet seasons, with a significant regionalization pattern of low concentrations in the east and high concentrations in the west. Groundwater F- was significantly negatively correlated with Ca2+ and positively correlated with pH, HCO3- and Na+. Important factors identified as having an effect on groundwater F- in the study area included the balance of dissolution of fluorite and calcite, the weakly alkaline environment and cation exchange. In addition, hydrochemical types of high-fluoride groundwater in the study area were identified as mainly HCO3-Na and SO4·Cl-Na. The assessment of the risk of high groundwater fluoride to human health showed that children are more at risk compared to adults, with the risk during the dry season exceeding that over the wet season. It is recommended that water quality management in the study area prioritize the formulation of measures to mitigate high concentrations of fluoride in groundwater .

Long Non-Coding RNA CRNDE Regulates Angiogenesis in Hepatoblastoma by Targeting the MiR-203/VEGFA Axis.

OBJECTIVE: MiR-203 has been shown to participate in multiple malignancies, but the role of miR-203 in hepatoblastoma (HB) remains unclear. The aim of our study was to investigate the effects of miR-203 in HB. METHODS: A total of 15 pairs of HB tissues and para-tumour normal tissues were collected for the experiments. RT-qPCR and Western blotting were performed to detect the expression of CRNDE, miR-203, and VEGFA at the mRNA and/or protein levels, respectively. A dual luciferase assay verified the target relationship between miR-203 and the 3'UTR of VEGFA as well as miR-203 and CRNDE. In addition, MTT, wound healing, and tube formation assays were performed to assess the effects of miR-203, VEGFA, and CRNDE on cell proliferation, migration, and angiogenesis, respectively. RESULTS: Our data revealed that miR-203 expression was decreased in HB tissues, while long non-coding RNA (lncRNA) CRNDE expression was increased. The dysregulation of miR-203 and CRNDE was closely related to tumour size and stage. Moreover, overexpression of miR-203 inhibited angiogenesis. A dual luciferase assay verified that VEGFA is a direct target of miR-203 and that CRNDE binds to miR-203. Furthermore, our results showed that miR-203 suppressed cell viability, migration, and angiogenesis by regulating VEGFA expression. Additionally, it was confirmed that CRNDE promoted angiogenesis by negatively regulating miR-203 expression. CONCLUSION: lncRNA CRNDE targets the miR-203/VEGFA axis and promotes angiogenesis in HB. These results provide insight into the underlying mechanisms of HB and indicate that CRNDE and miR-203 might be potential targets for HB therapy.

Sevoflurane versus PRopofol combined with Remifentanil anesthesia Impact on postoperative Neurologic function in supratentorial Gliomas (SPRING): protocol for a randomized controlled trial.

BACKGROUND: Patients with intracranial tumors are more sensitive to anesthetics than the general population and are therefore more susceptible to postoperative neurologic and neurocognitive dysfunction. Sevoflurane or propofol combined with remifentanil are widely used general anesthetic regimens for craniotomy, with neither regimen shown to be superior to the other in terms of neuroprotective efficacy and anesthesia quality. There is no evidence regarding the variable effects on postoperative neurologic and neurocognitive functional outcome under these two general anesthetic regimens. This trial will compare inhalational sevoflurane or intravenous propofol combined with remifentanil anesthesia in patients with supratentorial gliomas and test the hypothesis that postoperative neurologic function is equally affected between the two regimens. METHODS: This is a prospective, single-center, randomized parallel arm equivalent clinical trial, which is approved by China Ethics Committee of Registering Clinical Trials (ChiECRCT-20,160,051). Patients with supratentorial gliomas diagnosed by magnetic resonance imaging will be eligible for the trial. Written informed consent will be obtained before randomly assigning each subject to either the sevoflurane-remifentanil or propofol-remifentanil group for anesthesia maintenance to achieve an equal-desired depth of anesthesia. Intraoperative intervention and monitoring will follow a standard anesthetic management protocol. All of the physiological parameters and other medications administered during the intervention will be recorded. The primary outcome will be neurologic function change assessed by National Institute of Health Stroke Scale (NIHSS) within 4 h after general anesthesia when observer's assessment of alertness/sedation (OAA/S) reaches 4. Secondary outcomes will include NIHSS and modified NIHSS change 1 and 2 days after general anesthesia, hemodynamic stability, intraoperative brain relaxation, quality of anesthesia emergence, quality of anesthesia recovery, postoperative cognitive function, postoperative pain, postoperative neurologic complications, as well as perioperative medical expense. DISCUSSION: This randomized equivalency trial will primarily compare the impacts of sevoflurane-remifentanil and propofol-remifentanil anesthesia on short-term postoperative neurologic function in patients with supratentorial gliomas undergoing craniotomy. The exclusion criteria are strict to ensure that the groups are comparable in all aspects. Repeated and routine neurologic evaluations after operation are always important to evaluate neurosurgical patients' recovery and any newly presenting complications. The results of this trial would help specifically to interpret anesthetic residual effects on postoperative outcomes, and perhaps would help the anesthesiologist to select the optimal anesthetic regimen to minimize its impact on neurologic function in this specific patient population. TRIAL REGISTRATION: The study was registered and approved by the Chinese Clinical Trial Registry (Chinese Clinical Trial Registry, ChiCTR-IOR-16009177). Principle investigator: Nan Lin (email address: linnan127@gmail.com) and Ruquan Han (email address: hanrq666@aliyun.com) Date of Registration: September 8th, 2016. Country of recruitment: China.

Effects of Dexmedetomidine on motor- and somatosensory-evoked potentials in patients with thoracic spinal cord tumor: a randomized controlled trial.

BACKGROUND: We hypothesized that the addition of dexmedetomidine in a clinically relevant dose to propofol-remifentanil anesthesia regimen does not exert an adverse effect on motor-evoked potentials (MEP) and somatosensory-evoked potentials (SSEP) in adult patients undergoing thoracic spinal cord tumor resection. METHODS: Seventy-one adult patients were randomized into three groups. Propofol group (n = 25): propofol-remifentanil regimenand the dosage was adjusted to maintain the bispectral index (BIS) between 40 and 50. DP adjusted group (n = 23): Dexmedetomidine (0.5 µg/kg loading dose infused over 10 min followed by a constant infusion of 0.5 µg/kg/h) was added to the propofol-remifentanil regimen and propofol was adjusted to maintain BIS between 40 and 50. DP unadjusted group (n = 23): Dexmedetomidine (administer as DP adjusted group) was added to the propofol-remifentanil regimen and propofol was not adjusted. All patients received MEP, SSEP and BIS monitoring. RESULTS: There were no significant changes in the amplitude and latency of MEP and SSEP among different groups (P > 0.05). The estimated propofol plasma concentration in DP adjusted group (2.7 ± 0.3 µg/ml) was significantly lower than in propofol group (3.1 ± 0.2 µg/ml) and DP unadjusted group (3.1 ± 0.2 µg/ml) (P = 0.000). BIS in DP unadjusted group (35 ± 5) was significantly lower than in propofol group (44 ± 3) (P = 0.000). CONCLUSIONS: The addition of dexmedetomidine to propofol-remifentanil regimen does not exert an adverse effect on MEP and SSEP monitoring in adult patients undergoing thoracic spinal cord tumor resection. TRIAL REGISTRATION: The study was registered with the Chinese Clinical Trial Registry on January 31st, 2014. The reference number was ChiCTR-TRC-14004229.

Stomatal maturomics: hunting genes regulating guard cell maturation and function formation from single-cell transcriptomes.

Stomata play critical roles in gas exchange and immunity to pathogens. While many genes regulating early stomatal development up to the production of young guard cells (GCs) have been identified in Arabidopsis, much less is known about how young GCs develop into mature functional stomata. Here we perform a maturomics study on stomata, with "maturomics" defined as omics analysis of the maturation process of a tissue or organ. We develop an integrative scheme to analyze three public stomata-related single-cell RNA-seq datasets and identify a list of 586 genes that are specifically up-regulated in all three datasets during stomatal maturation and function formation. The list, termed sc_586, is enriched with known regulators of stomatal maturation and functions. To validate the reliability of the dataset, we selected two candidate G2-like transcription factor genes, MYS1 and MYS2, to investigate their roles in stomata. These two genes redundantly regulate the size and hoop rigidity of mature GCs, and the mys1 mys2 double mutants cause mature GCs with severe defects in regulating their stomatal apertures. Taken together, our results provide a valuable list of genes for studying GC maturation and function formation.

Intraoperative blood pressure and cardiac complications after aneurysmal subarachnoid hemorrhage: a retrospective cohort study.

BACKGROUND: Previous studies report that intraoperative hypotension worsens outcomes after aneurysmal subarachnoid hemorrhage (aSAH). However, the hypotensive harm threshold for major adverse cardiovascular events (MACE) remains unclear. METHODS: The authors included aSAH patients who had general anesthesia for aneurysmal clipping/coiling. MACE were defined by a composite of acute myocardial injury, acute myocardial infarction, and other cardiovascular complications identified by electrocardiogram and echocardiography. The authors initially used logistic regression and change-point analysis based on the second derivative to identify mean arterial pressure (MAP) of 75 mmHg as the harm threshold. Thereafter, our major exposure was MAP below 75 mmHg characterized by area, duration, and time-weighted average. The area below 75 mmHg represents the severity and duration of exposure and was defined as the sum of all areas below a specified threshold using the trapezoid rule. Time-weighted average MAP was derived by dividing area below the threshold by the duration of anesthesia. All analyses were adjusted for baseline risk factors including age greater than 70 years, female sex, severity of intracerebral hemorrhage, history of cardiovascular disease, and preoperative elevated myocardial enzymes. RESULTS: Among 1029 patients enrolled, 254 (25%) developed postoperative MACE. Patients who experienced MACE were slightly older (59±11 vs. 54±11 years), were slightly more often women (69 vs. 58%), and had a higher prevalence of cardiovascular history (65 vs. 47%). Adjusted cardiovascular risk increased nearly linearly over the entire range of observed MAP. However, there was a slight inflexion at MAP of 75 mmHg. MACE was significantly associated with area [adjusted odds ratios (aOR) 1.004 per 10 mmHg.min, 95% CI: 1.001-1.007, P =0.002), duration (aOR 1.031 per 10 min, 95% CI: 1.009-1.054, P =0.006), and time-weighted average (aOR 3.516 per 10 mmHg, 95% CI: 1.818-6.801, P <0.001) of MAP less than 75 mmHg. CONCLUSIONS: Lower blood pressures were associated with cardiovascular complications over the entire observed range, but worsened when MAP was less than 75 mmHg. Pending trial data to establish causality, it may be prudent to keep MAP above 75 mmHg in patients having surgical aSAH repairs to reduce the risk of MACE.

Intravenous tranexamic acid for intracerebral meningioma resections: A randomized, parallel-group, non-inferiority trial.

STUDY OBJECTIVES: Tranexamic acid (TXA) is an antifibrinolytic that is widely used to reduce surgical bleeding. However, TXA occasionally causes seizures and the risk might be especially great after neurosurgery. We therefore tested the hypothesis that TXA does not meaningfully increase the risk of postoperative seizures within 7 days after intracranial tumor resections. DESIGN: Randomized, double-blind, placebo-controlled, non-inferiority trial. SETTING: Beijing Tiantan Hospital, Capital Medical University. PATIENTS: 600 patients undergoing supratentorial meningioma resection were included from October 2020 to August 2022. INTERVENTIONS: Patients were randomly assigned to a single dose of 20 mg/kg of TXA after induction (n = 300) or to the same volume of normal saline (n = 300). MEASUREMENT: The primary outcome was postoperative seizures occurring within 7 days after surgery, analyzed in both the intention-to-treat and per-protocol populations. Non-inferiority was defined by an upper limit of the 95% confidence interval for the absolute difference being <5.5%. Secondary outcomes included incidence of non-epileptic complication within 7 days, changes in hemoglobin concentration, estimated intraoperative blood loss. Post hoc analyses included the types and timing of seizures, oozing assessment, and a sensitivity analysis for the primary outcome in patients with pathologic diagnosis of meningioma. MAIN RESULTS: All 600 enrolled patients adhered to the protocol and completed the follow-up for the primary outcome. Postoperative seizures occurred in 11 of 300 (3.7%) of patients randomized to normal saline and 13 of 300 (4.3%) patients assigned to tranexamic acid (mean risk difference, 0.7%; 1-sided 97.5% CI, -∞ to 4.3%; P = 0.001 for noninferiority). No significant differences were observed in any secondary outcome. Post hoc analysis indicated similar amounts of oozing, calculated blood loss, recurrent seizures, and timing of seizures. CONCLUSION: Among patients having supratentorial meningioma resection, a single intraoperative dose of TXA did not significantly reduce bleeding and was non-inferior with respect to postoperative seizures after surgery. REGISTRY INFORMATION: This trial was registered at clinicaltrials.gov (NCT04595786) on October 22, 2020, by Dr.Yuming Peng.

Risk factors prediction of 6-month mortality after noncardiac surgery of older patients in China: a multicentre retrospective cohort study.

BACKGROUND: Identifying the risk factors associated with perioperative mortality is crucial, particularly in older patients. Predicting 6-month mortality risk in older patients based on large datasets can assist patients and surgeons in perioperative clinical decision-making. This study aimed to develop a risk prediction model of mortality within 6 months after noncardiac surgery using the clinical data from 11 894 older patients in China. MATERIALS AND METHODS: A multicentre, retrospective cohort study was conducted in 20 tertiary hospitals. The authors retrospectively included 11 894 patients (aged ≥65 years) who underwent noncardiac surgery between April 2020 and April 2022. The least absolute shrinkage and selection operator model based on linear regression was used to analyse and select risk factors, and various machine learning methods were used to build predictive models of 6-month mortality. RESULTS: The authors predicted 12 preoperative risk factors associated with 6-month mortality in older patients after noncardiac surgery. Including laboratory-associated risk factors such as mononuclear cell ratio and total blood cholesterol level, etc. Also including medical history associated risk factors such as stroke, history of chronic diseases, etc. By using a random forest model, the authors constructed a predictive model with a satisfactory accuracy (area under the receiver operating characteristic curve=0.97). CONCLUSION: The authors identified 12 preoperative risk factors associated with 6-month mortality in noncardiac surgery older patients. These preoperative risk factors may provide evidence for a comprehensive preoperative anaesthesia assessment as well as necessary information for clinical decision-making by anaesthesiologists.

Intraoperative arterial pressure and delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage after surgical clipping: A retrospective cohort study.

Background: Delayed cerebral ischemia (DCI) is the major predictor of poor outcomes in patients with aSAH. Previous studies have attempted to assess the relationship between controlling blood pressure and DCI. However, the management of intraoperative blood pressure in reducing the occurrence of DCI still remains inconclusive. Methods: All patients with aSAH who received general anesthesia for surgical clipping between January 2015 and December 2020 were prospectively reviewed. Patients were divided in the DCI group or the non-DCI group depending on whether DCI occurred or not. Intraoperative arterial pressure was measured every minute and recorded in an electronic anesthesia recording system along with intraoperative medication and other vital signs. The initial neurological function score, aneurysm characteristics, surgical and anesthetic information, and outcomes were compared between the DCI and the non-DCI groups. Results: Among 534 patients who were enrolled, a total of 164 (30.71%) patients experienced DCI. The baseline characteristics of patients were similar between the groups. The World Federation of Neurosurgical Societies (WFNS) Scale > 3, age ≥ 70 years, and the modified Fisher Scale > 2 were significantly higher in patients with DCI than those without. Though it was the second derivative of the regression analysis, 105 mmHg was adopted as the threshold for intraoperative hypotension and was not associated with DCI. Conclusions: The threshold of 105 mmHg was adopted as intraoperative hypotension even though it was the second derivative of the regression analysis and could not be proved to be associated with delayed cerebral ischemia adjusted by the baseline severity of aSAH and age.

The Influence of Trigeminocardiac Reflex on Postoperative Cardiac Adverse Events in Patients Undergoing Cerebellopontine Angle Tumor Resections: A Case-Control Study.

OBJECTIVE: To assess the potential impact of the trigeminocardiac reflex (TCR) on postoperative adverse cardiac events and to identify predictors of the TCR in cerebellopontine angle surgery. METHODS: Patients undergoing elective cerebellopontine angle surgery from October 1, 2015, to September 30, 2020, were recruited consecutively for this retrospective case-control study. The TCR was evaluated by reviewing electronic anesthesia records and defined as a drop in heart rate was >20%. Controls were identified from the same retrospective cohort and matched by age, sex, and similar (±5 days) surgery date in the ratio of 1:2. RESULTS: Of 2446 patients, 68 (2.78%) experienced TCR episodes. A total of 97 TCR episodes occurred among the 68 patients. In 2 TCR episodes, severe cardiac complications developed after surgery-myocardial injury in one case and cardiac arrest in the other case. The prevalence of adverse cardiovascular events was higher in the TCR group (60.3% vs. 36.0%, P = 0.001) than in the control group. The independent risk factor for the TCR in the multivariate condition logistic regression was tumor compression of the brainstem (odds ratio = 2.36, 95% confidence interval 1.40-3.95; P = 0.001). CONCLUSIONS: Intraoperative TCR episodes seemed to be associated with postoperative adverse cardiac events in patients undergoing cerebellopontine angle surgery. Moreover, tumor compression of the brainstem might be a risk factor for TCR episodes.

Effect of dexmedetomidine on postoperative delirium in patients undergoing awake craniotomies: study protocol of a randomized controlled trial.

INTRODUCTION: Postoperative delirium (POD) is a common complication, and it has a high incidence in neurosurgery patients. Awake craniotomy (AC) has been widely performed in patients with glioma in eloquent and motor areas. Most of the surgical procedure is frontotemporal craniotomy, and the operation duration has been getting longer. Patients undergoing AC are high-risk populations for POD. Dexmedetomidine (Dex) administration perioperatively might help to reduce the incidence of POD. The purpose of this study is to investigate the effect of Dex on POD in patients undergoing AC. METHODS: The study is a prospective, single-center, double-blinded, paralleled-group, randomized controlled trial. Patients undergoing elective AC will be randomly assigned to the Dex group and the control group. Ten minutes before urethral catheterization, patients in the Dex group will be administered with a continuous infusion at a rate of 0.2 µg/kg/h until the end of dural closure. In the control group, patients will receive an identical volume of normal saline in the same setting. The primary outcome will be the cumulative incidence and severity of POD. It will be performed by using the confusion assessment method in the first 5 consecutive days after surgery. Secondary outcomes include quality of intraoperative awareness, stimulus intensity of neurological examination, pain severity, quality of recovery and sleep, and safety outcomes. DISCUSSION: This study is to investigate whether the application of Dex could prevent POD in patients after undergoing AC and will provide strong evidence-based clinical practice on the impact of intraoperative interventions on preventing POD in AC patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05195034. Registered on January 18, 2022.

Intraoperative infusion of dexmedetomidine for prevention of postoperative delirium in elderly patients undergoing craniotomy: a protocol of randomised clinical trial.

INTRODUCTION: Postoperative delirium (POD) is a common surgical complication. The incidence is 19% in neurological procedures, and advanced age is a risk factor for neurological procedures. Many studies have shown that dexmedetomidine (DEX) reduced the incidence of delirium after non-cardiac surgery in elderly patients. However, there are few studies focus on the effect of DEX on POD in elderly patients undergoing neurosurgery. METHODS AND ANALYSIS: This is a randomised, double-blinded, paralleled-group and controlled trial. Patients older than 65 years and scheduled for elective craniotomy will be randomly assigned to the DEX group and the control group. After endotracheal intubation, patients in the DEX group will be administered with continuous DEX infusion at rate of 0.4 µg/kg/hour until the surgical haemostasis. In the control group, patients will receive the identical volume of normal saline in the same setting. The primary outcome is the incidence of POD during the first 5 days. Delirium will be evaluated through a combination of three methods, including the Richmond Agitation Sedation Scale (RASS), the confusion assessment method for ICU (CAM-ICU) and the 3 min diagnostic interview for CAM (3D-CAM). The RASS, CAM-ICU and 3D-CAM will be evaluated two times per day (08:00-10:00 and 18:00-20:00 hours) during the first postoperative 5 days. Secondary outcomes include pain severity score, quality of recovery, quality of sleep, cognitive function, psychological health state, intraoperative data, physiological status, length of stay in ICU and hospital, hospitalisation costs, non-delirium complications, and 30-day all-cause mortality. ETHICS AND DISSEMINATION: The protocol (V.4.0) has been approved by the medical ethics committee of Beijing Tiantan Hospital, Capital Medical University (KY2021-194-03). The findings of the study will be disseminated in a peer-reviewed journal and at a scientific conference. TRIAL REGISTRATION NUMBER: NCT05168280.