Anaesthesia-related mortality within 24 h following 9,391,669 anaesthetics in 10 cities in Hubei Province, China: a serial cross-sectional study.

Background: The mortality risk related to anaesthesia in China remains poorly characterized. The objective of this study was to evaluate the anaesthesia-related mortality in terms of its incidence, changes, causes and preventability in Hubei, China, between 2017 and 2021 using a series of annual surveys. Methods: We prospectively collected information on patient, surgical, anaesthesia, and hospital characteristics for 9,391,669 anaesthesia procedures performed between 2017 and 2021 in 10 cities within Hubei Province, China. Anaesthesia-related death was defined as death that deemed to be entirely or partially attributable to anaesthesia, occurring within 24 h following anaesthesia administration. All fatalities were scrutinized consecutively to determine their root causes and preventability. The incidence and patterns of anaesthesia-related deaths were analysed from 2017 to 2021. A mixed-effects model with a Poisson link function was fitted to evaluate the city-level annual changes in risk-adjusted incidence of anaesthesia-related deaths. Findings: 600 cases of anaesthetic deaths occurred from 2017 to 2021, yielding an incidence of 6.4 per 100,000 anaesthesia procedures [95% confidence interval (95% CI): 5.9, 6.9], and most were preventable (71.3%). There was a significant decrease from 2017 to 2021, in the incidences of anaesthesia-related death across all patients, those with American Society of Anaesthesiologists physical status (ASAPS) ≥III, and those who had general anaesthesia, with a percentage reduction of 57.6%, 59.1%, and 55.9%, respectively. The risk-adjusted annual changes indicated significant downward trends for the incidence of anaesthetic mortality from 2017 to 2018, 2019, 2020, and 2021. For instance, the risk-adjusted annual changes for the anaesthetic mortality incidence from 2017 to 2021 was -2.5 (95% CI: -1.4, -4.7). Interpretation: In this large, comprehensive database study conducted in Central China, the anaesthesia-related death incidence was 6.4 per 100,000. Notably, the incidence of anaesthesia-related deaths decreased between 2017 and 2021. However, further in-depth analysis is needed to understand the extent to which these trends represent a change in patient safety. Funding: Innovation and optimization of perioperative respiratory system management strategy (Hubei Technological Innovation Special Fund, 2019ACA167).

STIM2 Suppression Blocks Glial Activation to Alleviate Brain Ischemia Reperfusion Injury via Inhibition of Inflammation and Pyroptosis.

Cerebral ischemia/reperfusion injury (CIRI) involves various pathogenic mechanisms, including cytotoxicity, apoptosis, inflammation, and pyroptosis. Stromal interactive molecule 2 (STIM2) is implicated in cerebral ischemia. Consequently, this study investigates the biological functions of STIM2 and its related mechanisms in CIRI progression. Middle cerebral artery occlusion/reperfusion (MCAO/R) mouse models and oxygen-glucose deprivation/reoxygenation (OGD/R) cellular models were established. STIM2 level was upregulated in experimental CIRI models, as shown by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunofluorescence staining. Brain infarction and edema were attenuated by STIM2 knockdown, as 2,3,5-triphenyltetrazolium chloride (TTC) staining and brain water content evaluation revealed. STIM2 knockdown relieved neuronal apoptosis, microglia activation, inflammation and pyroptosis in MCAO/R mice, as detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, enzyme-linked immunosorbent assay (ELISA) and western blotting. Results of flow cytometry, ELISA, western blotting and cell counting kit-8 (CCK-8) assays also showed that STIM2 knockdown inhibited inflammation, apoptosis and pyroptosis in OGD/R-treated BV2 cells. Moreover, STIM2 knockdown inhibited apoptosis and pyroptosis in PC12 cells incubated with conditioned medium collected from OGD/R-exposed BV2 cells. Mechanistically, lncRNA Malat1 (metastasis associated lung adenocarcinoma transcript 1) positively regulated STIM2 expression by sponging miR-30d-5p. Their binding relationship was confirmed by luciferase reporter assays. Finally, lncRNA Malat1 elevation or miR-30d-5p knockdown abolished the sh-STIM2-induced inhibition in cell damage. In conclusion, STIM2 knockdown in microglia alleviates CIRI by inhibiting microglial activation, inflammation, apoptosis, and pyroptosis.

Development and validation of nomograms to predict preoperative anxiety and postoperative pain in patients undergoing gynecological surgery: An observational analysis.

BACKGROUND: Perioperative anxiety and pain are associated with patient dissatisfaction, postoperative complications, and prolonged hospital stay. Early identification of high-risk patients with preoperative anxiety and postoperative pain will be useful for the implementation of preventive management. METHODS: Patients, who underwent gynecological surgery in our hospital between March 2022 and September 2022, were consecutively enrolled. Perioperative anxiety and pain were evaluated with the Visual Analogue Scale of Anxiety (VAA) and Visual Analogue Scale of Pain (VAS), respectively. Step Akaike Information Criterion analysis was performed to identify risk factors and logistic regression was used to establish nomograms, followed by discrimination, calibration, and clinical utility evaluation. RESULTS: A total of 197 patients were included for analysis, including 116 and 81 patients who were randomized to training and test groups, respectively. The prediction model of preoperative moderate to severe anxiety identified four preoperative relevant factors: age, sleep duration, preoperative pain, and regular exercise before gynecological surgery. The model had an area under the receiver operating characteristics curve of 0.808 (0.729, 0.887) and 0.754 (0.634, 0.875) in the training and test groups, respectively. The prediction model of postoperative moderate to severe pain identified four relevant factors: preoperative pain, surgery type, VAA before anesthesia, and patient-controlled analgesia. The model had an area under the receiver operating characteristics curve of 0.867 (0.798, 0.935) and 0.852 (0.761, 0.943) in the training and test groups, respectively. CONCLUSIONS: The established nomograms accurately identified high-risk patients with preoperative anxiety and postoperative pain before gynecological surgery. Clinical registration at: www.chictr.org.cn (ChiCTR2200057757).

Sub-Anesthesia Dose of S-Ketamine Reduces Postoperative Pain and Anxiety in Patients Receiving Breast and Thyroid Surgery: A Randomized, Controlled Trial.

BACKGROUND: Postoperative pain and anxiety affect patients' recovery and increase the family burden. S-ketamine presents analgesic effects and anti-depressive effects in clinics. The effect of a sub-anesthesia dose of S-ketamine on postoperative pain and anxiety remains to be clarified. OBJECTIVES: This study aimed to evaluate the analgesic and anxiolytic effects of a sub-anesthesia dose of S-ketamine on postoperative pain and anxiety and explored the risk factors for postoperative pain in patients receiving breast or thyroid surgery under general anesthesia. STUDY DESIGN: A randomized, double-blind, controlled trial. SETTING: A university hospital. METHODS: One hundred twenty patients receiving breast or thyroid surgery, stratified by surgery type, were randomized to S-ketamine and control groups in a 1:1 ratio. S-ketamine (0.3 mg/kg) or an equal volume of normal saline was administrated after anesthesia induction. Visual analog scale (VAS) of pain and self-rating anxiety scale (SAS) were tested before surgery and on postoperative day 1, 2, and 3. VAS and SAS score between the 2 groups were compared, and the risk factors for postoperative moderate to severe pain were explored with logistic regression analysis. RESULTS: Intraoperative S-ketamine decreased VAS and SAS scores on postoperative day 1, 2, and 3 (P < 0.05, 2-way ANOVA for repeated measurements followed by Bonferroni post-analysis). Subgroup analysis showed S-ketamine decreased VAS and SAS scores both in breast surgery and thyroid surgery patients on postoperative day 1, 2, and 3. Logistic regression identified S-ketamine and regular exercise are protective factors, and anxiety before surgery is a risk factor for postoperative moderate to severe pain (P < 0.05). LIMITATIONS: The anxiety score in our study is not so high, which may under-evaluate the anxiolytic effect of S-ketamine. However, S-ketamine decreased the SAS scores postoperatively in our study. CONCLUSIONS: Intraoperative sub-anesthesia dose of S-ketamine reduces postoperative pain and anxiety intensity. Anxiety before surgery is a risk factor, and S-ketamine and regular exercise are protective factors for postoperative pain. The study was registered at www.chictr.org.cn with the number: ChiCTR2200060928.

Development and validation of a nomogram for blood transfusion during intracranial aneurysm clamping surgery: a retrospective analysis.

PURPOSE: Intraoperative blood transfusion is associated with adverse events. We aimed to establish a machine learning model to predict the probability of intraoperative blood transfusion during intracranial aneurysm surgery. METHODS: Patients, who underwent intracranial aneurysm surgery in our hospital between January 2019 and December 2021 were enrolled. Four machine learning models were benchmarked and the best learning model was used to establish the nomogram, before conducting a discriminative assessment. RESULTS: A total of 375 patients were included for analysis in this model, among whom 108 received an intraoperative blood transfusion during the intracranial aneurysm surgery. The least absolute shrinkage selection operator identified six preoperative relative factors: hemoglobin, platelet, D-dimer, sex, white blood cell, and aneurysm rupture before surgery. Performance evaluation of the classification error demonstrated the following: K-nearest neighbor, 0.2903; logistic regression, 0.2290; ranger, 0.2518; and extremely gradient boosting model, 0.2632. A nomogram based on a logistic regression algorithm was established using the above six parameters. The AUC values of the nomogram were 0.828 (0.775, 0.881) and 0.796 (0.710, 0.882) in the development and validation groups, respectively. CONCLUSIONS: Machine learning algorithms present a good performance evaluation of intraoperative blood transfusion. The nomogram established using a logistic regression algorithm showed a good discriminative ability to predict intraoperative blood transfusion during aneurysm surgery.

MiR-361-3p alleviates cerebral ischemia-reperfusion injury by targeting NACC1 through the PINK1/Parkin pathway.

Ischemic stroke is a nervous system disease with high rates of disability and mortality. MicroRNAs have been reported to modulate cerebral ischemia. The current study aimed to study the role of miR-361-3p in cerebral ischemia-reperfusion (I/R) injury. Experimental results revealed that miR-361-3p level was downregulated in a middle cerebral artery occlusion-induced ischemic stroke mouse model and in oxygen-glucose deprivation/reoxygenation-stimulated SH-SY5Y cells. After overexpressing miR-361-3p, the percentage of brain infarct volume and neurobehavioral scores in mice were significantly reduced, and the neuronal apoptosis was inhibited. Moreover, miR-361-3p overexpression could limit the production of reactive oxygen species (ROS). Furthermore, we investigated the underlying molecular mechanisms of miR-361-3p and identified that miR-361-3p combined with NACC1 3'UTR to negatively modulate its expression. In addition, NACC1 interacts with the PINK1/Parkin pathway in neurons. NACC1 overexpression could rescue the impacts of miR-361-3p mimics on cell apoptosis, ROS production and the PINK1/Parkin pathway. In conclusion, miR-361-3p could improve ischemia brain injury by targeting NACC1 through the PINK1/Parkin pathway. Therefore, miR-361-3p may serve as a potential therapeutic target for the brain injury after I/R.

Exercise Reduces Morphine-Induced Hyperalgesia and Antinociceptive Tolerance.

Chronic morphine intake for treating various pain is frequently concomitant with morphine-induced hyperalgesia and tolerance. The mechanisms can be explained by the activation of p38-MAPK proteins in microglia in the spinal cord horn. Exercise has been shown to prevent the development of microglia overactivation. Thus, we designed to test whether exercise prevents the morphine-induced hyperalgesia and tolerance as well as suppression of p38 phosphorylation. A p38 inhibitor SB203580, exercise, and exercise preconditioning were used for treating morphine-induced hyperalgesia and tolerance development in the present study. The behavior tests for hyperalgesia and tolerance were performed in male Wistar rats before and after morphine administration. Western blotting and immunostaining for examining phosphorylated-p38 expression were performed after the behavior tests. Our results showed that SB203580 and exercise, but not exercise preconditioning, prevented the occurrence of morphine-induced hyperalgesia and tolerance. Meanwhile, exercise decreased morphine-induced phosphorylated-p38 overexpression. In summary, exercise prevented the development of morphine-induced hyperalgesia and tolerance. The mechanism may be related to inhibition of p38 phosphorylation.

Down-regulation of ASICs current and the calcium transients by disrupting PICK1 protects primary cultured mouse cortical neurons from OGD-Rep insults.

Acid sensing ion channels (ASICs), activated by lowering extracellular pH, play an important role in normal synaptic transmission in brain and in the pathology of brain ischemia. ASICs activation involving in glutamate receptor-independent ischemic brain injury has been generally accepted, and PICK1 is recently shown to be one of partner proteins interacting with ASICs through its PDZ domain. Here we showed that ASICs and PICK1 played key roles in OGD-Rep process. In wild-type cultured cortical neurons, not only the amplitude of ASICs current and the calcium transients induced by acidosis were both increased after OGD-Rep, but also the total protein levels of ASIC1 and ASIC2a were up-regulated progressively after ischemia insults, indicating that ASICs play a vital role in neuronal ischemia. However, these activities were reversed with PICK1-knockout after OGD-Rep, accompanied with the dramatically down-regulating the protein abundances of ASIC1 and ASIC2a, which suggested the neuroprotection activity in brain ischemia by PICK1-knockout. These results indicate that knocking-out PICK1 gene casts the neuroprotection effect by reducing ASICs current and the calcium transients in OGD-Rep neuronal cells, which will offer a promising strategy in the therapy of brain ischemia.

Application of controlled hypotension combined with autotransfusion in spinal orthomorphia.

BACKGROUND: Idiopathic scoliosis is a common spinal deformity in teenagers, which is managed mainly by orthomorphia. However, due to great trauma, long operative duration and large blood loss, a great amount of blood transfusion is needed during the surgery. Allogeneic blood transfusion should be reduced in order to release blood insufficient, decline blood transfusion expense, as well as avoid transfusion diseases. OBJECTIVE: The objective of the following study is to investigate the value of controlled hypotension combined with autotransfusion in idiopathic scoliosis orthomorphia and in order to reduce surgical bleeding and reduction in blood transfusion. SUBJECTS AND METHODS: Intra-operative controlled hypotension was performed during posterior orthomorphia surgery on all the 46 cases of idiopathic scoliosis, 17 cases in which were served as the control group, who underwent allogeneic blood transfusion without autotransfusion, whereas the other 29 cases were served as the experimental group, who underwent autotransfusion that including reinfusion of pre-operative deposited autologous blood and intra-operative salvaged autologous blood. The blood loss volume and transfusion status in two groups were observed. RESULTS AND CONCLUSION: Blood loss volume in the control group was 400-1000 (835.3 ± 167.5) mL and that in the experimental group was 350-1400 (812.1 ± 152.7) mL, there was no marked difference between the two groups (P > 0.05). The volume of allogeneic blood transfusion in the control group was 500-1800 (855.9 ± 321.1) mL, which was greater than that in the experimental group ((0-1300 (337.9 ± 258.3) mL) (P < 0.01). The results suggested that controlled hypotension reduces intraoperative bleeding and post-operative autotransfusion minimizes the need of allogeneic blood transfusion.

A lipoxin A4 analog ameliorates blood-brain barrier dysfunction and reduces MMP-9 expression in a rat model of focal cerebral ischemia-reperfusion injury.

LXA(4) methyl ester (LXA(4)ME), a lipoxin A(4) analog, reduces ischemic insult in the rat models of transient or permanent cerebral ischemic injury. We investigated whether LXA(4)ME could ameliorate blood-brain barrier (BBB) dysfunction after stroke by reducing matrix metalloproteinase (MMP)-9 expression. Adult male rats were subjected to 2-h middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion. Brain infarctions were detected by triphenyltetrazolium chloride (TTC) staining. BBB dysfunction was determined by examining brain edema and Evans Blue extravasation. Temporal expression of MMP-9 was determined by zymography and Western blot. The presence of tissue inhibitors of metalloproteinase-1 (TIMP-1) was also determined by Western blot in tissue protein sample. Brain edema and Evans Blue leakage were significantly reduced after stroke in the LXA(4)ME group and were associated with reduced brain infarct volumes. MMP-9 activity and expression were inhibited by LXA(4)ME after stroke. In addition, LXA(4)ME significantly increased TIMP-1 protein levels. Our results indicate that LXA(4)ME reduces brain injury by improving BBB function in a rat model of MCAO, and that a relationship exists between BBB permeability and MMP-9 expression following ischemic insult. Furthermore, these results suggest that LXA(4)ME-mediated reduction of MMP-9 following stroke are attributed to increased TIMP-1 expression.

Neuroprotective effect of lipoxin A4 methyl ester in a rat model of permanent focal cerebral ischemia.

Neuroprotective effect of lipoxin A(4) methyl ester (LXA(4) ME) was tested in a rat model of permanent middle cerebral artery occlusion. LXA(4) ME was administrated through intracerebroventricular injection immediately after middle cerebral artery was occluded. Administration of LXA(4) ME ameliorated neurological deficit, reduced infarct volume, attenuated histological damage, and decreased number of apoptotic neuron induced by ischemic insult. These neuroprotective effects of LXA(4) ME were associated with inhibition of neutrophil infiltration, lipid peroxidation, and astrocyte activation. In addition, LXA(4) ME also attenuated proinflammatory cytokines (TNF-alpha and IL-1beta) production. These data suggest that LXA(4) ME protects neuron against permanent cerebral ischemia by inhibiting inflammatory responses.

Lipoxin A4 analogue protects brain and reduces inflammation in a rat model of focal cerebral ischemia reperfusion.

Inflammation, which is known to be detrimental to the neurological outcome during the acute phase after ischemia, provides a potential preventative or therapeutic approach for acute stroke. Lipoxins are endogenous lipoxygenase derived eicosanoids and evokes protective actions in a range of pathophysiologic processes. Here, we evaluated the efficacy of 5 (S), 6 (R)-lipoxin A(4) methyl ester (LXA(4) ME), a stable synthetic analogue of lipoxin A(4) in cerebral ischemia reperfusion injury in rats. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 2h. Intracerebroventricular administration of LXA(4) ME immediately after onset of ischemia ameliorated neurological dysfunctions, reduced infarction volume and attenuated neuronal apoptosis. Moreover, Treatment with LXA(4) ME suppressed neutrophils infiltration and lipid peroxidation levels; inhibited the activation of microglia and astrocytes; reduced the expression of pro-inflammatory cytokines TNF-alpha and IL-1beta; and up-regulated the expression of anti-inflammatory cytokines IL-10 and TGF-beta1 in the ischemic brain. In addition, activation of NF-kappaBeta was inhibited by LXA(4) ME treatment. These results demonstrate that treatment of LXA(4) ME affords strong neuroprotective effect against cerebral ischemia reperfusion injury, and that these effects might be associated with its anti-inflammatory property.