Development of interpretable machine learning models for prediction of acute kidney injury after noncardiac surgery: a retrospective cohort study.

BACKGROUND: Early identification of patients at high-risk of postoperative acute kidney injury (AKI) can facilitate the development of preventive approaches. This study aimed to develop prediction models for postoperative AKI in noncardiac surgery using machine learning algorithms. The authors also evaluated the predictive performance of models that included only preoperative variables or only important predictors. MATERIALS AND METHODS: Adult patients undergoing noncardiac surgery were retrospectively included in the study (76 457 patients in the discovery cohort and 11 910 patients in the validation cohort). AKI was determined using the KDIGO criteria. The prediction model was developed using 87 variables (56 preoperative variables and 31 intraoperative variables). A variety of machine learning algorithms were employed to develop the model, including logistic regression, random forest, extreme gradient boosting, and gradient boosting decision trees. The performance of different models was compared using the area under the receiver operating characteristic curve (AUROC). Shapley Additive Explanations (SHAP) analysis was employed for model interpretation. RESULTS: The patients in the discovery cohort had a median age of 52 years (IQR: 42-61 years), and 1179 patients (1.5%) developed AKI after surgery. The gradient boosting decision trees algorithm showed the best predictive performance using all available variables, or only preoperative variables. The AUROCs were 0.849 (95% CI: 0.835-0.863) and 0.828 (95% CI: 0.813-0.843), respectively. The SHAP analysis showed that age, surgical duration, preoperative serum creatinine, and gamma-glutamyltransferase, as well as American Society of Anesthesiologists physical status III were the most important five features. When gradually reducing the features, the AUROCs decreased from 0.852 (including the top 40 features) to 0.839 (including the top 10 features). In the validation cohort, the authors observed a similar pattern regarding the models' predictive performance. CONCLUSIONS: The machine learning models the authors developed had satisfactory predictive performance for identifying high-risk postoperative AKI patients. Furthermore, the authors found that model performance was only slightly affected when only preoperative variables or only the most important predictive features were included.

Activation of mitochondrial DNA-mediated cGAS-STING pathway contributes to chronic postsurgical pain by inducing type I interferons and A1 reactive astrocytes in the spinal cord.

Chronic postsurgical pain (CPSP) is increasingly recognized as a public health issue. Recent studies indicated the innate immune pathway of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) was involved in pain regulation. However, the detailed mechanisms remain unclear. Previous studies found A1 reactive astrocytes in the spinal cord contributed to CPSP. This study aimed to investigate the roles and mechanisms of the cGAS-STING pathway in regulating the generation of A1 reactive astrocytes during CPSP. First, CPSP model was established using skin/muscle incision and retraction (SMIR) in rats. We found that cGAS-STING pathway was activated accompanied with an increase in mitochondrial DNA in the cytosol in the spinal cord following SMIR. Second, a STING inhibitor C-176 was intrathecally administrated. We found that C-176 decreased the expression of type I interferons and A1 reactive astrocytes in the spinal cord, and alleviated mechanical allodynia in SMIR rats. Third, cyclosporin A as a mitochondrial permeability transition pore blocker was intrathecally administrated. We found that cyclosporin A decreased the leakage of mitochondrial DNA and inhibited the activation of cGAS-STING pathway. Compared with C-176, cyclosporin A exhibits similar analgesic effects. The expression of type I interferons and A1 reactive astrocytes in the spinal cord were also down-regulated after intervention with cyclosporin A. Moreover, simultaneous administration of cyclosporin A and C-176 did not show synergistic effects in SMIR rats. Therefore, our study demonstrated that the cGAS-STING pathway activated by the leakage of mitochondrial DNA contributed to chronic postsurgical pain by inducing type I interferons and A1 reactive astrocytes in the spinal cord.

Predictive value of the geriatric nutrition risk index for postoperative delirium in elderly patients undergoing cardiac surgery.

AIMS: The aims of the study were to determine the relationship between preoperative geriatric nutritional risk index (GNRI) and the occurrence of postoperative delirium (POD) in elderly patients after cardiac surgery and to evaluate the additive value of GNRI for predicting POD. METHODS: The data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC-IV) database. Patients who underwent cardiac surgery and were aged 65 or older were included. The relationship between preoperative GNRI and POD was investigated using logistic regression. We determined the added predictive value of preoperative GNRI for POD by measuring the changes in the area under the receiver operating characteristic curve (AUC) and calculating the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: A total of 4286 patients were included in the study, and 659 (16.1%) developed POD. Patients with POD had significantly lower GNRI scores than patients without POD (median 111.1 vs. 113.4, p < 0.001). Malnourished patients (GNRI ≤ 98) had a significantly higher risk of POD (odds ratio, 1.83, 90% CI, 1.42-2.34, p < 0.001) than those without malnutrition (GNRI > 98). This correlation remains after adjusting for confounding variables. The addition of GNRI to the multivariable models slightly but not significantly increases the AUCs (all p > 0.05). Incorporating GNRI increases NRIs in some models and IDIs in all models (all p < 0.05). CONCLUSIONS: Our results showed a negative association between preoperative GNRI and POD in elderly patients undergoing cardiac surgery. The addition of GNRI to POD prediction models may improve their predictive accuracy. However, these findings were based on a single-center cohort and will need to be validated in future studies involving multiple centers.

Prognostic significance of preoperative nutritional status for postoperative acute kidney injury in older patients undergoing major abdominal surgery: a retrospective cohort study.

BACKGROUND: The association between malnutrition and postoperative acute kidney injury (AKI) has not been well studied. In this study, the authors examined the association between preoperative nutritional status and postoperative AKI in older patients who underwent major abdominal surgery, as well as the predictive value of malnutrition for AKI. MATERIALS AND METHODS: The authors retrospectively included patients aged 65 or older who underwent major elective abdominal surgery. The nutritional status of the patient was evaluated using three objective nutritional indices, such as the geriatric nutritional risk index (GNRI), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT). AKI was determined using the KDIGO criteria. The authors performed logistic regression analysis to investigate the association between preoperative nutritional status and postoperative AKI, as well as the predictive value of nutritional scores for postoperative AKI. RESULTS: A total of 2775 patients were included in the study, of which 707 (25.5%), 291 (10.5%), and 517 (18.6%) had moderate to severe malnutrition according to GNRI, PNI, and CONUT calculations. After surgery, 144 (5.2%) patients developed AKI, 86.1% at stage 1, 11.1% at stage 2, and 2.8% at stage 3 as determined by KDIGO criteria. After adjustment for traditional risk factors, worse nutritional scores were associated with a higher AKI risk. In addition to traditional risk factors, these nutritional indices improved the predictive ability of AKI prediction models, as demonstrated by significant improvements in integrated discrimination and net reclassification. CONCLUSIONS: Poor preoperative nutritional status, as assessed by GNRI, PNI, and CONUT scores, was associated with an increased risk of postoperative AKI. Incorporating these scores into AKI prediction models improved their performance. These findings emphasize the need for screening surgical patients for malnutrition risk. Further research is needed to determine whether preoperative malnutrition assessment and intervention can reduce postoperative AKI incidence.

Postoperative short-term mortality between insulin-treated and non-insulin-treated patients with diabetes after non-cardiac surgery: a systematic review and meta-analysis.

Background: Diabetes mellitus is an independent risk factor for postoperative complications. It has been reported that insulin-treated diabetes is associated with increased postoperative mortality compared to non-insulin-treated diabetes after cardiac surgery; however, it is unclear whether this finding is applicable to non-cardiac surgery. Objective: We aimed to assess the effects of insulin-treated and non-insulin-treated diabetes on short-term mortality after non-cardiac surgery. Methods: Our study was a systematic review and meta-analysis of observational studies. PubMed, CENTRAL, EMBASE, and ISI Web of Science databases were searched from inception to February 22, 2021. Cohort or case-control studies that provided information on postoperative short-term mortality in insulin-treated diabetic and non-insulin-treated diabetic patients were included. We pooled the data with a random-effects model. The Grading of Recommendations, Assessment, Development, and Evaluation system was used to rate the quality of evidence. Results: Twenty-two cohort studies involving 208,214 participants were included. Our study suggested that insulin-treated diabetic patients was associated with a higher risk of 30-day mortality than non-insulin-treated diabetic patients [19 studies with 197,704 patients, risk ratio (RR) 1.305; 95% confidence interval (CI), 1.127 to 1.511; p < 0.001]. The studies were rated as very low quality. The new pooled result only slightly changed after seven simulated missing studies were added using the trim-and-fill method (RR, 1.260; 95% CI, 1.076-1.476; p = 0.004). Our results also showed no significant difference between insulin-treated diabetes and non-insulin-treated diabetes regarding in-hospital mortality (two studies with 9,032 patients, RR, 0.970; 95% CI, 0.584-1.611; p = 0.905). Conclusion: Very-low-quality evidence suggests that insulin-treated diabetes was associated with increased 30-day mortality after non-cardiac surgery. However, this finding is non-definitive because of the influence of confounding factors. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246752, identifier: CRD42021246752.

Pharmacological inhibition of the cGAS-STING signaling pathway suppresses microglial M1-polarization in the spinal cord and attenuates neuropathic pain.

Neuroinflammation plays a vital role in the development of neuropathic pain and is mediated mainly by microglia. Suppressing microglial M1-polarization attenuates neuropathic pain. Recently, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has emerged as a key mediator of inflammation and shows potential in modulating microglial polarization. In this study, we evaluated whether cGAS-STING is a potential therapeutic target. Spared nerve injury (SNI) surgery was conducted in adult male rats to establish a neuropathic pain model. We showed that SNI promoted microglial M1-polarization and induced cGAS-STING pathway activation in the spinal cord. Double-label immunofluorescence assays showed that cGAS-STING activation mainly occurred in neurons and microglia but not astrocytes. We further conducted in vitro experiments using BV-2 microglial cells. The results showed that LPS-induced microglial M1-polarization was accompanied by cGAS-STING pathway activation, but cGAS-STING inhibition by antagonists suppressed LPS-induced microglial M1-polarization. In vivo, we also showed that a cGAS antagonist and a STING antagonist suppressed the microglial M1-polarization and ameliorated the mechanical allodynia induced by SNI. These findings suggested that the cGAS-STING pathway might be a potential therapeutic target for treating neuropathic pain. However, further research is warranted to verify our findings in female rodents.

Preoperative screening of patients at high risk of obstructive sleep apnea and postoperative complications: A systematic review and meta-analysis.

STUDY OBJECTIVE: To determine the association between postoperative complications and a high versus low risk of obstructive sleep apnea (OSA) as determined via screening tools. DESIGN: Systematic review and meta-analysis of cohort studies. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched from their inception to January 5, 2021. SETTING: Operating room, postoperative recovery area, and ward. PATIENTS: Adult patients scheduled for surgery. INTERVENTIONS: We used Review Manager 5.4 to pool the data. The quality of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation system. MEASUREMENTS: The primary outcome was the composite endpoint of postoperative respiratory complications. The secondary outcomes were postoperative cardiac and neurological complications, intensive care unit (ICU) admission, and mortality. MAIN RESULTS: Twenty-six studies with 50,592 patients were included. A STOP-Bang score ≥ 3 (versus <3) was associated with higher incidences of postoperative respiratory (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.66-2.68) and neurological complications (OR, 3.60; 95% CI, 1.56-8.31). A STOP-Bang score ≥ 5 (versus <5) was associated with higher incidences of postoperative respiratory (OR, 2.37; 95% CI, 1.11-5.04) and cardiac complications (OR, 4.95; 95% CI, 1.22-20.00) and higher in-hospital mortality (OR, 26.39; 95% CI, 2.89-241.30). A Berlin score ≥ 2 (versus <2) was not associated with the incidence of postoperative complications, ICU admission, or mortality. The quality of evidence for all outcomes was very low. CONCLUSIONS: Very low-quality evidence suggested that a high risk of OSA, as assessed using the STOP-Bang questionnaire, was associated with a higher incidence of postoperative respiratory complications, and may also be associated with higher incidences of postoperative cardiac and neurological complications than a low risk of OSA. Since most of the included studies did not adjust for confounding factors, our findings need to be interpreted with caution. PROSPERO registration number: CRD42021220236.

Intensive glucose control during the perioperative period for diabetic patients undergoing surgery: An updated systematic review and meta-analysis.

STUDY OBJECTIVE: To evaluate the impact of intensive glucose control on diabetic patients undergoing surgery. DESIGN: A systematic review and meta-analysis of randomized controlled trials. PubMed, CENTRAL, EMBASE, ISI Web of Science, and CINAHL databases were searched from inception to 13 December 2020. SETTING: Operating room, postoperative recovery area and ward, up to 30 days after surgery. PATIENTS: Diabetic patients undergoing surgery. INTERVENTIONS: We used Review Manager 5.4 to pool the data with a random-effects model. The quality of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation system. MEASUREMENTS: The primary outcomes were infectious complications, postoperative mortality, and hypoglycaemia. The secondary outcomes included atrial fibrillation, myocardial infarction, stroke, delirium, renal failure, postoperative mechanical ventilation time, length of intensive care unit (ICU) stay, and hospital stay. MAIN RESULTS: Thirteen studies involving 1582 participants were included. Compared with conventional glucose control, intensive glucose control was associated with a lower risk of infectious complications (risk ratio [RR], 0.35; 95% confidence interval [CI], 0.19-0.63; low-quality evidence), atrial fibrillation (RR, 0.55; 95% CI, 0.42-0.71; high-quality evidence), and renal failure (RR, 0.38; 95% CI, 0.15-0.95; moderate-quality evidence), as well as a shorter length of stay in the ICU (mean difference (MD), -0.55 day; 95% CI, -1.05 to -0.05 days; very-low-quality evidence) and hospital (MD, -1.61 days; 95% CI, -2.78 to -0.44 days; very-low-quality evidence). However, intensive glucose control was associated with a higher risk of hypoglycaemia (RR, 3.00; 95% CI, 1.97-4.55; high-quality evidence). There were no significant differences in postoperative mortality, myocardial infarction, stroke, delirium, or postoperative mechanical ventilation time. CONCLUSIONS: Intensive glucose control in diabetic patients is associated with a reduction in some adverse postoperative outcomes including infectious complications, but also appears to increase the risk of hypoglycaemia. Further well-designed studies may be needed to determine appropriate regimens to reduce hypoglycaemia incidence. PROSPERO REGISTRATION NUMBER: CRD42021226138.

Resveratrol ameliorates sevoflurane-induced cognitive impairment by activating the SIRT1/NF-κB pathway in neonatal mice.

Sevoflurane, the most commonly used inhaled anesthetic in pediatric anesthesia, has been reported to induce cognitive impairment in developing brain in preclinical and clinical settings. However, the mechanism and therapeutic measures of this developmental neurotoxicity need to be further investigated. Resveratrol, a natural polyphenolic agent, has been reported to improve cognitive function in neurological disorders and aging models through anti-inflammatory activity. However, its effect on sevoflurane-induced cognitive impairment in developing mice remains unknown. The present study was designed to investigate the therapeutic potential of resveratrol on sevoflurane-induced cognitive impairment. Six-day-old mice received anesthesia with 3% sevoflurane 2 h daily on postnatal days (P) 6, P7 and P8. About 100 mg/kg resveratrol were intraperitoneally administered for 6 consecutive days to neonatal mice before anesthesia. Sevoflurane exposure significantly suppressed the expression of Sirtuin 1 (SIRT1) and activated microglia in hippocampi. Furthermore, the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were markedly increased after sevoflurane exposure. Strikingly, resveratrol pretreatment ameliorated sevoflurane-induced SIRT1 inhibition and microglial activation. Of note, resveratrol reversed sevoflurane-induced imbalance of M1/M2 microglia ratio revealed by increasing mRNA level of clusters of differentiation 206 (CD206) and decreasing mRNA levels of clusters of differentiation 86 (CD86) and suppressor of cytokine signaling 3 (SOCS3). Consequently, sevoflurane-induced cognitive impairment in developing mice was ameliorated by resveratrol pretreatment. Taken together, repeated sevoflurane exposure to the developing brain resulted in SIRT1 inhibition, NF-κB acetylation, and microglial activation. Resveratrol pretreatment ameliorated cognitive impairment in developing mice received sevoflurane exposure by modulating SIRT1-NF-κB pathway in microglia. In this regard, our findings open novel directions to explore promising therapeutic targets for preventing the developmental neurotoxicity of sevoflurane.

Resveratrol Mitigates Hippocampal Tau Acetylation and Cognitive Deficit by Activation SIRT1 in Aged Rats following Anesthesia and Surgery.

Postoperative cognitive dysfunction (POCD) is a sever postsurgical neurological complication in the elderly population. As the global acceleration of population ageing, POCD is proved to be a great challenge to the present labor market and healthcare system. In the present study, our findings showed that tau acetylation mediated by SIRT1 deficiency resulted in tau hyperphosphorylation in the hippocampus of the aged POCD model and consequently contributed to cognitive impairment. Interestingly, pretreatment with resveratrol almost restored the expression of SIRT1, reduced the levels of acetylated tau and hyperphosphorylated tau in the hippocampus, and improved the cognitive performance in the behavioral tests. What is more, we observed that microglia-derived neuroinflammation resulting from SIRT1 inhibition in microglia probably aggravated the tau acetylation in cultured neurons in vitro. Our findings supported the notion that activation SIRT1 provided dually beneficial effect in the aged POCD model. Taken together, our findings provided the initial evidence that tau acetylation was associated with cognitive impairment in the aged POCD model and paved a promising avenue to prevent POCD by inhibiting tau acetylation in a SIRT1-dependent manner.

Topical application of magnesium to prevent intubation-related sore throat in adult surgical patients: a systematic review and meta-analysis.

BACKGROUND: Postoperative sore throat negatively affects patient satisfaction and recovery. We conducted a systematic review and meta-analysis to examine the efficacy of preoperative topical administration of magnesium sulfate in preventing postoperative sore throat in adult patients. METHODS: We searched Medline, EMBASE, China National Knowledge Infrastructure, and the Cochrane Central Register of Controlled Trials from inception to 6 October, 2018. We included randomized-controlled trials that assessed the efficacy and safety of topical application of magnesium preoperatively in adult patients who underwent endotracheal intubation for general anesthesia. We then pooled the data using a random-effects model and conducted a trial sequential analysis on the incidence of sore throat. Our primary outcome was the incidence of sore throat at 24 hr after surgery/extubation. Our secondary outcomes included the severity of sore throat at 24 hr after surgery/extubation and adverse events. RESULTS: Eleven randomized-controlled trials involving 1,096 patients were included in this study. Topical application of magnesium was associated with reduced incidence of postoperative sore throat (risk ratio, 0.31; 95% confidence interval [CI], 0.21 to 0.45) as well as reduced severity of postoperative sore throat (standardized mean difference, - 2.66; 95% CI, - 3.89 to - 1.43). Three studies reported that significant adverse events were not associated with topical magnesium. The trial sequential analysis suggested that there is adequate evidence supporting the efficacy of topical magnesium in preventing postoperative sore throat. CONCLUSION: Our study suggests that preoperative topical magnesium can effectively prevent postoperative sore throat. TRIAL REGISTRATION: PROSPERO (CRD42018110019); registered 26 September, 2018.

Perioperative activation of spinal α7 nAChR promotes recovery from preoperative stress-induced prolongation of postsurgical pain.

Preoperative stress could delay the recovery of postoperative pain and has been reported to be a risk factor for chronic postsurgical pain. As stress could facilitate the proinflammatory activation of microglia, we hypothesized that these cells may play a vital role in the development of preoperative stress-induced pain chronification after surgery. Our experiments were conducted in a rat model that consists of a single prolonged stress (SPS) procedure and plantar incision. A previous SPS exposure induced anxiety-like behaviors, prolonged incision-induced mechanical allodynia, and potentiated the activation of spinal microglia. Based on the results from ex vivo experiments, spinal microglia isolated from SPS-exposed rats secreted more proinflammatory cytokines upon challenge with LPS. Our results also demonstrated that microglia played a more important role than astrocytes in the initiation of SPS-induced prolongation of postsurgical pain. We further explored the therapeutic potential of agonism of α7 nAChR, an emerging anti-inflammatory target, for SPS-induced prolongation of postsurgical pain. Multiple intrathecal (i.t.) injections of PHA-543613 (an α7 nAChR agonist) or PNU-120596 (a type II positive allosteric modulator) during the perioperative period shortened the duration of postsurgical pain after SPS and suppressed SPS-potentiated microglia activation, but their effects were abolished by pretreatment with methyllycaconitine (an α7 nAChR antagonist; i.t.). Based on the results from ex vivo experiments, the anti-inflammatory effects of PHA-543613 and PNU-120596 may have been achieved by the direct modulation of microglia. In conclusion, stress-induced priming of spinal microglia played a key role in the initiation of preoperative stress-induced prolongation of postsurgical pain, and PHA-543613 and PNU-120596 may be potential candidates for preventing pain chronification after surgery.

Aerosolized corticosteroids to prevent postoperative sore throat in adults: A systematic review and meta-analysis.

BACKGROUND: Postoperative sore throat negatively affects patient recovery and satisfaction levels. We conducted a systematic review and meta-analysis to assess the efficacy and safety of aerosolized corticosteroids in the prevention of postoperative sore throat in adults undergoing tracheal intubation for surgery. METHODS: We searched Medline, EMBASE, China National Knowledge Infrastructure, and the Cochrane Central Register of Controlled Trials for eligible studies from inception to 13 May 2018. We included randomized controlled trials that assessed the efficacy and safety of aerosolized corticosteroids, compared either with non-analgesic or analgesic controls, in adults undergoing tracheal intubation for surgery. Incidence and severity of sore throat 24 hours postoperatively and adverse events were the primary outcomes. RESULTS: Nine randomized controlled trials involving 984 patients were included. Compared with non-analgesic control, aerosolized corticosteroids were associated with a reduced incidence (risk ratio [RR], 0.39; 95% confidence interval [CI], 0.26-0.58) and were likely associated with decreased severity (standardized mean difference [SMD], -0.96; 95% CI, -2.52, 0.59) of postoperative sore throat. Among these, four trials reported that there were no adverse events. Trial sequential analysis (TSA) suggested that the evidence on the incidence of postoperative sore throat, in comparison with the non-analgesic control, was not definitive (TSA-adjusted CI, 0.07-1.98). The GRADE quality of evidence on each outcome was very low. CONCLUSIONS: Aerosolized corticosteroids may be superior to non-analgesic methods in preventing postoperative sore throat, but the evidence for efficacy and safety is still limited and not definitive.

Dehydrocorydaline attenuates bone cancer pain by shifting microglial M1/M2 polarization toward the M2 phenotype.

Bone cancer pain remains a major challenge in patients with primary or metastatic bone cancer due to a lack of understanding the mechanisms. Previous studies have revealed the two distinct functional polarization states of microglia (classically activated M1 and alternatively activated M2) in the spinal cord in nerve injury-induced neuropathic pain. However, whether microglia in the spinal cord polarize to M1 and M2 phenotypes and contribute to the development of bone cancer pain remains unclear. In this study, we used a mouse model with bone cancer to characterize the M1/M2 polarization of microglia in the spinal cord during the development of bone cancer pain, and investigated the antinociceptive effects of dehydrocorydaline, an alkaloidal component isolated from Rhizoma corydalis on bone cancer pain. Our results show that microglia in the spinal cord presented increased M1 polarization and decreased M2 polarization, while overproduction of IL-1ß and inhibited expression of IL-10 was detected during bone cancer pain development. Intraperitoneal administration of dehydrocorydaline (10 mg/kg) had significant antinociceptive effects on day 14 after osteosarcoma cell implantation, accompanied by suppressed M1 phenotype and upregulated M2 phenotype of microglia in the spinal cord, while alleviated inflammatory response was observed then. These results suggest that the imbalanced polarization of microglia toward the M1 phenotype in the spinal cord may contribute to the development of bone cancer pain, while dehydrocorydaline helps to attenuate bone cancer pain, with microglial polarization shifting toward the M2 phenotype in the spinal cord.

Intraoperative electroacupuncture relieves remifentanil-induced postoperative hyperalgesia via inhibiting spinal glial activation in rats.

Background Accumulating studies have suggested that remifentanil, the widely-used opioid analgesic in clinical anesthesia, can activate the pronociceptive systems and enhance postoperative pain. Glial cells are thought to be implicated in remifentanil-induced hyperalgesia. Electroacupuncture is a complementary therapy to relieve various pain conditions with few side effects, and glial cells may be involved in its antinociceptive effect. In this study, we investigated whether intraoperative electroacupuncture could relieve remifentanil-induced postoperative hyperalgesia by inhibiting the activation of spinal glial cells, the production of spinal proinflammatory cytokines, and the activation of spinal mitogen-activated protein kinases. Methods A rat model of remifentanil-induced postoperative hyperalgesia was used in this study. Electroacupuncture during surgery was conducted at bilateral Zusanli (ST36) acupoints. Behavior tests, including mechanical allodynia and thermal hyperalgesia, were performed at different time points. Astrocytic marker glial fibrillary acidic protein, microglial marker Iba1, proinflammatory cytokines, and phosphorylated mitogen-activated protein kinases in the spinal cord were detected by Western blot and/or immunofluorescence. Results Mechanical allodynia and thermal hyperalgesia were induced by both surgical incision and remifentanil infusion, and remifentanil infusion significantly exaggerated and prolonged incision-induced pronociceptive effects. Glial fibrillary acidic protein, Iba1, proinflammatory cytokines (interleukin-1ß and tumor necrosis factor-α), and phosphorylated mitogen-activated protein kinases (p-p38, p-JNK, and p-ERK1/2) were upregulated after surgical incision, remifentanil infusion, and especially after their combination. Intraoperative electroacupuncture significantly attenuated incision- and/or remifentanil-induced pronociceptive effects, spinal glial activation, proinflammatory cytokine upregulation, and phosphorylated mitogen-activated protein kinase upregulation. Conclusions Our study suggests that remifentanil-induced postoperative hyperalgesia can be relieved by intraoperative electroacupuncture via inhibiting the activation of spinal glial cells, the upregulation of spinal proinflammatory cytokines, and the activation of spinal mitogen-activated protein kinases.

Prophylactic Corticosteroids for Prevention of Postextubation Stridor and Reintubation in Adults: A Systematic Review and Meta-analysis.

BACKGROUND: Corticosteroid administration before elective extubation has been used to prevent postextubation stridor and reintubation. We updated a systematic review to identify which patients would benefit from prophylactic corticosteroid administration before elective extubation. METHODS: We searched PubMed, EMBASE, the Wanfang Database, the China Academic Journal Network Publishing Database, and the Cochrane Central Register of Controlled Trials for eligible trials from inception through February 29, 2016. All randomized controlled trials were eligible if they examined the efficacy and safety of systemic corticosteroids given prior to elective extubation in mechanically ventilated adults. We pooled data using the DerSimonian and Laird random-effects model. RESULTS: We identified 11 trials involving 2,472 participants for analysis. Use of prophylactic corticosteroids was associated with a reduced incidence of postextubation airway events (risk ratio [RR], 0.43; 95% CI, 0.29-0.66) and reintubation (RR, 0.42; 95% CI, 0.25-0.71) compared with placebo or no treatment. This association was prominent in participants at high risk for the development of postextubation airway complications, defined using the cuff-leak test, with a reduced incidence of postextubation airway events (RR, 0.34; 95% CI, 0.24-0.48) and reintubation (RR, 0.35; 95% CI, 0.20-0.64). This association was not found in trials with unselected participants. Adverse events were rare. CONCLUSIONS: Administration of prophylactic corticosteroids before elective extubation was associated with significant reductions in the incidence of postextubation airway events and reintubation, with few adverse events. It is reasonable to select patients at high risk for airway obstruction who may benefit from prophylactic corticosteroids.

Glucocorticoid-Potentiated Spinal Microglia Activation Contributes to Preoperative Anxiety-Induced Postoperative Hyperalgesia.

Clinically, preoperative anxiety adversely affected postoperative hyperalgesia. As stress-induced glucocorticoids (GCs) were reported to sensitize the activation of microglia, the present study investigated whether and how GCs and microglia played in the process of preoperative anxiety-induced postoperative hyperalgesia. The study used an animal model that exposed rats to single prolonged stress (SPS) procedure to induce preoperative anxiety-like behaviors 24 h before the plantar incisional surgery. Behavioral testing revealed that preoperative SPS enhanced the mechanical allodynia induced by plantar incision. SPS was also found to induce elevated circulating corticosterone levels, potentiate the activation of spinal microglia, and increase the expression of spinal proinflammatory cytokines. Inhibition of microglia by pretreatment with minocycline attenuated the SPS-enhanced mechanical allodynia, and this was accompanied by decreased activation of spinal microglia and expression of proinflammatory cytokines. Another experiment was conducted by administering RU486, the GC receptor (GR) antagonist, to rats. The results showed that RU486 suppressed SPS-induced and SPS-potentiated proinflammatory activation of spinal microglia and revealed analgesic effects. Together, these data indicated that inhibition of stress-induced GR activation attenuated the preoperative anxiety-induced exacerbation of postoperative pain, and the suppression of spinal microglia activation may underlie this anti-hyperalgesia effect. Pending further studies, these findings suggested that GR and spinal microglia may play important roles in the development of preoperative anxiety-induced postoperative hyperalgesia and may serve as novel targets to prevent this phenomenon.

Nitrous oxide-based techniques versus nitrous oxide-free techniques for general anaesthesia.

BACKGROUND: Nitrous oxide has been used for over 160 years for the induction and maintenance of general anaesthesia. It has been used as a sole agent but is most often employed as part of a technique using other anaesthetic gases, intravenous agents, or both. Its low tissue solubility (and therefore rapid kinetics), low cost, and low rate of cardiorespiratory complications have made nitrous oxide by far the most commonly used general anaesthetic. The accumulating evidence regarding adverse effects of nitrous oxide administration has led many anaesthetists to question its continued routine use in a variety of operating room settings. Adverse events may result from both the biological actions of nitrous oxide and the fact that to deliver an effective dose, nitrous oxide, which is a relatively weak anaesthetic agent, needs to be given in high concentrations that restrict oxygen delivery (for example, a common mixture is 30% oxygen with 70% nitrous oxide). As well as the risk of low blood oxygen levels, concerns have also been raised regarding the risk of compromising the immune system, impaired cognition, postoperative cardiovascular complications, bowel obstruction from distention, and possible respiratory compromise. OBJECTIVES: To determine if nitrous oxide-based anaesthesia results in similar outcomes to nitrous oxide-free anaesthesia in adults undergoing surgery. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014 Issue 10); MEDLINE (1966 to 17 October 2014); EMBASE (1974 to 17 October 2014); and ISI Web of Science (1974 to 17 October 2014). We also searched the reference lists of relevant articles, conference proceedings, and ongoing trials up to 17 October 2014 on specific websites (http://clinicaltrials.gov/, http://controlled-trials.com/, and http://www.centerwatch.com). SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing general anaesthesia where nitrous oxide was part of the anaesthetic technique used for the induction or maintenance of general anaesthesia (or both) with any general anaesthesia using a volatile anaesthetic or propofol-based maintenance of anaesthesia but no nitrous oxide for adults undergoing surgery. Our primary outcome was inhospital case fatality rate. Secondary outcomes were complications and length of stay. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted the outcome data. We used meta-analysis for data synthesis. Heterogeneity was examined with the Chi² test and by calculating the I² statistic. We used a fixed-effect model if the measure of inconsistency was low for all comparisons (I² statistic < 50%); otherwise we used a random-effects model for measures with high inconsistency. We undertook subgroup analyses to explore inconsistency and sensitivity analyses to evaluate whether the results were robust. We assessed the quality of evidence of the main outcomes using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. MAIN RESULTS: We included 35 trials (13,872 adult participants). Seven included studies were at low risk of bias. We identified eight studies as awaiting classification since we could not obtain the full texts, and had insufficient information to include or exclude them. We included data from 24 trials for quantitative synthesis. The results of meta-analyses showed that nitrous oxide-based techniques increased the incidence of pulmonary atelectasis (odds ratio (OR) 1.57, 95% confidence interval (CI) 1.18 to 2.10, P = 0.002), but had no effects on the inhospital case fatality rate, the incidence of pneumonia, myocardial infarction, stroke, severe nausea and vomiting, venous thromboembolism, wound infection, or the length of hospital stay. The sensitivity analyses suggested that the results of the meta-analyses were all robust except for the outcomes of pneumonia, and severe nausea and vomiting. Two trials reported length of intensive care unit (ICU) stay but the data were skewed so were not pooled. Both trials reported that nitrous oxide-based techniques had no effects on the length of ICU stay. We rated the quality of evidence for two outcomes (pulmonary atelectasis, myocardial infarction) as high, four outcomes (inhospital case fatality rate, stroke, venous thromboembolism, length of hospital stay) as moderate, and three (pneumonia, severe nausea and vomiting, wound infection rate) as low. AUTHORS' CONCLUSIONS: Given the evidence from this Cochrane review, the avoidance of nitrous oxide may be reasonable in participants with pre-existing poor pulmonary function or at high risk of postoperative nausea and vomiting. Since there are eight studies awaiting classification, selection bias may exist in our systematic review.

Shenqi Fuzheng Injection for advanced gastric cancer: a systematic review of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness of Shenqi Fuzheng Injection (, SFI) combined with chemotherapy for advanced gastric cancer. METHODS: Randomized controlled trials (RCTs) from 10 databases were searched for this meta-analysis till December 31, 2012 without language restriction. Grey literature and potential unpublished literature was also searched. The key search terms were "chemotherapy", "Shenqi Fuzheng Injection" and "advanced gastric cancer". Criteria were built to select these clinical trials, in which SFI combined with chemotherapy was compared with chemotherapy alone for advanced gastric cancer. The methodological quality of each RCT was assessed using the Cochrane risk of bias tool. RevMan 5.1 software was applied for data analyses. RESULTS: Thirteen RCTs involving 860 patients met the selection criteria (all articles were from Chinese databases). The meta-analysis showed positive results for the use of SFI combined with chemotherapy according to quality of life in terms of the scores when compared with chemotherapy alone. Positive results were also obtained for the combination treatment, in terms of complete remission and partial remission efficacy rate, body weight and decreased adverse events including nausea and vomiting at grade 3-4, oral mucositis at grade 1-2, leucopenia at grade 3-4, and myelo-suppression at grade 1-2. CONCLUSIONS: This systematic review found encouraging albeit limited evidence for SFI combined with chemotherapy. However, to obtain stronger evidence without the drawbacks of trial design and the quality of studies, we recommend comparative effectiveness researches to test the effectiveness of combination treatment.

Does overweight affect outcomes in patients undergoing gastrectomy for cancer? A meta-analysis of 25 cohort studies.

OBJECTIVE: Overweight was regarded as one of the risk factors for poor outcome after gastrectomy, but its influence on the surgical and postoperative outcomes of gastrectomy was unclear. METHODS: Comprehensive searches were conducted to include cohort studies which evaluated the influence of overweight on the surgical and postoperative outcomes of gastrectomy. Data was analyzed by RevMan 5.0. RESULTS: Twenty-five cohort studies (18 518 patients) were included. Overweight patients were associated with longer operation time (mean difference 20.88, 95% confidence interval 14.07, 27.69), more intraoperative blood loss (mean difference 35.45, 95% confidence interval 9.24, 61.67), and less retrieved lymph nodes (mean difference -2.17, 95% confidence interval -3.51, -0.83) than normal patients undergoing laparoscopy-assisted gastrectomy. And overweight patients were associated with longer operation time (mean difference 26.31, 95% confidence interval 21.92, 30.70), more intraoperative blood loss (mean difference 130.02, 95% confidence interval 75.49, 184.55), less retrieved lymph nodes (mean difference -3.18, 95% confidence interval -4.74, -1.61), longer postoperative hospital stay (mean difference 2.37, 95% confidence interval 0.03, 4.70) and more postoperative complications (risk ratio 1.53, 95% confidence interval 1.29, 1.80) than normal patients in open gastrectomy. CONCLUSIONS: Overweight might affect the clinical results of both laparoscopy-assisted and open gastrectomy, especially for open gastrectomy.