The efficacy and safety of remifentanil patient-controlled versus epidural analgesia in labor: A meta-analysis and systematic review.

BACKGROUND: Remifentanil patient-controlled analgesia (rPCA) and epidural analgesia (EA) has been used for pain relief in labor. We aimed to evaluate the efficacy and safety of rPCA versus EA in labor, to provide evidence support for clinical analgesia and pain care. METHODS: We searched PubMed, EMBASE, ScienceDirect, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang and Weipu databases for RCTs comparing rPCA and EA in labor until February 15, 2022. Two researchers independently screened literature and extracted data. RevMan 5.3 software was used for data analysis. RESULTS: A total of 10 RCTs involving 3086 parturients were enrolled, 1549 parturients received rPCA and 1537 received EA. Meta-analysis indicated that the incidence of intrapartum maternal fever within 1 hour of labor analgesia (OR = 0.43, 95%CI: 0.30~0.62), after 1 hour of labor analgesia (OR = 0.42, 95%CI: 0.20~0.90) in the rPCA was significantly less than that of EA (all P<0.05). The incidence of respiratory depression (OR = 3.56, 95%CI: 2.45~5.16, P<0.001) in the rPCA was significantly higher than that of EA. There were no significant differences in the incidence of Apgar scores<7 at 5 minutes (OR = 1.18, 95%CI: 0.71~1.96, P = 0.53), the patients' satisfaction of pain relief during labor analgesia (SMD = 0.03, 95%CI: -0.40~0.46, P = 0.90) between rPCA and EA (all P>0.05). CONCLUSION: rPCA can be an optional alternative to EA with similar pain relief and less risk of intrapartum maternal fever. However, rPCA was associated with increased risk of respiratory depression. Future studies with rigorous design and larger sample size are needed to provide more reliable evidences for clinical rPCA and EA use.

Electroacupuncture attenuates surgical pain-induced delirium-like behavior in mice via remodeling gut microbiota and dendritic spine.

Surgical pain is associated with delirium in patients, and acupuncture can treat pain. However, whether electroacupuncture can attenuate the surgical pain-associated delirium via the gut-brain axis remains unknown. Leveraging a mouse model of foot incision-induced surgical pain and delirium-like behavior, we found that electroacupuncture stimulation at specific acupoints (e.g., DU20+KI1) attenuated both surgical pain and delirium-like behavior in mice. Mechanistically, mice with incision-induced surgical pain and delirium-like behavior showed gut microbiota imbalance, microglia activation in the spinal cord, somatosensory cortex, and hippocampus, as well as an enhanced dendritic spine elimination in cortex revealed by two-photon imaging. The electroacupuncture regimen that alleviated surgical pain and delirium-like behavior in mice also effectively restored the gut microbiota balance, prevented the microglia activation, and reversed the dendritic spine elimination. These data demonstrated a potentially important gut-brain interactive mechanism underlying the surgical pain-induced delirium in mice. Pending further studies, these findings revealed a possible therapeutic approach in preventing and/or treating postoperative delirium by using perioperative electroacupuncture stimulation in patients.

Role of lipocalin-2 in surgery-induced cognitive decline in mice: a signal from neuron to microglia.

BACKGROUND: Perioperative neurocognitive disorders (PNDs) are common complications observed among surgical patients. Accumulating evidence suggests that neuroinflammation is one of the major contributors to the development of PNDs, but the underlying mechanisms remain unclear. METHODS: qPCR and ELISA analysis were used for detecting LCN2 and cytokine levels. cx3cr1CreER/-:: R26iDTR/- crossed mouse line was used for microglia depletion; intracranial injection of recombinant LCN2 (rLCN2) and adeno-associated viruses (AAV)-mediated shRNA silencing approaches were used for gain and loss of function, respectively. Combing with in vitro microglia cell culture, we have studied the role of LCN2 in surgery-induced cognitive decline in mice. RESULTS: We revealed that Lcn2 mRNA and protein levels were greatly increased in mouse hippocampal neurons after surgery. This surgery-induced elevation of LCN2 was independent of the presence of microglia. Gain of function by intracranial injection of rLCN2 protein into hippocampus disrupted fear memory in naive mice without surgery. Conversely, silencing LCN2 in hippocampus by AAV-shRNA protected mice from surgery-induced microglia morphological changes, neuroinflammation and cognitive decline. In vitro, application of rLCN2 protein induced the expression of several pro-inflammatory cytokines in both BV-2 and primary microglia culture. CONCLUSIONS: These data suggest LCN2 acts as a signal from neuron to induce proinflammatory microglia, which contributes to surgery-induced neuroinflammation and cognitive decline in mice.

The effect of different depths of anesthesia monitored using Narcotrend on cognitive function in elderly patients after VATS lobectomy.

OBJECTIVE: The purpose of this study was to examine the effects of various depths of anesthesia monitored using Narcotrend on cognitive function in elderly patients after video-assisted thoracic surgery (VATS) lobectomy. METHODS: A total of 73 elderly patients who underwent VATS lobectomy were selected and divided into a control group (n=36) and an observation group (n=37) using a random number table. Both groups received general anesthesia. The Narcotrend index (NTI) of the control group was maintained at 50-59 and that of the observation group was maintained at 30-39. RESULTS: The heart period (HP) and mean arterial pressure (MAP) from both groups were decreased first, and then were increased during T1-T5; the MAP levels at T2, T3 , and T4 were lower in the observation group than in the control group (P < 0.05). The propofol dosage was higher and the awake to extubation time was greater in the observation group than in the control group (P < 0.05). The visual analogue scale (VAS) score was lower in the observation group than in the control group at 6 h and 12 h after surgery (P < 0.05). The left and right regional cerebral oxygen saturation (rSO2) at T3 -T4 was higher in the observation group and the cerebral oxygen extraction ratio (CERO2) was lower in the observation group than in the control group (P < 0.05). CONCLUSION: The anesthetic depth that maintained an NTI of 30-39 as monitored using Narcotrend could improve cerebral oxygen metabolism, inhibit the inflammatory reaction, and reduce the incidence of postoperative cognitive dysfunction (POCD) in patients after VATS lobectomy.

Emerging Roles of Microglia in Neuro-vascular Unit: Implications of Microglia-Neurons Interactions.

Microglia, which serve as the defensive interface of the nervous system, are activated in many neurological diseases. Their role as immune responding cells has been extensively studied in the past few years. Recent studies have demonstrated that neuronal feedback can be shaped by the molecular signals received and sent by microglia. Altered neuronal activity or synaptic plasticity leads to the release of various communication messages from neurons, which in turn exert effects on microglia. Research on microglia-neuron communication has thus expanded from focusing only on neurons to the neurovascular unit (NVU). This approach can be used to explore the potential mechanism of neurovascular coupling across sophisticated receptor systems and signaling cascades in health and disease. However, it remains unclear how microglia-neuron communication happens in the brain. Here, we discuss the functional contribution of microglia to synapses, neuroimmune communication, and neuronal activity. Moreover, the current state of knowledge of bidirectional control mechanisms regarding interactions between neurons and microglia are reviewed, with a focus on purinergic regulatory systems including ATP-P2RY12R signaling, ATP-adenosine-A1Rs/A2ARs, and the ATP-pannexin 1 hemichannel. This review aims to organize recent studies to highlight the multifunctional roles of microglia within the neural communication network in health and disease.

Preoperative assessment of cognitive function and risk assessment of cognitive impairment in elderly patients with orthopedics: a cross-sectional study.

BACKGROUND: Preexisting cognitive impairment is emerging as a predictor of poor postoperative outcomes in seniors. Nevertheless, cognitive impairment in a large proportion of geriatric patients has not been well identified and diagnosed. METHODS: This is a cross-sectional study. Mini-mental state examination scale was used to assess the cognitive function of elderly patients aged ≥65 years undergoing orthopedic surgery preoperatively. The baseline, living habits and laboratory examination results of two groups were compared, and a multivariable logistic regression model was used to identify independent predictors of preoperative cognitive impairment. RESULTS: A total of 374 elderly patients with orthopedic surgery indications met the inclusion criteria, and 28.61% of them had preoperative cognitive impairment. Multivariable logistic regression analysis showed that age (OR = 1.089, P < 0.001), subjective sleep disorders (OR = 1.996, P = 0.021), atherosclerosis (OR = 2.367, P = 0.017), and high cholesterol level (OR = 1.373, P = 0.028) were independent risk factors for preoperative cognitive impairment, while high education level performed as a protective factor (compared with the illiterate group, primary school group: OR = 0.413, P = 0.009; middle school or above group: OR = 0.120, P < 0.001). CONCLUSIONS: The prevalence of preoperative cognitive dysfunction in geriatric elective orthopedic surgical patients was high. Our study identified venerable age, low level of education, subjective sleep disorders, atherosclerosis, and high cholesterol level as risk factors for preoperative cognitive impairment in these patients. Understanding these risk factors contributes to assisting in prevention and directed interventions for the high-risk population.

Effects of general anesthesia versus local anesthesia in primary hepatocellular carcinoma patients presenting for thermal ablation surgery: a multiple center retrospective cohort study with propensity score matching.

BACKGROUND: Whether anesthesia methods affect the prognosis of tumor patients is controversial. With the aim of comparing the effects of general anesthesia (GA) and local anesthesia (LA) in primary hepatocellular carcinoma (HCC) patients presenting for elective thermal ablation (TA) surgeries, a multiple center retrospective cohort study was designed and implemented. METHODS: Patients who received elective TA surgery under GA or LA from Jan. 2014 to Dec. 2016 and met the eligibility criteria were included. Survival analysis was used to identify the influence of anesthesia methods on recurrence-free survival (RFS) and overall survival (OS). Propensity score matching (PSM) was used to minimize the bias between the GA group and the LA group. RESULTS: A total of 244 patients with GA and 245 with LA were eligible for analysis. After PSM, 178 patients remained in each group. In the matched groups, GA showed a significantly higher recurrence rate compared with LA by both the Kaplan-Meier survival analyses (P=0.011) and multivariable Cox regression analyses (P=0.002). The multivariable Cox regression model also revealed that GA had a hazard ratio (HR) of 1.746 (P=0.036) for death compared with the LA group. CONCLUSIONS: GA is associated with decreased RFS and OS after surgery compared with LA in HCC patients undergoing TA surgery. Prospective trials exploring the effects of different anesthetic methods on cancer outcome in these patients are warranted.

Risk Factors for Emergence Agitation in Adults Undergoing Thoracoscopic Lung Surgery: A Case-Control Study of 1,950 Patients.

OBJECTIVE: The present study investigated the incidence of and risk factors for emergence agitation (EA) in adult patients after thoracoscopic lung surgery. DESIGN: A retrospective case-control study. SETTING: Single-center university hospital. PARTICIPANTS: The study comprised 1,950 adult patients who underwent elective lung surgery from January to December 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Preoperative, surgical, and anesthesia-related data were collected. EA was assessed with the Riker Sedation-Agitation Scale and defined as a Riker score ≥5. Univariate analyses and multivariate logistic regression analysis were used to identify risk factors for EA. The incidence of EA was 14.1%. The results of the multivariate analysis showed that male sex (odds ratio [OR] 1.877, 95% confidence interval [CI] 1.341-2.627), age ≥65 years (OR 1.424, 95% CI 1.074-1.889), body mass index ≥24 kg/m2 (OR 1.409, 95% CI 1.070-1.856), American Society of Anesthesiologists physical status Ⅲ or Ⅳ (OR 2.654, 95% CI 1.189-5.924), cigarette smoking (OR 1.553, 95% CI 1.108-2.177), duration of surgery (OR 1.006, 95% CI 1.003-1.009), intraoperative tachycardia (OR 1.721, 95% CI 1.058-2.802), intraoperative hypotension (OR 1.636, 95% CI 1.064-2.514), intraoperative hypertension (OR 1.608; 95% CI 1.056-2.448), and rescue analgesia (OR 1.810, 95% CI 1.235-2.653) were independent risk factors for EA. However, wound infiltration (OR 0.679, 95% CI 0.507-0.908) and the use of dexmedetomidine (OR 0.663, 95% CI 0.490-0.869) appeared to be protective factors against EA. CONCLUSION: EA is a common complication after thoracoscopic lung surgery, especially within a certain population. Adequate perioperative management, which comprises wound infiltration, the maintenance of intraoperative hemodynamic stability, sufficient analgesia, and the use of dexmedetomidine, should be adopted to reduce the incidence of EA.

Pharmacist-driven multidisciplinary initiative continuously improves postoperative nausea and vomiting in female patients undergoing abdominal surgery.

WHAT IS KNOWN AND OBJECTIVE: The incorrect or insufficient prophylaxis of postoperative nausea and vomiting (PONV) is common in practice. A clinical pharmacist-led guidance team (CPGT) was established and included in general surgery teams. OBJECTIVE: This study aimed to evaluate the effects of the CPGT on the improvement of PONV and prophylaxis administration. METHODS: A prospective before-after study was conducted on 156 female patients undergoing abdominal surgery at a Chinese tertiary teaching hospital from December 2016 to December 2017. A total of 82 patients were enrolled in the preintervention period, and 74 patients were included in the post-intervention period. The CPGT established the evidence-based criteria for prophylactic anti-emetic administration and conducted interventions, including a review of medical records, provision of feedback, educational outreach, and dedicated support. Primary outcomes included the incidence of PONV within 24 hours of surgery, administered number of prophylactic anti-emetics, and accuracy of the timing for prophylactic anti-emetics. Outcomes were analysed by logistic regression or multivariable linear regression. RESULTS AND DISCUSSION: After intervention, patients reported significantly less PONV (33.78% vs 56.10%; odds ratio [OR]: 0.29; numbers needed to treat [NNT]: 3.47), vomiting (29.73% vs 45.12%; OR: 0.42; NNT: 5.16) and nausea (31.08% vs 56.10%; OR: 0.24; NNT: 3.19) within 24 hours of surgery. The accuracy of the timing for prophylactic anti-emetics significantly increased (OR: 3.66; P: .003). Anaesthesiologists administered increased numbers of prophylactic anti-emetics (OR: 5.82; P < .001). The improvement of PONV did not decrease during the four-month period after intervention (P: .639). WHAT IS NEW AND CONCLUSION: The CPGT is a valuable service model to continuously improve PONV and optimize prophylaxis administration.

The Mitochondrial Chaperone TRAP1 as a Candidate Target of Oncotherapy.

Tumor necrosis factor receptor-associated protein 1 (TRAP1), a member of the heat shock protein 90 (Hsp90) chaperone family, protects cells against oxidative stress and maintains mitochondrial integrity. To date, numerous studies have focused on understanding the relationship between aberrant TRAP1 expression and tumorigenesis. Mitochondrial TRAP1 is a key regulatory factor involved in metabolic reprogramming in tumor cells that favors the metabolic switch of tumor cells toward the Warburg phenotype. In addition, TRAP1 is involved in dual regulation of the mitochondrial apoptotic pathway and exerts an antiapoptotic effect on tumor cells. Furthermore, TRAP1 is involved in many cellular pathways by disrupting the cell cycle, increasing cell motility, and promoting tumor cell invasion and metastasis. Thus, TRAP1 is a very important therapeutic target, and treatment with TRAP1 inhibitors combined with chemotherapeutic agents may become a new therapeutic strategy for cancer. This review discusses the molecular mechanisms by which TRAP1 regulates tumor progression, considers its role in apoptosis, and summarizes recent advances in the development of selective, targeted TRAP1 and Hsp90 inhibitors.

Effects of peri-operative intravenous administration of dexmedetomidine on emergence agitation after general anesthesia in adults: a meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of the current meta-analysis was to assess the effect of dexmedetomidine on emergence agitation (EA) and the recovery outcomes after general anesthesia in adults. METHODS: We searched the PubMed, the Cochrane Central Register of Controlled Trials, Embase, Web of Science and clinicaltrials.gov for relevant randomized controlled trials (RCTs) investigating the effects of dexmedetomidine on the EA in adults after general anesthesia compared with placebo. The primary outcome was the incidence of EA. Secondary outcomes included other recovery outcomes after general anesthesia. RESULTS: Twelve RCTs (842 participants) met the eligibility criteria. A conventional random-effects meta-analysis demonstrated that peri-operative intravenous dexmedetomidine could be effective for the prevention of EA [risk ratio (RR) 0.49, Trial Sequential Analysis (TSA)-adjusted 95% confidence interval (CI) 0.35-0.68, P<0.00001]. In addition, the TSA indicated that the meta-analysis for the incidence of EA reached the required information size (370). Lower number of patients receiving dexmedetomidine required analgesia (P=0.0009). Extubation time was longer (P=0.03) and hypotension (P=0.03) was more common with dexmedetomidine. Moreover, no difference was found in the other outcomes. CONCLUSION: Dexmedetomidine was shown to effectively decrease the incidence of EA and to reduce postoperative analgesic requirements. Yet, other recovery outcomes including extubation time, length of PACU stay, postoperative residual sedation, hypotension, bradycardia as well as postoperative nausea and vomiting provided no data that could be used to form final conclusions.

Correction to: Inhibition of T cell immunoglobulin and mucin-1 (TIM-1) protects against cerebral ischemia-reperfusion injury.

Following publication of the original article [1], the authors reported that the given name of Liqing Wang was incorrectly published as Liqiang Wang. The original article has been updated.

Inhibition of T cell immunoglobulin and mucin-1 (TIM-1) protects against cerebral ischemia-reperfusion injury.

BACKGROUND: The T cell Ig domain and mucin domain (TIM)-1 protein expressed on the surface of Th2 cells regulates the immune response by modulating cytokine production. The present study aimed to investigate the role and possible mechanism of TIM-1 in cerebral ischemia-reperfusion injury. METHODS: Western blot was used to detect TIM-1 and apoptosis-related protein expression, whereas TIM-1 mRNA was examined using quantitative real-time reverse transcription PCR. Flow cytometry and a TdT-mediated biotin-16-dUTP nick-end labeling (TUNEL) assay were used to detect the percentage of apoptotic cells and a pathological examination was performed. The migration of neutrophils and macrophages was analyzed by immunohistochemistry. RESULTS: Our results suggest that TIM-1 expression was transiently increased 24 h or 48 h following middle cerebral artery occlusion (MCAO)/reperfusion. The infarct size was markedly increased in MCAO, whereas treatment with a TIM-1-blocking mAb could reduce the infarct size. TIM-1 blocking mAb effectively reduced the number of neutrophils, macrophage functionality, cytokine (i.e., IL-6, IL-1ß, and TNF-α) and chemokine (i.e., CXCL-1 and CXCL-2) production in the brain tissue. The effect of in vitro T cell damage on neurons was significantly reduced following treatment with a TIM-1 blocking mAb or the knockdown of TIM-1 in co-cultured T cells and neurons. CONCLUSION: Take together, these results indicated that TIM-1 blockade ameliorated cerebral ischemia-reperfusion injury. Thus, TIM-1 disruption may serve as a novel target for therapy following MCAO.

Intraoperative dexmedetomidine infusion is associated with reduced emergence agitation and improved recovery profiles after lung surgery: a retrospective cohort study.

PURPOSE: This retrospective cohort study aimed to investigate the association between intraoperative dexmedetomidine infusion and emergence agitation (EA), and recovery profiles after lung surgery in adult patients. It was hypothesized that dexmedetomidine was associated with reduced EA and improved recovery profiles. PATIENTS AND METHODS: A single-center chart review was conducted on elective lung surgeries in adults between January and December 2016. The primary outcome was the incidence of EA in postanesthesia care units (PACUs). The secondary outcomes included rescue analgesia, shivering, time to extubation, residual sedation, postoperative pulmonary events, duration of PACU stay, length of hospital stay, and intraoperative hemodynamic changes. Univariate and multivariate regression analyses were used to analyze data. RESULTS: Among 2,468 patients, 814 received an intraoperative dexmedetomidine infusion. Intraoperative dexmedetomidine infusion was associated with a lower incidence of EA (10.9% vs 15.0%; adjusted OR, 0.67; 95% CI, 0.51-0.87; P=0.003), rescue analgesia (7.6% vs 12.2%; adjusted OR, 0.63; 95% CI, 0.47-0.86; P=0.003), shivering (4.2% vs 6.6%; adjusted OR, 0.58; 95% CI, 0.38-0.88; P=0.010), and intraoperative bradycardia (18.6% vs 12.6%; adjusted OR, 1.51; 95% CI, 1.19-1.92; P=0.001). No differences were observed in residual sedation, duration of PACU stay, postoperative pulmonary events, and length of hospital stay between the groups. CONCLUSION: This retrospective study suggested that intraoperative dexmedetomidine infusion was associated with a lower incidence of EA, rescue analgesia, and shivering in adults after lung surgery. Intraoperative bradycardia was the main side effect.

Goal-directed fluid therapy does not reduce postoperative ileus in gastrointestinal surgery: A meta-analysis of randomized controlled trials.

BACKGROUND: Perioperative goal-directed fluid therapy (GDFT) aiming to maintain individual fluid balance based on sensitive parameters was prevalent in major surgery, especially in enhanced recovery after surgery (ERAS) pathway. This meta-analysis was conducted for the purpose of evaluating whether GDFT impacts on occurrence of postoperative ileus and whether its application is worthwhile in gastrointestinal surgery. METHODS: A systematic search of RCTs compared GDFT with other fluid management in patients undergoing gastrointestinal surgery from the PubMed, Web of Science, Embase, Cochrane Library databases was implemented. The primary outcome is incidence of postoperative ileus. Other outcome measures were length of hospital stay (LOS), postoperative morbidity and mortality. Subgroup analysis was planed a prior to verify the definite role of GDFT. RESULTS: 12 trials consisted of 1836 patients were included in the final analysis. GDFT did not influence the occurrence of postoperative ileus (relative risk, RR 0.71, 95% confidence interval, CI 0.47-1.07, P = .10), with moderate heterogeneity (I = 29%, P = .16). No difference was found between GDFT and control groups in LOS (mean difference -0.17 days, 95% CI -0.73 to 0.39, P = .55), total complication rate (RR 0.92, 95% CI 0.81-1.05, P = .23), and 30-day mortality (RR 0.91, 95% CI 0.47-1.75, P = .77). In other secondary outcomes, only wound infection rate was lower in the GDFT group (RR 0.68, 95% CI 0.50-0.93, P = .02). When performed subgroup analysis, GDFT was superior in reduction ileus only when compared with standard therapy or in those outside ERAS. CONCLUSIONS: It is possible that GDFT dose not affect the occurrence of postoperative ileus in gastrointestinal surgery. It scarcely influences postoperative morbidity and mortality as well. However, lower incidence of ileus is observed in GDFT group either outside ERAS or compared with standard fluid therapy. Probably, GDFT may not be necessary in the ERAS pathway or if a hybrid approach is adopted.

Interleukin-19 alleviates brain injury by anti-inflammatory effects in a mice model of focal cerebral ischemia.

Stroke causes brain injury with neuroinflammation which exacerbates the neuronal damage. Recent studies show that anti-inflammatory cytokine interleukin-19 (IL-19) plays a critical part in the inflammatory and ischemic vascular diseases, yet its potential role in ischemic stroke is unknown. Here, we tested the hypothesis that IL-19 exerts protective effects against brain ischemia by modulating inflammation after stroke. Mice were injected intraperitoneally with 10ng/g per day recombinant mouse IL-19 starting pre-stroke, and were subjected to transient middle cerebral artery occlusion. Infarct volume was assessed by triphenyltetrazolium chloride and neurobehavioral outcome by neurological scores. Inflammation was measured using real-time quantitative PCR, immunochemistry, and fluorescence-activated cell sorting. Infarct volume at 72h after stroke was significantly smaller in IL-19 treated group and focal neurological score was significantly better. IL-19 treatment markedly attenuated elevation of the expression of TNF-α and IL-6 mRNA, suppressed increases in the number of microglia, macrophages, CD4+ T cells, CD8+ T cells as well as B cells, and blocked activation of macrophages and neutrophils in the ischemic brain. In peripheral blood, IL-19 injection helped to robustly preserve the reduced immune cells, including macrophages, CD4+ T cells, CD8+ T cells and B cells, compared to control group. IL-19 reduced brain infarction and attenuated neurological deficits following stroke in mice, probably by inhibiting infiltration and activation of immune cells, and by suppressing increases in gene expression of proinflammatory cytokines. This may identify IL-19 as a new therapeutic to limit neuroinflammation after stroke.