Repeated Neonatal Exposure to Sevoflurane Induces Age-Dependent Impairments in Cognition and Synaptic Plasticity in Mice.

BACKGROUND: Sevoflurane is a volatile anesthetic that is widely used in pediatric anesthesia due to its low toxicity. However, whether neonatal exposure to sevoflurane induces long-lasting cognitive impairment remains unclear. It has been reported that neuronal injury is the main cause of sevoflurane-induced learning and memory disabilities in the development of brain. But, the specific mechanism is not well elucidated. The injury of synapse occurs earlier than that of neuronal cell in brain injury. The synaptic plasticity is involved in learning and memory. METHODS: We compared the learning and memory ability of neonatal mice to sevoflurane for once or three times in vitro and synaptic plasticity as well as neuronal excitability in vivo. In this study, neonatal C57BL/6J mice were exposed to 3% sevoflurane for 2 h on postnatal day 7 (P7) or once daily for 3 consecutive days (P7/8/9). The Morris water maze test was performed to evaluate the cognitive performance on P31 and P61, respectively. Theta burst stimulation-induced long-term potentiation (LTP) was measured in acute hippocampal slices from P38 and P68 mice to assess the synaptic plasticity. Primary hippocampal neurons were isolated from 24-h-old mice and exposed to different doses of sevoflurane (1, 2, and 3 minimum alveolar anesthetic concentration [MAC]) for 6 h to examine the neuronal excitability. RESULTS: The results showed that compared with the control, repeated exposure to sevoflurane resulted in significant cognitive impairment in adolescent mice, while showing no effect on adult mice. Repeated exposure to sevoflurane remarkably attenuated hippocampal LTP of adolescent mice, which turned to normal in adult mice. No significant difference of LTP was observed between control mice and one-dose sevoflurane-treated mice both in adolescent and adult mice. In primary hippocampal neurons, 2 MAC and 3 MAC sevoflurane delayed neuronal excitation and dose-dependently reduced the number of evoked action potentials compared with control. These effects disappeared after a 24-h recovery. CONCLUSIONS: These data suggested that sevoflurane may impair cognitive performance and neuronal plasticity when administered repeatedly or in a high MAC during infancy, which is noticeable during adolescence but alleviates during adulthood.

Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non-inferiority, phase III trial.

BACKGROUND AND AIM: Remimazolam tosilate (RT) is a new short-acting GABA(A) receptor agonist, having potential to be an effective option for procedural sedation. Here, we aimed to compare the efficacy and safety of RT with propofol in patients undergoing upper gastrointestinal endoscopy. METHODS: This positive-controlled, non-inferiority, phase III trial recruited patients at 17 centers, between September 2017 and November 2017. A total of 384 patients scheduled to undergo upper gastrointestinal endoscopy were randomly assigned to receive RT or propofol. Primary endpoint was the success rate of sedation. Adverse events (AEs) were recorded to evaluate safety. RESULTS: The success rate of sedation in the RT group was non-inferior to that in the propofol group (97.34% vs 100.00%; difference in rate -2.66%, 95% CI -4.96 to -0.36, meeting criteria for non-inferiority). Patients in the RT group had longer time to adequate sedation (P < 0.0001) but shorter time to fully alert (P < 0.0001) than that in the propofol group. The incidences of hypotension (13.04% vs 42.86%, P < 0.0001), treatment-related hypotension (0.54% vs 5.82%, P < 0.0001), and respiratory depression (1.09% vs 6.88%, P = 0.0064) were significantly lower in the RT group. AEs were reported in 74 (39.15%) patients in the RT group and 114 (60.32%) patients in the propofol group, with significant difference (P < 0.0001). CONCLUSION: This trial established non-inferior sedation success rate of RT compared with propofol. RT allows faster recovery from sedation compared with propofol. The safety profile is favorable and appears to be superior to propofol, indicating that it was feasible and well tolerated for patients.

Abnormally low Bispectral index and severe hypoglycemia during maintenance of and recovery from general anesthesia in diabetic retinopathy surgery: two case reports.

BACKGROUND: Hypoglycemia is one of the most fatal complications during the perioperative period. General anesthesia or sedation can mask a hypoglycemia-altered mental status. Acute hypoglycemia might result in permanent brain injury. There is no way to detect hypoglycemia during general anesthesia, except for intermittent blood glucose monitoring. CASE PRESENTATION: Hypoglycemia is associated with changes in electroencephalogram readings. Here, we report two cases of patients with an abnormally low Bispectral Index (BIS) associated with diabetic retinopathy surgery, one in the recovery stage of general anesthesia and the other in the maintenance of general anesthesia. Hemodynamics were stable. Severe hypoglycemia (1.6 mmol/L and 2.2 mmol/L) was then detected. BIS increased with the correction of severe hypoglycemia. CONCLUSIONS: For diabetic patients, when the intraoperative BIS value is abnormally low, hypoglycemia should be considered. Severe hypoglycemia may be presented in BIS monitoring during general anesthesia.

Effect of perioperative goal-directed hemodynamic therapy on postoperative recovery following major abdominal surgery-a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Goal-directed hemodynamic therapy (GDHT) has been used in the clinical setting for years. However, the evidence for the beneficial effect of GDHT on postoperative recovery remains inconsistent. The aim of this systematic review and meta-analysis was to evaluate the effect of perioperative GDHT in comparison with conventional fluid therapy on postoperative recovery in adults undergoing major abdominal surgery. METHODS: Randomized controlled trials (RCTs) in which researchers evaluated the effect of perioperative use of GDHT on postoperative recovery in comparison with conventional fluid therapy following abdominal surgery in adults (i.e., >16 years) were considered. The effect sizes with 95% CIs were calculated. RESULTS: Forty-five eligible RCTs were included. Perioperative GDHT was associated with a significant reduction in short-term mortality (risk ratio [RR] 0.75, 95% CI 0.61-0.91, p = 0.004, I 2 = 0), long-term mortality (RR 0.80, 95% CI 0.64-0.99, p = 0.04, I 2 = 4%), and overall complication rates (RR 0.76, 95% CI 0.68-0.85, p < 0.0001, I 2 = 38%). GDHT also facilitated gastrointestinal function recovery, as demonstrated by shortening the time to first flatus by 0.4 days (95% CI -0.72 to -0.08, p = 0.01, I 2 = 74%) and the time to toleration of oral diet by 0.74 days (95% CI -1.44 to -0.03, p < 0.0001, I 2 = 92%). CONCLUSIONS: This systematic review of available evidence suggests that the use of perioperative GDHT may facilitate recovery in patients undergoing major abdominal surgery.

Airway management education: simulation based training versus non-simulation based training-A systematic review and meta-analyses.

BACKGROUND: Simulation-based training (SBT) has become a standard for medical education. However, the efficacy of simulation based training in airway management education remains unclear. METHODS: The aim of this study was to evaluate all published evidence comparing the effectiveness of SBT for airway management versus non-simulation based training (NSBT) on learner and patient outcomes. Systematic review with meta-analyses were used. Data were derived from PubMed, EMBASE, CINAHL, Scopus, the Cochrane Controlled Trials Register and Cochrane Database of Systematic Reviews from inception to May 2016. Published comparative trials that evaluated the effect of SBT on airway management training in compared with NSBT were considered. The effect sizes with 95% confidence intervals (CI) were calculated for outcomes measures. RESULTS: Seventeen eligible studies were included. SBT was associated with improved behavior performance [standardized mean difference (SMD):0.30, 95% CI: 0.06 to 0.54] in comparison with NSBT. However, the benefits of SBT were not seen in time-skill (SMD:-0.13, 95% CI: -0.82 to 0.52), written examination score (SMD: 0.39, 95% CI: -0.09 to 0.86) and success rate of procedure completion on patients [relative risk (RR): 1.26, 95% CI: 0.96 to 1.66]. CONCLUSION: SBT may be not superior to NSBT on airway management training.

Glucose may attenuate isoflurane-induced caspase-3 activation in H4 human neuroglioma cells.

BACKGROUND: The commonly used inhaled anesthetic isoflurane has been shown to induce caspase-3 activation. However, the underlying mechanism(s) and targeted intervention(s) remain largely to be determined. Isoflurane may induce caspase-3 activation via causing accumulation of reactive oxygen species (ROS), mitochondrial dysfunction, and reduction in adenosine triphosphate (ATP) levels. Therefore, we performed a hypothesis-generation study to determine whether glucose could attenuate isoflurane-induced caspase-3 activation, ROS accumulation, mitochondrial dysfunction, and ATP reduction in cultured cells. METHODS: H4 human neuroglioma cells (H4 cells) were treated with 2% isoflurane or the control condition plus saline or 50 mM glucose for 6 or 3 hours. Caspase-3 activation, cell viability, levels of ROS and ATP, and mitochondrial membrane potential were determined at the end of the experiments by Western blot analysis and fluorescence assay. RESULTS: We found that the glucose treatment might attenuate isoflurane-induced caspase-3 activation and reduction of cell viability in H4 cells. Moreover, the glucose treatment mitigated the isoflurane-induced increase in ROS levels and reduction in ATP levels in H4 cells. Unexpectedly, we observed that the glucose treatment might not inhibit the isoflurane-induced decrease in mitochondrial membrane potential in H4 cells. CONCLUSIONS: Pending further studies, these results suggested that glucose might attenuate isoflurane-induced caspase-3 activation through a mitochondria-independent reduction in ROS levels and enhancement in ATP levels. These findings have established a system and suggest that it is worth performing more research to further investigate whether glucose can attenuate anesthesia neurotoxicity.

Comparison of drug-induced sleep endoscopy and upper airway computed tomography in obstructive sleep apnea patients.

The purpose of the present study was to evaluate the associations between the findings of drug-induced sleep endoscopy (DISE) and upper airway computed tomography (UACT) in obstructive sleep apnea (OSA) patients. This study was a non-randomized, prospective, clinical trial. We used DISE to identify the obstruction pattern according to VOTE classification. All 62 study subjects (all men) showed velum-related obstruction; 47 (75.8%) had lateral oropharyngeal obstruction, 45 (72.6%) had tongue-base-related obstruction, and 6 (9.7%) had epiglottal obstruction. The following UACT measurements significantly differed between subjects with and without lateral oropharyngeal obstruction (P < 0.05): airway length, laryngopharynx length, mandibular plane to hyoid distance, minimum lateral dimension of the retroglossal airway, retropalatal anteroposterior/lateral dimension, and retroglossal anteroposterior/lateral dimension. None of the UACT measurements significantly differed between subjects with and without tongue-base-related or epiglottal obstruction. These results indicate that in OSA patients, obstruction related to the lateral oropharyngeal walls can be identified using these UACT measurements. Thus, UACT, which is performed during wakefulness, can partially replace DISE, which is both time consuming and costly.

Inhibition of neuron-specific CREB dephosphorylation is involved in propofol and ketamine-induced neuroprotection against cerebral ischemic injuries of mice.

Propofol and ketamine may provide certain degree of neuroprotection, but the underlying mechanism remains unclear to date. The cAMP response element-binding protein (CREB) was proposed that its phosphorylation at Ser133 (P-CREB) constituted a convergence point involved in neuroprotection. The purpose of this study was to determine whether different dosages of propofol and ketamine could provide neuroprotection against permanent middle cerebral artery occlusion (MCAO)-induced ischemic injuries and the involvement of P-CREB. Eighty adult male BALB/c mice that underwent 6 h MCAO were randomly divided into eight groups: Sham-operation; MCAO + saline; MCAO + 25, 50, 100 mg/kg propofol; and MCAO + 25, 50, 100 mg/kg ketamine (intraperitoneal injection 30 min following MCAO). We found that 50, 100 (not 25) mg/kg propofol, and 25 (not 50 and 100) mg/kg ketamine could significantly reduce the infarct volume, edema ratio and neurological deficit (n = 10 per group) as well as inhibit the decrease of P-CREB level in peri-infarct region when compared with that of MCAO + saline group (n = 6 per group). In addition, the results of double-labeled immunofluorescent staining showed that P-CREB co-localized with neuron-specific marker, NeuN, in the peri-infarct region of 50 mg/kg propofol and 25 mg/kg ketamine treated 6 h MCAO mice (n = 4 per group). These results suggested that inhibition of neuron-specific P-CREB dephosphorylation in the peri-infarct region is involved in high dose propofol and low dose ketamine-induced neuroprotection of 6 h MCAO mice.

Sevoflurane induced neurotoxicity in neonatal mice links to a GSK3ß/Drp1-dependent mitochondrial fission and apoptosis.

Mitochondria damage and apoptosis were found associated with sevoflurane induced neurotoxicity in developing brains of rodent and neuro cell lines. The detailed upstream mechanism remains unclear. This study explored whether sevoflurane induces neurotoxicity by activating a GSK3ß (glycogen synthase kinase 3ß)/Drp1 (dynamin-related protein-1)-dependent mitochondrial fission and apoptosis. Our results showed that sevoflurane exposure promoted mitochondria fission in hippocampus of neonatal mice, resulted in a prolonged escape latency from P32 (32-day-postnatal) to P35, and decreased platform crossing times on P36 as compared to the control treatment. Additionally, sevoflurane upregulated GSK3ß stability and activation, promoted phosphorylation of Drp1 at Ser616 along with its translocation to mitochondria and resulted in increasing cytochrome c and cleaved casepase-3 in hippocampus of neonatal mice and in human SK-N-SH cells. Simultaneously, sevoflurane promoted the interaction between Drp1 and GSK3ß. Furthermore, GSK3ß activated phosphorylation of Drp1 at Ser616, induced mitochondrial fission, loss of mitochondrial membrane potential (MMP) and apoptosis in SK-N-SH cells, which was attenuated by TDZD-8, an inhibitor of GSK3ß. In conclusion, sevoflurane induced neurotoxicity links to a GSK3ß/Drp1 dependent mitochondrial fission and apoptosis.

The potential dual effects of anesthetic isoflurane on hypoxia-induced caspase-3 activation and increases in ß-site amyloid precursor protein-cleaving enzyme levels.

BACKGROUND: ß-Amyloid protein (Aß) accumulation, caspase activation, apoptosis, and hypoxia-induced neurotoxicity have been suggested to be involved in Alzheimer disease neuropathogenesis. Aß is produced from amyloid precursor protein through proteolytic processing by the aspartyl protease ß-site amyloid precursor protein-cleaving enzyme (BACE) and γ-secretase. Inhaled anesthetics have long been considered to protect against neurotoxicity. However, recent studies have suggested that the inhaled anesthetic isoflurane may promote neurotoxicity by inducing caspase activation and apoptosis, and by increasing levels of BACE and Aß. We therefore sought to determine whether isoflurane can induce concentration-dependent dual effects on hypoxia-induced caspase-3 activation and increases in BACE levels: protection versus promotion. METHODS: H4 human neuroglioma cells were treated with hypoxia (3% O(2)) alone, different concentrations of isoflurane (0.5% and 2%), and the combination of hypoxia and 0.5% or 2% isoflurane. The levels of caspase-3 cleavage (activation), BACE, and Bcl-2 were determined by Western blot analysis. RESULTS: We show for the first time that treatment with 0.5% isoflurane for 8 hours attenuated, whereas treatment with 2% isoflurane for 8 hours enhanced, hypoxia-induced caspase-3 activation and increases in BACE levels. The 2% isoflurane treatment also enhanced a hypoxia-induced decrease in Bcl-2 levels. CONCLUSIONS: These results suggest a potential concept that isoflurane has dual effects (protection versus promotion) on hypoxia-induced toxicity, which may act through Bcl-2 family proteins. These findings could lead to more systematic studies to determine the potential dual effects of anesthetics on Alzheimer disease-associated neurotoxicity.

2-Deoxy-D-glucose attenuates isoflurane-induced cytotoxicity in an in vitro cell culture model of H4 human neuroglioma cells.

BACKGROUND: ß-Amyloid protein (Aß) accumulation and caspase activation have been shown to contribute to Alzheimer disease neuropathogenesis. Aß is produced from amyloid precursor protein through proteolytic processing by aspartyl protease ß-site amyloid precursor protein-cleaving enzyme (BACE). The inhaled anesthetic isoflurane has been shown to induce caspase activation and increase levels of BACE and Aß. However, the underlying mechanisms and interventions of the isoflurane-induced neurotoxicity remain largely to be determined. The glucose analog 2-deoxy-d-glucose (2-DG) has neuroprotective effects. Therefore, we sought to determine whether 2-DG can reduce caspase-3 activation and the increase in the levels of BACE and reactive oxygen species (ROS) induced by isoflurane. METHODS: H4 human neuroglioma cells were treated with saline or 2-DG (5 mM) for 1 hour followed by a control condition or 2% isoflurane for 6 hours. The levels of caspase-3 cleavage (activation), BACE, cytosolic calcium, and ROS were determined. Two-way analysis of variance was used to assess the interactions of 2-DG and isoflurane on caspase-3 activation, and levels of BACE and ROS. RESULTS: In H4 human neuroglioma cells, 2-DG reduced the caspase-3 activation (477% vs 186%, F = 8.68; P = 0.019) and the increase in BACE levels (345% vs 123%, F = 42.24; P = 0.0002) induced by isoflurane. 2-DG decreased the levels of cytosolic calcium and ROS (100% vs 66%, F = 1.94; P = 0.014). CONCLUSIONS: These results suggest that 2-DG may decrease oxidative stress and increase cytosolic calcium levels, thus attenuating isoflurane-induced neurotoxicity.

Morphine pretreatment protects against cerebral ischemic injury via a cPKCγ-mediated anti-apoptosis pathway.

It has been reported that morphine pretreatment (MP) can exert neuroprotective effects, and that protein kinase C (PKC) participates in the initiation and development of ischemic/hypoxic preconditioning in the brain. However, it remains unknown whether PKC is involved in MP-induced neuroprotection. The aim of the present study, which included in vivo and in vitro experiments, was to determine whether the conventional γ isoform of PKC (cPKCγ) was involved in the protective effects of MP against cerebral ischemic injury. The present study included an in vivo experiment using a mouse model of middle cerebral artery occlusion and an in vitro experiment using neuroblastoma N2a cells with oxygen-glucose deprivation (OGD). Furthermore, a cPKCγ antagonist, Go6983, was used to determine the involvement of cPKCγ in the protective effects of MP against cerebral ischemic injury. In the in vivo experiment, neurological deficits, ischemic infarct volume, neural cell damage, apoptosis and caspase-3 activation were evaluated. In the in vitro experiment, flow cytometry was used to determine the activation of caspase-3 in N2a cells with OGD. It was found that MP protected against cerebral ischemic injury. However, intracerebroventricular injection of the cPKCγ antagonist before MP attenuated the neuroprotective effect of MP and increased the activation of cleaved caspase-3. These findings suggested that MP may provide protection against cerebral ischemic injury via a cPKCγ-mediated anti-apoptosis pathway.

Enhancement of Aggression Induced by Isolation Rearing is Associated with a Lack of Central Serotonin.

Isolation rearing (IR) enhances aggressive behavior, and the central serotonin (5-hydroxytryptamine, 5-HT) system has been linked to IR-induced aggression. However, whether the alteration of central serotonin is the cause or consequence of enhanced aggression is still unknown. In the present study, using mice deficient in central serotonin Tph2-/- and Lmx1b-/-, we examined the association between central serotonin and aggression with or without social isolation. We demonstrated that central serotonergic neurons are critical for the enhanced aggression after IR. 5-HT depletion in wild-type mice increased aggression. On the other hand, application of 5-HT in Lmx1b-/- mice inhibited the enhancement of aggression under social isolation conditions. Dopamine was downregulated in Lmx1b-/- mice. Similar to 5-HT, L-DOPA decreased aggression in Lmx1b-/- mice. Our results link the serotoninergic system directly to aggression and this may have clinical implications for aggression-related human conditions.

Different effects of propofol and dexmedetomidine sedation on electroencephalogram patterns: Wakefulness, moderate sedation, deep sedation and recovery.

Sedation induces changes in electroencephalography (EEG) dynamics. However, the distinct EEG dynamic characteristics at comparable sedation levels have not been well studied, resulting in potential interpretation errors in EEG monitoring during sedation. We aimed to analyze the EEG dynamics of dexmedetomidine and propofol at comparable sedation levels and to explore EEG changes with increased sedation levels for each agent. We measured the Bispectral Index (BIS) and 20-channel EEG under dexmedetomidine and propofol sedation from wakefulness, moderate sedation, and deep sedation to recovery in healthy volunteers (n = 10) in a randomized, 2-day, crossover study. Observer's Assessment of Alertness and Sedation (OAA/S) score was used to assess sedation levels. Despite similar changes in increased delta oscillations, multiple differences in the EEG spatiotemporal dynamics were observed between these two agents. During moderate sedation, both dexmedetomidine and propofol induced increased spindle power; however, dexmedetomidine decreased the global alpha/beta/gamma power, whereas propofol decreased the alpha power in the occipital area and increased the global spindle/beta/gamma power. During deep sedation, dexmedetomidine was associated with increased fronto-central spindle power and decreased global alpha/beta/gamma power, but propofol was associated with increased theta/alpha/spindle/beta power, which was maximized in the frontal area. The transition of topographic alpha/spindle/beta power distribution from moderate sedation to deep sedation completely differed between these two agents. Our study demonstrated that there was a distinct hierarchy of EEG changes with increased sedation depths by propofol and dexmedetomidine. Differences in EEG dynamics at the same sedation level might account for differences in the BIS value and reflect the different sedation mechanisms. EEG-based clinical sedation monitoring should consider the effect of drug types on EEG dynamics.

Acupuncture and Lifestyle Myopia in Primary School Children-Results from a Transcontinental Pilot Study Performed in Comparison to Moxibustion.

Background: Lifestyle risks for myopia are well known and the disease has become a major global public health issue worldwide. There is a relation between reading, writing, and computer work and the development of myopia. Methods: Within this prospective pilot study in 44 patients aged between 6 and 12 years with myopia we compared possible treatment effects of acupuncture or moxibustion. The diopters of the right and left eye were evaluated before and after the two treatment methods. Results: Myopia was improved in 14 eyes of 13 patients (15.9%) within both complementary methods. Using acupuncture an improvement was observed in seven eyes from six patients out of 22 patients and a similar result (improvement in seven eyes from seven patients out of 22 patients) was noticed in the moxibustion group. The extent of improvement was better in the acupuncture group (p = 0.008 s., comparison before and after treatment); however, group analysis between acupuncture and moxibustion revealed no significant difference. Conclusions: Possible therapeutic aspects with the help of evidence-based complementary methods like acupuncture or moxibustion have not yet been investigated adequately in myopic patients. Our study showed that both acupuncture and moxibustion can improve myopia of young patients. Acupuncture seems to be more effective than moxibustion in treating myopia, however group analysis did not prove this trend. Therefore, further Big data studies are necessary to confirm or refute the preliminary results.

Comparison of NREM sleep and intravenous sedation through local information processing and whole brain network to explore the mechanism of general anesthesia.

BACKGROUND: The mechanism of general anesthesia (GA) has been explored for hundreds of years, but unclear. Previous studies indicated a possible correlation between NREM sleep and GA. The purpose of this study is to compare them by in vivo human brain function to probe the neuromechanism of consciousness, so as to find out a clue to GA mechanism. METHODS: 24 healthy participants were equally assigned to sleep or propofol sedation group by sleeping ability. EEG and Ramsay Sedation Scale were applied to determine sleep stage and sedation depth respectively. Resting-state functional magnetic resonance imaging (RS-fMRI) was acquired at each status. Regional homogeneity (ReHo) and seed-based whole brain functional connectivity maps (WB-FC maps) were compared. RESULTS: During sleep, ReHo primarily weakened on frontal lobe (especially preoptic area), but strengthened on brainstem. While during sedation, ReHo changed in various brain areas, including cingulate, precuneus, thalamus and cerebellum. Cingulate, fusiform and insula were concomitance of sleep and sedation. Comparing to sleep, FCs between the cortex and subcortical centers (centralized in cerebellum) were significantly attenuated under sedation. As sedation deepening, cerebellum-based FC maps were diminished, while thalamus- and brainstem-based FC maps were increased. CONCLUSION: There're huge distinctions in human brain function between sleep and GA. Sleep mainly rely on brainstem and frontal lobe function, while sedation is prone to affect widespread functional network. The most significant differences exist in the precuneus and cingulate, which may play important roles in mechanisms of inducing unconciousness by anesthetics. TRIAL REGISTRATION: Institutional Review Board (IRB) ChiCTR-IOC-15007454.

Goal-directed fluid therapy for reducing risk of surgical site infections following abdominal surgery - A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Surgical site infections (SSIs) become a key indicator of quality of care. This meta-analysis aimed to determine the effect of goal-directed fluid therapy (GDFT) on the risk of SSIs after abdominal surgery. METHODS: MEDLINE, Embase, CINAHL, Scopus, the Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews were searched for randomized controlled trials (RCTs), from inception to May 2016 that compared the incidence of SSIs in abdominal surgical patients with or without GDFT treatment. . Data were pooled and risk ratio (RR) as well as weighted mean differences (WMD) with their 95% confidence intervals (CI) was calculated using either fixed or random effects models, depending on heterogeneity (I2). RESULTS: A total of 29 eligible RCTs with 5317 patients were included in this analysis. GDFT significantly reduced the incidence of SSIs after abdominal surgery. The pooled RR was 0.74 (95% CI: 0.63 to 0.86) with low heterogeneity (I2 = 4%). Length of hospital stay was significantly reduced in the GDFT group (WMD: -1.16 days, 95% CI: -1.92 to -0.40, p = 0.003; I2 = 81%). CONCLUSION: This systematic review suggests that perioperative GDFT is associated with a reduction in the incidence of SSIs after abdominal surgery.

The Role of Obstruction Length and Height in Predicting Outcome of Velopharyngeal Surgery.

OBJECTIVE: To measure obstruction length and height using drug-induced sleep endoscopy (DISE) in obstructive sleep apnea (OSA) patients and to evaluate their association with outcomes of velopharyngeal surgery. STUDY DESIGN: Prospective cohort study. SETTING: University medical center. METHODS: Forty-three consecutive patients with OSA were evaluated by DISE using dexmedetomidine. The 2 new parameters, obstruction length (defined as the distance from the most superior point of the collapse to the most inferior point of the collapse) and obstruction height (the distance from the posterior border of the nasal septum to the most proximal point of the collapse), were measured by both DISE and a pressure transducer catheter method before surgery. All of the patients received velopharyngeal surgery, including revised uvulopalatopharyngoplasty with uvula preservation and transpalatal advancement pharyngoplasty. We followed up with all of the patients using polysomnography at least 3 months after surgery. RESULTS: Twenty-six (60.5%) patients were responders, and 17 (39.5%) were nonresponders. The mean obstruction length and obstruction height were 1.3 ± 0.5 cm (range, 0.4-2.2 cm) and 3.4 ± 0.9 cm (range, 1.1-5.0 cm), respectively. Nonresponders had a longer obstruction length and a shorter obstruction value. Multivariate logistic regression analysis revealed that obstruction length >1.4 cm (odds ratio [OR], 0.21; 95% confidence interval [CI], 0.04-0.98; P = .048) and obstruction height ≥3.2 cm (OR, 9.35; 95% CI, 1.79-48.80; P = .008) were the only independent predictors of velopharyngeal surgery success. CONCLUSIONS: Accurate measurement of obstruction length and height can be performed with both DISE and a pressure transducer catheter method. The 2 parameters can predict the outcome of velopharyngeal surgery.

Different effects of anesthetic isoflurane on caspase-3 activation and cytosol cytochrome c levels between mice neural progenitor cells and neurons.

Commonly used anesthetic isoflurane has been reported to promote Alzheimer's disease (AD) neuropathogenesis by inducing caspase-3 activation. However, the up-stream mechanisms of isoflurane's effects remain largely to be determined. Specifically, there is a lack of a good model/system to elucidate the underlying mechanism of the isoflurane-induced caspase-3 activation. We therefore set out to assess and compare the effects of isoflurane on caspase-3 activation in neural progenitor cells (NPCs) and in primary neurons from wild-type (WT) and AD transgenic (Tg) mice. The NPCs and neurons were obtained, cultured and then treated with either 2% isoflurane or under control condition for 6 h. The NPCs or neurons were harvested at the end of the treatment and were subjected to Western blot analysis. Here we showed for the first time that the isoflurane treatment induced caspase-3 activation in neurons, but not in NPCs, from either WT or AD Tg mice. Consistently, the isoflurane treatment increased cytosol levels of cytochrome c, a potential up-stream mechanism of isoflurane-induced caspase-3 activation in the mice neurons, but not NPCs. Finally, the isoflurane treatment induced a greater casapse-3 activation in the neurons, but not the NPCs, from AD Tg mice as compared to the WT mice. These data demonstrated that investigation and comparison of isoflurane's effects between mice NPCs and neurons would serve as a model/system to determine the underlying mechanism by which isoflurane induces caspase-3 activation. These findings would promote more research to investigate the effects of anesthetics on AD neuropathogenesis and the underlying mechanisms.

The potential dual effects of anesthetic isoflurane on Aß-induced apoptosis.

ß-amyloid protein (Aß)-induced neurotoxicity is the main component of Alzheimer's disease (AD) neuropathogenesis. Inhalation anesthetics have long been considered to protect against neurotoxicity. However, recent research studies have suggested that the inhalation anesthetic isoflurane may promote neurotoxicity by inducing apoptosis and increasing Aß levels. We therefore set out to determine whether isoflurane can induce dose- and time-dependent dual effects on Aß-induced apoptosis: protection versus promotion. H4 human neuroglioma cells, primary neurons from naive mice, and naive mice were treated with Aß and/or isoflurane, and levels of caspase-3 cleavage (activation), apoptosis, Bcl-2, Bax, and cytosolic calcium were determined. Here we show for the first time that the treatment with 2% isoflurane for six hours or 30 minutes potentiated, whereas the treatment with 0.5% isoflurane for six hours or 30 minutes attenuated, the Aß-induced caspase-3 activation and apoptosis in vitro. Moreover, anesthesia with 1.4% isoflurane for two hours potentiated, whereas the anesthesia with 0.7% isoflurane for 30 minutes attenuated, the Aß-induced caspase-3 activation in vivo. The high concentration isoflurane potentiated the Aß-induced reduction in Bcl-2/Bax ratio and caused a robust elevation of cytosolic calcium levels. The low concentration isoflurane attenuated the Aß-induced reduction in Bcl-2/Bax ratio and caused only a mild elevation of cytosolic calcium levels. These results suggest that isoflurane may have dual effects (protection or promotion) on Aß-induced toxicity, which potentially act through the Bcl-2 family proteins and cytosolic calcium. These findings would lead to more systematic studies to determine the potential dual effects of anesthetics on AD-associated neurotoxicity.