Effects of individualized positive end-expiratory pressure on intraoperative oxygenation and postoperative pulmonary complications in patients requiring pneumoperitoneum with Trendelenburg position: A systematic review and meta-analysis.

BACKGROUND: Whether individualized positive end-expiratory pressure (PEEP) improves intraoperative oxygenation and reduces postoperative pulmonary complications (PPCs) remains unclear. This systematic review and meta-analysis examined whether individualized PEEP is associated with improved intraoperative oxygenation and reduce PPCs for patients needing pneumoperitoneum with the Trendelenburg position during surgery. METHODS: Medline, Embase, the Cochrane Library, and www.clinicaltrials.gov were searched for randomized controlled trials evaluating the effects of individualized PEEP on intraoperative oxygenation and PPCs in patients who required Trendelenburg positioning with pneumoperitoneum. The primary outcome was the oxygenation (PaO2/FiO2) during the procedure. Secondary outcomes included PPCs, intraoperative respiratory mechanics (driving pressure, compliance), and vasopressor consumption. DerSimonian-Laird random effects models were used to calculate mean differences (MDs) and log risk ratios (log RRs) with 95% confidence intervals (CIs). The Cochrane Risk-of-Bias tool 2.0 was applied to assess the risk of bias in included studies. The protocol of this meta-analysis has been registered in PROSPERO. RESULTS: We included 14 studies (1121 patients) that employed different individualized PEEP strategies. Compared with control groups, individualized PEEP groups exhibited a significantly improved intraoperative PaO2/FiO2 (MD=56.52 mm Hg, 95% CI: [33.98, 79.06], P<0.001) and reduced incidence of PPCs (log RR=-0.50, 95% CI: [-0.84, -0.16], P=0.004). Individualized PEEP reduced driving pressure while improving respiratory compliance. Intraoperative vasopressor consumption was similar between both groups. The weighted mean PEEP in the individual PEEP groups was 13.2 [95% CI, 11.7, 14.6] cmH2O. No evidence indicated that one individualized PEEP strategy is superior to others. CONCLUSIONS: Individualized PEEP seems to work positively for lung protection in the Trendelenburg position and pneumoperitoneum in patients undergoing general anesthesia.

Neural Network Mechanisms Underlying General Anesthesia: Cortical and Subcortical Nuclei.

General anesthesia plays a significant role in modern medicine. However, the precise mechanism of general anesthesia remains unclear, posing a key scientific challenge in anesthesiology. Advances in neuroscience techniques have enabled targeted manipulation of specific neural circuits and the capture of brain-wide neural activity at high resolution. These advances hold promise for elucidating the intricate mechanisms of action of general anesthetics. This review aims to summarize our current understanding of the role of cortical and subcortical nuclei in modulating general anesthesia, providing new evidence of cortico-cortical and thalamocortical networks in relation to anesthesia and consciousness. These insights contribute to a comprehensive understanding of the neural network mechanisms underlying general anesthesia.

Rationally Designed Highly Potent NKT Cell Agonists with Different Cytokine Selectivity through Hydrogen-Bond Interaction.

Synthetic α-galactosylceramide (αGalCer) and its analogues as powerful agonists for natural killer T (NKT) cell manipulation have received significant attention in immunotherapy and adjuvant development. However, identifying new potent NKT cell agonists, especially those with Th1 selectivity that promote anticancer effects, remains a challenging task. In this work, we introduced a sulfonamide group into the acyl chain of αGalCer to form additional hydrogen bonds to intensify the glycolipid/CD1d interaction. Two compounds GCS-11 and GCS-12 demonstrated remarkable potency while exhibiting different cytokine induction patterns. Compared to αGalCer, the Th1-biased GCS-11 exhibited a 6-fold increase in IFN-γ but not IL-4, while the Th1/2-balanced GCS-12 elicited 7- and 5-fold increase in IFN-γ and IL-4, respectively, in vivo. These findings place them among the most potent NKT cell agonists, with superior antitumor effects. Therefore, hydrogen-bond-involved derivatization could be a powerful strategy to develop potent and polarized NKT cell agonists for various immunotherapies.

Characteristics associated with effectiveness in postoperative delirium research: a systematic review of randomised controlled trials with meta-regression and meta-analysis.

BACKGROUND: Postoperative delirium remains prevalent despite extensive research through randomised trials aimed at reducing its incidence. Understanding trial characteristics associated with interventions' effectiveness facilitates data interpretation. METHODS: Trial characteristics were extracted from eligible trials identified through two systematic literature searches. Multivariable meta-regression was used to investigate trial characteristics associated with effectiveness estimated using odds ratios. Meta-analysis was used to investigate pooled effectiveness. RESULTS: We identified 201 eligible trials. Compared with China, trials from the USA/Canada (ratio of odds ratio, 1.89; 95% confidence interval, 1.45-2.45) and Europe/Australia/New Zealand (1.67; 1.29-2.18) had an 89% and 67% higher odds ratio, respectively, suggesting reduced effectiveness. The effectiveness was enhanced when the incidence of postoperative delirium increased (0.85; 0.79-0.92, per 10% increase). Trials with concerns related to deviations from intended interventions reported increased effectiveness compared with those at low risk (0.69; 0.53-0.90). Compared with usual care, certain interventions appeared to have reduced the incidence of postoperative delirium in low-risk trials with low-to-moderate certainty of evidence. However, these findings should be considered inconclusive because of challenges in grouping heterogeneous interventions, the limited number of eligible trials, the prevalence of small-scale studies, and potential publication bias. CONCLUSIONS: The effectiveness of postoperative delirium trials varied based on the region of trial origin, the incidence of delirium, and the risk of bias. The limitations caution against drawing definitive conclusions from different bodies of evidence. These findings highlight the imperative need to improve the quality of research on a global scale. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023413984).

Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain.

Ketamine (KET) and isoflurane (ISO) are two widely used general anesthetics, yet their distinct and shared neurophysiological mechanisms remain elusive. In this study, we conducted a comparative analysis of the effects of KET and ISO on c-Fos expression across the mouse brain, utilizing hierarchical clustering and c-Fos-based functional network analysis to evaluate the responses of individual brain regions to each anesthetic. Our findings reveal that KET activates a wide range of brain regions, notably in the cortical and subcortical nuclei involved in sensory, motor, emotional, and reward processing, with the temporal association areas (TEa) as a strong hub, suggesting a top-down mechanism affecting consciousness by primarily targeting higher order cortical networks. In contrast, ISO predominantly influences brain regions in the hypothalamus, impacting neuroendocrine control, autonomic function, and homeostasis, with the locus coeruleus (LC) as a connector hub, indicating a bottom-up mechanism in anesthetic-induced unconsciousness. KET and ISO both activate brain areas involved in sensory processing, memory and cognition, reward and motivation, as well as autonomic and homeostatic control, highlighting their shared effects on various neural pathways. In conclusion, our results highlight the distinct but overlapping effects of KET and ISO, enriching our understanding of the mechanisms underlying general anesthesia.

The effect of restrictive vs. liberal fluid protocols on ocular parameters in patients undergoing prone spine surgery: a randomized controlled trial.

BACKGROUND: Elevated intraocular pressure (IOP) and optic nerve edema occurring during prone surgeries may cause ocular and optic nerve ischaemia injury. We hypothesized that a liberal fluid protocol might further increase IOP and optic nerve sheath diameter (ONSD) than a restrictive fluid protocol for patients in the prone position. METHODS: A single-centre, prospective and randomized trial was conducted. Patients were randomly allocated into 2 groups: the liberal fluid infusion group, in which repeated bolus doses of Ringer's lactate solution were given to maintain pulse pressure variation (PPV) within 6~9%, and the restrictive fluid infusion group, where PPV was maintained within 13-16%. IOP and ONSD were measured in both eyes at 10min after the anaesthesia induction in the supine position, 10min after the prone position placement, and 1h and 2h since the prone position was placed, at the conclusion of surgery, and returned to the supine position. RESULTS: A total of 97 patients were recruited and completed the study. IOP increased significantly from 12±3mmHg in the supine position to 31±5 mmHg (p<0.001) at the end of surgery in the liberal fluid infusion group and from 12±2 to 28±4 mmHg (p<0.001) in the restrictive fluid infusion group. There was a statistically significant difference in the change of IOP over time between the two groups (p=0.019). ONSD increased significantly from 5.3±0.3mm in the supine position to 5.5±0.3mm (p<0.001) at the end of surgery in both groups (both p<0.001). There was no statistically significant difference in the change of ONSD over time between the two groups (p>0.05). CONCLUSIONS: Compared to the restrictive fluid protocol, the liberal fluid protocol increased IOP but not ONSD in patients undergoing prone spine surgery. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov ( https://clinicaltrials.gov ) prior to patient enrollment, ID: NCT03890510, on March 26, 2019. The principal investigator was Xiao-Yu Yang.

Divergent Neural Activity in the VLPO During Anesthesia and Sleep.

The invention of general anesthesia (GA) represents a significant advance in modern clinical practices. However, the exact mechanisms of GA are not entirely understood. Because of the multitude of similarities between GA and sleep, one intriguing hypothesis is that anesthesia may engage the sleep-wake regulation circuits. Here, using fiber photometry and micro-endoscopic imaging of Ca2+ signals at both population and single-cell levels, it investigates how various anesthetics modulate the neural activity in the ventrolateral preoptic nucleus (vLPO), a brain region essential for the initiation of sleep. It is found that different anesthetics primarily induced suppression of neural activity and tended to recruit a similar group of vLPO neurons; however, each anesthetic caused comparable modulations of both wake-active and sleep-active neurons. These results demonstrate that anesthesia creates a different state of neural activity in the vLPO than during natural sleep, suggesting that anesthesia may not engage the same vLPO circuits for sleep generation.

The effectiveness of scalp nerve block on hemodynamic response in craniotomy: a systematic review and meta-analysis of randomized trials.

INTRODUCTION: Strategies that blunt noxious stimuli and stabilize hemodynamics may reduce perioperative cardiovascular complications and enhance recovery after craniotomy. EVIDENCE ACQUISITION: Our systematic literature review and meta-analysis investigated whether scalp nerve block (SNB) reduces the acute hemodynamic response compared with non-SNB (scalp infiltration or control) in adult patients undergoing elective craniotomy. We searched MEDLINE, EMBASE, CENTRAL, and two Chinese databases for randomized trials. Primary outcomes included mean arterial pressure and heart rate during skull pin insertion and surgical incision in craniotomy. Secondary outcomes included incidence of hypertension and dosage of intraoperative analgesic opioids used. Random-effects models were used for meta-analyses. EVIDENCE SYNTHESIS: SNB significantly reduced the mean arterial pressure (mean difference: -14.00 mmHg; 95% confidence interval [CI]: -19.71 to -8.28) and heart rate (mean difference: -11.55 beat/min; 95% CI: -19.31 to -3.80), when compared with non-SNB during skull pin insertion. A similar trend was observed during skin incisions (SNB vs. non-SNB, mean difference in mean arterial pressure: -9.46 mmHg; 95% CI: -14.53 to -4.38; mean difference in heart rate: -9.34 beat/min; 95% CI: -15.40 to -3.28). Subgroup analysis showed that, compared with scalp infiltration, SNB reduced mean arterial pressure and heart during pin insertion but not during skin incisions. SNB also reduced the incidence of intraoperative hypertension, but no difference was observed in intraoperative opioid consumption when compared with non-SNB. CONCLUSIONS: SNB alleviated the craniotomy-associated hemodynamic response. SNB may be superior to scalp infiltration in maintaining hemodynamic stability during pin insertion. However, high-quality trials are still needed to provide more conclusive evidence.

Scalp Nerve Block, Local Anesthetic Infiltration, and Postoperative Pain After Craniotomy: A Systematic Review and Network Meta-analysis of Randomized Trials.

The most efficacious methods for controlling postoperative pain in craniotomy remain unknown. A systematic review and network meta-analysis were performed to compare the efficacies of different strategies of scalp nerve block (SNB), scalp infiltration (SI), and control in patients undergoing craniotomy. MEDLINE, Embase, and CENTRAL databases were searched for randomized controlled trials. The primary outcome was postoperative 24-hour pain score, and the secondary outcome was opioid consumption within the first 24 hour after surgery. The effect was estimated using the between-group mean difference and ranked using the surface under the cumulative ranking curve (SUCRA) score. Twenty-four randomized trials were identified for inclusion. SNB using ropivacaine reduced postoperative 24-hour pain score when compared with control (mean difference [95% credible interval], -2.04 [-3.13, -0.94]; low quality), and when compared with SI using ropivacaine (-1.77 [-3.04, -0.51]; low quality) or bupivacaine (-1.96 [-3.65, -0.22]; low quality). SNB using ropivacaine was likely the most efficacious method for pain control (SUCRA, 91%), and also reduced opioid consumption within the first postoperative 24 hours as compared with control (mean difference [95% credible interval], -11.91 [-22.42, -1.4]; low quality). SNB using bupivacaine, lidocaine, and epinephrine combined, and SNB using ropivacaine, were likely the most efficacious methods for opioid consumption reduction (SUCRA, 88% and 80%, respectively). In summary, different methods of SNB / SI seem to have different efficacies after craniotomy. SNB using ropivacaine may be superior to other methods for postcraniotomy pain control; however, the overall quality of evidence was low.

Effect of scalp nerve block with ropivacaine on postoperative pain in pediatric patients undergoing craniotomy: A randomized controlled trial.

Background: Scalp nerve block (SNB) is widely used for postoperative pain control, intraoperative hemodynamic control, and opioid-sparing in adult craniotomies. However, there are few studies of SNB in pediatric patients undergoing craniotomy. In the present study, we aimed to investigate the effect of SNB on postoperative pain, intraoperative hemodynamic stability, and narcotic consumption in pediatric craniotomy under general anesthesia. Methods: This trial is a single-center, prospective, randomized, and double-blind study. A total of 50 children aged between 2 and 12 years who are undergoing elective brain tumor surgery will be randomly allocated in a 1:1 ratio to receive either 0.2% ropivacaine for SNB (group SNB, intervention group, n = 25) or the same volume of saline (group Ctrl, control group, n = 25). The primary outcome was to assess the score of postoperative pain intensity at time 1, 4, 8, 12, 24, and 48 h postoperatively using the FLACC score method. Secondary outcomes were to record intraoperative hemodynamic variables (MAP and HR) during skull-pin fixation, skin incision and end of skin closure, intraoperative total consumption of remifentanil and propofol, postoperative opioid consumption, and the incidence of postoperative nausea and vomiting. Results: Fifty patients were analyzed (n = 25 in SNB group; n = 25 in control group). Compared to the control group, postoperative pain intensity was significantly relieved in the SNB group up to 8 h post-operatively. In addition, SNB provided good intraoperative hemodynamic stability, reduced intraoperative overall propofol and remifentanil consumption rate, and postoperative fentanyl consumption compared to the control group. However, the incidence of postoperative nausea and vomiting was not different between SNB and the control group. Conclusions: In pediatric craniotomies, SNB with 0.2% ropivacaine provides adequate postoperative pain control and good intraoperative hemodynamic stability during noxious events compared to the control group. Clinical trial registration: Chinese Clinical Trial Registry [No: ChiCTR2100050594], Prospective registration.

CuCl2·2H2O/TBHP mediated synthesis of ß-enaminones via coupling reaction of vinyl azides with aldehydes.

A facile and efficient oxidative functionalization of vinyl azides with aldehydes furnishing a diverse array of ß-acylated enaminones was developed. The cross coupling was accomplished in the presence of CuCl2·2H2O/TBHP and produced the desired ß-acylated enaminones in a (Z)-stereo-selective and atom-economic manner, which make this protocol particularly attractive. In the transformation, the new C-C and C-N bonds were formed via a one-pot strategy including the process of radical addition and recombination.

H2O2-mediated room temperature synthesis of 2-arylacetophenones from arylhydrazines and vinyl azides in water.

An environmentally benign, cost-efficient and practical methodology for the room temperature synthesis of 2-arylacetophenones in water has been discovered. The facile and efficient transformation involves the oxidative radical addition of arylhydrazines with α-aryl vinyl azides in the presence of H2O2 (as a radical initiator) and PEG-800 (as a phase-transfer catalyst). From the viewpoint of green chemistry and organic synthesis, the present protocol is of great significance because of using cheap, non-toxic and readily available starting materials and reagents as well as amenability to gram-scale synthesis, which provides an attractive strategy to access 2-arylacetophenones.

Facile, eco-friendly, catalyst-free synthesis of polyfunctionalized quinoxalines.

A novel, facile and eco-friendly synthesis of quinoxalines from [Formula: see text] and 1,2-diamines was developed. An attractive feature of this protocol is that the desired products could be generated efficiently in water and without any catalyst, which is in accordance with the aim of green chemistry. A plausible mechanism has been proposed.

Comparison of Ultrasonography-guided Bilateral Intercostal Nerve Blocks and Conventional Patient-controlled Intravenous Analgesia for Pain Control After the Nuss Procedure in Children: A Prospective Randomized Study.

OBJECTIVES: Patients experience severe pain after pectus excavatum (PE) surgery. The aim of this prospective, randomized study was to compare analgesic effects of ultrasonography-guided bilateral intercostal nerve blocks (UG-ICNBs) with those of conventional patient-controlled intravenous analgesia (PCIA) on acute pain after the Nuss procedure for PE repair in children. METHODS: A prospective randomized study was performed in children with PE who were scheduled for the Nuss procedure. Participants were randomly assigned to receive either UG-ICNBs or PCIA for postoperative analgesia. Faces Pain Scale-Revised scores, opioid consumption, analgesia-associated side effects (respiratory depression, pruritus, nausea, vomiting) during the first 24 hours, and lengths of stay in the postanesthesia care unit (PACU) and hospital were recorded after the surgery. RESULTS: Sixty-two children undergoing the Nuss procedure were enrolled in the trial. Faces Pain Scale-Revised scores were significantly decreased in the UG-ICNBs group compared with the PCIA group for up to 6 hours after surgery. The opioid doses required in the PACU and during the first 24 hours after surgery were significantly greater in the PCIA group compared with the UG-ICNBs group. Accordingly, patients in the UG-ICNBs group showed a lower incidence of analgesia-associated side effects and faster PACU discharge compared with the PCIA group. CONCLUSIONS: Our study suggests that UG-ICNBs might be more effective than PCIA for postoperative analgesia in children who undergo the Nuss procedure for PE.

Propofol post-conditioning induced long-term neuroprotection and reduced internalization of AMPAR GluR2 subunit in a rat model of focal cerebral ischemia/reperfusion.

We previously reported that propofol (20 mg/kg/h) post-conditioning provided acute (up to 24 h) neuroprotection in rats with transient middle cerebral artery occlusion. In this study, we extend these data by examining long-term protection and exploring underlying mechanisms involving AMPA receptor GluR2 subunit internalization. Rats were treated with propofol 20 mg/kg/h after 60 min of occlusion (beginning of reperfusion for 4 h). Propofol post-conditioning reduced infarct volume and improved spatial memory deficiencies (up to 28 days) induced by ischemia/reperfusion injury. Additionally, Propofol post-conditioning promoted neurogenesis in the dentate gyrus of hippocampus, as measured by bromodeoxyuridine and neuron-specific nuclear protein immunofluorescence-double staining at day 28 after reperfusion. Finally, propofol post-conditioning increased the surface expression of AMPA receptor GluR2 subunit, thus inhibited the internalization of this part until 28 days after stroke. In conclusion, our data suggest that propofol post-conditioning provides long-term protection against focal cerebral ischemia/reperfusion injury in rats. Furthermore, we found that the inhibition of AMPA receptor GluR2 subunit internalization may contributed to this long-term neuroprotection.