Nerve Growth Factor/Tyrosine Kinase A Receptor Pathway Enhances Analgesia in an Experimental Mouse Model of Bone Cancer Pain by Increasing Membrane Levels of δ-Opioid Receptors.

BACKGROUND: The role of nerve growth factor (NGF)/tyrosine kinase A receptor (TrKA) signaling, which is activated in a variety of pain states, in regulating membrane-associated δ-opioid receptor (mDOR) expression is poorly understood. The hypothesis was that elevated NGF in bone cancer tumors could upregulate mDOR expression in spinal cord neurons and that mDOR agonism might alleviate bone cancer pain. METHODS: Bone cancer pain (BCP) was induced by inoculating Lewis lung carcinoma cells into the femoral marrow cavity of adult C57BL/6J mice of both sexes. Nociceptive behaviors were evaluated by the von Frey and Hargreaves tests. Protein expression in the spinal dorsal horn of animals was measured by biochemical analyses, and excitatory synaptic transmission was recorded in miniature excitatory synaptic currents. RESULTS: The authors found that mDOR expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.18 ± 0.01 g vs. mean ± SD: 0.13 ± 0.01 g, n = 4, P < 0.001) and that administration of the DOR agonist deltorphin 2 (Del2) increased nociceptive thresholds (Del2 vs. vehicle, median [25th, 75th percentiles]: 1.00 [0.60, 1.40] g vs. median [25th, 75th percentiles]: 0.40 [0.16, 0.45] g, n = 10, P = 0.001) and reduced miniature excitatory synaptic current frequency in lamina II outer neurons (Del2 vs. baseline, mean ± SD: 2.21 ± 0.81 Hz vs. mean ± SD: 2.43 ± 0.90 Hz, n = 12, P < 0.001). Additionally, NGF expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.36 ± 0.03 vs. mean ± SD: 0.16 ± 0.02, n = 4, P < 0.001), and elevated NGF was associated with enhanced mDOR expression via TrKA signaling. CONCLUSIONS: Activation of mDOR produces analgesia that is dependent on the upregulation of the NGF/TrKA pathway by increasing mDOR levels under conditions of BCP in mice.

ABO blood types may affect transient neurological events after surgical revascularization in patients with moyamoya disease: a retrospective single center study.

BACKGROUND: Moyamoya disease (MMD) is a cerebrovascular disease with unknown cause. Patients with MMD disease usually experience transient neurological events (TNEs) after revascularization surgery. This retrospective single-center study was aimed to explore the risk factors of postoperative TNEs after surgical revascularization in patients with MMD. METHODS: We selected 324 patients who underwent surgical revascularization between January 2017 and September 2022 in our center. The perioperative characteristics of the patients were recorded and the outcome was TNEs after surgery. An analysis of risk factors contributing to postoperative TNEs by using logistic regression model. RESULTS: Three hundred twelve patients were enrolled, and the incidence of postoperative TNEs was 34% in our study. Males were more likely to suffer from postoperative TNEs (OR = 2.344, p = 0.002). Preoperative ischemic presentation (OR = 1.849, p = 0.048) and intraoperative hypotension (OR = 2.332, p = 0.002) were associated with postoperative TNEs. Compared to patients with blood type O, patients with blood type A (OR = 2.325, p = 0.028), B (OR = 2.239, p = 0.027) and AB (OR = 2.938, p = 0.019) had a significantly higher incidence of postoperative TNEs. A risk prediction model for postoperative TNEs was established, and the established risk prediction area under the receiver operating characteristic curve (ROC) of the model was 0.741. CONCLUSIONS: Males, preoperative ischemic presentation and intraoperative hypotension were associated with postoperative TNEs. We also found a possible link between postoperative TNEs and ABO blood types after surgical revascularization for moyamoya patients.

The duration of chronic low back pain is associated with acute postoperative pain intensity in lumbar fusion surgery: a prospective observational study.

BACKGROUND: Pre-existing chronic pain has been associated with severe postoperative pain. In this study, we sought to prospectively analyse the association between the duration of chronic low back pain and the intensity of acute postoperative pain after lumbar fusion surgery. METHODS: A total of 330 patients who underwent lumbar fusion surgery were divided into three groups (chronic low back pain less than 1 year, one to 5 years, and more than 5 years) based on the duration of chronic pain. On the first postoperative day, the maximum pain scores of each patient were recorded during the day and at night. Bivariate correlation and logistic regression were performed to identify relationships between acute postoperative pain and related variables (age, sex, smoking history, body mass index, operation history, duration of surgery, level of preoperative pain, aetiology of back pain, Self-rating Anxiety Scale, Self-rating Depression Scale, FRAIL scale, and duration of chronic low back pain). If the postoperative pain score was > 3 when the patient reported was at rest, the patients were treated with postoperative intravenous self-controlled analgesia or rescue analgesics if necessary. RESULTS: There was an association between severe acute postoperative pain and the duration of chronic low back pain. In terms of VAS day, multivariable logistic regression showed the duration of chronic low back pain was not statistically significant (OR = 2.48, 95% CI: 0.900 to 6.828, p = 0.0789). The result is uncertain because the confidence interval included the null after controlling for SAS, SDS, BMI, and aetiology of back pain. In terms of VAS night, patients with a duration of chronic low back pain of more than 5 years were more likely having moderate to severe acute postoperative pain (VAS > 3) compared to patients with a duration of chronic low back pain less than 1 year (OR = 3.546, 95% CI: 1.405 to 8.95, p = 0.0074). Hospital stay, the pain score on the day of discharge and the pain score after 3 months displayed no significant difference among the three groups (P > 0.05). However, the need for postoperative rescue analgesics was different among the three groups (P < 0.05). CONCLUSION: The longer the duration of chronic pain was, the higher the incidence of moderate to severe acute postoperative pain was and the greater the amount of analgesics required after surgery. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registration Center ( http://www.chictr.org.cn/index.aspx , clinical trial number: ChiECRCT20200165, date of registration: July 6, 2020).

Remifentanil requirement for i-gel insertion is reduced in male patients with Parkinson's disease undergoing deep brain stimulator implantation: an up-and-down sequential allocation trial.

BACKGROUND: Laryngeal mask airways have been widely used in clinical practice. The aim of this study was to investigate whether the remifentanil requirement for facilitation of i-gel insertion in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery was different from that in non-PD (NPD) patients undergoing intracranial surgery. STUDY DESIGN: An up-and-down sequential allocation trial. METHODS: Male patients aged between 40 and 64 years old were enrolled. The first patient in each group (PD and NPD) group received an effect-site concentration (Ce) of remifentanil (Minto pharmacokinetic model) of 4.0 ng.ml-1 during a target-controlled infusion (TCI) of 3.5 µg.ml-1 propofol (Marsh pharmacokinetic model). The next dose of remifentanil was determined by the response of the previous patient. The Ce of remifentanil required for i-gel insertion in 50% of patients (EC50) was estimated by the modified Dixon's up-and-down method and by probit analysis. RESULTS: The PD group included 24 patients and the NPD group included 23. The EC50 of remifentanil for i-gel insertion during a TCI of 3.5 µg.ml-1 propofol estimated by the modified Dixon's up-and-down method in PD patients (2.38 ± 0.65 ng.ml-1) was significantly lower than in NPD patients (3.21 ± 0.49 ng.ml-1) (P = 0.03). From the probit analysis, the EC50 and EC95 (effective Ce in 95% of patients) of remifentanil were 1.95 (95% CI 1.52-2.36) ng.ml-1 and 3.12 (95% CI 2.53-5.84) ng.ml-1 in PD patients and 2.85 (95% CI 2.26-3.41) ng.ml-1 and 4.57 (95% CI 3.72-8.54) ng.ml-1 in NPD patients, respectively. CONCLUSIONS: The remifentanil requirement for successful i-gel insertion is reduced in male PD patients undergoing DBS implantation during propofol TCI induction. Clinicians should closely monitor the remifentanil requirement in patients with PD. TRIAL REGISTRATION: Registered at http://www.chictr.org.cn ( ChiCTR1900021760 ).

Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway.

BACKGROUND: Morphine, a µ-opioid receptor (MOR) agonist, has been shown to be related to the activity of cancer cells, and a higher morphine dosage reduces the survival time of patients with lung cancer. However, the effect of morphine on the malignant behavior of lung cancer cells remains unclear. The aim of this study was to investigate the specific molecular mechanism by which morphine regulates the malignant biological behavior of non-small cell lung cancer. METHODS: Immunofluorescence staining and Western blot analyses were performed to detect MOR expression. H460 non-small cell lung cancer cells were used in this study, and cell proliferation, the cell cycle and apoptosis were evaluated using Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Cell migration and invasion were detected using wound healing and Transwell assays. The effect of morphine on lung cancer development in vivo was examined by performing a xenograft tumor assay following morphine treatment. RESULTS: Morphine promoted the growth of H460 cells both in vivo and in vitro. Morphine enhanced cell migration and invasion, modified cell cycle progression through the S/G2 transition and exerted an antiapoptotic effect on H460 cells. Additionally, morphine increased Rous sarcoma oncogene cellular homolog (Src) phosphorylation and activated the phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Treatment with the MOR antagonist methylnaltrexone (MNTX) and the Src inhibitor protein phosphatase 1 (PP1) reduced the phosphorylation induced by morphine. Furthermore, MNTX, PP1, and the PI3K/AKT inhibitor deguelin reversed the antiapoptotic effect of morphine on lung cancer cells. CONCLUSION: Morphine promotes the malignant biological behavior of H460 cells by activating the MOR and Src/mTOR signaling pathways.

Type of anesthesia and quality of recovery in male patients undergoing lumbar surgery: a randomized trial comparing propofol-remifentanil total i.v. anesthesia with sevoflurane anesthesia.

BACKGROUND: Previous studies have shown that women achieve a better quality of postoperative recovery from total intravenous anesthesia (TIVA) than from inhalation anesthesia, but the effect of anesthesia type on recovery in male patients is unclear. This study therefore compared patient recovery between males undergoing lumbar surgery who received TIVA and those who received sevoflurane anesthesia. METHODS: Eighty male patients undergoing elective one- or two-level primary transforaminal lumbar interbody fusion (TLIF) were randomly divided into two groups: the TIVA group (maintenance was achieved with propofol and remifentanil) or sevoflurane group (SEVO group: maintenance was achieved with sevoflurane and remifentanil). The quality of recovery-40 questionnaire (QoR-40) was administered before surgery and on postoperative days 1 and 2 (POD1 and POD2). Pain scores, postoperative nausea and vomiting, postoperative hospital stay, anesthesia consumption, and adverse effects were recorded. RESULTS: The QoR-40 scores were similar on the three points (Preoperative, POD1 and POD2). Pain scores were significantly lower in the SEVO group than in the TIVA group on POD1 (30.6 vs 31.4; P = 0.01) and POD2 (32 vs 33; P = 0.002). There was no significant difference in the postoperative hospital stay or complications in the postanesthesia care unit between the TIVA group and the SEVO group. CONCLUSIONS: This study demonstrates that the quality of recovery is not significantly different between male TLIF surgery patients who receive TIVA and those who receive sevoflurane anesthesia. Patients in the TIVA group had better postoperative analgesic effect on POD2. TRIAL REGISTRATION: This was registered at http://www.chictr.org.cn (registration number ChiCTR-IOR-16007987, registration date: 24/02/2016).

Weight Gain Before the Third Trimester and Risk of Hypertensive Disorders of Pregnancy: A Prospective Cohort Study.

BACKGROUND The association between excessive gestational weight gain (GWG) and the risk of hypertensive disorders of pregnancy (HDP) remains uncertain in women with increased water retention in late gestation associated with the pathophysiology of HDP. This study aimed to investigate the association between GWG before the third trimester and the risk of HDP. MATERIAL AND METHODS This was a prospective cohort study in singleton-pregnant women in Tianjin, China, from 2016. Generalized linear models were used to analyze the relationship between weight gain and the risk of HDP. RESULTS A total of 5295 singleton-pregnant women were included. Even after adjusting for relevant confounders, weight gain at approximately 28 weeks remained an independent risk factor for HDP in the normal-weight group. Compared to the reference of low weight gain (+1 SD was associated with an approximately 2.0 times greater likelihood of HDP (RR: 2.08, 95% CI: 1.06-4.08). Moreover, there was a positive relationship between weight gain in the short interval of early pregnancy and risk of HDP in overweight women. CONCLUSIONS Excessive weight gain before the third trimester was associated with a greater risk of developing HDP among women with early-pregnancy normal weight, which may provide a chance to identify subsequent hypertensive disorders. Additional research is needed to determine whether early-pregnancy weight gain is associated with HDP risk.

Comparison of Adrenaline and Dexmedetomidine in Improving the Cutaneous Analgesia of Mexiletine in Response to Skin Pinpricks in Rats.

BACKGROUND: Adrenaline (Adr) and dexmedetomidine (Dex) are commonly used adjuvants of local anesthetics; however, the difference in the improvement of analgesia of local anesthetics between the 2 adjuvants remains unclear. OBJECTIVE: The objective of this experimental research was to evaluate the cutaneous analgesic effect of mexiletine (Mex) by coadministration with Dex or Adr. METHODS: The effect of a nociceptive block was assessed based on the inhibition of the cutaneous trunci muscle reflex in response to skin pinpricks in rats. The analgesic activity of Mex alone and Mex coadministered with Dex or Adr was evaluated after subcutaneous injections. Subcutaneous injections of drugs or combinations include Mex 0.6, 1.8, and 6.0 µmol; Adr 13.66 nmol; Dex 1.05600 nmol; saline; and Mex 1.8 and 6.0 µmol, respectively, combined with Dex 0.01056, 0.10560, and 1.05600 nmol or Adr 0.55, 2.73, and 13.66 nmol, with each injection dose of 0.6 mL. RESULTS: Subcutaneous injections of Mex elicited dose-related cutaneous analgesia. Compared with Mex (1.8 µmol), adding Dex or Adr to Mex (1.8 µmol) solutions for skin nociceptive block potentiated and prolonged the action. Mex (6.0 µmol) combined with Dex or Adr extended the duration of cutaneous analgesia when compared with Mex (6.0 µmol) alone. A high dose of Adr is more effective with Mex 1.8 µmol than that of Dex, whereas medium and low doses were less effective. Mex 6.0 µmol combined with any dose of Adr is superior to that of Dex. CONCLUSIONS: Both Dex and Adr improve the sensory block and enhance the nociceptive block duration of Mex. But in most cases, Adr is superior to Dex. It may be that different mechanisms of action of the 2 adjuvants lead to the differences.

Effect of sex differences in remifentanil requirements for inhibiting the response to a CO2 pneumoperitoneum during propofol anesthesia: an up-and-down sequential allocation trial.

BACKGROUND: A CO2 pneumoperitoneum during a laparoscopic procedure causes violent hemodynamic changes. However, the remifentanil required to inhibit the cardiovascular response to a CO2 pneumoperitoneum combined with propofol remains unknown. Moreover, the sex of the patient may influence the response to opioids, which can affect this requirement. The main objective of this study was to compare the required median effective concentration (EC50) of remifentanil for inhibiting the cardiovascular response to a CO2 pneumoperitoneum between female and male patients during propofol anesthesia. METHODS: The current study is an up-and-down sequential allocation trial. Forty-six patients with American Society of Anesthesiologists physical status I or II, a body mass index 18 to 30 kg/m2, aged 20 to 60 years, and scheduled for laparoscopic surgery were enrolled. Induction of anesthesia was performed by target-controlled infusion. The effective effect-site concentration (Ce) of propofol was 4 µg/ml. The Ce of remifentanil was initially 4 ng/ml and then adjusted to a predetermined level after I-gel laryngeal mask airway insertion. The Ce of remifentanil for each patient was determined by the response of the previous patient using the modified Dixon "up-and-down" method. The first patient received remifentanil at 5.0 ng/ml Ce, and the step size between patients was 0.5 ng/ml. RESULTS: Patients characteristics including age, body mass index, American Society of Anesthesiologists physical status, type of surgery and surgery duration, were comparable between male and female patients. The EC50 of remifentanil required to inhibit the response to a CO2 pneumoperitoneum based on the Dixon "up-and-down" method in women (4.17 ± 0.38 ng/ml) was significantly lower than that in men (5.00 ± 0.52 ng/ml) during propofol anesthesia (P = 0.01). CONCLUSIONS: The EC50 of remifentanil required to inhibit the response to a CO2 pneumoperitoneum was lower in women than in men during propofol anesthesia. TRIAL REGISTRATION: The study was registered at http://www.chictr.org.cn (ChiCTR-IOR-17011906, 8th, July, 2017).

SIRT1 Activation Attenuates Bone Cancer Pain by Inhibiting mGluR1/5.

Bone cancer pain (BCP), which is induced by primary or metastatic bone cancer, remains a clinically challenging problem due to the poor understanding of its mechanisms. Sirtuin 1 (SIRT1) plays an important role in various pain models. Intrathecal administration of SRT1720, a SIRT1 activator, attenuates BCP in a rat model. However, the expression and activity of SIRT1 during the development and maintenance of BCP remain unknown. Furthermore, the underlying mechanism of SIRT1 in BCP remains ambiguous. In this study, we detected the time course of SIRT1 expression and activity in the spinal cord of mice with BCP and examined whether SRT1720 alleviated BCP by inhibiting metabotropic glutamatergic receptor (mGluR) 1/5 expression. In addition, we downregulated spinal SIRT1 expression in normal mice through an intrathecal injection of AAV-SIRT1-shRNA and then assessed pain behavior and mGluR1/5 expression. Mice with BCP developed significant mechanical allodynia and spontaneous flinching, accompanied by decreased levels of the SIRT1 protein, mRNA, and activity in the spinal cord. The SRT1720 treatment produced an analgesic effect on tumor-bearing mice and decreased the spinal levels of the mGluR1/5 protein and mRNA. In contrast, the AAV-SIRT1-shRNA treatment induced pain behavior in normal mice and increased the spinal levels of the mGluR1/5 protein and mRNA. The results suggested a critical role for SIRT1 in the development and maintenance of BCP and further indicated that activation of SIRT1 in the spinal cord by SRT1720 functionally reverses BCP in mice by inhibiting mGluR1/5.

Dexmedetomidine Promotes SH-SY5Y Cell Resistance Against Impairment of Iron Overload by Inhibiting NF-κB Pathways.

Iron overload is a common pathophysiological state underlying many diseases that has a detrimental influence on cells. The protective effects of Dexmedetomidine (Dex), a high selective alpha-2-adrenoceptor agonist, have been revealed through many experimental models, whereas no study reports its effects on an iron overload model. To elucidate these effects, we used FeCl2 with or without Dex to treat SH-SY5Y cells for 24 h and then detected indicators of oxidative stress, inflammation and apoptosis and investigated possible mechanisms further. After treatment with FeCl2 for 24 h, cell viability decreased in a dose dependent manner, and Dex promoted cell survival in FeCl2 incubation, also in a dose-dependent manner. Compared with the FeCl2 group, 20 µM Dex significantly attenuated ROS accumulation, reduced pro-inflammatory cytokine expression, and inhibited apoptosis. Furthermore, 20 µM concentration of Dex remarkably downregulated the expression of pro-apoptotic protein and activation of caspase 3 while increasing anti-apoptotic protein expression. Additionally, Dex also effectively suppressed the expression of NF-κB and its activation. In conclusion, Dex exerted anti-oxidative stress, anti-inflammation, and anti-apoptosis effects on FeCl2-treated SH-SY5Y cells, possibly by inhibiting NF-κB signaling pathway.

Effects of Dexmedetomidine-Isoflurane versus Isoflurane Anesthesia on Brain Injury After Cardiac Valve Replacement Surgery.

OBJECTIVES: To compare dexmedetomidine combined with isoflurane versus isoflurane anesthesia on brain injury after cardiac surgery. DESIGN: A prospective, randomized, single-blind study. SETTING: University hospital. PARTICIPANTS: Adult patients undergoing elective valve replacement surgery. INTERVENTIONS: Ninety-seven patients scheduled for valve replacement surgery were randomly divided into 2 groups: dexmedetomidine and isoflurane (Dex-Iso, n = 50) and isoflurane alone (Iso, n = 47). Dexemedetomidine was infused at 0.6 µg/kg as a bolus, followed with 0.2 µg/kg/h until the end of surgery. MEASUREMENTS AND MAIN RESULTS: Jugular blood samples were drawn for analysis of matrix metalloproteinase-9 (MMP-9) and glial fibrillary acidic protein (GFAP) levels on time points of: T1 (before induction); T2 (5 minutes after cardiopulmonary bypass [CPB] onset); T3 (after CPB off); T4 (the first day after operation); T5 (the second day after operation). Plasma lactate levels in arterial and jugular venous blood also were quantified. The difference between arterial and jugular bulb venous blood lactate levels (AVDL) was calculated. An antisaccadic eye movement (ASEM) test was carried out on the day before the operation and the seventh day postoperatively. In both groups, serum MMP-9 and GFAP concentrations increased after CPB, with the peak values occurring after CPB. At time point T5, MMP-9 and GFAP levels were close to those at T1. MMP-9 concentrations in the Dex-Iso group were lower than the Iso group at T3 and T4. GFAP concentrations in the Dex-Iso group were lower at T3 but were higher than the Iso group at T2. No significant differences were found in AVDL between the 2 groups perioperatively except at T2. The ASEM scores decreased significantly postoperatively. There was no significant difference in the ASEM scores between the 2 treatment groups before and after the operation. CONCLUSIONS: The use of dexmedetomidine decreased the biochemical markers of brain injury but did not improve the neuropsychological test result after cardiac surgery.

I-gel Laryngeal Mask Airway Combined with Tracheal Intubation Attenuate Systemic Stress Response in Patients Undergoing Posterior Fossa Surgery.

BACKGROUND: The adverse events induced by intubation and extubation may cause intracranial hemorrhage and increase of intracranial pressure, especially in posterior fossa surgery patients. In this study, we proposed that I-gel combined with tracheal intubation could reduce the stress response of posterior fossa surgery patients. METHODS: Sixty-six posterior fossa surgery patients were randomly allocated to receive either tracheal tube intubation (Group TT) or I-gel facilitated endotracheal tube intubation (Group TI). Hemodynamic and respiratory variables, stress and inflammatory response, oxidative stress, anesthesia recovery parameters, and adverse events during emergence were compared. RESULTS: Mean arterial pressure and heart rate were lower in Group TI during intubation and extubation (P < 0.05 versus Group TT). Respiratory variables including peak airway pressure and end-tidal carbon dioxide tension were similar intraoperative, while plasma ß-endorphin, cortisol, interleukin-6, tumor necrosis factor-alpha, malondialdehyde concentrations, and blood glucose were significantly lower in Group TI during emergence relative to Group TT. Postoperative bucking and serious hypertensions were seen in Group TT but not in Group TI. CONCLUSION: Utilization of I-gel combined with endotracheal tube in posterior fossa surgery patients is safe which can yield more stable hemodynamic profile during intubation and emergence and lower inflammatory and oxidative response, leading to uneventful recovery.

Intranasal Dexmedetomidine on Stress Hormones, Inflammatory Markers, and Postoperative Analgesia after Functional Endoscopic Sinus Surgery.

BACKGROUND: A strong ongoing intraoperative stress response can cause serious adverse reactions and affect the postoperative outcome. This study evaluated the effect of intranasally administered dexmedetomidine (DEX) in combination with local anesthesia (LA) on the relief of stress and the inflammatory response during functional endoscopic sinus surgery (FESS). METHODS: Sixty patients undergoing FESS were randomly allocated to receive either intranasal DEX (DEX group) or intranasal saline (Placebo group) 1 h before surgery. Stress hormones, inflammatory markers, postoperative pain relief, hemodynamic variables, blood loss, surgical field quality, body movements, and satisfaction were assessed. RESULTS: Plasma epinephrine, norepinephrine, and blood glucose levels were significantly lower in DEX group as were the plasma IL-6 and TNF-α levels (P < 0.05). The weighted areas under the curve (AUCw) of the VAS scores were also significantly lower in DEX group at 2-12 h after surgery (P < 0.001). Furthermore, hemodynamic variables, blood loss, body movements, discomfort with hemostatic stuffing, surgical field quality, and satisfaction scores of patients and surgeons were significantly better (P < 0.05) in DEX group. CONCLUSIONS: Patients receiving intranasal DEX with LA for FESS exhibited less perioperative stress and inflammatory response as well as better postoperative comfort with hemostatic stuffing and analgesia.

Single-dose, bilateral paravertebral block plus intravenous sufentanil analgesia in patients with esophageal cancer undergoing combined thoracoscopic-laparoscopic esophagectomy: a safe and effective alternative.

OBJECTIVE: Paravertebral block (PVB) has been shown to be an ideal aid for analgesia after thoracic or abdominal surgery. The authors studied the safety and efficacy of the single-dose and bilateral ultrasound-guided (USG)-PVB before combined thoracoscopic-laparoscopic esophagectomy (TLE) along with intravenous sufentanil analgesia as a method of pain relief in comparison with intravenous sufentanil as a sole analgesic agent. DESIGN: Prospective, randomized study. SETTING: Single university hospital. PARTICIPANTS: Fifty-two patients undergoing TLE. INTERVENTIONS: A USG-PVB was performed before surgery using a solution of 30 mL of 0.5% ropivacaine by 3 injections of 10 mL each at the right T5 and bilateral T8 (PVB group, n=26) or the saline injection of 10 mL at every site (control group, n=26). MEASUREMENTS AND MAIN RESULTS: Successful PVBs were achieved in all patients of the PVB group. Intraoperative mean remifentanil usage and end-tidal sevoflurane concentration were lower in the PVB group (p<0.001). Hemodynamic parameters were stable in both groups. Postoperative pain scores both at rest and on coughing were lower during the first 8 hours in the PVB group than those in the control group (p<0.05). Cumulative sufentanil consumption delivered by patient-controlled analgesia (PCA) was significantly lower in the PVB group at all time points (p<0.05). Postoperative pulmonary function was better at the third postoperative day in the PVB group (p<0.05), with quicker hospital discharge and lower hospital costs (p<0.05). CONCLUSIONS: The single-dose and bilateral PVB given before TLE combined with sufentanil may provide better postoperative analgesia and early discharge in patients undergoing TLE.

Frailty is a Risk Factor for Postoperative Complications in Older Adults with Lumbar Degenerative Disease: A Prospective Cohort Study.

Objective: Frailty, representing the physiological reserve and tolerance of the body, serves as a crucial evaluation index of the overall status of the older adults. This study aimed to investigate the prevalence of preoperative frailty and its impact on postoperative outcomes among older adults with lumbar degenerative disease in China. Patients and Methods: In this prospective study, a total of 280 patients aged 60 and above, diagnosed with lumbar degenerative disease and scheduled for surgical intervention were enrolled. The prevalence of frailty pre-surgery was evaluated using the Tilburg Frailty Indicator (TFI) and the modified Frailty Index 11 (mFI-11). The primary outcome was postoperative complication within 30 days post-surgery. The secondary outcomes were the length of hospital stay, hospital costs, reoperation within 30 days post-surgery and unplanned readmission within 30 days post-discharge. Both univariable and multivariable logistic regression were employed to screen and identify the risk factors predisposing patients to postoperative complications. Results: A total of 272 older adults were included in the study ultimately. The frailty detection rates of TFI and mFI-11 were 15.8% (43/272) and 10.7% (29/272) respectively. Thirty-four patients (12.5%) encountered complications. Significantly elevated rates of complications, prolonged hospital stays, increased hospital costs, and heightened readmission rates were observed in the frail group compared to the non-frail group (P<0.05). Univariable analysis showed that the potential factors related to complications are TFI, mFI-11 and albumin. Multivariable logistic regression revealed that TFI was an independent risk factor for postoperative complications (OR=5.371, 95% CI: 2.338-12.341, P < 0.001). Conclusion: Frailty was an independent predictor of postoperative complications in older adults undergoing lumbar fusion surgery. Frailty assessment should be performed in such patients to improve preoperative risk stratification and optimize perioperative management strategies.

Comparison of Ciprofol-Based and Propofol-Based Total Intravenous Anesthesia on Microvascular Decompression of Facial Nerve with Neurophysiological Monitoring: A Randomized Non-Inferiority Trial.

Purpose: Ciprofol is a recently developed short-acting gamma-aminobutyric acid receptor agonist with a higher potency than that of propofol. As a new sedative drug, there are few clinical studies on ciprofol. We sought to examine the safety and efficacy of ciprofol use for general anesthesia in neurosurgical individuals undergoing neurosurgical surgery with intraoperative neurophysiological monitoring (IONM). Patients and Methods: This single-center, non-inferiority, single-blind, randomized controlled trial was conducted from September 13, 2022 to September 22, 2023. 120 patients undergoing elective microvascular decompression surgery (MVD) with IONM were randomly assigned to receive either ciprofol or propofol. The primary outcome of this study was the amplitude of intraoperative compound muscle action potential decline, and the secondary outcome included the indexes related to neurophysiological monitoring and anesthesia outcomes. Results: The mean values of the primary outcome in the ciprofol group and the propofol group were 64.7±44.1 and 53.4±35.4, respectively. Furthermore, the 95% confidence interval of the difference was -25.78 to 3.12, with the upper limit of the difference being lower than the non-inferiority boundary of 6.6. Ciprofol could achieve non-inferior effectiveness in comparison with propofol in IONM of MVD. The result during anesthesia induction showed that the magnitude of the blood pressure drop and the incidence of injection pain in the ciprofol group were significantly lower than those in the propofol group (P<0.05). The sedative drug and norepinephrine consumption in the ciprofol group was significantly lower than that in the propofol group (P<0.05). Conclusion: Ciprofol is not inferior to propofol in the effectiveness and safety of IONM and the surgical outcome. Concurrently, ciprofol is more conducive to reducing injection pain and improving hemodynamic stability, which may be more suitable for IONM-related surgery, and has a broad application prospect.

Intraoperative transcutaneous electroacupoint stimulation on early postoperative fatigue in patients with Parkinson's disease undergoing deep brain stimulation surgery.

Background: In this clinical trial, we evaluated the effects of transcutaneous electroacupoint stimulation (TEAS) on postoperative fatigue (POF) in Parkinson disease (PD) patients undergoing deep brain stimulation (DBS) surgery. Methods: A total 60 PD patients undergoing DBS surgery were enrolled. They were randomized to receive either electrical stimulation [alternative frequency 2/10 Hz, dense and disperse, intensity adjusted to the maximum tolerated by the participants (6-15 mAmp)] via surface electrodes (TEAS group) or surface electrodes only without electrical stimulation (Con group) at bilateral Zusanli and Sanyinjiao acupuncture points. All participants received their assigned intervention (TEAS or Con) during the 1st stage of surgery [(except during microelectrode recording (MER)] and the entire 2nd stage of surgery. Intraoperative anesthetic requirements were adjusted based on bispectral index (BIS) monitor. POF was assessed by Christensen fatigue scales (ChrFS), along with Quality of Recovery-15 (QoR-15) and mini-mental state examination (MMSE) postoperatively over a 7-day-period. We recorded the usage of rescue analgesics and anti-emetics. Results: Fifty-nine patients' datasets were included for final analyses. Fewer patients in TEAS experienced severe POF (defined as ChrFS ≥6) at T3 than those in the Con group (TEAS vs. Con: 7 vs. 22, p < 0.001). During the 1st stage of surgery, more patients in Con group required dexmedetomidine infusion (TEAS vs. Con: 2 vs. 6; P < 0.01). Total dosages of propofol and remifanil during the 2nd stage of surgery were TEAS vs. Con: 374.7 ± 61.2 vs 421.5 ± 81.9; p < 0.001 and 572.3 ± 82.0 vs. 662 ± 148.2; P < 0.001, respectively. Postoperative rescue analgesics (TEAS vs. Con: 2 vs. 6; P < 0.001) were used less in the TEAS group. TEAS patients reported better POF, MMSE and QoR15 scores than those in the Con group during most of the assessment period. Conclusions: Intraoperative TEAS decreased the severity of POF, reduced intraoperative anesthetic requirements and facilitated post-DBS recovery in this group of PD patients.

Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice.

Anxiety-associated symptoms following acute stress usually become extinct gradually within a period of time. However, the mechanisms underlying how individuals cope with stress to achieve the extinction of anxiety are not clear. Here we show that acute restraint stress causes an increase in the activity of GABAergic neurons in the CeA (GABACeA) in male mice, resulting in anxiety-like behaviors within 12 hours; meanwhile, elevated GABACeA neuronal CX3CL1 secretion via MST4 (mammalian sterile-20-like kinase 4)-NF-κB-CX3CL1 signaling consequently activates microglia in the CeA. Activated microglia in turn inhibit GABACeA neuronal activity via the engulfment of their dendritic spines, ultimately leading to the extinction of anxiety-like behaviors induced by restraint stress. These findings reveal a dynamic molecular and cellular mechanism in which microglia drive a negative feedback to inhibit GABACeA neuronal activity, thus facilitating maintenance of brain homeostasis in response to acute stress.

Spinal sirtuin 2 attenuates bone cancer pain by deacetylating FoxO3a.

Bone cancer pain (BCP) is refractory to currently used analgesics. Recently, sirtuin 2 (SIRT2) was reported to play a vital role in neuropathic pain but its role in BCP remains unknown. It was hypothesized that spinal SIRT2 attenuates BCP by deacetylating FoxO3a and suppressing oxidative stress. The mouse model of BCP established by injecting tumor cells into the intramedullary space of the femur demonstrated that spinal SIRT2 and FoxO3a were downregulated in BCP development. Intrathecal administration of LV-SIRT2 reduced pain hypersensitivity (mechanical and thermal nociception) in BCP mice. Spinal SIRT2 overexpression upregulated FoxO3a and antioxidant genes (SOD2 and catalase) and inhibited FoxO3a acetylation, phosphorylation, and ubiquitination. Moreover, intrathecal administration of SIRT2 shRNA induced pain hypersensitivity in normal mice. Spinal SIRT2 knockdown downregulated FoxO3a and antioxidant genes and increased FoxO3a acetylation, phosphorylation, and ubiquitination. In summary, spinal SIRT2 increases FoxO3a expression in BCP mice and inhibits oxidative stress by deacetylating FoxO3a and further reducing FoxO3a phosphorylation, ubiquitination, and degradation, leading to BCP relief.