Correlation Between Anesthesia Methods and Adverse Short-Term Postoperative Outcomes Depending on Frailty: A Prospective Cohort Study.

Purpose: This study aims to investigate how the type of anesthesia used during major orthopedic surgery may impact adverse short-term postoperative outcomes depending on frailty. Methods: To conduct this investigation, we recruited individuals aged 65 years and older who underwent major orthopedic surgery between March 2022 and April 2023 at a single institution. We utilized the FRAIL scale to evaluate frailty. The primary focus was on occurrences of death or the inability to walk 60 days after the surgery. Secondary measures included death within 60 days; inability to walk without human assistance at 60 days; death or the inability to walk without human assistance at 30 days after surgery, the first time out of bed after surgery, postoperative blood transfusion, length of hospital stay, hospital costs, and the occurrence of surgical complications such as dislocation, periprosthetic fracture, infection, reoperation, wound complications/hematoma. Results: In a study of 387 old adult patients who had undergone major orthopedic surgery, 41.3% were found to be in a frail state. Among these patients, 262 had general anesthesia and 125 had neuraxial anesthesia. Multifactorial logistic regression analyses showed that anesthesia type was not linked to complications. Instead, frailty (OR 4.04, 95% CI 1.04 to 8.57, P< 0.001), age (OR 1.05, 95% CI 1.00-1.10, P= 0.017), and aCCI scores, age-adjusted Charlson Comorbidity Index, (OR 1.36, 95% CI 1.12 to 1.66, P= 0.002) were identified as independent risk factors for death or new walking disorders in these patients 60 days after surgery. After adjusting for frailty, anesthesia methods was not associated with the development of death or new walking disorders in these patients (P > 0.05). Conclusion: In different frail populations, neuraxial anesthesia is likely to be comparable to general anesthesia in terms of the incidence of short-term postoperative adverse outcomes.

Downregulated CAV-1 in mouse spinal cord may alleviate bone cancer pain by inhibiting the ERK/CREB pathway.

BACKGROUND: This study aimed to assess the potential function of Caveolin-1 (CAV-1) in mice with bone cancer pain. METHOD: Using a mice bone cancer pain model we explored the contribution of CAV-1 expression to bone cancer pain on the 14th day after surgery, mice in the tumor group were randomized and treated with increasing doses of the CAV-1 inhibitor, methyl-beta-cyclodextrin. Pain was assessed by monitoring the number of spontaneous flinches (NSF) and paw withdrawal mechanical threshold (PMWT)mechanical withdrawal threshold (MWT). The localization and expression of CAV-1 in mouse neurons was also determined. Additionally, the protein levels of CAV-1, extracellular signal regulated kinase (ERK) 1/2, cAMP response element-binding protein (CREB) were monitored in mouse spinal cord tissues by western blotting. RESULTS: CAV-1 was remarkably upregulated in the spinal cord of the tumor group on the 4th day after surgery, then downregulated on day 10, and upregulated again at day 14. Such CAV-1 levels were maintained until day 28. In the tumor group, the expression of p-ERK1/2 and p-CERB were upregulated at day 14 after surgery. Intrathecal injection of methyl-beta-cyclodextrin (MCD) downregulated p-ERK1/2 and p-CERB expression which correlated with alleviation of pain. CONCLUSION: Inhibition of CAV-1 in the spinal cord alleviates bone cancer pain in mice which correlates with inhibition of the ERK/CREB pathway.

LncRNA RUNX1-IT1 is downregulated in gastric cancer and suppresses the maturation of miR-20a by binding to its precursor.

BACKGROUND: RUNX1-IT1 has been characterized as a tumor suppressive long non-coding RNA (lncRNA) in several types of cancer but not gastric cancer (GC). This study aimed to explore the role of RUNX1-IT1 in GC. METHODS: The expression of RUNX1-IT1, microRNA (miR)-20a precursor and mature miR-20a in GC and healthy tissues donated by GC patients (n=62) were measured by RT-qPCR. Correlation analysis was performed by linear regression. The expression of mature miR-20a and miR-20a precursor in cells with overexpression of RUNX1-IT1 was also determined by RT-qPCR. Cell invasion and migration were evaluated by Transwell assays. RESULTS: RUNX1-IT1 was downregulated in GC. Across GC tissues, RUNX1-IT1 and mature miR-20a were inversely correlated. However, RUNX1-IT1 and miR-20a precursor were not closely correlated. RUNX1-IT1 and miR-20a precursor were predicted to interact with each other, and overexpression of RUNX1-IT1 in GC cells decreased the expression levels of mature miR-20a. Transwell assay showed that the enhancing effect of miR-20a on cell invasion and migration was reduced by overexpression of RUNX1-IT1. CONCLUSIONS: RUNX1-IT1 may suppress the GC cell movement by inhibiting the maturation of miR-20a.

Protective effect of dexmedetomidine on lung injury during one-lung ventilation in elderly patients undergoing radical esophagectomy

Abstract This study investigated the protective effect of dexmedetomidine (Dex) on lung injury during one-lung ventilation (OLV) in elderly patients undergoing radical esophagectomy with remote ischemic preconditioning (RIPC). Fifty-four esophageal cancer patients undergoing radical esophagectomy were divided into control, RIPC and RIPC+Dex group. During the anesthesia and ventilation in surgery, the RIPC was performed in RIPC group, and the intravenous infusion of Dex based on RIPC was conducted in RIPC+Dex group. At the time immediately before OLV beginning (T1), 60 min of OLV (T2) and end of surgery (T3), the oxygenation index (OI) and respiratory index (RI) were recorded, and the serum superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) levels were determined. Results showed that, compared with RIPC group, in RIPC+Dex group the OI at T2 and T3 increased, the RI at T2 and T3 decreased, the serum SOD level at T3 increased, the serum MDA level at T3 decreased, the serum TNF-α and IL-6 levels at T2 and T3 decreased (all P < 0.05). In conclusion, for elderly patients undergoing radical esophagectomy with RIPC, Dex can effectively inhibit the oxidative stress and inflammatory response during OLV, thus alleviating the lung injury and reducing the postoperative complications.

The NLRP3-related inflammasome modulates pain behavior in a rat model of trigeminal neuropathic pain.

AIMS: Nod-like receptor family pyrin domain containing 3 (NLRP3) may play an important role in neuropathic pain. Treatment for trigeminal neuropathic pain remains a challenge, as common drugs either do not demonstrate beneficial therapeutic effects or induce intolerance in patients. MAIN METHODS: In a rat model of trigeminal neuropathic pain, pain caused by the malpositioning of dental implants is similar to that experienced by humans. We used masculine Sprague-Dawley rats with inferior alveolar nerve damage as a model to investigate the differential regulation of NLRP3. First, we confirmed the level of NLRP3 in the medullary dorsal horn and variation of pain response behavior after silencing the expression of NLRP3 inflammasome bodies in rats with trigeminal neuropathic pain. Second, under localized anesthesia, we extracted the lower left second molar, implanted a micro-dental implant, and deliberately injured the inferior alveolar nerve. KEY FINDINGS: After nerve damage, the level of NLRP3-related inflammasomes was upregulated in microglia and the expression of a component of the inflammasome gradually increased during postoperative days 3-21. The suppression of adenovirus-shRNA-NLRP3 on postoperative day 1 markedly inhibited the expression of pro-inflammatory cytokines and the activation of the inflammasome and mechanical allodynia. Furthermore, it attenuated cell death in microglia, as evidenced by increased Bcl-2, Bcl-xL, Bax, and Bik expression. SIGNIFICANCE: The level of NLRP3 in the dorsal horn is a pivotal factor in trigeminal neuropathic pain, and inhibition of the early expression of NLRP3 might serve as a potential therapeutic approach.

Effects of dexmedetomidine as an adjuvant in thoracic paravertebral block on EC50 of propofol for successful laryngeal mask insertion: a randomized controlled trial.

BACKGROUND: Dexmedetomidine as an adjuvant can improve the duration and the quality of thoracic paravertebral block (TPVB); however, its quantitative effect on propofol infusion is unclear. This study aimed to investigate the effect of dexmedetomidine as an adjuvant in TPVB on the medium effective concentration (EC50) of propofol for successful laryngeal mask insertion. METHODS: Sixty breast cancer patients who underwent elective modified radical mastectomy were enrolled and randomized at a 1:1 ratio into control group (Group C, n=30) or dexmedetomidine group (Group D, n=30). Ultrasound-guided T3 paravertebral block was performed before induction of anesthesia. In Group C, 0.5% ropivacaine 0.3 mL/kg was injected into T3 paravertebral space, while subjects in Group D received 0.5% ropivacaine 0.3 mL/kg with dexmedetomidine (1 µg/kg). Propofol target-controlled infusion (TCI) was performed, with an initial target effect-site concentration of 5 µg/mL determined for both groups. The laryngeal mask was inserted once the effect chamber achieved the target concentration. Subsequent target concentrations were adjusted by Dixon up-down sequential method, where dose modifications were performed by 0.5 mg/mL intervals, based on the success of the laryngeal mask insertion. Probit analysis was used to determine the propofol EC50. Mean arterial pressure (MAP), heart rate (HR), bispectral index (BIS) and application of atropine or ephedrine was recorded. Participants, TPVB giver, and data recorder were blinded to group assignment. RESULTS: Propofol EC50 for successful laryngeal mask insertion were statistically significant, with 5.256 µg/mL (95% CI: 4.833, 5.738 µg/mL) in Group C and 3.172 µg/mL (95% CI: 2.701, 3.621 µg/mL) in Group D. Both groups displayed significantly lower MAP and HR, post propofol TCI (P<0.05). However, subjects in Group D exhibited lower MAP and HR levels compared to patients in Group C (P<0.05). Application of atropine (0% vs. 10%) and ephedrine (20.0% vs. 13.3%) were not significantly different between two groups. CONCLUSIONS: Dexmedetomidine, administered as an adjuvant in TPVB, can reduce the TCI concentration of propofol for successful laryngeal mask placement in females. The target concentration of propofol requires adjustment and close monitoring of hemodynamic changes, post induction is warranted. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800016614.

Changes in the concentrations of mediators in exhaled breath condensate during cardiac valve replacement under cardiopulmonary bypass and their relations with postoperative acute respiratory distress syndrome.

To investigate the changes in the concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and 8-iso-prostaglandin F2α (8-isoPGF2α) in exhaled breath condensate (EBC) in patients undergoing cardiac valve replacement under cardiopulmonary bypass (CPB) and its relationship with postoperative acute respiratory distress syndrome (ARDS).A prospective, case-control study was performed on 55 patients undergoing elective cardiac valve replacement under cardiopulmonary bypass, between November 2017 and May 2019. According to the diagnosis of postoperative ARDS, the patients were divided into ARDS group and control group. We compared the clinical characteristics, outcomes, respiratory mechanics, oxygenation parameters, and mediators in the 2 groups immediately after tracheal intubation (T1), at the end of CPB (T2), and 2 hours (T3) and 6 hours (T4) after CPB, and calculated the receiver operating characteristic curve (ROC), sensitivity, and specificity of the corresponding mediators.ARDS occurred in 29 patients after CPB. The ARDS group exhibited prolonged postoperative ventilator support, time to extubation, length of stay in the ICU, and postoperative length of stay. The peak airway pressure (Ppeak) and plat airway pressure (Pplat) at T4 were higher in the ARDS group compared with the control group. The alveolar-arterial oxygen partial pressure [P(A-a)O2] and respiratory index (RI) were higher and PaO2/FiO2 was lower in the ARDS group at T2-4 compared with the control group. The levels of EBC and serum mediators in the ARDS group were significantly higher at T2-4 compared with those in the control group. All the mediators in EBC were correlated significantly with those in the serum in the ARDS group (r = 0.7314, 0.898, 0.8386, 0.792) and control group (r = 0.6093, 0.8524, r = 0.7828, r = 0.6575) (P < .001). Meanwhile, the area under the curve (AUC) of IL-8 in EBC was significantly lower at T2 and the AUC of IL-6 in EBC was significantly higher at T4 than in serum (P < .05). In addition, all of the mediators in EBC had a certain accuracy in diagnose of postoperative ARDS.EBC analysis could be used to predict the high incidence of ARDS after cardiac valve replacement under CPB.

Siglec-G Deficiency Ameliorates Hyper-Inflammation and Immune Collapse in Sepsis via Regulating Src Activation.

Hyper-inflammation during acute phase and sequential hypo-inflammation during immunosuppressive phase in macrophages/monocytes lead to multiorgan failure syndrome and immune collapse of sepsis, in which toll-like receptor (TLR)-triggered inflammatory responses play a major role. Here, we reported that Siglecg deficiency attenuated TLR4-triggered pro-inflammatory cytokine production and increased anti-inflammatory cytokine [interleukin-10 [IL-10]] production in vivo and in vitro at both acute and immunosuppressive phases. Siglecg deficiency also protected mice from lipopolysaccharide (LPS)-induced sepsis with less inflammation in the lung and less tissue destruction in the spleen. Siglec-G inhibited proto-oncogene tyrosine-protein kinase Src (Src) activation via recruiting and activating tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1 (SHP1) through immunoreceptor tyrosine-based inhibitory motif (ITIM) domain. Src could inhibit TLR4-induced inflammatory cytokines and promote anti-inflammatory cytokine IL-10. Mechanical investigation showed that Src could interact with and phosphorylate STAT3. Src could also promote HIF1α degradation through activating GSK3ß. Our study reveals that Siglec-G orchestrates TLR-induced inflammation, which outlines that blocking Siglec-G or activating Src may be a promising strategy for both acute and chronic inflammatory diseases.

Comparison of Postoperative Pain and Residual Gas Between Restrictive and Liberal Fluid Therapy in Patients Undergoing Laparoscopic Cholecystectomy.

BACKGROUND: Different fluid regimens are used in the clinical management of perioperative fluid therapy, but there still is the argument about which fluid regimen is better for patients. This study was mainly designed to compare different fluid regimens on postoperative pain and residual gas in patients undergoing laparoscopic cholecystectomy. METHODS: A total of 100 patients were equally randomized to receive restrictive fluid infusion (n=50) with lactated Ringer (LR) solution 5 mL/kg/h or liberal fluid infusion (n=50), with 30 mL/kg/h lactated Ringer solution. Postoperative pain was evaluated at 1, 6, and 24 hours after surgery using a visual analog scale (VAS). Postoperative subdiaphragmatic residual gas was monitored by x-ray at 24 hours after surgery. RESULTS: Patients in the restrictive group had significantly higher VAS pain scores at 6 hours after surgery than those in the liberal group (P=0.009). The incidence of subdiaphragmatic residual gas in the restrictive group was higher than in the liberal group (P=0.045). Patients who had residual gas had higher VAS pain scores than those with no residual gas in the restrictive group at 6 hours after surgery (P=0.02). CONCLUSIONS: Patients undergoing laparoscopic cholecystectomy with restrictive fluid therapy may suffer more severe postoperative pain than those receiving liberal fluid therapy. It suggests that the higher incidence of subdiaphragmatic residual gas may have occurred with restrictive fluid therapy.

Association between APOE epsilon 4 allele and postoperative cognitive dysfunction: a meta-analysis.

BACKGROUND: Carriers of the apolipoprotein E epsilon 4 allele (APOEε4) may be at increased risk of postoperative cognitive dysfunction (POCD), but this association has not been reported consistently. We conducted a meta-analysis to derive a more precise conclusion. METHODS: The PubMed, EBSCO and EMBASE databases were searched for eligible studies published in English before March 2013. The association between APOEε4 and POCD was expressed by the odds ratio (OR) with 95% confidence interval (CI). Funnel plots were constructed and publication bias assessed by Egger's test. RESULTS: Nine studies encompassing 1063 APOEε4 carriers and 2983 noncarriers were included. At about 1-week postsurgery, a significant association between APOEε4 and POCD was found (OR 1.83, 95% CI: 1.18-2.85), but the association was no longer significant after removing one large study (OR 1.35, 95% CI: 0.92-1.97). Stratified analysis of cardiac/vascular surgery patients also yielded no significant correlation (OR 1.62, 95% CI: 0.80-3.28). One to three months postsurgery, neither the overall analysis (OR 1.56, 95% CI: 0.87-2.81) nor the stratified analysis of cardiac/vascular surgery patients (OR 3.33, 95% CI: 0.55-20.22) indicated a significant correlation. APOEε4 was also not correlated with POCD at 1-year postsurgery (OR 1.15, 95% CI: 0.71-1.86). No evidence of publication bias was revealed by Egger's test. CONCLUSIONS: The APOEε4 allele was associated with a significantly increased POCD risk about 1-week postsurgery, but the association depended on one large study. No association was found 1-3 months and 1-year postsurgery.

Association of IL-6 polymorphisms with hepatocellular carcinoma risk: evidences from a meta-analysis.

The associations between IL-6 gene single nucleotide polymorphisms (SNPs) and risk of hepatocellular carcinoma (HCC) are controversial. We performed a meta-analysis to provide more credible evidence. We searched for relevant studies published up to 2013 by performing an efficient searching strategy. Odds ratios (OR) with 95% confidence interval (95% CI) was used to estimate the strength of the associations between IL-6 polymorphisms and HCC risk. We identified eight case-control studies involving 1,448 HCC cases and 3,160 controls. Our estimation specifically focused on two SNPs of the IL-6 gene, -174 G/C and -572 G/C. The combined results showed that association between IL-6-174 G/C polymorphism and risk of HCC was significant under additive model (CC vs. GG: OR 0.36; 95% CI, 0.16, 0.85) and recessive model (GG+CG vs. CC: OR 2.82; 95% CI 1.26, 6.28). However, the IL-6-572 G/C polymorphism was not associated with HCC risk. In conclusion, IL-6-174 G/C, but not -572 G/C polymorphism could be a candidate for susceptibility to HCC. However, the results should be cautiously interpreted due to the limited number of the included studies.