OXY-SCORE and Volatile Anesthetics: A New Perspective of Oxidative Stress in EndoVascular Aneurysm Repair-A Randomized Clinical Trial.

An aortic aneurysm (AA) is a life-threatening condition. Oxidative stress may be a common pathway linking multiple mechanisms of an AA, including vascular inflammation and metalloproteinase activity. Endovascular aneurysm repair (EVAR) is the preferred surgical approach for AA treatment. During surgery, inflammation and ischemia-reperfusion injury occur, and reactive oxygen species (ROS) play a key role in their modulation. Increased perioperative oxidative stress is associated with higher postoperative complications. The use of volatile anesthetics during surgery has been shown to reduce oxidative stress. Individual biomarkers only partially reflect the oxidative status of the patients. A global indicator of oxidative stress (OXY-SCORE) has been validated in various pathologies. This study aimed to compare the effects of the main volatile anesthetics, sevoflurane and desflurane, on oxidative status during EVAR. Eighty consecutive patients undergoing EVAR were randomized into two groups: sevoflurane and desflurane. Plasma biomarkers of oxidative damage (protein carbonylation and malondialdehyde) and antioxidant defense (total thiols, glutathione, nitrates, superoxide dismutase, and catalase activity) were measured before surgery and 24 h after EVAR. The analysis of individual biomarkers showed no significant differences between the groups. However, the OXY-SCORE was positive in the desflurane group (indicating a shift towards antioxidants) and negative in the sevoflurane group (favoring oxidants) (p < 0.044). Compared to sevoflurane, desflurane had a positive effect on oxidative stress during EVAR. The OXY-SCORE could provide a more comprehensive perspective on oxidative stress in this patient population.

Links between mutations in functionally separate arms of mitochondrial complex I and responses to volatile anesthetics.

BACKGROUND: Individuals with mitochondrial defects, especially those in Complex I of the electron transport chain, exhibit behavioral hypersensitivity and toxicity to volatile anesthetics. In Drosophila melanogaster, mutation of ND23 (NDUFS8 in mammals), which encodes a subunit of the matrix arm of Complex I, sensitizes flies to toxicity from isoflurane but not an equipotent dose of sevoflurane. Also, in ND23 flies, both anesthetics activate expression of stress response genes, but to different extents. Here, we investigated the generality of these findings by examining flies mutant for ND2 (ND2 in mammals), which encodes a subunit of the membrane arm of Complex I. METHODS: The serial anesthesia array was used to expose ND2del1 and ND2360114 flies to precise doses of isoflurane, sevoflurane, and oxygen. Behavioral sensitivity was assessed by a climbing assay and toxicity by percent mortality within 24 h of exposure. Changes in expression were determined by qRT-PCR of RNA isolated from heads at 0.5 h after anesthetic exposure. RESULTS: Unlike ND2360114, ND2del1 did not affect behavioral sensitivity to isoflurane or sevoflurane. Furthermore, sevoflurane in hyperoxia as well as anoxia caused mortality of ND2del1 but not ND2360114 flies. Finally, the mutations had different effects on induction of stress response gene expression by the anesthetics. CONCLUSION: Mutations in different arms of Complex I resulted in different behavioral sensitivities and toxicities to isoflurane and sevoflurane, indicating that (i) the anesthetics have mechanisms of action that involve arms of Complex I to different extents and (ii) the lack of behavioral hypersensitivity does not preclude susceptibility to anesthetic toxicity.

Inhalation Anesthetics Play a Janus-Faced Role in Self-Renewal and Differentiation of Stem Cells.

Inhalation anesthesia stands as a pivotal modality within clinical anesthesia practices. Beyond its primary anesthetic effects, inhaled anesthetics have non-anesthetic effects, exerting bidirectional influences on the physiological state of the body and disease progression. These effects encompass impaired cognitive function, inhibition of embryonic development, influence on tumor progression, and so forth. For many years, inhaled anesthetics were viewed as inhibitors of stem cell fate regulation. However, there is now a growing appreciation that inhaled anesthetics promote stem cell biological functions and thus are now regarded as a double-edged sword affecting stem cell fate. In this review, the effects of inhaled anesthetics on self-renewal and differentiation of neural stem cells (NSCs), embryonic stem cells (ESCs), and cancer stem cells (CSCs) were summarized. The mechanisms of inhaled anesthetics involving cell cycle, metabolism, stemness, and niche of stem cells were also discussed. A comprehensive understanding of these effects will enhance our comprehension of how inhaled anesthetics impact the human body, thus promising breakthroughs in the development of novel strategies for innovative stem cell therapy approaches.

Lidocaine combined with general anesthetics impedes metastasis of breast cancer cells via inhibition of TGF-ß/Smad-mediated EMT signaling by reprogramming tumor-associated macrophages.

Surgical resection is the best-known approach for breast cancer treatment. However, post-operative metastases increase the rate of death. The potential effect of anesthetic drugs on long-term tumor growth, risk of metastasis, and recurrence after surgery has been investigated in cancer patients. However, the underlying mechanisms remain unclear. Therefore, we aimed to elucidate the anti-metastatic effect of lidocaine combined with common anesthetics and its mechanisms of action on lung metastasis in breast cancer models. The combination of lidocaine with propofol or sevoflurane inhibited the growth of TNBC cells compared to treatment alone. In addition, the combination effectively inhibited cancer cell migration and invasion. It suppressed tumor growth and increased the survival rate in breast 4 T1 orthotopic models. More importantly, it inhibited lung metastasis and recurrence compared with groups treated with a single anesthetic. In co-culture with TAMs and TNBC cells, lidocaine not only reduced M2-tumor-associated macrophages (TAM) that were increased by sevoflurane or propofol but also increased M1 macrophage polarization, impeding tumor growth in TNBC. Also, we found that the transforming growth factor-ß (TGF-ß) derived from TAMs increased EMT signaling in TNBC cells, and that lidocaine affected cancer cells as well as M2-TAMs, inducing M2 to M1 reprogramming and decreasing TGF-ß/Smads-mediated EMT signaling in TNBC cells, leading to inhibition of cancer metastasis and recurrence. These findings suggest lidocaine combined with general anesthetics as a potential therapeutic approach for the inhibition of recurrence and metastasis of breast cancer patients undergoing curative resection.

Impact of general anesthesia type on chronic postsurgical pain following video-assisted thoracoscopic surgery for lung cancer: a retrospective propensity-matched cohort study.

Background: Anesthetic agents are potential modifiable factors that can mitigate chronic postsurgical pain (CPSP) development. This study aimed to investigate the association between propofol-based total intravenous anesthesia (TIVA) and the occurrence of CPSP following video-assisted thoracoscopic surgery (VATS) for lung cancer resection. Methods: This single-center retrospective cohort study included adult patients with lung cancer who underwent elective VATS between January 2018 and December 2022. Patients were divided based on the maintenance anesthetic used (propofol vs. sevoflurane). The primary outcome was the presence of CPSP, defined as any level of surgical site pain recorded within 3-6 months postoperatively. The authors investigated the association between anesthetic agents and CPSP using propensity score matching with stabilized inverse probability of treatment weighting (sIPTW) to adjust for confounders. Additionally, multivariable logistic regression was used to further adjust for intraoperative opioid use that sIPTW could not account for. The robustness of these associations was evaluated using the E-value. Results: Of the 833 patients analyzed, 461 received propofol and 372 sevoflurane. The overall incidence of CPSP was 43.3%. After sIPTW, the use of TIVA was significantly associated with a lower incidence of CPSP (odds ratio [OR]: 0.75, 95% confidence interval [CI]: 0.57-0.99, P = 0.041), and remained significant after adjusting for intraoperative remifentanil equivalent dose (OR: 0.73, 95% CI: 0.55-0.96, P = 0.026). The E-values were 1.08 and 1.17, respectively. Conclusions: Propofol-based TIVA is associated with reduced CPSP occurrence in VATS for lung cancer. Further prospective studies are needed to confirm the results.

Establishment of the Meyer-Overton correlation in an artificial membrane without protein.

BACKGROUND: The potency of anesthetics with various structures increases exponentially with lipophilicity, which is the Meyer-Overton (MO) correlation discovered over 120 years ago. The MO correlation was also observed with various biological effects and chemicals, including alcohols; thus, the correlation represents a fundamental relationship between chemicals and organisms. The MO correlation was explained by the lipid and protein theories, although the principle remains unknown because these are still debating. METHODS: The gentle hydration method was used to form giant unilamellar vesicles (GUVs) consisting of high- and low-melting phospholipids and cholesterol in the presence of n-alcohols (C2-C12). Confocal fluorescence microscopy was used to determine the percentage of GUVs with domains in relation to the n-alcohol concentrations. RESULTS: n-Alcohols inhibited the domain formation of GUVs, and the half inhibitory concentration (IC50) in the aqueous phase (Cw) decreased exponentially with increasing chain length (lipophilicity). In contrast, the membrane concentrations (Cm) of alcohols for the inhibition, which is a product of the membrane-water partition coefficient and the IC50 values, remained constant irrespective of the chain length. CONCLUSIONS: The MO correlation is established in GUVs, which supports the lipid theory. When alcohols reach the same critical concentration in the membrane, similar biological effects appear irrespective of the chain length, which is the principle underlying the MO correlation. GENERAL SIGNIFICANCE: The protein theory states that a highly lipophilic compound targets minor membrane proteins due to the low Cw. However, our lipid theory states that the compound targets various membrane proteins due to the high Cm.

2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery" provides recommendations to guide clinicians in the perioperative cardiovascular evaluation and management of adult patients undergoing noncardiac surgery. METHODS: A comprehensive literature search was conducted from August 2022 to March 2023 to identify clinical studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: Recommendations from the "2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery" have been updated with new evidence consolidated to guide clinicians; clinicians should be advised this guideline supersedes the previously published 2014 guideline. In addition, evidence-based management strategies, including pharmacological therapies, perioperative monitoring, and devices, for cardiovascular disease and associated medical conditions, have been developed.

A hypothalamus-lateral periaqueductal gray GABAergic neural projection facilitates arousal following sevoflurane anesthesia in mice.

BACKGROUND: The lateral hypothalamus (LHA) is an evolutionarily conserved structure that regulates basic functions of an organism, particularly wakefulness. To clarify the function of LHAGABA neurons and their projections on regulating general anesthesia is crucial for understanding the excitatory and inhibitory effects of anesthetics on the brain. The aim of the present study is to investigate whether LHAGABA neurons play either an inhibitory or a facilitatory role in sevoflurane-induced anesthetic arousal regulation. METHODS: We used fiber photometry and immunofluorescence staining to monitor changes in neuronal activity during sevoflurane anesthesia. Opto-/chemogenetic modulations were employed to study the effect of neurocircuit modulations during the anesthesia. Anterograde tracing was used to identify a GABAergic projection from the LHA to a periaqueductal gray (PAG) subregion. RESULTS: c-Fos staining showed that LHAGABA activity was inhibited by induction of sevoflurane anesthesia. Anterograde tracing revealed that LHAGABA neurons project to multiple arousal-associated brain areas, with the lateral periaqueductal gray (LPAG) being one of the dense projection areas. Optogenetic experiments showed that activation of LHAGABA neurons and their downstream target LPAG reduced the burst suppression ratio (BSR) during continuous sevoflurane anesthesia. Chemogenetic experiments showed that activation of LHAGABA and its projection to LPAG neurons prolonged the anesthetic induction time and promoted wakefulness. CONCLUSIONS: In summary, we show that an inhibitory projection from LHAGABA to LPAGGABA neurons promotes arousal from sevoflurane-induced loss of consciousness, suggesting a complex control of wakefulness through intimate interactions between long-range connections.

Outcomes in patients who received ECMO and/or volatile anesthetics as rescue therapies for status asthmaticus☠.

BACKGROUND: In the state of Kentucky, many status asthmaticus (SA) patients require care in the Pediatric Intensive Care Unit (PICU) and a fraction of these patients may receive "rescue therapies" with inhaled volatile anesthetics (IVA) and/or Extracorporeal Membrane Oxygenation (ECMO). We present a series of such patients with the objective of comparing the clinical parameters of individual patients who received inhaled volatile anesthesia and subsequently the need for ECMO. METHODS: Children between 2 and 18 years of age admitted to our PICU from January 2014 to July 2020 with SA were reviewed and categorized as 1) patients who received IVA alone, 2) patients who received IVA and then subsequently ECMO, and 3) patients on ECMO alone. RESULTS: A total of 1772 children with SA episodes were identified with a mortality of 13 patients. Seven children with SA were identified who received either IVA, ECMO, or both. One patient received only IVA, 5 received both IVA and ECMO and one received only ECMO. All received standard asthma therapies of steroids, albuterol, magnesium sulphate, and aminophylline prior to escalation. Six out of seven refractory SA received IVA, and five (83%) of those were subsequently escalated to ECMO. There was an improvement in mean pH after cannulation compared to IVA. pCO2 levels had no improvement after IVA administration but decreased by an average of 20 points after ECMO. Patients peak inspiratory pressures decreased within the 1st 24 h of ECMO cannulation from a mean of 30 to 18. There were no other complications related to ECMO placement. CONCLUSION: While we cannot decisively draw any conclusions from our study due to the small sample, it was noted that there was no clear advantage of using IVA prior to ECMO in our patients. Most patients who received IVA were escalated to ECMO indicating that early ECMO cannulation may be beneficial. Given the high cost and potential complications of both, there is a need for the development of well-defined guidelines for severe SA management in the PICU.

Use of Loco-regional Anesthesia in Austere Environments: A Review by and for Special Forces Medics.

Special Forces increasingly operate in austere environments, which are known to have limited medical support and prolonged evacuation times. On the battlefield, pain remains the first complaint of casualties and can impact direct autonomic stability, recovery, and the development of posttraumatic stress disorder. Although medical education has been improving, medical providers still encounter difficulties, such as lack of human and material resources, while trying to achieve pain management. This article summarizes a survey sent to 35 Special Operations medical providers and suggests possible strategies to address challenges to pain management on the battlefield. Potential solutions have been gathered through medical texts, medical/NATO documents, and medical expertise. Nerves blocks have been identified as valuable tools for pain management in the current battlefield environment, where prolonged evacuation and limited freedom of movement are the norm. The survey showed that, although the vast majority of providers had already received lectures on regional anesthesia, 83% were not trained in it, and 54% had never been made aware of multimodal analgesia. This lack of familiarity highlights knowledge and training gaps in nerve block techniques. Diffusion blocks are a very low-risk, useful, and safe pain management technique, which requires less skill sustainment and resources than more complex techniques. The use of epinephrine as adjunct can be useful for decreasing local anesthetic toxicity and increasing long-term pain management. The need for both education on and training in the use of nerve blocks has been identified by the Special Operations health provider community.

Frailty Is Associated With Increased Care Dependence in Patients Following Major Vascular Surgery.

OBJECTIVE: To assess if frailty scoring can predict increased frailty and care dependence requiring a change in living situation in patients with peripheral artery disease (PAD) following major vascular surgery. DESIGN: A single center, retrospective cohort study. SETTING: Fiona Stanley Hospital, a tertiary center located in Perth, Western Australia. PARTICIPANTS: Seventy-nine patients with PAD who underwent major vascular surgery at the study hospital in 2022 were enrolled. INTERVENTION: Baseline Clinical Frailty Scale (CFS) scores were assigned retrospectively. A quantitative analysis using two partitions, CFS 1-3 (not frail) versus 4-9 (frail) was used. Cases were screened for hospital-acquired complications, and records were reviewed to assess the level of care dependence at the time of discharge and 6 months following. MEASUREMENTS AND MAIN RESULTS: The primary outcome was to assess if frailty predicts increased care dependence. Secondary outcomes included unplanned readmissions and hospital-acquired complications in this cohort. A logistic regression was performed to predict the effects of age and baseline, discharge, and 6-month CFS on the likelihood of change in living situation. Baseline frailty was associated with a higher frailty score at discharge (p = 0.001), which persisted at 6 months (p = 0.001). There was no difference in American Society of Anesthesiologists classification, sex, age, 30-day mortality, or in-hospital complications between groups. After correcting for age, a lower baseline CFS (odds ratio 0.19, confidence interval 0.04-0.84, p = 0.028) and discharge CFS (odds ratio 34.00, confidence interval 3.88-298.42, p = 0.001) predicts the likelihood of patients having a change in living situation after surgery. CONCLUSIONS: Frail patients with PAD undergoing major vascular surgery are at significant risk of functional decline, necessitating a change in living situation to meet their increased care needs. This increased care dependence persisted 6 months following discharge.

Correlation between anesthetic concentration and low Apgar scores in neonates born via Cesarean sections under general anesthesia.

OBJECTIVES: This study aimed to compare plasma concentrations of anesthetic drugs administered during Cesarean section with low Apgar score in neonates deliveried under general anesthesia and analyze associated risk factors. METHODS: Data from 76 neonates undergoing Cesarean section under general anesthesia with blood concentrations of anesthetic drugs were analyzed. A low Apgar score was defined as ≤ 7. Perioperative maternal and neonatal data were collected and analyzed. Neonates were divided into a control group (Group CON, n = 65) and a low Apgar score group (Group LAS, n = 11) based on Apgar score. RESULTS: There were no significant differences in the plasma concentrations of anesthetic drugs in maternal artery, umbilical vein or umbilical artery blood between the two groups. Risk factors for neonatal low Apgar scores during Cesarean section under general anesthesia were premature delivery (aOR 10.2, 95% CI = 1.8-56.9) and preoperative fetal distress (aOR 9.6, 95% CI = 1.3-69.0). The prediction model was: probability = 1/(e­Y), Y= -4.607 + 2.318× (premature delivery) + 2.261× (fetal distress) (yes = 1, no = 0). The Hosmer-Lemeshow test showed χ²= 9.587, P = 0.213, and the area under the curve (AUC) was 0.850 (0.670 ~ 1.000). With a cutoff value of 0.695, sensitivity and specificity were 81.8% and 87.7%, respectively. CONCLUSIONS: There was no correlation between blood concentration of general anesthetic drugs and Apgar score or occurrence of neonatal low Apgar scores. Premature delivery and preoperative fetal distress were identified as independent risk factors for neonatal low Apgar scores after Cesarean section under general anesthesia.

Assessing the effectiveness of greater occipital nerve block in chronic migraine: a systematic review and meta-analysis.

BACKGROUND & AIMS: Chronic migraine poses a global health burden, particularly affecting young women, and has substantial societal implications. This study aimed to assess the efficacy of Greater Occipital Nerve Block (GONB) in individuals with chronic migraine, focusing on the impact of local anesthetics compared with placebo. METHODS: A meta-analysis and systematic review were conducted following the PRISMA principles and Cochrane Collaboration methods. Eligible studies included case-control, cohort, and randomized control trials in adults with chronic migraine, adhering to the International Classification of Headache Disorders, third edition (ICHD3). Primary efficacy outcomes included headache frequency, duration, and intensity along with safety assessments. RESULTS: Literature searches across multiple databases yielded eight studies for qualitative analysis, with five included in the final quantitative analysis. A remarkable reduction in headache intensity and frequency during the first and second months of treatment with GONB using local anesthetics compared to placebo has been reported. The incidence of adverse events did not differ significantly between the intervention and placebo groups. CONCLUSION: The analysis emphasized the safety and efficacy of GONB, albeit with a cautious interpretation due to the limited number of studies and relatively small sample size. This study advocates for further research exploring various drugs, frequencies, and treatment plans to enhance the robustness and applicability of GONB for chronic migraine management.

Quadratus lumborum block for procedural and postprocedural analgesia in renal cell carcinoma percutaneous cryoablation.

This study assesses the efficacy of the quadratus lumborum block (QLB) in the management of procedural and periprocedural pain associated with small renal mass cryoablation. To the best of our knowledge, this is the first study that examines the use of QLB for pain management during percutaneous cryoablation of renal cell carcinoma (RCC). A single-center retrospective review was conducted for patients who underwent cryoablation for RCC with QLB between October 2020 and October 2021. The primary study endpoint included a total dose of procedural conscious sedation and administered, postprocedural analgesia. Technical success in cryoablation was achieved in every case. No patients required additional analgesic during or after the procedure, and no complications resulted from the use of the QLB. The QLB procedure appears to be an effective locoregional block for the management of procedural and periprocedural pain associated with renal mass cryoablation.

The efficient method to get better raw brain signal on rat anesthetics experiment.

This paper introduces an efficient methodology for conducting rat anesthesia experiments, aimed at enhancing the quality of raw brain signals obtained. The proposed approach enables the acquisition of animal brain signals during experiments without the confounding influence of muscle noise. Initially, the use of alpha-chloralose (a-c) in conjunction with Isoflurane is introduced to induce anesthesia in rats. Subsequently, Dexdomitor is administered to prevent muscular movements during the collection of brain signals, further refining the signal quality. Experimental outcomes conclusively demonstrate that our anesthesia method produces cleaner raw signals and exhibits improved robustness during data acquisition, outperforming existing methods that rely solely on Isoflurane or the Ketamine-Xylazine combination. Notably, this improved performance is achieved with minimal alterations to vital physiological parameters, including body temperature, respiration, and heart rates. Moreover, the efficacy of a-c in maintaining anesthesia for up to 7 h stands in contrast to the shorter durations achievable with continuous Isoflurane administration or the 30-min window offered by Ketamine-Xylazine, highlighting the practical advantages of our proposed method. Finally, post-experiment observations confirmed that the animals gradually returned to normal behavior without any signs of distress or adverse effects, indicating that our method was both effective and safe.

Neddylation signaling inactivation by tetracaine hydrochloride suppresses cell proliferation and alleviates vemurafenib-resistance of melanoma.

Tetracaine, a local anesthetic, exhibits potent cytotoxic effects on multiple cancer; however, the precise underlying mechanisms of its anti-cancer activity remain uncertain. The anti-cancer activity of tetracaine was found to be the most effective among commonly used local anesthetics in this study. After tetracaine treatment, the differentially expressed genes in melanoma cells were identified by the RNAseq technique and enriched in the lysosome signaling pathway, cullin family protein binding, and proteasome signaling pathway through Kyoto Encyclopedia of Genes and Genomes. Additionally, the ubiquitin-like neddylation signaling pathway, which is hyperactivated in melanoma, could be abrogated due to decreased NAE2 expression after tetracaine treatment. The neddylation of the pro-oncogenic Survivin, which enhances its stability, was significantly reduced following treatment with tetracaine. The activation of neddylation signaling by NEDD8 overexpression could reduce the antitumor efficacy of tetracaine in vivo and in vitro. Furthermore, vemurafenib-resistant melanoma cells showed higher level of neddylation, and potential substrate proteins undergoing neddylation modification were identified through immunoprecipitation and mass spectrometry. The tetracaine treatment could reduce drug resistance via neddylation signaling pathway inactivation in melanoma cells. These findings demonstrate that tetracaine effectively inhibits cell proliferation and alleviates vemurafenib resistance in melanoma by suppressing the neddylation signaling pathway, providing a promising avenue for controlling cancer progression.

Influence of Anesthetic Regimes on Extracellular Vesicles following Remote Ischemic Preconditioning in Coronary Artery Disease.

Remote ischemic preconditioning (RIPC) reduces ischemia-reperfusion injury in aortocoronary bypass surgery, potentially via extracellular vesicles (EVs) and their micro-RNA content. Clinical data implicate that propofol might inhibit the cardioprotective RIPC effect. This prospective, randomized study investigated the influence of different anesthetic regimes on RIPC efficacy and EV micro-RNA signatures. We also assessed the impact of propofol on cell protection after hypoxic conditioning and EV-mediated RIPC in vitro. H9c2 rat cardiomyoblasts were subjected to hypoxia, with or without propofol, and subsequent simulated ischemia-reperfusion injury. Apoptosis was measured by flow cytometry. Blood samples of 64 patients receiving anesthetic maintenance with propofol or isoflurane, along with RIPC or sham procedures, were analyzed, and EVs were enriched using a polymer-based method. Propofol administration corresponded with increased Troponin T levels (4669 ± 435.6 pg/mL), suggesting an inhibition of the cardioprotective RIPC effect. RIPC leads to a notable rise in miR-21 concentrations in the group receiving propofol anesthesia (fold change 7.22 ± 6.6). In vitro experiments showed that apoptosis reduction was compromised with propofol and only occurred in an EV-enriched preconditioning medium, not in an EV-depleted medium. Our study could clinically and experimentally confirm propofol inhibition of RIPC protection. Increased miR-21 expression could provide evidence for a possible inhibitory mechanism.

2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery" provides recommendations to guide clinicians in the perioperative cardiovascular evaluation and management of adult patients undergoing noncardiac surgery. METHODS: A comprehensive literature search was conducted from August 2022 to March 2023 to identify clinical studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: Recommendations from the "2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery" have been updated with new evidence consolidated to guide clinicians; clinicians should be advised this guideline supersedes the previously published 2014 guideline. In addition, evidence-based management strategies, including pharmacological therapies, perioperative monitoring, and devices, for cardiovascular disease and associated medical conditions, have been developed.

Local anesthetic tetracaine hydrochloride induces pyroptosis via caspase-3/gasdermin E in uveal melanoma.

BACKGROUND: Evasion of pyroptosis is an effective survival strategy employed by cancer cells to evade immune cell attacks and drug-induced cytotoxicity. Exploring potent molecules capable of inducing pyroptosis in cancer cells has significant clinical implications for the control of cancer progression. Unexpectedly, we found that the local anesthetic tetracaine hydrochloride (TTC) induced pyroptosis, specifically in uveal melanoma but not in acral or cutaneous melanoma. METHODS: We investigated the effects of TTC on various melanoma cell lines and performed transcriptome sequencing of TTC-treated uveal melanoma cells. The role of gasdermin E (GSDME), an executive protein responsible for pyroptosis, was explored using CRISPR-Cas13d knockdown, caspase-3 inhibitor treatment, and western blot analysis. Differential gene expression and pathway enrichment analyses were performed. Furthermore, we used tissue microarrays to assess GSDME expression levels in melanoma tissues from different anatomical sites. RESULTS: TTC significantly induced pyroptosis specifically in uveal melanoma cells with high GSDME expression levels. TTC treatment could lead to GSDME cleavage by the caspase-3 in uveal melanoma C918 cells. GSDME knockdown or caspase-3 inhibition suppressed TTC-induced pyroptosis. Transcriptome analysis revealed differentially expressed genes enriched in signaling pathways related to pyroptosis, immunity, and cytokines. CONCLUSIONS: This study showed that the local anesthetic TTC effectively induces pyroptosis in uveal melanoma through the caspase-3/GSDME pathway, highlighting its potential application in immunotherapy. Notably, the use of TTC has potential as an agent for inducing pyroptosis and as an adjuvant anticancer therapy in uveal melanoma.

A comparison of steroid dose with or without local anesthetic in lumbar interlaminar epidural steroid injections.

INTRODUCTION: Epidural steroid injections (ESIs) are commonly used as a treatment for lumbar radiculopathy. Currently, most research on comparative efficacy of various steroids in epidural steroid injections is focused on transforaminal ESIs (TFESIs). Through this study, we aimed to compare various steroid doses with or without local anesthetic in interlaminar ESIs (ILESIs). METHODS: We reviewed charts for all adult patients who received ILESIs identified by CPT code 62323 between January 2017 to April 2021. Baseline demographic data including age, sex, BMI, and smoking status were recorded. NRS pain scores before the injection and percentage of pain relief at 1-month follow-up were recorded. We compared percentage of patients reporting pain relief at 1 month follow-up of low-dose dexamethasone alone (5 mg), to low-dose dexamethasone mixed with local anesthetic, and to high-dose dexamethasone (10 mg) mixed with local anesthetic, specifically for ILESIs. RESULTS: Data were available for 311 patients. There was no significant difference in pain relief between the 3 groups at 1 month follow-up. The majority of patients had moderate to significant improvement in pain, supporting the use of ILESIs. Moreover, low-dose steroid with local anesthetic was found to be as efficacious as high-dose steroid alone. Although not statistically significant, the addition of local anesthetic to low-dose or high-dose steroid increased the percentage of patients reporting moderate to significant pain relief. CONCLUSION: ILESIs with non-particulate steroids provide moderate to significant pain improvement in the short term, with low-dose steroid mixed with local anesthetic being as efficacious as a high-dose steroid.