Uncovering essential anesthetics-induced exosomal miRNAs related to hepatocellular carcinoma progression: a bioinformatic investigation.

BACKGROUND: Anesthetic drugs may alter exosomal microRNA (miRNA) contents and mediate cancer progression and tumor microenvironment remodeling. Our study aims to explore how the anesthetics (sevoflurane and propofol) impact the miRNA makeup within exosomes in hepatocellular carcinoma (HCC), alongside the interconnected signaling pathways linked to the tumor immune microenvironment. METHODS: In this prospective study, we collected plasma exosomes from two groups of HCC patients (n = 5 each) treated with either propofol or sevoflurane, both before anesthesia and after hepatectomy. Exosomal miRNA profiles were assessed using next-generation sequencing (NGS). Furthermore, the expression data from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) was used to pinpoint the differentially expressed exosomal miRNAs (DEmiRNAs) attributed to the influence of propofol or sevoflurane in the context of HCC. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to dissect the signaling pathways and biological activities associated with the identified DEmiRNAs and their corresponding target genes. RESULTS: A total of 35 distinct DEmiRNAs were exclusively regulated by either propofol (n = 9) or sevoflurane (n = 26). Through TCGA-LIHC database analysis, 8 DEmiRNAs were associated with HCC. These included propofol-triggered miR-452-5p and let-7c-5p, as well as sevoflurane-induced miR-24-1-5p, miR-122-5p, miR-200a-3p, miR-4686, miR-214-3p, and miR-511-5p. Analyses revealed that among these 8 DEmiRNAs, the upregulation of miR-24-1-5p consistently demonstrated a significant association with lower histological grades (p < 0.0001), early-stage tumors (p < 0.05) and higher survival (p = 0.029). Further analyses using GSEA and GSVA indicated that miR-24-1-5p, along with its target genes, were involved in governing the tumor immune microenvironment and potentially inhibiting tumor progression in HCC. CONCLUSIONS: This study provided bioinformatics evidence suggesting that sevoflurane-induced plasma exosomal miRNAs may have a potential impact on the immune microenvironment of HCC. These findings established a foundation for future research into mechanistic outcomes in cancer patients.

Congenital Sub-Mitral Aneurysm: Anesthetics and Surgical Management.

ABSTRACT: A sub-mitral left ventricular aneurysm is a rare condition. It is a congenital outpouching of the left ventricular wall, invariably occurring adjacent to the posterior mitral leaflet. Sub-mitral aneurysm (SMA) has usually been reported as a consequence of myocardial ischemia (MI), rheumatic heart disease, tuberculosis, and infective endocarditis. Nevertheless, there have been few case reports of congenital SMA in India. It usually presents with symptoms of heart failure. We report a rare case of congenital SMA in a 27-year-old young Indian and its successful management through a trans-aneurysmal approach.

O-GlcNAcylation levels remain stable regardless of the anaesthesia in healthy rats.

Anaesthetics are used daily in human and veterinary medicine as well as in scientific research. Anaesthetics have an impact on cell homeostasis especially through modulation of protein post-translational modifications. O-GlcNAcylation, a ubiquitous post-translational modification, plays a role in many biological processes. The aims of this study were to evaluate whether (1) anaesthesia influences O-GlcNAcylation and (2) its stimulation affects physiological parameters. Male Wistar rats (n = 38) were anaesthetized with ketamine-xylazine or isoflurane. They randomly received either an intravenous injection of Ringer's lactate or NButGT (10mg/kg) in order to increase O-GlcNAcylation levels. One hour after induction of anaesthesia, haemodynamic parameters and plasmatic markers were evaluated. Heart, brain and lungs were harvested and O-GlcNAcylation levels and O-GlcNAc-related enzymes were evaluated by western blot. Cardiac and pulmonary O-GlcNAcylation levels and cardiac, cerebral and pulmonary O-GlcNAc associated enzyme expression were not impacted with anaesthesia. Compared with ketamine-xylazine, isoflurane had a lower impact on blood pressure, heart rate and glycaemia. Pharmacological stimulation of O-GlcNAcylation by NButGT did not affect the physiological parameters. This study offers unprecedented insights into the regulation of O-GlcNAcylation and O-GlcNAc related enzymes during anaesthesia. Pharmacological stimulation of O-GlcNAcylation over a 1-h period did not disrupt the physiological balance in healthy anaesthetized rats.

Anaesthetics reduce the viability of adipose-derived stem cells.

Adipose-derived stem cells (ADSCs) are characterized by their low immunogenicity and unique immunosuppressive properties, providing many opportunities for autologous transplantation in regenerative medicine and plastic surgery. These methods are characterized by low rejection rates and intense stimulation of tissue regeneration. However, procedures during which fat tissue is harvested occur under local anaesthesia. To better understand the effects and mechanisms of anaesthetic compounds in cosmetic and therapeutic procedures, the present study used a mixture of these compounds (0.1% epinephrine, 8.4% sodium bicarbonate, and 4% articaine) and examined their impact on a human adipose-derived stem cell line. The results showed anesthetics' negative, dose-dependent effect on cell viability and proliferation, especially during the first 24 h of incubation. After extending the exposure to 48 and 72 h of incubation, cells adapted to new culture conditions. In contrast, no significant changes were observed in immunophenotype, cell cycle progression, and apoptosis. The results obtained from this study provide information on the effect of the selected mixture of anaesthetics on the characteristics and function of ASC52telo cells. The undesirable changes in the metabolic activity of cells suggest the need to search for new drugs to harvest cells with unaltered properties and higher efficacy in aesthetic medicine treatments.

Is there a future for nitrous oxide in anaesthetic practice?

Although nitrous oxide is widely used for analgesia and anxiolysis, its use is under scrutiny because of concerns about its environmental impact and potential implications for mental health. This article discusses the advantages and disadvantages of this agent.

Neutrophils and Anesthetic Drugs: Implications in Onco-Anesthesia.

Apart from being a significant line of defense in the host defense system, neutrophils have many immunological functions. Although there are not many publications that accurately present the functions of neutrophils in relation to oncological pathology, their activity and implications have been studied a lot recently. This review aims to extensively describe neutrophils functions'; their clinical implications, especially in tumor pathology; the value of clinical markers related to neutrophils; and the implications of neutrophils in onco-anesthesia. This review also aims to describe current evidence on the influence of anesthetic drugs on neutrophils' functions and their potential influence on perioperative outcomes.

Heparin-induced DRESS syndrome in a paediatric patient and successful anaesthetic management in cardiovascular bypass surgery: case report.

BACKGROUND: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin. CASE PRESENTATION: We report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia. CONCLUSION: The severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient's needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions.

Effects of Thermal Insulation on Recovery and Comfort of Patients Undergoing Holmium Laser Lithotripsy.

BACKGROUND Patients with urolithiasis often undergo transurethral ureteroscopic holmium laser lithotripsy, a procedure that can be affected by perioperative thermal management. This study examines the impact of compound thermal insulation management on patient recovery and comfort during transurethral ureteroscopic holmium laser lithotripsy. MATERIAL AND METHODS In this study, 551 patients who underwent transurethral ureteroscopic holmium laser lithotripsy from April 2019 to December 2022 were randomly assigned to either an observation group (n=276) or control group (n=275). Both groups received routine surgical care, with the observation group additionally receiving compound thermal insulation management. We recorded and compared perioperative body temperature changes, anesthetic resuscitation indicators (bispectral index recovery time, extubation time, fully awake time, Postanesthesia Care Unit retention time), comfort level (General Comfort Questionnaire), and quality of life (Nottingham Health Profile). We also compared the incidence of complications. RESULTS There was no significant difference in body temperature between groups at the start surgery. However, the observation group showed significantly higher temperatures during and at the end of surgery. Anesthetic resuscitation indicators were significantly better in the observation group. Both groups showed improved comfort and quality of life after surgery, with more significant improvements in the observation group. The observation group also had a lower incidence of complications, such as hypothermia and rigor. CONCLUSIONS Compound thermal insulation management during transurethral ureteroscopic holmium laser lithotripsy improved perioperative temperature maintenance, accelerated postoperative recovery, reduced complication rates, and enhanced patient comfort and quality of life.

A Review of the Current Status of Anesthetic Management of Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic connective tissue disease of immunological etiology. In the course of the disease, symptoms of the musculoskeletal system predominate, but other systems can also be affected. The disease may require long-term treatment, and patients often require surgery on damaged joints. Complications of the disease and drug interactions may contribute to difficulties in perioperative care; therefore, knowledge is required to provide appropriate care. When anesthetizing a patient with RA, we should pay special attention to preoperative evaluation, taking a medical history, risk of difficult intubation or cardiac incidents, respiratory insufficiency, and frequent pulmonary infections. It is important to be aware of perioperative glucocorticoids supplementation, especially in patients with suspected adrenal insufficiency. Postoperative management, such as pain management, early rehabilitation, and restart of pharmacotherapy play, an important role in the patient's recovery. Special attention should be paid to perioperative management in pregnant women, as the disease is a significant risk factor for complications, and some anesthetic procedures can be noxious to the fetus. Due to the nature of the disease, it can be challenging for the anesthesiologist to provide good and appropriate pain medications, symptom management, and other necessary techniques that are done to anesthetize the patient properly. This work is based on the available literature and the authors' experience. This article aims to review the current status of anesthetic management of patients with rheumatoid arthritis.

Alfaxalone is an effective anesthetic for the electrophysiological study of anoxia-tolerance mechanisms in western painted turtle pyramidal neurons.

Anoxia in the mammalian brain leads to hyper-excitability and cell death; however, this cascade of events does not occur in the anoxia-tolerant brain of the western painted turtle, Chrysemys picta belli. The painted turtle has become an important anoxia-tolerant model to study brain, heart, and liver function in the absence of oxygen, but being anoxia-tolerant likely means that decapitation alone is not a suitable method of euthanasia. Many anesthetics have long-term effects on ion channels and are not appropriate for same day experimentation. Using whole-cell electrophysiological techniques, we examine the effects of the anesthetic, Alfaxalone, on pyramidal cell action potential amplitude, threshold, rise and decay time, width, frequency, whole cell conductance, and evoked GABAA receptors currents to determine if any of these characteristics are altered with the use of Alfaxalone for animal sedation. We find that Alfaxalone has no long-term impact on action potential parameters or whole-cell conductance. When acutely applied to naïve tissue, Alfaxalone did lengthen GABAA receptor current decay rates by 1.5-fold. Following whole-animal sedation with Alfaxalone, evoked whole cell GABAA receptor current decay rates displayed an increasing trend with 1 and 2 hours after brain sheet preparation, but showed no significant change after a 3-hour washout period. Therefore, we conclude that Alfaxalone is a suitable anesthetic for same day use in electrophysiological studies in western painted turtle brain tissue.

Dexmedetomidine for Preventing Sleep Disturbance after Ambulatory Anesthesia: A Case Report.

Propofol anesthesia may impact a patient's sleep quality in the immediate postprocedure timeframe. We describe a 24-year-old man presenting for gastrostomy-jejunostomy tube replacement who reported debilitating sleep-onset disturbances after 3 previous anesthetic exposures for the same procedure. Review of the patient's records revealed the recurring use of propofol infusion. We proposed using dexmedetomidine infusion to potentially avoid another extended sleep disturbance. Following a dexmedetomidine-centered plan, the patient reported experiencing his usual sleep pattern without side-effects for 5 consecutive days postprocedure. This case highlights the potential for propofol-induced sleep disturbance in the ambulatory setting, which may be avoided with dexmedetomidine administration.

Anesthetic Management of a Patient with MIRAGE Syndrome: A Case Report.

MIRAGE syndrome consists of Myelodysplasia, Infection, Growth restriction, Adrenal hypoplasia, Genital phenotypes, and Enteropathy. We report the uneventful anesthesia management of a 6-year-old female patient with MIRAGE syndrome. We think it can guide anesthesiologists caring for patients with this syndrome to find the appropriate method for them.

Anaesthesia-related morbidity associated with recumbent, low-field magnetic resonance imaging of horses.

CASE HISTORY: Medical records from 2009 to 2021 from a private equine referral hospital in Rochester, NH, USA were analysed for cases that underwent general anaesthesia for low-field MRI of the distal limb. These were used to determine peri-anaesthetic morbidity and mortality. CLINICAL FINDINGS AND OUTCOME: Two hundred and forty-three anaesthetic episodes were recorded in horses undergoing low-field MRI. The peri-anaesthetic complication rate prior to discharge was 6.2% (15/243). No patients experienced a fatal complication. Ninety two of the 243 patients had multiple sites imaged, 90/243 received pre-anaesthetic dantrolene, 134/243 received intra-anaesthetic dobutamine, and 15/243 were positioned in dorsal recumbency. Complications included: abdominal discomfort ("colic"; 9/243), myopathy (4/243), hyphaema (1/243) and carpal fracture (1/243). At the time of discharge, 14/15 complications had resolved. Of 135 horses for which data were available 55 became hypotensive during the procedure (lowest mean arterial pressure < 65 mmHg). Median body weight was 553 (min 363, max 771) kg. Horses were anaesthetised for a median of 150 (min 45, max 210) minutes. There was no evidence of an association between higher body weight (p = 0.051) or longer duration of anaesthesia (p = 0.421) and development of an anaesthetic complication. For categorical variables (dantrolene administration pre-anaesthesia, dobutamine administration during anaesthesia, hypotension (mean < 65 mmHg) during anaesthesia, dorsal vs. lateral recumbency, and imaging of single vs. multiple sites), the 95% CI for the OR included 1, indicating a lack of effect of the variable on the odds of complication. CLINICAL RELEVANCE: The cases included in this series suggest that low-field MRI under general anaesthesia is a viable option for diagnostic imaging in otherwise healthy horses. Complications occur, but most resolve before discharge.

Anesthetic Management of a Patient with Madelung's Disease Presenting with a Giant Cervical Lipoma: A Case Report.

Madelung's disease is characterized by the presence of multiple symmetric and nonencapsulated facial, neck, and upper trunk lipomas. Depending on the location and size of lipomas, there may be concerns for difficult airway management and cardiovascular collapse. We present the anesthetic management case of a patient with cervical and mediastinal lipomas who underwent elective cervical lipoma resection.

Unilateral Sacral Erector Spinae Plane Block for Thigh Amputation: Case Report.

Selection of anesthetic technique for thigh amputation is complicated by patients' comorbid conditions. The sacral erector spinae plane block (ESPB) is an emerging technique with potential as a primary anesthetic for thigh amputation. We detail a case involving a 79-year-old undergoing thigh amputation, where sacral ESPB proved insufficient, prompting a shift to spinal anesthesia. This instance underscores the necessity for further investigation into the reliability of the sacral ESPB for lower limb surgeries. Until such evidence is established, caution is advised in relying solely on the sacral ESPB for thigh amputations, and consideration of alternative techniques is recommended.

The effect of anesthetic blockade of greater occipital nerve during the withdrawal period of the medication overuse headache treatment.

Background and purpose:

Discontinua­tion of medication still remains a key element in the treatment of medication overuse headache (MOH), but there is no consensus on the withdrawal procedure. We aimed to share the promising results of anesthetic blockade of greater occipital nerve (GON), which can be an alternative to existing treatments during the early withdrawal period of MOH treatment.

This study was conducted using regular electronic medical records and headache diaries of patients diagnosed with MOH and treated with anesthetic GON blockade with 0.5% bupivacaine solution in a specia­lized headache outpatient clinic. A total of 86 patients who developed MOH while being followed up for chronic migraine were included in the study.

The treatment schemes for MOH are based on expert consensus and withdrawal strategies are the most challenging part of treatment. In our study, numerical rating scale for headache intensity, overused medication consumption per month, headache frequency (day/month) and the duration of each attack (hour/day) decreased significantly in the first month compared to pre-treatment (p < 0.01). 

Conclusion – Our study suggests that GON blockade can be used as a good alternative therapy in the treatment of MOH.

Anesthesia and the neurobiology of consciousness.

In the 19th century, the discovery of general anesthesia revolutionized medical care. In the 21st century, anesthetics have become indispensable tools to study consciousness. Here, I review key aspects of the relationship between anesthesia and the neurobiology of consciousness, including interfaces of sleep and anesthetic mechanisms, anesthesia and primary sensory processing, the effects of anesthetics on large-scale functional brain networks, and mechanisms of arousal from anesthesia. I discuss the implications of the data derived from the anesthetized state for the science of consciousness and then conclude with outstanding questions, reflections, and future directions.