Effect of propofol and sevoflurane on postoperative fatigue after laparoscopic hysterectomy.

BACKGROUND: Postoperative fatigue syndrome (POFS) is an important factor in postoperative recovery. However, the effect of anesthetic drugs on postoperative fatigue in female patients has been rarely studied. This study compared the effects of maintaining general anesthesia with propofol or sevoflurane on the incidence of POFS in patients undergoing laparoscopic hysterectomy. METHODS: This prospective, single-blind, randomized controlled trial enrolled patients scheduled for laparoscopic hysterectomy. Eligible patients were randomized into the propofol and sevoflurane groups. The primary outcome was the incidence of POFS within 30 Days, defined by a simplified identity consequence fatigue scale (ICFS-10) scores≥24 or Visual Analogue Scale (VAS) scores of fatigues>6. Secondary outcomes were perioperative grip strength, early ambulation and anal exhaust after surgery, and inpatient days. RESULTS: 32 participants were assigned to the propofol group (P) and 33 to the sevoflurane group (S). Incidence of POFS on postoperative D1 was P (8/32) vs. S (10/33) (p = 0.66, 95% confidence interval [CI]: 16.4-27.00); D3 P (2/32) vs. S (5/33) (p = 0.45,95% CI:5.96-23.76). POFS were not found on postoperative D5 and D30. There were no differences in perioperative grip strength, early ambulation and anal exhaust after surgery, and inpatient days between the two groups. CONCLUSIONS: POFS after scheduled laparoscopic hysterectomy was unaffected by anesthesia with propofol vs. sevoflurane. The incidence of POFS was highest on the first postoperative day, at 27.7%, and declined progressively over the postoperative 30 days. Trial registration Chinese Clinical Trial Registry (No. ChiCTR 2,000,033,861), registered on 14/06/2020).

Baseline symptom-related white matter tracts predict individualized treatment response to 12-week antipsychotic monotherapies in first-episode schizophrenia.

There is significant heterogeneity in individual responses to antipsychotic drugs, but there is no reliable predictor of antipsychotics response in first-episode psychosis. This study aimed to investigate whether psychotic symptom-related alterations in fractional anisotropy (FA) and mean diffusivity (MD) of white matter (WM) at the early stage of the disorder may aid in the individualized prediction of drug response. Sixty-eight first-episode patients underwent baseline structural MRI scans and were subsequently randomized to receive a single atypical antipsychotic throughout the first 12 weeks. Clinical symptoms were evaluated using the eight "core symptoms" selected from the Positive and Negative Syndrome Scale (PANSS-8). Follow-up assessments were conducted at the 4th, 8th, and 12th weeks by trained psychiatrists. LASSO regression model and cross-validation were conducted to examine the performance of baseline symptom-related alterations FA and MD of WM in the prediction of individualized treatment outcome. Fifty patients completed both clinical follow-up assessments by the 8th and 12th weeks. 30 patients were classified as responders, and 20 patients were classified as nonresponders. At baseline, the altered diffusion properties of fiber tracts in the anterior thalamic radiation, corticospinal tract, callosum forceps minor, longitudinal fasciculi (ILF), inferior frontal-occipital fasciculi (IFOF) and superior longitudinal fasciculus (SLF) were related to the severity of symptoms. These abnormal fiber tracts, especially the ILF, IFOF, and SLF, significantly predicted the response to antipsychotic treatment at the individual level (AUC = 0.828, P < 0.001). These findings demonstrate that early microstructural WM changes contribute to the pathophysiology of psychosis and may serve as meaningful individualized predictors of response to antipsychotics.

Assessing the Global, Regional, and National Impact of High Body Mass Index on Alzheimer's Disease and Other Dementias Between 1990 and 2019.

BACKGROUND: Obesity significantly increases Alzheimer's disease (AD) and dementia risk. Understanding the link between a high body mass index (BMI) and these conditions is crucial for effective management and prevention. OBJECTIVE: We aimed to estimate the burden of AD and other dementias attributed to high BMI from 1990 to 2019 based on sex, age, and socio-demographic indicators (SDI) at global, regional, and national levels. METHODS: We collected data on deaths, disability-adjusted life years (DALYs), age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR) from the 2019 Global Burden of Disease study for AD and dementia attributed to high BMI. We explored the correlation between SDI levels and ASDR. RESULTS: In 2019, there were 198,476.2 deaths (95% UI: 32,695.4-593,366.4) and 3,159,912.4 DALYs (848,330.5-8,042,531) attributed to high BMI. Numbers of deaths, DALYs, ASMR, and ASDR increased since 1990. Females had higher deaths, ASMR, and ASDR than males. Mortality and DALYs rates increased with age. ASMR and ASDR increased across five SDI levels, with the highest rise in Low-middle SDI. High-income North America had the most deaths [30,993.9 (5,101.7-89,912.9)], while North Africa and the Middle East had the highest ASMR [4.61 (0.79-13.64)] and ASDR [72.56 (20.98-181.16)] in 2019. CONCLUSIONS: The burden of AD and other dementias attributed to high BMI increased since 1990 globally and is still heaviest in developed regions. Females accounted predominantly for the burden than males. Timely measures are needed to against high BMI.

Realizing tunneling electroresistance effect in the Au/h-BN/In2Se3/Au vertical ferroelectric tunnel junction.

Two-dimensional (2D) ferroelectric tunnel junctions (FTJs) have great potential in the design of non-volatile memory devices due to the tunneling electroresistance (TER) effect and the fact that it is not constrained by critical thickness. Incorporation of 2D ferroelectric materials in realistic FTJs inevitably involves the contacts to the traditional three-dimensional (3D) metals. However, how to design the FTJs by combining the 2D ferroelectric materials with the 3D metals still needs to be studied. In this work, we design a vertical 3D FTJ by adopting the 3D metal Au as the left and right electrodes and the 2D ferroelectric material In2Se3 together with h-BN as the central scattering region. By density functional theory combined with the non-equilibrium Green's function (NEGF) method, we demonstrate that the h-BN intercalation with a large bandgap plays the role of good "insulator," which breaks the symmetry of the left and right electrodes. As a result, we obtain the TER ratio of about 170%, and it can be further improved to about 1200% if two layers of In2Se3 (2L-In2Se3) are adopted as the tunneling barrier layer. Our results provide another way for the design and application of ferroelectric memory devices based on 2D ferroelectric materials.

Tunnel electroresistance effect in a two-dimensional organic ferroelectric tunnel junction.

Two-dimensional (2D) ferroelectric materials have important application potential in device miniaturization due to their characteristics of only being a few atomic layers thick and non-volatility. How to design high-performance ferroelectric memory devices based on 2D ferroelectric materials has attracted extensive attention. In this work, based on the 2D organic ferroelectric material semi-hydroxylized graphane (SHLGA), which has in-plane ferroelectric polarization along three different directions, we construct a 2D organic ferroelectric tunnel junction (FTJ). By means of density functional theory (DFT) and the non-equilibrium Green's function (NEGF) method, we calculate the transport properties of the FTJ under different polarizations and obtain a giant tunnel electroresistance (TER) ratio of 7.55 × 104%. We find that the mechanism behind the TER effect in the organic SHLGA is based on the unique built-in electric field. That is, among the three ferroelectric polarization directions, any two directions have an angle of 120°. As a result, the built-in electric fields along the transport direction of the FTJ under different ferroelectric polarization directions are different. Moreover, our study shows that the giant TER effect can also be achieved by utilizing the asymmetry of the polarization along the transport direction of the ferroelectric material itself, which provides another route for the design of 2D FTJs.

Peripheral Nerve Block and Peri-operative Neurocognitive Disorders in Older Patients With Hip Fractures: A Systematic Review With Meta-analysis.

Background: Poor pain control and opioid use are risk factors for perioperative neurocognitive disorders (PND). The peripheral nerve block (PNB) can reduce pain and opioid consumption. This systematic review aimed to investigate the effects of PNB on PND in older patients with hip fractures. Methods: The PubMed, Cochrane Central Registers of Controlled Trial, Embase and ClinicalTrials.gov databases were searched from inception until November 19, 2021 for all randomized controlled trials (RCTs) comparing PNB with analgesics. The quality of the selected studies was assessed according to Version 2 of the Cochrane tool for assessing the risk of bias in RCTs. The primary outcome was the incidence of PND. Secondary outcomes included pain intensity and the incidence of postoperative nausea and vomiting. Subgroup analyses were based on population characteristics, type and infusion method of local anesthetics, and type of PNB. Results: Eight RCTs comprising 1015 older patients with hip fractures were included. Compared with analgesics, PNB did not reduce the incidence of PND in the elderly hip fracture population comprising patients with intact cognition and those with pre-existing dementia or cognitive impairment (risk ratio [RR] = .67; 95% confidence interval [CI] = .42 to 1.08; P = .10; I2 = 64%). However, PNB reduced the incidence of PND in older patients with intact cognition (RR = .61; 95% CI = .41 to .91; P = .02; I2 = 0%). Fascia iliaca compartment block, bupivacaine, and continuous infusion of local anesthetics were found to reduce the incidence of PND. Conclusions: PNB effectively reduced PND in older patients with hip fractures and intact cognition. When the study population included patients with intact cognition and those with pre-existing dementia or cognitive impairment, PNB showed no reduction in the incidence of PND. These conclusions should be confirmed with larger, higher-quality RCTs.

Involvement of iNOS-induced reactive enteric glia cells in gastrointestinal motility disorders of postoperative Ileus mice.

Postoperative ileus (POI) is the cessation or reduction of gastrointestinal (GI) motility after surgery. Reactive enteric glial cells (EGCs) are critical for maintaining bowel function. However, the triggering mechanisms and downstream effects of reactive EGCs in POI were poorly understood. The goal of this current study was to investigate whether the inducible nitric oxide synthase (iNOS)-driven reactive EGCs participated in GI motility disorders and mechanisms underlying altered GI motility in POI. Intestinal manipulation (IM)-induced POI mice and iNOS-/- mice were used in the study. Longitudinal muscle and myenteric plexuses (LMMPs) from the distal small intestine were stained by immunofluorescence. Our results found that the GI motility disorders occurred in the IM-induced POI mice, and reactive EGCs were observed in LMMPs. Glial metabolic inhibitor gliotoxin fluorocitrate (FC) treatment or iNOS gene knockout attenuated GI motility dysfunction. In addition, we also found that FC treatment or iNOS gene knockout significantly inhibited the fluorescence intensity macrophage colony-stimulating factor (M-CSF), which reduced M2 phenotype macrophages activation in LMMPs of IM-induced POI mice. Our findings demonstrated that iNOS-driven reactive EGCs played a key role and were tightly linked to the MMs homeostasis in the POI mice. EGCs are emerging as a new frontier in neurogastroenterology and a potential therapeutic target.

Effects of Propofol on Perioperative Sleep Quality in Patients Undergoing Gastrointestinal Endoscopy: A Prospective Cohort Study.

PURPOSE: Some patients experience sleep disturbances after endoscopy performed under sedation. This study aimed to evaluate the effects of propofol on sleep quality after gastrointestinal endoscopy (GE). DESIGN: This study was a prospective cohort study. METHODS: This study enrolled 880 patients who underwent GE. Patients who chose to undergo GE under sedation received intravenous propofol, whereas the control group did not. The Pittsburgh Sleep Quality Index (PSQI) was measured before GE (PSQI-1) and 3 weeks (PSQI-2) after GE. The Groningen Sleep Score Scale (GSQS) was used before GE (GSQS-1) and 1 (GSQS-2) and 7 days (GSQS-3) after GE. FINDINGS: There was a significant increase in GSQS scores from baseline to days 1 and 7 after GE (GSQS-2 vs GSQS-1, P < .001, GSQS-3 vs GSQS-1, P = .008). However, no significant changes were observed in the control group (GSQS-2 vs GSQS-1, P = .38, GSQS-3 vs GSQS-1, P = .66). On day 21, there were no significant changes in the baseline PSQI scores over time in either group (sedation group, P = .96; control group, P = .95). CONCLUSIONS: GE with propofol sedation negatively affected sleep quality for 7 days after GE but not 3 weeks after GE.

Activation of astrocytes in the basal forebrain in mice facilitates isoflurane-induced loss of consciousness and prolongs recovery.

OBJECTIVES: General anesthesia results in a state of unconsciousness that is similar to sleep. In recent years, increasing evidence has reported that astrocytes play a crucial role in regulating sleep. However, whether astrocytes are involved in general anesthesia is unknown. METHODS: In the present study, the designer receptors exclusively activated by designer drugs (DREADDs) approach was utilized to specifically activate astrocytes in the basal forebrain (BF) and observed its effect on isoflurane anesthesia. One the other side, L-α-aminoadipic acid was used to selectively inhibit astrocytes in the BF and investigated its influence on isoflurane-induced hypnotic effect. During the anesthesia experiment, cortical electroencephalography (EEG) signals were recorded as well. RESULTS: The chemogenetic activation group had a significantly shorter isoflurane induction time, longer recovery time, and higher delta power of EEG during anesthesia maintenance and recovery periods than the control group. Inhibition of astrocytes in the BF delayed isoflurane-induced loss of consciousness, promoted recovery, decreased delta power and increased beta and gamma power during maintenance and recovery periods. CONCLUSIONS: The present study suggests that astrocytes in the BF region are involved in isoflurane anesthesia and may be a potential target for regulating the consciousness state of anesthesia.

Recognition, possible source, and risk assessment of organic pollutants in surface water from the Yongding River Basin by non-target and target screening.

Organic pollutants in aquatic environment could have important implications on pollution stress on aquatic organisms and even on the risk of human exposure. Thus, revealing their occurrence in aquatic environment is essential for water quality monitoring and ecological risk purposes. In this study, a comprehensive two-dimensional gas chromatography connected with time-of-flight mass spectrometry (GC × GC-TOF-MS) was applied, to enable non-target and target analysis of pollutants in the Yongding River Basin. Based on the isotopic patterns, accurate masses and standard substances, certain environmental contaminants were tentatively identified which including polycyclic aromatic hydrocarbon (PAHs), organochlorine pesticides (OCPs), phenols, amines, etc. The compounds with the highest concentration were naphthalene (109.0 ng/L), 2,3-benzofuran (51.5 ng/L) and 1,4-dichlorobenzene (35.9 ng/L) in Guishui River. Wastewater treatment plants (WWTPs) discharges were a main source of pollutants in Yongding River Basin, as the types of compounds screened in the downstream river were relatively similar to those from WWTPs. According to the target analysis, a number of pollutants were selected due to the acute toxicity and cumulative discharge from WWTPs and downstream rivers. Three PAHs (naphthalene, Benzo(b)fluoranthene and pyrene) homologues showed moderate risk to fish and H. Azteca in Yongding River Basin, while the rest of the measured chemicals showed low ecological impact across the entire study area based on the risk assessment. The results are helpful for understanding the necessity of high-throughput screening analysis for assessing water quality of rivers and the discharge emissions of pollutants from WWTPs to the river environment.

Brain Structure Measurements Predict Individualized Treatment Outcome of 12-Week Antipsychotic Monotherapies in First-episode Schizophrenia.

BACKGROUND AND HYPOTHESIS: Early prediction of treatment response to antipsychotics in schizophrenia remains a challenge in clinical practice. This study aimed to investigate if brain morphometries including gray matter volume and cortical thickness could serve as potential predictive biomarkers in first-episode schizophrenia. STUDY DESIGN: Sixty-eight drug-naïve first-episode patients underwent baseline structural MRI scans and were subsequently randomized to receive a single antipsychotic throughout the first 12 weeks. Assessments for symptoms and social functioning were conducted by eight "core symptoms" selected from the Positive and Negative Syndrome Scale (PANSS-8) and the Personal and Social performance scale (PSP) multiple times during follow-ups. Treatment outcome was evaluated as subject-specific slope coefficients for PANSS-8 and PSP scores using linear mixed model. LASSO regression model were conducted to examine the performance of baseline gray matter volume and cortical thickness in prediction of individualized treatment outcome. STUDY RESULTS: The study showed that individual brain morphometries at baseline, especially the orbitofrontal, temporal and parietal cortex, pallidum and amygdala, significantly predicted 12-week treatment outcome of PANSS-8 (r[predicted vs observed] = 0.49, P = .001) and PSP (r[predicted vs observed] = 0.40, P = .003) in first-episode schizophrenia. Moreover, the gray matter volume performed better than cortical thickness in the prediction the symptom changes (P = .034), while cortical thickness outperformed gray matter volume in the prediction of outcome of social functioning (P = .029). CONCLUSIONS: These findings provide initial evidence that brain morphometry have potential to be used as prognostic predictors for antipsychotic response in patients, encouraging the future investigation of the translational value of these measures in precision psychiatry.

Zinc finger E-box binding homebox 2 alleviated experimental osteoarthritis in rats.

AIMS: Osteoarthritis (OA) is a chronic inflammatory disease, characterized by degradation of extracellular matrix, apoptosis of chondrocytes and inflammation in articular cartilage. Zinc finger E-box binding homebox 2 (ZEB2), a transcription repressor, has been demonstrated with anti-inflammatory role in some cells. The analysis from GEO data reveals that ZEB2 expression is upregulated in articular cartilage of OA patients and experimental OA rodents. This study aims to confirm the function of ZEB2 in OA process. MATERIAL AND METHODS: The experimental OA was induced by anterior cruciate ligament transaction (ACLT) in rats, and the adenovirus loaded with ZEB2 coding sequence was intra-articularly injected into rats (1 × 10 PFU). The primary articular chondrocytes were stimulated by interleukin-1ß (IL-1ß) (10 ng/ml) to mimic the osteoarthritic injury, and transfected with the adenovirus carrying ZEB2 coding or silencing sequence. The apoptosis, content of extracellular matrix, inflammation, and the activity of NFκB signaling in chondrocytes and cartilage were determined. RESULTS: ZEB2 was highly expressed in osteoarthritic cartilage tissues and IL-1ß-treated chondrocytes. The overexpression of ZEB2 restrained ACLT- or IL-1ß administration-induced apoptosis, matrix degradation and inflammation in vivo or in vitro, evidenced by changed levels of cleaved caspase-3/PARP, collagen-II, aggrecan, matrix metalloproteinase 3/13, tumor necrosis factor-α and interleukin-6. Additionally, the phosphorylation of NFκB p65, IκBα and IKKα/ß, and the nuclear translocation of p65 was blocked by ZEB2, implying inactivation of this signaling. CONCLUSIONS: ZEB2 mitigated osteoarthritic symptoms in rats and chondrocytes, and NFκB signaling might be involved. These findings may provide novel insights for clinical treatment of OA.

Transversus Thoracis Muscle Plane Block in Paediatric Patients Who Underwent Minimally Invasive Closure of Transthoracic Ventricular Septal Defect: A Retrospective Study.

Objective: Minimally invasive closure of transthoracic ventricular septal defect (VSD) has been widely used in paediatric patients. This retrospective study aimed to explore the use of transversus thoracis muscle plane block (TTMPB) in the minimally invasive closure of transthoracic VSD in paediatric patients. Methods: From September 28, 2017, to July 25, 2022, a total of 119 paediatric patients scheduled for minimally invasive transthoracic VSD closure were considered for inclusion. Results: In total, 110 patients were included in the final analysis. Perioperative fentanyl consumption of the TTMPB group was not different from that of the non-TTMPB group (5.90 ± 1.32 µg/kg vs. 6.25 ± 1.74 µg/kg, p = 0.473). Both the time to extubation and postanesthesia care unit (PACU) stay were significantly shorter in the TTMPB group than in the non-TTMPB group (10.94 ± 10.31 min vs. 35.03 ± 23.52 min for extubation, and 42.55 ± 16.83 min vs. 59.98 ± 27.94 min for PACU stay, both p < 0.001). Furthermore, the postoperative paediatric intensive care unit (PICU) stay in the TTMPB group was significantly shorter than in the non-TTMPB group (1.04 ± 0.28 d vs. 1.34 ± 1.05 d, p = 0.005). Multivariate analysis demonstrated that TTMPB was significantly associated with shorter time to extubation (p < 0.001) and PACU stay (p = 0.001) but not postoperative PICU stay (p = 0.094). Discussion. This study showed that TTMPB was a beneficial and safe regional anaesthesia technique for paediatric patients who underwent minimally invasive closure of transthoracic VSD, although prospective randomized controlled trials are needed to confirm the results.

A review of sensors for classification and subtype discrimination of cancer: Insights into circulating tumor cells and tumor-derived extracellular vesicles.

Liquid biopsy can reflect the state of tumors in vivo non-invasively, thus providing a strong basis for the early diagnosis, individualized treatment monitoring and prognosis of tumors. Circulating tumor cells (CTCs) and tumor-derived extracellular vesicles (tdEVs) contain information-rich components, such as nucleic acids and proteins, and they are essential markers for liquid biopsies. Their capture and analysis are of great importance for the study of disease occurrence and development and, consequently, have been the subject of many reviews. However, both CTCs and tdEVs carry the biological characteristics of their original tissue, and few reviews have focused on their function in the staging and classification of cancer. In this review, we focus on state-of-the-art sensors based on the simultaneous detection of multiple biomarkers within CTCs and tdEVs, with clinical applications centered on cancer classification and subtyping. We also provide a thorough discussion of the current challenges and prospects for novel sensors with the ultimate goal of cancer classification and staging. It is hoped that these most advanced technologies will bring new insights into the clinical practice of cancer screening and diagnosis.

Integrative time series of cellular, humoral and molecular response revealed immunotoxicity of bifenthrin to Chinese rare minnow (Gobiocypris rarus) following Pseudomonas fluorescens challenge.

Bifenthrin is a common pesticide that is widespread in aquatic environments. Although it has been shown to be toxic to aquatic organisms, its immunotoxicity and mechanism are unclear. Herein, we reported the immunotoxicity of bifenthrin on adult Chinese rare minnow (Gobiocypris rarus) after 28 days of exposure to different concentrations of bifenthrin (0.1, 0.3, and 1.0 µg/L) and 36-h Pseudomonas fluorescens challenge. Bifenthrin inhibited the fish humoral immune response to bacteria by altering the lymphocyte and neutrophil ratios and decreasing the production of lysozyme, complement component 3, immunoglobulin M, and C-reactive protein, particularly were 1.0 µg/L. Bifenthrin caused intestinal damage and significantly reduced the volume of intestinal mucus at 12 and 36 hours postinjection (hpi) (p < 0.05). Moreover, 1.0 µg/L bifenthrin significantly increased the fish mortality and bacterial loads at 12 and 36 hpi (p < 0.05). RNA-seq analysis revealed several enriched genes involved in pathogen attachment and recognition, inflammatory responses, and complement system at the early-to-mid stage of infection (4-12 hpi). Overall, our results corroborated that bifenthrin induced immunotoxicity in Gobiocypris rarus, resulting in immune dysfunction of fish and increasing their sensitivity to bacterial infection and accelerating mortality. Moreover, 4-12 hpi was better than 36 hpi for analyzing immune responses against pathogen infection in fish exposed to bifenthrin.

Effects of Dexmedetomidine on Systemic Inflammation and Postoperative Complications in Laparoscopic Pancreaticoduodenectomy: A Double-blind Randomized Controlled Trial.

BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) may induce intense inflammatory response which might be related to the patient's outcomes. Clinical dexmedetomidine (DEX) has been widely used for opioid-sparing anesthesia and satisfactory sedation. The objective of this study was to investigate the influence of DEX on inflammatory response and postoperative complications in LPD. METHODS: Ninety-nine patients undergoing LPD were randomly assigned to two groups: normal saline (NS) and DEX. The primary outcome was the neutrophil-to-lymphocyte ratio (NLR) differences postoperatively within 48 h. Secondary outcomes were postoperative complications, the length of postoperative hospital stay and the incidence of ICU admission. Other outcomes included anesthetics consumption and intraoperative vital signs. RESULTS: NLR at postoperative day 2 to baseline ratio decreased significantly in the DEX group (P = 0.032). Less major complications were observed in the DEX group such as pancreatic fistula, delayed gastric emptying and intra-abdominal infection (NS vs. DEX, 21.7% vs. 13.6%, P = 0.315; 10.9% vs. 2.3%, P = 0.226; 17.4% vs. 11.4%, P = 0.416, respectively) though there were no statistical differences. Three patients were transferred to the ICU after surgery in the NS group, while there was none in the DEX group (P = 0.242). The median postoperative hospital stay between groups were similar (P = 0.313). Both intraoperative propofol and opioids were less in the DEX group (P < 0.05). CONCLUSIONS: Intraoperative DEX reduced the early postoperative inflammatory response in LPD. It also reduced the use of narcotics that may related to reduced major complications, which need additional research further.

Measurement of tissue oxygen saturation during arthroscopic surgery of knee with a tourniquet.

BACKGROUND: Tourniquets provide better tissue visibility during arthroscopic surgery. However, multiple postoperative adverse events associated with ischemia may be caused by excessive inflation pressure and duration. We aimed to evaluate the degree of tourniquet-induced ischemia using a noninvasive continuous real-time monitoring method and the relationship between changes in tissue oxygen saturation (StO2) and blood biochemical markers of ischemic injuries in patients undergoing arthroscopic knee surgery. METHODS: This was a prospective observational study using near-infrared spectroscopy (NIRS). Data were collected from 29 consecutive patients who underwent arthroscopic procedures. Twenty-five patients underwent anterior cruciate ligament reconstruction, and four underwent meniscal repair. We investigated tourniquet-induced changes in StO2, monitored using NIRS, and blood biochemical markers of ischemic injuries. RESULTS: A significant decrease in the mean StO2 from the baseline was observed during tourniquet inflation in the operative legs. The average decrease in the mean StO2 was 58%. A comparison of mean StO2 between the nonoperative and operative legs before tourniquet deflation showed that mean values of StO2 in the operative legs were significantly lower than those in the nonoperative legs. No significant clinical relationships were observed between changes in StO2 and blood biochemical markers of ischemic injuries (creatine kinase) (p = 0.04, r = 0.38) or tourniquet duration (p = 0.05, r = 0.366). CONCLUSIONS: Our results demonstrated that StO2 could be used to evaluate tissue perfusion in real time but did not support the hypothesis that StO2 is a useful method for predicting the degree of tourniquet-induced injury during arthroscopic knee surgery.

A Multicenter, Randomized, Double-Blind, Positive-Controlled, Non-Inferiority, Phase III Clinical Trial Evaluating the Efficacy and Safety of Emulsified Isoflurane for Anesthesia Induction in Patients.

BACKGROUND: Emulsified isoflurane was designed to circumvent the deficiencies of inhalation anesthetics, which have a longer time to onset, result in a higher drug consumption, and for which a specific anesthesia machine is required for clinical use. The aim of this study was to compare the efficacy and safety of emulsified isoflurane with propofol for anesthesia induction in adults patients. METHODS: This multicenter, randomized, double-blind, positive-controlled, non-inferiority, phase III clinical trial compared the efficacy and safety of emulsified isoflurane with propofol for anesthesia induction. Each patient in the emulsified isoflurane group received a single bolus injection of 12% emulsified isoflurane at a dose of 30 mg/kg, and each patient in the propofol group received a single bolus injection of 0.8% propofol at a dose of 2 mg/kg. The primary outcome of the efficacy evaluation was the proportion of participants with successful anesthesia induction, which was regarded as a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of < 1 and lack of use of other sedative drugs. A number of secondary efficacy outcomes were also assessed. Safety was monitored based on (1) adverse events, (2) repeated measurement of vital signs; (3) physical examination, (4) routine laboratory examinations of hematology, biochemistry, urine, coagulation function, and (5) 12-lead electrocardiogram. RESULTS: A total of 416 patients were enrolled (n = 208 in each group) and 398 patients were administered study drug. The proportion of participants with successful anesthesia induction was 100% with a 95% confidence interval of - 1.9% to + 1.9% for the emulsified isoflurane and propofol groups, which met the predesigned non-inferiority criteria of 5%. The study demonstrated the non-inferiority of sedation produced by emulsified isoflurane compared to propofol. Among the secondary efficacy outcomes, emulsified isoflurane showed a better cardiovascular stability than propofol. The number of patients from the emulsified isoflurane group who experienced drug-related adverse events was significantly higher than that of patients from the propofol group. However, there was no significant difference between the two groups in terms of adverse events or drug-related adverse events of grades 3-5. CONCLUSIONS: Emulsified isoflurane exhibited non-inferiority of anesthesia/sedation compared to propofol in patients undergoing anesthesia induction. CLINICAL TRIAL REGISTRATION: ChiCTR2000038185, registered on 12 December, 2020 ( www.chictr.org.cn ).

Efficacy and safety of remimazolam besylate in bronchoscopy for adults: A multicenter, randomized, double-blind, positive-controlled clinical study.

Background: With the development of fiberoptic bronchoscopy in the diagnosis and treatment of various pulmonary diseases, the anesthesia/sedation requirements are becoming more demanding, posing great challenges for patient safety while ensuring a smooth examination/surgery process. Remimazolam, a brand-new ultra-short-acting anesthetic, may compensate for the shortcomings of current anesthetic/sedation strategies in bronchoscopy. Methods: This study was a prospective, multicenter, randomized, double-blind, parallel positive controlled phase 3 clinical trial. Subjects were randomized to receive 0.2 mg/kg remimazolam besylate or 2 mg/kg propofol during bronchoscopy to evaluate the efficacy and safety of remimazolam. Results: A total of 154 subjects were successfully sedated in both the remimazolam group and the propofol group, with a success rate of 99.4% (95%CI of the adjusted difference -6.7 × 10%-6% to -5.1 × 10%-6%). The sedative effect of remimazolam was noninferior to that of propofol based on the prespecified noninferiority margin of -5%. Compared with the propofol group, the time of loss of consciousness in the remimazolam group (median 61 vs. 48s, p < 0.001), the time from the end of study drug administration to complete awakening (median 17.60 vs. 12.80 min, p < 0.001), the time from the end of bronchoscopy to complete awakening (median 11.00 vs. 7.00 min, p < 0.001), the time from the end of study drug administration to removal of monitoring (median 19.50 vs. 14.50 min, p < 0.001), and the time from the end of bronchoscopy to removal of monitoring (median 12.70 vs. 8.60 min, p < 0.001) were slightly longer. The incidence of Adverse Events in the remimazolam group and the propofol group (74.8% vs. 77.4%, p = 0.59) was not statistically significant, and none of them had Serious Adverse Events. The incidence of hypotension (13.5% vs. 29.7%, p < 0.001), hypotension requiring treatment (1.9% vs. 7.7%, p = 0.017), and injection pain (0.6% vs. 16.8%, p < 0.001) were significantly lower in the remimazolam group than in the propofol group. Conclusion: Moderate sedation with 0.2 mg/kg remimazolam besylate is effective and safe during bronchoscopy. The incidence of hypotension and injection pain was less than with propofol, but the time to loss of consciousness and recovery were slightly longer. Clinical Trial Registration: clinicaltrials.gov, ChiCTR2000039753.

Dexmedetomidine decreases the 50% effective dose (ED50) of intravenous propofol required to prevent tracheal intubation response in Beagles.

OBJECTIVE: To determine the 50% effective dose (ED50) of intravenous propofol required for successfully preventing tracheal intubation response in Beagles co-induced with dexmedetomidine. ANIMALS: 36 adult male Beagles. PROCEDURES: The dogs were randomly assigned to either group D1, group D2, or group C (received 1 µg/kg, 2 µg/kg dexmedetomidine intravenously, or the same amount of normal saline as dexmedetomidine, 10 mL). The first dog in each group received 6 mg/kg of propofol for induction. The pump speed of propofol was 600 mL/h. The dosage varied with increments or decrements of 0.5 mg/kg based on the Dixon up-and-down method. The duration of eye-opening after propofol administration was recorded. Changes in heart rate (HR) and respiratory rate (RR) were recorded at 5 timepoints: after entering the operation room and prior to propofol administration (T1), 1 and 3 min after propofol administration (T2 and T3), 3 and 5 min after intubation (T4 and T5). RESULTS: The required ED50 of propofol that prevented tracheal intubation response in D1, D2, and C groups were 6.4 mg/kg (95% CI, 6.1 to 6.7 mg/kg), 5.8 mg/kg (95% CI, 5.67 to 6 mg/kg), and 8.3 mg/kg (95% CI, 8 to 8.5 mg/kg), respectively. The recovery time of group D2 was significantly longer than that of groups D1 and C (P < .05). The differences in HR among the 3 groups were significant from T2 up to T5 timepoint (P < .05). The differences in RR among the 3 groups were significant at T2 and T3 timepoints (P < .05). CLINICAL RELEVANCE: Dexmedetomidine pre-injection reduces the amount of propofol required for endotracheal intubation response in Beagles, thereby reducing the respiratory inhibition induced by propofol.