A multi-center study to predict the risk of intraoperative hypothermia in gynecological surgery patients using preoperative variables.

OBJECTIVES: Hypothermia is highly common in patients undergoing gynecological surgeries under general anesthesia, so the length of hospitalization and even the risk of mortality are substantially increased. Our aim was to develop a simple and practical model to preoperatively identify gynecological surgery patients at risk of intraoperative hypothermia. METHODS: In this retrospective study, we collected data from 802 patients who underwent gynecological surgery at three medical centers from June 2022 to August 2023. We further allocated the patients to a training group, an internal validation group, or an external validation group. The preliminary predictive factors for intraoperative hypothermia in gynecological patients were determined using the least absolute shrinkage and selection operator (LASSO) method. The final predictive factors were subsequently identified through multivariate logistic regression analysis, and a nomogram for predicting the occurrence of hypothermia was established. RESULTS: A total of 802 patients were included, with 314 patients in the training cohort (mean age 48.5 ± 12.6 years), 130 patients in the internal validation cohort (mean age 49.9 ± 12.5 years), and 358 patients in the external validation cohort (mean age 47.6 ± 14.0 years). LASSO regression and multivariate logistic regression analyses indicated that body mass index, minimally invasive surgery, baseline heart rate, baseline body temperature, history of previous surgery, and aspartate aminotransferase level were associated with intraoperative hypothermia in gynecological surgery patients. This nomogram was constructed based on these six variables, with a C-index of 0.712 for the training cohort. CONCLUSIONS: We established a practical predictive model that can be used to preoperatively predict the occurrence of hypothermia in gynecological surgery patients. CLINICAL TRIAL REGISTRATION: chictr.org.cn, identifier ChiCTR2300071859.

ATF4 inhibits TRPV4 function and controls itch perception in rodents and nonhuman primates.

ABSTRACT: Acute and chronic itch are prevalent and incapacitating, yet the neural mechanisms underlying both acute and chronic itch are just starting to be unraveled. Activated transcription factor 4 (ATF4) belongs to the ATF/CREB transcription factor family and primarily participates in the regulation of gene transcription. Our previous study has demonstrated that ATF4 is expressed in sensory neurons. Nevertheless, the role of ATF4 in itch sensation remains poorly understood. Here, we demonstrate that ATF4 plays a significant role in regulating itch sensation. The absence of ATF4 in dorsal root ganglion (DRG) neurons enhances the itch sensitivity of mice. Overexpression of ATF4 in sensory neurons significantly alleviates the acute and chronic pruritus in mice. Furthermore, ATF4 interacts with the transient receptor potential cation channel subfamily V member 4 (TRPV4) and inhibits its function without altering the expression or membrane trafficking of TRPV4 in sensory neurons. In addition, interference with ATF4 increases the itch sensitivity in nonhuman primates and enhances TRPV4 currents in nonhuman primates DRG neurons; ATF4 and TRPV4 also co-expresses in human sensory neurons. Our data demonstrate that ATF4 controls pruritus by regulating TRPV4 signaling through a nontranscriptional mechanism and identifies a potential new strategy for the treatment of pathological pruritus.

Effectiveness of general anaesthesia with remimazolam tosilate on intraoperative haemodynamics and postoperative recovery: study protocol for a randomised, positive-controlled, pragmatic clinical trial (GARTH trial).

INTRODUCTION: It is encouraged to estimate the effectiveness of components within the enhanced recovery after surgery (ERAS) protocol through patient-reported outcomes, alongside doctor-reported outcomes and length of hospital stay. At present, studies on the contributions of optimal anaesthetic drugs within the ERAS protocol to patient-reported and doctor-reported outcomes are limited. Therefore, this study aims to pragmatically evaluate the effectiveness and safety of general anaesthesia (GA) with remimazolam tosilate within the ERAS protocol on intraoperative haemodynamics and postoperative recovery in adults undergoing elective surgeries, compared with propofol. METHODS AND ANALYSIS: This study is a single-centre, randomised, blinded, positive-controlled, pragmatic clinical trial. A total of 900 patients, aged ≥18 years old, scheduled for an elective surgical procedure under GA will be included. Patients will be randomised in a 1:1 ratio to the remimazolam group (the GA with remimazolam tosilate within the ERAS protocol group) or propofol group (the GA with propofol within the ERAS protocol group), stratified by general surgery, thoracic surgery and other surgeries (including urological surgery and otolaryngology surgery). The primary outcomes include the 24-hour postoperative quality of recovery-40 score and the rate of intraoperative hypotension. Secondary endpoints include the rate of sedative hypotension requiring treatment, the haemodynamic profiles, the 72-hour postoperative quality of recovery-40 score, the functional anaesthetic capability, adverse events and complications, quality of life within 3 months as well as economic health outcomes. ETHICS AND DISSEMINATION: This study protocol has been approved by the ethics committee of Guangdong Provincial People's Hospital (KY-H-2022-005-03-08). Dissemination plans will be presented at scientific meetings and in scientific publications. TRIAL REGISTRATION NUMBER: ChiCTR2200062520.

Construction of a risk index system for the prediction of chronic post-surgical pain after video-assisted thoracic surgery for lung resection: A modified Delphi study.

In the present study, several research methods were adopted, including literature retrieval, theoretical analysis, and qualitative research, and then the draft of the prognostic factors for the chronic post-surgical pain (CPSP) index system after video-assisted thoracoscopic surgery (VATS) for lung resection was constructed. A Delphi survey was used for the study of 24 experts in the field of pain from three different grade-A tertiary hospitals in Guangzhou, China. In the two rounds of survey, the experts rated these indicators for the importance and feasibility of measurement (round 1, n = 21 participants; round 2, n = 20). Finally, we calculated Kendall's W index as a measure of consensus. A general consensus was reached on predicting CPSP after VATS, consisting of 10 first-level domains and 64 second-level indicators, involving biological, psychological and social perspectives. This study provides a comprehensive draft of risk factors developed and identified by experts to inform research-based evidence on chronic pain. Increased clinical awareness and a full understanding of how to screen and identify people with CPSP problems may lead to earlier recognition of chronic pain and greater facilitation of professional prevention.

Ultrasound-guided brachial plexus block at the clavicle level: A review.

The supraclavicular block (SCB) and the infraclavicular block (ICB) are introduced to meet upper extremity surgery, where the transducer or the insertion point is placed superiorly and inferiorly at the approximate midpoint of the clavicle, respectively. These two approaches are highly appealing since they clearly exhibited each cord and its associated anatomy. In addition, it directed the needle accurately with real-time imaging by ultrasound guidance. Therefore, it brought higher success rates and fewer complications. Numerous trials have recently been conducted to examine the SCB and ICB regarding the new approach, injection techniques, block dynamics, and complication of hemidiaphragmatic paresis. It was found that both approaches could improve block effectiveness and postoperative analgesia for upper extremity surgery, according to recent studies at the level of the clavicular brachial plexus block. However, there is still a lack of work comparing the clinical performance and effectiveness of both approaches with ultrasonography. This review aims to outline the current available data from clinical trials along with case reports about these two approaches and to describe the findings published in the literature during the previous 5 years. Based on these findings, we attempt to determine whether there exists a one-size-fits-all approach that has the potential to meet upper extremity surgery.

A single dose of ketamine relieves fentanyl-induced-hyperalgesia by reducing inflammation initiated by the TLR4/NF-κB pathway in rat spinal cord neurons.

A large amount of clinical evidence has revealed that ketamine can relieve fentanyl-induced hyperalgesia. However, the underlying mechanism is still unclear. In the current study, a single dose of ketamine (5 mg/kg or 10 mg/kg), TAK-242 (3 mg/kg), or saline was intraperitoneally injected into rats 15 min before four subcutaneous injections of fentanyl. Results revealed that pre-administration of ketamine alleviated fentanyl-induced hyperalgesia according to hind paw-pressure and paw-withdrawal tests. High-dose ketamine can reverse the expression of toll-like receptor-dimer (d-TLR4), phospho- nuclear factor kappa-B (p-NF-κB, p-p65), cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) 1 d after fentanyl injection in the spinal cord. Moreover, fentany-linduced-hyperalgesia and changes in the expression of the aforementioned proteins can be attenuated by TAK-242, an inhibitor of TLR4, as well as ketamine. Importantly, TLR4, p-p65, COX-2, and IL-1ß were expressed in neurons but not in glial cells in the spinal cord 1 d after fentanyl injection. In conclusion, results suggested that a single dose of ketamine can relieve fentanyl-induced-hyperalgesia via the TLR4/NF-κB pathway in spinal cord neurons.

Immune system changes in those with hypertension when infected with SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) outbreak has become an evolving global health crisis. With an increasing incidence of primary hypertension, there is greater awareness of the relationship between primary hypertension and the immune system [including CD4+, CD8+ T cells, interleukin-17 (IL-17)/T regulatory cells (Treg) balance, macrophages, natural killer (NK) cells, neutrophils, B cells, and cytokines]. Hypertension is associated with an increased risk of various infections, post-infection complications, and increased mortality from severe infections. Despite ongoing reports on the epidemiological and clinical features of COVID-19, no articles have systematically addressed the role of primary hypertension in COVID-19 or how COVID-19 affects hypertension or specific treatment in these high-risk groups. Here, we synthesize recent advances in understanding the relationship between primary hypertension and COVID-19 and its underlying mechanisms and provide specific treatment guidelines for these high-risk groups.

Effects of double vs triple injection on block dynamics for ultrasound-guided intertruncal approach to the supraclavicular brachial plexus block in patients undergoing upper limb arteriovenous access surgery: study protocol for a double-blinded, randomized controlled trial.

BACKGROUND: Ultrasound-guided intertruncal approach (IA) has been proposed to be an alternative and promising approach to the supraclavicular block (SCB), in which double injection (DI) of local anesthetics (LA) is sequentially administered between intertruncal planes. We would like to apply a refined injection technique, named triple injection (TI) technique, based on the 3 separate compartments visualized by ultrasound. The aim of this study is to compare the percentage of patients with complete sensory blockade at 20 min of DI vs TI technique, when they are applied in patients undergoing upper limb arteriovenous access surgery. METHODS: This study is a prospective parallel-group randomized controlled trial. A total of 86 end-stage renal disease patients will be randomly allocated to receive IA-SCB using either DI or TI technique with identical LA (0.5% ropivacaine 24 mL). The primary outcome is the percentage of patients with complete sensory blockade of all 4 terminal nerves (median, ulnar, radial, and musculocutaneous nerves) of the brachial plexus measured at 20 min after injection. The secondary outcomes will consist of the sensory or motor blockade of all individual nerves, onset times, performance time, diaphragmatic paralysis, surgical anesthesia, and adverse events. DISCUSSION: It is expected that ultrasound-guided IA-SCB with the TI technique results in better block dynamic in patients undergoing upper limb arteriovenous access surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100045075 .

Efficacy and safety of rhomboid intercostal block for analgesia in breast surgery and thoracoscopic surgery: a meta-analysis.

BACKGROUND: Rhomboid intercostal block (RIB) is a new regional anesthesia technique that provides postoperative analgesia for breast surgery and thoracoscopic surgery. The published papers are not yet fully integrated and do not adequately address the impact and safety of the RIB on postoperative pain. METHODS: The PubMed, Web of Science and Embase were searched from 2016 to 2021 for all available randomized controlled trials (RCTs) that evaluated the analgesic efficacy and safety of RIB after thoracic surgery and breast surgery. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. The primary outcome was Postoperative Numerical Rating Scale (NRS) scores of patients at rest recorded 0-1, 6-8, 24 h after surgery. The secondary outcomes included rate of postoperative nausea and vomiting (PONV), postoperative fentanyl consumption and presence of complications of the block. RESULTS: From 81 records identified, four studies met our inclusion criteria, including 216 patients (RIB:108 patients; no block: 108 patients). In the primary outcome, RIB group showed significantly lower postoperative NRS at rest at first 0-1 h and 6-8 h (weighted mean difference [WMD] = -1.55; 95% confidence internal [CI] = -2.92 to -0.19; p < 0.05), (WMD = -0. 69; 95% CI = -1.29 to -0. 09; p < 0. 05). And there was no significant difference between groups in NRS at rest at 24 h (WMD = -0.78; 95% CI = -1.64 to -0.08; p = 0.77). Also, RIB group showed significantly lower postoperative NRS of breast surgery and thoracoscopic surgery at 0-1 h (WMD = -3.00; 95% CI = -3.13 to -2.87; p < 0.01), (WMD = -1.08; 95% CI = -1.98 to -0.18; p < 0.05). In the secondary outcome, the analysis also showed RIB group had significant lower of POVN rates (summary relative risk (RR) = 0.212;95%CI = 0.10 to 0.45; p < 0. 01) and the postoperative consumption of fentanyl (WMD = -57.52;95%CI = -106.03 to -9.02; p < 0. 05). CONCLUSION: This review shows that RIB was more effective in controlling acute pain after breast surgery and thoracoscopic surgery than general analgesia. And it is a trend that RIB may be a kind of effective and safe nerve bock technology and it requires further studies.

Intertruncal versus classical approach to the ultrasound-guided supraclavicular brachial plexus block for upper extremity surgery: study protocol for a randomized non-inferiority trial.

BACKGROUND: Ultrasound-guided intertruncal approach (IA) to the supraclavicular block (SB) is recently proposed as a new approach for local anesthetic (LA) injection in terms of the classical approach (CA) at the level of the first rib. The CA-SB has been proven to result in satisfying sensorimotor block, but associate with a high risk of intraneural injection. The aim of this randomized non-inferiority study is to explore whether IA-SB can obtain similar block dynamics, as the CA-SB, but avoiding an intraneural injection during the whole nerve block procedure. METHODS: The total 122 patients undergoing elective upper extremity surgery will be randomly allocated to receive either an IA-SB or a CA-SB using a double-injection (DI) technique. In the IA-SB group, a portion of LA (15 mL) is injected accurately to the intertruncal plane between the middle and lower trunks under real-time ultrasound guidance; then, the remaining volume (10 mL) is carefully distributed to the other intertruncal plane between the upper and middle trunks. In the CA-SB group, the DI technique will be carried out as described in Tran's study. The primary outcome is the percentage of patients with a complete sensory blockade at 20 min with a predefined non-inferiority margin of - 5%. The secondary outcomes include the sensory-motor blockade of all 4 terminal nerves, onset times of the individual nerves within 30 min, block-related variables, and adverse events. DISCUSSION: The results will provide sensory-motor blockade-related parameters and safety of the ultrasound-guided intertruncal approach to the supraclavicular block, thereby promoting clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000040199 . Registered on 25 November 2020.

Interactions Between Specific Immune Status of Pregnant Women and SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the Coronavirus Disease 2019 (COVID-19) global pandemic. Because it is a new and highly contagious coronavirus, most people, especially pregnant women, lack immunity. It is therefore important to understand the interaction between why pregnant women are susceptible to SARS-CoV-2 and the specific immune systems of pregnant women. Here, we provide an overview of the changes that occur in the immune system during pregnancy, the activation and response of the immune system in pregnant women with COVID-19, adverse pregnancy outcomes in pregnant women with COVID-19, and the treatment and prevention of COVID-19 in this population.

Effects of processed Aconiti tuber on the extinction and reinstatement of morphine-induced conditioned place preference in rats.

AIM OF THE STUDY: To investigate the effect of processed Aconiti tuber (PAT) administered during or after the time of conditioned place preference (CPP) training on the extinction and reinstatement of morphine-priming CPP in rats. The dynorphin level in rats' nucleus accumbens (NAc) is detected as a target of the Dynorphin/Kappa Opioid Receptor (KOR) system for the possible mechanism. MATERIALS AND METHODS: Eight groups of rats were subcutaneously (s.c.) injected with morphine (10mg/kg) (on days 2,4,6,8) or saline (1ml/kg) (on days 3,5,7,9) alternately for 8 days. Five groups, including groups (Mor + Water, Mor + PAT (1.0/3.0g/kg) (S) and Sal + PAT(1.0/3.0g/kg)), were orally given distilled water or PAT 1.0 or 3.0 g/kg daily on days 1-8 during CPP training while other three groups, including groups (Sal + Water and Mor + PAT (1.0/3.0g/kg)(P), were given distilled water or PAT daily from day 10 until CPP was extinct. Morphine 1mg/kg (s.c.) was used to reinstate the extinct CPP and the CPP scores were recorded. The dynorphin concentration in nucleus accumbens (NAc) was assayed by radioimmunoassay after the last CPP measurement. RESULTS: 1) The CPP extinction shortened in Mor + PAT (1.0/3.0 g/kg) (S) groups but extended in Mor + PAT (1.0/3.0 g/kg)(P) groups. 2) Morphine-priming CPP did not change either in Mor + PAT (1.0/3.0 g/kg) (S) or Mor + PAT (1.0/3.0 g/kg)(P) groups. 3) The dynorphin concentration in NAc increased either in Mor + PAT (1.0/3.0 g/kg)(S) or Mor + PAT (1.0/3.0 g/kg)(P) groups. CONCLUSIONS: 1) PAT shortened the extinction from morphine induced CPP when administrated before CPP acquisition, whereas it extended the extinction when administrated after CPP formation. 2) PAT administrated during or after CPP training did not affect morphine-priming reinstatement of morphine induced CPP. 3) Dynorphin/KOR system might be a target to regulate morphine-induced CPP extinction but not reinstatement.

Comparison of ultrasound-guided supraclavicular and costoclavicular brachial plexus block using a modified double-injection technique: a randomized non-inferiority trial.

Ultrasound-guided costoclavicular block (CC-approach) is a recently described brachial plexus block (BPB) and an alternative approach to the supraclavicular approach (SC-approach). The relevant sonoanatomy is analogous in terms of the brachial plexus and its adjacent artery for both approaches. In the present study, we hypothesized that the two approaches will result in similar block dynamics when used the modified double-injection (MDI) technique. One hundred and twelve patients were randomly allocated to receive either a SC- or CC-approach with MDI technique. In the CC group, half the volume was injected adjacent to the medial cord of the brachial plexus, the procedure was guided by ultrasound and verified by nerve stimulator, subsequently the second half was injected close to the lateral cord. In the SC group, the MDI technique was carried out as described in our previous study. Sensory and motor blockade of all four terminal nerves were assessed with a 3-point scale. The primary outcome was the proportion of complete sensory blockade at 15 min with a predefined non-inferiority margin of -13%. The proportion of subjects at 15 min was comparable between the SC group and the CC group (91 vs 87%, absolute difference: -3%). No significant differences were found for complete motor blockade and onset times of the individual nerves within 30 min, and block-related serious adverse events (all P>0.05). We conclude that the MDI technique applied to a costoclavicular and supraclavicular block resulted in similar block dynamics. In addition, it may provide a promising alternative technique when considering the use of multipoint injection.

A practice of anesthesia scenario design for emergency cesarean section in patients with COVID-19 infection based on the role of standard patient.

The new coronavirus (COVID-19) has been characterized as a world pandemic by WHO since March 11, 2020. Although it is likely that COVID-19 transmission is primarily via droplets and close contact, airborne transmission and fecal-oral route remains a possibility. The medical staff working in the operating room, such as anesthesiologists, surgeons and nurses, are at high risk of exposure to virus due to closely contacting patients. The perioperative management is under great challenge while performing surgeries for patients suffering COVID-19, including emergency cesarean section, which is one of the most common surgeries under such circumstances. How to prevent medical staff from cross-infection is an issue of great concern. In this article, we give a practice of anesthesia scenario design for emergency cesarean section in a supposed standard patient suffering COVID-19, aimed to optimize the work flow and implement the protective details through simulation of a real operation scenario, which may be useful for training and clinical practice of anesthesia management for patients suffering COVID-19 or other fulminating infectious diseases.

Acetylcholine Muscarinic Receptors in Ventral Hippocampus Modulate Stress-Induced Anxiety-Like Behaviors in Mice.

Chronic stress exposure increases the risk of developing various neuropsychiatric illnesses. The ventral hippocampus (vHPC) is central to affective and cognitive processing and displays a high density of acetylcholine (ACh) muscarinic receptors (mAChRs). However, the precise role of vHPC mAChRs in anxiety remains to be fully investigated. In this study, we found that chronic restraint stress (CRS) induced social avoidance and anxiety-like behaviors in mice and increased mAChR expression in the vHPC. CRS increased the vHPC ACh release in behaving mice. Moreover, CRS altered the synaptic activities and enhanced neuronal activity of the vHPC neurons. Using pharmacological and viral approaches, we showed that infusing the antagonist of mAChRs or decreasing their expression in the vHPC attenuated the anxiety-like behavior and rescued the social avoidance behaviors in mice probably due to suppression of vHPC neuronal activity and its excitatory synaptic transmission. Our results suggest that the changes of neuronal activity and synaptic transmission in the vHPC mediated by mAChRs may play an important role in stress-induced anxiety-like behavior, providing new insights into the pathological mechanism and potential pharmacological target for anxiety disorders.

Accidental awareness while under general anaesthesia.

Accidental awareness during general anaesthesia may cause many intraoperative discomforts and bring further moderate to severe long-term symptoms including flashbacks, nightmares, hyperarousal or post-traumatic stress disorder. The incidence of awareness varied from 0.017% to 4% among studies. The relatively reliable incidence of intraoperative awareness with postoperative recall is 0.02%. The reason causing awareness was unclear. Insufficient anaesthetic dosing was thought as the principal cause. Even awareness was not comprehensively understood, some endeavors have been raised to prevent or reduce it, including i) Reducing the insufficient anaesthetic dosing induced by negligence; ii) Providing close clinical observation and clinical parameters from the monitor such as bispectral index or electroencephalogram, as well as isolated forearm technique and passive brain-computer interface may bring some effects sometimes. Because current studies still have some flaws, further trials with new detecting approach, superior methodology and underlying aetiology are needed to unfasten the possible factors causing awareness.