Hemodynamic changes in the prone position according to fluid loading after anaesthesia induction in patients undergoing lumbar spine surgery: a randomized, assessor-blind, prospective study.

INTRODUCTION: A change from the supine to prone position causes hemodynamic alterations. We aimed to evaluate the effect of fluid preloading in the supine position, the subsequent hemodynamic changes in the prone position and postoperative outcomes. PATIENTS AND METHODS: This prospective, assessor-blind, randomized controlled trial was conducted between March and June 2023. Adults scheduled for elective orthopaedic lumbar surgery under general anaesthesia were enrolled. In total, 80 participants were randomly assigned to fluid maintenance (M) or loading (L) groups. Both groups were administered intravenous fluid at a rate of 2 ml/kg/h until surgical incision; Group L was loaded with an additional 5 ml/kg intravenous fluid for 10 min after anaesthesia induction. The primary outcome was incidence of hypotension before surgical incision. Secondary outcomes included differences in the mean blood pressure (mBP), heart rate, pleth variability index (PVi), stroke volume variation (SVV), pulse pressure variation (PPV), stroke volume index and cardiac index before surgical incision between the two groups. Additionally, postoperative complications until postoperative day 2 and postoperative hospital length of stay were investigated. RESULTS: Hypotension was prevalent in Group M before surgical incision and could be predicted by a baseline PVi >16. The mBP was significantly higher in Group L immediately after fluid loading. The PVi, SVV and PPV were lower in Group L after fluid loading, with continued differences at 2-3 time points for SVV and PPV. Other outcomes did not differ between the two groups. CONCLUSION: Fluid loading after inducing general anaesthesia could reduce the occurrence of hypotension until surgical incision in patients scheduled for surgery in the prone position. Additionally, hypotension could be predicted in patients with a baseline PVi >16. Therefore, intravenous fluid loading is strongly recommended in patients with high baseline PVi to prevent hypotension after anaesthesia induction and in the prone position. TRIAL NUMBER: KCT0008294 (date of registration: 16 March 2023).

Fluid preloading could reduce the occurrence of hypotension in the prone position. Hypotension could be predicted in patients with a baseline PVi >16. Intravenous fluid preloading is strongly recommended in patients with high baseline PVi to prevent hypotension after anaesthesia induction and in the prone position.

Comparison of Hemodynamic Parameters Based on the Administration of Remimazolam or Sevoflurane in Patients under General Anesthesia in the Beach Chair Position: A Single-Blinded Randomized Controlled Trial.

Background: We aimed to evaluate whether the administration of remimazolam as a maintenance agent for general anesthesia affects the occurrence of hypotension compared with sevoflurane when switching to the beach chair position (BCP). Methods: We conducted a prospective randomized controlled trial from June 2023 to October 2023 in adult patients undergoing orthopedic surgery under general anesthesia in the BCP. A total of 78 participants were randomly allocated to the remimazolam (R) or sevoflurane (S) groups. The primary outcome was the incidence of hypotension that occurred immediately after switching to a BCP. The secondary outcomes included differences between the study groups in perioperative blood pressure (BP), heart rate (HR), endotracheal tube extubation time, postoperative complications, and hospital length of stay (LOS). Results: The incidence of hypotension immediately after switching to a BCP was significantly higher in the S group. The risk factors associated with hypotension included sevoflurane administration and a high baseline systolic BP. In the receiver operating characteristic curve analysis for the occurrence of hypotension after the transition to a BCP, the cutoff value for systolic BP was 142 mmHg. The perioperative BP and HR were higher in the R group at several timepoints. Postoperative endotracheal tube extubation time was shorter in the R group. There were no significant differences in the postoperative complications or hospital LOS between the two groups. Conclusions: Remimazolam should be considered as an anesthetic agent to prevent hypotension when switching to BCP, and hypotension may occur frequently in patients with high baseline BP.

Korean clinical practice guidelines for diagnostic and procedural sedation.

Safe and effective sedation depends on various factors, such as the choice of sedatives, sedation techniques used, experience of the sedation provider, degree of sedation-related education and training, equipment and healthcare worker availability, the patient's underlying diseases, and the procedure being performed. The purpose of these evidence-based multidisciplinary clinical practice guidelines is to ensure the safety and efficacy of sedation, thereby contributing to patient safety and ultimately improving public health. These clinical practice guidelines comprise 15 key questions covering various topics related to the following: the sedation providers; medications and equipment available; appropriate patient selection; anesthesiologist referrals for high-risk patients; pre-sedation fasting; comparison of representative drugs used in adult and pediatric patients; respiratory system, cardiovascular system, and sedation depth monitoring during sedation; management of respiratory complications during pediatric sedation; and discharge criteria. The recommendations in these clinical practice guidelines were systematically developed to assist providers and patients in sedation-related decision making for diagnostic and therapeutic examinations or procedures. Depending on the characteristics of primary, secondary, and tertiary care institutions as well as the clinical needs and limitations, sedation providers at each medical institution may choose to apply the recommendations as they are, modify them appropriately, or reject them completely.

Comparison of oxygen reserve index according to the remimazolam or dexmedetomidine for intraoperative sedation under regional anesthesia-A single-blind randomized controlled trial.

Introduction: We aimed to evaluate the difference in intraoperative oxygen reserve index (ORi) between the sedatives remimazolam (RMMZ) and dexmedetomidine (DEX). Methods: Seventy-eight adult patients scheduled for sedation under regional anesthesia were randomly assigned to either the DEX (n = 39) or RMMZ (n = 39) group. The primary outcome was the difference in perioperative ORi between the groups. The secondary outcomes included respiratory depression, hypo- or hypertension, heart rate (HR), blood pressure, respiratory rate and postoperative outcomes. Additionally, the number of patients who experienced a decrease in intraoperative ORi to < 50% and the associated factors were analyzed. Results: The ORi was significantly higher in the RMMZ group at 15 min after sedation maintenance. There were no significant differences in respiratory depression between the two groups. The intraoperative HR was significantly higher in the RMMZ group after the induction of sedation, 15 min after sedation maintenance, and at the end of surgery. No other results were significantly different between the two groups. The incidence of a decrease in intraoperative ORi to < 50% was significantly higher in the DEX group. Factors associated with a decrease in the intraoperative ORi to < 50% were diabetes mellitus, low baseline peripheral oxygen saturation (SpO2), and DEX use. In the receiver operating characteristic curve analysis for a decrease in the intraoperative ORi to < 50%, the cutoff baseline SpO2 was 97%. Conclusion: RMMZ is recommended as a sedative for patients with a low baseline SpO2 and intraoperative bradycardia. Further studies should be conducted to establish the criteria for a significant ORi reduction.

Suppression of DAPK1 reduces ischemic brain injury through inhibiting cell death signaling and promoting neural remodeling.

The role of death-associated protein kinase1 (DAPK1) in post-stroke functional recovery is controversial, as is its mechanism of action and any neural remodeling effect after ischemia. To assess the debatable role of DAPK1, we established the middle cerebral artery occlusion (MCAo) model in DAPK1 knockout mice and Sprague-Dawley (SD) rats. We identified that the genetic deletion of the DAPK1 as well as pharmacological inhibition of DAPK1 showed reduced brain infarct volume and neurological deficit. We report that DAPK1 inhibition (DI) reduces post-stroke neuronal death by inhibiting BAX/BCL2 and LC3/Beclin1 mediated apoptosis and autophagy, respectively. Histological analysis displayed a reduction in nuclear condensation, neuronal dissociation, and degraded cytoplasm in the DI group. The DI treatment showed enhanced dendrite spine density and neurite outgrowth, upregulated neural proliferation marker proteins like brain-derived neurotrophic factor, and reduced structural abnormalities of the cortical pyramidal neurons. This research shows that DAPK1 drives cell death, its activation exacerbates functional recovery after cerebral ischemia and shows that oxazolone-based DI could be an excellent candidate for stroke and ischemic injury intervention.

Changes in Keyboard Typing Accuracy and Spatial Perception after Cardiovascular Fitness Exercise.

Background: This study aimed to identify the association between cardiopulmonary exercise and neurological activation by measuring dictation accuracy and the extent of spatial perception. Methods: First of all, the body composition of subjects was analyzed to verify their physical abnormality. The subjects were given treadmill exercise using modified Bruce protocol. Before and after the treadmill exercise, a spatial perception test and dictation task with auditory and visual stimulation were carried out to identify the changes in neurological activation. Results: The scores of spatial perception after treadmill exercise were higher than those before treadmill exercise (p < 0.05). In addition, the speed of the post-treadmill dictation task with visual stimulation was significantly increased compared to that of the pre-treadmill dictation task (p < 0.05). However, the accuracy of the post-treadmill dictation task with visual stimulation was significantly decreased compared to that of the pre-treadmill dictation task (p < 0.05). Conclusion: In this study, it was shown that spatial perception and speed of visual dictation were increased after treadmill exercise. These results suggest that cardiovascular fitness exercise increases spatial perception and typing speed by facilitating neurological activation.

Assessment of functional roles and therapeutic potential of integrin receptors in osteoarthritis: A systematic review and meta-analysis of preclinical studies.

BACKGROUND: Integrins are heterodimeric transmembrane receptors that mediate a variety of biological function and plays a critical role in osteoarthritis (OA) pathogenesis, which may provide new targets for the development of OA therapies. However, the roles of integrins in different stages of OA remain elusive. OBJECTIVES: This study aimed to synthesize all published preclinical evidence on the roles of integrin receptors in different stages of OA to identify the potential target for drug development in alleviating OA pathogenesis. METHODS: Major electronic databases were used to identify related original articles. The methodological quality of all included studies was appraised using the SYRCLE risk of bias tool. We used the generic inverse variance with random effects model to calculate standardized mean differences (SMDs) and 95% confidence interval (CI). RESULTS: Seventeen studies were included in this systematic review. Integrin α5ß1 activation increases the histopathological score both in early [SMD, 6.39; 95%CI (2.90, 9.87); p = 0.0003] and late [SMD, 3.41; 95%CI (2.44, 4.38); p < 0.00001] stage of OA. Integrin α5ß1 also increased the core catabolic factors like MMP-3, IL-1ß, and TNF-α. Interestingly, the inactivation of α5ß1 integrin did not change the histopathological score (p = 0.84). Similarly, ß1 integrin notably increased histopathological score at both stages of OA [early; SMD, 7.13; 95%CI (2.01, 12.24); p = 0.006]; [late; SMD, 10.25; 95%CI (5.11, 15.39); p < 0.0001], and increased the MMP-13 levels. However, integrin ß1 was upregulated at the early stage and downregulated at the late stage of OA. Furthermore, α2ß1 integrin significantly increased histopathological score [SMD, 3.14; 95%CI (2.18, 4.10); p < 0.00001] and MMP-13 [SMD, 2.24; 95%CI (0.07, 4.41); p = 0.04]. Deactivating integrin α1ß1 increased histopathological score in late [SMD, 1.53; 95%CI (0.80, 2.26); p < 0.0001], but not in early [SMD, 0.90; 95%CI (-1.65, 3.45); p = 0.49] stage of OA. CONCLUSION: This study provides evidence that α5ß1, α2ß1, and α1ß1 integrin might be the potential target for future drug development in alleviating OA pathogenesis. Further work is required to establish our findings through activating/deactivating these receptors in different stages of OA.

Application of the New Preoperative Frailty Risk Score in Elderly Patients Undergoing Emergency Surgery.

BACKGROUND: Predicting preoperative frailty risk in emergency surgery is difficult with limited information because preoperative evaluation is not commonly performed properly. A recent study attempted to predict preoperative frailty risk using only diagnostic and surgical codes that can be extracted from the electronic medical records system. OBJECTIVE: This study aimed to validate whether the prediction model of preoperative frailty risk presented in the previous study is well applied to other medical hospitals' data. METHODS: This is a retrospective cohort study including 1,557 patients (≥75 years old) who were admitted to a single institution for emergency operations between January 1, 2010, and December 31, 2019, for study analysis. The Charlson comorbidity index, Hospital Frailty Risk Score, and the recently developed Operation Frailty Risk Score (OFRS) were calculated using the patient's diagnostic and operation codes. The predictive performances of these calculated risk scores and the American Society of Anesthesiologists-Physical Status classification for postoperative 90-day mortality were compared by using the receiver operating characteristic curve analysis. FINDINGS: The predictive performance of the OFRS, Charlson comorbidity index, American Society of Anesthesiologists-Physical Status, and Hospital Frailty Risk Score for postoperative 90-day mortality was 0.81, 0.630, 0.699, and 0.549 on a c-statistics basis, respectively. CONCLUSIONS: The OFRS using diagnostic and operation codes may show the best predictive performance for 90-day mortality compared to other risk scores, and it can be the clinically applicable model to evaluate the preoperative frailty risk in elderly patients undergoing emergency surgery.

Pre- and post-conditioning with poly I:C exerts neuroprotective effect against cerebral ischemia injury in animal models: A systematic review and meta-analysis.

BACKGROUND: Toll-like receptor (TLR) agonist polyinosinic-polycytidylic acid (poly I:C) exerts neuroprotective effects against cerebral ischemia (CI), but concrete evidence supporting its exact mechanism of action is unclear. METHODS: We evaluated the neuroprotective role of poly I:C by assessing CI indicators such as brain infarct volume (BIV), neurological deficit score (N.S.), and signaling pathway proteins. Moreover, we performed a narrative review to illustrate the mechanism of action of TLRs and their role in CI. Our search identified 164 articles and 10 met the inclusion criterion. RESULTS: Poly I:C reduces BIV and N.S. (p = 0.00 and p = 0.03). Interestingly, both pre- and post-conditioning decrease BIV (preC p = 0.04 and postC p = 0.00) and N.S. (preC p = 0.03 and postC p = 0.00). Furthermore, poly I:C upregulates TLR3 [SMD = 0.64; CIs (0.56, 0.72); p = 0.00], downregulates nuclear factor-κB (NF-κB) [SMD = -1.78; CIs (-2.67, -0.88); p = 0.0)], and tumor necrosis factor alpha (TNF-α) [SMD = -16.83; CIs (-22.63, -11.02); p = 0.00]. CONCLUSION: We showed that poly I:C is neuroprotective and acts via the TLR3/NF-κB/TNF-α pathway. Our review indicated that suppressing TLR 2/4 may illicit neuroprotection against CI. Further research on simultaneous activation of TLR3 with poly I:C and suppression of TLR 2/4 might open new vistas for the development of therapeutics against CI.

Neurodegenerative effect of DAPK1 after cerebral hypoxia-ischemia is associated with its post-transcriptional and signal transduction regulations: A systematic review and meta-analysis.

Cerebral hypoxia-ischemia (CHI) causes brain aging, neurological disorders, cognitive decline, motor function impairment, and mortality. Inhibiting death-associated protein kinase 1 (DAPK1) has shown therapeutic potential against CHI, but several reports contradict its protective function, mechanism of activation, and signal transduction. Here, we systematically reviewed the role and the activation mechanism of DAPK1, and quantitatively assess the efficacy of DAPK1 inhibition (DI) methods in neuroprotection, following a CHI in animal models. Embase and PubMed were searched for relevant studies. Overall, 13 studies met the inclusion criteria, and the SYRCLE Risk of bias tool (RoB) tool was used to assess RoB. StataSE 16 was used for meta-analysis and network meta-analysis (NMA). Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated to estimate the effect size. DI was associated with the reduction of brain infarct volume (BIV) [SMD = -1.70, 95% CI (-2.10, -1.30); p = 0.00], neurological score (N.S.), neuronal degeneration, with no change in the level of in cell death [SMD = -0.83, 95% CI (-2.00, 0.35); p = 0.17], indicating the protective role of DI against CHI. No differences were found in DAPK1 mRNA and protein levels [SMD = 0.50, 95% CI (-0.05, 1.04); p = 0.07] {single-study driven; upregulated after exclusion (p = 0.01, I2 = 36.43)}, whereas phospho-DAPK1 [SMD = -2.22, 95% CI (-3.69, -0.75); p = 0.00] was downregulated and phosphorylated myosin light chain [SMD = 3.37, 95% CI (2.51, 4.96); p = 0.00] was upregulated between CHI and sham groups. Furthermore, we performed NMA to understand the molecular level at which DI offers maximum protection against BIV. Post-transcriptional inhibition (PTI; SUCRA, 82.6%) and gene knockout showed best (KO; SUCRA, 81.3%), signal transduction inhibition (STI; SUCRA, 49.5%) offered 3rd best, while catalytic activity inhibition (CAI; SUCRA, 0.3%) exhibited the lowest reduction in BIV against CHI. The results demonstrate that DI has a neuroprotective effect against CHI and DAPK1 might be regulated at the post-transcriptional and post-translational levels after CHI. Inhibiting DAPK1 at the post-transcriptional level and blocking multiple signal transduction pathways of DAPK1 could lead to better functional recovery against CHI. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

General anesthesia for old Werner syndrome patient: a case report.

Werner syndrome (WS) is a rare autosomal recessive, premature aging disorder whose clinical manifestations include short stature, bilateral cataracts, diabetes mellitus, hypertension, and atherosclerosis. WS first manifests during adolescence and patients usually die at 40-50 years of age. Only symptomatic treatment options available according to clinical manifestations. In anesthetic management, they need to be considered to elderly patients. Difficult intubation is expected and the patients are regarded as a high-risk group for anesthesia, owing to the concomitant cardiovascular and cerebrovascular disorders. The anesthetic management of WS requires a meticulous preoperative history taking, physical examination, and preparation for cardiovascular events.

Metataxonomic investigation of the microbial community in the trachea and oropharynx of healthy controls and diabetic patients using endotracheal tubes.

BACKGROUND: Although the study of respiratory microbiota has been an active field of research, obtaining the appropriate respiratory samples for healthy controls remains to be a challenge. As such, this study aims to evaluate the use of endotracheal tube washing as a viable control for sputum samples. METHODS: A total of 14 subjects, including 8 healthy respiratory controls and 6 diabetic patients without any respiratory disease, were enrolled in this study, during which the endotracheal tubes used in their scheduled routine surgery were collected. Pre-operative oral gargles were also collected from non-diabetic subjects. RESULTS: 16S amplicon sequencing revealed similar taxa composition in endotracheal tube washings and oral gargles in the healthy control subjects, although the relative abundance of 11 genus level operational taxonomic units was significantly different between the two sample sources. The diabetic subjects showed relatively lower diversity than those of non-diabetic subjects. The proportion range of the most abundant taxa detected in each endotracheal tube washings were 10.1-33.2%. CONCLUSION: Endotracheal tube washing fluid may provide healthy control samples for upper respiratory investigations without incurring any additional risk to the subject.

Predictive Model for the Assessment of Preoperative Frailty Risk in the Elderly.

Adequate preoperative evaluation of frailty can greatly assist in the efficient allocation of hospital resources and planning treatments. However, most of the previous frailty evaluation methods, which are complicated, time-consuming, and can have inter-evaluator error, are difficult to apply in urgent situations. Thus, the authors aimed to develop and validate a predictive model for pre-operative frailty risk of elderly patients by using diagnostic and operation codes, which can be obtained easily and quickly from electronic records. We extracted the development cohort of 1762 people who were hospitalized for emergency operations at a single institution between 1 January 2012 and 31 December 2016. The temporal validation cohort from 1 January 2017 to 31 December 2018 in the same center was set. External validation was conducted on 6432 patients aged 75 years or older from 2012 to 2015 who had emergency surgery in the Korean national health insurance database. We developed the Operation Frailty Risk Score (OFRS) by assessing the association of Operation Group and Hospital Frailty Risk Score with the 90-day mortality through logistic regression analysis. We validated the OFRS in both the temporal validation cohort and two external validation cohorts. In the temporal validation cohort and the external validation cohort I and II, the c-statistics for OFRS to predict 90-day mortality were 0.728, 0.626, and 0.619, respectively. OFRS from these diagnostic codes and operation codes may help evaluate the peri-operative frailty risk before emergency surgery for elderly patients where history-taking and pre-operative testing cannot be performed.

Melatonin Maintains Anabolic-Catabolic Equilibrium and Regulates Circadian Rhythm During Osteoarthritis Development in Animal Models: A Systematic Review and Meta-analysis.

Background: The driving force behind osteoarthritis (OA) pathogenesis is an anabolic-catabolic (a/c) imbalance. Melatonin (MT) is a key player in maintaining a/c stability and mitigates OA pathogenesis, but mechanisms underlying its effects remain poorly understood. Objectives: We performed a systematic review analyzing the experimental data that support the clinical applicability of MT in the treatment of OA pathogenesis, placing particular emphasis on the regulation of circadian rhythms and a/c balance. Methods: Major electronic databases and grey literature were used to identify related original articles. Methodological quality of all selected studies was evaluated using the SYRCLE risk of bias tool. Pooled mean differences (MDs)/standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to estimate the effect size. Results: Eleven trials were included in this systematic review. Compared with the control group, MT significantly decreased the levels of interleukin-1ß (IL-1ß; SMD = -5.45; 95% CI [-6.78, -4.12]; p < 0.00001, and histological grading scale (SMD = -3.46; 95% CI, [-5.24, -1.68]; p < 0.0001). MT significantly increased the transforming growth factor-ß1 (TGF-ß1; SMD = 1.17; 95% CI [0.31, 2.03]; p < 0.0007). Furthermore, core circadian clock genes Per2 and Cry1 mRNA levels were regulated by MT treatment in OA progression. Conclusion: MT may maintain a/c balance and regulate circadian rhythms during OA development. MT could be used in as adjunct with other interventions to manage pain and OA severity.