Regulation of Microglia and Macrophage Polarization via Apoptosis Signal-Regulating Kinase 1 Silencing after Ischemic/Hypoxic Injury

Inflammation is implicated in ischemic stroke and is involved in abnormal homeostasis. Activation of the immune system leads to breakdown of the blood–brain barrier and, thereby, infiltration of immune cells into the brain. Upon cerebral ischemia, infiltrated macrophages and microglia (resident CNS immune cell) are activated, change their phenotype to M1 or M2 based on the microenvironment, migrate toward damaged tissue, and are involved in repair or damage. Those of M1 phenotype release pro-inflammatory mediators, which are associated with tissue damage, while those of M2 phenotype release anti-inflammatory mediators, which are related to tissue recovery. Moreover, late inflammation continually stimulates immune cell infiltration and leads to brain infarction. Therefore, regulation of M1/M2 phenotypes under persistent inflammatory conditions after cerebral ischemia is important for brain repair. Herein, we focus on apoptosis signal-regulating kinase 1 (ASK1), which is involved in apoptotic cell death, brain infarction, and production of inflammatory mediators after cerebral ischemia. We hypothesized that ASK1 is involved in the polarization of M1/M2 phenotype and the function of microglia and macrophage during the late stage of ischemia/hypoxia. We investigated the effects of ASK1 in mice subjected to middle cerebral artery occlusion and on BV2 microglia and RAW264.7 macrophage cell lines subjected to oxygen-glucose deprivation. Our results showed that ASK1 silencing effectively reduced Iba-1 or CD11b-positive cells in ischemic areas, suppressed pro-inflammatory cytokines, and increased anti-inflammatory mediator levels at 7 days after cerebral ischemia. In cultured microglia and macrophages, ASK1 inhibition, induced by NQDI-1 drug, decreased the expression and release of M1-associated factors and increased those of M2-associated factors after hypoxia/reperfusion (H/R). At the gene level, ASK1 inhibition suppressed M1-associated genes and augmented M2-associated genes. In gap closure assay, ASK1 inhibition reduced the migration rate of microglia and macrophages after H/R. Taken together, our results provide new information that suggests ASK1 controls the polarization of M1/M2 and the function of microglia and macrophage under sustained-inflammatory conditions. Regulation of persistent inflammation via M1/M2 polarization by ASK1 is a novel strategy for repair after ischemic stroke

Resting-state prefrontal EEG biomarker in correlation with postoperative delirium in elderly patients

Postoperative delirium (POD) is associated with adverse outcomes in elderly patients after surgery. Electroencephalography (EEG) can be used to develop a potential biomarker for degenerative cerebral dysfunctions, including mild cognitive impairment and dementia. This study aimed to explore the relationship between preoperative EEG and POD. We included 257 patients aged >70 years who underwent spinal surgery. We measured the median dominant frequency (MDF), which is a resting-state EEG biomarker involving intrinsic alpha oscillations that reflect an idle cortical state, from the prefrontal regions. Additionally, the mini-mental state examination and Montreal cognitive assessment (MoCA) were performed before surgery as well as 5 days after surgery. For long-term cognitive function follow up, the telephone interview for cognitive status™ (TICS) was performed 1 month and 1 year after surgery. Fifty-two (20.2%) patients were diagnosed with POD. A multivariable logistic regression analysis that included age, MoCA score, Charlson comorbidity index score, Mini Nutritional Assessment, and the MDF as variables revealed that the MDF had a significant odds ratio of 0.48 (95% confidence interval 0.27–0.85). Among the patients with POD, the postoperative neurocognitive disorders could last up to 1 year. Low MDF on preoperative EEG was associated with POD in elderly patients undergoing surgery. EEG could be a novel potential tool for identifying patients at a high risk of POD

Development of Machine Learning Models Predicting Estimated Blood Loss during Liver Transplant Surgery

The incidence of major hemorrhage and transfusion during liver transplantation has decreased significantly over the past decade, but major bleeding remains a common expectation. Massive intraoperative hemorrhage during liver transplantation can lead to mortality or reoperation. This study aimed to develop machine learning models for the prediction of massive hemorrhage and a scoring system which is applicable to new patients. Data were retrospectively collected from patients aged >18 years who had undergone liver transplantation. These data included emergency information, donor information, demographic data, preoperative laboratory data, the etiology of hepatic failure, the Model for End-stage Liver Disease (MELD) score, surgical history, antiplatelet therapy, continuous renal replacement therapy (CRRT), the preoperative dose of vasopressor, and the estimated blood loss (EBL) during surgery. The logistic regression model was one of the best-performing machine learning models. The most important factors for the prediction of massive hemorrhage were the disease etiology, activated partial thromboplastin time (aPTT), operation duration, body temperature, MELD score, mean arterial pressure, serum creatinine, and pulse pressure. The risk-scoring system was developed using the odds ratios of these factors from the logistic model. The risk-scoring system showed good prediction performance and calibration (AUROC: 0.775, AUPR: 0.753)

Multiple cerebral infarction and paradoxical air embolism during hepatectomy using the Cavitron Ultrasonic Surgical Aspirator -A case report-

A venous air embolism and paradoxical air embolism (PAE) are serious complications in patients undergoing a hepatectomy. We report a case of PAE and cerebral infarctions in a patient undergoing a hepatic resection using a Cavitron Ultrasonic Surgical Aspirator (CUSA®). A 65-year-old woman underwent a left lobe hepatectomy. During the middle phase of the liver resection with CUSA®, there was a sudden decrease in arterial blood pressure, end-tidal carbon dioxide and SpO2. With resuscitation, intraoperative ultrasonography revealed massive air emboli in both her left and right heart, which lasted for 40 min. The hepatectomy was completed after the disappearance of the air emboli from her heart. After surgery, her mental status was stuporous. The brain CT and MRI revealed multiple acute cerebral infarctions. Finally, she died from septic shock. This case highlights the need for anesthetists and surgeons to be aware of the potential for CUSA®-related massive PAE

The Relationship of the Anthropometric Variables to the Infusion Rate of Rocuronium in the Elderly

We have determined the infusion rates of rocuronium in the elderly and young adult patients during sevoflurane and nitrous oxide anesthesia. The correlation of some anthropometric predictors with infusion rate of rocuronium was also investigated for both elderly and young adult. Participating patients were assigned to one of two groups: 1) young adult patients aged 20 to 50 years (n = 30); 2) elderly patients aged over 65 years (n = 30). The anthropometric variables such as height, weight, ratio of weight to body surface area, subscapularis and suprailiac skin folds, body surface area, body mass index and % ideal body weight were evaluated as predictors for infusion rate. The infusion rate in elderly patients was significantly less compared with that in young adult patients (p < 0.05). In elderly patients, no anthropometric predictor was related to the infusion rate of rocuronium. This suggests that the infusion rate of rocuronium for an elderly patient needs to be individualized by monitoring neuromuscular transmission to avoid excessive dose

Comparison of Remifentanil and Fentanyl for Postoperative Pain Control after Abdominal Hysterectomy

Purpose: In this randomized, double-blind study, we investigated the analgesic efficacy and side effects of continuous constant-dose infusions of remifentanil after total abdominal hysterectomy and compared it to fentanyl. Materials and Methods: Fifty-six adult female patients scheduled for elective total abdominal hysterectomy were enrolled in this study. Patients were randomly assigned to two groups according to fentanyl (group F, n = 28) or remifentanil (group R, n = 28) for postoperative analgesia. Patients in group F were given fentanyl intravenously with an infusion rate of fentanyl 0.5 μg/kg/hr; group R was given remifentanil with an infusion rate of remifentanil 0.05 μg/kg/ min for 2 days. Pain intensity at rest, occurrence of postoperative nausea and vomiting (PONV), dizziness, pruritus, and respiratory depression were assessed 1 hr after arrival at the post-anesthesia care unit, at 6; 12; 24; and 48 hr postoperation and 6 hr post-infusion of the study drug. Pain was evaluated by using visual analogue scale (VAS; 0- 10). The time that patients first requested analgesics was recorded as well as additional analgesics and antiemetics. Results: There were no significant differences in VAS, time to first postoperative analgesics, and additional analgesics between the 2 groups. The incidences and severities of PONV and opioid related side effects were not different between the groups; however, there were 3 episodes (10.7%) of serious respiratory depression in group R. Conclusion: Continuous infusion technique of remifentanil did not reveal any benefits compared to fentanyl. Furthermore, it is not safe for postoperative analgesia in the general ward

Analgesic Effect of Intrathecal Morphine Combined with Low-Dose Bupivacaine on Postoperative Analgesia after Liver Resection: A Randomized Controlled Study

Although intrathecal morphine and bupivacaine are increasingly implemented in effective postoperative pain control, there is a lack of consensus on the dosage as high doses of bupivacaine may inadvertently cause unwanted side effects. The purpose of this study was to compare the effects of intrathecal morphine injection and low-dose bupivacaine with morphine injection. In total, 90 patients were divided into 3 groups: (1) sham injection for the control group; (2) morphine 400 mcg for the morphine group (M); and (3) morphine 400 mcg and bupivacaine 5 mg for the morphine and bupivacaine group (M + B). Our primary outcome was time to first rescue analgesic. The VAS (visual analogue scale) pain score was compared until POD (postoperative day)1. Total fentanyl dose was compared until POD2. Side effects were monitored until POD3. Although time to first rescue was significantly shorter in the control group compared to group M and group M + B (p p = 0.023; p = 0.010). The addition of 5 mg bupivacaine may be insufficient in providing further analgesic benefits; however, higher doses may aggravate side effects