Search

Background Liver transplantation (LT) may be associated with massive blood loss and the need for allogeneic blood transfusion. Intraoperative blood salvage autotransfusion (IBSA) can reduce the need for allogeneic blood transfusion. This study aimed to investigate the effectiveness of blood salvage in LT. Methods Among 355 adult patients who underwent elective living-donor LT between January 1, 2019, and December 31, 2022, 59 recipients without advanced hepatocellular carcinoma received IBSA using Cell Saver (CS group). Based on sex, age, model for end-stage liver disease (MELD) score, preoperative laboratory results, and other factors, 118 of the 296 recipients who did not undergo IBSA were matched using propensity score (non-CS group). The primary outcome was the amount of intraoperative allogenic red blood cell (RBC) transfusion. Comparisons were made between the two groups regarding the amount of other blood components transfused and postoperative laboratory findings. Results The transfused allogeneic RBC for the CS group was significantly lower than that of the non-CS group (1,506.0 vs. 1,957.5 ml, P = 0.026). No significant differences in the transfused total fresh frozen plasma, platelets, cryoprecipitate, and estimated blood loss were observed between the two groups. The postoperative allogeneic RBC transfusion was significantly lower in the CS group than in the non-CS group (1,500.0 vs. 2,100.0 ml, P = 0.039). No significant differences in postoperative laboratory findings were observed at postoperative day 1 and discharge. Conclusions Using IBSA during LT can effectively reduce the need for perioperative allogeneic blood transfusions without causing subsequent coagulopathy.

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.

IntroductionAny persistent degree of cognitive impairment in older adults is a concern as it can progress to dementia. This study aimed to determine the incidence and risk factors for early postoperative cognitive dysfunction (POCD) in elderly patients undergoing spine surgery.MethodsPatients were enrolled from a previous prospective observational study after screening for normal cognitive function using the Mini Mental State Examination (MMSE). Cognitive function was evaluated before surgery and at 1 week, month, and year post-surgery using MMSE and Montreal Cognitive Assessment scores (MoCA). Mild cognitive impairment (MCI) was determined using the MoCA scores adjusted for age. POCD was defined as a drop of three or more points on the MMSE 1 week post-surgery. Multivariate logistic analysis was performed to identify POCD risk factors.ResultsA total of 427 patients were included. Eighty-five (20%) had pre-existing MCI. The MCI group showed lower MoCA scores at each time point (baseline, 1 week after surgery, 1 month after surgery, 1 year after surgery) compared to the non-MCI group. Those in the MCI group had a higher rate of admission to intensive care unit after surgery, postoperative delirium, and POCD 1 week post-surgery, than those in the non-MCI group (16.5% vs. 6.7%, p = 0.008; 27.1% vs. 15.8%, p = 0.024; and 18.8% vs. 8.2%, p 70 years. POCD was seen in ~20% of patients with pre-existing MCI, and ~ 10% of those without. Benzodiazepine use, significant comorbidities, pre-existing MCI, and depressive tendencies were risk factors for POCD.

Background: The role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the pathogenesis of hepatic encephalopathy (HE) is unclear. Mitochondrial reactive oxygen species (mtROS) is a signal for NLRP3 inflammasome activation. Therefore, we aimed to determine whether mtROS-dependent NLRP3 inflammasome activation is involved in HE, using in vivo and in vitro models. Methods: Bile duct ligation (BDL) in C57/BL6 mice was used as an in vivo HE model. NLRP3 activation was assessed in the hippocampus. Immunofluorescence staining was performed to determine the cellular source of NLRP3 in the hippocampal tissue. For the in vitro experiment, BV-2 microglial cells were primed with lipopolysaccharide (LPS), followed by ammonia treatment. NLRP3 activation and mitochondrial dysfunction were measured. Mito-TEMPO was used to suppress mtROS production. Results: BDL mice showed cognitive impairment with hyperammonemia. Both the priming and activation steps of NLRP3 inflammasome activation were processed in the hippocampus of BDL mice. Moreover, intracellular ROS levels increased in the hippocampus, and NLRP3 was mainly expressed in the microglia of the hippocampus. In LPS-primed BV-2 cells, ammonia treatment induced NLRP3 inflammasome activation and pyroptosis, with elevation of mtROS and altered mitochondrial membrane potential. Pretreatment with Mito-TEMPO suppressed mtROS production and the subsequent NLRP3 inflammasome activation and pyroptosis under LPS and ammonia treatment in BV-2 cells. Conclusions: Hyperammonemia in HE may be involved in mtROS overproduction and subsequent NLRP3 inflammasome activation. Further studies using NLRP3-specific inhibitor or NLRP3 knockout mice are needed to elucidate the important role of NLRP3 inflammasome in HE development.

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.

Abstract The early detection of graft failure in pediatric liver transplantation is crucial for appropriate intervention. Graft failure is associated with numerous perioperative risk factors. This study aimed to develop an individualized predictive model for 90-days graft failure in pediatric liver transplantation using machine learning methods. We conducted a single-center retrospective cohort study. A total of 87 liver transplantation cases performed in patients aged

BackgroundHepatic resection of Klatskin tumors usually requires postoperative intensive care unit (ICU) admission because of its high morbidity and mortality. Identifying surgical patients who will benefit most from ICU admission is important because of scarce resources but remains difficult. Sarcopenia is characterised by the loss of skeletal muscle mass and is associated with poor surgical outcomes.MethodsWe retrospectively analysed th.e relationship between preoperative sarcopenia and postoperative ICU admission and length of ICU stay (LOS-I) in patients who underwent hepatic resection for Klatskin tumors. Using preoperative computed tomography scans, the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra was measured and normalised to the patient’s height. Using these values, the optimal cut-off for diagnosing sarcopenia was determined using receiver operating characteristic curve analysis for each sex.ResultsOf 330 patients, 150 (45.5%) were diagnosed with sarcopenia. Patients with preoperative sarcopenia presented significantly more frequently to the ICU (77.3% vs. 47.9%, p < 0.001) and had longer total LOS-I (2.45 vs 0.89 days, p < 0.001). Moreover, patients with sarcopenia showed a significantly higher postoperative length of hospital stay, severe complication rate, and in-hospital mortality.ConclusionsSarcopenia correlated with poor postoperative outcomes, especially with the increased requirement of postoperative ICU admission and prolonged LOS-I after hepatic resection in patients with Klatskin tumors.

Abstract Here, we aimed to compare the effects of two anesthetic methods (desflurane inhalation anesthesia vs. propofol-based total intravenous anesthesia (TIVA)] on corrected QT interval (QTc) values during living donor liver transplantation. Altogether, 120 patients who underwent living donor liver transplantation were randomized to either the desflurane or TIVA group. The primary outcome was intraoperative QTc change. Other electrocardiogram, hemodynamic findings and postoperative outcomes were examined as secondary outcomes. QTc values were prolonged intraoperatively in both groups; however, the change was smaller in the TIVA group than in the desflurane group (PGroup × Time 500 ms in the desflurane group than in the TIVA group (63.3% vs. 28.3%, P

Background Dynamic preload indices may predict fluid responsiveness in end-stage liver disease. However, their usefulness in patients with altered vascular compliance is uncertain. This study is the first to evaluate whether dynamic indices can reliably predict fluid responsiveness in patients undergoing liver transplantation with a high femoral-to-radial arterial pressure gradient (PG). Methods Eighty liver transplant recipients were retrospectively categorized as having a normal (n = 56) or high (n = 24, difference in systolic pressure ≥ 10 mmHg and/or mean pressure ≥ 5 mmHg) femoral-to-radial arterial PG, measured immediately after radial and femoral arterial cannulation. The ability of dynamic preload indices (stroke volume variation, pulse pressure variation [PPV], pleth variability index) to predict fluid responsiveness was assessed before the surgery. Fluid replacement of 500 ml of crystalloid solution was performed over 15 min. Fluid responsiveness was defined as ≥ 15% increase in the stroke volume index. The area under the receiver-operating characteristic curve (AUC) indicated the prediction of fluid responsiveness. Results Fourteen patients in the normal, and eight in the high PG group were fluid responders. The AUCs for PPV in the normal, high PG groups and total patients were 0.702 (95% confidence interval [CI] 0.553–0.851, P = 0.008), 0.633 (95% CI 0.384–0.881, P = 0.295) and 0.667 (95% CI 0.537–0.798, P = 0.012), respectively. No other index predicted fluid responsiveness. Conclusion PPV can be used as a dynamic index of fluid responsiveness in patients with end-stage liver disease but not in patients with altered vascular compliance.

The aim of this study was to investigate the impact of noise exposure in an intensive care unit (ICU) environment on the development of postoperative delirium in a mouse model that mimics the ICU environment. Additionally, we aimed to identify the underlying mechanisms contributing to delirium and provide evidence for reducing the risk of delirium. In this study, to mimic an ICU environment, lipopolysaccharide (LPS)-injected sepsis mouse models were exposed to a 75 dB noise condition. Furthermore, we assessed neurobehavioral function and observed the level of neuroinflammatory response and blood–brain barrier (BBB) integrity in the hippocampal region. The LPS-injected sepsis mouse model exposed to noise exhibited increased anxiety-like behavior and cognitive impairment. Moreover, severe neuroinflammation and BBB disruption were detected in the hippocampal region. This study provides insights suggesting that persistent noise exposure under systemic inflammatory conditions may cause cognitive dysfunction and anxiety- like behavior via the mediation of BBB disruption and neuroinflammation. As a result, we suggest that the detailed regulation of noise exposure may be required to prevent the development of postoperative delirium.

Abstract Background Postoperative pain is a common phenomenon after surgery and is closely associated with the development of postoperative cognitive dysfunction (POCD). Persistent pain and systemic inflammation caused by surgery have been suggested as key factors for the development of POCD. Fractalkine (CX3CL1) and its receptor, the CX3C chemokine receptor 1 (CX3CR1), are known to play a key role in pain and inflammation signaling pathways. Recent studies have shown that the regulation of CX3CR1/L1 signaling influences the development of various diseases including neuronal diseases. We determined whether CX3CR1/L1 signaling is a putative therapeutic target for POCD in a mouse model. Methods Adult (9–11 weeks) male mice were treated with neutralizing antibody to block CX3CR1/L1 signaling both before and after surgery. Inflammatory and behavioral responses including pain were assessed postoperatively. Also, CX3CR1 mRNA level was assessed. Hippocampal astrocyte activation, Mao B expression, and GABA expression were assessed at 2 days after surgery following neutralizing antibody administration. Results The behavioral response indicated cognitive dysfunction and development of pain in the surgery group compared with the control group. Also, increased levels of pro-inflammatory cytokines and CX3CR1 mRNA were observed in the surgery group. In addition, increased levels of GABA and increased Mao B expression were observed in reactive astrocytes in the surgery group; these responses were attenuated by neutralizing antibody administration. Conclusions Increased CX3CR1 after surgery is both necessary and sufficient to induce cognitive dysfunction. CX3CR1 could be an important target for therapeutic strategies to prevent the development of POCD.

Abstract Postoperative delirium is a common neuropsychiatric syndrome resulting a high postsurgical mortality rate and decline in postdischarge function. Extensive research has been performed on both human and animal delirium-like models due to their clinical significance, focusing on systematic inflammation and consequent neuroinflammation playing a key role in the pathogenesis of postoperative cognitive dysfunctions. Since animal models are widely utilized for pathophysiological study of neuropsychiatric disorders, this study aimed at examining the validity of the scopolamine-induced delirium-like mice model with respect to the neuroinflammatory hypothesis of delirium. Male C57BL/6 mice were treated with intraperitoneal scopolamine (2 mg/kg). Neurobehavioral tests were performed to evaluate the changes in cognitive functions, including learning and memory, and the level of anxiety after surgery or scopolamine treatment. The levels of pro-inflammatory cytokines (IL-1β, IL-18, and TNF-α) and inflammasome components (NLRP3, ASC, and caspase-1) in different brain regions were measured. Gene expression profiles were also examined using whole-genome RNA sequencing analyses to compare gene expression patterns of different mice models. Scopolamine treatment showed significant increase in the level of anxiety and impairments in memory and cognitive function associated with increased level of pro-inflammatory cytokines and NLRP3 inflammasome components. Genetic analysis confirmed the different expression patterns of genes involved in immune response and inflammation and those related with the development of the nervous system in both surgery and scopolamine-induced mice models. The scopolamine-induced delirium-like mice model successfully showed that analogous neuropsychiatric changes coincides with the neuroinflammatory hypothesis for pathogenesis of delirium.

Background Bile duct ligation (BDL) has been used for experimental research on hepatic encephalopathy (HE) caused by chronic liver disease. However, little research has been done on a BDL model in C57BL/6 mouse. Therefore, we evaluated the suitability of a BDL model in C57BL/6 mouse for the study of HE and determined which behavioral tests are appropriate for the identification of HE in this model. Methods Twelve to fourteen-week-old male C57BL/6 mice were randomly assigned to either sham group or BDL group. Histological changes in liver were confirmed by hematoxylin/eosin and Masson’s trichrome staining. Liver function alterations were detected by alanine aminotransferase (ALT) and ammonia levels. To identify behavioral changes, open field, elevated plus maze, novel object recognition, and passive avoidance tests were performed. Results Inflammatory liver injury and fibrosis were observed 14 days after BDL. ALT and ammonia levels were significantly higher in BDL group than in sham group. There were no differences in general locomotor activity or anxiety between the groups. No difference was observed between these two groups in the novel object recognition test, but BDL group showed significant learning/memory impairment in the passive avoidance test compared to sham group. Conclusions Fourteen days of BDL in 12–14-week-old male C57BL/6 mice is a clinically relevant model for HE, as these mice have liver fibrosis with impaired liver function, hyperammonemia, and learning/memory impairment. Passive avoidance can be used as the major behavioral test in this model of HE.

Background Patients with hemifacial microsomia may have a difficult airway due to the accompanying mandibular deformity. Fiberoptic bronchoscope-guided intubation is commonly used method for difficult airway management. However, awake fiberoptic nasotracheal intubation has several disadvantages, including difficulty in advancement of the endotracheal tube (ETT) due to the resistance between the ETT and bronchoscope. Wire-guided fiberoptic nasotracheal intubation may help to overcome the drawbacks of the conventional method. Case An 18-year-old man with hemifacial microsomia was scheduled for double-jaw surgery. In preoperative evaluation, he had severe retrognathia and expected difficult airway. We successfully performed wire-guided fiberoptic nasotracheal intubation combined with high-flow nasal cannula and deep sedation without any complications. Conclusions A guidewire may be useful, in case of difficultly in advancing the ETT or if a smaller tube is required, while performing intubation with FOB in patients with difficult airways.

Dexmedetomidine (Dex), widely used as a sedative in surgical procedures and intensive care units, induces sympatholytic, anxiolytic, analgesic, and sedative effects. Postoperative cognitive dysfunction (POCD) is routinely observed in postoperative care following surgery and general anesthesia. The NLRP3 inflammasome complex plays a critical role in innate immune response by detecting pathogenic microorganisms and activating pro-inflammatory cytokines. Although there are numerous protective effects of Dex among the neurological diseases, specific mechanisms including NLRP3 inflammasome-mediated neuroinflammation via oxidative stress response in a POCD model are not fully understood. Here, we investigated whether Dex exhibits neurocognitive effects through the NLRP3 inflammasome signaling in a POCD mouse model using a neurobehavioral test and ELISA analysis. We also confirmed the level of oxidative stress-related response in the in vitro system in the POCD model. Furthermore, we evaluated the NLRP3 inflammasome complex by immunoprecipitation analysis. In summary, the results of the present study indicated that Dex showed a neuroprotective effect in the POCD model by reducing oxidative stress response through NLRP3 inflammasome-mediated neuroinflammation.

Background Considering the functional role of red blood cells (RBC) in maintaining oxygen supply to tissues, RBC transfusion can be a life-saving intervention in situations of severe bleeding or anemia. RBC transfusion is often inevitable to address intraoperative massive bleeding; it is a key component in safe perioperative patient management. Unlike general medical resources, packed RBCs (pRBCs) have limited availability because their supply relies entirely on voluntary donations. Additionally, excessive utilization of pRBCs may aggravate prognosis or increase the risk of developing infectious diseases. Appropriate perioperative RBC transfusion is, therefore, crucial for the management of patient safety and medical resource conservation. These concerns motivated us to develop the present clinical practice guideline for evidence-based efficient and safe perioperative RBC transfusion management considering the current clinical landscape. Methods This guideline was obtained after the revision and refinement of exemplary clinical practice guidelines developed in advanced countries. This was followed by rigorous evidence-based reassessment considering the healthcare environment of the country. Results This guideline covers all important aspects of perioperative RBC transfusion, such as preoperative anemia management, appropriate RBC storage period, and leukoreduction (removal of white blood cells using filters), reversal of perioperative bleeding tendency, strategies for perioperative RBC transfusion, appropriate blood management protocols, efforts to reduce blood transfusion requirements, and patient monitoring during a perioperative transfusion. Conclusions This guideline will aid decisions related to RBC transfusion in healthcare settings and minimize patient risk associated with unnecessary pRBC transfusion.

Objective This study was performed to compare the use of a video laryngoscope-guided lightwand versus a single lightwand for tracheal intubation performed by non-experts in cervical spine-immobilized patients. Methods In total, 318 patients under general anesthesia were assigned either to the single lightwand group (Group L) or the video laryngoscope-guided lightwand group (Group VL) at a 1:1 ratio. First- or second-grade residents performed tracheal intubation with the assigned device after applying semi-hard fitted cervical collars to the patients. Outcomes, including the success rate and airway complications, were compared between the two groups. Results There were no significant differences in demographics or airway-related characteristics between the two groups. The success rate of intubation on the first attempt was significantly higher in Group VL than in Group L (90% vs. 64%, respectively). Postoperative complications, including oral mucosal bleeding, hoarseness, and sore throat scores at 1 and 24 hours after surgery, were significantly lower in Group VL than in Group L. Conclusions The use of a video laryngoscope-guided lightwand for tracheal intubation can be useful for non-experts who encounter difficult airway situations.

The outbreak of the coronavirus disease 2019 (COVID-19) began at the end of 2019. COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with COVID-19 may exhibit poor clinical outcomes. Some patients with severe COVID-19 experience cytokine release syndrome (CRS) or a cytokine storm—elevated levels of hyperactivated immune cells—and circulating pro-inflammatory cytokines, including interleukin (IL)-1β and IL-18. This severe inflammatory response can lead to organ damage/failure and even death. The inflammasome is an intracellular immune complex that is responsible for the secretion of IL-1β and IL-18 in various human diseases. Recently, there has been a growing number of studies revealing a link between the inflammasome and COVID-19. Therefore, this article summarizes the current literature regarding the inflammasome complex and COVID-19.

Abstract Pericytes are believed to originate from either mesenchymal or neural crest cells. It has recently been reported that pericytes play important roles in the central nervous system (CNS) by regulating blood-brain barrier homeostasis and blood flow at the capillary level. However, the origin of CNS microvascular pericytes and the mechanism of their recruitment remain unknown. Here, we show a new source of cerebrovascular pericytes during neurogenesis. In the CNS of embryonic day 10.5 mouse embryos, CD31+F4/80+ hematopoietic lineage cells were observed in the avascular region around the dorsal midline of the developing midbrain. These cells expressed additional macrophage markers such as CD206 and CD11b. Moreover, the CD31+F4/80+ cells phagocytosed apoptotic cells as functionally matured macrophages, adhered to the newly formed subventricular vascular plexus, and then divided into daughter cells. Eventually, these CD31+F4/80+ cells transdifferentiated into NG2/PDGFRβ/desmin-expressing cerebrovascular pericytes, enwrapping and associating with vascular endothelial cells. These data indicate that a subset of cerebrovascular pericytes derive from mature macrophages in the very early phase of CNS vascular development, which in turn are recruited from sites of embryonic hematopoiesis such as the yolk sac by way of blood flow.

BackgroundThe elderly have been reported to show anatomical and physiologic changes in the upper airway, which might affect the supraglottic airway (SGA) performance in geriatric populations. This study aimed to evaluate the clinical efficacy of the classic laryngeal mask airway (LMA-C) in the elderly compared with young adult patients.MethodsFifty patients aged 65-85 years (elderly group) and 50 patients aged 20-40 years (young group) who were scheduled for surgery using the LMA-C for general anesthesia were enrolled in this prospective, non-randomized, comparative study. Manipulations required during insertion, success rate, insertion time, oropharyngeal leak pressure, gastric insufflation, and intraoperative inadequate ventilation with the LMA-C were assessed. Fiberoptic evaluation was used to determine the position of the LMA-C.ResultsIn the elderly group, the insertion success rate on the first attempt was significantly lower than that in the young group (84 vs. 96%, P = 0.02). The insertion time in the elderly group was significantly longer than that in the young group (28.5 ± 19.6 vs. 22.2 ± 6.4 seconds, P = 0.001). However, there was no difference in oropharyngeal leak pressure or fiberoptic grade between the two groups after proper placement of the LMA-C. During the surgery, inadequate ventilation events occurred more frequently in the elderly group than in the young group (31.3 vs. 4.0%, P < 0.001).ConclusionsThe clinical efficacy of the LMA-C in elderly patients was inferior to that in young adult patients. Therefore, further studies are required to determine the type of SGA that can provide excellent clinical efficacy in the geriatric population.

Cognitive symptoms are prevalent in the elderly and are associated with an elevated risk of developing dementia. Disease-driven changes can cause cognitive disabilities in memory, attention, and language. The inflammasome is an innate immune intracellular complex that has a critical role in the host defense system, in that it senses infectious pathogen-associated and endogenous danger-associated molecular patterns. An unbalanced or dysregulated inflammasome is associated with infectious, inflammatory, and neurodegenerative diseases. Due to its importance in such pathological conditions, the inflammasome is an emerging drug target for human diseases. A growing number of studies have revealed links between cognitive symptoms and the inflammasome. Several studies have shown that reducing the inflammasome component mitigates cognitive symptoms in diseased states. Therefore, understanding the inflammasome regulatory mechanisms may be required for the prevention and treatment of cognitive symptoms. The purpose of this review is to discuss the current understanding of the inflammasome and its relationships with cognitive symptoms in various human diseases.

Postoperative cognitive dysfunction (POCD) may be driven by transference of the innate immune response to the brain after aseptic surgical damage. Macrophages are key mediators of innate immunity that can display a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype. Erythropoietin (EPO) is a hematopoietic hormone that exerts anti-inflammatory effects by influencing macrophage function. We hypothesized that EPO would prevent POCD by promoting macrophage phenotype switching to the M2 phenotype post-surgery. To evaluate the effects of EPO on POCD and macrophage polarization post-surgery, we administered EPO (5,000 U/kg) with or without an arginase inhibitor (amino-6-boronohexanoic acid, 10 mg/kg) to ICR mice before and after abdominal surgery. Forty-eight hours post-surgery, we assessed memory, synapse function, and macrophage/microglial phenotypes in the spleen and hippocampus. We also investigated M1/M2 phenotypes in RAW264.7 and BV2 cells stimulated with lipopolysaccharide and interferon-γ (M1 inducers) in the presence or absence of EPO. EPO prevented POCD, decreased surgery-related synaptic dysfunction, and attenuated pro-inflammatory cytokine generation in the hippocampus. Moreover, EPO suppressed M1-related genes expression and promoted M2 genes expression in the spleen and hippocampus post-surgery. Furthermore, EPO decreased the proportions of macrophages/microglia expressing an M1 surface marker (CD40) and increased those expressing an M2 surface marker (CD206). Arginase inhibition abolished the beneficial effects of EPO on POCD. In vitro, EPO treatment promoted switching of RAW264.7 and BV2 cells stimulated with M1 inducers to an M2 phenotype. In conclusion, EPO prevents POCD by promoting macrophage phenotype switching toward the M2 phenotype.

BackgroundIntravenous tissue-type plasminogen activator (tPA) is recognized as the standard treatment for ischemic stroke. However, its narrow therapeutic window and association with an increased risk of intracranial hemorrhage have required caution when used. In this context, several approaches are required to deal with the shortcomings of such a double-edged drug. Anesthetics are known to protect against ischemic reperfusion injury, and their protective role in ischemic post-conditioning is crucial for reducing ischemia-related injury. The aim of this study was to assess the effect of isoflurane post-treatment on intracranial hemorrhage and cerebral infarction after tPA treatment for transient cerebral ischemia.MethodsCerebral ischemia was modeled in male Sprague-Dawley rats (n = 32) by occluding the right middle cerebral artery for 1 h, followed by intravenous tPA administration. Rats were randomly divided into control and isoflurane post-treatment group, and isoflurane post-treatment group was post-treated by administering 1.5% isoflurane for 1 h from the start of reperfusion. Twenty-four h after reperfusion, neurobehavioral changes were assessed. The extent of cerebral infarction and intracranial hemorrhage were also assessed by quantification of infarction volume and cerebral hemoglobin concentration from brain tissue, respectively.ResultsNeurobehavioral testing showed better functional outcomes in the isoflurane post-treatment group than the control group. The extent of cerebral infarction and intracranial hemorrhage were both reduced in isoflurane post-treatment group compared to control group.ConclusionsIsoflurane post-treatment may mitigate infarction volume and intracranial hemorrhage in tPA-exaggerated brain injury. Our findings provide an encouraging novel approach for enhancing clinical outcomes in tPA-exaggerated brain injury.

We report a case of possible venous air embolism (VAE) during trans pars plana vitrectomy with air-fluid exchange of the vitreous cavity. Shortly after initiation of air-fluid exchange, decreases in end-tidal CO2, oxygen saturation, and blood pressure were observed. The patient rapidly progressed to cardiac arrest unresponsive to cardiopulmonary resuscitation, and recovered after the application of percutaneous cardiopulmonary support. Prompt termination of air infusion is needed when VAE is suspected during air-fluid exchange, and extracorporeal life support should be considered in fatal cases. Although the incidence is rare the possibility of VAE during ophthalmic surgery clearly exists, and therefore awareness and vigilant monitoring seem critical.

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.

BackgroundActive upper respiratory tract infection (URI), orotracheal intubation and use of inhalation anesthetics are known risk factors for perioperative respiratory adverse events (RAE). This study investigated the risk factors of perioperative RAE in children with these risk factors.MethodsThe records of 159 children who underwent general anesthesia with an orotracheal tube and inhalation were reviewed. These patients also had at least one of the following URI symptoms on the day of surgery: clear or green nasal secretion, dry or moist cough, nasal congestion, or fever. RAE such as laryngospasm, bronchospasm, oxygen desaturation and sustained cough were collected before induction, during intubation, during extubation, after extubation and in the postanesthesia care unit.ResultsForty-five patients had RAE. The patients with RAE were younger than those without RAE. There were more passive smokers and a greater number of intubation attempts in patients with RAE than in those without RAE. The type of surgery and type of inhalation agents were not different between patients with and without RAE. Passive smoking was the only independent risk factor for RAE.ConclusionsIn children with an active URI using orotracheal tube and inhalation anesthetics, passive smoking is an important risk factor for RAE.

Conditions of increased oxidative stress including cerebral ischemia can lead to blood-brain barrier (BBB) dysfunction via matrix metalloproteinase (MMP). It is known that MMP-9 in particular is released from brain endothelial cells is involved in the neuronal cell death that occurs after cerebral ischemia. In the intracellular signaling network, apoptosis signal-regulating kinase 1 (ASK1) is the main activator of the oxidative stress that is part of the pathogenesis of cerebral ischemia. ASK1 also promotes apoptotic cell death and brain infarction after ischemia and is associated with vascular permeability and the formation of brain edema. However, the relationship between ASK1 and MMP-9 after cerebral ischemia remains unknown. Therefore, the aim of the present study was to determine whether blocking ASK1 would affect MMP-9 activity in the ischemic brain and cultured brain endothelial cells. Our results showed that ASK1 inhibition efficiently reduced MMP-9 activity in vivo and in vitro. In endothelial cell cultures, ASK1 inhibition upregulated phosphatidylinositol 3-kinase (PI3K)/Akt/nuclear factor erythroid 2 NF-E2-related factor 2 (Nrf-2)/heme oxygenase-1 (HO-1) signals and downregulated cyclooxygenase-2 (Cox-2) signals after hypoxia/reperfusion. Additionally, in neuronal cell cultures, cell death occurred when neurons were incubated with endothelial cell-conditioned medium (EC-CM) obtained from the hypoxia/reperfusion group. However, after incubation with EC-CM and following treatment with the ASK1 inhibitor NQDI-1, neuronal cell death was efficiently decreased. We conclude that suppressing ASK1 decreases MMP-9 activity in brain endothelial cells, and leading to decreased neuronal cell death after ischemic injury.

BackgroundThe objective of this retrospective study was to determine if there are any differences in grafted kidney function in recipients of kidney transplantation (KT) when donors and recipients were anesthetized with sevoflurane compared to desflurane.MethodsSeventy-three pairs of donors-recipients were anesthetized with sevoflurane (Sevo group) and 71 pairs were anesthetized with desflurane (Des group). We retrospectively investigated the blood urea nitrogen (BUN) levels, creatinine (Cr) levels, and estimated glomerular filtration rates (eGFR) of the recipients in both groups for 1 year postoperatively. We tested non-inferiority for serum creatinine at discharge and 1 year after KT. Short-term (1 year) outcomes of KT were assessed by the incidence of delayed graft function (DGF), acute rejection episodes (ARE), and graft failure.ResultsThere were no differences in BUN, Cr, eGFR, or outcomes of KT at 1 year postoperatively. Specifically, the 95% confidence interval for the difference in creatinine levels between the Sevo and Des groups was less than the margin of equivalence at the time of discharge and 1 year after surgery. The occurrences of DGF, ARE, and graft failure were comparable between the groups.ConclusionsCompared to desflurane, sevoflurane had no adverse effects on grafted renal function or on the short-term outcome of renal transplantation.

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.

Background: Liver transplantation (LT) may be associated with massive blood loss and the need for allogeneic blood transfusion. Intraoperative blood salvage autotransfusion (IBSA) can reduce the need for allogeneic blood transfusion. This study aimed to investigate the effectiveness of blood salvage in LT. Methods: Among 355 adult patients who underwent elective living-donor LT between January 1, 2019, and December 31, 2022, 59 recipients without advanced hepatocellular carcinoma received IBSA using Cell Saver (CS group). Based on sex, age, model for end-stage liver disease (MELD) score, preoperative laboratory results, and other factors, 118 of the 296 recipients who did not undergo IBSA were matched using propensity score (non-CS group). The primary outcome was the amount of intraoperative allogenic red blood cell (RBC) transfusion. Comparisons were made between the two groups regarding the amount of other blood components transfused and postoperative laboratory findings. Results: The transfused allogeneic RBC for the CS group was significantly lower than that of the non-CS group (1,506.0 vs. 1,957.5 ml, P = 0.026). No significant differences in the transfused total fresh frozen plasma, platelets, cryoprecipitate, and estimated blood loss were observed between the two groups. The postoperative allogeneic RBC transfusion was significantly lower in the CS group than in the non-CS group (1,500.0 vs. 2,100.0 ml, P = 0.039). No significant differences in postoperative laboratory findings were observed at postoperative day 1 and discharge. Conclusions: Using IBSA during LT can effectively reduce the need for perioperative allogeneic blood transfusions without causing subsequent coagulopathy. [ABSTRACT FROM AUTHOR]