Real-time monitoring of cortical brain activity in response to acute pain using wide-area Ca2+ imaging.

Previous human and rodent studies indicated that nociceptive stimuli activate many brain regions that is involved in the somatosensory and emotional sensation. Although these studies have identified several important brain regions involved in pain perception, it has been a challenge to observe neural activity directly and simultaneously in these multiple brain regions during pain perception. Using a transgenic mouse expressing G-CaMP7 in majority of astrocytes and a subpopulation of excitatory neurons, we recorded the brain activity in the mouse cerebral cortex during acute pain stimulation. Both of hind paw pinch and intraplantar administration of formalin caused strong transient increase of the fluorescence in several cortical regions, including primary somatosensory, motor and retrosplenial cortex. This increase of the fluorescence intensity was attenuated by the pretreatment with morphine. The present study provides important insight into the cortico-cortical network during pain perception.

Comparative efficacy of ultrasound guidance or conventional anatomical landmarks for neuraxial puncture in adult patients: a systematic review and network meta-analysis.

BACKGROUND: Preprocedural, real-time, and computer-aided three-dimensional ultrasound has been widely used for neuraxial puncture; however, the optimal guidance is unclear. We examined the comparative efficacy of three ultrasound guidance and anatomical landmarks for neuraxial puncture in adults. METHODS: We searched for randomised controlled studies comparing the efficacy of ultrasound guidance and anatomical landmarks for neuraxial puncture in adults using electronic databases and unpublished studies. The primary outcomes were first-pass success and patient satisfaction. A random-effects network meta-analysis (NMA) was used. RESULTS: We identified 74 eligible studies (7090 patients). Preprocedural ultrasound and real-time ultrasound-guided neuraxial puncture improved first-pass success compared with anatomical landmarks (risk ratio [RR] 1.6; 95% credible interval [CrI] 1.3-1.9; RR 1.9; 95% CrI 1.3-2.9, respectively, moderate confidence). Computer-aided ultrasound-guided neuraxial puncture also increased first-pass success (RR 1.8; 95% CrI 0.97-3.3, low confidence), although estimates were imprecise. However, real-time ultrasound-guided neuraxial puncture resulted in minimal difference in first-pass success compared with preprocedural ultrasound (RR 1.2; 95% CrI 0.8-1.8, moderate confidence). Preprocedural ultrasound improved patient satisfaction slightly compared with anatomical landmark use (standardised mean differences 0.28; 95% CrI 0.092-0.47, low confidence). CONCLUSIONS: This NMA provides evidence supporting ultrasound-guided neuraxial puncture compared with use of anatomical landmarks, including indirect comparisons. Among the three ultrasound guidance methods, preprocedural ultrasound appears to be a better adjunctive option.

Association between postinduction hypotension and postoperative mortality: a single-centre retrospective cohort study.

PURPOSE: We aimed to elucidate whether postinduction hypotension (PIH), defined as hypotension between anesthesia induction and skin incision, and intraoperative hypotension (IOH) are associated with postoperative mortality. METHODS: We conducted a retrospective cohort study of adult patients with an ASA Physical Status I-IV who underwent noncardiac and nonobstetric surgery under general anesthesia between 2015 and 2021 at Nagoya City University Hospital. The primary and secondary outcomes were 30-day and 90-day postoperative mortality, respectively. We calculated four hypotensive indices (with time proportion of the area under the threshold being the primary exposure variable) to evaluate the association between hypotension (defined as a mean blood pressure < 65 mm Hg) and mortality using multivariable logistic regression models. We used propensity score matching and RUSBoost (random under-sampling and boosting), a machine-learning model for imbalanced data, for sensitivity analyses. RESULTS: Postinduction hypotension and IOH were observed in 82% and 84% of patients, respectively. The 30-day and 90-day postoperative mortality rates were 0.4% (52/14,210) and 1.0% (138/13,334), respectively. Postinduction hypotension was not associated with 30-day mortality (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.93 to 1.13; P = 0.60) and 90-day mortality (aOR, 1.01; 95% CI, 0.94 to 1.07; P = 0.82). Conversely, IOH was associated with 30-day mortality (aOR, 1.19; 95% CI, 1.12 to 1.27; P < 0.001) and 90-day mortality (aOR, 1.12; 95% CI, 1.06 to 1.19; P < 0.001). Sensitivity analyses supported the association of IOH but not PIH with postoperative mortality. CONCLUSION: Despite limitations, including power and residual confounding, postoperative mortality was associated with IOH but not with PIH.

RéSUMé: OBJECTIF: Nous avons cherché à déterminer si l'hypotension post-induction (HPI), définie comme une hypotension entre l'induction de l'anesthésie et l'incision cutanée, et l'hypotension peropératoire (HPO) étaient associées à la mortalité postopératoire. MéTHODE: Nous avons mené une étude de cohorte rétrospective de patient·es adultes ayant un statut physique I-IV selon l'ASA et ayant bénéficié d'une chirurgie non cardiaque et non obstétricale sous anesthésie générale entre 2015 et 2021 à l'Hôpital universitaire de la ville de Nagoya. Les critères d'évaluation principal et secondaire étaient la mortalité postopératoire à 30 et 90 jours, respectivement. Nous avons calculé quatre indices d'hypotension (la proportion temporelle de la zone sous le seuil étant la principale variable d'exposition) pour évaluer l'association entre l'hypotension (définie comme une tension artérielle moyenne < 65 mm Hg) et la mortalité à l'aide de modèles de régression logistique multivariée. Nous avons utilisé l'appariement par score de propension et le RUSBoost (sous-échantillonnage et boosting aléatoire), un modèle d'apprentissage automatique pour les données déséquilibrées, pour les analyses de sensibilité. RéSULTATS: Une HPI et une HPO ont été observées chez 82 % et 84 % des patient·es, respectivement. Les taux de mortalité postopératoire à 30 et 90 jours étaient respectivement de 0,4 % (52/14 210) et de 1,0 % (138/13 334). L'hypotension post-induction n'était pas associée à la mortalité à 30 jours (rapport de cotes ajusté [RCa], 1,03; intervalle de confiance [IC] à 95 %, 0,93 à 1,13; P = 0,60) et à la mortalité à 90 jours (RCa, 1,01; IC 95 %, 0,94 à 1,07; P = 0,82). À l'inverse, l'HPO était associée à une mortalité à 30 jours (RCa, 1,19; IC 95 %, 1,12 à 1,27; P < 0,001) et à la mortalité à 90 jours (RCa, 1,12; IC 95 %, 1,06 à 1,19; P < 0,001). Les analyses de sensibilité ont confirmé l'association de l'HPO, mais pas de l'HPI, avec la mortalité postopératoire. CONCLUSION: Malgré les limitations, y compris la puissance et persistance de facteurs confondants, la mortalité postopératoire était associée à l'hypotension peropératoire mais pas à l'hypotension post-induction seule.

Remimazolam anaphylaxis in a patient not allergic to brotizolam: a case report and literature review.

BACKGROUND: Remimazolam is a recently developed, ultrashort-acting benzodiazepine that is used as a general anesthetic. Some cases of remimazolam anaphylaxis have been reported, but its characteristics are not fully understood. We present an interesting case report and review of the literature to better understand remimazolam anaphylaxis. CASE PRESENTATION: A 75-year-old man scheduled for robot-assisted gastrectomy was administered remimazolam for the induction of general anesthesia. After intubation, low end-expiratory CO2, high airway pressure and concurrent circulatory collapse were observed. Bronchoscopy revealed marked tracheal and bronchial edema, which we diagnosed as anaphylaxis. The patient suffered cardiac arrest after bronchoscopy but recovered immediately with intravenous adrenaline administration and chest compressions. We performed skin prick tests for the drugs used during induction except for remimazolam, considering the high risk of systemic adverse reactions to remimazolam. We diagnosed remimazolam anaphylaxis because the skin prick test results for the other drugs used during anesthesia were negative, and these drugs could have been used without allergic reactions during the subsequent surgery. Furthermore, this patient had experienced severe anaphylactic-like reactions when he underwent cardiac surgery a year earlier, in which midazolam had been used, but it was not thought to be the allergen at that time. Based on these findings, cross-reactivity to remimazolam and midazolam was suspected. However, the patient had previously received another benzodiazepine, brotizolam, to which he was not allergic, suggesting that cross-reactivity of remimazolam may vary among benzodiazepines. In this article, we reviewed the 11 cases of remimazolam anaphylaxis that have been described in the literature. CONCLUSIONS: Remimazolam is an ultrashort-acting sedative; however, it can cause life-threatening anaphylaxis. In addition, its cross-reactivity with other benzodiazepines is not fully understood. To increase the safety of this drug, further research and more experience in its use are needed.

High preoperative serum strontium levels increase the risk of acute kidney injury after cardiopulmonary bypass.

BACKGROUND: Acute kidney injury (AKI) is a common complication of cardiac surgeries. The incidence of AKI after cardiac surgeries using cardiopulmonary bypass (CPB-AKI) is high, emphasizing the need to determine strategies to prevent CPB-AKI. This study investigates the correlation between CPB-AKI and trace metal levels in clinical and animal studies. METHODS: Samples and clinical data were obtained from 74 patients from the Nagoya City University Hospital and Okazaki City Hospital. Blood samples were collected before, immediately after, and 2 h after CPB withdrawal. Trace metal levels were measured using inductively coupled plasma mass spectrometry. Sr or vehicle treatment was orally administered to the rats to determine if Sr was associated with CPB-AKI. After the treatment, ischemia-reperfusion (IR) injury was induced, and serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured. RESULTS: In this clinical study, the incidence of CPB-AKI was found to be 28% (21/74). The body mass index and estimated glomerular filtration rate were significantly different in patients with AKI. The intensive care unit and hospital stay were longer in AKI patients than in non-AKI patients. The Na, Fe, and Sr levels were significantly higher in AKI patients before CPB. Also, Fe and Sr were higher immediately after CPB withdrawal, and Sr was higher 2 h after CPB withdrawal in AKI patients. Animal studies showed that Sr-treated rats had significantly increased SCr and BUN levels than vehicle-treated rats at 24 h post-IR injury. CONCLUSIONS: High preoperative serum Sr levels may be associated with CPB-AKI.

Efficacy of intravenous dexamethasone on postoperative pain after caesarean delivery under spinal anaesthesia with an intrathecal long-acting opioid: a systematic review and meta-analysis.

PURPOSE: Intravenous dexamethasone is recommended in elective caesarean delivery to decrease postoperative pain. However, the efficacy of spinal anaesthesia with an intrathecal long-acting opioid such as morphine or diamorphine for caesarean delivery has not been systematically investigated. METHODS: We searched all randomized controlled trials (RCTs) of pregnant women undergoing caesarean delivery under spinal anaesthesia with an intrathecal morphine or diamorphine via MEDLINE, CENTRAL, EMBASE, ICTRP, and ClinicalTrials.gov on May 18, 2022. Primary outcomes were time to first rescue analgesia, consumption of oral morphine equivalents, and incidence of drug-related adverse reactions. We evaluated the risk of bias for each outcome using the Risk of Bias 2. We conducted a meta-analysis using a random effects model. We evaluated the certainty of evidence with the GRADE approach. RESULTS: Five RCTs (455 patients) were included. The results of intravenous dexamethasone were as follows: time to first rescue analgesia (mean difference [MD] 0.99 h, 95% confidence interval [CI] - 0.86 to 2.84; very low certainty) and consumption of oral morphine equivalents (MD - 6.55 mg, 95% CI - 17.13 to 4.02; moderate certainty). No incidence of drug-related adverse reactions was reported (very low certainty). CONCLUSION: The evidence was very uncertain about the efficacy of intravenous dexamethasone on time to first rescue analgesia and the incidence of drug-related adverse reactions. Intravenous dexamethasone probably reduces the consumption of oral morphine equivalents. Anaesthesiologists might want to consider intravenous dexamethasone for postoperative pain after caesarean delivery under spinal anaesthesia with an intrathecal long-acting opioid.

Poly(I:C) promotes neurotoxic amyloid ß accumulation through reduced degradation by decreasing neprilysin protein levels in astrocytes.

Inflammation associated with viral infection of the nervous system has been involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD) and multiple sclerosis. Polyinosinic:polycytidylic acid (poly[I:C]) is a Toll-like receptor 3 (TLR3) agonist that mimics the inflammatory response to systemic viral infections. Despite growing recognition of the role of glial cells in AD pathology, their involvement in the accumulation and clearance of amyloid ß (Aß) in the brain of patients with AD is poorly understood. Neprilysin (NEP) and insulin-degrading enzyme (IDE) are the main Aß-degrading enzymes in the brain. This study investigated whether poly(I:C) regulated Aß degradation and neurotoxicity by modulating NEP and IDE protein levels through TLR3 in astrocytes. To this aim, primary rat primary astrocyte cultures were treated with poly(I:C) and inhibitors of the TLR3 signaling. Protein levels were assessed by Western blot. Aß toxicity to primary neurons was measured by lactate dehydrogenase release. Poly(I:C) induced a significant decrease in NEP levels on the membrane of astrocytes as well as in the culture medium. The degradation of exogenous Aß was markedly delayed in poly(I:C)-treated astrocytes. This delay significantly increased the neurotoxicity of exogenous Aß1-42. Altogether, these results suggest that viral infections induce Aß neurotoxicity by decreasing NEP levels in astrocytes and consequently preventing Aß degradation.

Trends and patterns in the practice of pediatric sedation for magnetic resonance imaging in Japan: A longitudinal descriptive study from 2012 to 2019.

BACKGROUND: Worldwide, pediatric sedation for magnetic resonance imaging is a standard practice; however, there are few studies on its trends and patterns. AIMS: This study aimed to investigate the trends and patterns of pediatric sedation for magnetic resonance imaging in Japan and determine the incidence of and risk factors for adverse events/interventions. METHODS: This longitudinal descriptive study assessed children (age < 15 years) who underwent sedation for magnetic resonance imaging between April 2012 and December 2019 in Japan using a nationwide claims database. We assessed the patients' demographic characteristics, time trends in sedatives, sedative patterns by age, and adverse events/interventions within two post-sedation days. Further, we used multivariable logistic regression models to explore factors related to the incidence of adverse events/interventions. RESULTS: We identified 29 187 cases (median age, 2.0 years; 55.2% males). The most common sedative was triclofos sodium (n = 18 812, 51.7%). There was an increasing trend in barbiturate use (17.0% [2012] to 25.0% [2019]) and decreasing trends in the use of triclofos sodium (56.4% [2012] to 47.7% [2019]) and chloral hydrate (15.6% [2012] to 10.8% [2019]). We identified 534 adverse events/interventions in 460 cases (1.5%). Multivariable logistic regression analyses revealed that the incidence of adverse events/interventions mainly increased with the number of sedatives (≥3; adjusted odds ratio, 5.10; 95% confidence interval, 3.67-7.10) and unscheduled setting (adjusted odds ratio, 6.28; 95% confidence interval, 4.85-8.61); further, it decreased with high hospital procedure volume (adjusted odds ratio, 0.62; 95% confidence interval, 0.49-0.78). CONCLUSIONS: Based on a Japanese real-world setting, there is an increasing trend in barbiturate use and decreasing trends in the use of triclofos sodium and chloral hydrate in pediatric sedation for magnetic resonance imaging. Low hospital procedure volumes were associated with an increased risk of adverse events/interventions.

Intercristal line determined by palpation in parturients in the sitting and the lateral decubitus positions: a prospective observational study.

PURPOSE: We aimed to investigate intersected vertebral level changes in the palpated intercristal line (PI-line) when shifting from a sitting to a lateral decubitus position in parturients. METHODS: We consecutively enrolled parturients with a gestational age of ≥36 weeks. The attending anesthesiologists palpated the superior aspects of the posterior iliac crests bilaterally in a sitting position and then in a lateral decubitus position. The blinded investigators performed the ultrasound and recorded the intersected segment level of the PI-line. The distance between any two consecutive vertebral interspaces was divided into 3 segments, and comparisons were made with 15 segments of five vertebral interspaces above the sacrum. The primary outcome was the concordance rate of intersected segment level of the PI-line between the two positions. We also examined the intersected segment level of the PI-line of the two positions and the magnitude of these changes. RESULTS: Thirty-nine parturients were analyzed. The concordance rate of intersected segment levels of the PI-line between the two positions was 21% (8/39). In 56% (22/39) of the parturients, the intersected segment level of the PI-line in the sitting position was more cephalad and 23% (9/39) were more caudal. Fifteen percent (6/39) of parturients had three or more segment differences between the two positions. CONCLUSIONS: The intersected segment level of the PI-line, measured with trisected segments in each vertebral interspace, was different between the sitting and the lateral decubitus positions in approximately 80% of the parturients. Notably, 15% (6/39) of the parturients had at least one vertebral interspace deviation.

Remimazolam for induction of anesthesia in elderly patients with severe aortic stenosis: a prospective, observational pilot study.

BACKGROUND: Remimazolam, a novel benzodiazepine, has been reported to cause less hypotension than propofol during induction of anesthesia. Therefore, remimazolam might be a valuable option in elderly patients with severe aortic stenosis who are considered to be the most vulnerable to hemodynamic instability. We aimed to evaluate the feasibility and hemodynamic effects of remimazolam as an induction agent in elderly patients with severe aortic stenosis. METHODS: This prospective, open-label, single-arm, observational pilot study was conducted in a university hospital between November 2020 and April 2021. We included 20 patients aged 65 years or older scheduled for transcatheter or surgical aortic valve replacement for severe aortic stenosis under general anesthesia. Patients were administered intravenous remimazolam infusion at 6 mg/kg/h combined with 0.25 µg/kg/min of remifentanil infusion. The primary outcome was the vasopressor dosage between the induction of anesthesia and the completion of tracheal intubation. The secondary outcomes included hemodynamic changes, bispectral index changes, and the time from the start of remimazolam infusion to loss of consciousness. We also recorded awareness during anesthesia induction and serious adverse events related to death, life-threatening events, prolonged hospitalizations, and disability due to permanent damage. RESULTS: Twenty patients aged 84 [79-86] (median [interquartile range]) with American Society of Anesthesiologists physical status 4 were analyzed. Ephedrine 0 [0-4] mg and phenylephrine 0.1 [0-0.1] mg were administered to 14/20 patients (3 doses in 1 patient, 2 doses in 4 patients, and one dose in 9 patients). Loss of consciousness was achieved at 80 [69-86] s after the remimazolam infusion was started. The mean arterial pressure decreased gradually after loss of consciousness but recovered immediately after tracheal intubation. The bispectral index values gradually decreased and reached < 60 at 120 s after loss of consciousness. Neither awareness during induction of anesthesia nor serious adverse events, such as severe bradycardia (< 40 bpm), life-threatening arrhythmia, myocardial ischemia, or anaphylactic reactions were observed. CONCLUSIONS: Remimazolam could be used as an induction agent with timely bolus vasopressors in elderly patients with severe aortic stenosis. TRIAL REGISTRATION: UMIN Clinical Trials Registry, identifier UMIN000042318 .

Comparison of hemostatic effect and safety between epinephrine and tramazoline during nasotracheal intubation: a double-blind randomized trial.

BACKGROUND: Nasal bleeding is the most common complication during nasotracheal intubation (NTI). To reduce nasal bleeding, the nasal mucosa is treated with vasoconstrictors (epinephrine [E] or tramazoline [T]) prior to NTI. This study aimed to determine whether E or T is more effective and safe for reducing nasal bleeding during NTI. METHODS: This study was preregistered on UMIN-CTR after being approved by the IRB of the School of Dentistry at Aichi Gakuin University. Written consent was received from all the patients. Total 206 patients aged 20-70 years and classified as 1-2 on American Society of Anesthesiologists-physical status were scheduled to undergo general anesthesia with NTI. At last, 197 patients were randomly divided into two groups and treated with either E (n = 99; 3 patients were discontinued) or T (n = 98; 2 patient were discontinued). After induction of general anesthesia, each patient's nasal mucosa was treated using either E or T. The E used in this study was BOSMIN® SOLUTION 0.1% (Daiichi-Sankyo Co., Ltd., Tokyo), and the T used in this study was TRAMAZOLIN Nasal Solution 0.118% AFP, (Alfresa Pharma Corporation, Osaka). E was diluted five times according to the package insert (final concentration of E = 0.02%), and T was used in its original solution. After 2 min, NTI was performed via the right nostril. Primary outcome were the presence of nasal bleeding (if bleeding was recognized at the posterior pharyngeal wall via nasal cavity during intubation, it was defined as bleeding) and the degree of bleeding (classified as none, mild, moderate, or severe). Secondary outcomes were arrhythmia, and hemodynamic (mean atrial pressure and heart rate) changes associated with vasoconstrictors. RESULTS: The presence of bleeding was comparable in both groups (12.5%, E; 14.5%, T; P = 0.63). No significant difference between the groups regarding the degree of bleeding (P = 0.78) was observed, with most patients having no bleeding (n = 84, E; n = 82, T). No severe bleeding and no arrhythmias induced by vasoconstrictor were observed in the two groups. CONCLUSIONS: Nasal treatment with E or T shows no difference in nasal bleeding during NTI. Although no arrhythmia associated with E was observed in this study, it has been reported in literature. Therefore, as frequency and degree of nasal bleeding were comparable, nasal treatment with T could reduce the risk of NTI. TRIAL REGISTRATION: UMIN-CTR (Registration No. UMIN000037907 ). Registered (05/09/2019).

The characteristics, types of intervention, and outcomes of postoperative patients who required rapid response system intervention: a nationwide database analysis.

PURPOSE: Improving the safety of general wards is a key to reducing serious adverse events in the postoperative period. We investigated the characteristics, treatment, and outcomes of postoperative patients managed by a rapid response system (RRS) in Japan to improve postoperative management. METHODS: This retrospective study analyzed cases requiring RRS intervention that were included in the In-Hospital Emergency Registry in Japan. We analyzed data reported by 34 Japanese hospitals between January 2014 and March 2018, mainly focusing on postoperative patients for whom the RRS was activated within 7 days of surgery. Non-postoperative patients, for whom the RRS was activated in all other settings, were used for comparison as necessary. RESULTS: There were 609 (12.7%) postoperative patients among the total patients in the registry. The major criteria were staff concerns (30.2%) and low oxygen saturation (29.7%). Hypotension, tachycardia, and inability to contact physicians were observed as triggers significantly more frequently in postoperative patients when compared with non-postoperative patients. Among RRS activations within 7 days of surgery, 68.9% of activations occurred within postoperative day 3. The ordering of tests (46.8%) and fluid bolus (34.6%) were major interventions that were performed significantly more frequently in postoperative patients when compared with non-postoperative patients. The rate of RRS activations resulting in ICU care was 32.8%. The mortality rate at 1 month was 16.2%. CONCLUSION: Approximately, 70% of the RRS activations occurred within postoperative day 3. Circulatory problems were a more frequent cause of RRS activation in the postoperative group than in the non-postoperative group.

Effects of the anesthesiologist's experience on postoperative hoarseness after double-lumen endotracheal tube intubation: a single-center propensity score-matched analysis.

BACKGROUND: Postoperative hoarseness after general anesthesia is associated with patient discomfort and dissatisfaction. A recent large retrospective study showed that single-lumen endotracheal tube intubation by a trainee did not alter the incidence of postoperative pharyngeal symptoms compared with intubation by a senior anesthesiologist. However, there is limited information about the relationship between the anesthesiologist's experience and hoarseness after double-lumen endotracheal tube intubation. We tested the hypothesis that double-lumen endotracheal tube intubation performed by a trainee increases the incidence of postoperative hoarseness compared to intubation by a senior anesthesiologist. METHODS: This retrospective observational study included patients who underwent lung resection between April 2015 and March 2018 at a university hospital. Double-lumen endotracheal tube intubation was carried out with a Macintosh laryngoscope. We divided the patients into 2 groups - one group comprised of patients who were intubated by a trainee anesthesiologist with < 2 years of experience, and the other group comprised of those who underwent intubation by a senior anesthesiologist with ≥2 years of experience. The primary outcome was the incidence of postoperative hoarseness 24 h after surgery and we collected data on postoperative hoarseness using a checklist of postanesthetic adverse events. One-to-one propensity score matching was conducted and P values < 0.05 were considered statistically significant. RESULTS: There was a total of 256 eligible patients, of which 153 underwent intubation by trainee anesthesiologists, and the remaining 103 patients were intubated by a senior anesthesiologist. The one-to-one propensity score matching resulted in 96 pairs of patients for the groups. The incidence of postoperative hoarseness 24 h after surgery was significantly higher in patients who were intubated by a trainee anesthesiologist than in patients who were intubated by a senior anesthesiologist (9.4% vs. 2.1%, respectively; P = 0.03). CONCLUSIONS: Double-lumen endotracheal tube intubation by trainee anesthesiologists with < 2 years of experience increased the incidence of postoperative hoarseness 24 h after surgery compared to intubation by senior anesthesiologists with ≥2 years of experience.

Detachment of Chain-Forming Neuroblasts by Fyn-Mediated Control of cell-cell Adhesion in the Postnatal Brain.

In the rodent olfactory system, neuroblasts produced in the ventricular-subventricular zone of the postnatal brain migrate tangentially in chain-like cell aggregates toward the olfactory bulb (OB) through the rostral migratory stream (RMS). After reaching the OB, the chains are dissociated and the neuroblasts migrate individually and radially toward their final destination. The cellular and molecular mechanisms controlling cell-cell adhesion during this detachment remain unclear. Here we report that Fyn, a nonreceptor tyrosine kinase, regulates the detachment of neuroblasts from chains in the male and female mouse OB. By performing chemical screening and in vivo loss-of-function and gain-of-function experiments, we found that Fyn promotes somal disengagement from the chains and is involved in neuronal migration from the RMS into the granule cell layer of the OB. Fyn knockdown or Dab1 (disabled-1) deficiency caused p120-catenin to accumulate and adherens junction-like structures to be sustained at the contact sites between neuroblasts. Moreover, a Fyn and N-cadherin double-knockdown experiment indicated that Fyn regulates the N-cadherin-mediated cell adhesion between neuroblasts. These results suggest that the Fyn-mediated control of cell-cell adhesion is critical for the detachment of chain-forming neuroblasts in the postnatal OB.SIGNIFICANCE STATEMENT In the postnatal brain, newly born neurons (neuroblasts) migrate in chain-like cell aggregates toward their destination, where they are dissociated into individual cells and mature. The cellular and molecular mechanisms controlling the detachment of neuroblasts from chains are not understood. Here we show that Fyn, a nonreceptor tyrosine kinase, promotes the somal detachment of neuroblasts from chains, and that this regulation is critical for the efficient migration of neuroblasts to their destination. We further show that Fyn and Dab1 (disabled-1) decrease the cell-cell adhesion between chain-forming neuroblasts, which involves adherens junction-like structures. Our results suggest that Fyn-mediated regulation of the cell-cell adhesion of neuroblasts is critical for their detachment from chains in the postnatal brain.

Comparison of disinfection effect between benzalkonium chloride and povidone iodine in nasotracheal intubation: a randomized trial.

BACKGROUND: Nasotracheal intubation can potentially result in microbial contamination from the upper respiratory tract to the lower respiratory tracts. However, an ideal nasotracheal disinfection method is yet to be determined. Therefore, we compared the disinfection effects between benzalkonium chloride and povidone iodine in nasotracheal intubation. METHODS: Overall, this study enrolled 53 patients aged 20-70 years who were classified into classes 1 and 2 as per American Society of Anesthesiologists-physical status and were scheduled to undergo general anesthesia with NTI. Patients who did not give consent (n = 2) and who has an allergy for BZK or PVI were excluded from the study. The patients were randomly divided into two groups on the basis of the disinfection method: BZK (n = 26, one patient was discontinued intervention) and PVI (n = 25). 50 patients were assessed finally. The subjects' nasal cavities were swabbed both before (A) and after disinfection (B), and the internal surface of the endotracheal tube was swabbed after extubation (C). The swabs were cultured on Brain heart infusion agar and Mannitol salt agar. The number of bacteria per swab was determined and the rates of change in bacterial count (B/A, C/B) were calculated. The growth inhibitory activity of the disinfectants on Staphylococcus aureus were also investigated in vitro. RESULTS: Although the initial disinfection effects (B/A) were inferior for benzalkonium chloride compared with those for povidone iodine, the effects were sustained for benzalkonium chloride (C/B). In the in vitro growth inhibitory assay against S. aureus, benzalkonium chloride showed higher inhibitory activity than povidone iodine. CONCLUSION: Although both disinfectants were inactivated or diffused/diluted over time, benzalkonium chloride maintained the threshold concentration and displayed antimicrobial effects longer than povidone iodine; therefore, benzalkonium chloride appeared to show a better sustained effect. Benzalkonium chloride can be used for creating a hygienic nasotracheal intubation environment with sustained sterilizing effects. TRIAL REGISTRATION: UMIN-CTR (Registration No. UMIN000029645 ). Registered 21 Oct 2017.

The usefulness of the McGrath MAC laryngoscope in comparison with Airwayscope and Macintosh laryngoscope during routine nasotracheal intubation: a randomaized controlled trial.

BACKGROUND: McGrath MAC video laryngoscope offers excellent laryngosopic views and increases the success rate of orotracheal intubation in some cases. The aim of this study was to determine the usefulness of McGrath MAC for routine nasotracheal intubation by comparing McGrath MAC with Airway scope and Macintosh laryngoscope. METHODS: A total of 60 adult patients with ASA physical status class 1 or 2, aged 20-70 years were enrolled in this study. Patients were scheduled for elective oral surgery under general anesthesia with nasotracheal intubation. Exclusion criteria included lack of consent and expected difficult airway. Patients were randomly allocated to three groups: McGrath MAC (n = 20), Airway scope (n = 20), and Macintosh laryngoscope (n = 20). After induction, nasotracheal intubation was performed by six expert anesthesiologists with more than 6 years of experience. RESULTS: There were no significant differences in preoperative airway assessment among the three groups. Successful tracheal intubation time was 26.8 ± 5.7 (mean ± standard deviation) s for McGrath MAC, 36.4 ± 11.0 s for Airway scope, and 36.5 ± 8.9 s for Macintosh laryngoscope groups. The time for successful tracheal intubation for McGrath MAC group was significantly shorter than that for Airway scope and Macintosh laryngoscope (p < 0.01). McGrath MAC significantly improved the Cormack Lehane grade for nasotracheal intubation compared with Macintosh laryngoscope (p < 0.05). CONCLUSION: McGrath MAC significantly facilitates routine nasotracheal intubation compared with Airwayscope and Macintosh laryngoscope by shortening the tracheal intubation time and improving the Cormack Lehane grade. TRIAL REGISTRATION: UMINCTR Registration number UMIN000023506 . Registered 5 Aug 2016.

The past, present and future of the postanesthesia care unit (PACU) in Japan.

The postanesthesia care unit (PACU), which is run and coordinated by anesthesiologists, delivers general medical supervision as well as close and constant care to patients who have just undergone a surgical procedure under anesthesia. Although PACU management has been considered a standard procedure in many developed countries since the 1940s, Japanese hospitals have tended to cease their management, and only 16.1% of hospitals in Japan currently have PACUs. In today's efficiency-required atmosphere in Japan, we need to consider a better postoperative management method, including facilities similar to the PACU, to prevent serious adverse events and improve the postoperative outcomes and quality of life. Nevertheless, the way postoperative patients are treated and cared for, and the location in which they receive such attention, will likely need to be modified to fit the Japanese style due to Japan's unique medical systems and traditions. Here, we describe the past, present and future of the PACU and postanesthesia care in Japan compared with other countries.

Simvastatin and atorvastatin facilitates amyloid ß-protein degradation in extracellular spaces by increasing neprilysin secretion from astrocytes through activation of MAPK/Erk1/2 pathways.

One of the major neuropathological hallmarks of Alzheimer's disease (AD) is the deposition of amyloid ß-protein (Aß) in the brain. Aß accumulation seems to arise from an imbalance between Aß production and clearance. Neprilysin (NEP) and insulin-degrading enzyme (IDE) are the important Aß-degrading enzymes in the brain, and deficits in their expression may promote Aß deposition in patients with sporadic late-onset AD. Statins, which are used clinically for reducing cholesterol levels, can exert beneficial effects on AD. Therefore, we examined whether various statins are associated with Aß degradation by inducing NEP and IDE expression, and then evaluating the relation between activation of intracellular signaling transduction, inhibition of cholesterol production, and morphological changes to astrocytes. Treating cultured rat astrocytes with simvastatin and atorvastatin significantly decreased the expression of NEP but not IDE in a concentration- and time-dependent manner. The decrease in NEP expression was a result of activation of extracellular signal-regulated kinase (ERK) but not the reduction of cholesterol synthesis pathway. This NEP reduction was achieved by the release to the extracellular space of cultured astrocytes. Furthermore, the cultured medium prepared from simvastatin- and atorvastatin-treated astrocytes significantly induced the degradation of exogenous Aß. These results suggest that simvastatin and atorvastatin induce the increase of Aß degradation of NEP on the extracellular of astrocytes by inducing ERK-mediated pathway activity and that these reagents regulate the differential mechanisms between the secretion of NEP, the induction of cholesterol reduction, and the morphological changes in the cultured astrocytes.

Guidelines for parenteral fluid management for terminal cancer patients.

BACKGROUND: Japan's first guidelines for parenteral fluid management for terminal cancer patients were issued in 2006. These guidelines focused on the fluid levels to administer to patients with a remaining life expectancy of 1-2 months. However, recent refinement of the concept of cachexia is prompting caregivers worldwide to rethink parenteral fluid management for terminal cancer patients. OBJECTIVE: Our objective was to develop guidelines for parenteral fluid management for terminal cancer patients with a remaining life expectancy of 1 month, a point when cachexia generally begins to severely adversely affect the body. METHODS: The Japanese Society for Palliative Medicine appointed a Guidelines Working Practitioner Group consisting of a multidisciplinary team of specialists. In response to 26 clinical questions on parenteral fluid management for terminal cancer patients, the Working Group used the Delphi method to reach consensus on the recommendability and evidence level of 89 relevant manuscripts identified through a systematic literature review. The Working Group then had an outside committee reviews the draft guidelines validity before authoring the final version. RESULTS: The resulting clinically aligned guidelines contain specific recommendations (25 recommendations on physical suffering/remaining life expectancy, 10 nursing-related recommendations and 4 ethical recommendations) assessed using the Delphi method and by an outside committee. CONCLUSIONS: Japanese Society for Palliative Medicine released a revised edition of the Guidelines for Parenteral Fluid Management for Terminal Cancer Patients, which are based on medical evidence and consider the pathologic features of cachexia. We recommend that caregivers carefully evaluate the clinical usefulness of the guidelines.