Relationship between muscle mass ratio and rocuronium dose required for maintaining deep neuromuscular blockade: A prospective observational study.

BACKGROUND: Deep neuromuscular blockade (NMB) has benefits in various surgical procedures, however, precise quantitative neuromuscular monitoring is crucial for its proper maintenance and recovery. Neuromuscular blocking agent dosage relies on actual body weight (ABW), but this varies among individuals. Therefore, this study hypothesizes that there is a correlation between the rocuronium requirement for deep NMB and muscle mass ratio measured by bioelectric impedance analysis. METHODS: Ninety adult female patients undergoing laparoscopic operation were enrolled in this study. Muscle and fat masses were assessed using a body composition analyser. Deep NMB, defined as a post-tetanic count of 1-2, was maintained through the continuous infusion of rocuronium. The primary outcome involves determining the correlation between the rocuronium dose required for deep NMB and the muscle mass ratio. Conversely, secondary outcomes included assessing the relationship between the rocuronium dose for deep NMB and fat mass ratio, and ABW. Additionally, we investigated their relationship with rocuronium onset time and profound blockade duration. RESULTS: No relationship was observed between the muscle mass ratio and rocuronium dose required for maintaining deep NMB (r = 0.059 [95% CI = 0.153-0.267], p = 0.586). Fat mass ratio and ABW showed no correlation with the rocuronium dose, whereas rocuronium onset time was positively correlated with muscle mass ratio (r = 0.327) and negatively correlated with fat mass ratio (r = -0.302), respectively. Profound blockade duration showed no correlation with any of the assessed variables. CONCLUSIONS: No correlation was detected between muscle mass ratio and the rocuronium dose required to achieve deep NMB.

Reduced side effects and improved pain management by continuous ketorolac infusion with patient-controlled fentanyl injection compared with single fentanyl administration in pelviscopic gynecologic surgery: a randomized, double-blind, controlled study.

BACKGROUND: A combination of opioids and adjunctive drugs can be used for intravenous patient-controlled analgesia (PCA) to minimize opioid-related side effects. We investigated whether two different analgesics administered separately via a dual-chamber PCA have fewer side effects with adequate analgesia than a single fentanyl PCA in gynecologic pelviscopic surgery. METHODS: This prospective, double-blind, randomized, and controlled study included 68 patients who underwent pelviscopic gynecological surgery. Patients were allocated to either the dual (ketorolac and fentanyl delivered by a dual-chamber PCA) or the single (fentanyl alone) group. Postoperative nausea and vomiting (PONV) and analgesic quality were compared between the two groups at 2, 6, 12, and 24 h postoperatively. RESULTS: The dual group showed a significantly lower incidence of PONV during postoperative 2-6 h (P = 0.011) and 6-12 h (P = 0.009). Finally, only two patients (5.7%) in the dual group and 18 (54.5%) in the single group experienced PONV during the entire postoperative 24 h and could not maintain intravenous PCA (odds ratio: 0.056, 95% CI [0.007, 0.229], P < 0.001). Despite the administration of less fentanyl via intravenous PCA during the postoperative 24 h in the dual group than in the single group (66.0 ± 77.8 vs. 383.6 ± 70.1 µg, P < 0.001), postoperative pain had no significant intergroup difference. CONCLUSIONS: Two different analgesics, continuous ketorolac and intermittent fentanyl bolus, administered via dual-chamber intravenous PCA, showed fewer side effects with adequate analgesia than conventional intravenous fentanyl PCA in gynecologic patients undergoing pelviscopic surgery.

Associations of Alcohol Consumption and Smoking Behaviors with Depressed Mood According to Gender in Korean Young Adults.

BACKGROUND: Recent studies have reported that chronic mental health problems often emerge in young adulthood. This study elucidated the independent effects of smoking and drinking on depressed mood in young adults by sex. METHODS: We used Data from the Korea National Health and Nutrition Examination Surveys conducted in 2014, 2016, and 2018. A total of 3,391 participants aged 19-35 years, without serious chronic diseases, were recruited for this study. Depression was evaluated using the Patient Health Questionnaire (PHQ-9). RESULTS: Smoking behavior, current smoking, and number of days smoked were significantly associated with higher PHQ-9 scores in both men and women (all P<0.05). However, past and ever smoking were positively associated with PHQ-9 scores only in women (all P<0.001). Regarding alcohol consumption, the age at which drinking first began was negatively associated with PHQ-9 scores in both men and women (all P<0.001), but the amount of alcohol consumed at 1 time was positively associated with PHQ-9 scores only in women (P=0.013). Men who drank 2-4 times a month and women who had not drunk during the past year had the lowest PHQ-9 scores. CONCLUSION: Smoking and alcohol consumption were independently associated with depressed mood in young Korean adults, which was more pronounced in women, and exhibited sex-specific characteristics.

The effect of intranasal dexmedetomidine administration on emergence agitation or delirium in pediatric patients after general anesthesia: A meta-analysis of randomized controlled trials.

BACKGROUND: Emergence agitation or delirium can occur in pediatric patients after anesthesia. Dexmedetomidine is known to reduce the impairment of postoperative cognitive function. AIMS: This study aimed to identify the role of intranasal administration of dexmedetomidine in lowering the development of emergence agitation or emergence delirium in pediatric patients after general anesthesia. METHODS: Electronic databases, including PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, were searched to identify studies. The primary outcome was the proportion of patients who underwent emergence agitation or emergence delirium after the surgery. Secondary outcomes included emergence time and incidence of postoperative nausea and/or vomiting. We estimated the odds ratio and mean difference with 95% confidence intervals for the determination of effect size using a random-effects model. RESULTS: In total, 2103 pediatric patients from 20 randomized controlled trials were included in the final analysis. The incidence of emergence agitation or emergence delirium was 13.6% in the dexmedetomidine group and 33.2% in the control group. The pooled effect size revealed that intranasal dexmedetomidine administration significantly reduced the incidence of postoperative emergence agitation or emergence delirium in pediatric patients undergoing surgery under general anesthesia (odds ratio 0.25, 95% confidence interval 0.18-0.34; p = .0000; I2 = 37.74%). Additionally, significant difference was observed in emergence time between the two groups (mean difference 2.42, 95% confidence interval 0.37-4.46; p = .021; I2 = 98.40%). Children in the dexmedetomidine group had a significantly lower incidence of postoperative nausea and/or vomiting than those in the control group (odds ratio 0.39, 95% confidence interval 0.24-0.64; p = .0002; I2 = 0.00%). CONCLUSIONS: Intranasal dexmedetomidine reduced the incidence of emergence agitation or emergence delirium in pediatric patients after general anesthesia.

Risks and outcome of fatal respiratory events after lung cancer surgery: cohort study in South Korea.

Background: Severe complications such as acute respiratory distress syndrome or respiratory failure can occur after lung cancer surgery. However, the prevalence and risk factors have not been well identified. The aim of this study was to investigate the prevalence of and risk factors for fatal respiratory events after lung cancer surgery in South Korea. Methods: The National Health Insurance Service database in South Korea was used to extract data of all adult patients who were diagnosed with lung cancer and underwent lung cancer surgery from January 1, 2011, to December 31, 2018, for a population-based cohort study. Diagnosis of acute respiratory distress syndrome or respiratory failure after surgery was defined as postoperative fatal respiratory event. Results: A total of 60,031 adult patients who received lung cancer surgery were included in the analysis. Among them, 0.5% (285/60,031) experienced fatal respiratory events after the lung cancer surgery. In multivariable logistic regression, some risk factors (older age, male sex, higher Charlson comorbidity index score, underlying severe disability, bilobectomy, pneumonectomy, redo-case, lower case volume, and open thoracotomy) for developing postoperative fatal respiratory events were identified. Moreover, the development of postoperative fatal respiratory events was associated with high in-hospital mortality, 1-year mortality, longer length of hospital stays, and higher total hospitalization costs. Conclusions: Postoperative fatal respiratory events might worsen the clinical outcomes of lung cancer surgery. The knowledge of potential risk factors related to postoperative fatal respiratory events could enable earlier intervention to reduce the occurrence of these events and improve the postoperative clinical outcome.

The antioxidant effect of preischemic dexmedetomidine in a rat model: increased expression of Nrf2/HO-1 via the PKC pathway

Abstract Background The precise underlying mechanism of antioxidant effects of dexmedetomidine-induced neuroprotection against cerebral ischemia has not yet been fully elucidated. Activation of Nuclear factor erythroid 2-related factor (Nrf2) and Heme Oxygenase-1 (HO-1) represents a major antioxidant-defense mechanism. Therefore, we determined whether dexmedetomidine increases Nrf2/HO-1 expression after global transient cerebral ischemia and assessed the involvement of Protein Kinase C (PKC) in the dexmedetomidine-related antioxidant mechanism. Methods Thirty-eight rats were randomly assigned to five groups: sham (n = 6), ischemic (n = 8), chelerythrine (a PKC inhibitor; 5 mg.kg-1 IV administered 30 min before cerebral ischemia) (n = 8), dexmedetomidine (100 µg.kg-1 IP administered 30 min before cerebral ischemia (n = 8), and dexmedetomidine + chelerythrine (n = 8). Global transient cerebral ischemia (10 min) was applied in all groups, except the sham group; histopathologic changes and levels of nuclear Nrf2 and cytoplasmic HO-1 were examined 24 hours after ischemia insult. Results We found fewer necrotic and apoptotic cells in the dexmedetomidine group relative to the ischemic group (p< 0.01) and significantly higher Nrf2 and HO-1 levels in the dexmedetomidine group than in the ischemic group (p< 0.01). Additionally, chelerythrine co-administration with dexmedetomidine attenuated the dexmedetomidine-induced increases in Nrf2 and HO-1 levels (p< 0.05 and p< 0.01, respectively) and diminished its beneficial neuroprotective effects. Conclusion Preischemic dexmedetomidine administration elicited neuroprotection against global transient cerebral ischemia in rats by increasing Nrf2/HO-1 expression partly via PKC signaling, suggesting that this is the antioxidant mechanism underlying dexmedetomidine-mediated neuroprotection.

Change in glottic view during intubation using a KoMAC videolaryngoscope: A retrospective analysis.

Intubation with videolaryngoscopy has become popular in various clinical settings. However, despite the use of a videolaryngoscope, difficult intubation still exists and intubation failure has been reported. This retrospective study assessed the efficacy of the 2 maneuvers in improving the glottic view during videolaryngoscopic intubation. The medical records of patients who underwent videolaryngoscopic intubation and whose glottal images were stored in electronic medical charts were reviewed. The videolaryngoscopic images were divided into 3 categories according to the applied optimization techniques as follows: conventional method, with the blade tip located in the vallecular; backward-upward-rightward pressure (BURP) maneuver; and epiglottis lifting maneuver. Four independent anesthesiologists scored the visualization of the vocal folds using the percentage of glottic opening (POGO, 0-100%) scoring system. A total of 128 patients with 3 laryngeal images were analyzed. The glottic view was the most improved in the epiglottis lifting maneuver among all the techniques. The median POGO scores were 11.3, 36.9, and 63.1 in the conventional method, BURP, and epiglottis lifting maneuver, respectively (P < .001). There were significant differences in the distribution of POGO grades according to the application of BURP and epiglottis lifting maneuvers. In the POGO grades 3 and 4 subgroups, the epiglottis lifting maneuver was more effective than the BURP maneuver in improving the POGO score Inadequate visualization of the vocal folds occurred even when intubation was performed using a videolaryngoscope. The application of optimization maneuvers, such as BURP and epiglottis lifting by the blade tip, could improve the glottic view.

Intraoperative 5-HT3 receptor antagonists decrease the prevalence of postoperative delirium in older adults undergoing hip fracture surgery: a single-center retrospective study.

PURPOSE: Postoperative delirium (POD) occurs commonly in older adults, resulting in unfavorable outcomes. Several recent clinical studies have suggested that 5-hydroxytryptamine 3 (5-HT3) receptor antagonists can treat and prevent POD. In this retrospective study, the association between 5-HT3 receptor antagonists and POD was investigated in older adults who underwent hip fracture surgery. METHODS: The electronic medical records of older adults aged ≥ 65 years who underwent hip fracture surgery between January 2011 and June 2018 were reviewed retrospectively. Multivariable logistic regression analysis was used to investigate the association between 5-HT3 receptor antagonists and the occurrence of POD. In addition to the incidence of POD, anesthesia-, surgery-, and patient-related factors related to POD were evaluated. RESULTS: Of the 1025 patients included, 813 (79.3%) were administered 5-HT3 receptor antagonists intraoperatively; 471 (45.9%) were administered ramosetron, and 342 (33.4%) were administered palonosetron. POD was identified in 242 patients (23.6%). Ramosetron and palonosetron reduced the POD incidence by 53% (odds ratio [OR] 0.47; 95% confidence interval [CI] 0.32‒0.71; P < 0.001) and 41% (OR 0.59; 95% CI 0.39‒0.89; P = 0.011), respectively. Additionally, age, American Society of Anesthesiologists physical status class 4, and male were confirmed as risk factors for POD. CONCLUSION: Intraoperative 5-HT3 receptor antagonists may be associated with a reduced risk of POD and can be considered one of the preventive strategies for POD in older adults undergoing hip fracture surgery.

Iron Oxide Nanoparticle-Incorporated Mesenchymal Stem Cells for Alzheimer's Disease Treatment.

Alzheimer's disease (AD) is a neurodegenerative disease with multifactorial pathogenesis. However, most current therapeutic approaches for AD target a single pathophysiological mechanism, generally resulting in unsatisfactory therapeutic outcomes. Recently, mesenchymal stem cell (MSC) therapy, which targets multiple pathological mechanisms of AD, has been explored as a novel treatment. However, the low brain retention efficiency of administered MSCs limits their therapeutic efficacy. In addition, autologous MSCs from AD patients may have poor therapeutic abilities. Here, we overcome these limitations by developing iron oxide nanoparticle (IONP)-incorporated human Wharton's jelly-derived MSCs (MSC-IONPs). IONPs promote therapeutic molecule expression in MSCs. Following intracerebroventricular injection, MSC-IONPs showed a higher brain retention efficiency under magnetic guidance. This potentiates the therapeutic efficacy of MSCs in murine models of AD. Furthermore, human Wharton's jelly-derived allogeneic MSCs may exhibit higher therapeutic abilities than those of autologous MSCs in aged AD patients. This strategy may pave the way for developing MSC therapies for AD.

Postoperative Delirium after Dexmedetomidine versus Propofol Sedation in Healthy Older Adults Undergoing Orthopedic Lower Limb Surgery with Spinal Anesthesia: A Randomized Controlled Trial.

BACKGROUND: Delirium is a critical postoperative complication in older patients. Based on the hypothesis that intraoperative dexmedetomidine sedation would lower postoperative delirium than propofol sedation would, the authors compared the incidence of postoperative delirium in older adults, using the mentioned sedatives. METHODS: This double-blinded, randomized controlled study included 748 patients, aged 65 yr or older, who were scheduled for elective lower extremity orthopedic surgery, between June 2017 and October 2021. Patients were randomized equally into two groups in a 1:1 ratio according to the intraoperative sedative used (dexmedetomidine vs. propofol). The postoperative delirium incidence was considered the primary outcome measure; it was determined using the confusion assessment method, on the first three postoperative days. The mean arterial pressure and heart rate were evaluated as secondary outcomes. RESULTS: The authors enrolled 732 patients in the intention-to-treat analyses. The delirium incidence was lower in the dexmedetomidine group than in the propofol group (11 [3.0%] vs. 24 [6.6%]; odds ratio, 0.42; 95% CI, 0.201 to 0.86; P = 0.036). During sedation, the mean arterial pressure (median [interquartile range] mmHg) was higher in the dexmedetomidine group (77 [71 to 84]) than in the propofol group (74 [69 to 79]; P < 0.001); however, it significantly fell lower (74 [68 to 80]) than that of the propofol group (80 [74 to 87]) in the postanesthesia care unit (P < 0.001). Lower heart rates (beats/min) were recorded with the use of dexmedetomidine than with propofol, both during sedation (60 [55 to 66] vs. 63 [58 to 70]) and in the postanesthesia care unit (64 [58 to 72] vs. 68 [62-77]; P < 0.001). CONCLUSIONS: Dexmedetomidine showed a lower incidence of postoperative delirium than propofol in healthy older adults undergoing lower extremity orthopedic surgery.

Pre-existing and new-onset depression among patients undergoing esophageal cancer surgery: a nationwide cohort study in South Korea.

BACKGROUND: Esophageal cancer is believed to be related to psychological stress. This study aimed to examine the prevalence and risk factors for new-onset depression after esophageal cancer surgery among patients who had no pre-existing depression. In addition, we examined whether pre-existing depression affected postoperative 1-year mortality. METHODS: The National Health Insurance Service database in South Korea was used for data extraction in this population-based cohort study. This study included all adult patients diagnosed with esophageal cancer who underwent esophageal surgery between January 1, 2011, and December 31, 2018. RESULTS: A total of 7039 adult patients who underwent esophageal cancer surgery at 95 South Korean hospitals were included in the analyses. Of the total, 608 patients (8.6%) were diagnosed with new-onset depression within 1 year after esophageal cancer surgery. Female sex, adjuvant chemotherapy, increased Charlson comorbidity index, pre-existing anxiety disorder, and pre-existing insomnia disorder were potential risk factors for new-onset depression. In multivariable Cox regression analysis, the pre-existing depression group showed a 1.27-fold (hazard ratio: 1.27; 95% confidence interval: 1.08-1.48; P = 0.004) higher risk of 1-year all-cause mortality than those who had no pre-existing depression. CONCLUSION: In South Korea, 8.6% of patients are newly diagnosed with depression after esophageal cancer surgery, and some potential risk factors have been identified. Moreover, pre-existing depression was associated with increased 1-year all-cause mortality. Patients with esophageal cancer and pre-existing depression may be at high risk, requiring interventions after esophageal cancer surgery.

The antioxidant effect of preischemic dexmedetomidine in a rat model: increased expression of Nrf2/HO-1 via the PKC pathway.

BACKGROUND: The precise underlying mechanism of antioxidant effects of dexmedetomidine-induced neuroprotection against cerebral ischemia has not yet been fully elucidated. Activation of Nuclear factor erythroid 2-related factor (Nrf2) and Heme Oxygenase-1 (HO-1) represents a major antioxidant-defense mechanism. Therefore, we determined whether dexmedetomidine increases Nrf2/HO-1 expression after global transient cerebral ischemia and assessed the involvement of Protein Kinase C (PKC) in the dexmedetomidine-related antioxidant mechanism. METHODS: Thirty-eight rats were randomly assigned to five groups: sham (n...=...6), ischemic (n...=...8), chelerythrine (a PKC inhibitor; 5...mg.kg-1 IV administered 30...min before cerebral ischemia) (n...=...8), dexmedetomidine (100.....g.kg-1 IP administered 30...min before cerebral ischemia (n...=...8), and dexmedetomidine...+...chelerythrine (n...=...8). Global transient cerebral ischemia (10...min) was applied in all groups, except the sham group; histopathologic changes and levels of nuclear Nrf2 and cytoplasmic HO-1 were examined 24...hours after ischemia insult. RESULTS: We found fewer necrotic and apoptotic cells in the dexmedetomidine group relative to the ischemic group (p...<...0.01) and significantly higher Nrf2 and HO-1 levels in the dexmedetomidine group than in the ischemic group (p...<...0.01). Additionally, chelerythrine co-administration with dexmedetomidine attenuated the dexmedetomidine-induced increases in Nrf2 and HO-1 levels (p...<...0.05 and p...<...0.01, respectively) and diminished its beneficial neuroprotective effects. CONCLUSION: Preischemic dexmedetomidine administration elicited neuroprotection against global transient cerebral ischemia in rats by increasing Nrf2/HO-1 expression partly via PKC signaling, suggesting that this is the antioxidant mechanism underlying dexmedetomidine-mediated neuroprotection.

Combination of Dexamethasone and Tofacitinib Reduces Xenogeneic MSC-Induced Immune Responses in a Mouse Model of Alzheimer's Disease.

We have recently reported on how transplantation of human mesenchymal stem cells (MSCs) into the mouse parenchyma generated immune responses. To facilitate the clinical translation of MSC-based AD therapy, the safety and efficacy of human derived MSCs (hMSCs) must be confirmed in the pre-clinical stage. Thus, it is imperative to investigate measures to reduce immune responses exerted via xenotransplantation. In this study, immunosuppressants were co-administered to mice that had received injections of hMSCs into the parenchyma. Prior to performing experiments using transgenic AD mice (5xFAD), varying immunosuppressant regimens were tested in wild-type (WT) mice and the combination of dexamethasone and tofacitinib (DexaTofa) revealed to be effective in enhancing the persistence of hMSCs. According to transcriptome sequencing and immunohistochemical analyses, administration of DexaTofa reduced immune responses generated via transplantation of hMSCs in the parenchyma of 5xFAD mice. Significant mitigation of amyloid burden, however, was not noted following transplantation of hMSCs alone or hMSCs with DexaTofa. The efficacy of the immunosuppressant regimen should be tested in multiple AD mouse models to promote its successful application and use in AD stem cell therapy.

Total intravenous anesthesia induced and maintained by a combination of remimazolam and remifentanil without a neuromuscular blocking agent: a prospective, observational pilot study.

BACKGROUND: A novel short-acting benzodiazepine, Remimazolam, has recently been approved for general anesthesia and sedation. Hence, we investigated the feasibility and safety of remimazolam during the induction and maintenance of general anesthesia without using a neuromuscular blocking agent (NMBA) in patients undergoing hysteroscopic surgery. METHODS: This prospective observational study included 38 patients undergoing hysteroscopic surgery. Remimazolam and remifentanil were the main anesthetic agents without an NMBA, and a supraglottic airway was inserted to protect the airway. The induction time, amount of each anesthetic agent used during anesthesia, intraoperative bispectral index (BIS) hemodynamic parameters, and recovery profiles were measured. RESULTS: General anesthesia was successfully administered to 37 patients using remimazolam and remifentanil without NMBA. The induction doses of remimazolam and remifentanil were 0.4 mg/kg (interquartile range [IQR] 0.34-0.47 mg/kg) and 1.07 µg/kg (IQR, 0.90-1.29 µg/kg), respectively. Additionally, the maintenance doses of remimazolam and remifentanil were 1.14 mg/kg/h (IQR, 0.88-1.55 mg/kg/h) and 0.06 µg/kg/min (IQR, 0.04-0.08 µg/kg/min), respectively. Intraoperative BIS values had risen temporarily > 60 in eight patients (21.6%) despite administration of 2 mg/kg/h of remimazolam; thus, they were treated with supplementary midazolam. The median recovery time was 7 min (IQR, 5-8 min) after 40 min (IQR, 40.0-57.5 min) of total mean anesthesia time. There was no correlation between the infusion dose of remimazolam and recovery profiles, such as recovery time, final BIS of anesthesia, modified observer assessment of alertness/sedation (OAA/S) scale or post-anesthesia recovery (PAR) score when arriving at the PACU, and length of stay in the PACU (all P > 0.05). CONCLUSION: Remimazolam can be combined with remifentanil without an NMBA in female patients who undergo hysteroscopic surgery, during which a supraglottic airway is a feasible method to protect the airway. TRIAL REGISTRATION: The study protocol was registered at ClinicalTrials.gov (NCT05025410) on 27/08/2021.

The voiding VAS score is a simple and useful method for predicting POUR after laparoscopy for benign gynaecologic diseases: a pilot study.

The aim of this study was to identify an appropriate scoring system for predicting postoperative urinary retention (POUR) after gynaecological laparoscopic surgery for benign disease. We analysed 99 patients who underwent gynaecological laparoscopic surgery for benign disease. All patients were asked to complete self-administered questionnaires, including the International Prostate Symptom Score (IPSS), voiding visual analogue scale (VAS), and Brief Pain Inventory-Korean version. Of the 99 patients, 27 (27.3%) experienced urinary retention at least once, while 72 (72.7%) did not. The preoperative and postoperative IPSS scores were not associated with the development of POUR. However, the voiding VAS score was significantly lower in patients that developed POUR (p = .014). In conclusion, our results show that the voiding VAS score is a simple and useful method for identifying patients at risk of POUR after gynaecologic laparoscopic surgery for benign disease. IMPACT STATEMENTWhat is already known on this subject? Postoperative urinary retention (POUR) is an often underestimated complication defined as inability to void during the postoperative period despite a full bladder. Undetected POUR may lead to complications such as urinary tract infection, bladder distention, and bladder dysfunction. Routine assessment of POUR by bladder ultrasonography in all surgical patients places a larger workload on the nursing staff.What do the results of this study add? Among the self-scoring assessment tools, the voiding VAS provided the most accurate reflection of POUR in patients undergoing gynaecologic laparoscopic surgery for benign disease.What are the implications of these findings for clinical practice and/or further research? As laparoscopy is the most widely employed surgical procedure in gynaecology, our findings could have significant implications for postoperative care in daily clinical practice.

Loss of RARRES1 function Promotes Follicular Lymphomagenesis and Inhibits B cell Differentiation in Mice.

Retinoic acid receptor responder 1 (RARRES1) is among the most commonly methylated loci in multiple cancers. RARRES1 regulates mitochondrial and fatty acid metabolism, stem cell differentiation, and survival of immortalized cell lines in vitro. Here, we created constitutive Rarres1 knockout (Rarres1-/-) mouse models to study RARRES1 function in vivo. Rarres1-/- embryonic fibroblasts regulated tubulin glutamylation, cell metabolism, and survival, recapitulating RARRES1 function in immortalized cell lines. In two mouse strains, loss of Rarres1 led to a markedly increased dose-dependent incidence of follicular lymphoma (FL). Prior to lymphoma formation, Rarres1-/- B cells have compromised activation, maturation, differentiation into antibody-secreting plasma cells, and cell cycle progression. Rarres1 ablation increased B cell survival and led to activation of the unfolded protein response (UPR) and heat shock response (HSR). Rarres1 deficiency had differential effects on cellular metabolism, with increased bioenergetic capacity in fibroblasts, and minor effects on bioenergetics and metabolism in B cells. These findings reveal that RARRES1 is a bona fide tumor suppressor in vivo and the deletion in mice promotes cell survival, and reduces B cell differentiation with B cell autonomous and non-autonomous functions.

Intracerebroventricular Administration of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Induces Transient Inflammation in a Transgenic Mouse Model and Patients with Alzheimer's Disease.

Previously we conducted a Phase I/IIa clinical trial in nine patients with mild to moderate Alzheimer's disease (AD). Unexpectedly, all patients who were given injections of human-umbilical cord-blood-derived mesenchymal stem cells (hUCB-MSCs) developed fever which subsided after 24 h. Several possible causes of transient fever include bacterial infection, inflammatory reaction from the cell culture media composition, or the cells themselves. To delineate these causes, first we compared the levels of several cytokines in the cerebrospinal fluid (CSF) of AD patients who received saline (placebo) or hUCB-MSC injections, respectively. Compared to the placebo group, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and c-reactive protein (CRP) levels were increased in the hUCB-MSC group. Negative bacterial culture results of the CSF samples and the fact that the same hUCB-MSC administration procedure was used for both the placebo and hUCB-MSC groups ruled out the bacterial infection hypothesis. However, it was not yet clear as to whether the transplanted cells or the composition of the cell culture media generated the transient fever. Therefore, we carried out intracerebroventricular (ICV) injections of hUCB-MSCs in a 5xFAD mouse model of AD. Interestingly, we discovered that pro-inflammatory cytokine levels were higher in the hUCB-MSC group. Taken together, our data suggest that the cause of transient inflammatory response observed from both the clinical trial and mouse study was due to the transplanted hUCB-MSCs.

Standard digit-based versus 90° rotation technique for supraglottic airway device insertion: a meta-analysis of randomized controlled trials.

BACKGROUND: Prompt insertion and placement of supraglottic airway (SGA) devices in the correct position are required to secure the airway. This meta-analysis was performed to validate the usefulness of the 90° rotation technique as compared with the standard digit-based technique for the insertion of SGA devices in anesthetized patients in terms of insertion success rate, insertion time, and postoperative complications. METHODS: A literature search of PubMed, EMBASE, CENTRAL, CINAHL, Scopus, and Web of Science was conducted. Randomized controlled trials, without limitations on publication period, language, journal, or region, until July 2021, that compared the 90° rotation and the standard digit-based techniques for insertion of SGA devices in anesthetized patients were included. RESULTS: The first-attempt (risk ratio [RR]: 1.16, 95% CI [1.09, 1.25], P < 0.001) and overall success rates (RR: 1.06, 95% CI [1.03, 1.09], P < 0.001) were significantly higher in the 90° rotation group. The insertion time was shorter in the 90° rotation group (mean difference: -4.42 s, 95% CI [-6.70, -2.15 s], P < 0.001). The incidences of postoperative sore throat (RR: 0.63, 95% CI [0.49, 0.83], P < 0.001) and blood staining (RR: 0.28, 95% CI [0.20, 0.39], P < 0.001) were lower in the 90° rotation group. CONCLUSIONS: The use of the 90° rotation technique increases the success rate of SGA device insertion and decreases postoperative complications as compared with that of the standard digit-based technique in anesthetized patients.

Immediate retrograde amnesia induced by midazolam: a prospective, nonrandomized cohort study.

BACKGROUND: Midazolam, a short-acting benzodiazepine, has sedative, anxiolytic, amnestic, and anticonvulsant effect. Given its advantages of rapid onset, short duration, and low toxicity, midazolam is optimal for any procedural sedation. Midazolam is known to cause anterograde amnesia; however, the possibility of retrograde amnesia has also been raised. This prospective cohort, nonrandomized study evaluated the presence and extent of retrograde amnesia induced by midazolam during cesarean delivery. METHODS: One-hundred parturients scheduled for elective cesarean delivery under spinal anesthesia were enrolled. As soon as giving birth, 6 picture cards were shown to the patients in one min intervals, and then midazolam (0.1 mg/kg) was given or not according to the patients' preference. This overall retrograde recall rate of six cards was the primary outcome of our study, which was asked by a blinded investigator. RESULTS: The overall retrograde card recall rate was lower in the midazolam group compared to the control group (77.0 ± 13.4 vs. 87.7 ± 3.9%, p <0.001), especially at one min before midazolam administration (58 vs. 88%, p <0.001). Decreased memory trend was observed as time progressed toward midazolam administration in the midazolam group (p = 0.035). More patients answered 'yes' to the factitious event in the midazolam group than in the control group (26% vs. 4%, p = 0.004). CONCLUSION: Intravenous midazolam could cause a brief-period retrograde amnesia in visual and event memory. Moreover, there were more spurious reports of intraoperative factitious events in the midazolam group, implying that episodic memories were also affected by midazolam.

Immediate retrograde amnesia induced by midazolam: A prospective, non-randomised cohort study.

BACKGROUND: Midazolam, a short-acting benzodiazepine, has sedative, anxiolytic, amnestic and anticonvulsant effects. Given its advantages of rapid onset, short duration and low toxicity, midazolam is optimal for any procedural sedation. Midazolam is known to cause anterograde amnesia; however, the possibility of retrograde amnesia has also been raised. This prospective cohort, non-randomised study evaluated the presence and extent of retrograde amnesia induced by midazolam during caesarean delivery. METHODS: One hundred parturients scheduled for elective caesarean delivery under spinal anaesthesia were enrolled. As soon as giving birth, six picture cards were shown to the patients in 1-min intervals, and then midazolam (0.1 mg/kg) was given or not according to the patients' preference. This overall retrograde recall rate of six cards was the primary outcome of our study, which was asked by a blinded investigator. RESULTS: The overall retrograde card recall rate was lower in the midazolam group compared with the control group (77.0 ± 13.4 vs. 87.7 ± 3.9%, P < .001), especially at 1 minute before midazolam administration (58% vs. 88%, P < .001). Decreased memory trend was observed as time progressed towards midazolam administration in the midazolam group (P = .035). More patients answered 'yes' to the factitious event in the midazolam group than in the control group (26% vs. 4%, P = .004). CONCLUSION: Intravenous midazolam could cause a brief-period retrograde amnesia in visual and event memory. Moreover, there were more spurious reports of intraoperative factitious events in the midazolam group, implying that episodic memories were also affected by midazolam.