Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity.

The mammalian cytoplasmic multi-tRNA synthetase complex (MSC) is a depot system that regulates non-translational cellular functions. Here we found that the MSC component glutamyl-prolyl-tRNA synthetase (EPRS) switched its function following viral infection and exhibited potent antiviral activity. Infection-specific phosphorylation of EPRS at Ser990 induced its dissociation from the MSC, after which it was guided to the antiviral signaling pathway, where it interacted with PCBP2, a negative regulator of mitochondrial antiviral signaling protein (MAVS) that is critical for antiviral immunity. This interaction blocked PCBP2-mediated ubiquitination of MAVS and ultimately suppressed viral replication. EPRS-haploid (Eprs+/-) mice showed enhanced viremia and inflammation and delayed viral clearance. This stimulus-inducible activation of MAVS by EPRS suggests an unexpected role for the MSC as a regulator of immune responses to viral infection.

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.

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.

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.

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.

Reduced virulence of the MARTX toxin increases the persistence of outbreak-associated Vibrio vulnificus in host reservoirs.

Opportunistic bacteria strategically dampen their virulence to allow them to survive and propagate in hosts. However, the molecular mechanisms underlying virulence control are not clearly understood. Here, we found that the opportunistic pathogen Vibrio vulnificus biotype 3, which caused an outbreak of severe wound and intestinal infections associated with farmed tilapia, secretes significantly less virulent multifunctional autoprocessing repeats-in-toxin (MARTX) toxin, which is the most critical virulence factor in other clinical Vibrio strains. The biotype 3 MARTX toxin contains a cysteine protease domain (CPD) evolutionarily retaining a unique autocleavage site and a distinct ß-flap region. CPD autoproteolytic activity is attenuated following its autocleavage because of the ß-flap region. This ß-flap blocks the active site, disabling further autoproteolytic processing and release of the modularly structured effector domains within the toxin. Expression of this altered CPD consequently results in attenuated release of effectors by the toxin and significantly reduces the virulence of V. vulnificus biotype 3 in cells and in mice. Bioinformatic analysis revealed that this virulence mechanism is shared in all biotype 3 strains. Thus, these data provide new insights into the mechanisms by which opportunistic bacteria persist in an environmental reservoir, prolonging the potential to cause outbreaks.

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.

Makes caterpillars floppy-like effector-containing MARTX toxins require host ADP-ribosylation factor (ARF) proteins for systemic pathogenicity.

Upon invading target cells, multifunctional autoprocessing repeats-in-toxin (MARTX) toxins secreted by bacterial pathogens release their disease-related modularly structured effector domains. However, it is unclear how a diverse repertoire of effector domains within these toxins are processed and activated. Here, we report that Makes caterpillars floppy-like effector (MCF)-containing MARTX toxins require ubiquitous ADP-ribosylation factor (ARF) proteins for processing and activation of intermediate effector modules, which localize in different subcellular compartments following limited processing of holo effector modules by the internal cysteine protease. Effector domains structured tandemly with MCF in intermediate modules become disengaged and fully activated by MCF, which aggressively interacts with ARF proteins present at the same location as intermediate modules and is converted allosterically into a catalytically competent protease. MCF-mediated effector processing leads ultimately to severe virulence in mice via an MCF-mediated ARF switching mechanism across subcellular compartments. This work provides insight into how bacteria take advantage of host systems to induce systemic pathogenicity.

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.

Structural basis of inactivation of Ras and Rap1 small GTPases by Ras/Rap1-specific endopeptidase from the sepsis-causing pathogen Vibrio vulnificus.

Multifunctional autoprocessing repeats-in-toxin (MARTX) toxins are secreted by Gram-negative bacteria and function as primary virulence-promoting macromolecules that deliver multiple cytopathic and cytotoxic effector domains into the host cytoplasm. Among these effectors, Ras/Rap1-specific endopeptidase (RRSP) catalyzes the sequence-specific cleavage of the Switch I region of the cellular substrates Ras and Rap1 that are crucial for host innate immune defenses during infection. To dissect the molecular basis underpinning RRSP-mediated substrate inactivation, we determined the crystal structure of an RRSP from the sepsis-causing bacterial pathogen Vibrio vulnificus (VvRRSP). Structural and biochemical analyses revealed that VvRRSP is a metal-independent TIKI family endopeptidase composed of an N-terminal membrane-localization and substrate-recruitment domain (N lobe) connected via an inter-lobe linker to the C-terminal active site-coordinating core ß-sheet-containing domain (C lobe). Structure-based mutagenesis identified the 2His/2Glu catalytic residues in the core catalytic domain that are shared with other TIKI family enzymes and that are essential for Ras processing. In vitro KRas cleavage assays disclosed that deleting the N lobe in VvRRSP causes complete loss of enzymatic activity. Endogenous Ras cleavage assays combined with confocal microscopy analysis of HEK293T cells indicated that the N lobe functions both in membrane localization via the first α-helix and in substrate assimilation by altering the functional conformation of the C lobe to facilitate recruitment of cellular substrates. Collectively, these results indicate that RRSP is a critical virulence factor that robustly inactivates Ras and Rap1 and augments the pathogenicity of invading bacteria via the combined effects of its N and C lobes.

Screening for Neuraminidase Inhibitor Resistance Markers among Avian Influenza Viruses of the N4, N5, N6, and N8 Neuraminidase Subtypes.

Several subtypes of avian influenza viruses (AIVs) are emerging as novel human pathogens, and the frequency of related infections has increased in recent years. Although neuraminidase (NA) inhibitors (NAIs) are the only class of antiviral drugs available for therapeutic intervention for AIV-infected patients, studies on NAI resistance among AIVs have been limited, and markers of resistance are poorly understood. Previously, we identified unique NAI resistance substitutions in AIVs of the N3, N7, and N9 NA subtypes. Here, we report profiles of NA substitutions that confer NAI resistance in AIVs of the N4, N5, N6, and N8 NA subtypes using gene-fragmented random mutagenesis. We generated libraries of mutant influenza viruses using reverse genetics (RG) and selected resistant variants in the presence of the NAIs oseltamivir carboxylate and zanamivir in MDCK cells. In addition, two substitutions, H274Y and R292K (N2 numbering), were introduced into each NA gene for comparison. We identified 37 amino acid substitutions within the NA gene, 16 of which (4 in N4, 4 in N5, 4 in N6, and 4 in N8) conferred resistance to NAIs (oseltamivir carboxylate, zanamivir, or peramivir) as determined using a fluorescence-based NA inhibition assay. Substitutions conferring NAI resistance were mainly categorized as either novel NA subtype specific (G/N147V/I, A246V, and I427L) or previously reported in other subtypes (E119A/D/V, Q136K, E276D, R292K, and R371K). Our results demonstrate that each NA subtype possesses unique NAI resistance markers, and knowledge of these substitutions in AIVs is important in facilitating antiviral susceptibility monitoring of NAI resistance in AIVs.IMPORTANCE The frequency of human infections with avian influenza viruses (AIVs) has increased in recent years. Despite the availability of vaccines, neuraminidase inhibitors (NAIs), as the only available class of drugs for AIVs in humans, have been constantly used for treatment, leading to the inevitable emergence of drug-resistant variants. To screen for substitutions conferring NAI resistance in AIVs of N4, N5, N6, and N8 NA subtypes, random mutations within the target gene were generated, and resistant viruses were selected from mutant libraries in the presence of individual drugs. We identified 16 NA substitutions conferring NAI resistance in the tested AIV subtypes; some are novel and subtype specific, and others have been previously reported in other subtypes. Our findings will contribute to an increased and more comprehensive understanding of the mechanisms of NAI-induced inhibition of influenza virus and help lead to the development of drugs that bind to alternative interaction motifs.

Association of Preoperative Serum Chloride Levels With Mortality and Morbidity After Noncardiac Surgery: A Retrospective Cohort Study.

BACKGROUND: Postoperative hyperchloremia is known to be related to increases in mortality and morbidity after surgery. However, the relationship between preoperative hyperchloremia and hypochloremia and postoperative mortality and morbidity is not well established. Our aim was to evaluate the relationship between preoperative hyperchloremia or hypochloremia, as assessed using preoperative serum chloride tests, and 90-day mortality and morbidity after noncardiac surgery. METHODS: In this retrospective cohort study, we reviewed the medical records of patients >20 years of age who underwent noncardiac surgery between January 2010 and December 2016. Patients were categorized into one of the following groups on the basis of the results of serum chloride testing performed within 1 month before surgery: normochloremia, 97-110 mmol·L; hyperchloremia, >110 mmol·L; and hypochloremia, <97 mmol·L. The primary end point of this study was the difference in postoperative 90-day mortality among the preoperative serum chloride groups. The secondary end point was the difference in postoperative acute kidney injury incidence among the preoperative serum chloride groups. RESULTS: A total of 106,505 patients were included in the final analysis (2147 were allocated to the preoperative hypochloremia group and 617 to the hyperchloremia group). Multivariable Cox regression analysis revealed significantly increased 90-day mortality in the hypochloremia (hazard ratio, 1.46; 95% CI, 1.16-1.84; P = .001) and hyperchloremia (hazard ratio, 1.76; 95% CI, 1.13-2.73; P = .013) groups when compared with the normochloremia group. In addition, multivariable logistic regression analysis revealed a 1.83-fold increased odds of acute kidney injury in the preoperative hypochloremia group when compared with the normochloremia group (odds ratio, 1.83; 95% CI, 1.53-2.19; P < .001). CONCLUSIONS: Preoperative hypochloremia and hyperchloremia were related to increased 90-day mortality after noncardiac surgery. In addition, preoperative hypochloremia was related to an increased risk for postoperative acute kidney injury.

Midazolam Premedication Facilitates Mask Ventilation During Induction of General Anesthesia: A Randomized Clinical Trial.

BACKGROUND: During induction of general anesthesia, proper mask ventilation is crucial for supplying sufficient oxygen to unconscious patients. Midazolam has a relaxing effect on airway muscles. We hypothesized that sedative premedication with midazolam would facilitate mask ventilation during anesthetic induction. METHODS: Patients undergoing elective surgery under general anesthesia were randomized into 2 groups. The midazolam group received midazolam premedication at the reception area, 3 minutes before transfer to the operating room. Patients in the control group were treated with normal saline as a placebo. The primary outcome was difficulty of mask ventilation during induction, as evaluated using the Warters scales. RESULTS: A total of 97 patients completed the analysis: 49 in the control group and 48 in the midazolam group. The patients in the midazolam group showed a significantly lower mask ventilation difficulty score on the Warters scale than that of the control group (mean [standard deviation], 0.92 [1.13] vs 0.19 [0.57]; estimated difference [95% confidence interval], 0.73 [0.37-1.09]; P < .001). The incidence of difficult mask ventilation (≥2 Warters scale) was significantly lower in the midazolam group than in the control group (risk ratio [95% confidence interval], 0.15 [0.03-0.72]; P = .015). CONCLUSIONS: This randomized clinical trial demonstrated that midazolam premedication enhanced mask ventilation during induction of general anesthesia.

Comparison of standard versus 90° rotation technique for LMA Flexible™ insertion: a randomized controlled trial.

BACKGROUND: Insertion of a flexible laryngeal mask airway (LMA Flexible) is known to be more difficult than that of a conventional laryngeal mask airway. The 90° rotation technique can improve the success rate with a conventional laryngeal mask airway but its effect with the LMA Flexible remains unknown. We assessed whether the 90° rotation technique increased the first-attempt success rate of LMA Flexible insertion versus the standard technique. METHODS: In total, 129 female patients undergoing breast surgery were analyzed. The primary endpoint was success at the first attempt. The insertion time, number of trials, number of manipulations required, and oropharyngeal leak pressure were also evaluated. Heart rate and mean blood pressure were recorded 1 min before and 1 min after insertion. Blood staining on the LMA Flexible after removal and postoperative sore throat were checked. RESULTS: The first-attempt success rates were comparable between the groups (93% vs. 98.3%, P = .20). The insertion time, number of trials and manipulations, hemodynamic variables, and complications, such as blood staining and sore throat, did not differ between the groups. CONCLUSIONS: The 90° rotation technique is a good alternative to the standard technique for insertion of the LMA Flexible. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03028896 ). It was registered retrospectively at Jan 19th, 2017.

Preoperative 5-aminolevulinic acid administration for brain tumor surgery is associated with an increase in postoperative liver enzymes: a retrospective cohort study.

BACKGROUND: Besides 5-aminolevulinic acid (5-ALA), liver enzyme elevation after brain tumor surgery can be caused by anesthesia and medications. In this retrospective study, we determined whether preoperative 5-ALA administration is associated with postoperative elevation of liver enzymes (PELE) in brain tumor patients and identified predictive factors for PELE in patients treated with 5-ALA. METHODS: In 179 patients undergoing brain tumor surgery with preoperative normal values of liver enzymes, laboratory data on serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin (T.bil) levels were collected preoperatively and through postoperative day (POD) 45. RESULTS: Ninety-nine PELEs (ALT, 56; AST, 34; ALP, 5; and TB, 4) were observed in 62 (34.6%) patients. Four (4.2%) patients treated with 5-ALA showed grade 3 elevation of transaminases based on the Common Terminology Criteria for Adverse Effects. Preoperative 5-ALA treatment was predictive of PELE (odds ratio [95% confidence interval], 2.30 [1.14-4.67]; P = 0.021). In patients treated with 5-ALA (n = 95), 70 PELEs (ALT, 39; AST, 22; ALP, 5; and TB, 4) were observed in 41 (43.2%) patients and significant predictive factors for PELE were preoperative ALT level (1.10 [1.04-1.17]; P = 0.001) and body mass index (BMI, 1.29 [1.08-1.56]; P = 0.006). In patients treated with 5-ALA, 13 and 36 patients, of 39 patients whose maximum postoperative ALT levels > 40 U/L, showed the normal value of serum ALT on PODs 14 and 45, respectively. Only three patients showed ALT elevation > 40 U/L on PODs 15-45, with a downward trend. CONCLUSIONS: The use of 5-ALA for brain tumor surgery in patients with preoperative normal values of liver enzymes was associated with increased transient PELE, but a low incidence of severely elevated liver transaminases levels. When 5-ALA is administered to patients with the upper normal value of preoperative serum ALT and overweight, attention is paid to PELE.

A Comparison of Hemostatic Properties between Monopolar and Bipolar Hysteroscopic Surgery using Rotational Thromboelastometry: A Randomized Trial.

OBJECTIVE: Systemic absorption of irrigation fluid can lead to a disturbed coagulation cascade. We compared the changes in hemostatic properties on using nonelectrolyte solution in monopolar hysteroscopic surgery (HS) with that on using isotonic saline in bipolar HS via rotational thromboelastometry (ROTEM) analysis. METHODS: A total of 54 patients were randomized into 2 groups: 1 group underwent monopolar HS using a mixture of 2.7% sorbitol and 0.54% mannitol (the HSMP group), whereas the other group underwent bipolar HS using 0.9% isotonic saline (the HSBP group). The effects of these 2 methods on coagulation were assessed via pre and postoperative laboratory tests, including estimation of the international normalized ratio of prothrombin time and activated partial thromboplastin time and ROTEM analysis. In addition, the hemoglobin, hematocrit, and electrolyte levels and the platelet count were analyzed. RESULTS: Patient characteristics, volume of irrigation fluid absorbed, and type of procedure were comparable between the 2 groups. There were no significant differences in the pre and postoperative values of ROTEM parameters between the 2 groups. Most postoperative ROTEM parameters, as compared with preoperative values, changed in both groups; clot formation time was prolonged, and the α-angle and maximum clot firmness were decreased. All ROTEM parameters were maintained within the normal range. Hematological parameters, including hemoglobin and hematocrit levels and platelet count, were significantly decreased postoperatively in both groups compared to the preoperative values. No pre and postoperative hematological and hemostatic parameters were significantly different between the 2 groups. CONCLUSION: Irrigation fluid absorbed in healthy women during HS caused hypocoagulable changes in the blood, irrespective of the irrigant type, and no significant differences between HS using monopolar and bipolar electrodes were demonstrated.

Physician turnover and its association with mortality after non-cardiac surgery: a retrospective cohort analysis of patients in South Korea.

PURPOSE: To assess the association between physician turnover, mortality, and length of hospital stay after non-cardiac surgery in South Korea. METHODS: This retrospective cohort study is based on analysis of the medical records of patients who underwent non-cardiac surgery between January, 2010 and December, 2016. The primary outcomes were the differences in 30-day, 90-day, and overall mortality between non-cardiac surgery performed during the turnover period and that performed during the non-turnover period. RESULTS: The subjects of the analysis were 106,832 patients who underwent non-cardiac surgery. Among them, 17,788 patients underwent surgery during the turnover period and 89,044 underwent surgery during the non-turnover period. Multivariable Cox regression analysis revealed no significant differences in postoperative 30-day mortality (P = 0.427), 90-day mortality (P = 0.854), or overall mortality (P = 0.928) between surgery conducted during the turnover period and that conducted during the non-turnover period. Surgery performed during the physician turnover period was associated with a 0.21-day increase compared with surgery performed during the non-turnover period (coefficient: 0.21, 95% confidence interval: 0.00-0.42, P = 0.038). CONCLUSIONS: Physician turnover was not associated with postoperative 30-day, 90-day, or overall mortality after non-cardiac surgery. However, the length of hospital stay was slightly longer for patients who underwent non-cardiac surgery in the turnover period.

Pre-operative assessment of 30-day mortality risk after major surgery: the role of the quick sequential organ failure assessment: A retrospective observational study.

BACKGROUND: The quick Sequential Organ Failure Assessment (qSOFA) is intended for the assessment of the prognosis and risk of sepsis. It may also help predict the mortality risk of nonseptic patients. OBJECTIVE: This study investigated the relationship between pre-operative qSOFA scores and 30-day mortality after major surgery. It also evaluated the predictive value of qSOFA scores combined with the American Society of Anesthesiologists (ASA) physical status and Charlson comorbidity index (CCI). DESIGN: A retrospective observational study. SETTING: Single tertiary academic hospital. PATIENTS: Medical records of patients who underwent major surgery (estimated blood loss >500 ml; surgery time >2 h) between January 2010 and December 2017 were examined. MAIN OUTCOME MEASURES: The qSOFA score was measured within 24 h before surgery, and its association with 30-day mortality was analysed using multivariable logistic regression. A receiver-operating characteristic curve analysis was used to investigate the predictive power of the pre-operative qSOFA scores combined with the ASA physical status and with CCI. RESULTS: A total of 6336 patients were included in the final analysis, and 91 (1.4%) died within 30 days. The multivariable logistic regression analysis including all covariates indicated that 30-day mortality was 2.43-times higher for the score 1 group than for the score 0 group (P = 0.002), and it was 3.54-times higher for the score at least 2 group than for the score 0 group (P < 0.001). The area under the curve (AUC) of the pre-operative qSOFA, ASA physical status and CCI were 0.69, 0.55 and 0.57, respectively. When the pre-operative qSOFA score was combined with the ASA physical status or CCI, the AUCs were 0.73 and 0.72, respectively. CONCLUSION: Higher pre-operative qSOFA scores within 24 h of surgery were associated with increased 30-day mortality. Pre-operative qSOFA scores have better predictive value for 30-day mortality when combined with the ASA physical status or CCI.

Association Between Perioperative Fluid Balance and 30-Day Unplanned Readmission After Major Abdominal Surgery.

Perioperative positive fluid balance (FB) increases postoperative complication and length of hospital stay. We aimed to investigate 30-day unplanned readmission after major abdominal surgery based on perioperative FB (%) on postoperative days (POD) 0 to 3. This retrospective cohort study analyzed medical records of patients who underwent elective major abdominal surgery (surgery time >2 hours, estimated blood loss >500 mL) at a single tertiary academic hospital from January 2010 to December 2017. Cumulative FB was calculated by total input fluid - output fluid in liters × weight (kg)-1 on admission × 100 during POD 0 (24 hours), 0 to 1 (48 hours), 0 to 2 (72 hours), and 0 to 3 (96 hours). Of the 3650 patients in the final analysis, 503 (13.8%) had unplanned readmission within 30 days. In the multivariable logistic regression analysis, FB on POD 0 (24 hours), 0 to 1 (48 hours), 0 to 2 (72 hours), and 0 to 3 (96 hours) showed no significant association with 30-day unplanned readmission (all P > .05). However, an increase of 10 000 points in the total relative value unit scores was associated with 5% increase in 30-day unplanned readmission (odds ratio = 1.05, 95% confidence interval = 1.02-1.07; P = .001), and 1-hour increase in surgery time was associated with 10% increase in 30-day unplanned readmission (odds ratio = 1.10, 95% confidence interval = 1.05-1.15; P < .001). This study showed that perioperative FB is not associated with 30-day unplanned readmission rate after a major abdominal surgery. Total relative value unit scores and duration of surgery were significantly associated with 30-day unplanned readmission rate after major abdominal surgery in a single tertiary academic hospital.