Severity of SARS-CoV-2 infection in pregnant women and their neonates during the Omicron period compared to the pre-Omicron period: A retrospective cohort study.

AIM: To compare the clinical outcomes among women diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy, and their neonates, during the period when the Omicron variant predominated in Japan with those of the pre-Omicron variant period. METHODS: We conducted a retrospective single-center cohort study between August 1, 2020, and June 30, 2022. The cohort was divided into pre-Omicron group (August 1, 2020 to November 30, 2021) and Omicron group (December 1, 2021 to June 30, 2022). The primary outcome was maternal intensive care unit (ICU) admission during the perinatal period. The secondary outcomes were maternal oxygen administration before and after delivery, preterm birth (PTB), and low birth weight (LBW). RESULTS: During the study period, 81 pregnant women were admitted to the hospital with SARS-CoV-2 infection (pre-Omicron period, n = 28; Omicron period, n = 53). SARS-CoV-2 infection during the Omicron period was associated with lower risk of maternal ICU admission (adjusted-odds ratio [aOR]: 0.10, 95% confidence interval [CI]: 0.01-1.23, p = 0.072), oxygen administration via a nasal cannula or mask (aOR: 0.18, 95% CI: 0.03-0.96, p = 0.045), PTB (aOR: 0.15, 95% CI: 0.04-0.51, p = 0.002), and LBW (aOR: 0.13, 95% CI: 0.03-0.55, p = 0.005). CONCLUSION: Among pregnant women, SARS-CoV-2 infection during the Omicron period was associated with reduced risk of maternal ICU admission, requiring supplemental oxygen, PTB, and LBW. This can be attributable to lower virulence of the Omicron variant and higher vaccination coverage during the Omicron period.

α-Tocopherol transfer protein mediates protective hypercapnia in murine ventilator-induced lung injury.

RATIONALE: Hypercapnia is common in mechanically ventilated patients. Experimentally, 'therapeutic hypercapnia' can protect, but it can also cause harm, depending on the mechanism of injury. Hypercapnia suppresses multiple signalling pathways. Previous investigations have examined mechanisms that were known a priori, but only a limited number of pathways, each suppressed by CO2, have been reported. OBJECTIVE: Because of the complexity and interdependence of processes in acute lung injury, this study sought to fill in knowledge gaps using an unbiased screen, aiming to identify a specifically upregulated pathway. METHODS AND RESULTS: Using genome-wide gene expression analysis in a mouse model of ventilator-induced lung injury, we discovered a previously unsuspected mechanism by which CO2 can protect against injury: induction of the transporter protein for α-tocopherol, α-tocopherol transfer protein (αTTP). Pulmonary αTTP was induced by inspired CO2 in two in vivo murine models of ventilator-induced lung injury; the level of αTTP expression correlated with degree of lung protection; and, absence of the αTTP gene significantly reduced the protective effects of CO2. α-Tocopherol is a potent antioxidant and hypercapnia increased lung α-tocopherol in wild-type mice, but this did not alter superoxide generation or expression of NRF2-dependent antioxidant response genes in wild-type or in αTTP-/- mice. In concordance with a regulatory role for α-tocopherol in lipid mediator synthesis, hypercapnia attenuated 5-lipoxygenase activity and this was dependent on the presence of αTTP. CONCLUSIONS: Inspired CO2 upregulates αTTP which increases lung α-tocopherol levels and inhibits synthesis of a pathogenic chemoattractant.

Midazolam inhibits the formation of amyloid fibrils and GM1 ganglioside-rich microdomains in presynaptic membranes through the gamma-aminobutyric acid A receptor.

Recent studies have suggested that a positive correlation exists between surgical interventions performed under general anesthesia and the risk of developing Alzheimer's disease (AD) in the late postoperative period. It has been reported that amyloid ß-protein (Αß) fibrillogenesis, which is closely related to AD, is accelerated by exposure to anesthetics. However, the mechanisms underlying these effects remain uncertain. This study was designed to investigate whether the anesthetic midazolam affects Αß fibrillogenesis, and if so, whether it acts through GM1 ganglioside (GM1) on the neuronal surface. Midazolam treatment decreased GM1 expression in the detergent-resistant membrane microdomains of neurons, and these effects were regulated by the gamma-aminobutyric acid-A receptor. Midazolam inhibited Αß fibril formation from soluble Αß on the neuronal surface. In addition, midazolam suppressed GM1-induced fibril formation in a cell-free system. Moreover, midazolam inhibited the formation of Αß assemblies in synaptosomes isolated from aged mouse brains. These finding suggested that midazolam has direct and indirect inhibitory effects on Αß fibrillogenesis.

A short period of fasting before surgery conserves basal metabolism and suppresses catabolism according to indirect calorimetry performed under general anesthesia.

It is recommended that the period of fasting before elective surgery should be shortened to facilitate a rapid recovery by preventing catabolism. We examined the effects of a short period of fasting on metabolism by performing indirect calorimetry (IC) under general anesthesia. A prospective observational study involving 26 consecutive patients who underwent elective surgery and whose metabolism was evaluated using IC during anesthesia was conducted. The patients were divided into two groups, those who fasted for <8 h (group S) and those who fasted for >10 h (group L). Oxygen consumption, the volume of carbon dioxide emissions (VCO2), the respiratory quotient (RQ), resting energy expenditure (REE), and basal energy expenditure (BEE) were compared. The REE, VCO2, and RQ of group L (17.7 ± 2.3 kcal/kg/day, 118.5 ± 20.8 ml/min, and 0.71 ± 0.12, respectively) were significantly lower than those of group S (19.7 ± 2.3 kcal/kg/day, 143.6 ± 30.9 ml/min, and 0.81 ± 0.09, respectively) (P < 0.05). In group L, the relationship between REE and BEE was weaker (r(2) = 0.501) and the BEE-REE slope was less steep (REE = 0.419BEE + 509.477) than those seen in group S (r(2) = 0.749 and REE = 1.113BEE - 376.111, respectively). Our findings suggest that a short period of fasting (<8 h) before surgery is more strongly associated with the conservation of basal metabolism.

[Incidence, Risk Factors, and Effects on Outcome of Postoperative Delirium in Patients Undergoing Esophagectomy].

BACKGROUND: Postoperative delirium (POD) is a common but serious complication after major surgery. The aim of this study was to investigate the incidence and effects on outcome of POD in esophagectomy patients, and to identify risk factors for developing POD. METHODS: A retrospective medical record review was conducted for all patients who had received esophagectomy for esophageal cancer during a three-year period. RESULTS: In a total of 71 patients, the overall incidence of POD was 20%. Multivariable regression analysis identified two independent risk factors for POD: older age (70) and preoperative electrolyte abnormalities. Patients with delirium had a higher incidence of respiratory complications and longer hospital stays compared with the non-delirium patients. CONCLUSIONS: The incidence of POD in patients undergoing esophagectomy is 20%. The risk factors of POD are older age and preoperative electrolyte abnormalities. POD negatively impacts postoperative respiratory complications and hospital stay.

Propofol and thiopental suppress amyloid fibril formation and GM1 ganglioside expression through the γ-aminobutyric acid A receptor.

BACKGROUND: The incidence of Alzheimer disease may increase after surgical interventions. Amyloid ß-protein (Aß) fibrillogenesis, which is closely related to Alzheimer disease, is reportedly accelerated by exposure to anesthetics. However, the effects of GM1 ganglioside (GM1) on Αß fibrillogenesis have not yet been reported. The current study was designed to examine whether the anesthetics propofol and thiopental are associated with Αß assembly and GM1 expression on the neuronal cell surface. METHODS: PC12N cells and cultured neuronal cells were treated with propofol or thiopental, and GM1 expression in treated and untreated cells was determined by the specific binding of horseradish peroxidase-conjugated cholera toxin subunit B (n = 5). The effects of an inhibitor of the γ-aminobutyric acid A receptor was also examined (n= 5). In addition, the effects of the anesthetics on GM1 liposome-induced Αß assembly were investigated (n = 5). Finally, the neurotoxicity of the assembled Αß fibrils was studied by the lactate dehydrogenase release assay (n = 6). RESULTS: Propofol (31.2 ± 4.7%) and thiopental (34.6 ± 10.5%) decreased GM1 expression on the cell surface through the γ-aminobutyric acid A receptor. The anesthetics inhibited Αß fibril formation from soluble Αß in cultured neurons. Moreover, propofol and thiopental suppressed GM1-induced fibril formation in a cell-free system (propofol, 75.8 ± 1.9%; thiopental, 83.6 ± 1.9%) and reduced the neurotoxicity of a mixture containing Aß and GM1 liposomes (propofol, 35.3 ± 16.4%; thiopental, 21.3 ± 11.6%). CONCLUSIONS: Propofol and thiopental have direct and indirect inhibitory effects on Αß fibrillogenesis.

Perioperative Management of a Patient With Severe Cold Agglutinin Disease Undergoing Total Hip Arthroplasty With a Cemented Stem: A Case Report.

Patients with cold agglutinin disease who undergo total hip arthroplasty (THA) are rarely encountered. Patients with cold agglutinin disease are very sensitive to cold ambient temperatures and require scrupulous perioperative body-temperature management. However, THA requires a cementing procedure that exposes patients to cold temperatures during surgery and may result in autoimmune hemolytic anemia in these patients. Thus, perioperative management of patients with cold agglutinin disease undergoing THA requires more than just scrupulous systemic temperature management. Here, we present the successful perioperative management of a patient with severe cold agglutinin disease who underwent THA with a cemented stem.

Skin-traction method prevents the collapse of the internal jugular vein caused by an ultrasound probe in real-time ultrasound-assisted guidance.

PURPOSE: Real-time ultrasound-assisted guidance for catheterization of the internal jugular vein (IJV) is known to be useful, especially for a small-sized vein, which is difficult to catheterize. However, one of the problems with real-time ultrasound-assisted guidance is that the ultrasound probe itself can collapse the vein. We have developed a novel "skintraction method (STM)", in which the puncture point of the skin over the IJV is stretched upwards with several pieces of surgical tape in the cephalad and caudal directions with the aim being to facilitate catheterization of the IJV. We examined whether this method increased the compressive force required to collapse the IJV. METHODS: In ten volunteers, the compressive force required to collapse the right IJV, and the cross-sectional area and anteroposterior and transverse diameters of the IJV were measured with ultrasound imaging in the supine position (SP) with or without the STM or in the Trendelenburg position of 10 degrees head-down (TP) without the STM. RESULTS: The compressive force to required to collapse the vein was increased significantly with the STM, while the crosssectional area and anteroposterior diameter of the vein in the SP with STM were similar to those in the TP without the STM. CONCLUSION: With the STM, not only the cross-sectional area but also the compressive force required to collapse the IJV increased. Thus, the STM may facilitate real-time ultrasoundassisted guidance for catheterization of the IJV by maintaining the cross-sectional area of the vein during the guidance.

Lactic acid increases aquaporin 4 expression on the cell membrane of cultured rat astrocytes.

The water channel protein aquaporin (AQP) may play roles in the homeostasis of water content in the brain and brain edema. One possible mechanism of brain edema is glial swelling due to lactic acidosis associated with ischemia. Here, we investigated the effect of lactic acid on the expression and cellular distribution of AQP 4 in cultured rat astrocytes. After 24h of incubation, the AQP4 expression level increased maximally with 35mM lactic acid. The AQP4 expression levels also increased with hydrochloric acid or acetic acid. In contrast, with sodium lactate, the AQP4 levels did not increase. The increase in AQP4 expression level occurred without a significant increase in AQP4 mRNA expression level by lactic acid. Under the conditions of de novo protein synthesis inhibition with cycloheximide, lactic acid increased the AQP4 expression level. Furthermore, lactic acid increased the AQP4 expression level on the cell surface of the astrocytes, as determined by a cell surface biotinylation assay and immunocytochemical examination. The increase in AQP4 expression level on the cell membrane of astrocytes induced by lactic acid may be a new regulation mechanism of AQP4 in the brain.

Comparison of anesthetic management and outcomes of robot-assisted vs pure laparoscopic radical prostatectomy.

STUDY OBJECTIVE: Limited data are available regarding the anesthetic management and outcome of patients undergoing pure laparoscopic radical prostatectomy (LRP) and robotic-assisted LRP (RALP). Therefore, our primary objective was to compare the anesthetic management between these 2 groups. Our secondary objective was to determine the incidence of adverse outcomes associated with RALP, which requires an extreme Trendelenburg position. DESIGN: A retrospective observational study. SETTING: University teaching hospital. PATIENTS: A total of 223 men, consisting of 97 LRP patients and 126 RALP patients, treated during a 3-year period (January 2010-December 2012) were retrospectively studied. INTERVENTIONS: None. MEASUREMENTS: Information on patient demographics, type of anesthesia, anesthetic/pneumoperitoneum/surgical times, intraoperative fluids and blood products, estimated blood loss, intraoperative and postoperative opioid use, postoperative analgesic consumption, length of stay in the postanesthesia care unit, postoperative complications, and hospital stays was collected and compared. MAIN RESULTS: The estimated blood loss was higher in LRP patients than in RALP patients (median, 550 mL vs 200 mL; P < .001). Likewise, 24% of the LRP patients received intraoperative transfusions compared with 0.79% of the RALP patients (P < .001). The RALP patients had a longer anesthesia time (median, 276 vs 259 minutes; P = .032) and a greater intraoperative use of opioids (P < .001). The incidence of complications was similar in both groups with the exception of postoperative nausea and vomiting, which were observed more frequently among the RALP patients than among the LRP patients (33% vs 16%; P = .007). CONCLUSIONS: This is the first report to compare the anesthetic management of RALP vs LRP. Anesthesiologists can expect RALP surgery to be associated with less blood loss and a need for fewer blood products than traditional LRP surgery. The anesthetic outcome of RALP was generally satisfactory except for a high incidence of postoperative nausea and vomiting.

[Evaluation of preoperative anxiety in patients with and without premedication].

BACKGROUND: The purpose of this investigation was to determine whether elimination of premedication before general anesthesia affects preoperative anxiety. METHODS: Subjects were assigned to one of two groups: a sedative group (0.5 mg midazolam i.m., n = 111) or a no-premedication group (n = 98). We used patients' responses to a questionnaire to compare the no-premedication group and the sedative group. RESULTS: Eighty-three percent of patients in the no-premedication group entered the operating room ambulatory. The responses concerning preoperative anxiety were not different between the two groups. There was a high rate of recall of the conversation before anesthesia induction in the no-premedication group, and most of these patients replied that making conversation before general anesthesia was beneficial to them. Increases in heart rate and blood pressure at the point of entrance to operating room were observed in the no-premedication group, but the degrees of increase were not considered clinically important. CONCLUSION: We conclude that elimination of premedication does not increase anxiety in comparison with patients receiving sedatives, but makes patients feel comfortable by way of preoperative conversation. Elimination of premedication also makes ambulatory entrance possible, both improving safety with respect to patient identification and reducing the demand on nursing.

[A comparison of perioperative factors with two methods of coronary artery bypass grafting (CABG): off-pump and conventional].

BACKGROUND: The safety and efficiency of off-pump coronary artery bypass grafting (OPCAB) are still controversial. The purpose of this study was to evaluate this approach in comparison with the conventional cardiopulmonary bypass technique (cCABG). METHODS: A retrospective review of patients who had undergone coronary artery bypass grafting independently without other operations between January 1, 1999 and September 30, 2001 was performed. The patients were divided into two groups: those who underwent OPCAB and the remainder for cCABG. The perioperative factors of the two groups were compared. RESULTS: A total of 152 OPCAB and 142 cCABG cases were reviewed. Compared with cCABG, OPCAB significantly reduced the amount of catecholamine needed on admission to ICU, intubation time, overall hospital length of stay, and neurologic events. There were also trends for decreases in ICU length of stay, mortality, and renal failure. On the other hand, OPCAB did not affect perioperative blood loss. CONCLUSIONS: Overall OPCAB is safer and more efficient than cCABG. However, we have to note in anesthetic management that OPCAB does not reduce blood loss.

IV injection of polystyrene beads for mouse model of sepsis causes severe glomerular injury.

BACKGROUND: Infusion fluids may be contaminated with different types of particulates that are a potential health hazard. Particulates larger than microvessels may cause an embolism by mechanical blockage and inflammation; however, it has been reported that particulates smaller than capillary diameter are relatively safe. Against such a background, one report showed that polystyrene beads smaller than capillary diameter decreased tissue perfusion in ischemia-reperfusion injury. This report suggested that polystyrene beads from 1.5- to 6-µm diameter (dia.) may have unfavorable effects after pretreatment. Here, we investigated whether injection of polystyrene beads (3- and 6-µm dia.) as an artificial contaminant of intravenous fluid after lipopolysaccharide (LPS) injection affected mortality and organ damage in mice. METHODS: Mice were divided into four groups and injected: polystyrene beads only, LPS only, polystyrene beads 30 min after LPS, or saline. A survival study, histology, blood examination, and urine examination were performed. RESULTS: The survival rate after LPS and polystyrene bead (6-µm dia.) injection was significantly lower than that of the other three groups. In the kidney sections, injured glomeruli were significantly higher with LPS and polystyrene bead injection than that of the other three groups. LPS and polystyrene bead injection decreased the glomerular filtration rate and led to renal failure. Inflammatory reactions induced with LPS were not significantly different between with or without polystyrene beads. Polystyrene beads were found in urine after LPS and polystyrene bead injection. CONCLUSIONS: Injection of polystyrene beads after LPS injection enhanced glomerular structural injury and caused renal function injury in a mouse sepsis model.

Ketamine reduces amyloid ß-protein degradation by suppressing neprilysin expression in primary cultured astrocytes.

Pathological accumulation of cortical amyloid ß-protein (Aß) is an early and consistent feature of Alzheimer's disease (AD). Aß levels in the brain are determined by production and catabolism. Previous studies have suggested that deficits in the brain expression of neprilysin (NEP) and the insulin-degrading enzyme (IDE), which are both proteases involved in amyloid degradation, may promote Aß deposition in patients with sporadic late-onset AD. Because the incidence of AD increases after surgical intervention, we examined whether ketamine, which is a general anaesthetic with neuroprotective properties for excitotoxic ischaemic damage, is associated with Aß degradation by inducing NEP and IDE expression. The non-competitive N-methyl-d-aspartate receptor antagonist ketamine and MK801 significantly decreased the expression of NEP, but not IDE, in a concentration- and time-dependent manner through the dephosphorylation of p38 mitogen-activated protein kinase (MAPK) in cultured rat astrocytes. Furthermore, NEP-reduced reagents significantly suppressed the degradation of exogenous Aß in cultured astrocytes. These results suggested that ketamine suppresses the Aß degradation of NEP by reducing p38 MAPK-mediated pathway activity.

A comparison between dosages and plasma concentrations of dexmedetomidine in clinically ill patients: a prospective, observational, cohort study in Japan.

BACKGROUND: Dexmedetomidine is a highly selective central α2-agonist with anesthetic and analgesic properties for patients in intensive care units. There is little information about the relationship between dosage and plasma concentration during long drug infusions of dexmedetomidine in critically ill patients, especially in Asians. In addition, the administration of dexmedetomidine with a dosage of 0.2-0.7 µg/kg/h in Japan is different from that with a dosage of 0.2-1.4 µg/kg/h in European countries and the USA. There has been concern about obtaining an effective concentration with a small dosage and estimating the relationship between dosage and plasma concentration. We conducted a prospective, observational, cohort study measuring plasma dexmedetomidine concentrations. METHODS: Plasma dexmedetomidine concentrations of 67 samples from 34 patients in an intensive care unit for 2 months were measured by ultra performance liquid chromatography coupled with tandem mass spectrometry using single-blind method, and the correlation coefficient between dosages and plasma concentrations was estimated. Exclusion criteria included young patients (<16 years) and samples obtained from patients in which the dosage of dexmedetomidine was changed within 3 h. RESULTS: Among the patients, 20 (58.8%) of the 34 received dexmedetomidine at 0.20-0.83 µg/kg/h, and in 40 of the 67 samples for which dexmedetomidine had been administered, this occurred for a median duration of 18.5 h (range, 3-87 h). The range of the dexmedetomidine plasma concentration was 0.22-2.50 ng/ml. By comparison with other studies, with a dosage of 0.2-0.7 µg/kg/h, the patients in this setting could obtain an effective dexmedetomidine concentration. The plasma dexmedetomidine concentration was moderately correlated with the administered dosage (r = 0.653, P < 0.01). The approximate linear equation was y = 0.171x + 0.254. The range of Richmond Agitation-Sedation Scale was 0 to -5. CONCLUSIONS: We concluded that, with a dosage of 0.2-0.83 µg/kg/h, the patients in this setting could obtain an effective dexmedetomidine concentration of 0.22-2.50 ng/ml. In addition, the plasma dexmedetomidine concentration was moderately correlated with the administered dosage (r = 0.653, P < 0.01). TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) UMIN000009115.

A new enteral diet, MHN-02, which contains abundant antioxidants and whey peptide, protects against carbon tetrachloride-induced hepatitis.

BACKGROUND: Inflammatory or oxidative stress is related to various diseases, including not only inflammatory diseases, but also diabetes, cancer, and atherosclerosis. The aim of this study was to evaluate the anti-inflammatory effects of a new enteral diet, MHN-02, which contains abundant antioxidants and whey peptide. The study also investigated the ability of MHN-02 to attenuate lethality, liver injury, the production of inflammatory cytokines, and the production of oxidized products using a carbon tetrachloride-induced rat model of severe fulminant hepatitis. METHODS: Male Sprague-Dawley rats were fed either a control diet or the MHN-02 diet for 14 days and injected with 2 mL/kg of carbon tetrachloride. Survival of rats was monitored from day 0 to day 3. To evaluate liver injury, inflammation, and oxidative stress, blood and liver samples were collected, and aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, interleukin 6, tumor necrosis factor-α, and superoxide dismutase activity as a free radical scavenger were measured. A portion of the liver was evaluated histologically. RESULTS: The survival rates of rats receiving the MHN-02 diet and the control diet were 90% and 55%, respectively. In the MHN-02 diet group, levels of serum liver enzymes and serum cytokines were significantly lower than in the control group. Superoxide dismutase activity in the MHN-02 diet was significantly higher in the MHN-02 group. Pathological lesions were significantly larger in the control group. CONCLUSION: Supplementation of enteral diets containing whey peptide and antioxidants may protect against severe hepatitis.

Orotracheal intubation with an AirWay Scope in a patient with Treacher Collins syndrome.

Treacher Collins syndrome (TCS) is a congenital malformation of craniofacial development; in these patients conventional direct laryngoscopy is very difficult and often unsuccessful because of the upper airway malformation. A 20-year-old man with TCS was scheduled for elective tympanoplasty. The patient showed the characteristic facial appearance of TCS, and a difficult airway was anticipated. After careful anesthesia induction, direct laryngoscopy with Macintosh blade no. 4 of a direct laryngoscope failed to visualize the epiglottis, even with cricoid pressure, resulting in a grade 4 Cormack and Lehane view. Next, the AirWay Scope was easily inserted, and his glottic opening was clearly visualized. An 8.0-mm-internal-diameter tracheal tube was then advanced into the trachea without any difficulty. The AirWay Scope is a very useful airway device for orotracheal intubation; it provides an excellent view of the glottis without requiring alignment of the oral, pharyngeal, and laryngeal axes, and appears to be promising for use in patients with a difficult airway.

Interleukin-1beta induces the expression of aquaporin-4 through a nuclear factor-kappaB pathway in rat astrocytes.

Interleukin (IL)-1beta is known to play a role in the formation of brain edema after various types of injury. Aquaporin (AQP)4 is also reported to be involved in the progression of brain edema. We tested the hypothesis that AQP4 is induced in response to IL-1beta. We found that expression of AQP4 mRNA and protein was significantly up-regulated by IL-1beta in cultured rat astrocytes, and that intracerebroventricular administration of IL-1beta increased the expression of AQP4 protein in rat brain. The effects of IL-1beta on induction of AQP4 were concentration and time dependent. The effects of IL-1beta on AQP4 were mediated through IL-1beta receptors because they were abolished by co-incubation with IL-1 receptor antagonist. It appeared that IL-1beta increased the level of AQP4 mRNA without involvement of de novo protein synthesis because cycloheximide, a protein synthesis inhibitor, did not inhibit the effects of IL-1beta. Inhibition of the nuclear factor-kappaB (NF-kappaB) pathway blocked the induction of AQP4 by IL-1beta in a concentration-dependent manner. These findings show that IL-1beta induces expression of AQP4 through a NF-kappaB pathway without involvement of de novo protein synthesis in rat astrocytes.