Oxygen reserve index versus conventional peripheral oxygen saturation for prevention of hypoxaemia: A randomised controlled trial.

BACKGROUND: Hypoxaemia occurs frequently during paediatric laryngeal microsurgery. OBJECTIVE: The oxygen reserve index is a noninvasive and continuous parameter to assess PaO2 levels in the range of 100 to 200 mmHg. It ranges from 0 to 1.0. We investigated whether monitoring the oxygen reserve index can reduce the incidence of SpO2 90% or less. DESIGN: Randomised controlled trial. SETTING: A tertiary care paediatric hospital. PARTICIPANTS: Paediatric patients aged 18 years or less scheduled to undergo laryngeal microsurgery. INTERVENTION: The patients were randomly allocated to the oxygen reserve index or control groups, and stratified based on the presence of a tracheostomy tube. Rescue intervention was performed when the oxygen reserve index was 0.2 or less and the SpO2 was 94% or less in the oxygen reserve index and control groups, respectively. MAIN OUTCOME MEASURE: The primary outcome was the incidence of SpO2 90% or less during the surgery. RESULTS: Data from 88 patients were analysed. The incidence of SpO2 ≤ 90% did not differ between the oxygen reserve index and control groups [P = 0.114; 11/44, 25% vs. 18/44, 40.9%; relative risk: 1.27; and 95% confidence interval (CI): 0.94 to 1.72]. Among the 128 rescue interventions, SpO2 ≤ 90% event developed in 18 out of 75 events (24%) and 42 out of 53 events (79.2%) in the oxygen reserve index and control groups, respectively (P < 0.001; difference: 55.2%; and 95% CI 38.5 to 67.2%). The number of SpO2 ≤ 90% events per patient in the oxygen reserve index group (median 0, maximum 3) was less than that in the control group (median 0, maximum 8, P = 0.031). CONCLUSION: Additional monitoring of the oxygen reserve index, with a target value of greater than 0.2 during paediatric airway surgery, alongside peripheral oxygen saturation, did not reduce the incidence of SpO2 ≤ 90%.

Risk factors for chloral hydrate sedation failure in pediatric patients: a retrospective analysis.

Background: This study aimed to investigate the risk factors for chloral hydrate sedation failure and complications in a tertiary children's hospital in South Korea. Methods: A retrospective analysis of pediatric procedural sedation with chloral hydrate between January 1, 2021, and March 30, 2022, was performed. The collected data included patient characteristics, sedation history, and procedure. Multivariable regression analysis was performed to identify the risk factors for procedural sedation failure and complications. Results: A total of 6691 procedural sedation were included in the analysis; sedation failure following chloral hydrate (50 mg/kg) occurred in 1457 patients (21.8%) and was associated with a higher rate of overall complications compared to those with successful sedation (17.5% [225 / 1457] vs. 6.2% [322 / 5234]; P < 0.001; odds ratio, 3.236). In the multivariable regression analysis, the following factors were associated with increased risk of sedation failure: general ward or intensive care unit inpatient (compared with outpatient); congenital syndrome; oxygen dependency; history of sedation failure or complications with chloral hydrate; procedure more than 60 min; and magnetic resonance imaging, radiotherapy, or procedures with painful or intense stimuli (all P values < 0.05). Factors contributing to the complications included general ward inpatient, congenital syndromes, congenital heart disease, preterm birth, oxygen dependency, history of complications with chloral hydrate, and current sedation failure with chloral hydrate (all P values < 0.05). Conclusions: To achieve successful sedation with chloral hydrate, the patient's sedation history, risk factors, and the type and duration of the procedure should be considered.

Effect of positive end expiratory pressure on non-hypoxic apnea time and atelectasis during induction of anesthesia in infant: A randomized controlled trial.

INTRODUCTION: This study aimed to assess the impact of positive-end-expiratory pressure (PEEP) on the non-hypoxic apnea time in infants during anesthesia induction with an inspired oxygen fraction of 0.8. METHODS: This age stratified randomized controlled trial included patients under 1 year of age. Preoxygenation was performed using an inspired oxygen fraction of 0.8 for 2 min. Inspired oxygen fraction of 0.8 was administered via a face mask with volume-controlled ventilation at a tidal volume of 6 mL.kg-1, with or without 7 cmH2O of PEEP. Tracheal intubation was performed after 3 min of ventilation; however, it was disconnected from the breathing circuit. Ventilation was resumed once the pulse oximetry readings reached 95%. The primary outcome was the non-hypoxic apnea time, defined as the time from the cessation of ventilation to achieving a pulse oximeter reading of 95%. The secondary outcome measures included the degree of atelectasis assessed by ultrasonography and the presence of gastric air insufflation. RESULTS: Eighty-four patients were included in the final analysis. In the positive end-expiratory pressure group, the atelectasis score decreased (17.0 vs. 31.5, p < .001; mean difference and 95% CI of 11.6, 7.5-15.6), while the non-hypoxic apnea time increased (80.1 s vs. 70.6 s, p = .005; mean difference and 95% CI of -9.4, -16.0 to -2.9), compared to the zero end-expiratory pressure group, among infants who are 6 months old or younger, not in those aged older than 6 months. DISCUSSION: The application of positive end-expiratory pressure reduced the incidence of atelectasis and extended the non-hypoxic apnea time in infants who are 6 months old or younger. However, it did not affect the incidence of atelectasis nor the non-hypoxic apnea time in patients aged older than 6 months.

Toxicological Evaluation Verifies the Safety of Oral Administration of Steamed Mature Silkworm Powder in Rats.

Globally, the edible insect industry is emerging due to its potential contributions to food security and environmental sustainability. Edible insects are rapidly being integrated into the development of alternative foods and new pharmaceuticals. Silkworms, known for their high protein content, are not only a potential new source of human food and animal feed but have also been traditionally used for medicinal purposes. However, conventional silkworms are difficult to ingest. To address this, we have developed a steamed and freeze-dried mature silkworm larva powder (SMSP), and it is essential to investigate its potential toxicity and food safety for further studies and applications. Therefore, this study aimed to evaluate the toxicity of SMSP. A toxicity assessment of SMSP was conducted according to OECD guidelines. An oral repeat-administration study was performed on male and female SD rats at doses of 625, 1250, and 2500 mg/kg/day for 4 and 13 weeks. No toxicological changes were observed in clinical signs, body weight, water and food intake, urine tests, hematology, clinical biochemistry, gross findings, or histopathological examination. In conclusion, the no observed adverse effect level (NOAEL) of SMSP was 2500 mg/kg/day, with no target organs identified in either sex of the rats. These results suggest that SMSP is safe, is without side effects and has potential for use as an edible ingredient and in health functional food applications.

Mechanism of Methylene Blue Inducing the Disulfide Bond Formation of Tubulin-Associated Unit Proteins.

Methylene blue (MB) has recently completed a Phase-3 clinical trial as leuco-methylthioninium (LMT) bis(hydromethanesulfonate) for treating Alzheimer's disease. Herein, we investigated the mechanism underlying the MB inhibition of tubulin-associated unit (tau) aggregation by focusing on tau monomers. We found that MB causes disulfide bond formation, resulting in strong nuclear magnetic resonance chemical shift perturbations in a large area of tau proteins. The oxidized form of MB, namely methylthioninium (MT+), specifically catalyzed the oxidation of cysteine residues in tau proteins to form disulfide bonds directly using O2. This process is independent of the MT+-to-LMT redox cycle. Moreover, MT+ preferentially oxidized C291 and C322 in the lysine-rich R2 and R3 domains. Under in vivo brain physoxia conditions, LMT may convert to MT+, possibly interfering with tau fibrillation via disulfide bond formation.

Association between metabolic dysfunction-associated steatotic liver disease and myosteatosis measured by computed tomography.

BACKGROUND: In 2023, the concept of metabolic dysfunction-associated steatotic liver disease (MASLD) was introduced as an alternative to non-alcoholic fatty liver disease (NAFLD). We aimed to assess the quantity and quality of skeletal muscle using each of these diagnostic classifications. METHODS: This cross-sectional study included 18 154 participants (11 551 [63.6%] men and 6603 [36.4%] women, mean age 53.0 ± 8.8). The participants were classified into four categories: neither steatotic liver disease (SLD), NAFLD only, MASLD only or both SLDs. An appendicular skeletal muscle mass adjusted for body mass index of <0.789 for men and <0.512 for women was defined as sarcopenia. The total abdominal muscle area (TAMA) at the L3 vertebral level was segmented into normal-attenuation muscle area (NAMA), low-attenuation muscle area and intermuscular/intramuscular adipose tissue. Myosteatosis was defined by a T-score < -1.0 of the NAMA/TAMA index, which was calculated by dividing the NAMA by the TAMA and multiplying by 100. RESULTS: Using subjects with neither SLD as a reference, the multivariable-adjusted odds ratios (ORs) for sarcopenia were significantly increased in those with MASLD, with adjusted ORs (95% confidence interval [CI]) of 2.62 (1.94-3.54) in the MASLD-only group and 2.33 (1.92-2.82) in the both SLDs group, while the association was insignificant in those with NAFLD only (adjusted OR [95% CI]: 2.16 [0.67-6.94]). The OR for myosteatosis was also elevated in the MASLD groups, with an OR (95% CI) of 1.75 (1.52-2.02) in subjects with MASLD only and 1.70 (1.57-1.84) in those with both SLDs, while it was slightly decreased in subjects with NAFLD only (0.52 [0.29-0.95]). CONCLUSIONS: Employing the MASLD concept rather than that of the NAFLD proved to be more effective in distinguishing individuals with reduced muscle mass and compromised muscle quality.

Dissemination of pathogenic bacteria is reinforced by a MARTX toxin effector duet.

Multiple bacterial genera take advantage of the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin to invade host cells. Secretion of the MARTX toxin by Vibrio vulnificus, a deadly opportunistic pathogen that causes primary septicemia, the precursor of sepsis, is a major driver of infection; however, the molecular mechanism via which the toxin contributes to septicemia remains unclear. Here, we report the crystal and cryo-electron microscopy (EM) structures of a toxin effector duet comprising the domain of unknown function in the first position (DUF1)/Rho inactivation domain (RID) complexed with human targets. These structures reveal how the duet is used by bacteria as a potent weapon. The data show that DUF1 acts as a RID-dependent transforming NADase domain (RDTND) that disrupts NAD+ homeostasis by hijacking calmodulin. The cryo-EM structure of the RDTND-RID duet complexed with calmodulin and Rac1, together with immunological analyses in vitro and in mice, provide mechanistic insight into how V. vulnificus uses the duet to suppress ROS generation by depleting NAD(P)+ and modifying Rac1 in a mutually-reinforcing manner that ultimately paralyzes first line immune responses, promotes dissemination of invaders, and induces sepsis. These data may allow development of tools or strategies to combat MARTX toxin-related human diseases.

Terfenadine, a histamine H1 receptor antagonist, induces apoptosis by suppressing STAT3 signaling in human colorectal cancer HCT116 cells.

Introduction: Colorectal cancer is a highly aggressive and metastatic cancer with inadequate clinical outcomes. Given the crucial role of histamine and histamine receptors in colorectal carcinogenesis, this study aimed at exploring the anticancer effects of terfenadine against colorectal cancer HCT116 cells and elucidate its underlying mechanism. Methods: Herein, we examined the effect of terfenadine on growth and proliferation of HCT116 cells in vitro and in vivo. Various experimental techniques such as flow cytometry, western blot, immunoprecipitation, luciferase assay were employed to unveil the mechanism of cell death triggered by terfenadine. Results: Terfenadine markedly attenuated the viability of HCT116 cells by abrogating histamine H1 receptor (H1R) signaling. In addition, terfenadine modulated the balance of Bax and Bcl-2, triggering cytochrome c discharge in the cytoplasm, thereby stimulating the caspase cascade and poly-(ADP-ribose) polymerase (PARP) degradation. Moreover, terfenadine suppressed murine double minute-2 (Mdm2) expression, whereas p53 expression increased. Terfenadine suppressed STAT3 phosphorylation and expression of its gene products by inhibiting MEK/ERK and JAK2 activation in HCT116 cells. Furthermore, treatment with U0126, a MEK inhibitor, and AG490, a JAK2 inhibitor, dramatically diminished the phosphorylations of ERK1/2 and JAK2, respectively, leading to STAT3 downregulation. Likewise, terfenadine diminished the complex formation of MEK1/2 with ß-arrestin 2. In addition, terfenadine dwindled the phosphorylation of PKC substrates. Terfenadine administration (10 mg/kg) substantially retarded the growth of HCT116 tumor xenografts in vivo. Conclusion: Terfenadine induces the apoptosis of HCT116 cells by abrogating STAT3 signaling. Overall, this study supports terfenadine as a prominent anticancer therapy for colorectal cancer.

Machine Learning-Based Etiologic Subtyping of Ischemic Stroke Using Circulating Exosomal microRNAs.

Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study explored the utility of circulating microRNAs encapsulated in extracellular vesicles (EV-miRNAs) to distinguish the following ischemic stroke subtypes: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and small artery occlusion (SAO). Using next-generation sequencing (NGS) and machine-learning techniques, we identified differentially expressed miRNAs (DEMs) associated with each subtype. Through patient selection and diagnostic evaluation, a cohort of 70 patients with acute ischemic stroke was classified: 24 in the LAA group, 24 in the SAO group, and 22 in the CES group. Our findings revealed distinct EV-miRNA profiles among the groups, suggesting their potential as diagnostic markers. Machine-learning models, particularly logistic regression models, exhibited a high diagnostic accuracy of 92% for subtype discrimination. The collective influence of multiple miRNAs was more crucial than that of individual miRNAs. Additionally, bioinformatics analyses have elucidated the functional implications of DEMs in stroke pathophysiology, offering insights into the underlying mechanisms. Despite limitations like sample size constraints and retrospective design, our study underscores the promise of EV-miRNAs coupled with machine learning for ischemic stroke subtype classification. Further investigations are warranted to validate the clinical utility of the identified EV-miRNA biomarkers in stroke patients.

Atmospheric particulate matter and hypoxaemia in Korean children receiving general anaesthesia: A retrospective analysis.

BACKGROUND: The association between the concentration of atmospheric particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia in children receiving general anaesthesia is unclear. OBJECTIVE: To investigate the association between the exposure to particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% for more than 1 min, in children. DESIGN: Retrospective study. SETTING: Single-centre. PARTICIPANTS: Children aged 18 years or younger who received general anaesthesia between January 2019 and October 2020. INTERVENTION: Information on daily levels of particulate matter with a diameter 10 µm or less and 2.5 µm or less measured within a neighbourhood corresponding to the area defined by the hospital's zip code was obtained from publicly available air-quality data. MAIN OUTCOME MEASURES: The primary outcome was intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% lasting for more than 1 min, manually verified by anaesthesiologists using vital sign registry data extracted at 2 s intervals. RESULTS: Of the patients finally analysed, 3.85% (489/13 175) experienced intra-operative hypoxaemia. Higher levels of particulate matter 10 µm or less in diameter (≥81 µg m -3 , 17/275, 6.2%) were associated with an increased occurrence of intra-operative hypoxaemia compared with lower particulate matter concentrations [<81 µg m -3 , 472/12 900, 3.7%; adjusted odds ratio, 1.71; 95% confidence interval (CI), 1.04 to 2.83; P  = 0.035]. CONCLUSION: The level of particulate matter on the day of surgery pose a risk of intra-operative hypoxaemia in children receiving general anaesthesia. If the concentrations of particulate matter 10 µm or less in diameter on the day of surgery are high, children receiving general anaesthesia should be managed with increased caution.

Effects of goal-directed analgesia using the analgesia nociception index in children undergoing surgery for moyamoya disease: A randomised controlled trial.

BACKGROUND: The potential benefits of Analgesia Nociception Index guided intra-operative analgesia on intra-operative opioid consumption remains to be demonstrated in paediatric anaesthesia. OBJECTIVES: This study aimed to explore the effects of Analgesia Nociception Index guided analgesia on sufentanil consumption during anaesthesia and postoperative pain scores in paediatric patients with moyamoya disease. DESIGN: A prospective randomised controlled study. SETTING: Seoul National University Children's Hospital, Seoul, Republic of Korea. PATIENTS: A total of 40 children scheduled for encephaloduroarteriosynangiosis. MAIN OUTCOME MEASURES: The primary outcome was total intra-operative sufentanil consumption, and the secondary outcomes included postoperative pain scores and incidence of opioid-related adverse events. RESULTS: The Analgesia Nociception Index group showed lower intra-operative sufentanil consumption (in µg kg -1  h -1 ) compared with the Standard group (0.30 ±â€Š0.12 and 0.39 ±â€Š0.17, respectively; mean difference, -0.09; 95% confidence interval, -0.19 to 0.00; P  = 0.049). Postoperatively, compared with the Standard group, the Analgesia Nociception Index group reported lower median pain scores at 18 and 24 h and maximum pain within 24 h (1 [0 to 2] vs. 3 [2 to 5]; P  = 0.004, 1 [0 to 2] vs. 3 [1 to 4]; P  = 0.041, and 4 [3 to 5] vs. 5 [4 to 7]; P  = 0.045, respectively), with fewer patients experiencing nausea (3 [15%] vs. 10 [50%], P  = 0.043). CONCLUSION: The Analgesia Nociception Index guided analgesic protocol can reduce intra-operative sufentanil consumption and postoperative pain within 24 h with fewer nausea symptoms in paediatric patients with moyamoya disease who undergo encephaloduroarteriosynangiosis. TRIAL REGISTRATION NUMBER: NCT05672212.

Determination of optimal positive end-expiratory pressure using electrical impedance tomography in infants under general anesthesia: Comparison between supine and prone positions.

AIMS: This study determined the optimal positive end-expiratory pressure levels in infants in supine and prone positions under general anesthesia using electrical impedance tomography (EIT). METHODS: This prospective observational single-centre study included infants scheduled for surgery in the prone position. An electrical impedance tomography sensor was applied after inducing general anesthesia. The optimal positive end-expiratory pressure in the supine position was determined in a decremental trial based on EIT and compliance. Subsequently, the patient's position was changed to prone. Electrical impedance tomography parameters, including global inhomogeneity index, regional ventilation delay, opening pressure, the centre of ventilation, and pendelluft volume, were continuously obtained up to 1 h after prone positioning. The optimal positive end-expiratory pressure in the prone position was similarly determined. RESULTS: Data from 30 infants were analyzed. The mean value of electrical impedance tomography-based optimal positive end-expiratory pressure in the prone position was significantly higher than that in the supine position [10.9 (1.6) cmH2O and 6.1 (0.9) cmH2O, respectively (p < .001)]. Significant differences were observed between electrical impedance tomography- and compliance-based optimal positive end-expiratory pressure. Peak and mean airway, plateau, and driving pressures increased 1 h after prone positioning compared with those in the supine position. In addition, the centre of ventilation for balance in ventilation between the ventral and dorsal regions improved. CONCLUSION: The prone position required higher positive end-expiratory pressure than the supine position in mechanically ventilated infants under general anesthesia. EIT is a promising tool to find the optimal positive end-expiratory pressure, which needs to be individualized.

Targeting cyclooxygenase-2 for chemoprevention of inflammation-associated intestinal carcinogenesis: An update.

Mounting evidence from preclinical and clinical studies suggests that persistent inflammation functions as a driving force in the journey to cancer. Cyclooxygenase-2 (COX-2) is a key enzyme involved in inflammatory signaling. While being transiently upregulated upon inflammatory stimuli, COX-2 has been found to be consistently overexpressed in human colorectal cancer and several other malignancies. The association between chronic inflammation and cancer has been revisited: cancer can arise when inflammation fails to resolve. Besides its proinflammatory functions, COX-2 also catalyzes the production of pro-resolving as well as anti-inflammatory metabolites from polyunsaturated fatty acids. This may account for the side effects caused by long term use of some COX-2 inhibitory drugs during the cancer chemopreventive trials. This review summarizes the latest findings highlighting the dual functions of COX-2 in the context of its implications in the development, maintenance, and progression of cancer.

Genomic and Metabolomic Analyses of Nocardiopsis maritima YSL2 as the Mycorrhizosphere Bacterium of Suaeda maritima (L.) Dumort.

Nine bacteria were isolated from the episphere of Suaeda maritima (L.) Dumort. Among them, the bacterial strain YSL2 displayed the highest antimicrobial activity on agar plates and exhibited significant novelty compared with other bacteria based on 16S rRNA analysis. Consequently, Nocardiopsis maritima YSL2T was subjected to phenotypic characterization and whole-genome sequencing. Phylogenetic analysis revealed its close association with Nocardiopsis aegyptia SNG49T. Furthermore, genomic analysis of strain YSL2T revealed the presence of various gene clusters, indicating its potential for producing antimicrobial secondary metabolites. Upon cultivation on a large scale, maritiamides A and B (1 and 2) were isolated and characterized as cyclic hexapeptides based on nuclear magnetic resonance, ultraviolet, infrared, and mass spectrometric data. The absolute configurations of the amino acid residues in the maritiamides were determined through chiral derivatization, utilizing FDAA and GITC. Maritiamides 1 and 2 exhibited promising antibacterial activities against Staphylococcus epidermidis and weakly inhibited the growth of Escherichia coli and Pseudomonas fluorescens.

Effectiveness of head-mounted ultrasound display for radial arterial catheterisation in paediatric patients by anaesthesiology trainees: A randomised clinical trial.

BACKGROUND: The effectiveness of head mounted real-time ultrasound displays (hereafter referred to as 'smart glasses') in improving hand-eye coordination in less experienced individuals, such as trainees in anaesthesia, is unclear. OBJECTIVES: To compare the first-attempt success rate of smart glasses-assisted ultrasound-guided paediatric radial artery catheterisation with conventional ultrasound guided catheterisation performed by anaesthesiology trainees. DESIGN: Prospective randomised controlled trial. SETTINGS: Tertiary university hospital from September 2021 to February 2023. PATIENTS: One hundred and twenty-two paediatric patients (age <7 years, weight ≥3 kg) who required radial artery cannulation during general anaesthesia. INTERVENTIONS: The participants were randomly assigned to either the ultrasound screen group (control) or the smart glasses group prior to radial artery catheterisation. MAIN OUTCOME MEASURES: The primary outcome was the first attempt success rate. Secondary outcomes included the number of attempts, use of transfixion technique, overall complication rate, and clinical anaesthesiology (CA) year of the operators. RESULTS: A total of 119 paediatric patients were included in the analysis. The smart glasses group exhibited higher first-attempt success rate than did the control group (89.8% [53/59] vs. 71.7% [43/60]; P  = 0.023; odds ratio (OR) 3.49; (95% confidence interval (CI) 1.27-9.6). The overall number of attempts [median, 1; interquartile range (IQR), 1-1; range, 1-3 vs. median, 1; IQR, 1-2; range, 1-4; P   =  0.006], use of transfixion technique (12/59 [20.3%] vs. 28/60 [46.7%]; P  = 0.002), and overall complication rate (6.8% [4/59] vs. 30.0% [18/60]; P  = 0.002) were lower in the smart glasses group than in the control group. However, among paediatric anaesthesiology fellows (CA 5 years), the first- (89.3% [25/28] vs. 80.8% [21/26]; P  = 0.619) and second-attempt success rates (96.4% [27/28] vs. 80.8% [21/26]; P  = 0.163) did not differ between the two groups. CONCLUSIONS: Smart glasses-assisted ultrasound guided radial artery catheterisation improved the first attempt success rate among anaesthesiology trainees, reducing the number of attempts and overall complication rates in small paediatric patients. Smart glasses were more effective for anaesthesia residents (CA 2-4 years) but were not effective for paediatric anaesthesiology fellows (CA 5 years). TRIAL REGISTRATION: ClinicalTrials.gov (NCT05030649) ( https://classic.clinicaltrials.gov/ct2/show/NCT05030649 ).

Isolation of New Diterpenoids from the Halophyte, Vitex rotundifolia, and their Antioxidant and Anti-inflammatory Activities.

In this study, three diterpenoids (1-3), including one known compound (1), were isolated from the fruits of Vitex rotundifolia and their structures were determined via spectroscopic analysis. In lipopolysaccharide-stimulated RAW264.7 cells, these compounds dose-dependently decreased the intracellular reactive oxygen species levels and nitric oxide production compared to those in the control cells. At 25 µM/mL, these compounds also diminished the protein expression of the pro-inflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-6, with compound 3 exhibiting the most potent inhibitory effect.

Lyoprotectant Constituents Suited for Lyophilization and Reconstitution of Stem-Cell-Derived Extracellular Vesicles.

Stem-cell-derived extracellular vesicles (EVs) are emerging as an alternative approach to stem cell therapy. Successful lyophilization of EVs could enable convenient storage and distribution of EV medicinal products at room temperature for long periods, thus considerably increasing the accessibility of EV therapeutics to patients. In this study, we aimed to identify an appropriate lyoprotectant composition for the lyophilization and reconstitution of stem-cell-derived EVs. MSC-derived EVs were lyophilized using different lyoprotectants, such as dimethyl sulfoxide, mannitol, trehalose, and sucrose, at varying concentrations. Our results revealed that a mixture of trehalose and sucrose at high concentrations could support the formation of amorphous ice by enriching the amorphous phase of the solution, which successfully inhibited the acceleration of buffer component crystallization during lyophilization. Lyophilized and reconstituted EVs were thoroughly evaluated for concentration and size, morphology, and protein and RNA content. The therapeutic effects of the reconstituted EVs were examined using a tube formation assay with human umbilical vein endothelial cells. After rehydration of the lyophilized EVs, most of their generic characteristics were well-maintained, and their therapeutic capacity recovered to levels similar to those of freshly collected EVs. The concentrations and morphologies of the lyophilized EVs were similar to the initial features of the fresh EV group until day 30 at room temperature, although their therapeutic capacity appeared to decrease after 7 days. Our study suggests an appropriate composition of lyoprotectants, particularly for EV lyophilization, which could encourage the applications of stem-cell-derived EV therapeutics in the health industry.

Ultrasound-guided selective supraclavicular nerve block for postoperative pain control in children receiving Hickman catheter or chemoport insertion: A randomized controlled trial.

BACKGROUND: Optimal pain management after insertion of a central venous catheter in children remains unclear. AIM: This study aimed to evaluate the effects of a selective supraclavicular nerve block on postoperative analgesia in pediatric patients undergoing hickman catheter or chemoport insertion. METHODS: Fifty patients aged 3-18 years scheduled for elective Hickman or chemoport insertion were randomized into two groups of 25 each: one group received an ultrasound-guided selective supraclavicular nerve block with 0.1 mL/kg of 0.5% ropivacaine (SSCNB group), and the other group did not receive a nerve block (control group). The primary outcome was the postoperative Wong-Baker Faces Pain Rating Scale score measured between 10 and 30 min after surgery. Secondary outcomes included pain scores at 1, 3, and 24 h after the surgery, block-related complications, length of stay in the postanesthesia care unit, postoperative analgesic consumption, and time to first analgesic use 24 h after surgery. RESULTS: The worst pain score within 30 min in the recovery room was significantly lower in the SSCNB group compared to the control group (6 [5-7] vs. 3 [2-4]; median difference, -3; 95% CI, -4 to -1; p < .001). Pain scores at 1, 3, and 24 h after surgery were also significantly lower in the SSCNB group. The need for both opioid and non-opioid analgesics in the postoperative period was significantly lower in the SSCNB group (36.0% vs. 0%; p = .002 and 44.0% vs. 16.0%; mean difference, -28%; 95% CI, -56 to 0.19; p = .033, respectively), while other secondary outcomes were not significantly different between the two groups. CONCLUSIONS: Ultrasound-guided SSCNB is an effective method for managing postoperative pain in children undergoing Hickman catheter or chemoport insertion, reducing the need for analgesics within 24 h after surgery.

Perioperative Respiratory-Adverse Events Following General Anesthesia Among Pediatric Patients After COVID-19.

BACKGROUND: The perianesthetic morbidity, mortality risk and anesthesia-associated risk after preoperative coronavirus disease 2019 (COVID-19) omicron variant in pediatric patients have not been fully demonstrated. We examined the association between preoperative COVID-19 omicron diagnosis and the incidence of overall perioperative adverse events in pediatric patients who received general anesthesia. METHODS: This retrospective study included patients aged < 18 years who received general anesthesia between February 1 and June 10, 2022, in a single tertiary pediatric hospital. They were divided into two groups; patients in a COVID-19 group were matched to patients in a non-COVID-19 group during the omicron-predominant period in Korea. Data on patient characteristics, anesthesia records, post-anesthesia records, COVID-19-related history, symptoms, and mortality were collected. The primary outcomes were the overall perioperative adverse events, including perioperative respiratory adverse events (PRAEs), escalation of care, and mortality. RESULTS: In total, 992 patients were included in the data analysis (n = 496, COVID-19; n = 496, non-COVID-19) after matching. The overall incidence of perioperative adverse events was significantly higher in the COVID-19 group than in the non-COVID-19 group (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.89-1.94). The difference was significant for PRAEs (OR, 2.00; 95% CI, 1.96-2.02) but not in escalation of care or mortality. The most pronounced difference between the two groups was observed in instances of high peak inspiratory pressure ≥ 25 cmH2O during the intraoperative period (OR, 11.0; 95% CI, 10.5-11.4). Compared with the non-COVID-19 group, the risk of overall perioperative adverse events was higher in the COVID-19 group diagnosed 0-2 weeks before anesthesia (OR, 6.5; 95% CI, 2.1-20.4) or symptomatic on the anesthesia day (OR, 6.4; 95% CI, 3.30-12.4). CONCLUSION: Pediatric patients with the preoperative COVID-19 omicron variant had increased risk of PRAEs. Patients within 2 weeks after COVID-19 or those with symptoms had a higher risk of PRAEs.