Effective dose of intranasal remimazolam for preoperative sedation in preschool children: a dose-finding study using Dixon's up-and-down method.

Background: Most preschool children are distressed during anesthesia induction. While current pharmacological methods are useful, there is a need for further optimization to an "ideal" standard. Remimazolam is an ultra-short-acting benzodiazepine, and intranasal remimazolam for pre-induction sedation may be promising. Methods: This study included 32 preschool children who underwent short and minor surgery between October 2022 and January 2023. After pretreatment with lidocaine, remimazolam was administered to both nostrils using a mucosal atomizer device. The University of Michigan Sedation Score (UMSS) was assessed for sedation 6, 9, 12, 15, and 20 min after intranasal atomization. We used Dixon's up-and-down method, and probit and isotonic regressions to determine the 50% effective dose (ED50) and 95% effective dose (ED95) of intranasal remimazolam for pre-induction sedation. Results: Twenty-nine pediatric patients were included in the final analysis. The ED50 and ED95 of intranasal remimazolam for successful pre-induction sedation, when processed via probit analysis, were 0.65 (95% confidence interval [CI], 0.59-0.71) and 0.78 mg/kg (95% CI, 0.72-1.07), respectively. In contrast, when processed by isotonic regression, they were 0.65 (95% CI: 0.58-0.72 mg/kg) and 0.78 mg/kg (95% CI: 0.69-1.08 mg/kg), respectively. At 6 min after intranasal remimazolam treatment, 81.2% (13/16) of "positive" participants were successfully sedated with a UMSS ≧ 1. All the "positive" participants were successfully sedated within 9 min. Conclusion: Intranasal remimazolam is feasible for preschool children with a short onset time. For successful pre-induction sedation, the ED50 and ED95 of intranasal remimazolam were 0.65 and 0.78 mg/kg, respectively.

A prediction model of elderly hip fracture mortality including preoperative red cell distribution width constructed based on the random survival forest (RSF) and Cox risk ratio regression.

An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients. With further research, a treatment algorithm can be developed to potentially identify patients at high risk of preoperative mortality. INTRODUCTION: Red blood cell distribution width (RDW) is an independent predictor of various disease states in elderly individuals, but its association with the prognosis of elderly hip fracture patients is controversial. This study aimed to evaluate the prognostic value of RDW in such patients, construct a prediction model containing RDW using random survival forest (RSF) and Cox regression analysis, and compare RDW in patients with and without anemia. METHODS: We retrospectively analyzed the data of elderly patients who underwent hip fracture surgery, selected the best variables using RSF, stratified the independent variables by Cox regression analysis, constructed a 1-year mortality prediction model of elderly hip fracture with RDW, and conducted internal validation and external validation. RESULTS: Two thousand one hundred six patients were included in this study. The RSF algorithm selects 12 important influencing factors, and Cox regression analysis showed that eight variables including preoperative RDW (pre-RDW) were independent risk factors for death within 1-year after hip fracture surgery in elderly patients. Stratified analysis showed that pre-RDW was still independently associated with 1-year mortality in the non-anemia group and not in the anemia group. The nomogram prediction model had high differentiation and fit, and the prediction model constructed by the total cohort of patients was also used for validation of patients in the anemia patients and obtained good clinical benefits. CONCLUSION: An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients.

Emerging Role for Exosomes in the Progress of Stem Cell Research.

Exosomes are small secretory vesicles that are involved in intercellular communication. Exosomes are secreted by many types of cells and exert important functions in plasma-membrane exchange as well as the transport of bioactive substances, such as proteins, messenger ribonucleic acids (mRNAs), micro ribonucleic acids (miRNAs) and organelles. Exosomes may regulate physiological processes by altering gene regulatory networks or epigenetic recombination. Recent studies have shown that exosomes secreted by stem cells can effectively transport proteins, mRNAs and miRNAs and play important roles in the regulation of tissue regeneration. This report reviews current progress in exosome studies as well as their emerging roles in stem cell research and potential clinical use.

Bezold-Jarisch reflex occurred in a pediatric patient with giant intra-abdominal teratoma during induction of anesthesia: A case report.

RATIONALE: Bezold-Jarisch reflex (BJR) occurs when the cardioinhibitory receptors in the walls of ventricles are activated by various stimuli, with typical features of bradycardia, vasorelaxation, and hypotension. This reflex usually happens in parturient intrathecal anesthesia, as a result of decreased venous return by compression of inferior vena cava, but it is only rarely reported during general anesthesia. PATIENT CONCERNS: Severe bradycardia and hypotension, indicating BJR, occurred during the induction of general anesthesia in a 3-month-old female child with giant intra-abdominal teratoma. DIAGNOSES: A giant intra-abdominal teratoma was detected by computed tomography scanning. The decreased left ventricular ejection faction along with increased troponin I and N-terminal pro-B-type natriuretic peptide indicated a preoperative mild cardiac dysfunction. BJR was diagnosed on the basis of the severe bradycardia and hypotension observed during the induction of general anesthesia, INTERVENTIONS:: Atropine failed to increase heart rate. Cardiopulmonary resuscitation was initiated immediately and epinephrine was injected intravenously because of sudden circulatory collapse. Soon after the return of spontaneous circulation, a central venous line was placed and invasive blood pressure was monitored. Vital signs and homeostasis were kept stable during teratoma resection. OUTCOMES: The child was extubated after emergence from anesthesia in the operating room. Eleven days later, she had recovered without complications and was discharged. LESSONS: General anesthesia should be induced with great care in patients with giant intra-abdominal masses, and the patient should be kept in the left-lateral table tilt position before induction.

Anatomic variations of neck vessels and the course of pediatric internal jugular veins.

BACKGROUND: Landmark-guided internal jugular vein cannulation is difficult for pediatric patients but useful, especially when ultrasound equipment is unavailable. Therefore, it is important to define the adjacent anatomic characteristics of the pediatric internal jugular vein. METHODS: In 210 children the course of the internal jugular vein, and common carotid and vertebral arteries was measured from the level of the cricoid cartilage to the supraclavicular area using ultrasound. RESULTS: From the level of the cricoid cartilage to the supraclavicular area, vessel diameter increased with internal jugular vein increasing by 12%, and common carotid and vertebral arteries increasing by 5% each. From the level of the cricoid cartilage to the supraclavicular area, the number of patients with a medial common carotid artery position relative to the internal jugular vein increased, whereas those with a lateral position decreased; the number of patients with nonoverlapped common carotid artery-internal jugular vein increased, and those with totally overlapped decreased. In contrast, the overlapping status of vertebral artery-internal jugular vein changes oppositely. More than 97.14% of the vertebral artery lies lateral to the internal jugular vein at these levels. The minimal vertebral artery-internal jugular vein depth decreased from 0.46±0.20 to 0.37±0.19 cm. The angle from the internal jugular vein line to the horizontal line of the body was 83.35±9.04 degrees. CONCLUSION: The common carotid artery and internal jugular vein are farther apart as one moves down the neck, whereas the vertebral artery and internal jugular vein are getting together. Additionally, the diameter of the internal jugular vein increased.

Alterations of gene profiles in Leydig-cell-regenerating adult rat testis after ethane dimethane sulfonate-treatment.

Only occupying about 1%-5% of total testicular cells, the adult Leydig cell (ALC) is a unique endocrine cell that produces androgens. Rat Leydig cells regenerate after these cells in the testis are eliminated with ethane dimethane sulfonate (EDS). In this study, we have characterized Leydig cell regeneration and messenger ribonucleic acids (mRNA) profiles of EDS treated rat testes. Serum testosterone, testicular gene profiling and some steroidogenesis-related proteins were analyzed at 7, 21, 35 and 90 days after EDS treatment. Testicular testosterone levels declined to undetectable levels until 7 days after treatment and then started to recover. Seven days after treatment, 81 mRNAs were down-regulated greater than or equal to two-fold, with 48 becoming undetectable. These genes increased their expression 21 days and completely returned to normal levels 90 days after treatment. The undetectable genes include steroidogenic pathway proteins: steroidogenic acute regulatory protein, Scarb1, Cyp11a1, Cyp17a1, Hsd3b1, Cyp1b1 and Cyp2a1. Seven days after treatment, there were 89 mRNAs up-regulated two-fold or more including Pkib. These up-regulated mRNAs returned to normal 90 days after treatment. Cyp2a1 did not start to recover until 35 days after treatment, indicating that this gene is only expressed in ALCs not in the precursor cells. Quantitative polymerase chain reaction, western blotting and semi-quantitative immunohistochemical staining using tissue array confirmed the changes of several randomly picked genes and their proteins.

Time-course changes of steroidogenic gene expression and steroidogenesis of rat Leydig cells after acute immobilization stress.

Leydig cells secrete testosterone, which is essential for male fertility and reproductive health. Stress increases the secretion of glucocorticoid (corticosterone, CORT; in rats), which decreases circulating testosterone levels in part through a direct action by binding to the glucocorticoid receptors (NR3C1) in Leydig cells. The intratesticular CORT level is dependent on oxidative inactivation of glucocorticoid by 11ß-hydroxysteroid dehydrogenase 1 (HSD11B1) in Leydig cells. In the present study, we investigated the time-course changes of steroidogenic gene expression levels after acute immobilization stress in rats. The plasma CORT levels were significantly increased 0.5, 1, 3 and 6 h after immobilization stress, while plasma testosterone levels were significantly reduced 3 and 6 h, after stress and luteinizing hormone (LH) did not change. Immobilization stress caused the down-regulation of Scarb1, Star and Cyp17a1 expression levels in the rat testis starting at the first hour of stress, ahead of the significant decreases of plasma testosterone levels. Other mRNA levels, including Cyp11a1, Hsd3b1 and Hsd17b3, began to decline after 3 h. Hsd11b1 and Nos2 mRNA levels did not change during the course of stress. Administration of glucocorticoid antagonist RU486 significantly restored plasma testosterone levels. In conclusion, Scarb1, Star and Cyp17a1 expression levels are more sensitive to acute stress, and acute immobilization stress causes the decline of the steroidogenic pathway via elevating the levels of glucocorticoid, which binds to NR3C1 in Leydig cells to inhibit steroidogenic gene expression.