Combined sedation in pediatric magnetic resonance imaging: determination of median effective dose of intranasal dexmedetomidine combined with oral midazolam.

BACKGROUND: The exact median effective dose (ED50) of intranasal dexmedetomidine combined with oral midazolam sedation for magnetic resonance imaging (MRI) examination in children remains unknow and the aim of this study was to determine the ED50 of their combination. METHODS: This is a prospective dose-finding study. A total of 53 children aged from 2 months to 6 years scheduled for MRI examination from February 2023 to April 2023 were randomly divided into group D (to determine the ED50 of intranasal dexmedetomidine) and group M (to determine the ED50 of oral midazolam). The dosage of dexmedetomidine and midazolam was adjusted according to the modified Dixon's up-and-down method, and the ED50 was calculated with a probit regression approach. RESULTS: The ED50 of intranasal dexmedetomidine when combined with 0.5 mg∙kg- 1 oral midazolam was 0.39 µg∙kg- 1 [95% confidence interval (CI) 0.30 to 0.46 µg∙kg- 1] while the ED50 of oral midazolam was 0.17 mg∙kg- 1 (95% CI 0.01 to 0.29 mg∙kg- 1) when combined with 1 µg∙kg- 1 intranasal dexmedetomidine. The sedation onset time of children with successful sedation in group D was longer than in group M (30.0[25.0, 38.0]vs 19.5[15.0, 35.0] min, P < 0.05). No other adverse effects were observed in the day and 24 h after medication except one dysphoria. CONCLUSION: This drug combination sedation regimen appears suitable for children scheduled for MRI examinations, offering a more precise approach to guide the clinical use of sedative drugs in children. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2300068611(24/02/2023).

Comparison of volume-controlled ventilation, pressure-controlled ventilation and pressure-controlled ventilation-volume guaranteed in infants and young children in the prone position: A prospective randomized study.

STUDY OBJECTIVE: To explore if the pressure-controlled ventilation (PCV) and pressure-controlled ventilation-volume guaranteed (PCV-VG) modes are superior to volume-controlled ventilation (VCV) in optimizing intraoperative respiratory mechanics in infants and young children in the prone position. DESIGN: A single-center prospective randomized study. SETTING: Children's Hospital, Zhejiang University School of Medicine. PATIENTS: Pediatric patients aged 1 month to 3 years undergoing elective spinal cord detethering surgery. INTERVENTIONS: Patients were randomly allocated to the VCV group, PCV group and PCV-VG group. The target tidal volume (VT) was 8 mL/kg and the respiratory rate (RR) was adjusted to maintain a constant end tidal CO2. MEASUREMENTS: The primary outcome was intraoperative peak airway pressure (Ppeak). Secondary outcomes included other respiratory and ventilation variables, gas exchange values, serum lung injury biomarkers concentration, hemodynamic parameters and postoperative respiratory complications. MAIN RESULTS: A total of 120 patients were included in the final analysis (40 in each group). The VCV group showed higher Ppeak at T2 (10 min after prone positioning) and T3 (30 min after prone positioning) than the PCV and PCV-VG groups (T2: P = 0.015 and P = 0.002, respectively; T3: P = 0.007 and P = 0.009, respectively). The prone-related decrease in dynamic compliance was prevented by PCV and PCV-VG ventilation modalities at T2 and T3 than by VCV (T2: P = 0.008 and P = 0.015, respectively; T3: P = 0.015 and P = 0.014, respectively). Additionally, there were no significant differences in other secondary outcomes among the three groups. CONCLUSION: In infants and young children undergoing spinal cord detethering surgery in the prone position, PCV-VG may be a better ventilation mode due to its ability to mitigate the increase in Ppeak and decrease in Cdyn while maintaining consistent VT.

NAA10 gene related Ogden syndrome with obstructive hypertrophic cardiomyopathy: A rare case report.

RATIONALE: Ogden syndrome is an exceptionally rare X-linked disease caused by mutations in the NAA10 gene. Reported cases of this syndrome are approximately 20 children and are associated with facial dysmorphism, growth delay, developmental disorders, congenital heart disease, and arrhythmia. PATIENT CONCERNS: We present the clinical profile of a 3-year-old girl with Ogden syndrome carrying a de novo NAA10 variant [NM_003491:c.247C>T, p.(Arg83Cys)]. During infancy, she exhibited features such as left ventricular hypertrophy, protruding eyeballs, and facial deformities. DIAGNOSIS: Clinical diagnosis included Ogden syndrome, congenital heart disease (obstructive hypertrophic cardiomyopathy, left ventricular outflow tract obstruction, mitral valve disease, tricuspid valve regurgitation), tonsillar and adenoidal hypertrophy, and speech and language delay. INTERVENTIONS: The girl was considered to have hypertrophic cardiomyopathy (HCM) and received oral metoprolol as a treatment for HCM at our hospital. The drug treatment effect was not ideal, and her hypertrophy myocardial symptoms were aggravated and she had to be hospitalized for surgery. OUTCOMES: The girl underwent a modified Morrow procedure under cardiopulmonary bypass and experienced a favorable postoperative recovery. No pulmonary infections or significant complications were observed during this period. The patient's family expressed satisfaction with the treatment process. LESSONS: The case emphasizes the HCM of Odgen syndrome, and early surgery should be performed if drug treatment is ineffective.

The effect of age on outpatient pediatric procedural sedation with intranasal dexmedetomidine and oral midazolam.

Procedural sedation for diagnostic examination is a common practice in children. The study aims to analyze the sedative effect and safety of intranasal dexmedetomidine combined with oral midazolam in outpatient pediatric procedural sedation across different age groups and to assess the incidence of sedation failure. From February 2021 to September 2021, children who underwent procedural sedation were retrospectively enrolled. The children were divided into 4 groups based on age: the infant group (0 to 1 year old), toddler group (1 to 3 years old), preschool group (3 to 6 years old), and school-age group (6 to 12 years old). Two-mcg/kg intranasal dexmedetomidine and 0.5-mg/kg oral midazolam were used for sedation. The sedation success rate after rescue, sedation success rate, onset time of sedation, and the sedation time were recorded. The incidence of adverse events and the risk factors for sedation failure were also analyzed. A total of 4758 patients were identified. After exclusion, 3149 patients were ultimately enrolled. The combination of 2-mcg/kg intranasal dexmedetomidine and 0.5-mg/kg oral midazolam resulted in a total success rate of 99.7% and a sedation success rate of 91.4%. The sedation success rate varied among the four groups: 90.2% in the infant group, 93.1% in the toddler group, 92.7% in the preschool group, and 78.4% in the school-age group. The sedation success rate was significantly lower in the school-age group compared to the other three groups (P < 0.001). The onset time of sedation was shorter in infant (22 min, IQR: 18-28 min, P < 0.001) and longer in the school-age group (30 min, IQR: 25-35 min, P < 0.05). Additionally, the infants had a longer sedation time (110 min, IQR: 90-135 min, P < 0.001) and a higher rate of delayed recovery (27.5%, all P < 0.001). The incidence of adverse events was low (4.70%), which bradycardia (2.03%) being the most common. Age (0-1 year and > 6 years), weight, ASA class II, and history of failed sedation were identified as risk factors of sedation failure.   Conclusion: Intranasal administration of 2-mcg/kg dexmedetomidine combined with oral administration of 0.5-mg/kg midazolam was found to be efficient and safety for pediatric procedural sedation. Different age groups of children exhibited distinct sedation characteristics, and age was identified as a risk factor affecting the efficacy of sedation. What is Known: • Procedural sedation for diagnostic examination is a common practice in children. • The combination of dexmedetomidine with midazolam can improve sedative effects. What is New: • The success rate of sedation using a combination of 2-mcg/kg intranasal dexmedetomidine and 0.5-mg/kg oral midazolam was significantly lower in school-age children as compared to infants, toddlers, and preschoolers. • The onset time of sedation increased with age, and the sedation time was found to be longer in infant patients.

Anesthesia management experience for pediatric day-case PDA ligation under thoracoscopy assisted by a robot: a retrospective study.

BACKGROUND: To summarize the anesthesia management experience for pediatric day-case patent ductus arteriosus (PDA) ligation under robot-assisted thoracoscopy and explore the key points of anesthesia management for this procedure. METHODS: The clinical data of 72 pediatric patients who underwent robot-assisted thoracoscopic day-case PDA ligation at the Children's Hospital, Zhejiang University School of Medicine from April 2021 to February 2023 were retrospectively analyzed. 0.3% ropivacaine local infiltration combined with S-ketamine 0.2 mg/kg intravenous injection was used for postoperative analgesia The patient's basic information and intraoperative conditions were analyzed, which included gender, age, weight, surgery time, anesthesia time, extubation time, intraoperative blood loss, MAP before pneumothorax, PaCO2 before pneumothorax, etc. Postoperative conditions were also monitored, such as PACU stay time, agitation during the recovery period, pain, and the incidence of nausea and vomiting. After discharge, the recovery status was assessed. RESULTS: A total of 70 pediatric patients who met the criteria for day-case PDA ligation were included in this study. Before the occurrence of pneumothorax, the mean arterial pressure (MAP) of these 70 patients was 69.58 ± 12.52 mmHg, and during controlled hypotension, the MAP was 54.96 ± 11.23 mmHg. Before the occurrence of pneumothorax, the partial pressure of carbon dioxide (PaCO2) was 38.69 ± 3.38 mmHg, and during controlled hypotension, the PaCO2 was 51.42 ± 4.05 mmHg. Three cases experienced agitation during the recovery period, and four cases had mild pain, but there was no moderate or severe pain, nausea, or vomiting. Only 1 case of postoperative respiratory tract infection and 1 case of postoperative pneumothorax occurred. Within 30 days after discharge, the unplanned revisit rate, unplanned readmission rate, and surgical wound infection rate were all 0. The residual shunt rate detected by echocardiography was 0 after 1 month. CONCLUSIONS: The children under the robot-assisted thoracoscopic day case PDA surgeries in this study have limited trauma, little bleeding, and little postoperative pain, though still at a risk of respiratory infection and pneumothorax.

Risk factors for intraoperative hypothermia in infants during general anesthesia: A retrospective study.

This study aimed to determine the incidence and evaluate the risk factors and outcomes of intraoperative hypothermia (IH) during general anesthesia in infants. Retrospective analysis of prospectively collected data. A total of 754 infants younger than 1 year old who underwent surgery under general anesthesia were included. Intraoperative body temperature fluctuations, surgical and anesthetic data, postoperative complications, and infant outcomes were recorded. Logistic regression algorithms were used to evaluate potential risk factors. Among the 754 infants, 47.88% developed IH (<36 °C) and 15.4% of them experienced severe hypothermia (<35 °C). The average lowest temperature in hypothermia patients was 35.06 ± 0.69°C with a duration of 82.23 ± 50.59 minutes. Neonates tended to experience hypothermia (37.7% vs 7.6%, P < .001) and prematurity was more common in patients with IH (29.4% vs 16.8%, P < .001). Infants with hypothermia experienced a longer length of stay in the post anesthesia care units and intensive care units, postoperative hospitalizations, and tracheal extubation as well as a higher rate of postoperative hemorrhage than those with normothermia (all P < .05). Several factors were proved to be associated with an increased risk of IH after multivariate analysis: neonate (odds ratio [OR] = 3.685, 95% CI 1.839-7.382), weight (OR = 0.599, 95% CI 0.525-0.683), American society of anesthesiologists (OR = 3.418, 95% CI 2.259-5.170), fluid > 20 mL/kg (OR = 2.380, 95% CI 1.389-4.076), surgery time >60 minutes (OR = 1.785, 95% CI 1.030-3.093), and pre-warming (OR = 0.027, 95% CI 0.014-0.052). This retrospective study found that neonates, lower weight, longer surgery times, more fluid received, higher American society of anesthesiologists stage, and no pre-warming were all significant risk factors for IH during general anesthesia in infants.

RAGE Is a Receptor for SARS-CoV-2 N Protein and Mediates N Protein-induced Acute Lung Injury.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (N-protein) increases early in body fluids during infection and has recently been identified as a direct inducer for lung injury. However, the signal mechanism of N-protein in the lung inflammatory response remains poorly understood. The goal of this study was to determine whether RAGE (receptor for advanced glycation endproducts) participated in N-protein-induced acute lung injury. The binding between N-protein and RAGE was examined via assays for protein-protein interaction. To determine the signaling mechanism in vitro, cells were treated with recombinant N-protein and assayed for the activation of the RAGE/MAPK (mitogen-activated protein kinase)/NF-ĸB pathway. RAGE deficiency mice and antagonist were used to study N-protein-induced acute lung injury in vivo. Binding between N-protein and RAGE was confirmed via flow cytometry-based binding assay, surface plasmon resonance, and ELISA. Pull-down and coimmunoprecipitation assays revealed that N-protein bound RAGE via both N-terminal and C-terminal domains. In vitro, N-protein activated the RAGE-ERK1/2-NF-ĸB signaling pathway and induced a proinflammatory response. RAGE deficiency subdued N-protein-induced proinflammatory signaling and response. In vivo, RAGE was upregulated in the BAL and lung tissue after recombinant N-protein insult. RAGE deficiency and small molecule antagonist partially protected mice from N-protein-induced acute lung injury. Our study demonstrated that RAGE is a receptor for N-protein. RAGE is partially responsible for N-protein-induced acute lung injury and has the potential to become a therapeutic target for treating coronavirus disease.

Use of extracorporeal membrane oxygenation during resection of recurrent laryngeal papillomatosis: A case report.

RATIONALE: Recurrent laryngeal papillomatosis (RLP) is a common benign tumor in the larynx of children, which is characterized by high recurrence rate and rapid growth, leading to clinical symptoms such as hoarseness and difficulty breathing. Low-temperature plasma radiofrequency ablation (RFA) is the main treatment, but ventilation problems are often encountered during surgery. PATIENT CONCERNS: We report a case of a 2-year-old child with RLP who underwent low-temperature plasma RFA with the assistance of a laryngoscope. However, the surgery had to be temporarily stopped due to ventilation difficulties and difficulty in maintaining blood oxygen saturation during the procedure. DIAGNOSIS: The child was diagnosed with RLP. INTERVENTIONS: The child underwent low-temperature plasma RFA supported by laryngoscopy assisted by ECMO. OUTCOMES: Despite ventilation problems during surgery, the use of ECMO support helped maintain good oxygen saturation in the child and provided a clear surgical field, enabling the tumor to be quickly and cleanly removed. Therefore, the use of ECMO provided critical support during the surgery. LESSONS: This case highlights the importance of airway management during laryngeal papillomatosis surgery. A thorough airway assessment should be performed before anesthesia, and early use of ECMO can reduce harm to the child and ensure the child's safety.

Risk factors and outcomes of intraoperative hypothermia in neonatal and infant patients undergoing general anesthesia and surgery.

Objective: The incidence of intraoperative hypothermia remains high in pediatric patients during anesthesia and surgery even though core body temperature monitoring and warming systems have been greatly improved in recent years. We analyzed the risk factors and outcomes of intraoperative hypothermia in neonates and infants undergoing general anesthesia and surgery. Methods: The data on the incidence of intraoperative hypothermia, other clinical characteristics, and outcomes from electronic records of 1,091 patients (501 neonates and 590 infants between 28 days and 1 year old), who received general anesthesia and surgery, were harvested and analyzed. Intraoperative hypothermia was defined as a core temperature below 36°C during surgery. Results: The incidence of intraoperative hypothermia in neonates was 82.83%, which was extremely higher than in infants (38.31%, p < 0.001)-the same as the lowest body temperature (35.05 ± 0.69°C vs. 35.40 ± 0.68°C, p < 0.001) and the hypothermia duration (86.6 ± 44.5 min vs. 75.0 ± 52.4 min, p < 0.001). Intraoperative hypothermia was associated with prolonged PACU, ICU, hospital stay, postoperative bleeding, and transfusion in either age group. Intraoperative hypothermia in infants was also related to prolonged postoperative extubation time and surgical site infection. After univariate and multivariate analyses, the age (OR = 0.902, p < 0.001), weight (OR = 0.480, p = 0.013), prematurity (OR = 2.793, p = 0.036), surgery time of more than 60 min (OR = 3.743, p < 0.001), prewarming (OR = 0.081, p < 0.001), received >20 mL/kg fluid (OR = 2.938, p = 0.004), and emergency surgery (OR = 2.142, p = 0.019) were associated with hypothermia in neonates. Similar to neonates, age (OR = 0.991, p < 0.001), weight (OR = 0.783, p = 0.019), surgery time >60 min (OR = 2.140, p = 0.017), pre-warming (OR = 0.017, p < 0.001), and receive >20 mL/kg fluid (OR = 3.074, p = 0.001) were relevant factors to intraoperative hypothermia in infants along with the ASA grade (OR = 4.135, p < 0.001). Conclusion: The incidence of intraoperative hypothermia was still high, especially in neonates, with a few detrimental complications. Neonates and infants each have their different risk factors associated with intraoperative hypothermia, but younger age, lower weight, longer surgery time, received more fluid, and no prewarming management were the common risk factors.

SARS-CoV-2 N Protein Induces Acute Lung Injury in Mice via NF-ĸB Activation.

Background: Infection of SARS-CoV-2 may cause acute respiratory syndrome. It has been reported that SARS-CoV-2 nucleocapsid protein (N-protein) presents early in body fluids during infection. The direct involvement of N-protein in lung injury is poorly understood. Methods: Recombinant N-protein was pretreated with polymyxin B, a lipopolysaccharide (LPS)-neutralizing agent. C57BL/6, C3H/HeJ (resistant to LPS), and C3H/HeN (control for C3H/HeJ) mice were exposed to N-protein via intratracheal administration to examine acute lung injury. In vitro, bone marrow-derived macrophages (BMDMs) were cultured with N-protein to study phosphorylation of nuclear factor kappa B (NF-ĸB) p65, macrophage polarization, and expression of proinflammatory cytokines. Results: N-protein produced acute lung injury in C57BL/6 mice, with elevated protein permeability, total cell count, neutrophil infiltration, and proinflammatory cytokines in the bronchioalveolar lavage. N-protein also induced lung injury in both C3H/HeJ and C3H/HeN mice, indicating that the effect could not be attributed to the LPS contamination. N-protein triggered phosphorylation of NF-ĸB p65 in vitro, which was abolished by both N-protein denaturation and treatment with an antibody for N-protein, demonstrating that the effect is N-protein specific. In addition, N-protein promoted M1 macrophage polarization and the expression of proinflammatory cytokines, which was also blocked by N-protein denaturation and antibody for N-protein. Furthermore, N-protein induced NF-ĸB p65 phosphorylation in the lung, while pyrrolidine dithiocarbamate, an NF-ĸB inhibitor, alleviated the effect of N-protein on acute lung injury. Conclusions: SARS-CoV-2 N-protein itself is toxic and induces acute lung injury in mice. Both N-protein and NF-ĸB pathway may be therapeutic targets for treating multi-organ injuries in Coronavirus disease 2019 (COVID-19).

Explainable machine-learning predictions for complications after pediatric congenital heart surgery.

The quality of treatment and prognosis after pediatric congenital heart surgery remains unsatisfactory. A reliable prediction model for postoperative complications of congenital heart surgery patients is essential to enable prompt initiation of therapy and improve the quality of prognosis. Here, we develop an interpretable machine-learning-based model that integrates patient demographics, surgery-specific features and intraoperative blood pressure data for accurately predicting complications after pediatric congenital heart surgery. We used blood pressure variability and the k-means algorithm combined with a smoothed formulation of dynamic time wrapping to extract features from time-series data. In addition, SHAP framework was used to provide explanations of the prediction. Our model achieved the best performance both in binary and multi-label classification compared with other consensus-based risk models. In addition, this explainable model explains why a prediction was made to help improve the clinical understanding of complication risk and generate actionable knowledge in practice. The combination of model performance and interpretability is easy for clinicians to trust and provide insight into how they should respond before the condition worsens after pediatric congenital heart surgery.

Understanding risk factors for postoperative mortality in neonates based on explainable machine learning technology.

PURPOSE: We aimed to introduce an explainable machine learning technology to help clinicians understand the risk factors for neonatal postoperative mortality at different levels. METHODS: A total of 1481 neonatal surgeries performed between May 2016 and December 2019 at a children's hospital were included in this study. Perioperative variables, including vital signs during surgery, were collected and used to predict postoperative mortality. Several widely used machine learning methods were trained and evaluated on split datasets. The model with the best performance was explained by SHAP (SHapley Additive exPlanations) at different levels. RESULTS: The random forest model achieved the best performance with an area under the receiver operating characteristic curve of 0.72 in the validation set. TreeExplainer of SHAP was used to identify the risk factors for neonatal postoperative mortality. The explainable machine learning model not only explains the risk factors identified by traditional statistical analysis but also identifies additional risk factors. The visualization of feature contributions at different levels by SHAP makes the "black-box" machine learning model easily understood by clinicians and families. Based on this explanation, vital signs during surgery play an important role in eventual survival. CONCLUSIONS: The explainable machine learning model not only exhibited good performance in predicting neonatal surgical mortality but also helped clinicians understand each risk factor and each individual case.

Study of risk factors for intraoperative hypothermia during pediatric burn surgery.

Background: Intraoperative hypothermia (core temperature <36.0°C) is common during the perioperative period and can result in adverse consequences, especially in children. We aimed to determine the incidence of intraoperative hypothermia and its risk factors in pediatric patients during burn surgery. Methods: In the present study we enrolled 197 pediatric patients with burn injury undergoing surgical debridement and skin grafting. Factors, such as total burn surface area (TBSA), were collected and analyzed to identify the potential risk factors for intraoperative hypothermia. Results: The incidence of intraoperative hypothermia among all patients was 17.8%. Compared with patients with normothermia, children with hypothermia were associated with larger TBSA (25% vs 15%, p<0.001) and with less intraoperative active warming (34.28% vs 54.93%, p<0.05). In addition, compared with patients with moderate-degree burn, patients with severe and extremely severe burn were associated with much higher risk of intraoperative hypothermia [severe: odds ratio (OR)=3.805, 95% confidence interval (CI)=1.396-10.368, p=0.009; extremely severe: OR=6.933, 95% CI=2.604-18.462, p<0.001]. TBSA was the only independent risk factor that emerged as being strongly associated with intraoperative hypothermia (OR=1.068, p=0.001) and could be used to predict the occurrence of hypothermia when combined with other factors. TBSA for predicting intraoperative hypothermia by receiver operating characteristic (ROC) curve analysis showed a good predictive ability with an area under the ROC curve of 0.758. Conclusion: TBSA is an important risk factor for intraoperative hypothermia in pediatric patients with burn.

Effect of nalbuphine on rocuronium injection pain.

Objective: Rocuronium-associated intravenous injection pain occurs frequently in children during induction of anesthesia. The aim of this study was to systematically evaluate the benefits of nalbuphine in patients with rocuronium-associated injection pain. Methods: Ninety children undergoing tonsillectomy and adenoidectomy in our hospital between October 2019 and September 2020 were randomly divided into the following groups, with 30 patients per group: control group (group C), lidocaine group (group L), and nalbuphine group (group N). Routine 0.1 mg/kg midazolam and 2 mg/kg propofol were injected intravenously. After sedation, children in group C, group L, and group N were administered an intravenous injection of saline, lidocaine (10 mg/mL), or nalbuphine hydrochloride (2 mg/mL), respectively, at a dosage of 0.1 mL/kg. Intravenous injection of rocuronium stock solution (0.6 mg/kg) was administered 2 minutes later. Pain was evaluated using Ambeshs 4-pointscale. The incidence of rocuronium injection pain was compared among the three groups, and postoperative adverse reactions, such as drowsiness, bradycardia, hypotension, and respiratory depression, were evaluated. Results: The incidence of injection pain among children in group N was significantly lower than that in group C and group L (p<0.05). The incidence of drowsiness in group N was significantly higher than that in the other groups (p<0.05). The incidences of hypotension, bradycardia, and respiratory depression were not significantly different among the three groups (p>0.05). Conclusions: Intravenous nalbuphine during induction of anesthesia effectively prevented rocuronium-associated injection pain in children. Drowsiness is a complication.

Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization.

Mesenchymal stem cells (MSCs) are adult stromal cells that reside in virtually all postnatal tissues. Due to their regenerative and immunomodulatory capacities, MSCs have attracted growing attention during the past two decades. MSC-derived extracellular vesicles (MSC-EVs) are able to duplicate the effects of their parental cells by transferring functional proteins and genetic materials to recipient cells without cell-to-cell contact. MSC-EVs also target macrophages, which play an essential role in innate immunity, adaptive immunity, and homeostasis. Recent studies have demonstrated that MSC-EVs reduce M1 polarization and/or promote M2 polarization in a variety of settings. In this review, we discuss the mechanisms of macrophage polarization and roles of MSC-EV-induced macrophage polarization in the outcomes of cardiovascular, pulmonary, digestive, renal, and central nervous system diseases. In conclusion, MSC-EVs may become a viable alternative to MSCs for the treatment of diseases in which inflammation and immunity play a critical role.

Recommendation about the perioperative prevention of infection to healthcare workers and the anesthesia management of children with SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely and persistently over 100 countries. New challenges have occurred in the perioperative management of airway and anesthesia in children diagnosed with SARS-CoV-2 infection. According to current publications and to our own experiences in anesthesia management for cases with SARS-CoV-2 suspected, we reviewed concerns about the perioperative prevention of SARS-CoV-2 to medical staff and the anesthesia strategy to the patient.

Differential effects of extracellular vesicles from aging and young mesenchymal stem cells in acute lung injury.

Old age is a known risk factor for mortality in acute respiratory distress syndrome (ARDS)/acute lung injury. Mesenchymal stem cells (MSCs) possess potent immunomodulatory properties, while aging MSCs have reduced capacity. Recent studies have demonstrated that MSC-derived extracellular vesicles (MSC-EVs) are able to mimic MSCs in alleviating acute lung injury. The goals of this study were to determine whether EVs from young and aging MSCs had differential effects on lipopolysaccharide (LPS)-induced lung injury in young mice and unravel the underlying mechanisms. Our results showed that both aging and young MSC-EVs had similar physical and phenotypical properties. As their parental cells, young MSC-EVs alleviated LPS-induced acute lung injury, while aging MSC-EVs did not exhibit the protective effects. In contrast to young MSC-EVs, aging MSC-EVs failed to alter macrophage phenotypes and reduce macrophage recruitment. In addition, the internalization of aging MSC-EVs by macrophages was significantly lower compared with that of young MSC-EVs. Furthermore, aging and young MSC-EVs differed in levels of several miRNAs relating macrophage polarization. In conclusion, aging and young MSC-EVs have differential effects in alleviating acute lung injury and macrophage polarization, which may be associated with internalization of EVs and their miRNA content.

Changes and correlations of serum interleukins, adhesion molecules and soluble E-selectin in children with allergic rhinitis and asthma.

OBJECTIVE: To observe the changes and correlations of serum interleukins (ILs), adhesion molecules and soluble E-selectin (sE-selectin) in children with allergic rhinitis, asthma and both diseases. METHODS: A total of 45 children with allergic rhinitis, 40 with asthma and 45 with allergic rhinitis complicated with asthma treated from September 2016 to January 2018 were selected. Meanwhile, 30 healthy subjects who received physical examinations were included as a control group. The levels of serum IL-4, IL-5, IL-10, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), and sE-selectin were detected by double-antibody sandwich ELISA, and their correlations were subjected to Spearman's correlation analysis. RESULTS: The serum IL levels of allergic rhinitis, asthma and complication groups were significantly higher than those of control group (P<0.01), and the levels of complication group significantly exceeded those of asthma group (P<0.05). The serum levels of IL-5 and IL-10 in complication group significantly exceeded those of allergic rhinitis group (P<0.05). Compared with control group, serum sICAM-1, sVCAM-1, and sE-selectin levels significantly increased in other three groups (P<0.01). Such levels of complication group were significantly higher than those of allergic rhinitis and asthma groups (P<0.05). Serum IL-10 level was positively correlated with that of IL-4 (r=0.965, P<0.05), and sE-selectin level was positively correlated with those of sICAM-1 and sVCAM-1 (r=0.915, P<0.01; r=0.892, P<0.01). CONCLUSION: Serum IL-4, IL-5, IL-10, adhesion molecules and sE-selectin are all involved in the pathogenesis of allergic rhinitis and asthma, which can be used to evaluate the degrees of respiratory allergic diseases.

Plasma levels of alarmin HNPs 1-3 associate with lung dysfunction after cardiac surgery in children.

BACKGROUND: Early onset of lung injury is considerable common after cardiac surgery and is associated with increasing in morbidity and mortality, but current clinical predictors for the occurrence of this complication always have limited positive warning value. This study aimed to evaluate whether elevated plasma levels of human neutrophil peptides (HNPs) 1-3 herald impaired lung function in infants and young children after cardiac surgery necessitating cardiopulmonary bypass (CPB). METHODS: Consecutive children younger than 3 years old who underwent cardiac surgery were prospectively enrolled. Plasma concentrations of HNPs 1-3 and inflammatory cytokines were measured before, and immediately after CPB, as well as at 1 h, 12 h, and 24 h after CPB. RESULTS: Thirty patients were enrolled, 18 (60%) of whom were infants. Plasma levels of HNPs 1-3 and the pro-inflammatory cytokine interleukin-6 (IL-6) significantly increased immediately after CPB (P < 0.001), while IL-8 increased 1 h after the CPB operation (P = 0.002). The anti-inflammatory cytokine IL-10 levels were also significantly elevated immediately after CPB compared with the baseline (P < 0.001). The stepwise multiple linear regression analysis showed that the plasma HNPs 1-3 levels immediately after CPB was independent correlated with the declined lung function, as reflected by the PaO2/FiO2 ratio on the first 2 days after operation (for the first day: OR, -1.067, 95% CI, -0.548 to -1.574; P < 0.001; for the second day: OR, -0.667, 95% CI, -0.183 to -1.148; P = 0.009) and prolonged mechanical ventilation time (OR, 0.039, 95% CI, 0.005 to 0.056; P = 0.011). Plasma levels of HNPs 1-3 and IL-10 returned to the baseline values, while IL-6 and IL-8 levels remained significantly higher than baseline 24 h after CPB (P ≤ 0.01). CONCLUSIONS: Elevated HNPs 1-3 levels immediately after CPB correlate with impaired lung function, and HNPs 1-3 could serve as a quantifiable early alarmin biomarker for onset of lung injury in infants and young children undergoing cardiac surgery with CPB.

Human adipose-derived mesenchymal stem cells alleviate obliterative bronchiolitis in a murine model via IDO.

BACKGROUND: Long-term survival of lung transplantation is hindered by the development of obliterative bronchiolitis (OB). Adipose-derived stem cells (ASCs) were documented to have more potent immunosuppressive ability than mesenchymal stem cells (MSCs) from bone marrow and placenta. The goal of our study is to evaluate the effect of repeated administration of ASCs on OB and the involvement of indoleamine 2,3-dioxygenase (IDO) mediating the protective effect of ASCs in a heterotopic tracheal transplantation (HTT) model. METHODS: For studies in vitro, ASCs were treated with interferon-γ (IFN-γ). For in vivo study, tracheas from BALB/c or C57BL/6 donors were transplanted into C57BL/6 recipients to create a HTT model. On days 0, 1, 3, 5, 8, 12, 15, 20 and 25 post-transplant, the allogeneic recipient mice were administered intravenously with phosphate buffered saline, 1 × 106 human ASCs, or 1 × 106 human ASCs plus 1-methyltryptophan (1-MT), an IDO inhibitor. On days 3, 7, 14 and 28, serum, trachea and spleen samples were harvested for analysis. RESULTS: ASCs homed to heterotopic tracheal grafts after infusion. Multiple doses of ASCs significantly increased tracheal IDO levels in allografts. There were significant increases in graft and serum IFN-γ levels in allografts compared with isografts. IFN-γ elevated IDO expression and activity in ASCs in vitro. ASCs alleviated OB in allografts as evidenced by reduced epithelial loss, epithelial apoptosis, and intraluminal obstruction. The effects of ASCs on OB were blocked by 1-MT. 1-MT also blocked the alterations in pro and anti-inflammatory cytokines as well as CD3+ T cell infiltration induced by ASCs. ASCs induced not only splenic levels of CD4+CD25+Foxp3+ regulatory T cells (Treg) but also IL-10 and TGF-ß-producing Treg. Furthermore, IDO inhibition abolished the changes of splenic Treg induced by ASCs. In addition, Treg reduction by cyclophosphamide treatment did not alter the effects of ASCs on tracheal IDO expression in allografts confirming Treg induction is downstream of IDO. CONCLUSIONS: Repeated doses of ASCs are capable of ameliorating OB. ASCs act at least in part via elevating IDO expression. ASCs promote the generation of Treg and suppress T cell infiltration via an IDO-dependent mechanism.