Lung-Protective Ventilation for Pediatric Acute Respiratory Distress Syndrome: A Nonrandomized Controlled Trial.

OBJECTIVES: Despite the recommendation for lung-protective mechanical ventilation (LPMV) in pediatric acute respiratory distress syndrome (PARDS), there is a lack of robust supporting data and variable adherence in clinical practice. This study evaluates the impact of an LPMV protocol vs. standard care and adherence to LPMV elements on mortality. We hypothesized that LPMV strategies deployed as a pragmatic protocol reduces mortality in PARDS. DESIGN: Multicenter prospective before-and-after comparison design study. SETTING: Twenty-one PICUs. PATIENTS: Patients fulfilled the Pediatric Acute Lung Injury Consensus Conference 2015 definition of PARDS and were on invasive mechanical ventilation. INTERVENTIONS: The LPMV protocol included a limit on peak inspiratory pressure (PIP), delta/driving pressure (DP), tidal volume, positive end-expiratory pressure (PEEP) to F io2 combinations of the low PEEP acute respiratory distress syndrome network table, permissive hypercarbia, and conservative oxygen targets. MEASUREMENTS AND MAIN RESULTS: There were 285 of 693 (41·1%) and 408 of 693 (58·9%) patients treated with and without the LPMV protocol, respectively. Median age and oxygenation index was 1.5 years (0.4-5.3 yr) and 10.9 years (7.0-18.6 yr), respectively. There was no difference in 60-day mortality between LPMV and non-LPMV protocol groups (65/285 [22.8%] vs. 115/406 [28.3%]; p = 0.104). However, total adherence score did improve in the LPMV compared to non-LPMV group (57.1 [40.0-66.7] vs. 47.6 [31.0-58.3]; p < 0·001). After adjusting for confounders, adherence to LPMV strategies (adjusted hazard ratio, 0.98; 95% CI, 0.97-0.99; p = 0.004) but not the LPMV protocol itself was associated with a reduced risk of 60-day mortality. Adherence to PIP, DP, and PEEP/F io2 combinations were associated with reduced mortality. CONCLUSIONS: Adherence to LPMV elements over the first week of PARDS was associated with reduced mortality. Future work is needed to improve implementation of LPMV in order to improve adherence.

Plasma profiles of inflammatory cytokines in children with moderate to severe traumatic brain injury: a prospective cohort study.

The role of inflammatory cytokines in children with moderate to severe TBI (m-sTBI) is still incompletely understood. We aimed to investigate the associations between early plasma expression profiles of inflammatory cytokines and clinical outcomes in children with m-sTBI. We prospectively recruited children admitted to the intensive care unit (ICU) of a tertiary pediatric hospital due to m-sTBI from November 2022 to May 2023. Plasma interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, interferon (IFN)-α, IFN-γ and tumor necrosis factor (TNF)-α concentrations were detected by flow cytometry on admission and on days 5 to 7. The primary outcome was in-hospital mortality. The secondary outcome was the 6-month functional outcome assessed by the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score, dichotomized as favorable (1-4) or unfavorable (5-8). Fifty patients and 20 healthy controls were enrolled. Baseline IL-6, IL-8 and IL-10 levels were significantly higher in TBI patients than in healthy controls. Twelve patients died in the hospital. Compared with survivors, nonsurvivors had significantly increased baseline IL-6 and IL-8 levels. Baseline IL-5, IL-6 and IL-8 levels were also significantly greater in children with unfavorable versus favorable outcomes. The area under the receiver operating characteristic curve (AUC) of the IL-6 and IL-8 levels and motor Glasgow Coma Scale (GCS) score for predicting in-hospital mortality was 0.706, 0.754, and 0.776, respectively. Baseline IL-1ß, IL-2, IL-4, IL-10, IL-12p70, IL-17A, IFN-γ, IFN-α and TNF-α levels were not associated with in-hospital mortality or an unfavorable 6-month outcome. On days 5 to 7, the IL-6 and IL-8 levels were significantly decreased in survivors but increased in nonsurvivors compared to their respective baselines. CONCLUSION: After m-sTBI, the plasma profiles of inflammatory cytokines are markedly altered in children. The trends of IL-6 and IL-8 expression vary among m-sTBI children with different outcomes. Elevated plasma IL-6 and IL-8 levels are related to in-hospital mortality and unfavorable 6-month outcomes. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2200065505). Registered November 7, 2022. WHAT IS KNOWN: • Inflammation is an important secondary physiological response to TBI. WHAT IS NEW: • The plasma profiles of inflammatory cytokines are markedly altered in children with m-sTBI. Elevated IL-6 and IL-8 levels are related to mortality and unfavorable outcomes.

Relationship between thrombocytopenia and prognosis in children with septic shock: a retrospective cohort study.

Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation, potentially influencing the course of the disease. However, there are few studies specifically evaluating the impact of thrombocytopenia on the prognosis of pediatric patients. Therefore, the study investigates effects of early thrombocytopenia in the prognosis of children with septic shock. Pediatric patients with septic shock from 2015 to 2022 were included monocentrically. Thrombocytopenia was defined as a platelet count of <100 × 109/L during the first 24 hours of septic shock onset. The primary outcome was the 28-day mortality. Propensity score matching was used to pair patients with different platelet counts on admission but comparable disease severity. A total of 419 pediatric patients were included in the analysis. Patients with thrombocytopenia had higher 28-day mortality (55.5% vs. 38.7%, p = .005) compared to patients with no thrombocytopenia. Thrombocytopenia was associated with reduced 28-PICU free days (median value, 0 vs. 13 days, p = .003) and 28-ventilator-free (median value, 0 vs. 19 days, p = .001) days. Among thrombocytopenia patients, those with platelet count ≤50 × 109/L had a higher 28-day mortality rate (63.6% vs. 45%, p = .02). Multiple logistic regression showed that elevated lactate (adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.04-1.17; P <0.001) and white blood cell (WBC) count (OR = 0.97; 95% CI: 0.95-0.99; p = .003) were independent risk factors for the development of thrombocytopenia. Thrombocytopenia group had increased bleeding events, blood product transfusions, and development of organ failure. In Kaplan-Meier survival estimates, survival probabilities at 28 days were greater in patients without thrombocytopenia (p value from the log-rank test, p = .004). There were no significant differences in the type of pathogenic microorganisms and the site of infection between patients with and without thrombocytopenia. In conclusion, thrombocytopenia within 24 hours of shock onset is associated with an increased risk of 28-day mortality in pediatric patients with septic shock.

What is the context? Septic shock is a life-threatening disease worldwide, leading to higher mortality.Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation.Although it is known that platelets are associated with prognosis, most studies have focused on adult populations. Limited data are available on the incidence of thrombocytopenia and its correlation with clinical outcomes , specifically, in pediatric patients with sepsis and septic shock. What is new? The present study suggests that thrombocytopenia within 24 hours of septic shock onset reflects a reliable tool for predicting the prognosis of septic shock in pediatric patients.Furthermore, elevated lactate and reduced white-blood-cell count were independent risk factors for the development of thrombocytopenia in pediatric patients with septic shock. What is the impact? This study suggests that thrombocytopenia within 24 hours of septic shock onset is associated with an increased risk of 28-day mortality and decreased ventilation-free, PICU-free days in pediatric patients with septic shock. In septic shock, thrombocytopenia is also associated with increased bleeding events, blood product transfusions, and organ dysfunction.

Severe Pneumonia in PICU Admissions: The Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN) Observational Cohort Study, 2020-2022.

OBJECTIVES: Mortality from pneumonia is three times higher in Asia compared with industrialized countries. We aimed to determine the epidemiology, microbiology, and outcome of severe pneumonia in PICUs across the Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN). DESIGN: Prospective multicenter observational study from June 2020 to September 2022. SETTING: Fifteen PICUs in PACCMAN. PATIENTS: All children younger than 18 years old diagnosed with pneumonia and admitted to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical, microbiologic, and outcome data were recorded. The primary outcome was PICU mortality. Univariate and multivariable logistic regression was performed to investigate associations between PICU mortality and explanatory risk factors on presentation to the PICU. Among patients screened, 846 of 11,778 PICU patients (7.2%) with a median age of 1.2 years (interquartile range, 0.4-3.7 yr) had pneumonia. Respiratory syncytial virus was detected in 111 of 846 cases (13.1%). The most common bacteria were Staphylococcus species (71/846 [8.4%]) followed by Pseudomonas species (60/846 [7.1%]). Second-generation cephalosporins (322/846 [38.1%]) were the most common broad-spectrum antibiotics prescribed, followed by carbapenems (174/846 [20.6%]). Invasive mechanical ventilation and noninvasive respiratory support was provided in 438 of 846 (51.8%) and 500 of 846 (59.1%) patients, respectively. PICU mortality was 65 of 846 (7.7%). In the multivariable logistic regression model, age (adjusted odds ratio [aOR], 1.08; 95% CI, 1.00-1.16), Pediatric Index of Mortality 3 score (aOR, 1.03; 95% CI, 1.02-1.05), and drowsiness (aOR, 2.73; 95% CI, 1.24-6.00) were associated with greater odds of mortality. CONCLUSIONS: In the PACCMAN contributing PICUs, pneumonia is a frequent cause for admission (7%) and is associated with a greater odds of mortality.

Design and On-Orbit Performance of Ku-Band Phased-Array Synthetic-Aperture Radar Payload System.

The current emphasis in the advancement of space-based synthetic-aperture radar (SAR) is on lightweight payloads under 100 kg with resolutions surpassing 1 m. This focus is directed toward meeting the launch criteria for multiple satellites on a single rocket and cutting costs. This article discusses the creation and progress of a Ku-band SAR payload for the Taijing-4(03) satellite, launched on 23 January 2024 and accompanied by four other satellites. The SAR payload design was customized to meet the demands of a micro-nano satellite platform, resulting in a lightweight, flat design weighing less than 80 kg, seamlessly integrated with the plate-shaped satellite platform. The article also introduces a beam optimization strategy for the phased array SAR antenna, significantly boosting the SAR system's performance. The SAR payload provides various operating modes like slide-spot, strip, Scan 1, Scan 2, and others, with a maximum achievable resolution exceeding 1 m. Extensive in-orbit testing of the payload produced numerous high-quality SAR images with potential uses in emergency disaster mitigation, safeguarding ecosystems, monitoring forests, managing crops, tracking sea ice, and more.

Effect of intravenous immunoglobulin on the outcome of children with septic shock in a PICU: a retrospective cohort study.

The therapeutic efficacy of intravenous immuneglobulin (IVIG) on children with septic shock remains uncertain. Therefore, we endeavored to investigate the impact of administering intravenous immunoglobulin (IVIG) in the pediatric intensive care unit (PICU) on patient with septic shock. We retrospectively analyzed the data of children admitted to the PICU due to septic shock from January 2017 to December 2021 in a tertiary pediatric hospital. The main outcome was in-hospital mortality. Total 304 patients were enrolled. There were no significant differences in the PRISM-III score (11 vs. 12, P = 0.907), PIM-3 score (0.08 vs. 0.07, P = 0.544), pSOFA score (10 vs. 10, P = 0.852) between the No IVIG group and the IVIG group. Children who received IVIG required more continuous renal replacement therapy (CRRT) support (43% vs. 24%, P = 0.001) and longer duration of mechanical ventilation (MV) (6 vs. 3 days, P = 0.002), and longer length of stay (LOS) of PICU (7 vs. 4 days, P = 0.001) and LOS of hospital (18 vs. 11 days, P = 0.001) than children who did not receive. The 28-day survival analysis (P = 0.033) showed better survival rates in IVIG group, while the in-hospital mortality (43% vs. 52%, P = 0.136) was no significant difference. In the propensity score matched analysis, 71 pairs were established. The length of CRRT (2 vs. 3 days, P = 0.744), duration of mechanical ventilation (5 vs. 4 days, P = 0.402), LOS of PICU (7 vs. 5 days, P = 0.216), LOS of hospital (18 vs. 13 days, P = 0.290), in-hospital mortality (44% vs. 44%, P = 1.000) and 28-day survival analysis (P = 0.748) were not statistically different. After inverse probability weighted analysis, there was still no difference in mortality between the two groups (51% vs. 48%, P = 0.665). CONCLUSION: In children with septic shock, the use of intravenous immunoglobulin as an adjuvant therapy does not reduce in-hospital mortality. WHAT IS KNOWN: • Guidelines suggest against the routine use of intravenous immuneglobulin in children with septic shock. Some small observational studies have reported conflicting result. WHAT IS NEW: • The use of intravenous immunoglobulin as an adjuvant therapy does not reduce in-hospital mortality in children with septic shock.

Safety and efficacy of corticosteroids in ARDS patients: a systematic review and meta-analysis of RCT data.

PURPOSE: Acute respiratory distress syndrome (ARDS) is an acute and critical disease among children and adults, and previous studies have shown that the administration of corticosteroids remains controversial. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to evaluate the safety and efficacy of corticosteroids. METHODS: The RCTs investigating the safety and efficacy of corticosteroids in ARDS were searched from electronic databases (Embase, Medline, and the Cochrane Central Register of Controlled Trials). The primary outcome was 28-day mortality. Heterogeneity was assessed using the Chi square test and I2 with the inspection level of 0.1 and 50%, respectively. RESULTS: Fourteen RCTs (n = 1607) were included for analysis. Corticosteroids were found to reduce the risk of death in patients with ARDS (relative risk (RR) = 0.78, 95% confidence interval (CI): 0.70-0.87; P < 0.01). Moreover, no significant adverse events were observed, compared to placebo or standard support therapy. Further subgroup analysis showed that variables, such as adults (RR = 0.78; 95% CI: 0.70-0.88; P < 0.01), non-COVID-19 (RR = 0.71; 95% CI: 0.62-0.83; P < 0.01), methylprednisolone (RR = 0.70; 95% CI: 0.56-0.88; P < 0.01), and hydrocortisone (RR = 0.79; 95% CI: 0.63-0.98; P = 0.03) were associated with 28-day mortality among patients who used corticosteroids. However, no association was found, regarding children (RR = 0.21; 95% CI: 0.01-4.10; P = 0.30). CONCLUSION: The use of corticosteroids is an effective approach to reduce the risk of death in ARDS patients. However, this effect is associated with age, non-COVID-19 diseases, and methylprednisolone and hydrocortisone use. Therefore, evidence suggests patients with age ≥ 18 years and non-COVID-19 should be encouraged during the corticosteroid treatment. However, due to substantial differences in the use of corticosteroids among these studies, questions still remain regarding the dosage, optimal corticosteroid agent, and treatment duration in patients with ARDS.

Effects of rapamycin and OSI-027 on α-SMA in lung tissue of SD rat pups with hyperoxic lung injury.

OBJECTIVE: To investigate the effect and significance of mammalian target of rapamycin (mTOR) inhibitors on the expression of α-SMA in lung injury induced by high volume fraction of inspired oxygen (hyperoxygen) in SD rat pups. METHODS: Seventy-two Sprague-Dawley rat pups (age: 3 weeks) were randomly divided into air + saline, hyperoxia + saline, hyperoxia + OSI-027, and hyperoxia + rapamycin groups. Animal models were constructed (n = 18). Hyperoxia was induced by continuous administration of 90% oxygen. Normal saline, OSI-027, and rapamycin are administered by intraperitoneal injection on 1d, 3d, 6d, 8d, 10d, 13d of the observation period, respectively. Following assessments were made on the 3rd, 7th, and 14th day of modeling: pathological changes in lung tissues, lung injury score, Western Blot to assess the distribution and expressions of mTOR, pS6K1, and α-SMA protein in lung tissues. RESULTS: In terms of time factors, the protein expressions of mTOR, pS6K1, and α-SMA increased with time. Except for the air group, the lung injury scores of the other groups increased with time, In terms of grouping factors, lung injury score in the air group was significantly lower than that in the other groups. In the hyperoxia group, the protein expressions of mTOR, PS6K1, and α-SMA were significantly higher than those in the other groups. The lung injury score in the hyperoxia group was significantly higher than that in the other groups. The lung injury score in the hyperoxia OSI group was significantly lower than that in the hyperoxia rapamycin group. CONCLUSION: In hyperoxia lung injury, inhibiting the activation of mTOR signaling pathway can effectively reduce the expression of α-SMA; however, only mTORC1/2 dual inhibitor OSI-027 exhibited an anti-proliferative effect, and alleviated hyperoxia-induced lung injury and fibrosis in SD rat pups.

Association Between Anticholinergic Drug Burden and Adequacy of Enteral Nutrition in Critically Ill, Mechanically Ventilated Pediatric Patients.

OBJECTIVES: Enteral nutrition delivery is limited by intolerance and interruptions in critically ill children. Anticholinergic properties of frequently administered medications may contribute to altered gastric motility and enteral nutrition intolerance in this population. We examined the association between the anticholinergic burden of administered medications using the Anticholinergic Drug Scale and adequacy of enteral nutrition delivery. DESIGN: Secondary analysis of data from a previously characterized PICU cohort. SETTING: Multidisciplinary PICU in a quaternary academic medical center. PATIENTS: Younger than or equal to 18 years, on mechanical ventilation and received enteral nutrition within the first 3 days of PICU admission. MEASUREMENTS AND MAIN RESULTS: Daily Anticholinergic Drug Scale score, demographic data, and clinical data were obtained from the primary study. Percent enteral energy adequacy ([kcal delivered ÷ kcal prescribed] × 100) during the first 3 days of PICU admission was calculated. Forty-two patients received enteral nutrition, with median age (interquartile range) 5 years (1.09-12.54 yr), and 62% were male. Median Anticholinergic Drug Scale score was inversely correlated with energy adequacy, with a median 9% decline in energy adequacy per 1-point increase in Anticholinergic Drug Scale score (coefficient, -9.3; 95% CI, -13.43 to -5.27; R2 = 0.35; p < 0.0001). Median hours of enteral nutrition interruptions directly correlated with Anticholinergic Drug Scale score (coefficient, 1.5; 95% CI, 0.531-2.54; R2 = 0.19; p = 0.004). Severity score was greater in patients with less than or equal to 25% enteral energy adequacy and directly correlated with median Anticholinergic Drug Scale score. CONCLUSIONS: Anticholinergic burden from medications administered in the PICU is a potentially modifiable factor for suboptimal enteral nutrition delivery.

Traumatic Brain Injury Outcomes in 10 Asian Pediatric ICUs: A Pediatric Acute and Critical Care Medicine Asian Network Retrospective Study.

OBJECTIVES: Traumatic brain injury remains an important cause of death and disability. We aim to report the epidemiology and management of moderate to severe traumatic brain injury in Asian PICUs and identify risk factors for mortality and poor functional outcomes. DESIGN: A retrospective study of the Pediatric Acute and Critical Care Medicine Asian Network moderate to severe traumatic brain injury dataset collected between 2014 and 2017. SETTING: Patients were from the participating PICUs of Pediatric Acute and Critical Care Medicine Asian Network. PATIENTS: We included children less than 16 years old with a Glasgow Coma Scale less than or equal to 13. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We obtained data on patient demographics, injury circumstances, and PICU management. We performed a multivariate logistic regression predicting for mortality and poor functional outcomes. We analyzed 380 children with moderate to severe traumatic brain injury. Most injuries were a result of road traffic injuries (174 [45.8%]) and falls (160 [42.1%]). There were important differences in temperature control, use of antiepileptic drugs, and hyperosmolar agents between the sites. Fifty-six children died (14.7%), and 104 of 324 survivors (32.1%) had poor functional outcomes. Poor functional outcomes were associated with non-high-income sites (adjusted odds ratio, 1.90; 95% CI, 1.11-3.29), Glasgow Coma Scale less than 8 (adjusted odds ratio, 4.24; 95% CI, 2.44-7.63), involvement in a road traffic collision (adjusted odds ratio, 1.83; 95% CI, 1.04-3.26), and presence of child abuse (adjusted odds ratio, 2.75; 95% CI, 1.01-7.46). CONCLUSIONS: Poor functional outcomes are prevalent after pediatric traumatic brain injury in Asia. There is an urgent need for further research in these high-risk groups.

The impact of high frequency oscillatory ventilation on mortality in paediatric acute respiratory distress syndrome.

BACKGROUND: High-frequency oscillatory ventilation (HFOV) use was associated with greater mortality in adult acute respiratory distress syndrome (ARDS). Nevertheless, HFOV is still frequently used as rescue therapy in paediatric acute respiratory distress syndrome (PARDS). In view of the limited evidence for HFOV in PARDS and evidence demonstrating harm in adult patients with ARDS, we hypothesized that HFOV use compared to other modes of mechanical ventilation is associated with increased mortality in PARDS. METHODS: Patients with PARDS from 10 paediatric intensive care units across Asia from 2009 to 2015 were identified. Data on epidemiology and clinical outcomes were collected. Patients on HFOV were compared to patients on other modes of ventilation. The primary outcome was 28-day mortality and secondary outcomes were 28-day ventilator- (VFD) and intensive care unit- (IFD) free days. Genetic matching (GM) method was used to analyse the association between HFOV treatment with the primary outcome. Additionally, we performed a sensitivity analysis, including propensity score (PS) matching, inverse probability of treatment weighting (IPTW) and marginal structural modelling (MSM) to estimate the treatment effect. RESULTS: A total of 328 patients were included. In the first 7 days of PARDS, 122/328 (37.2%) patients were supported with HFOV. There were significant differences in baseline oxygenation index (OI) between the HFOV and non-HFOV groups (18.8 [12.0, 30.2] vs. 7.7 [5.1, 13.1] respectively; p < 0.001). A total of 118 pairs were matched in the GM method which found a significant association between HFOV with 28-day mortality in PARDS [odds ratio 2.3, 95% confidence interval (CI) 1.3, 4.4, p value 0.01]. VFD was indifferent between the HFOV and non-HFOV group [mean difference - 1.3 (95%CI - 3.4, 0.9); p = 0.29] but IFD was significantly lower in the HFOV group [- 2.5 (95%CI - 4.9, - 0.5); p = 0.03]. From the sensitivity analysis, PS matching, IPTW and MSM all showed consistent direction of HFOV treatment effect in PARDS. CONCLUSION: The use of HFOV was associated with increased 28-day mortality in PARDS. This study suggests caution but does not eliminate equivocality and a randomized controlled trial is justified to examine the true association.

Insulin-like growth factor 2 regulates the proliferation and differentiation of rat adipose-derived stromal cells via IGF-1R and IR.

BACKGROUND: Insulin-like growth factor 2 (IGF2), an essential component of the stem cell niche, has been reported to modulate the proliferation and differentiation of stem cells. Previously, a continuous expression of IGF2 in tissues was reported to maintain the self-renewal ability of several types of stem cells. Therefore, in this study, we investigated the expression of IGF2 in adipose tissues and explored the effects of IGF2 on adipose-derived stromal cells (ADSCs) in vitro. METHODS: The expression pattern of IGF2 in rat adipose tissues was determined by gene expression and protein analyses. The effect of IGF2 on proliferation, stemness-related marker expression and adipogenic and osteogenic differentiation was systematically investigated. Furthermore, antagonists of IGF2-specific receptors-namely, BMS-754807 and picropodophyllin-were added to explore the underlying signal transduction mechanisms. RESULTS: IGF2 levels displayed a tendency to decrease with age in rat adipose tissues. After the addition of IGF2, isolated ADSCs displayed higher proliferation and expression of the stemness-related markers NANOG, OCT4 and SOX2 and greater differentiation potential to adipocytes and osteoblasts. Additionally, both type 1 insulin-like growth factor receptor (IGF-1R) and insulin receptor (IR) participated in the IGF2-mediated promotion of stemness in ADSCs. CONCLUSIONS: Our findings indicate that IGF2 could enhance the stemness of rat ADSCs via IGF-1R and IR and may highlight an effective method for the expansion of ADSCs for clinical application.

Hydrogen protects against hyperoxia-induced apoptosis in type II alveolar epithelial cells via activation of PI3K/Akt/Foxo3a signaling pathway.

Oxidative stress is regarded as a key regulator in the pathogenesis of prolonged hyperoxia-induced lung injury, which causes injury to alveolar epithelial cells and eventually leads to development of bronchopulmonary dysplasia (BPD). Many studies have shown that hydrogen has a protective effect in a variety of cells. However, the mechanisms by which hydrogen rescues cells from damage due to oxidative stress in BPD remains to be fully elucidated. This study sought to evaluate the effects of hydrogen on hyperoxia-induced lung injury and to investigate the underlying mechanism. Primary type II alveolar epithelial cells (AECIIs) were divided into four groups: control (21% oxygen), hyperoxia (95% oxygen), hyperoxia + hydrogen, and hyperoxia + hydrogen + LY294002 (a PI3K/Akt inhibitor). Proliferation and apoptosis of AECIIs were assessed using MTS assay and flow cytometry (FCM), respectively. Gene and protein expression were detected by quantitative polymerase chain reaction (q-PCR) and western blot analysis. Stimulation with hyperoxia decreased the expression of P-Akt, P- FoxO3a, cyclinD1 and Bcl-2. Hyperoxic conditions increased levels of Bim, Bax, and Foxo3a, which induced proliferation restriction and apoptosis of AECIIs. These effects of hyperoxia were reversed with hydrogen pretreatment. Furthermore, the protective effects of hydrogen were abrogated by PI3K/Akt inhibitor LY294002. The results indicate that hydrogen protects AECIIs from hyperoxia-induced apoptosis by inhibiting apoptosis factors and promoting the expression of anti-apoptosis factors. These effects were associated with activation of the PI3K/Akt/FoxO3a pathway.

The Wnt7b/ß-catenin signaling pathway is involved in the protective action of calcitonin gene-related peptide on hyperoxia-induced lung injury in premature rats.

BACKGROUND: Calcitonin gene-related peptide (CGRP) can protect against hyperoxia-induced lung injury, making the upregulation of CGRP a potential therapeutic approach for this type of injury. However, the effects of CGRP on the Wnt7b/ß-catenin signaling pathway are unclear. In this study, we investigated the roles of CGRP and the Wnt7b/ß-catenin signaling pathway in hyperoxia-induced lung injury. METHODS: Premature Sprague Dawley (SD) rats were exposed to 21, 40, 60 and 95% oxygen for 3, 7 and 14 days. The animals' body weights, survival rates and endogenous CGRP levels were measured. Lung samples were harvested for histological analyses and measurements of malondialdehyde (MDA) concentration and total antioxidant capacity (TAOC). We also assessed the MDA concentration and TAOC in the lung tissues after administration of 200 nmol/kg CGRP8-37 (a CGRP antagonist). Finally, alveolar epithelial type II (AEC II) cells were isolated from premature rats, exposed to 21 or 95% oxygen for 3, 7 and 14 days, and treated with 10- 8 mol/l exogenous CGRP. The protein expressions of Wnt7b and ß-catenin were assessed using western blotting, and TCF and c-myc mRNA expressions were assessed using qPCR. RESULTS: Rats exposed to 60 and 95% oxygen had significantly lower body weights and survival rates than the 21 and 40% groups, and the decrease was time dependent. Endogenous CGRP was elevated in the lung tissues of premature rats exposed to 95% oxygen. CGRP8-37 induced apparent inflammation in the lung tissue and alveolar structural remodeling. In addition, the expression levels of Wnt7b and ß-catenin were markedly increased after exposure for 3 days. They peaked at 7 days, then declined at 14 days. The levels of TCF/c-myc in AEC II cells increased significantly after CGRP treatment when compared with cells that had only undergone hyperoxia. CONCLUSIONS: CGRP protected against hyperoxia-induced lung injury in premature rats. This process involves the Wnt7b/ß-catenin signaling pathway.

The relationship and influencing factors of critical thinking and medical ethical decision-making among pediatric medical students.

Pediatric diseases possess unique characteristics, requiring pediatricians to have strong critical thinking skills and sound ethical decision-making abilities. This study aims to investigate and analyze the critical thinking dispositions of pediatric medical students and their impact on ethical decision-making levels, and to propose suggestions for improving teaching methods. A cross-sectional study design was adopted, using the Chinese version of the California Critical Thinking Disposition Inventory (CCTDI-CV) and an ethical decision-making questionnaire. An online survey was conducted among 240 pediatric medical students at Chongqing Medical University, collecting participants' basic demographic information. The study described the CCTDI-CV scores and ethical decision-making questionnaire scores (mean ±â€…standard deviation), with distribution and trend analyses performed using t tests and H-tests. Pearson correlation analysis was used to examine the relationship between the 2, and regression analysis was conducted to explore factors influencing ethical decision-making abilities. A total of 229 students (95.4%) completed the survey. The overall average score of critical thinking disposition among pediatric medical students was 287.96 ±â€…39.09, with 139 students (60.70%) demonstrating positive or highly positive critical thinking dispositions. Ethical decision-making abilities were excellent in 85 students (37.12%). There was a significant positive correlation between critical thinking abilities and ethical decision-making abilities (R = 0.774, P < .001), particularly with analysis abilities, systematic abilities, and cognitive maturity showing higher correlations with total ethical decision-making scores. CCTDI-CV scores had a significant positive impact on ethical decision-making levels (P < .001), with factors such as family background and high school performance also significantly influencing ethical decision-making abilities (P < .001). Chinese pediatric medical students generally exhibit strong critical thinking and ethical decision-making abilities. Critical thinking plays a crucial role in medical ethical decision-making, with family background and high school performance being important influencing factors. Educators should focus more on developing multidimensional critical thinking skills to enhance students' ethical decision-making abilities, thereby improving overall healthcare service quality. The study results also provide new perspectives for international pediatric medical educators.

Definition, risk factors, and outcome analysis of prolonged mechanical ventilation in children.

OBJECTIVE: This study aims to explore the time threshold for defining prolonged mechanical ventilation (PMV) in children, along with its risk factors and outcomes. METHODS: A prospective cohort study was conducted on children aged 29 days-18 years, who were consecutively admitted to two Pediatric Intensive Care Units (PICUs) at Children's Hospital of Chongqing Medical University, from October 2020 to June 2021. The study included patients receiving mechanical ventilation (MV) for more than 2 days (each day >6 h). Participants were divided into five groups based on the duration of MV (2-7 days, 8-14 days, 15-21 days, 21-30 days, >30 days) to compare rates of extubation failure, all-cause mortality one month post-discharge, incidence of ventilator-associated pneumonia, tracheotomy rates, total hospital stay, PICU stay, and overall hospital costs. The most clinically and statistically significant outcome variables were selected. The Youden index was used to determine the MV duration with the most significant impact on overall outcomes, defining this as PMV. Baseline characteristics, treatment information, and outcomes were compared between PMV and non-PMV groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for PMV occurrence. RESULTS: A total of 382 subjects were included in the study. The distribution of children across the five MV duration groups was 44.2%, 27.7%, 10.7%, 8.9%, and 8.4% respectively. The rates of at least one extubation failure in each group were 5.9%, 10.4%, 41.5%, 41.2%, and 46.9% (p < .05). Statistically significant differences were observed among groups in terms of tracheotomy rates, all-cause mortality at 1 month postdischarge, median total hospital stay, median PICU stay, and hospital costs (p < .05). Defining PMV, the most appropriate time point calculated was 12.5 days, based on at least one extubation failure and/or death within 1 month postdischarge. Higher PIM-3 scores, weight for age <-2SD, admission for respiratory distress/insufficient ventilation and/or hemodynamic instability/shock/arrhythmia, noninvasive ventilation on the first day, and undergoing blood transfusion treatment were identified as risk factors for PMV (p < .05). CONCLUSION: In children, MV for ≥13 days significantly increases mortality rates, extubation failure and tracheotomy rates, duration of PICU and total hospital stay and costs. We suggest defining PMV as MV ≥13 days, particularly for children undergoing MV for respiratory illnesses. This definition can assist clinicians in developing appropriate treatment strategies by focusing on risk factors and providing reliable prognostic consultation to patients' families.

Critical Thinking Disposition and Influencing Factors Among Sophomore Pediatric Medical Students.

Objective: The second year of undergraduate medical education is a critical phase transitioning from basic medical knowledge to specialized learning, requiring strong critical thinking abilities. Pediatric diseases, with their unique characteristics, demand active critical thinking from pediatricians. This study aims to investigate and analyze the critical thinking dispositions of second-year pediatric medical students, identify influencing factors, and propose recommendations for improving teaching methods. Methods: This cross-sectional study employed the Chinese version of the California Critical Thinking Disposition Inventory (CTDI-CV) and conducted an online survey among 240 second-year pediatric medical students at Chongqing Medical University, Chongqing, China. The study described the overall CTDI-CV scores and sub-dimension scores (mean ± standard deviation) and analyzed the distribution of critical thinking dispositions using t-tests and trend analysis. Results: A total of 229 students (95.4%) completed the survey, with 58.95% being female. The overall mean critical thinking score was 287.96 ± 39.09, and 139 students (60.70%) exhibited positive or highly positive critical thinking dispositions. Rural students scored lower than non-rural students (t = -2.773, P = 0.0069), while only children scored higher than non-only children (t = 2.659, P = 0.0086). Higher high school academic ranking was associated with higher scores (H = 23.85, P < 0.001). Students whose parents had a bachelor's degree or higher scored significantly better (t = 2.373, P = 0.0188). Interest in pediatrics was linked to higher scores (H = 15.36, P = 0.0015). Positive correlations were found between analyticity, inquisitiveness, and self-confidence (r ≥ 0.75). Conclusion: Second-year pediatric medical students in China generally display strong critical thinking abilities. Factors such as family background, academic performance, parental education level, and interest in pediatrics significantly influence these abilities. Pediatric educators should account for these individual differences to better enhance critical thinking development in students and improve teaching strategies accordingly.

Comparing the clinical characteristics and outcomes of septic shock children with and without malignancies: a retrospective cohort study.

OBJECTIVE: There is an amelioration in mortality rates of septic shock patients with malignancies over time, but it remains uncertain in children. Therefore, the authors endeavored to compare the clinical characteristics, treatment needs, and outcomes of septic shock children with or without malignancies. METHODS: The authors retrospectively analyzed the data of children admitted to the PICU due to septic shock from January 2015 to December 2022 in a tertiary pediatric hospital. The main outcome was in-hospital mortality. RESULTS: A total of 508 patients were enrolled. The proportion of Gram-negative bacteria and fungal infections in children with malignancies was significantly higher than those without malignancies. Septic shock children with malignancies had a longer length of stay (LOS) in the hospital (21 vs. 11 days, p<0.001). However, there were no statistically significant differences in the LOS of PICU (5 vs. 5 days, p = 0.591), in-hospital mortality (43.0 % vs. 49.4 %, p = 0.276), and 28-day mortality (49.2 % vs. 44.7 %, p = 0.452). The 28-day survival analysis (p = 0.314) also showed no significant differences. CONCLUSION: Although there are significant differences in the bacterial spectrum of infections, the septic shock children with or without malignancies showed a similar mortality rate. The septic shock children with malignancies had longer LOS of the hospital.

Regional citrate anticoagulation for continuous renal replacement therapy in newborns.

Background: Regional citrate anticoagulant (RCA) is recommended as the preferred anticoagulant regimen for continuous renal replacement therapy (CRRT) in adults; however, it is rarely reported in neonates due to concerns associated with their immature liver. Few studies have reported on the use of RCA to evaluate the safety and efficacy of RCA-CRRT in neonates. Method: In this retrospective observational study, we reviewed the clinical records of neonates who underwent RCA-CRRT at our pediatric intensive care unit between September 2015 to January 2021. Results: A total of 23 neonates underwent 57 sessions of RCA-CRRT. Their mean age was 10.1 ± 6.9 days and mean weight was 3.0 ± 0.7 kg (range, 0.95-4 kg). The mean filter life was 31.54 ± 19.58 h (range, 3.3-72.5 h). Compared to pretreatment values, the total-to-ionized calcium ratio (T/iCa) on RCA-CRRT increased (2.00 ± 34 0.36 vs. 2.19 ± 0.40, P = 0.056) as did the incidence of T/iCa levels >2.5 (11.4 vs. 14.3, P = 0.477), albeit not significantly. Using a post-treatment T/iCa threshold of 2.5, we divided all the cases into citrate accumulation (CA) and non-CA (NCA) groups. Compared with the NCA group, the CA group had significantly higher body weight (3.64 ± 0.32 kg vs. 2.95 ± 0.41 kg, P = 0.033) and significantly lower blood flow rate per body weight ml/kg/min (3.08 ± 0.08 vs. 4.07 ± 0.71, P = 0.027); however, there was no significant difference between the two groups in terms of age, corrected gestational age, the PRISM-III score, and biochemical tests. Conclusion: RCA-CRRT is safe and effective for neonates. After appropriate adjustments of the RCA-CRRT parameters, the incidence of CA was not higher in neonates than in children or adults, and CA was not found to be significantly correlated with age or corrected gestational age.

Novel blood product transfusion regimen to prevent clotting and citrate accumulation during continuous renal replacement therapy with regional citrate anticoagulation in children.

Objective: Introduce a novel protocol to prevent clotting and citrate accumulation (CA) from blood product transfusion (BPT) during continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in children. Methods: We prospectively compared fresh frozen plasma (FFP) and platelet transfusions between the two BPT protocols, direct transfusion protocol (DTP) and partial replacement of citrate transfusion protocol (PRCTP), in terms of the risks of clotting, citric accumulation (CA), and hypocalcemia. For DTP, blood products were directly transfused without any adjustment to the original RCA-CRRT regimen. For PRCTP, the blood products were infused into the CRRT circulation near the sodium citrate infusion point, and the dosage of 4% sodium citrate was reduced depending on the dosage of sodium citrate in the blood products. Basic information and clinical data were recorded for all children. Heart rate, blood pressure, ionized calcium (iCa) and various pressure parameters were recorded before, during and after BPT, as well as coagulation indicators, electrolytes, and blood cell counts before and after BPT. Results: Twenty-six children received 44 PRCTPs and 15 children received 20 DTPs. The two groups had similar in vitro ionized calcium (iCa) concentrations (PRCTP: 0.33 ± 0.06 mmol/L, DTP: 0.31 ± 0.04 mmol/L), total filter lifespan (PRCTP: 49.33 ± 18.58, DTP: 50.65 ± 13.57 h), and filter lifespan after BPT (PRCTP: 25.31 ± 13.87, DTP: 23.39 ± 11.34 h). There was no visible filter clotting during BPT in any of the two groups. The two groups had no significant differences in arterial pressure, venous pressure, and transmembrane pressure before, during, or after BPT. Neither treatment led to significant decreases in WBC, RBC, or hemoglobin. The platelet transfusion group and the FFP group each had no significant decrease in platelets, and no significant increases in PT, APTT, and D-dimer. The most clinically significant changes were in the DTP group, in which the ratio of total calcium to ionized calcium (T/iCa) increased from 2.06 ± 0.19 to 2.52 ± 0.35, the percentage of patients with T/iCa above 2.5 increased from 5.0% to 45%, and the level of in vivo iCa increased from 1.02 ± 0.11 to 1.06 ± 0.09 mmol/L (all p < 0.05). Changes in these three indicators were not significant in the PRCTP group. Conclusion: Neither protocol was associated with filter clotting during RCA-CRRT. However, PRCTP was superior to DTP because it did not increase the risk of CA and hypocalcemia.