Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD). METHODS: Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro-B-type natriuretic peptide) was an exploratory end point. RESULTS: A total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (n=187) or enalapril (n=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47-0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72-1.14]; P=0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children. CONCLUSIONS: In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02678312.

Comparison of the Ultrasound-Guided Supraclavicular and Infraclavicular Approaches for Subclavian Vein Cannulation in Children With Congenital Heart Disease.

OBJECTIVES: Central venous catheterization is used widely in critical pediatric patients. The authors sought to compare the success rate and safety of ultrasound-guided subclavian vein cannulation performed via infraclavicular and supraclavicular approaches. DESIGN: The authors compared the success rate of the first puncture and other information for cannulation in the children with congenital heart disease requiring central venous catheterization who were assigned randomly to the supraclavicular approach group (group A) or infraclavicular approach group (group B). SETTING: Medical university hospital pediatric cardiac intensive care units. PARTICIPANTS: Pediatric patients diagnosed with congenital heart disease in the preoperative period who were admitted to the cardiac intensive care unit and required subclavian vein catheterization. INTERVENTIONS: Ultrasound-guided subclavian vein cannulation. MEASUREMENTS AND MAIN RESULTS: Sixty-seven children were included in the study, with 32 in group A and 35 in group B. Notably, there was a significant difference in the success rate of the first puncture between groups A and B (90.6% v 71.4, %, p = 0.047). Furthermore, the access time in group A was 11.8 seconds (3.2-95), which was significantly shorter than that in group B (16.0 [6.5-227] seconds, p = 0.001). In addition, the catheter malposition rate in group A was significantly lower than that in group B (0% v 11.4%, p = 0.049). Conversely, there were no significant differences in the total access time, overall success rate, and complications (eg, pneumothorax, hemorrhage, puncture artery, and nerve injury) between the 2 groups. CONCLUSIONS: For children with congenital heart disease requiring central venous catheterization during the perioperative period, the subclavian vein is a feasible site for catheterization. The supraclavicular approach, especially the left side, has a higher first-puncture success rate, shorter access time, lower complications, and a trend of lower incidence of catheter malposition. However, a larger sample size of a randomized controlled study is expected to verify the advantages of ultrasound-guided subclavian catheterization in children.

Nebulized Budesonide Prevents Airway Inflammation in Children with High Total IgE Levels After Open Heart Surgery with Cardiopulmonary Bypass: A Prospective Randomized Controlled Trial.

Cardiopulmonary bypass (CPB) is a crucial technique used to repair congenital heart defects (CHD); however, it may induce inflammatory response, leading to airway inflammation and need for prolonged mechanical ventilation. In this study, we aimed to evaluate the effect of budesonide nebulization in children with high serum total immunoglobulin E (tIgE) levels undergoing surgical repair of CHD via CPB. We conducted a randomized, single-center, controlled trial at a tertiary teaching hospital. One-hundred and one children with high tIgE were enrolled and randomized into the budesonide nebulization group (BUD group, n = 50) or the normal saline nebulization group (NS group, n = 51) between January 2020 and December 2020. Budesonide or normal saline was administered through a vibrating mesh nebulizer during mechanical ventilation every 8 h. Blood and bronchoalveolar lavage fluid (BALF) samples were examined and data on airway mechanics and clinical outcomes were recorded. IL-6 and IL-8 levels in the blood and BALF samples significantly increased after CPB in both groups. Budesonide inhalation reduced IL-6 and IL-8 levels in the blood and BALF samples in children with high tIgE (P < 0.05). The mean airway pressure, PCO2, and oxygen index in the BUD group were significantly lower than those in the NS group after the first inhalation dose and persisted until almost 24 h after surgery. The peak inspiratory pressure and drive pressure were lower in the BUD group than in the NS group at nearly 24 h after surgery, with no significant difference at other time points. Additionally, the duration of mechanical ventilation, number of noninvasive ventilations after extubation, and number of patients using aerosol-inhaled bronchodilators after CICU in the BUD group were significantly lower than those in the NS group (P < 0.05). Children with high preoperative tIgE levels are at risk of airway inflammation after cardiopulmonary bypass. Inhaling budesonide during postoperative mechanical ventilation can reduce the intensity of inflammatory reactions, shorten the duration of mechanical ventilation, reduce airway pressure and the utilization of NIV after extubation.

Utilizing Spontaneous Ventilation Modes in Patients Underwent Corrective Surgery for Right Ventricular Outflow Tract Obstructive Congenital Heart Disease: A Crossover Study.

Background: This study aimed to determine whether the hemodynamics of patients with right ventricle outflow tract obstructive congenital heart disease (RVOTO-CHD) improve after corrective surgery by changing the ventilation mode. Methods: Patients with RVOTO-CHD who underwent corrective surgery were enrolled in this study. Echocardiography and advanced hemodynamic monitoring were performed using the pulse indicator continuous cardiac output (PiCCO) technology in the pressure-regulated volume control (PRVC) mode, followed with switching to the pressure support ventilation (PSV) mode and neurally adjusted ventilatory assist (NAVA) mode in random order. Results: Overall, 31 patients were enrolled in this study from April 2021 to October 2021. Notably, changing the ventilation mode from PRVC to a spontaneous mode (PSV or NAVA) led to better cardiac function outcomes, including right ventricular cardiac index (PRVC: 3.19 ± 1.07 L/min/ m 2 vs. PSV: 3.45 ± 1.32 L/min/ m 2 vs. NAVA: 3.82 ± 1.03 L/min/ m 2 , p < 0.05) and right ventricle contractility (tricuspid annular peak systolic velocity) (PRVC: 6.58 ± 1.40 cm/s vs. PSV: 7.03 ± 1.33 cm/s vs. NAVA: 7.94 ± 1.50 cm/s, p < 0.05), as detected via echocardiography. Moreover, in the NAVA mode, PiCCO-derived cardiac index (PRVC: 2.92 ± 0.54 L/min/ m 2 vs. PSV: 3.04 ± 0.56 L/min/ m 2 vs. NAVA: 3.20 ± 0.62 L/min/ m 2 , p < 0.05), stroke volume index (PRVC: 20.38 ± 3.97 mL/ m 2 vs. PSV: 21.23 ± 4.33 mL/ m 2 vs. NAVA: 22.00 ± 4.33 mL/ m 2 , p < 0.05), and global end diastolic index (PRVC: 295.74 ± 78.39 mL/ m 2 vs. PSV: 307.26 ± 91.18 mL/ m 2 vs. NAVA: 323.74 ± 102.87 mL/ m 2 , p < 0.05) improved, whereas extravascular lung water index significantly reduced (PRVC: 16.42 ± 7.90 mL/kg vs. PSV: 15.42 ± 5.50 mL/kg vs. NAVA: 14.4 ± 4.19 mL/kg, p < 0.05). Furthermore, peak inspiratory pressure, mean airway pressure, driving pressure, and compliance of the respiratory system improved in the NAVA mode. No deaths were reported in this study. Conclusions: We found that utilizing spontaneous ventilator modes, especially the NAVA mode, after corrective surgery in patients with RVOTO-CHD may improve their right heart hemodynamics and respiratory mechanics. However, further randomized controlled trials are required to verify the advantages of spontaneous ventilation modes in such patients. Clinical Trial Registration: NCT04825054.

Effect of high-energy and/or high-protein feeding in children with congenital heart disease after cardiac surgery: a systematic review and meta-analysis.

High-energy or high-protein feeding offers a promising approach to improving malnutrition in children after congenital heart surgery. However, the effect of high-energy or high-protein feeding in this population has not yet been systematically reviewed. Therefore, we aimed to assess the safety and effectiveness of high-energy or high-protein feeding in children after congenital heart surgery. Five electronic databases (PubMed, Embase, CENTRAL, CINAHL, and Scopus) were searched from inception to April 23, 2022. After screening the literature according to inclusion and exclusion criteria, a risk of bias assessment was performed using version 2 of the Cochrane risk-of-bias tool for randomized trials, and the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations system. Finally, the random effects model was used to perform a meta-analysis of all data. A total of 609 subjects from 9 studies were included for qualitative analysis, and meta-analyses were performed on data from 8 of these studies. The results showed that high-energy and/or high-protein feeding did not increase feeding intolerance (RR = 1.09, 95% CI: 0.80, 1.48) or fluid intake (MD = - 12.50 ml/kg/d, 95% CI: - 36.10, 11.10); however, the intervention was beneficial in increasing weight (MD = 0.5 kg, 95% CI: 0.23, 0.77) and reducing the duration of mechanical ventilation (MD = - 17.45 h, 95% CI: - 27.30, - 7.60), intensive care unit (ICU) stay (MD = - 1.45 days, 95% CI: - 2.36, - 0.54) and hospital stay (MD = - 2.82 days, 95% CI: - 5.22, - 0.43). However, high-energy and/or protein feeding did not reduce the infection rate (RR = 0.68, 95% CI: 0.25, 1.87) or mortality (RR = 1.50, 95% CI: 0.47, 4.82). CONCLUSION: The certainty of the evidence was graded as moderate to high, which suggests that high-energy and/or high-protein feeding may be safe in children after congenital heart surgery. Furthermore, this intervention improves nutrition and reduces the duration of mechanical ventilation, length of ICU stay, and length of hospital stay. However, the overall conclusion of this meta-analysis will need to be confirmed in a cohort of patients with different cardiac physiologies. WHAT IS KNOWN: • Malnutrition is highly prevalent in children with congenital heart disease (CHD) and can negatively affect the prognosis of these children. • High-energy and/or high-protein feeding can improve nutrition status and facilitate recovery; however, evidence on its safety and efficacy is lacking. WHAT IS NEW: • Pooled data suggest that high-energy and/or high-protein feeding does not increase fluid intake or feeding intolerance in children with CHD. • High-energy and/or high-protein feeding may reduce the duration of mechanical ventilation, length of intensive care unit stay, and length of hospital stay.

An electrochemical nitric oxide generator for in-home inhalation therapy in pulmonary artery hypertension.

BACKGROUND: Inhaled NO is a selective pulmonary vasodilator proven to be therapeutic for patients with pulmonary artery hypertension (PAH). The most common NO delivery system in clinical practice is cylinder-based, but unfortunately limited by its high costs, complicated delivery, and the requirement of an extensive supply chain, leaving vast unmet medical needs globally. METHODS: To address the need for rapid, affordable, and safe production of nitric oxide (NO) for in-home inhalation therapy in patients with PAH. We developed a novel portable device to derive NO from a nitrite complex solution with a copper(II)-ligand catalyst, and further examined its effectiveness in a porcine model of PAH. This model was established by using female Bama miniature pig and induced by monocrotaline (MCT) administration. RESULTS: This generator could rapidly and safely produce therapeutic NO at concentrations ranging from 0 to 100 parts per million (ppm) with the least disproportionated nitrogen dioxide (NO2) and byproducts. It could effectively alleviate pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in piglets with PAH, without causing major physiologic disruptions. CONCLUSIONS: Our electrochemical NO generator is able to produce the desired NO doses for pulmonary vasodilation in a safe and sustainable way, with low costs, which paves the way for its subsequent clinical trials in the patient with PAH and other common cardiopulmonary conditions with a high disease burden around the world.

Diagnostic Performance of Metagenomic Next-Generation Sequencing in Pediatric Patients: A Retrospective Study in a Large Children's Medical Center.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) has the potential to become a complementary, if not essential, test in some clinical settings. However, the clinical application of mNGS in a large population of children with various types of infectious diseases (IDs) has not been previously evaluated. METHODS: From April 2019 to April 2021, 640 samples were collected at a single pediatric hospital and classified as ID [479 (74.8%)], non-ID [NID; 156 (24.4%)], and unknown cases [5 (0.8%)], according to the final clinical diagnosis. We compared the diagnostic performance in pathogen detection between mNGS and standard reference tests. RESULTS: According to final clinical diagnosis, the sensitivity and specificity of mNGS were 75.0% (95% CI: 70.8%-79.2%) and 59.0% (95% CI: 51.3%-66.7%), respectively. For distinguishing ID from NID, the sensitivity of mNGS was approximately 45.0% higher than that of standard tests (75.0% vs 30.0%; P < 0.001). For fungal detection, mNGS showed positive results in 93.0% of cases, compared to 43.7% for standard tests (P < 0.001). Diagnostic information was increased in respiratory system samples through the addition of meta-transcriptomic sequencing. Further analysis also showed that the read counts in sequencing data were highly correlated with clinical diagnosis, regardless of whether infection was by single or multiple pathogens (Kendall's tau b = 0.484, P < 0.001). CONCLUSIONS: For pediatric patients in critical condition with suspected infection, mNGS tests can provide valuable diagnostic information to resolve negative or inconclusive routine test results, differentiate ID from NID cases, and facilitate accurate and effective clinical therapeutic decision-making.

Evaluation of acute kidney injury by urinary tissue inhibitor metalloproteinases-2 and insulin-like growth factor-binding protein 7 after pediatric cardiac surgery.

BACKGROUND: With adult patients, the measurement of [TIMP-2]*[IGFBP7] can predict the risk of moderate to severe AKI within 12 h of testing. In pediatrics, however, the performance of [TIMP-2]*[IGFBP7] as a predictor of AKI was less studied and yet to be widely utilized in clinical practice. This study was conducted to validate the utility of [TIMP-2]*[IGFBP7] as an earlier biomarker for AKI prediction in Chinese infants and small children. METHODS: We measured urinary [TIMP-2]*[IGFBP7] using NEPHROCHECK® at eight perioperative time points in 230 patients undergoing complex cardiac surgery and evaluated the performance of [TIMP-2]*[IGFBP7] for predicting severe AKI within 72 h of surgery. RESULTS: A total of 50 (22%) of 230 developed AKI stages 2-3 within 72 h after CPB initiation. In the AKI stage 2-3 patients, two patterns of serum creatinine (SCr) elevations were observed. The patients with only a transient increase in SCr within 24 h (< 24 h, early AKI 2-3) did not experience a worse outcome than patients in AKI stage 0-1. AKI stage 2-3 patients with SCr elevation after 24 h (24-72 h, late AKI 2-3), as well as AKI dialysis patients (together designated severe AKI), did experience worse outcomes. Compared to AKI stages 0-1, significant elevations of [TIMP-2]*[IGFBP7] values were observed in severe AKI patients at hours T2, T4, T12, and T24 following CPB initiation. The AUC for predicting severe AKI with [TIMP-2]*[IGFBP7] at T2 (AUC = 0.76) and maximum T2/T24 (AUC = 0.80) are higher than other time points. The addition of the NEPHROCHECK® test to the postoperative parameters improved the risk assessment of severe AKI. CONCLUSIONS: Multiple AKI phenotypes (early versus late AKI) were identified after pediatric complex cardiac surgery according to SCr-based AKI definition. Urinary [TIMP-2]*[IGFBP7] predicts late severe AKI (but not early AKI) as early as 2 h following CPB initiation. A higher resolution version of the Graphical abstract is available as Supplementary information.

What is the postoperative nutrition intake in children with congenital heart disease? A single-center analysis in China.

BACKGROUND: It is common that inadequate nutritional intake happens in patients with congenital heart disease (CHD), which can adversely affect the prognosis of patients. However, the details and reasons are not clear enough so far. Therefore, the primary aim of this study was to investigate the current nutritional requirements and energy intake on days 1-7 in the cardiac intensive care unit after surgery. Our secondary aim was to investigate potential factors that hinder nutritional supply and to compare the resting energy expenditure (REE) based on two methods, the Fick method and the Schofield equation. METHODS: Using retrospective analysis, we collected data from postoperative children with CHD at a children's hospital in Shanghai, China. We used the Fick method to calculate the REE, and compare the results with the actual enteral nutrition intake. Meanwhile, we recorded the initiation time of enteral nutrition, feeding intolerance, unfinished milk volume, etc. Then the correlation between the results of the Fick method and the equation method was calculated. RESULTS: A total of 49 patients were included, with a median age of 22 months (IQR 4.9, 57.3), and a median Aristotle basic complexity score of 8 (IQR 6.0, 9.8). The time interval for surgical intervention within 7 days after operation was 4 (IQR 2.5, 6). No statistical difference in REE on postoperative days 1-7. The average enteral nutrition energy provided 64.6 (33.6, 79.6)% of the REE, which showed a significant decrease on postoperative day 4, and then reached its lowest on postoperative day 5. The protein supply was 0.7 ± 0.3 kcal/kg/d. In addition, the REE calculated by the Fick method was moderately correlated with that estimated by the equation (r = 0.467, P = 0.001). CONCLUSIONS: The energy and protein supply in the acute postoperative period in children with CHD is inadequate. Fluid restriction and fasting may be the main causes. In addition, there is a moderate correlation between the REE calculated by the Fick method and that estimated by the equation.

Predictive factors contributing to prolonged recovery in patients after Fontan operation.

BACKGROUND: Prolonged recovery is a severe issue in patients after Fontan operation. However, predictive factors related to this issue are not adequately evaluated. The present study aimed to investigate potential predictive factors which can predict Fontan postoperative recovery. METHODS: We retrospectively reviewed the perioperative medical records of patients with Fontan surgery between January 2015 and December 2018, and divided patients with > 75%ile cardiac intensive care unit stay into prolonged recovery group. The others were assigned to standard recovery group. Patients that died or underwent a Fontan takedown were excluded. Statistical analysis was performed to compare data difference of the two groups. RESULTS: 282/307 cases fulfilled the inclusion criteria. Seventy patients were considered in prolonged recovery and 212 patients were defined as standard recovery. Pre- and intra-operative data showed a higher incidence of heterotaxy syndrome, longer cardiopulmonary bypass and aortic cross-clamp time in the prolonged recovery group. Postoperative information analysis displayed that ventilation time, oxygen index after extubation, hemodynamic data, inotropic score (IS), drainage volume, volume resuscitation, pulmonary hypertension (PH) treatment, and surgical reintervention were significantly different between the two groups. Higher IS postoperatively, and PH treatment and higher fluid resuscitation within two days were independent predictive factors for prolonged recovery in our multivariate model. C-statistic model showed a high predictive ability in prolonged recovery by using the three factors. CONCLUSIONS: Ventilation time, higher IS in postoperative day, and PH treatment and higher fluid resuscitation within two days were independent risk factors and have a high predictability for Fontan prolonged recovery.

Exposure to traffic-related fine particulate matter 2.5 causes respiratory damage via peroxisome proliferator-activated receptor gamma-regulated inflammation.

Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation. Peroxisome proliferator-activated receptor gamma (PPARγ) has been reported to regulate inflammatory responses in diverse cell types. Therefore, this work investigated the mechanisms of PPARγ in regulating traffic-related PM2.5-induced airway inflammation. Using the diffusion flame burner soot generation, traffic-related PM2.5 was generated and adsorbed. BALB/c male mice and human bronchial epithelial cells (16-HBE) were exposed to PM2.5 alone or co-treatment with rosiglitazone (RSG), an agonist of PPARγ. To the end of exposure, bronchoalveolar lavage fluid (BALF), venous blood and arterial blood, trachea, bronchus and lung tissues were collected. The levels of IL-1ß, IL-6, and IL-17 were detected by ELISA, and the cell types in BALF were counted. Hematoxylin-eosin (H&E) assay were used to analyze the pathological conditions of lung, bronchus, and pulmonary artery. Apoptosis was detected by TUNEL, and PPARγ expression in lung and bronchus was detected by immunohistochemical (IHC) staining. Western Blot was used to detect PPARγ, NF-kB, AP-1 and STAT3 expression in lung and bronchus. The viability was detected by MTT method. PM2.5 exposure caused pathological damage to the lung, bronchus and pulmonary artery tissue, which induced apoptosis of bronchial epithelial cells. PM2.5 exposure caused local inflammation of the whole body and airway. PPARγ expression increased after PM2.5 exposure. PM2.5 exposure regulated the downstream signaling pathways to affect the inflammatory response through PPARγ. Exposure to traffic-related PM2.5 caused respiratory damage via PPARγ-regulated inflammation.

Prediction value of regional oxygen saturation in intestine and kidney for acute kidney injury in children with congenital heart disease after surgery.

OBJECTIVE: To study the prediction value of regional oxygen saturation (rSO 2) in brain, intestine and kidney for acute kidney injury (AKI) in children with congenital heart disease after surgery. METHODS: Fifty-seven children with congenital heart disease (CHD), whose weight >2.5 kg and age≤1 year were treated in Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2020 to December 2020. The rSO 2 of brain, intestine and kidney were monitored with near-infrared spectroscopy continuously for 48 h after surgery. The predictive values of cerebral, intestinal and renal rSO 2 for occurrence and severity of postoperative AKI were analyzed. RESULTS: Among 57 patients, postoperative AKI developed in 38 cases (66.7%), including 18 cases of AKI-1 (47.4%), 9 cases of AKI-2 (23.7%) and 11 cases of AKI-3 (28.9%). There was no significant difference in cerebral rSO 2 between AKI group and non-AKI group ( F=0.012, P>0.05), while the intestinal rSO 2 and renal rSO 2 in AKI group were significantly lower than those in non-AKI group ( F=5.017 and 5.003, both P<0.05). There was no significant difference in brain rSO 2 between children with or without AKI-2 and above ( F=0.311, P>0.05), but the intestinal rSO 2 and renal rSO 2 in children with AKI-2 and above were lower than other children ( F=6.431 and 14.139, both P<0.05). The area under ROC curve (AUC) of intestinal rSO 2 3 h after surgery for predicting AKI was 0.823, and with intestinal rSO 2 3 h after surgery <85%, the sensitivity and specificity were 66.7% and 89.5%, respectively. The AUC of renal rSO 2 for the diagnosis of AKI at 31 h after surgery was 0.918, and with intestinal rSO 2 31 h after surgery <84%, the sensitivity and specificity were 72.2% and 84.2%, respectively. The AUC of intestinal rSO 23 h after surgery for the diagnosis of AKI-2 and above was 0.829, and with intestinal rSO 2 3 h after surgery <84%, the sensitivity and specificity were 62.2% and 90.0%, respectively. The AUC of renal rSO 2 for the diagnosis of AKI-2 and above was 0.826 at 34 h postoperatively, and with intestinal rSO 2 34 h after surgery <71%, the sensitivity and specificity were 91.9% and 55.0%, respectively. CONCLUSION: The monitoring of intestinal and renal rSO 2 can predict the occurrence and severity of postoperative AKI in children with congenital heart disease after surgery.

MIR3142HG promotes lipopolysaccharide-induced acute lung injury by regulating miR-450b-5p/HMGB1 axis.

The present study aimed to evaluate the potential roles of MIR3142HG, a novel long non-coding RNA (lncRNA) in lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was simulated by the treatment of LPS in human pulmonary microvascular endothelial cells (HPMECs). The expression of MIR3142HG, miR-450b-5p and high-mobility group box 1 (HMGB1) was determined by real-time PCR and western blotting. Functional analysis was performed through the assessment of cell viability, apoptosis and the production of proinflammatory cytokines. The interactions among MIR3142HG, miR-450b-5p and HMGB1 were analyzed by bioinformatics methods, dual-luciferase reporter and RNA pull-down assays. Using gain- and loss-of-function approaches, the in vitro functions of MIR3142HG and miR-450b-5p were subsequently assessed. MIR3142HG expression was upregulated, while miR-450b-5p was decreased in LPS-treated HPMECs. MIR3142HG knockdown protected against ALI induced by LPS through alleviating the apoptosis and inflammation of HPMECs. MIR3142HG impaired miR-450b-5p-mediated inhibition of HMGB1. Besides, the effects of MIR3142HG silencing could be alleviated by miR-4262 inhibition or HMGB1 overexpression. MIR3142HG mediated LPS-induced injury of HPMECs by targeting miR-450b-5p/HMGB1, suggesting that MIR3142HG might serve as a therapeutic potential for the treatment of ALI.

Postcardiotomy Extracorporeal Membrane Oxygenation in Neonates.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides circulatory support in children with congenital heart disease, particularly in the setting of cardiopulmonary failure and inability to wean from cardiopulmonary bypass. This study summarized the clinical application of ECMO in the treatment of heart failure after cardiac surgery in neonates. MATERIALS AND METHODS: Clinical data of 23 neonates who received ECMO support in our center from January 2017 to June 2019 were retrospectively analyzed. RESULTS: Twenty-three neonates, aged from 0 to 25 days and weight between 2,300 and 4,500 g, with heart failure postcardiotomy were supported with ECMO. The successful weaning rate was 78.26% and discharge rate was 52.17%. Bleeding and residual malformation were the most common complications. The univariate analysis showed that nonsurvivors were related to the factors such as higher lactate value of ECMO 12 and 24 hours (p = 0.008 and 0.001, respectively), longer time to lactate normalization (p = 0.001), lactate > 10 mmol/L before ECMO (p = 0.01), lower weight (p = 0.01), longer ECMO duration (p = 0.005), lower platelet count (p = 0.001), more surgical site bleeding (p = 0.001), and surgical residual malformation (p = 0.04). Further logistic regression analysis revealed that higher lactate value of ECMO 24 hours (p = 0.003), longer ECMO duration (p = 0.015), and surgical site bleeding (p = 0.025) were independent risk factors. CONCLUSION: ECMO was an effective technology to support the neonates with cardiopulmonary failure after open heart surgery. Control the lactate acidosis and surgical site bleeding event may be helpful for patients' recovery.

Elevated Arterial-Central Venous Carbon Dioxide Partial Pressure Difference Indicates Poor Prognosis in the Early Postoperative Period of Open Heart Surgery in Infants with Congenital Heart Disease.

BACKGROUND: Elevated arterial-central venous carbon dioxide partial pressure difference (AVCO2) may be an important marker to predict tissue and organ hypoperfusion in adults. We analyzed the hemodynamic data of infants with congenital heart disease who underwent corrective repair with cardiopulmonary bypass (CPB) to identify whether AVCO2 has clinical significance in early postoperative tissue hypoperfusion, occurrence of complications, and clinical outcomes. METHODS: Infants with clinical conditions of hypoperfusion, without volume responsiveness and with ineffective initial treatment, within 3 h of cardiac surgery were enrolled in this study. A pulse contour cardiac output catheter was used to monitor the cardiac index (CI). Eight measurements of arterial blood gas and central venous blood gas were taken within 42 h after surgery. Clinical data of all patients were recorded. RESULTS: A total of 69 children were enrolled in this study. Arteriovenous oxygen difference, AVCO2, lactic acid level, and vasoactive inotropic score in the hypoperfusion group (oxygen supply/oxygen consumption ratio [DO2/VO2] of ≤ 2) were significantly higher than those in the non-hypoperfusion group (DO2/VO2 > 2), while the CI in the hypoperfusion group was significantly lower than that in the non-hypoperfusion group. The cutoff value of AVCO2 to predict DO2/VO2 ≤ 2 was 12.3 within 42 h of surgery with area under the curve of 0.84. High AVCO2 is more likely to be associated with some complications and prolonged mechanical ventilation and length of stay in the intensive care unit. CONCLUSION: Elevated AVCO2 within 42 h of CPB in infants is associated with tissue and organ hypoperfusion and incidence of complications. Persistent or repeated increase in AVCO2 indicates poor prognosis.

Risk factors of malnutrition in Chinese children with congenital heart defect.

BACKGROUND: The study aimed to investigate the risk factors of malnutrition in children with congenital heart defect (CHD) in China. METHODS: This cohort study was performed at the biggest pediatric heart center in China; 3252 patients with CHD who underwent cardiac surgeries in 2013 were included. Anthropometric measurements included weight for age Z score (WAZ), weight for height Z score (WHZ), and height for age Z score (HAZ). The patients were classified as normal nutritional status and malnutrition, based on a cut-off Z score of <- 2. Factors associated with malnutrition were determined using logistic regression analysis. RESULTS: The prevalence of preoperative WAZ < -2 (underweight), HAZ < -2 (stunting), and WHZ < -2 (wasting) was 23.3, 23.3, and 14.3%, respectively. The multivariable analysis of preoperative malnutrition showed that hospitalization, age at surgery, risk adjustment for congenital heart surgery-1 > 3, mechanical ventilation, pulmonary hypertension, and acyanotic heart disease were associated with underweight. Parents' height, single ventricle, and cyanotic heart disease were associated with stunting. Hospitalization and pulmonary hypertension were associated with wasting. After surgery, the patients presented a significant improvement in growth within the first year in all three parameters and grew to the normal range of WAZ (- 0.3 ± 0.9, P < 0.001), HAZ (0.2 ± 0.8, P = 0.001), and WHZ (0.03 ± 0.6, P < 0.001) at 2 years after surgery. The prevalence of underweight, stunted, and wasting declined to 3.2, 2.7, and 1.9% 3 years after surgery. Malnutrition after surgery was associated with cardiac residual cardiac abnormalities (OR = 35.3, p < 0.0001), high Ross classification of heart function (OR = 27.1, p < 0.0001), and long-term taking oral diuretics (OR = 20.5, P = 0.001). CONCLUSIONS: Malnutrition is still a problem in children with CHD in China, especially before the surgery. There is need to strengthen the nutrition support for children with CHD before surgery. Hemodynamic factors were found to be the risk factors associated with malnutrition after operation.

Characteristics of Pulmonary Vascular Remodeling in a Porcine Model of Shunt-Associated Pulmonary Arterial Hypertension.

Lung biopsy is the gold standard for evaluating pathological changes in the pulmonary vascular bed. Knowing the distribution characteristics of pulmonary vascular lesions can improve the accuracy of lung biopsy. To investigate the distribution characteristics of pulmonary vascular remodeling, a reliable porcine model of shunt-associated pulmonary arterial hypertension (PAH) was established. Twenty piglets were randomly divided into the experimental group (n = 10) and the control group (n = 10). A modified Blalock-Taussig shunt (MBTS, left innominate artery to main pulmonary artery) was created surgically in the experimental group. Three months later, an invasive catheter was used to obtain hemodynamic parameters, and lung biopsy was performed to assess the remodeling of pulmonary vascular bed. MBTS was successfully implemented in six piglets. There's no significant difference in hemodynamic parameters of the two groups before the shunt. However, these parameters and right ventricular hypertrophy index of the experimental group were significantly increased after three months shunting. Pathological changes in the experimental group, including thickening of pulmonary artery media, intimal fibrosis, and right ventricular hypertrophy, were observed. Furthermore, the percentage of media thickness and medial area of the experimental group were significantly higher than control group. Histopathology showed that vascular remodeling of the lung was inhomogeneous and that the lateral lesion was more severe than other segments. These results indicated that MBTS could be used to establish a reliable porcine model of shunt-associated PAH and that multisite detection with different segments should be applied to assess the severity of pulmonary vascular remodeling.

The Nutritional Status of Pediatric Patients with Single Ventricle Undergoing a Bidirectional Glenn Procedure.

Single ventricle (SV) physiology is associated with growth retardation in children. The nutritional status of pediatric patients with SV undergoing a bidirectional Glenn (BDG) procedure vitally affects the feasibility of the next operation stages. To explore the nutritional status and to identify specific anthropometric parameters relevant to short-term surgical outcomes in children with SV after the BDG procedure, this study included 151 patients who underwent the BDG procedure. Anthropometric assessments and Infant and Child Feeding Index (ICFI) scores were used to evaluate nutritional status. There was a significant statistical correlation between ICFI and malnutrition in both the height-for-age Z-score (HAZ) and weight-for-age Z-score (WAZ) groups (P < 0.05). The clinical data, including ventilation time, nosocomial infection presence, pressure injury presence, peritoneal dialysis status, and total intensive care unit days, after BDG surgery were significantly different among the HAZ groups (P < 0.05), while nosocomial infection was different among the WAZ groups (P < 0.05). Children after BDG procedure had a high incidence of malnutrition, in addition to disease factors, the type and frequency of dietary intake were also important factors leading to worse clinical outcomes during hospitalization. Therefore, it is vital to maintain an optimal nutritional status in infants with SV who are undergoing a series of surgical procedures.

Characteristics of Pulmonary Vascular Remodeling in a Novel Model of Shunt-Associated Pulmonary Arterial Hypertension.

BACKGROUND Establishing a shunt-induced pulmonary arterial hypertension (PAH) model in mice would be of great scientific value, but no such models have been reported to date. Here, we established a shunt-associated PAH in mice to investigate the characteristics of pulmonary vascular remodeling, which provides a new platform for the in-depth study of PAH associated with congenital heart disease (CHD). MATERIAL AND METHODS Eighty mice were randomly divided into the heavy shunt group (n=32), the small shunt group (n=32), the sham operation group (n=8), and the control group (n=8). The septum of the abdominal aorta and inferior vena cava was cut directly to create a heavy abdominal aortocaval shunt. Pulmonary artery pressure, right ventricular hypertrophy index, and lung tissue morphology were evaluated in the 4th, 6th, 8th, and 12th weeks in the shunt groups. RESULTS Shunt-associated PAH by abdominal aortocaval shunt in mice was successfully established. The shunt patency rate was significantly higher in the heavy shunt group. Significant differences were observed between the heavy shunt group and other groups in terms of pulmonary artery pressure and the right ventricular hypertrophy index. Tissue sections revealed a thickened pulmonary intimal layer and muscular layer and stenosis of the lumen in the shunt groups. Immunofluorescent assay results showed significant proliferations of PAH smooth muscle cells and endothelial cells, consistent with the clinical pulmonary vascular remodeling seen in human patients with severe PAH. CONCLUSIONS Shunt-associated PAH established by directly cutting the septum between the abdominal aorta and inferior vena cava is a stable and reliable model for research on PAH associated with CHD.

Mechanical Ventilation After Bidirectional Superior Cavopulmonary Anastomosis for Single-Ventricle Physiology: A Comparison of Pressure Support Ventilation and Neurally Adjusted Ventilatory Assist.

We evaluated the effects of different respiratory assist modes on cerebral blood flow (CBF) and arterial oxygenation in single-ventricle patients after bidirectional superior cavopulmonary anastomosis (BCPA). We hypothesized that preserved auto-regulation of respiration during neurally adjusted ventilatory assist (NAVA) may have potential advantages for CBF and pulmonary blood flow regulation after the BCPA procedure. We enrolled 23 patients scheduled for BCPA, who underwent pressure-controlled ventilation (PCV), pressure support ventilation (PSV), and NAVA at two assist levels for all modes in a randomized order. PCV targeting large V T (15 mL × kg(-1)) resulted in lower CBF and oxygenation compared to targeting low V T (10 mL × kg(-1)). During PSV and NAVA, ventilation assist levels were titrated to reduce EAdi from baseline by 75 % (high assist) and 50 % (low assist). High assist levels during PSV (PSVhigh) were associated with lower PaCO2, PaO2, and O2SAT, lower CBF, and higher pulsatility index compared with those during NAVAhigh. There were no differences in parameters when using low assist levels, except for slightly greater oxygenation in the NAVAlow group. Modifying assist levels during NAVA did not influence hemodynamics, cerebral perfusion, or gas exchange. Targeting the larger V T during PCV resulted in hyperventilation, did not improve oxygenation, and was accompanied by reduced CBF. Similarly, high assist levels during PSV led to mild hyperventilation, resulting in reduced CBF. NAVA's results were independent of the assist level chosen, causing normalized PaCO2, improved oxygenation, and better CBF than did any other mode, with the exception of PSV at low assist levels.