Identification and analysis of inflammation-related biomarkers in tetralogy of Fallot.

Background: Studies have revealed that inflammatory response is relevant to the tetralogy of Fallot (TOF). However, there are no studies to systematically explore the role of the inflammation-related genes (IRGs) in TOF. Therefore, based on bioinformatics, we explored the biomarkers related to inflammation in TOF, laying a theoretical foundation for its in-depth study. Methods: TOF-related datasets (GSE36761 and GSE35776) were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between TOF and control groups were identified in GSE36761. And DEGs between TOF and control groups were intersected with IRGs to obtain differentially expressed IRGs (DE-IRGs). Afterwards, the least absolute shrinkage and selection operator (LASSO) and random forest (RF) were utilized to identify the biomarkers. Next, immune analysis was carried out. The transcription factor (TF)-mRNA, lncRNA-miRNA-mRNA, and miRNA-single nucleotide polymorphism (SNP)-mRNA networks were created. Finally, the potential drugs targeting the biomarkers were predicted. Results: There were 971 DEGs between TOF and control groups, and 29 DE-IRGs were gained through the intersection between DEGs and IRGs. Next, a total of five biomarkers (MARCO, CXCL6, F3, SLC7A2, and SLC7A1) were acquired via two machine learning algorithms. Infiltrating abundance of 18 immune cells was significantly different between TOF and control groups, such as activated B cells, neutrophil, CD56dim natural killer cells, etc. The TF-mRNA network contained 4 mRNAs, 31 TFs, and 33 edges, for instance, ELF1-CXCL6, CBX8-SLC7A2, ZNF423-SLC7A1, ZNF71-F3. The lncRNA-miRNA-mRNA network was created, containing 4 mRNAs, 4 miRNAs, and 228 lncRNAs. Afterwards, nine SNPs locations were identified in the miRNA-SNP-mRNA network. A total of 21 drugs were predicted, such as ornithine, lysine, arginine, etc. Conclusions: Our findings detected five inflammation-related biomarkers (MARCO, CXCL6, F3, SLC7A2, and SLC7A1) for TOF, providing a scientific reference for further studies of TOF.

A randomized trial of the inflammatory cytokines levels and the blood transfusion rate between miniaturized tubing group and conventional tubing group in congenital heart disease open heart surgeries.

INTRODUCTION: We aimed to compare the inflammatory cytokines levels of the miniaturized and conventional extracorporeal circuit system. The miniaturized extracorporeal circuit system may be fewer possible inflammation-induced or blood transfusion-related complications. METHODS: We performed a prospective randomized controlled trial (RCT) of 101 patients undergoing congenital heart surgery with CPB (cardiopulmonary bypass, weight ≤15 kg, age ≤2 years). Patients were divided into two different CPB groups randomly by random data form. Blood samples at five different time points and the ultrafiltration fluid before and after CPB were collected in all patients. IL-6, IL-8, and TNF alpha were respectively tested with Abcam ELISA kit. RESULTS: The IL-6 level of blood serum in two groups had no statistical differences between the two groups at all time points. The IL-8 level of blood serum in two groups had no statistical differences right after anesthesia and 5 min after CPB. However, IL-8 level was significantly higher in conventional extracorporeal circuit group than that in miniaturized extracorporeal circuit group at 6 h, 12 h and 24 h after CPB. Blood serum TNF alpha in conventional extracorporeal circuit group was significantly higher at 6 h after CPB than that in miniaturized extracorporeal circuit group. No statistical differences in TNF alpha were found between two groups right after anesthesia and at 5 min after CPB, 12 h and 24 h after CPB. In ultrafiltration fluid, no statistical differences were found in IL-6, IL-8 nor TNF alpha between two groups in all time. No statistical differences were found in ICU (intensive care unit) stay and mechanical ventilation time between the two groups. The blood transfusion rate was significantly lower in miniaturized extracorporeal circuit group. CONCLUSION: Implementing the miniaturized extracorporeal circuit system could decrease the inflammatory cytokines at a certain level. The blood transfusion rate is significantly lower in miniaturized extracorporeal circuit group This indicates the miniaturized extracorporeal circuit system might be a safer CPB strategy with fewer possible inflammation-induced or blood transfusion-related complications.

Coagulation after paediatric miniaturised versus conventional cardiopulmonary bypass: Retrospective cohort study.

BACKGROUND: Cardiopulmonary bypass (CPB) causes coagulation disorders after surgery. This study aimed to compare the coagulation parameters after congenital cardiac surgery with miniaturised CPB (MCPB) versus conventional CPB (CCPB). METHODS: We gathered information about children who underwent cardiac surgery between 1/1/2016 and 12/31/2019. Using propensity score-matched data, we compared the coagulation parameters and postoperative outcomes of the MCPB and CCPB groups. RESULTS: A total of 496 patients (327 with MCPB, 169 withCCPB) underwent congenital cardiac surgery, and 160 matched pairs in each group were enrolled in the analysis. Compared with CCPB children, MCPB children had a lowermean prothrombin time (14.9 ± 2.0 vs 16.4 ± 4.1; p < 0.001)and international normalised ratio (1.3 ± 0.2 vs. 1.4 ± 0.3; p < 0.001), but higher thrombin time (23.4 ± 20.4 vs 18.2 ± 4.4; p = 0.002). The CCPB group had greaterperioperative changes inprothrombin time, international normalised ratio, fibrinogen, and antithrombin III activity (all p < 0.01) but lower perioperative changesin thrombin time (p = 0.001) thanthe MCPB group. Ultra-fasttrack extubation and blood transfusionrates, postoperative blood loss, and intensive care unitlength of stay were considerably decreased in the MCPB group. There were no considerable intergroup differences in the activated partial thromboplastin time or platelet count. CONCLUSIONS: Compared with CCPB, MCPB was associated with lower coagulation changes and better early outcomes, including shorter intensive care unit stay and less postoperative blood loss.

Total anomalous pulmonary venous connection in 80 patients: Primary sutureless repair and outcomes.

Introduction: Total anomalous pulmonary venous connection (TAPVC) is a rare but critical cardiac anomaly, in which pulmonary veins are connected to an abnormal location rather than the left atrium. The prognosis can be extremely poor without intervention, with a mortality of 80% during infancy. The purpose of this research is to summarize the outcomes and relevant risk factors of 80 total anomalous pulmonary venous connection (TAPVC) patients who underwent primary TAPVC sutureless repair and discuss the indications and benefits of primary sutureless repair. Methods: This retrospective review included 80 patients with TAPVC who underwent primary sutureless repair at a single institution between January 2015 and December 2020. Patients were subdivided into 4 groups according to Darling's classification. Risk factors that increase the postoperative pulmonary vein flow velocity were explored by Multiple Linear regression. Results: Anatomic TAPVC subtypes included supracardiac 35 (43.8%), cardiac 24 (30%), infracardiac 17 (21.2%), and mixed 4 (5%). Median age at repair was 16.5 days and median weight was 3.5 kg. Preoperative pulmonary venous obstruction (PVO)was presented in 20 (25%) patients. There were 2 early deaths and 1 late death. 2 patients developed postoperative PVO and none required reintervention. Prolonged cardiopulmonary bypass time (CPB) (p = 0.009), preoperative pneumonia (p = 0.022) and gender (p = 0.041) were found to be associated with the increase of postoperative pulmonary vein flow velocity. Discussion: Under the primary sutureless technique, no statistical difference was observed among the 4 subgroups in terms of postoperative pulmonary vein flow velocity (p = 0.589). The primary sutureless technique may eliminate the differences between subtypes while decrease the postoperative PVO rate, which makes it applicable in any subtypes of TAPVC. Following the favorable outcomes in preventing postoperative PVO in all subtypes in this study, we advocate the indications for primary sutureless repair may expand further to all the TAPVC patients.

Impact of miniaturized cardiopulmonary bypass circuits on ultrafiltration during congenital heart surgery.

OBJECTIVE: To investigate whether the miniaturized cardiopulmonary bypass (CPB) system decreased the usage of ultrafiltration (UF), and to explore whether the non-UF with miniaturized CPB strategy could get good clinical results during congenital heart surgery. METHODS: We performed a retrospective analysis of all patients undergoing congenital heart surgery with CPB at Shenzhen Children's Hospital from 1 May 2015 to 30 September 2019. We classified patients to UF with miniaturized CPB group, non-UF with miniaturized CPB group, UF with conventional CPB group and non-UF with conventional CPB group. RESULTS: Of the 2145 patients, 721 (33.6%) were in the conventional CPB group, and 1424 (66.4%) were in the miniaturized CPB group. The UF rate was significantly lower in the miniaturized CPB group compared with that in the conventional CPB group (12.5% vs. 76.8%, p < 0.001). Compared with patients in the other groups, patients in the non-UF with miniaturized CPB group had a shorter postoperative MV time (p < 0.05), and a shorter length of stay in the ICU (p < 0.001) and hospital (p < 0.001). The age of children in the UF with miniaturized CPB group was relatively younger (median: 1.5 months, IQR: 0.3-4.6 months), and the preoperative weight was relatively lower (median: 3.9 kg, IQR: 3.2-5.4 kg). Moreover, this group of children had a relatively longer postoperative MV time and length of stay in the ICU and hospital. CONCLUSION: The miniaturized CPB system could decrease the usage of UF. Good results were achieved in children who did not use UF based on the miniaturized CPB circuit system during congenital heart surgery.

Effect of retrograde autologous priming based on miniaturized cardiopulmonary bypass in children undergoing open heart surgery: A STROBE compliant retrospective observational study.

To evaluate the effectiveness of retrograde autologous priming (RAP) based on miniaturized cardiopulmonary bypass (CPB) circuit in children undergoing open heart surgery.We performed a retrospective analysis of all patients (≤15 kg) who underwent open heart surgery with CPB in our center from January 1, 2017, to July 31, 2019. Propensity score matching was used to adjust for significant covariates, and multivariable stratified analysis was used to assess the association of the RAP technique with clinical outcomes.A total of 1111 patients were analyzed. There were 355 (32.0%) children who underwent RAP, and 756 (68.0%) were in the non-RAP group. After propensity score matching, there were a total of 638 patients, with 319 patients in each group. The bloodless priming rate was significantly higher (P = .013), and the ultrafiltration rate was significantly lower (P = .003) in the RAP group than in the non-RAP group. Compared with patients in the non-RAP group, patients in the RAP group had a shorter postoperative mechanical ventilation time (P < .001) and shorter lengths of stay in the intensive care unit (ICU) (P < .001) and the hospital (P < .001). No differences were noted in postoperative hematocrit (P = .920), postoperative 24-hour blood loss (P = .435), and hospital mortality (P = .563). In the stratified analysis, the difference remained statistically significant (P < .05) when the patient weight was >4 kg or the Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery (STAT) category was <3. However, when the patient weight was ≤4 kg or the STAT category was ≥3, there was no significant difference between the 2 groups in terms of bloodless priming, ultrafiltration, postoperative mechanical ventilation time, or length of stay in the ICU or the hospital (P > .05).The RAP technique based on miniaturized CPB system was safe and effective for children who underwent congenital heart surgery. The RAP technique can significantly reduce the priming volume, improve the rate of bloodless priming, and reduce blood product application. It was also associated with a shorter postoperative mechanical ventilation time and shorter lengths of stay in the ICU and the hospital.

Comparison of two cardiopulmonary bypass strategies with a miniaturized tubing system: a propensity score-based analysis.

INTRODUCTION: The existing cardiopulmonary bypass tubing system has already been significantly improved in our hospital by reducing the priming volume; thus, we further employed a new cardiopulmonary bypass strategy in children based on a miniaturized cardiopulmonary bypass circuit. We aimed to compare the effectiveness of new and conventional strategies by analyzing the outcomes after congenital heart surgery. METHODS: We performed a database analysis of all patients undergoing congenital heart surgery with cardiopulmonary bypass at Shenzhen Children's Hospital from 1 May 2015 to 30 June 2017. Propensity score matching was used to adjust for significant covariates, and multivariable regression models and stratified analysis were used to assess the association of cardiopulmonary bypass strategy with outcomes. RESULTS: Of 925 total patients, 55.35% were in the conventional strategy group and 44.65% were in the new strategy group. After propensity score matching, there were 610 patients in total, with 305 patients in each group. In the multivariable regression models, the cardiopulmonary bypass strategy was not significantly associated with successful early extubation (p > 0.05), reintubation (p > 0.05), or nasal continuous positive airway pressure (p > 0.05) rates. The new strategy group had fewer hospital stays (p = 0.04) and intensive care unit stays (p < 0.05) compared with patients who underwent conventional strategy. The difference remained statistically significant (p < 0.05) when The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category was <3. CONCLUSION: The implementation of a new cardiopulmonary bypass strategy, with selective ultrafiltration based on a miniaturized cardiopulmonary bypass circuit system, was safe and effective for children who underwent congenital heart surgery in a Chinese hospital. The new cardiopulmonary bypass strategy was associated with fewer hospital and intensive care unit stays.

[A preliminary investigation of relationship between serum apelin level and pulmonary artery pressure in children with congenital heart disease].

OBJECTIVE: To preliminarily investigate the relationship between serum apelin level and pulmonary artery pressure in children with congenital heart disease. METHODS: One hundred and twenty-six children with congenital heart disease undergoing surgical treatment were enrolled as subjects. The serum level of apelin was determined before surgery and at 7 days after surgery. The ratio of pulmonary artery systolic pressure to aortic systolic pressure (Pp/Ps) was calculated before extracorporeal circulation. According to the Pp/Ps value, patients were classified into non-pulmonary arterial hypertension (PAH) group, mild PAH group, moderate PAH group, and severe PAH group. Pulmonary artery mean pressure was estimated by echocardiography at 7 days after surgery. RESULTS: The non-PAH group had the highest serum level of apelin before and after surgery, followed by the mild PAH group, moderate PAH group, and severe PAH group (P<0.05). All groups had significantly increased serum levels of apelin at 7 days after surgery (P<0.05). The serum level of apelin was negatively correlated with pulmonary artery pressure before surgery (r=-0.51, P<0.05) and at 7 days after surgery (r=-0.54, P<0.05). CONCLUSIONS: The decrease in serum apelin level is associated with the development of pulmonary hypertension in children with congenital heart disease. The significance of serum apelin in predicting the development and degree of pulmonary hypertension in children with congenital heart disease deserves further studies.

[Protective effect of cold autologous blood cardioplegic solution on the heart of infants with cyanotic congenital heart disease].

OBJECTIVE: To study the protective effect of cold autologous blood cardioplegic solution on the heart of infants with cyanotic congenital heart disease (CCHD). METHODS: Ninety-six infants with CCHD who underwent cardiopulmonary bypass (CPB) were randomly and equally divided into three groups: histidine-tryptophan-ketoglutarate (HTK) solution, cold non-autologous blood cardioplegic solution, and cold autologous blood cardioplegic solution. The right auricular tissues were taken before aortic cross-clamping and at 30 minutes after aortic declamping, and ATP level and energy charge (EC) in the myocardium were measured. Venous blood was collected before and immediately after CPB, and the serum levels of creatine kinase (CK)-MB and cardiac troponin I (cTnI) were measured. The clinical parameters, such as the re-beat time and re-beat rate during CPB, cardiac index, dependence on positive inotropic agents, and left ventricular ejection fraction (LVEF) at 2 hours after CPB, the incidence rate of arrhythmia within 24 hours after CPB, and postoperative complications and mortality, were recorded. RESULTS: At 30 minutes after aortic declamping, the three groups showed significantly decreased ATP and EC levels (P<0.05), and the cold autologous blood group had significantly higher ATP and EC levels than the other two groups (P<0.05). Immediately after CPB, the three groups showed significantly increased serum levels of CK-MB and cTnI (P<0.05), and the cold autologous blood group had significantly lower serum levels of CK-MB and cTnI than the other two groups (P<0.05). The cold autologous blood group had significantly better outcomes than the other two groups in terms of the re-beat time during CPB and the dependence on positive inotropic agents and LVEF at 2 hours after CPB (P<0.05). CONCLUSIONS: Cold autologous blood cardioplegic solution is superior to HTK and cold non-autologous blood cardioplegic solutions in preserving myocardial energy and reducing myocardial injury in infants with CCHD who undergo CPB, thus providing a better protective effect on the heart.

[One-stage complete correction of 52 cases infantile aortic coarctation or interrupted aortic arch associated with intracardiac anomalies].

OBJECTIVE: To sum up one-stage complete correction of infantile aortic coarctation (CoA) or interrupted aortic arch (IAA) associated with intracardiac anomalies through median sternotomy. METHODS: The clinical data of 52 infants with CoA or IAA associated with intracardiac anomalies from May 2004 to March 2010 was analyzed. There were 32 male and 20 female, aged from 25 d to 7 months with a mean of (2.03 ± 0.15) months, weighted from 2.5 to 8.0 kg with a mean of (3.9 ± 0.5) kg. All of intracardiac defect were corrected by self-arcula cordisand. Forty cases with CoA were underwent by operative techniques, including resection with end to side anastomosis, extended end to side anastomosis (n = 34), and vertical incision and cross joint (n = 3). Three cases of pseudo-CoA were cut and ductus arteriosus or ligamentum arteriosus and dissected arch. Twelve cases of IAA were underwent by extended end to side anastomosis. RESULTS: The time of cardiopulmonary bypass was (98 ± 41) min, and all patients hemorrhaged (78 ± 13) ml during operation. One case of IAA associated with double outlet right ventricle died after 43 d post-operation because of left bronchial stenosis. The other patients were in good condition. The rate of aneurysm formation was 11% in 1 to 6 years' follow-up. CONCLUSIONS: One-stage complete correction of infantile CoA or IAA associated with intracardiac anomalies through median sternotomy yields excellent intermediate surgical results. This operative approach is beneficial, not only with shorten period of therapy and loss operative cost.

The number and function of circulating endothelial progenitor cells in patients with Kawasaki disease.

Kawasaki disease (KD) is associated with coronary artery injury. Studies have shown that the endothelial progenitor cell (EPC) participates in the process of arterial repair. Data have been reported that the number of EPC increased significantly in the subacute phase of KD. However, until now, there are no data about the functions of EPC in KD patients. The present study was designed to further investigate the number and functions of EPC in KD. Ten KD patients in the acute phase and ten healthy volunteers were recruited and attributed to the KD group and control group, respectively. The circulating CD34/kinase insert domain-containing receptor double positive cells were evaluated in the two groups using flow cytometry. In vitro assays were used to measure the functions of EPC, including proliferation, adhesion, and migration activities. The plasma levels of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), and high sensitivity C-reactive protein (hs-CRP) were also assessed in both groups. The number of EPC in the KD group was significantly higher than that of the control group (0.021 +/- 0.007% vs. 0.014 +/- 0.003%, P < 0.05). The migratory response of EPC was significantly decreased in the KD group, compared with that of the control group (5.50 +/- 1.78 vs. 3.40 +/- 1.35 cells/high power field, P < 0.01). Similarly, the proliferative and adhesive activities of EPC in the KD group were also decreased (0.47 +/- 0.08 vs. 0.66 +/- 0.07, P < 0.01; 6.5 +/- 2.12 vs. 11.2 +/- 2.04 cells/high power field, P < 0.01). The plasma NO, TNF-alpha, and hs-CRP levels in the KD group were higher than those of the control group (54.10 +/- 11.78 vs. 38.80 +/- 11.10 mumol/l, P < 0.01; 48.20 +/- 7.42 vs. 37.00 +/- 11.12 pg/ml, P < 0.05; 87.10 +/- 30.18 vs. 5.30 +/- 3.37 mg/l, P < 0.01). The number of circulating EPC positively correlated with the level of NO (r = 0.92, P < 0.001), and the functions of EPC negatively correlated with the levels of TNF-alpha and hs-CRP, respectively. In Kawasaki disease, the number of EPC was enhanced and the functions of EPC were attenuated. The two-way regulation of circulating EPC in KD patients may be associated with the disorders of cytokines or messengers in KD patients.

[Myocardial protection of cold autoblood cardioplegia in infants with congenital heart disease].

OBJECTIVE: To study the effects of cold autoblood cardioplegia on oxygen free radicals in the myocardium in infants who underwent cardiopulmonary bypass and to explore the possible mechanism of myocardial protection of autoblood cardioplegia. METHODS: Thirty infants with acyanotic congenital heat disease (CHD) (weight< or =8 kg) were randomized to receive cold crystalloid, cold blood or cold autoblood cardioplegia (n=10 each group) during cardiopulmonary bypass. The biopsy samples were taken from the right atrium just before heart arrest and after heart self-recovery for the measurement of malonaldehyde (MDA) and superoxide dismutase (SOD) contents. The time and the rate of the heart self-recovery to sinus rhythm, and the incidence of ventricular fibrillation were recorded during operation. The cardiac index (CI) and the dependence of positive inotropic drugs were monitored after operation. RESULTS: Before the operation, there were no significant differences in myocardial MDA (0.87+/-0.14, 0.88+/-0.11 and 0.86+/-0.15 nmol/mg prot, respectively) and SOD contents (61.3+/-3.4, 69.2+/-3.1 and 64.4+/-4.2 U/g, respectively) among the crystalloid, the blood and the autoblood cardioplegia groups. After operation, the myocardial MDA content increased (3.12+/-0.21, 2.93+/-0.27 and 1.67+/-0.15 nmol/mg prot, respectively) and SOD content (42.6+/-2.3, 44.6+/-3.1 and 57.7+/-2.1 U/g, respectively) decreased significantly in the three groups (P<0.05 or 0.01). The autoblood cardioplegia group had lower myocardial MDA content and higher SOD content than the crystalloid and the blood cardioplegia groups (P<0.05). The time of heart self-recovery was shortened and the dependence of positive inotropic drugs were reduced in the autoblood cardioplegia group compared with the crystalloid and the blood cardioplegia groups (P<0.05). Post-operational CI in the autoblood cardioplegia group was significantly higher than that in the blood and the crystalloid cardioplegia groups. There were significant differences in the time of heart self-recovery, the dependence of positive inotropic drugs and the CI between the blood and the crystalloid cardioplegia groups (P<0.05 or 0.01). CONCLUSIONS: Cold autoblood cardioplegia reduces oxygen free radicals in the myocardium, thus providing myocardial protections in infants undergoing cardiopulmonary bypass.