sTREM2 in the prognostic evaluation of acute lung injury after cardiac surgery in infants.

BACKGROUND: Previous studies have shown that TREM2 plays a protective role in acute lung injury (ALI). This prospective study aimed to investigate the role of sTREM2 as a forecasting factor for ALI in infants after pediatric cardiac surgery undergoing cardiopulmonary bypass (CPB). METHODS: Seventy-five consecutive patients younger than 1 year who underwent cardiac surgery were enrolled in this study. Sixty-one fulfilled the inclusion criteria and had been divided into ALI and non-ALI groups. Children's demographic characteristics and clinical data were collected. Perioperative sTREM2 levels were analyzed at five timepoints. RESULTS: In this study, children in the ALI group were younger, lighter, with higher RACHS-1 scores and underwent significantly longer CPB time. Post-CPB ALI had an impact on clinical outcomes, which contributed to a longer duration of mechanical ventilation, ICU and hospital stay than non-ALI group. Significant differences were manifested off-CPB, 1 h/6 h after CPB, and day 1 after surgery between the two groups. Binary logistic models revealed that off-CPB sTREM2 was significantly associated with the incidence of post-CPB ALI after adjustment. ROC analysis showed that the AUC of off-CPB sTREM2 level was 0.791, and the optimal cutoff value was 788.6 pg/ml. CONCLUSIONS: The off-CPB sTREM2 level was an independent prognostic factor for post-CPB ALI in infants. IMPACT: Plasma sTREM2 works together with downstream TREM2 to regulate inflammation response by binding the receptor to other cells. Previous studies have shown that TREM2 plays a protective role in ischemia-reperfusion and has anti-inflammatory effects on acute lung injury (ALI). This study analyzed the risk factors of post-cardiopulmonary bypass (CPB) ALI. We found that weight and off-CPB sTREM2 level were independent prognostic factors for post-CPB ALI. Plasma sTREM2 may serve as an early biomarker in the prognostic evaluation of acute lung injury after cardiac surgery in infants.

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

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

Serum soluble triggering receptor levels expressed on myeloid cells2 identify early acute kidney injury in infants and young children after pediatric cardiopulmonary bypass.

Background: Acute kidney injury (AKI) is a potential complication after cardiopulmonary bypass (CPB) of pediatric cardiac surgery and contributes to a certain amount of perioperative mortality. Serum soluble triggering receptor expressed on myeloid cells2 (sTREM2) is an inflammation-associated cytokine in circulation. Alterations of sTREM2 level have been reported in Alzheimer's disease, sepsis, and some other pathologic conditions. This study aimed to investigate the role of sTREM2 as a forecasting factor for AKI in infants and young children and other factors associated with early renal injury after pediatric CPB. Methods: A prospective cohort study with consecutive infants and young children ≤ 3 years old undergoing CPB from September 2021 to August 2022 was conducted in an affiliated university children's hospital. These patients were divided into an AKI group (n = 10) and a non-AKI group (n = 60). Children's characteristics and clinical data were measured. Perioperative sTREM2 levels were analyzed with enzyme-linked immunosorbent assay (ELISA). Results: In children developing AKI, the sTREM2 levels significantly decreased at the beginning of CPB compared to the non-AKI group. Based on binary logistic regression analysis and multivariable regression analysis, risk-adjusted classification for congenital heart surgery (RACHS-1), operation time, and the s-TREM2 level at the beginning of CPB (AUC = 0.839, p = 0.001, optimal cut-off value: 716.0 pg/ml) had predictive value for post-CPB AKI. When combining the sTREM2 level at the beginning of CPB and other indicators together, the area under the ROC curve enlarged. Conclusions: Operation time, RACHS-1 score, and sTREM2 level at the beginning of CPB were independent prognosis factors of post-CPB AKI in infants and young children ≤ 3 years old. Decreased sTREM2 identified post-CPB AKI, and ultimately hampered the outcomes. Our findings indicated that sTREM2 may be a protective factor for AKI after CPB in infants and young children ≤ 3 years old.

Non-spike and spike-specific memory T cell responses after the third dose of inactivated COVID-19 vaccine.

Background: During the COVID-19 epidemic, vaccination has become the most safe and effective way to prevent severe illness and death. Inactivated vaccines are the most widely used type of COVID-19 vaccines in the world. In contrast to spike-based mRNA/protein COVID-19 vaccines, inactivated vaccines generate antibodies and T cell responses against both spike and non-spike antigens. However, the knowledge of inactivated vaccines in inducing non-spike-specific T cell response is very limited. Methods: In this study, eighteen healthcare volunteers received a homogenous booster (third) dose of the CoronaVac vaccine at least 6 months after the second dose. CD4+ and CD8+ T cell responses against a peptide pool from wild-type (WT) non-spike proteins and spike peptide pools from WT, Delta, and Omicron SARS-CoV-2 were examined before and 1-2 weeks after the booster dose. Results: The booster dose elevated cytokine response in CD4+ and CD8+ T cells as well as expression of cytotoxic marker CD107a in CD8+ T cells in response to non-spike and spike antigens. The frequencies of cytokine-secreting non-spike-specific CD4+ and CD8+ T cells correlated well with those of spike-specific from WT, Delta, and Omicron. Activation-induced markers (AIM) assay also revealed that booster vaccination elicited non-spike-specific CD4+ and CD8+ T cell responses. In addition, booster vaccination produced similar spike-specific AIM+CD4+ and AIM+CD8+ T cell responses to WT, Delta, and Omicron, indicting strong cross-reactivity of functional cellular response between WT and variants. Furthermore, booster vaccination induced effector memory phenotypes of spike-specific and non-spike-specific CD4+ and CD8+ T cells. Conclusions: These data suggest that the booster dose of inactive vaccines broadens both non-spike-specific and spike-specific T cell responses against SARS-CoV-2.

Application of robot-assisted endoscopic technique in the treatment of patent ductus arteriosus in 106 children.

The objective is to evaluate and apply the robot-assisted endoscopic surgical technique for treatment of patent ductus arteriosus (PDA) in children. Clinical data of 106 children with PDA who underwent robot-assisted endoscopic operation were retrospectively analyzed from August, 2020 to March, 2022. Demographic and preoperative data were collected, including the patient's age, weight, diameter of the ductus arteriosus, operation time, length of postoperative hospital stay, postoperative complications and hospitalization cost. The age ranged from 6 months to 12 years with median age of 2.5 years. In addition, the weight ranged from 6.6 kg (kg) to 51.6 kg with median weight of 12.5 kg. Patients who received transcatheter PDA closure were also enrolled during the same period. Clinical features and perioperative data were compared between the two groups. All the 106 cases underwent robotically assisted surgery for PDA ligation. No one was converted to thoracotomy. The length of operation time was 15-84 min, with an average of 39.4 min. There was no obvious bleeding during the operation. The length of postoperative hospital stays were 1-3 days, with an average of 1.1 ± 0.2 days, which was significantly shorter than that of patients underwent transcatheter approach PDA closure (2.2 ± 0.2 days) (p < 0.05). The average hospitalization costs were US$ 8180 in the 106 patients, which were more expensive than that of ones who received transcatheter procedure (US$ 5076 ± 406) (p < 0.05). Only one case was found to have residual ductus shunt during early postoperative follow-up. One case was found with recurrent laryngeal nerve injury. The two cases recovered after 3 months of follow-up. The median duration of follow-up was 12 (1-20) months. No other short-term complications occurred during the follow-up period. Robotic surgical technique for PDA ligation in children is a safe, effective and reliable surgical method with less trauma, faster recovery and fewer surgical risks. This approach should be considered as an option in children patients requiring PDA ligation.

Analysis and comparison of failure causes of minimally invasive surgical closure of ventricular septal defects in children.

Objectives: The aims of the present study were to explore the causes of minimally invasive surgical ventricular septal defect (VSD) closure failure under transesophageal echocardiography guidance and thus to improve the success rate of surgical VSD closure. Methods: From January 2015 to December 2019, 522 children with VSD underwent minimally invasive surgical closure. Nineteen procedures (3.64%) were unsuccessful. The failure causes, VSD locations and surgical incision approaches were retrospectively analyzed. Results: Among the 19 patients (3.64%) with unsuccessful outcomes, 18 were switched to cardiopulmonary bypass (CPB) surgery, and 1 was closed successfully using an occlusion device a year later. The causes of failure included occlusion device shedding or shifting (n=6), failure of the guidewire (or the sheath) to pass through a small defect (n=5), device-related valve regurgitation (n=4), significant residual shunt (n=2), ventricular fibrillation (n=1), and continuous sharp blood pressure decreases (n=1). Patients with high VSD had a slightly higher failure rate than those with perimembranous VSD (p=0.049), and its key reason is the high proportion of occlusion device shedding or shifting (p=0.001). No significant difference in the failure rate was found between patients with different surgical incision approaches. Conclusions: Minimally invasive surgery has a high success rate for perimembranous VSDs. Occlusion device shedding or shifting is the most common cause of failure. The shedding or shifting risk of eccentric occlusion devices being used only for high VSDs is much greater than that of concentric occlusion devices being used for perimembranous VSDs, which increases the risk of conversion to CPB surgery for high VSDs.

Outcomes of One-Stage Surgical Repair for Berry Syndrome in Neonates.

BACKGROUND: Berry syndrome is a challenging disease for surgeons to make early diagnosis and successful surgical correction in the neonatal period. Here, we summarized the clinical features of three neonates with berry syndrome in our center to optimize the therapeutic effect in the future. METHODS: From January 2014 to December 2019, three neonates with berry syndrome underwent one-stage surgical repair in our center. We mainly used two different surgical techniques to repair it, and collected clinical data retrospectively from hospitalization history, outpatient records, and telephone follow-up. RESULTS: The age at operation was 28, 8, and 8 days and the body weight was 3.65, 3.86, and 3.0 kg, respectively. The morphology of the interrupted aortic arch (IAA) was type A in two patients and type B in one patient. The aortopulmonary window (APW) morphology was type IIa, III, and IIb, respectively. The phenotype of the IAA type B combined with APW type III in our second patient was reported for the first time so far. All patients survived and were followed up to date. The second patient using intra-aortic baffle experienced twice reoperation for right pulmonary artery (RPA) stenosis. All patients grew well so far. CONCLUSION: Once diagnosed in the neonatal period, berry syndrome can be safely corrected by one-stage surgical repair in experienced cardiac centers. Considering the variability of the location where the RPA arises from the posterior wall of the aorta, it is difficult to find the best surgical method for each patient.

Primary cardiac tumors in children: a center's experience.

BACKGROUND: Cardiac tumors which may induce sudden death are rare entities with an autopsy frequency of 0.001-0.030 %. This study aims to analyze the characteristics and outcome of pediatric patients with primary cardiac tumors treated in our center. METHODS: Sixteen patients with primary cardiac tumors treated at our center between January 2000 and December 2014 were included into this retrospective review. The patients' age ranged from 1 day to 13 years (mean age, 46 months), with weight ranging from 3.2 to 45 kg (mean weight 17.5 kg). All patients were diagnosed by echocardiography, magnetic resonance imaging and computed tomography. RESULTS: We did complete resection of the mass in 15 patients with cardiopulmonary bypass (CPB), whereas partial resection was done in one patient. Fifteen children recovered well, and one patient died of low cardiac output syndrome at 5 days after operation. Rhabdomyoma was the most frequent tumor type, followed by myxoma, fibroma, hemangioma; No malignant tumors were found. CONCLUSIONS: Echocardiography has provided consistent assessment of anatomy and function. Complete surgical resection is valuable treatment for cardiac mass when detected even in asymptomatic patients. Rhabdomyoma is the most frequent tumor type, followed by myxoma and fibroma.

Correlation between rs198388 and rs198389 polymorphismsin brainnatriuretic peptide (NPPB) gene and susceptibility to congenital heart diseases in a Chinese population.

OBJECTIVE: We discussed the correlation between SNP loci (rs198389 and rs198388) in brain natriuretic peptide gene (NPPB) and susceptibility to congenital heart diseases (CHD). METHOD: Multiplex SNaPshot technique was adopted for profiling of SNP genotypes at loci rs198389 and rs198388 in NPPB gene among 150 cases of CHDand 150 normal controls. RESULTS: The distribution frequency of 3 genotypes (AA, AG and GG) at locus rs198389 was 40.7%, 36.0% and 23.3% in CHD group, respectively, showing significant differences compared with the normal controls (P<0.001). Gallele was associated with higher risk of CHD (OR=2.48, 95% CI=1.77-3.48). The distribution frequency of CC, CTand TT genotypes at locus rs198388 was 60.7%, 17.3% and 22.0% in CHD group, respectively, also showing significant differences compared with the normal controls (P<0.001). C allele could increase the risk of CHD (OR=1.92, 95% CI=1.48-2.48). CONCLUSION: SNP loci rs198389 and rs198388 in NPPB gene were correlated with genetic susceptibility to CHD.

[Chromosome 22q11.2 microdeletion and phenotype analysis of patients with non-syndromic tetralogy of Fallot].

OBJECTIVE: To investigate the frequency and clinical phenotypes of 22q11.2 microdeletion in patients with non-syndromic tetralogy of Fallot (TOF). METHODS: Six-eight non-syndromic TOF patients (38 males and 30 females, aged 0-11 years) were selected and evaluated by history, physical examination and review of medical records. After informed consent was obtained, peripheral blood was drawn for genomic DNA extraction. Chromosome 22q11.2 microdeletion was screened by multiplex ligation-dependent probe amplification (MLPA). Suspected cases were confirmed with fluorescence in situ hybridization (FISH). Data was analyzed with SPSS 11.5 software. Phenotype-genotype correlations were assessed using Fisher's exact test. P values less than 0.05 on a 2-sided test were considered to be significant. RESULTS: Six-eight non-syndromic TOF children were screened for a 22q11.2 deletion, among which 59 (86.8%) presented pulmonary stenosis (PS) and 9 (13.2%) presented pulmonary atresia (PA). Seven patients (10.3%) were found to have carried a deletion. Among these, four had TOF-PS, three had TOF-PA. The frequency of 22q11.2 deletion in patients with TOF-PA (3/9, 33.3%) is much higher than that of TOF-PS (4/59, 6.80%) (P< 0.05). CONCLUSION: 22q11.2 microdeletion is present in approximately 10.3% of patients with non-syndromic TOF. The deletion tends to have a higher prevalence in patients with TOF-PA. 22q11.2 deletion should be screened in non-syndromic TOF children and genetic counselling may be provided.

[Evaluation of detection and analysis of chromosome 22q11.2 microdeletion by multiple ligation-dependent probe amplification assay].

OBJECTIVE: To evaluate multiplex ligation-dependent probe amplification (MLPA) assay detection in analysis of chromosome 22q11.2 microdeletion. METHODS: Between March 2008 and September 2009, thirty-two patients including 10 males and 16 females aged between years (3.6±3.1) were selected and evaluated by history, physical examination and medical records. Of these patients, sixteen patients who were previous diagnostic as 22q11.2 microdeletion were in positive control group, the other 16 healthy children were in negative control group. All the patients were detected by MLPA and fluorescence in situ hybridization (FISH) for the presence of a 22q11.2 microdeletion after informed consent. Diagnostic efficacy was assessed by sensitivity, specificity and Kappa analysis. RESULTS: We have applied the two assays of detection of chromosome 22q11.2 microdeletion in 32 patients. Sixteen patients in positive control group were found to have a 22q11.2 deletion and, with the deletion size of 3-Mb. However, as expected, chromosome 22q11.2 deletion was not found in negative control group. The MLPA results were in good agreement with that by FISH. Therefore, MLPA has high sensitivity and specificity. CONCLUSION: MLPA is a rapid, reliable, high-throughput and relatively economical alternative to FISH technology for the diagnosis of 22q11.2 microdeletion. It can provide reliable and helpful information for clinical diagnosis of 22q11.2 microdeletion syndrome.

True thymic hyperplasia in an infant.

True thymic hyperplasia is a very rare entity. We present an instance of idiopathic true massive thymic hyperplasia in a 9-month-old girl with a very large left-sided mediastinal mass noted on diagnostic imaging. Percutaneous biopsy revealed normal thymic tissue. Steroids were administered with no response. Surgery may be required in patients with respiratory distress unresponsive to steroids.

Total anomalous systemic venous drainage to the left atrium.

We present an unusual case of total anomalous systemic venous drainage in which the right superior vena cava, persistent left superior vena cava, inferior vena cava, and coronary sinus were present and unusually connected to the left atrium. Successful surgical correction was achieved, and the patient's recovery was uneventful. Various types of total anomalous systemic venous drainage are discussed, and classification of total anomalous systemic venous drainage is made under the consideration of creation of cardiopulmonary bypass.

Prognosis of pentalogy of Cantrell depends mainly on the severity of the intracardiac anomalies and associated malformations.

We believe the paper may be of particular interest to the readers of your journal. It is a commentary on van Hoorn et al: Pentalogy of Cantrell: two patients and a review to determine prognostic factors for optimal approach (Eur J Pediatr (2008) 167:29-35). The correct definition of pentalogy of Cantrell and ectopia cordis was described in the text and the determinant factor that affects the prognosis of pentalogy of Cantrell was discussed.

Facilitating effect of histamine on spatial memory deficits induced by dizocilpine as evaluated by 8-arm radial maze in SD rats.

AIM: To investigate whether or not histamine is involved in spatial memory deficits induced by dizocilpine (MK-801) as evaluated by 8-arm radial maze of rats. METHODS: 8-Arm (4-arm baited) radial maze was used to measure spatial memory in rats. RESULTS: Bilaterally intrahippocampal (ih) injection of MK-801 (0.3 microg/site) impaired working memory and reference memory in rats. Both histamine (50, 100 ng/site, ih) and intraperitoneal (ip) injection of histidine (100, 200 mg/kg) markedly improved the spatial memory deficits induced by MK-801. On the other hand, the ameliorating effect of histidine (100 mg/kg, ip) was completely antagonized by alpha-fluoromethylhistidine (alpha-FMH, 5 microg/site, ih), a potent and selective histidine decarboxylase (HDC) inhibitor, and H1-antagonist pyrilamine (1 microg/site, ih), but not by H2-antagonist cimetidine, even at a high dose (2.5 microg/site, ih). CONCLUSION: The hippocampal histamine plays an important role in the ameliorating effect on MK-801-induced spatial memory deficits, and its action is mediated through postsynaptic H1-receptor.