Association of PLXND1 with a novel subtype of anomalous pulmonary venous return.

Anomalous pulmonary venous return (APVR) is a potentially lethal congenital heart disease. Elucidating the genetic etiology is crucial for understanding its pathogenesis and improving clinical practice, whereas its genetic basis remains largely unknown because of complex genetic etiology. We thus performed whole-exome sequencing for 144 APVR patients and 1636 healthy controls and report a comprehensive atlas of APVR-related rare genetic variants. Novel singleton, loss-of-function and deleterious missense variants (DVars) were enriched in patients, particularly for genes highly expressed in the developing human heart at the critical time point for pulmonary veins draining into the left atrium. Notably, PLXND1, encoding a receptor for semaphorins, represents a strong candidate gene of APVR (adjusted P = 1.1e-03, odds ratio: 10.9-69.3), accounting for 4.17% of APVR. We further validated this finding in an independent cohort consisting of 82 case-control pairs. In these two cohorts, eight DVars were identified in different patients, which convergently disrupt the GTPase-activating protein-related domain of PLXND1. All variant carriers displayed strikingly similar clinical features, in that all anomalous drainage of pulmonary vein(s) occurred on the right side and incorrectly connected to the right atrium, which may represent a novel subtype of APVR for molecular diagnosis. Studies in Plxnd1 knockout mice further revealed the effects of PLXND1 deficiency on severe heart and lung defects and cellular abnormalities related to APVR such as abnormal migration and vascular formation of vascular endothelial cells. These findings indicate the important role of PLXND1 in APVR pathogenesis, providing novel insights into the genetic etiology and molecular subtyping for APVR.

Management Strategies for Congenital Heart Disease Comorbid with Airway Anomalies in Children.

OBJECTIVE: To assess management strategies for pediatric patients with the challenging combination of congenital heart diseases (CHDs) and airway anomalies. STUDY DESIGN: Patients diagnosed with CHD and airway anomalies in the Pediatric Cardiac Surgery Centre of Fuwai Hospital from January 2016 to December 2020 were included in this retrospective study. Patients were divided into three groups based on different management, including the conservative group, the slide group (slide tracheoplasty), and the suspension group (suspension with external stenting). Patients' data and computed tomography measurements from medical records were reviewed. RESULTS: A total of 139 patients were included in the cohort; 107 had conservative airway treatment (conservative group), 15 had slide tracheoplasty (slide group), and 17 had tracheal suspension operation (suspension group). The top three associated intracardiac anomalies were ventricular septal defect (n = 34, 24%), pulmonary artery sling (n = 22, 16%), and tetralogy of Fallot (n = 15, 11%). Compared with patients with conservative airway management (100 minutes [median], 62-152 [IQR]), the extra airway procedure prolonged cardiopulmonary bypass duration, with 202 minutes (IQR, 119-220) for the slide group and 150 minutes (IQR, 125-161) for the suspension group. Patients who underwent slide tracheoplasty required prolonged mechanical ventilation (129 minutes [median], 56-328 [IQR]). Of the total cohort, 6 in-hospital deaths, all in the conservative group, and 8 mid-to long-term deaths, with 6 in the conservative group, occurred. CONCLUSIONS: Both conservative and surgical management of CHD patients with airway anomalies have promising outcomes. Extra tracheobronchial procedures, especially the slide tracheoplasty, significantly prolonged cardiopulmonary bypass duration. Based on multidisciplinary team assessment, individualized management strategies should be developed for these patients.

Prevalence of the novel recombinant LSDV in east and Southeast Asia: Inducing skin and testicular damage in golden hamsters.

In June 2020, Lumpy Skin Disease Virus (LSDV) was first discovered in Guangdong, China. Whole-genome sequencing and evolutionary analysis indicate that this strain represents a novel recombinant vaccine strain. Our investigation has identified regions affected by LSD outbreaks prior to 2024, revealing widespread prevalence of LSDV across East Asia and Southeast Asia. Subsequent analysis of the physical and chemical characteristics of the strain revealed LSDV's resilience to high temperatures, varying pH levels, humidity, UV radiation, and light exposure. Among the tested disinfectants, potassium persulfate, glutaraldehyde, and benzalkonium bromide have demonstrated the most potent virucidal efficacy against LSDV while maintaining high safety profiles. Utilizing the Syrian hamster model, infection with this strain has resulted in the formation of skin nodules and testicular damage, providing valuable insights into the pathogenesis of LSDV. In conclusion, the comprehensive experimental data presented herein serve as a cornerstone for advancing biosafety protocols, facilitating effective prevention and control strategies, and fostering the development of small animal model for LSDV.

Construction of recombinant fluorescent LSDV for high-throughput screening of antiviral drugs.

Lumpy skin disease virus (LSDV) infection is a major socio-economic issue that seriously threatens the global cattle-farming industry. Here, a recombinant virus LSDV-ΔTK/EGFP, expressing enhanced green fluorescent protein (EGFP), was constructed with a homologous recombination system and applied to the high-throughput screening of antiviral drugs. LSDV-ΔTK/EGFP replicates in various kidney cell lines, consistent with wild-type LSDV. The cytopathic effect, viral particle morphology, and growth performance of LSDV-ΔTK/EGFP are consistent with those of wild-type LSDV. High-throughput screening allowed to identify several molecules that inhibit LSDV-ΔTK/EGFP replication. The strong inhibitory effect of theaflavin on LSDV was identified when 100 antiviral drugs were screened in vitro. An infection time analysis showed that theaflavin plays a role in the entry of LSDV into cells and in subsequent viral replication stages. The development of this recombinant virus will contribute to the development of LSDV-directed antiviral drugs and the study of viral replication and mechanisms of action.

Clinical Outcomes, Predictors, and Surgical Management of Infracardiac Total Anomalous Pulmonary Venous Connection.

This study sought to find the risk factors of postoperative pulmonary venous obstruction (PVO), PVO-related reintervention, and postoperative mortality, determine the relationship between pulmonary venous confluence (PVC) morphology and the clinical outcomes, and provide the basis for the selection of the optimal surgical strategy for infracardiac total anomalous pulmonary venous connection (TAPVC). From December 2009 to December 2023, 101 patients with infracardiac TAPVC undergoing surgical repair in our institution were included [Conventional surgery (CS) group, n = 73; Sutureless technique (ST) group, n = 28]. The Kaplan-Meier curve was used to demonstrate the survival estimates. The Cox proportional hazard model was used to identify risk factors for primary endpoints. There were 8 in-hospital deaths and 4 late deaths. The survival rates at 1, 5, and 10 years were 88.8%, 87.6%, and 87.6%, respectively, in the whole cohort. Multivariable analysis showed that prolonged cardiopulmonary bypass (CBP) time was associated with overall mortality and Y-shaped PVC has a trend for a higher mortality rate. Postoperative PVO occurred in 27 patients. Freedom from postoperative PVO at 1, 5, and 10 years were 81.8%, 69.9%, and 69.9%, respectively. Y-shaped PVC and preoperative PVO were incremental risk factors for PVO, but ST repair was a protective factor. Sixteen patients underwent PVO-related reintervention. Y-shaped PVC was the only independent risk factors for PVO-related reintervention while ST repair was a protective factor. Sutureless technique can achieve satisfactory outcomes for infracardiac TAPVC repair. Compared with CS repair, ST repair is significantly associated with decreased postoperative PVO and PVO-related reintervention. Y-shaped PVC is associated with a higher risk of PVO, PVO-related reintervention, and mortality, respectively. Patients with preoperative PVO are more likely to develop postoperative PVO.

Application of a Novel Mitral Valvuloplasty Strategy in Children with Mitral Regurgitation.

To retrospectively analyze the clinical efficacy of an innovative mitral valvuloplasty strategy in the treatment of mitral regurgitation in children. From January 2018 to December 2022, 140 patients undergoing surgical treatment for mitral regurgitation in our hospital were enrolled. Ninety patients underwent three-step standardized pediatric mitral valvuloplasty (group A) and 50 patients underwent simple annuloplasty (group B). The incidence of primary and secondary study endpoint was compared between the two groups, and the independent risk factors for the primary study endpoint were determined. Our primary study endpoint was a composite endpoint of postoperative functional mitral failure, postoperative heart failure, transplantation, and/or mortality. Secondary end points were defined as perioperative complications. During the follow-up period, there was no all-cause death. Primary endpoint events occurred in 22 patients, including 12 patients in group A and 10 patients in group B. There was no significant difference in the incidence of primary and secondary endpoint events between the two groups. Multivariate Cox proportional hazards regression analysis showed that younger age and residual mitral regurgitation at discharge were independent risk factors for the primary endpoint events, while type of MV repair was not an independent risk factor. Subgroup analysis based on age showed that primary endpoint events occurred in 4 patients in group A and 7 patients in group B in patients < 1 year old. The incidence of primary endpoint events in group A was lower than that in group B (6.06% vs. 20.59%, P = 0.041). In patients ≥ 1 year old, the primary endpoint event occurred in 8 cases in group A and 3 cases in group B. There was no significant difference in the incidence of primary endpoint events between groups A and B (33.33% vs. 18.75%, P = 0.312). The degree of mitral regurgitation at discharge was significantly improved compared with that before operation in both groups (P < 0.001), and the degree of mitral regurgitation at the last follow-up was not significantly worse than that at discharge (P = 0.090). The mid-term results of mitral valvuloplasty for mitral regurgitation in children are encouraging. The perioperative recovery and postoperative outcomes of three-step standardized mitral valvuloplasty in children are not inferior to those of annuloplasty alone. Three-step standardized pediatric mitral valvuloplasty has better postoperative outcomes than simple mitral annuloplasty, especially for patients younger than 1 year old. Children with residual mitral regurgitation at discharge should be followed up regularly to be alert to the occurrence of poor prognosis.

Clinical Outcomes and Predictors of Valved Homograft Conduits Used for Right Ventricular Outflow Tract Reconstruction.

We conducted a retrospective review of patients who underwent valved homograft conduits (VHC) for right ventricular outflow tract (RVOT) reconstruction at our center. Long-term outcomes were analyzed, and risk factors affecting the long-term durability of VHC were explored. Kaplan-Meier survival curves were used to evaluate survival, freedom from VHC reintervention, and freedom from VHC dysfunction. Multivariate Cox proportional hazards regression model was used to analyze the risk factors for late VHC dysfunction. A total of 290 patients who underwent VHC for RVOT reconstruction in our center were enrolled. Seven patients occurred early death, all of which were in the non-Ross group. Two hundred and sixty-five patients were followed up for 85 (0.3-176.0) months. Six patients occurred late death, all in the non-Ross group. Six patients underwent VHC reintervention. During the follow-up period, 52 patients developed VHC dysfunction. Freedom from VHC dysfunction was higher in the Ross group than in the non-Ross group in the whole cohort. Multivariate Cox regression analysis showed that age < 6 years and non-Ross operation were independent risk factors for VHC dysfunction. Freedom from VHC dysfunction was higher in the Ross group than in the non-Ross group in patients younger than 6 years of age at surgery. However, there was no significant difference in freedom from VHC dysfunction between the two groups in patients older than 6 years. Long-term outcomes of VHC for RVOT reconstruction are satisfactory. Age < 6 years and non-Ross operation are independent risk factors for VHC dysfunction. The long-term survival rate and durability of VHC in Ross group were better than those in non-Ross group. The advantage of long-term durability of VHC in the Ross group was mainly reflected in patients aged < 6 years at operation.

Long-Term Outcomes of Surgical Repair of Supracardiac Total Anomalous Pulmonary Venous Connection.

The conventional surgery (CS) of supracardiac total anomalous pulmonary venous connection (TAPVC) is not always effective particularly in the setting of complex anatomy such as the mixed variety of TAPVC. This study aimed to analyze the outcomes of surgical treatment of supracardiac TAPVC and determine the optimal strategy. From December 2009 to December 2023, patients with supracardiac TAPVC undergoing surgical repair in our institution were included. The Kaplan-Meier curve was used to demonstrate the survival estimates. The Cox proportional hazard model was used to identify risk factors for death and postoperative pulmonary venous obstruction (PVO). One hundred and eighty-three patients with supracardiac TAPVC underwent surgical repair [CS group, n = 102; modified L-shaped incision technique (MLIT) group, n = 81]. There were 8 in-hospital deaths and 16 late deaths. The survival rates at 1, 5, and 10 years were 89.0%, 85.0%, and 85.0%, respectively in the whole cohort. Multivariable analysis showed that lower weight (P = 0.031), prolonged CBP time (P = 0.007), preoperative PVO (P = 0.020), and emergency surgery (P = 0.001) were incremental risk factors for death, but using the MLIT was a protective factor for death (p = 0.028). In the CS group, patients with emergency operation had worse survival than patients with elective surgery (P < 0.001). However, in the MLIT group, patients with emergency operation had comparable survival to patients with elective surgery (P = 0.332). Postoperative PVO occurred in 30 patients. Fourteen patients underwent PVO-related reintervention. In the whole cohort, freedom from postoperative PVO at 1, 5, and 10 years were 87.5%, 80.6%, and 80.6%, respectively. Patients who underwent MLIT repair had a lower incidence of postoperative PVO (P < 0.001), and PVO-related reintervention (P = 0.019). Neonates(P = 0.033), aortic cross-clamp time (P = 0.012), preoperative PVO (P = 0.002), and using the CS (P = 0.005) were associated with postoperative PVO. In terms of postoperative PVO, MLIT had a protective effect compared with CS. In the CS group, Infant and Children patients had better freedom from postoperative PVO than Neonate patients (P < 0.001). However, in the MLIT group, Neonate patients had comparable freedom from postoperative PVO to Infant and Children patients (P = 0.332). The MLIT can achieve satisfactory outcomes for supracardiac TAPVC repair. Compared with CS, the MLIT was significantly associated with decreased death, postoperative PVO, and PVO-related reintervention. It is especially significant in improving the survival rate of patients undergoing emergency surgery and reducing the incidence of postoperative PVO in neonatal patients.

Long-Term Outcomes of Individualized Repair in Patients with Supravalvular Aortic Stenosis.

Various surgical techniques have been introduced to treat supravalvular aortic stenosis (SVAS). However, there is no consensus on the optimal approach. This study aimed to analyze the outcomes of surgical treatment of SVAS and determine the optimal strategy. The Kaplan-Meier curve was used to demonstrate the survival estimates. The Cox proportional hazard model was used to identify risk factors for residual aortic stenosis and residual stenosis-related reintervention. From December 2008 to December 2023, 98 patients with SVAS undergoing surgical repair in our institution were included [McGoon group, n = 62; Doty group, n = 36]. There were 2 in-hospital deaths and 1 late death. The survival rates at 1, 5, and 15 years were 98.0%, 96.7%, and 96.7%, respectively in the whole cohort. Residual aortic stenosis occurred in 18 patients. Multivariable analysis showed that preoperative gradient ≥ 90 mmHg (P = 0.002) and Williams syndrome (P = 0.002) were incremental risk factors for residual aortic stenosis, but surgical technique (P = 0.579) was not a risk factor for residual aortic stenosis. In the McGoon group, patients with diffuse type had worse freedom from residual aortic stenosis than patients with discrete type (P = 0.007). However, in the Doty group, patients with diffuse type had comparable freedom from residual aortic stenosis to patients with discrete type (P = 0.911). Residual stenosis-related reintervention occurred in 15 patients. Fifteen patients all underwent residual aortic stenosis-related reintervention. Of 15 patients, 6 patients also underwent residual pulmonary stenosis-related reintervention. On multivariate analysis, Williams syndrome (P < 0.001), preoperative sinotubular junction (STJ) z-score < - 3.5 (P = 0.051), and Doty repair (P = 0.033) were found to be independent risk factors associated with residual stenosis-related reintervention. In the whole cohort, freedom from residual stenosis-related reintervention at 1, 5, and 15 years were 97.8%, 89.3% and 76.1%, respectively. Surgical repair of SVAS can be safely achieved using different techniques, with similar long-term mortality. Compared with McGoon repair, Doty repair was significantly associated with decreased residual aortic stenosis rates in patients with diffuse-type SVAS. Patients with preoperative gradient ≥ 90 mmHg or Williams syndrome are more prone to residual aortic stenosis. Surgical technique was not associated with residual aortic stenosis rates. Williams syndrome, preoperative STJ z-score < - 3.5, and Doty repair are associated with higher residual stenosis-related reintervention rates.

Predictive Value of Myocardial Markers for Early Postoperative Mortality in Children with Congenital Heart Disease.

To investigate the influencing factors of postoperative creatine kinase-MB (CK-MB) elevation in children with congenital heart disease and its peak value in predicting early postoperative mortality. The clinical data of 521 children with congenital heart disease under the age of 14 who underwent elective surgery in Beijing Children's Hospital from December 2018 to December 2020 were retrospectively analyzed. Stepwise multiple linear regression was used to analyze independent risk factors for postoperative CK-MB elevation, receiver operating characteristic (ROC) curve was used to determine the predictive value of postoperative CK-MB peak, CK peak, and LDH peak on mortality, and linear correlation and regression analysis were used to analyze the interdependence among postoperative CK-MB peak, CK peak, and LDH peak, and multivariate Logistic regression was used to identify independent risk factors for early postoperative mortality. Preterm birth (P = 0.004), ventriculotomy (P = 0.009), the re-establish of bypass (P = 0.007), cardiopulmonary bypass time (P = 0.024), deep hypothermic circulatory arrest time (P = 0.000), assisted ventilation time (P = 0.049), CK peak (P = 0.000), and LDH peak (P = 0.000) were independently associated with increased postoperative CK-MB elevation. The ROC curve showed that CK-MB peak had the strongest predictive value for death (AUC = 0.924), followed by LDH peak (AUC = 0.864) and CK peak (AUC = 0.758). The cut-off value of the postoperative CK-MB peak was 144.5 IU/L, with a sensitivity of 87% and a specificity of 97%. CK-MB peak was moderately correlated with CK peak (Pearson Correlation coefficient r = 0.514, P = 0.000) and strongly correlated with LDH peak (Pearson Correlation coefficient r = 0.601, P = 0.000). Multivariate analysis showed that delayed chest closure (OR = 4.865, P = 0.004) and postoperative CK-MB peak (OR = 1.031, P = 0.000) were independent risk factors for postoperative mortality. The postoperative CK-MB peak has a certain predictive value for the early postoperative mortality of children with congenital heart disease. It is affected by many factors, and the risk of mortality is significantly increased in children with severely elevated postoperative CK-MB.

Application of right ventricular to pulmonary valved conduit in the surgical treatment of congenital heart disease.

Pulmonary valve replacement and right ventricular outflow tract reconstruction with valved conduits have been the shortcomings of paediatric cardiac surgeons in the treatment of CHD. In recent decades, encouraging achievements have been made in right ventricular outflow tract technology. Since Klinner reported the first right ventricle-to-pulmonary artery connection using unvalved conduits made of autologous pericardium in 1964, various right ventricle-to-pulmonary artery conduits have gradually been used in the treatment of various complex CHD. Compared with other materials, valved homograft conduit (VHC) is more consistent with physiological characteristics, better haemodynamics, easy suture and good haemostasis, anti-calcification, anti-infection, and without the need for lifelong anticoagulation, which makes VHC the best material for reconstruction of right ventricular outflow tract. However, due to the shortage of donor sources, other alternative conduits such as polytetrafuoroethylene valved conduits have been developed, and the results are not inferior to VHC in clinical application. The emerging tissue engineering technology is expected to utilise recipient-derived endothelial cells for implantation onto the decellularized VHC or degradable synthetic materials in order to construct a recipient-specific tissue-engineered valved conduit. This advancement holds great potential as an ideal biological transplant material and valve replacement for CHD. It will completely solve the problems of immune rejection and the growth of the conduit that cannot adapt to the physical growth of children. This review provides a comprehensive review of the clinical indications for right ventricle-to-pulmonary artery conduits application, optimal timing for surgery, current practices in utilising various types of external conduits, and considerations for re-replacement.

Progress of surgical treatment of anomalous left coronary artery from the pulmonary artery.

Anomalous left coronary artery from the pulmonary artery is a rare CHD. It is the most common type of anomalous coronary origin. It may cause myocardial ischaemia or infarction, mitral regurgitation, congestive heart failure, and early death in infancy if left untreated. Surgery is the only treatment for anomalous left coronary artery from the pulmonary artery. In recent years, with advancements in surgical techniques and the widespread utilisation of extracorporeal cardiac assist devices such as extracorporeal membrane oxygenation, the treatment outcomes for anomalous left coronary artery from the pulmonary artery have demonstrated significant improvements. However, the surgical indications and methods of anomalous left coronary artery from the pulmonary artery, especially the surgical methods of anomalous left coronary artery from the pulmonary artery with intramural coronary artery, and whether to treat mitral regurgitation at the same time are still controversial. The long-term complications and prognosis remain discouraging simultaneously, with significant variations in outcomes across different centres. The present review specifically addresses these aforementioned concerns. Based on the literature published at home and abroad, we found that no matter what type of anomalous left coronary artery from the pulmonary artery patients, even asymptomatic patients, regardless of the collateral circulation between the left and right coronary arteries, should immediately undergo surgical treatment to promote the recovery of left ventricular function. Based on different coronary artery anatomical morphology and preoperative cardiac function, the long-term follow-up results of individualised surgical treatment of anomalous left coronary artery from the pulmonary artery children show good prognosis, and most children have significant improvement in cardiac function. Patients with moderate to severe mitral regurgitation should undergo mitral valve operation at the same time as anomalous left coronary artery from the pulmonary artery repair. Mitral valvuloplasty can quickly improve mitral regurgitation and promote the early recovery of cardiac function after operation, and does not increase the risk of operation. Mechanical circulatory support is a safe and effective means of early postoperative transition for children with severe anomalous left coronary artery from the pulmonary artery. Anomalous left coronary artery from the pulmonary artery with intramural coronary artery is a rare anomaly. According to different anatomical types, different surgical methods can be used for anatomical correction, and satisfactory early and mid-term results can be obtained.

Long-term outcomes after the arterial switch operation.

OBJECTIVES: The aims of this study were to evaluate the 16-year experience with  arterial switch operation at Beijing Children's Hospital and to determine early and late mortality and late morbidity, to explore risk factors for late complications and reintervention, and finally to evaluate whether the neoaortic sinotubular junction reconstruction technique reduces late complications of arterial switch operation. METHODS: The clinical data of 185 patients with transposition of the great arteries who underwent arterial switch operation in Beijing Children's Hospital from January 2006 to January 2022 and 30 patients who underwent modified arterial switch operation with neoaortic sinotubular junction reconstruction technique in Fuwai Hospital during the same period were retrospectively analysed. Propensity score matching was also used to match the neoaortic sinotubular junction reconstruction patients in Fuwai Hospital with 30 non-neoaortic sinotubular junction reconstruction patients in Beijing Children's Hospital. RESULTS: There were 13 early deaths (7.03%) and five late deaths (3.01%). Nineteen patients (11.45%) developed new aortic valve regurgitation and 28 patients (16.87%) developed aortic root dilation. Late right ventricular outflow tract obstruction occurred in 33 patients (19.88%). Late reintervention occurred in 18 cases (10.84%). Multivariate analysis showed that aorto-pulmonary diameter mismatch, previous pulmonary artery banding, and mild moderate or above new aortic valve regurgitation at discharge were independent risk factors for late new aortic valve regurgitation and aortic root dilation. Low surgical weight was an independent risk factor specific to new aortic valve regurgitation, and bicuspid native pulmonary valve was an independent risk factor specific to aortic root dilation. Older surgical age and aortic root dilation were independent risk factors for late right ventricular outflow tract obstruction. Older surgical age, operation before 2014, late right ventricular outflow tract obstruction, and late aortic root dilation were independent risk factors for late intervention. Propensity score matching showed that new aortic valve regurgitation and aortic root dilation were not followed up in the neoaortic sinotubular junction reconstruction group, while seven cases of aortic root dilation and five cases of new aortic valve regurgitation occurred in the non-neoaortic sinotubular junction reconstruction group, respectively, and the differences were statistically significant (P = 0.003; P = 0.015). CONCLUSIONS: The increased incidence of new aortic valve regurgitation, aortic root dilation, and right ventricular outflow tract obstruction as children age is a major concern outcome in the future and may mean more late reintervention. neoaortic sinotubular junction reconstruction technique may reduce the incidence of new aortic valve regurgitation and aortic root dilation, and improve the late prognosis of arterial switch operation. Careful follow-up of neo-aortic valve and root function is imperative, especially in patients with aorto-pulmonary diameter mismatch, previous pulmonary artery banding, mild new aortic valve regurgitation at discharge, low surgical weight, and bicuspid native pulmonary valve structures.

Long-term outcomes of repair in children with total anomalous pulmonary venous connection.

OBJECTIVES: The clinical data of patients with total anomalous pulmonary venous connection who underwent repair in our centre in the past 13 years were reviewed. In this study, we systemically reviewed our experience in the optimal surgical strategy for patients with total anomalous pulmonary venous connection, aiming to provide evidence for clinical decision-making. METHODS: From January 1, 2009, to December 31, 2021, 122 patients undergoing surgical treatment for total anomalous pulmonary venous connection in our hospital were enrolled. Among them, 18 patients with single ventricle repair were excluded from the study. Multivariate analysis was used to determine the risk factors for early and late death and the risk factors for pulmonary vein obstruction. RESULTS: There were 64 males and 40 females. The median age at surgery was 107 days (range, 25 days-788 days), the median weight at surgery was 4.8 kg (range, 3 kg-22 kg), and the median follow-up was 59 months (range, 0-150 months). Seven patients died early after surgery and six died late after discharge. Multivariable analysis indicated that prolonged cardiopulmonary bypass time was the only independent risk factor for early postoperative mortality. Multivariate analysis did not identify risk factors for late death. Emergency surgery, preoperative moderate and severe pulmonary hypertension, and prolonged cardiopulmonary bypass time were independent risk factors for postoperative pulmonary vein obstruction. CONCLUSION: Early and long-term late outcomes of repair in patients with total anomalous pulmonary venous connection have been encouraging. Postoperative pulmonary vein obstruction remains a major problem for specialists worldwide. Pulmonary vein obstruction should be considered in children with preoperative emergency surgery, moderate to severe pulmonary hypertension and prolonged cardiopulmonary bypass time, and regular follow-up is necessary.

Innovation in surgical treatment of hypertrophic obstructive cardiomyopathy in children.

Hypertrophic cardiomyopathy is the second most common cardiomyopathy affecting children and adolescents and is the main cause of sudden death of young athletes. The natural prognosis of children with severe hypertrophic obstructive cardiomyopathy is not optimistic, and it is not uncommon for children with hypertrophic obstructive cardiomyopathy who do not respond to medication. Surgical treatment is often the only solution. Conventional surgical methods in the past include classic or modified extended Morrow operation, classic or modified Konno operation, and Ross-Konno operation. In recent years, with the development of minimally invasive surgery, various minimally invasive surgical methods have emerged endlessly. Because the incision of minimally invasive cardiac surgery is significantly smaller than that of traditional surgery, it causes less trauma, recovers quickly after surgery, and has the advantage of no difference in surgical effect compared with traditional median sternotomy. Tally endoscopic transmitral myectomy, RTM, minimally right thoracotomy, and other surgical methods have achieved encouraging results in adults and some older children with hypertrophic obstructive cardiomyopathy. The appearance of transapical beating-heart septectomy has brought the treatment of hypertrophic obstructive cardiomyopathy from the era of cardiopulmonary bypass and cardiac arrest to a new era of minimally invasive beating-heart surgery. In the past, there were few articles about the treatment of children with hypertrophic obstructive cardiomyopathy. This article reviewed the new progress and prognosis of surgical treatment of children with hypertrophic obstructive cardiomyopathy at home and abroad.

Individualised surgical treatment strategy for subaortic stenosis.

OBJECTIVES: The clinical data of patients with subaortic stenosis who underwent surgical treatment in our centre in the past 12 years were reviewed. The short-term and long-term clinical outcomes were analyzed, and the long-term outcomes of different surgical methods for subaortic stenosis were compared to determine the optimal surgical treatment strategy for subaortic stenosis. METHODS: From December 2010 to December 2022, 90 patients undergoing surgical treatment for subaortic stenosis in our hospital were enrolled. There were 55 males and 35 females with a median age of 72 (46,132) months and an average surgical weight of (21.35 ± 15.84) kg. According to the operation method, 90 patients were divided into group A (50 patients with simple subaortic membrane resection) and group B (40 patients with subaortic membrane and muscle resection or modified Konno procedure). RESULTS: There were three early deaths (3.33%). One late death occurred in group B. There was no significant difference in long-term survival rate between the two groups (p = 0.904). The preoperative left ventricular outflow tract pressure gradient in group B was (91.56 ± 36.98) mm Hg, which was higher than that in group A(51.13 ± 36.04)mm Hg(p < 0.001). There was no significant difference in immediate postoperative left ventricular outflow tract pressure gradient between group B [(5.44 ± 8.43) mm Hg] and group A [(7.82 ± 13.44) mm Hg] (p = 0.343). In the long-term follow-up, left ventricular outflow tract pressure gradient in group B was (5.86 ± 9.53) mm Hg, which was not statistically significant compared with group A (8.83 ± 14.52) mm Hg (p = 0.294). Eleven patients with moderate or greater aortic regurgitation (group A/group B: 3/8) underwent simultaneous aortic valvuloplasty. In group B, moderate or greater aortic regurgitation was significantly improved immediately after operation (p = 0.013) and was not significantly aggravated in long-term follow-up (p = 0.083), and there was no significant improvement in group A after operation and long-term follow-up. CONCLUSIONS: According to the different anatomical lesions of left ventricular outflow tract, the individualised surgical treatment strategy for patients with subaortic stenosis can achieve good long-term outcomes. The long-term survival rate and freedom from reoperation due to late left ventricular outflow tract obstruction after simple subaortic membrane resection and extended left ventricular outflow tract resection are comparable. For patients with moderate or greater aortic regurgitation before extended left ventricular outflow tract resection, simultaneous aortic valvuloplasty is beneficial to improve postoperative aortic valve function.

Development and application of a dual ERA method for the detection of Feline Calicivirus and Feline Herpesvirus Type I.

Feline calicivirus (FCV) and feline herpesvirus type I (FHV-1) are the most common viral pathogens responsible for cat respiratory diseases, and coinfection with these two pathogens is often found. In veterinary clinics, the main diagnostic methods for FCV and FHV-1 are test strips and polymerase chain reaction (PCR). However, the sensitivity of test strips are not sufficient, and PCR is time-consuming. Therefore, developing a rapid and high-performance clinical diagnostic test is imperative for the prevention and treatment of these diseases. Enzymatic recombinase amplification (ERA) is an automated isothermal nucleic acid amplification technique that maintains a constant temperature, and is both rapid and highly accurate. In this study, a dual ERA method was developed using the Exo probe for a differential detection of FCV and FHV-1. This dual ERA method demonstrated high performance with the detection limit of 101 copies for both viruses, and no cross-reactions with feline parvovirus virus and F81 cells. To test the utility of the method for clinical applications, 50 nasopharyngeal swabs from cats with respiratory symptoms were collected and tested. The positive rates of FCV and FHV-1 were 40% (20/50, 95% confidence interval [CI], 26.4 to 54.8%) and 14% (7/50, 95% CI, 5.8 to 26.7%), respectively. The rate of coinfection with FCV and FHV-1 was 10% (5/50, 95% CI, 3.3 to 21.8%). These results were in agreement with those found using quantitative real-time PCR. Therefore, this dual ERA method is a novel and efficient clinical diagnostic tool for FCV and FHV-1 detection.

Establishment and characterization of a HER2-enriched canine mammary cancerous myoepithelial cell line.

BACKGROUND: Canine mammary tumors (CMTs) have a poor prognosis, along with tumor recurrence and metastasis. Cell lines are vital in vitro models for CMT research. Many CMT epithelial cell lines were reported. However, canine mammary myoepithelial cells, the contractile component of the canine mammary tissue were overlooked. This study aimed at establishing such a cell line. CMT-1 cell line was obtained from a canine mammary tumor CMT-1 and characterized molecularly through qPCR, western blotting, immunochemistry and immunofluorescence. Its doubling time, cytogenetic analysis and migration rate were evaluated using growth study, karyotype analysis and wound healing assay respectively. To determine its tumorigenesis, xenograft transplantation was performed. RESULTS: CMT-1 tumor was a complex canine mammary carcinoma that stained negative to estrogen receptors (ER) and progesterone receptors (PR), but positive to human epidermal growth receptor-2 (HER2), defined as HER2-enriched subtype. In this study, a CMT-1 cell line obtained from CMT-1 tumor was immune-positive to vimentin, α-SMA, p63 and negative to E-cadherin (E-cad), indicating CMT-1 cells were myoepithelial cells. It was successfully cultured for more than 50 passages showing the same immunoreactivity to ER, PR, and HER2 as the primary canine tumor. The doubling time of CMT-1 cell line was 26.67 h. The chromosome number of CMT-1 cells ranged from 31 to 64. A potential spontaneous epithelial to mesenchymal transition (EMT) was noticed during cell cultures. Potential EMT-induced CMT-1 cells showed no significance in migration rate compared to the original CMT-1 cells. CMT-1 cells was able to grow on a 3D culture and formed grape-like, solid, and cystic mammospheres at different time period. Inoculation of CMT-1 cells induced a complex HER2-enriched mammary tumor with metastasis in mice. CONCLUSIONS: A canine cancerous HER2-enriched myoepithelial cell line was successfully established and a canine mammosphere developed from myoepithelial cells was documented in this study. We are expecting this novel cell line and its associated mammospheres could be used as a model to elucidate the role of myoepithelial cells in CMT carcinogensis in the future.

Congenital heart diseases with airway stenosis: a predictive nomogram to risk-stratify patients without airway intervention.

BACKGROUND: This study focused on congenital heart disease (CHD) patients complicated with airway stenosis (AS) without airway intervention and aimed to identify the patients with potential risks. METHODS: Patients diagnosed with CHD and AS were enrolled in this retrospective study. The primary outcome was defined as a postoperative mechanical ventilation duration of more than two weeks. We constructed a prediction model to predict the risk of prolonged mechanical ventilation (PMV). RESULTS: A total of 185 patients diagnosed with CHD and AS in Fuwai Hospital from July 2009 to December 2022 were included in the study. Weight at CHD surgery, cardiopulmonary bypass (CPB) duration, complex CHD and comorbid tracheobronchomalacia were identified as risk factors and included in the model. The ROC curve showed a good distinguishing ability, with an AUC of 0.847 (95% CI: 0.786-0.908). According to the optimal cut-off value of the ROC curve, patients were divided into high- and low-risk groups, and the subsequent analysis showed significant differences in peri-operative characteristics and in-hospital deaths. CONCLUSIONS: With the predictive model, several factors could be used to assess the risky patients with PMV. More attention should be paid to these patients by early identification and routine surveillance.

Feline Calicivirus P39 Inhibits Innate Immune Responses by Autophagic Degradation of Retinoic Acid Inducible Gene I.

Feline calicivirus (FCV) is a feline pathogen that can cause severe upper respiratory tract disease in cats, thus posing a major threat to their health. The exact pathogenic mechanism of FCV is still unclear, although it has been identified as having the ability to induce immune depression. In this study, we discovered that FCV infection triggers autophagy and that its non-structural proteins, P30, P32, and P39, are responsible for initiating this process. Additionally, we observed that altering autophagy levels via chemical modulation resulted in different influences on FCV replication. Moreover, our findings indicate that autophagy can modify the innate immunity induced by FCV infection, with increased autophagy further suppressing FCV-induced RIG-I signal transduction. This research provides insights into the mechanism of FCV replication and has the potential to aid in the development of autophagy-targeted drugs to inhibit or prevent FCV infection.