Background:Pediatric heart failure patients weighing less than 30 kg are prioritized for small axial flow blood pumps due to their smaller body size. This study aims to optimize the blade design of pediatric axial flow blood pumps by conducting orthogonal experiments on blade parameters and integrating hydraulic experiments with hemodynamic numerical simulations, so as to improve the hydraulic performance of pediatric blood pumps while reducing blood damage. Methods:This study employs a combination of computational fluid dynamics (CFD) and orthogonal experimentation to optimize six key parameters of the impeller blade. The optimal blade parameter model is determined through range analysis. The hydraulic performance of the optimized model is evaluated via in vitro experiments, which provide pressure and flow data. Additionally, hemodynamic performance is assessed using CFD, with key evaluation indices including flow field characteristics, pressure distribution, and shear stress distribution within the axial flow pump. Results:From an orthogonal experiment, six blade parameters were found to influence blood pump pressure head: the distance between the starting surface of the blade and the hub (W), blade height (h), blade length (L), blade wrapping angle (α), blade outlet angle (β), and blade inlet angle (γ). The approximately linear pressure-flow curve of the optimized axial blood pump meets design requirements at a pump speed of 10000 rpm, achieving a pressure head of 50.8 mmHg and a flow rate of 3L/min. Computational fluid dynamics analysis reveals a smooth flow field with a low maximum reflux rate of 0.16 % in sections I, II, and III. Pressure is evenly distributed, with a maximum of approximately 104Pa in the inner wall of the impeller area, working face of the impeller blade, and guide tail blade. There are no high shear stress areas, with shear stress below 200Pa accounting for approximately 95.08 % and areas exceeding 300Pa accounting for roughly 1.56 %. Conclusions:This study investigates the correlation between blade parameters and hydraulic performance in axial flow pumps used for blood pumping. The results of both flow field analysis and experimental studies, conducted using orthogonal experiments, demonstrate that the optimized blood pump exhibits enhanced performance in reducing both reflux rate and shear stress. These findings provide valuable insights for the design optimization of pediatric ventricular assist devices.

LZTR1 is a member of the BTB-Kelch protein family and participates in various cellular processes. Existing studies have reported its association with myocardial injury, which aligns with our clinical case observations, though its precise pathogenic mechanisms remain incompletely understood. Clinical investigations revealed that patient harboring pathogenic LZTR1 mutations displayed markedly diminished LZTR1 protein expression, which was clinically associated with progressive dilated cardiomyopathy (DCM) and decompensated heart failure (HF). To mechanistically interrogate this genotype-phenotype relationship, we established cardiac-specific Lztr1 knockdown mouse models through CRISPR-Cas9/AAV9-mediated gene targeting mutation system (CASAAV). These Lztr1-deficient mice recapitulated human DCM pathology, exhibiting severely compromised systolic function alongside disrupted mitochondrial, elevated cardiomyocyte apoptosis, and dysregulated Calcium (Ca2+) handling kinetics. Subsequently, we validated pathway alterations identified by transcriptomic sequencing, revealing that Lztr1 deficiency activates the RAP1/MAPK/AKT signaling pathway and leads to the disorder of Ca2+ homeostasis and apoptosis. These findings will facilitate further exploration of LZTR1 as a potential therapeutic target for DCM.

The leucine zipper-like transcriptional regulator 1 ( LZTR1 ) gene has been reported to be associated with many kinds of human diseases, including cardiac disease, Noonan syndrome, and schwannomatosis. In this study, peripheral blood mononuclear cells (PBMCs) derived from patient diagnosed with dilated cardiomyopathy (DCM) was successfully reprogrammed into the human induced pluripotent stem cells (iPSCs) line, harboring a distinct heterozygous mutation in the LZTR1 gene. The established patient-derived iPSCs expressed endogenous pluripotent markers, demonstrated the potential to differentiate into three germ layers (endoderm, mesoderm, and ectoderm), and exhibited a normal karyotype.

Objective We aimed to investigate the prognostic factors of pediatric extracorporeal cardiopulmonary resuscitation (ECPR). Methods The retrospective study included a total of 77 pediatric cases (7 neonates and 70 children) who underwent ECPR after in-hospital and out-of-hospital cardiac arrest between July 2007 and December 2022. Primary endpoints were complications, while secondary endpoints included all-cause in-hospital mortality. Results Among the 45 cases experiencing complications, 4 neonates and 41 children had multiple simultaneous complications, primarily neurological issues in 25 cases. Additionally, organ failure occurred in 11 cases, and immunodeficiency was present in two cases. Furthermore, 9 cases experienced bleeding events, and 13 cases showed thrombosis. Patients with complications had lower weight, shorter ECMO durations, and longer CPR durations. Non-survivors had longer CPR durations and shorter durations of ECMO, ICU stay, and mechanical ventilation compared to survivors. Complications were more prevalent in non-survivors, particularly organ failure and bleeding events. Conclusion Weight, CPR duration, and ECMO duration were associated with complications, suggesting areas for treatment optimization. The higher occurrence of complications in non-survivors underscores the importance of early detection and management to improve survival rates. Our findings suggest clinicians consider these factors in prognostic assessments to enhance the effectiveness of ECPR programs.

Background Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times, meriting further attention from clinicians. Meanwhile, the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood. Data sources A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed, Embase, and Wanfang databases. Searched keywords included “COVID-19 in children”, “severe pediatric COVID-19”, and “critical illness in children with COVID-19”. Results Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status. Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations, while various forms of cardiovascular and neurological involvement may also be seen. Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways, whose dysregulation in severe and critical diseases translates into adverse clinical manifestations. Multisystem inflammatory syndrome in children (MIS-C), a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure, denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity. Despite the considerable dissimilarities between the pediatric and adult immune systems, clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines. Conclusions Severe pediatric COVID-19 can affect multiple organ systems. The dysregulated immune pathways in severe COVID-19 shape the disease course, epitomize the vast functional diversity of the pediatric immune system and highlight the immunophenotypical differences between children and adults. Consequently, further research may be warranted to adequately address them in pediatric-specific clinical practice guidelines.

Background: Although evidence-based medicine proposes personalized care that considers the best evidence, it still fails to address personal treatment in many real clinical scenarios where the complexity of the situation makes none of the available evidence applicable. "Medicine-based evidence" (MBE), in which big data and machine learning techniques are embraced to derive treatment responses from appropriately matched patients in real-world clinical practice, was proposed. However, many challenges remain in translating this conceptual framework into practice. Objective: This study aimed to technically translate the MBE conceptual framework into practice and evaluate its perform-ance in providing general decision support services for outcomes after congenital heart disease (CHD) surgery. Methods: Data from 4774 CHD surgeries were collected. A total of 66 indicators and all diagnoses were extracted from each echocardiographic report using natural language processing technology. Combined with some basic clinical and surgical information, the distances between each patient were measured by a series of calculation formulas. Inspired by structure-mapping theory, the fusion of distances between different dimensions can be modulated by clinical experts. In addition to supporting direct analogical reasoning, a machine learning model can be constructed based on similar patients to provide personalized prediction. A user-operable patient similarity network (PSN) of CHD called CHDmap was proposed and developed to provide general decision support services based on the MBE approach. Results: Using 256 CHD cases, CHDmap was evaluated on 2 different types of postoperative prognostic prediction tasks: a binary classification task to predict postoperative complications and a multiple classification task to predict mechanical ventilation duration. A simple poll of the k-most similar patients provided by the PSN can achieve better prediction results than the average performance of 3 clinicians. Constructing logistic regression models for prediction using similar patients obtained from the PSN can further improve the performance of the 2 tasks (best area under the receiver operating characteristic curve=0.810 and 0.926, respectively). With the support of CHDmap, clinicians substantially improved their predictive capabilities. Conclusions: Without individual optimization, CHDmap demonstrates competitive performance compared to clinical experts. In addition, CHDmap has the advantage of enabling clinicians to use their superior cognitive abilities in conjunction with it to make decisions that are sometimes even superior to those made using artificial intelligence models. The MBE approach can be embraced in clinical practice, and its full potential can be realized.

目的 总结体外膜肺氧合(ECMO)救治儿童难治性心功能衰竭过程中左心引流的时机、风险和管理体会.方法 回顾性分析2015年1月至2023年2月浙江大学医学院附属儿童医院对难治性心功能衰竭患儿实施ECMO支持并行左心引流10例的治疗情况.并通过对PubMed、中国知网(CNKI)、万方数据库进行检索,对2000年1月至2023年2月数据库中报道的儿童ECMO下左心减压的病例进行文献总结复习.结果 10例患者中6例为暴发性心肌炎并心源性休克,4例为先天性心脏病术后(3例术中脱机困难,1例术后心跳骤停).死亡6例,存活4例.ECMO支持时间36～476 h,左心引流支持时间36～460 h.严重并发症包括颅内出血引起脑疝(2例)、脑梗伴肢体偏瘫(2例)、左室血栓(1例).死亡原因为心功能不能恢复(4例)、脑疝(2例).文献检索出4个研究机构关于儿童左心减压病例汇报.该中心临床结果结合文献对照分析.结论 左心引流能够有效卸载左室前负荷,促进心脏功能恢复.合理把握左心引流时机,预防出凝血,优化体循环/左心引流比例等管理细节,可降低重大并发症发生率.

Introduction Alzheimer’s disease (AD) is the most common type of dementia in the aging population characterized by a progressive decline of cognition that brings a significant burden for patients and society. The exact pathogenesis of AD is still elusive. AD progresses along a continuum from the preclinical stage, mild cognitive, and then dementia stages. Converging lines of evidence from research studies reveal that underlying pathological changes due to AD exist in the decades before symptom onset. However, a large portion of patients remains undiagnosed at the early stages of AD in clinical practice. The early and accurate identification of AD underlying pathology is fundamental for the diagnosis, disease monitoring, and management of AD patients. Notably, early diagnosis of AD is a critical step forward for the clinical trial, which facilitates the development of disease-modifying therapies. In recent years, immense affords have been made to illustrate the early pathological changes of AD. Progress in fluid biomarkers and image analyses facilitates the early and accurate diagnostic process for AD. Based on the evidence of several core pathological changes of AD, including amyloid-β (Aβ) deposition, phosphorylated tau (p-tau), and neurodegeneration, a research framework for AD defining was proposed in 2018. However, positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers evaluations have several limitations, including high cost, insufficient accessibility, and invasiveness, stint them as a first-line AD diagnostic evaluation. Emerging blood-based biomarkers are an exciting development in this field, since they may provide a convenient, cost-effective, and less invasive screening tool.

BackgroundAcute 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.MethodsA 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).ResultsIn 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.ConclusionsOperation 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.

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.

Idiopathic cardiomyopathy (ICM) is a rare pediatric disease with a poor prognosis.Current end-stage management of ICM is composed mostly of routine correcting heart failure (HF) and heart transplantation (HT). Some individuals die from a shortage of donor heart or non-suitability for HT.Mechanical circulation supports might improve the prognosis of end-stage patients.However, their applications have not been implemented for ICM children in China.Based upon current management guidelines for HF children, recent research advances of mechanical circulation support were summarized for optimal end-stage treatments of ICM children.

Background Pediatric acute fulminant myocarditis (AFM) is a very dangerous disease that may lead to acute heart failure or even sudden death. Previous reports have identified some prognostic factors in adult AFM; however, there is no such research on children with AFM on venoarterial extracorporeal membrane oxygenation (VA-ECMO). This study aimed to find relevant prognostic factors for predicting adverse clinical outcomes. Methods A retrospective analysis was performed in an affiliated university children’s hospital with consecutive patients receiving VA-ECMO for AFM from July 2010 to November 2020. These children were classified into a survivor group (n=33) and a non-survivor group (n=8). Patient demographics, clinical events, laboratory findings, and electrocardiographic and echocardiographic parameters were analyzed. Results Peak serum creatinine (SCr) and peak creatine kinase isoenzyme MB during ECMO had joint predictive value for in-hospital mortality (p=0.011, AUC=0.962). Based on multivariable logistic regression analysis, peak SCr level during ECMO support was an independent predictor of in-hospital mortality (OR=1.035, 95% CI 1.006 to 1.064, p=0.017, AUC=0.936, with optimal cut-off value of 78 μmol/L). Conclusion Tissue hypoperfusion and consequent end-organ damage ultimately hampered the outcomes. The need for left atrial decompression indicated a sicker patient on ECMO and introduced additional risk for complications. Earlier and more cautious deployment would likely be associated with decreased risk of complications and mortality.

Background Congenital heart disease(CHD)is one of the main supportive diseases of extracorporeal membrane oxygena-tion in children.The management of extracorporeal membrane oxygenation(ECMO)for pediatric CHD faces more severe challenges due to the complex anatomical structure of the heart,special pathophysiology,perioperative complications and various concomitant malformations.The survival rate of ECMO for CHD was significantly lower than other classifica-tions of diseases according to the Extracorporeal Life Support Organization database.This expert consensus aims to improve the survival rate and reduce the morbidity of this patient population by standardizing the clinical strategy.Methods The editing group of this consensus gathered 11 well-known experts in pediatric cardiac surgery and ECMO field in China to develop clinical recommendations formulated on the basis of existing evidences and expert opinions.Results The primary concern of ECMO management in the perioperative period of CHD are patient selection,cannulation strategy,pump flow/ventilator parameters/vasoactive drug dosage setting,anticoagulation management,residual lesion screening,fluid and wound management and weaning or transition strategy.Prevention and treatment of complications of bleeding,thromboembolism and brain injury are emphatically discussed here.Special conditions of ECMO management related to the cardiovascular anatomy,haemodynamics and the surgical procedures of common complex CHD should be considered.Conclusions The consensus could provide a reference for patient selection,management and risk identification of periop-erative ECMO in children with CHD.

OBJECTIVE:Acute kidney injury (AKI) is a common complication after pediatric cardiac surgery, and the early detection of AKI may allow for timely preventive or therapeutic measures. However, current AKI prediction researches pay less attention to time information among time-series clinical data and model building strategies that meet complex clinical application scenario. This study aims to develop and validate a model for predicting postoperative AKI that operates sequentially over individual time-series clinical data.MATERIALS AND METHODS:A retrospective cohort of 3386 pediatric patients extracted from PIC database was used for training, calibrating, and testing purposes. A time-aware deep learning model was developed and evaluated from 3 clinical perspectives that use different data collection windows and prediction windows to answer different AKI prediction questions encountered in clinical practice. We compared our model with existing state-of-the-art models from 3 clinical perspectives using the area under the receiver operating characteristic curve (ROC AUC) and the area under the precision-recall curve (PR AUC).RESULTS:Our proposed model significantly outperformed the existing state-of-the-art models with an improved average performance for any AKI prediction from the 3 evaluation perspectives. This model predicted 91% of all AKI episodes using data collected at 24 h after surgery, resulting in a ROC AUC of 0.908 and a PR AUC of 0.898. On average, our model predicted 83% of all AKI episodes that occurred within the different time windows in the 3 evaluation perspectives. The calibration performance of the proposed model was substantially higher than the existing state-of-the-art models.CONCLUSIONS:This study showed that a deep learning model can accurately predict postoperative AKI using perioperative time-series data. It has the potential to be integrated into real-time clinical decision support systems to support postoperative care planning.

体外膜肺氧合（extracorporeal membrane oxygenation, ECMO）技术已成为急性心功能衰竭患儿的临床首选治疗手段之一 [1]，其适用的儿科病种包括暴发性心肌炎 [2]和复杂先天性心脏病术后体外循环脱机困难等引起的严重心功能衰竭等 [3]。常用的插管方式包括颈部插管和正中插管 [4]。静脉-动脉体外膜氧合（veno-arterial ECMO, VA-ECMO）能有效恢复患儿全身循环灌注，但对左心室（left ventricle, LV）的潜在影响不容忽视 [5]。主动脉插管持续泵血增加主动脉根部压力和左室后负荷，进一步加重左室缺血和室性心律失常 [6]。左心室血栓可导致脑梗等致死性并发症 [7]。左心减压能快速有效降低左心负荷，为心脏功能恢复争取更多的时间 [8]。近年来，ECMO支持下，左心减压对于严重左室功能不全的患儿的重要性已得到广泛认可 [9]。截止2020年9月，浙江大学医学院附属儿童医院心脏中心共完成94例患儿V-A ECMO心脏支持，儿童80例（85.1%），新生儿14例（14.9%），撤机率59.6%。2010—2019年V-A ECMO支持下左心减压共完成5例，4例死亡、1例存活，现将相关临床资料和经验分析汇总如下。

女性患儿,1岁5个月,体重10 kg,因"咳嗽5d,喘息3 d,发现心率快1 d"于2019-01-16急诊收治入ICU.入院查体:体温38.1℃,心率174次/min,呼吸36次/min,血压 94/63 mmHg(1 mmHg=0.133 kPa),意识清,心音低,心律不齐.心电图提示阵发性室性心动过速(图1).

Objective:To investigate the preschool period neurodevelopmental status and analyze the perioperative data which associated with delayed neurodevelopment in patients underwent antergrade cerebral perfusion(ACP).Methods:To access the preschool period neurodevelopmental status in patients underwent ACP using Griffiths mental development scale-Chinese(GDS-C). Patients were classified as normal development group(ND) and low development group(LD) depending on the outcomes of assessment. Perioperative data including age, weight, CPB time, aortic cross-clamp time, mean arterial pressure, ACP time and flow were analyzed retrospectively.Results:62 children who met the inclusion criteria, of which 19 were accessed by GDS-C scale. Fourteen cases were lagged in general quotient(GQ) compared with normal children. The outcomes of assessment in six subscales of GDS-C scale indicated that 13 cases were delayed in language(C) and practical reasoning(F). Eight cases were delayed in locomotor(A) and personal-social(B). Eleven cases were delayed in eye-hand coordination(D). Ten cases were delayed in performance(E). The children in LD group had significant longer CPB time and aortic cross-clamp time than those in ND group. There were no differences between two groups in other perioperative data.Conclusion:The incidence of preschool period neurodevelopmental delay after ACP in infants is relatively high. In detailed analysis, their language and practical reasoning ability are lagged significantly. In addition, the longer time of CPB and aortic cross-clamp are associated with the neurodevelopmental delay.

Venoarterial extracorporeal membrane oxygenation (VA ECMO) has been considered as the first-line treatment for acute fulminant myocarditis (AFM) when traditional treat-ment is ineffective.Peripheral vascular VA ECMO can partially reduce right ventricular preload,but it can increase left ventricular(LV) afterload.1 The increased afterload may cause difficulty in LV blood ejection in patients with severely impaired LV function.In addi-tion,it may result in secondary LV dilatation,pulmonary edema,intraventricular throm-bosis,and even increased LV diastolic pressure,leading to myocardial ischemia and irreversible cardiac function,affecting the prognosis of the disease.2 Timely LV decompression can help to improve the prognosis.3 Here,we report a successful case of applying a surgical minimal invasive left atrial decompression method,and we discuss the appropriate timing and method of LV decompression during ECMO supporting in pediatric AFM.

出血与凝血功能障碍是先天性心脏病(以下简称先心病)手术后常见的并发症,严重者会影响患者预后,甚至直接或间接导致死亡.先心病手术后出凝血管理是围术期管理的重点和难点.手术后早期以旋转式血栓弹力监测(rotational thromboelastometry,ROTEM)算法为导向的出凝血管理在国外心脏手术病人中广泛应用,但国内尚无统一规范的出凝血管理流程,本文就小儿先心病手术后出凝血管理的研究进展进行综述.

心肺转流( cardiopulmonary bypass,CPB)心内直视术后可因心内畸形矫治不完全、心功能不全、低心排血量综合征、心律失常、外周阻力异常、肺动脉高压、低氧血症以及药物使用不当等多种原因致CPB脱机困难[1-2].本文报告与管理不当有关的2 例复杂先天性心脏病术后无法脱离CPB而采用体外膜氧合( extracorporeal membrane oxygenation, EC?MO)支持的情况及原因分析.