Therapeutic potential of melatonin in the intervertebral disc degeneration through inhibiting the ferroptosis of nucleus pulpous cells.

Ferroptosis, a novel type of cell death mediated by the iron-dependent lipid peroxidation, contributes to the pathogenesis of the intervertebral disc degeneration (IDD). Increasing evidence demonstrated that melatonin (MLT) displayed the therapeutic potential to prevent the development of IDD. Current mechanistic study aims to explore whether the downregulation of ferroptosis contributes to the therapeutic capability of MLT in IDD. Current studies demonstrated that conditioned medium (CM) from the lipopolysaccharide (LPS)-stimulated macrophages caused a series of changes about IDD, including increased intracellular oxidative stress (increased reactive oxygen species and malondialdehyde levels, but decreased glutathione levels), upregulated expression of inflammation-associated factors (IL-1ß, COX-2 and iNOS), increased expression of key matrix catabolic molecules (MMP-13, ADAMTS4 and ADAMTS5), reduced the expression of major matrix anabolic molecules (COL2A1 and ACAN), and increased ferroptosis (downregulated GPX4 and SLC7A11 levels, but upregulated ACSL4 and LPCAT3 levels) in nucleus pulposus (NP) cells. MLT could alleviate CM-induced NP cell injury in a dose-dependent manner. Moreover, the data substantiated that intercellular iron overload was involved in CM-induced ferroptosis in NP cells, and MLT treatment alleviated intercellular iron overload and protected NP cells against ferroptosis, and those protective effects of MLT in NP cells further attenuated with erastin and enhanced with ferrostatin-1(Fer-1). This study demonstrated that CM from the LPS-stimulated RAW264.7 macrophages promoted the NP cell injury. MLT alleviated the CM-induced NP cell injury partly through inhibiting ferroptosis. The findings support the role of ferroptosis in the pathogenesis of IDD, and suggest that MLT may serve as a potential therapeutic approach for clinical treatment of IDD.

A simple-to-use nomogram for predicting prolonged mechanical ventilation for children after Ebstein anomaly corrective surgery: a retrospective cohort study.

BACKGROUND: Prolonged mechanical ventilation (PMV) after pediatric cardiac surgery imposes a great burden on patients in terms of morbidity, mortality as well as financial costs. Ebstein anomaly (EA) is a rare congenital heart disease, and few studies have been conducted about PMV in this condition. This study aimed to establish a simple-to-use nomogram to predict the risk of PMV for EA children. METHODS: The retrospective study included patients under 18 years who underwent corrective surgeries for EA from January 2009 to November 2021. PMV was defined as postoperative mechanical ventilation time longer than 24 hours. Through multivariable logistic regression, we identified and integrated the risk factors to develop a simple-to-use nomogram of PMV for EA children and internally validated it by bootstrapping. The calibration and discriminative ability of the nomogram were determined by calibration curve, Hosmer-Lemeshow goodness-of-fit test and receiver operating characteristic (ROC) curve. RESULTS: Two hundred seventeen children were included in our study of which 44 (20.3%) were in the PMV group. After multivariable regression, we obtained five risk factors of PMV. The odds ratios and 95% confidence intervals (CI) were as follows: preoperative blood oxygen saturation, 0.876(0.805,0.953); cardiothoracic ratio, 3.007(1.107,8.169); Carpentier type, 4.644(2.065,10.445); cardiopulmonary bypass time, 1.014(1.005,1.023) and postoperative central venous pressure, 1.166(1.016,1.339). We integrated the five risk factors into a nomogram to predict the risk of PMV. The area under ROC curve of nomogram was 0.805 (95% CI, 0.725,0.885) and it also provided a good discriminative information with the corresponding Hosmer-Lemeshow p values > 0.05. CONCLUSIONS: We developed a nomogram by integrating five independent risk factors. The nomogram is a practical tool to early identify children at high-risk for PMV after EA corrective surgery.

Suppression of Myocardial Hypoxia-Inducible Factor-1α Compromises Metabolic Adaptation and Impairs Cardiac Function in Patients With Cyanotic Congenital Heart Disease During Puberty.

BACKGROUND: Cyanotic congenital heart disease (CCHD) is a complex pathophysiological condition involving systemic chronic hypoxia (CH). Some patients with CCHD are unoperated for various reasons and remain chronically hypoxic throughout their lives, which heightens the risk of heart failure as they age. Hypoxia activates cellular metabolic adaptation to balance energy demands by accumulating hypoxia-inducible factor 1-α (HIF-1α). This study aims to determine the effect of CH on cardiac metabolism and function in patients with CCHD and its association with age. The role of HIF-1α in this process was investigated, and potential therapeutic targets were explored. METHODS: Patients with CCHD (n=25) were evaluated for cardiac metabolism and function with positron emission tomography/computed tomography and magnetic resonance imaging. Heart tissue samples were subjected to metabolomic and protein analyses. CH rodent models were generated to enable continuous observation of changes in cardiac metabolism and function. The role of HIF-1α in cardiac metabolic adaptation to CH was investigated with genetically modified animals and isotope-labeled metabolomic pathway tracing studies. RESULTS: Prepubertal patients with CCHD had glucose-dominant cardiac metabolism and normal cardiac function. In comparison, among patients who had entered puberty, the levels of myocardial glucose uptake and glycolytic intermediates were significantly decreased, but fatty acids were significantly increased, along with decreased left ventricular ejection fraction. These clinical phenotypes were replicated in CH rodent models. In patients with CCHD and animals exposed to CH, myocardial HIF-1α was upregulated before puberty but was significantly downregulated during puberty. In cardiomyocyte-specific Hif-1α-knockout mice, CH failed to initiate the switch of myocardial substrates from fatty acids to glucose, thereby inhibiting ATP production and impairing cardiac function. Increased insulin resistance during puberty suppressed myocardial HIF-1α and was responsible for cardiac metabolic maladaptation in animals exposed to CH. Pioglitazone significantly reduced myocardial insulin resistance, restored glucose metabolism, and improved cardiac function in pubertal CH animals. CONCLUSIONS: In patients with CCHD, maladaptation of cardiac metabolism occurred during puberty, along with impaired cardiac function. HIF-1α was identified as the key regulator of cardiac metabolic adaptation in animals exposed to CH, and pubertal insulin resistance could suppress its expression. Pioglitazone administration during puberty might help improve cardiac function in patients with CCHD.

Effect of Sleep Disorder on Delirium in Post-Cardiac Surgery Patients.

BACKGROUND: Post-cardiac surgery patients exhibit a higher incidence of postoperative delirium (PD) compared to non-cardiac surgery patients. Patients with various cardiac diseases suffer from preoperative sleep disorder (SPD) induced by anxiety, depression, breathing disorder, or other factors. OBJECTIVE: To examine the effect of sleep disorder on delirium in post-cardiac surgery patients. METHODS: We prospectively selected 186 patients undergoing selective cardiac valve surgery. Preoperative sleep quality and cognitive function of all eligible participants were assessed through the Pittsburgh Sleep Quality Index (PSQI) and the Montreal Cognitive Assessment, respectively. The Confusion Assessment Method for Intensive Care Unit was used to assess PD from the first to seventh day postoperatively. Patients were divided into two groups according to the PD diagnosis: (1) No PD group and (2) the PD group. RESULTS: Of 186 eligible patients, 29 (15.6%) were diagnosed with PD. A univariate analysis showed that gender (p = 0.040), age (p = 0.009), SPD (p = 0.008), intraoperative infusion volume (p = 0.034), postoperative intubation time (p = 0.001), and intensive care unit stay time (p = 0.009) were associated with PD. A multivariate logistic regression analysis demonstrated that age (odds ratio (OR): 1.106; p = 0.001) and SPD (OR: 3.223; p = 0.047) were independently associated with PD. A receiver operating characteristic curve demonstrated that preoperative PSQI was predictive of PD (area under curve: 0.706; 95% confidence interval: 0.595-0.816). A binomial logistic regression analysis showed that there was a significant association between preoperative 6 and 21 PSQI scores and PD incidence (p = 0.009). CONCLUSIONS: Preoperative SPD was significantly associated with PD and a main predictor of PD.

Risk Factors for Prolonged Mechanical Ventilation After Total Cavopulmonary Connection Surgery: 8 Years of Experience at Fuwai Hospital.

OBJECTIVE: Prolonged mechanical ventilation (PMV) is closely associated with higher morbidity and mortality after total cavopulmonary surgery. The aim of the present study was to identify the clinical risk factors for PMV. DESIGN: A retrospective case-control study. SETTING: Fuwai Hospital. PARTICIPANTS: The study comprised 504 patients who underwent total cavopulmonary surgery from 2010 to 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The definition of PMV was derived from the Cox regression model for predicting postoperative length of hospital stay. Least absolute shrinkage and selection operator regression, logistic regression, and Cox regression were applied to identify predictors for PMV. Patients with mechanical ventilation time >9 hours were identified as having PMV. Independent predictors of PMV included age, intraoperative maximum vasoactive-inotropic score, minimal temperature during cardiopulmonary bypass, postoperative prothrombin time, alkaline phosphatase and total bilirubin levels, and postoperative fluid balance. These predictors also were achieved in the Cox regression for predicting the duration of mechanical ventilation. Patients with PMV were associated with increased blood transfusions, more consumption of vasopressin and antipulmonary hypertension medication, higher incidence of reintubation, more renal replacement treatment, longer intensive care unit stay, greater hospitalization costs, and more specialist visits. CONCLUSIONS: Age at surgery, maximal vasoactive-inotropic score and minimal temperature during cardiopulmonary bypass, postoperative prothrombin time, alkaline phosphatase and total bilirubin levels, and postoperative fluid balance were demonstrated to be independent predictors of PMV. Adopting a comprehensive strategy of perioperative management that targets the identified risk factors might significantly lower the risk of PMV and improve in-hospital outcomes, and furthermore, patients with PMV might need more specialist visits.

A Propensity-Score Matched Analysis on Outcomes Using Recombinant Activated Factor VII in Pediatric Cardiac Surgery.

OBJECTIVE: To evaluate the effect of recombinant activated factor VII (rFVIIa) administration on outcomes in pediatric cardiac surgery patients with postoperative bleeding. DESIGN: A propensity score-matched retrospective study. SETTING: Single tertiary medical center. PARTICIPANTS: The study comprised 151 patients who received treatment with rFVIIa and were matched with control patients at a 1:2 ratio. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoints were thrombotic events, renal replacement therapy (RRT), and mortality. The secondary endpoints were length of intensive care unit stay and the reexploration rate. Patients in the rFVIIa group showed no significant differences in thrombotic events (odds ratio [OR] 1.03; 95% confidence interval [CI] 0.48-2.21; p = 0.948), mortality (OR 0.94; 95% CI 0.42-2.13; p = 0.891), and RRT (OR 1.38; 95% CI 0.73-2.58; p = 0.319). However, patients in the rFVIIa group experienced a prolonged length of intensive care unit stay (5.65 [3.00-12.28] d v 3.91 [1.83-6.77] d) and an increased reexploration rate (8.2% v 3.1%). High-dose rFVIIa was an independent risk factor of thrombotic events (OR 5.17; 95% CI 1.19-22.49; p = 0.029). CONCLUSION: This study found that rFVIIa is not associated with increased risks of postoperative thrombotic events, mortality, or RRT in pediatric patients undergoing cardiac surgery. Nevertheless, rFVIIa was associated with longer intensive care unit stay and increased reexploration rate. Furthermore, the risk for thrombotic events may increase with high-dose rFVIIa.

Predictors of Short-term Outcomes Following Repair of Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery in Chinese Children: A Case-Control Study.

OBJECTIVE: To analyze the predictive factors associated with prolonged mechanical ventilation (PMV) and prolonged duration of inotropic support (PDIS) following anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) surgery with possible concomitant mitral valve procedure (MVP) in a relatively young population. DESIGN: A retrospective case-control study. SETTING: Fuwai hospital. PARTICIPANTS: Pediatric patients with ALCAPA surgery from July 2010 to October 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PMV was defined as a mechanical ventilation time ≥48 hours and PDIS as a duration of inotropic support ≥6 days. Univariate analysis, logistic regression analysis, and receiver operating characteristic curve analysis were used to identify independent predictors of PMV and PDIS. The independent predictors of PMV were found to be the left ventricular end-diastolic diameter z-score (LVEDDz), estimate of glomerular filtration rate (eGFR) and maximum vasoactive-inotropic score (VISm). The odds ratios and 95% confidence intervals for these predictors of PMV were the following: LVEDDz, 1.58 (1.19-2.09); eGFR, 0.96 (0.93-0.998); and VISm, 1.08 (1.01-1.17). The predictor of PDIS was LVEDDz at 1.65 (1.26-2.15). One patient died during hospitalization, and there was no reoperation. Thirty-seven patients received concomitant MVP with no hospital mortality. At discharge, mitral regurgitation (MR) had improved in all patients with MR. Patients with PMV were associated with more acute kidney injury, PDIS, and longer ICU and hospital stays. CONCLUSIONS: In relatively young individuals who received ALCAPA surgery and possible concomitant MVP, short-term outcomes are favorable. Based on their experience bias, the authors recommend combining LVEDDz, eGFR, and VISm to predict PMV and applying LVEDDz for PDIS.

Alda-1 Attenuates Lung Ischemia-Reperfusion Injury by Reducing 4-Hydroxy-2-Nonenal in Alveolar Epithelial Cells.

OBJECTIVES: Excessive oxidative stress is a main cause of lung ischemia-reperfusion injury, which often results in respiratory insufficiency after open-heart surgery for a cardiopulmonary bypass. Previous studies demonstrate that the activation of aldehyde dehydrogenase-2 could significantly reduce the oxidative stress mediated by toxic aldehydes and attenuate cardiac and cerebral ischemia-reperfusion injury. However, both the involvement of aldehydes and the protective effect of the aldehyde dehydrogenase-2 agonist, Alda-1, in lung ischemia-reperfusion injury remain unknown. DESIGN: Prospective laboratory and animal investigation were conducted. SETTING: State Key Laboratory of Cardiovascular Disease. SUBJECTS: Primary human pulmonary alveolar epithelial cells, human pulmonary microvascular endothelial cells, and Sprague-Dawley rats. INTERVENTIONS: A hypoxia/reoxygenation cell-culture model of human pulmonary alveolar epithelial cell, human pulmonary microvascular endothelial cell, and an isolated-perfused lung model were applied to mimic lung ischemia-reperfusion injury. We evaluated the effects of Alda-1 on aldehyde dehydrogenase-2 quantity and activity, on aldehyde levels and pulmonary protection. MEASUREMENTS AND MAIN RESULTS: We have demonstrated that ischemia-reperfusion-induced pulmonary injury concomitantly induced aldehydes accumulation in human pulmonary alveolar epithelial cells and lung tissues, but not in human pulmonary microvascular endothelial cells. Moreover, Alda-1 pretreatment significantly elevated aldehyde dehydrogenase-2 activity, increased surfactant-associated protein C, and attenuated elevation of 4-hydroxy-2-nonenal, apoptosis, intercellular adhesion molecule-1, inflammatory response, and the permeability of pulmonary alveolar capillary barrier, thus alleviated injury. CONCLUSIONS: Our study indicates that the accumulation of 4-hydroxy-2-nonenal plays an important role in lung ischemia-reperfusion injury. Alda-1 pretreatment can attenuate lung ischemia-reperfusion injury, possibly through the activation of aldehyde dehydrogenase-2, which in turn removes 4-hydroxy-2-nonenal in human pulmonary alveolar epithelial cells. Alda-1 pretreatment has clinical implications to protect lungs during cardiopulmonary bypass.

Utilization of a novel patient-specific 3D-printing template for percutaneous endoscopic transforaminal discectomy: results from a randomized controlled trial.

Background: The learning curve for percutaneous endoscopic transforaminal discectomy (PETD) is steep, especially for the puncturing and localization procedures. The implementation of 3D printing technology may solve this problem. Methods: A novel individualized 3D-printing template (3D-PT) was designed and utilized in PETD. A prospective randomized controlled trial was performed. A total of 28 patients with lumbar disc herniation treated with PETD were analyzed. Of these, 14 patients were treated with the assistance of 3D printing technology (3D-PT group) in conjunction with fluoroscopy, while the remaining 14 patients were treated exclusively under the guidance of C-arm fluoroscopy (control group). Results: The number of puncture attempts in the 3D-PT group was significantly less than in the control group (1.36 ± 0.63 vs. 6.07 ± 3.08, p = 0.000). The 3D-PT group exhibited a significant reduction in both intraoperative puncture fluoroscopies (2.71 ± 1.27 vs. 12.14 ± 6.15, p = 0.000) and the overall number of fluoroscopies (2.71 ± 1.27 vs. 17.43 ± 6.27, p = 0.000). In the 3D-PT group, there was a significant reduction in both the puncture time (5.77 ± 1.82 vs. 13.99 ± 4.36, p = 0.000) and the total operation time (60.39 ± 9.78 vs. 76.25 ± 17.78, p = 0.007). Complications were not observed in either group. Conclusion: The application of the novel individualized 3D-PT for PETD is effective and safe. The technique has substantial potential and is worth widely promoting.

A Gender-, Age-, and Weight Status-Specific Analysis of the High Prevalence of Hyperuricemia Among Chinese Children and Adolescents with Obesity.

Objective: To explore the gender-, age-, and weight status-specific prevalence of hyperuricemia (HUA) and its associated risk factors among Chinese children and adolescents with obesity. Methods: A total of 1329 children aged 2-17 years, who were diagnosed with obesity and hospitalized in our center from January 2016 to December 2022 were recruited. They were divided into mild obesity, moderate obesity, and severe obesity groups. HUA was defined as fasting serum uric acid level >420 µmol/L for boys and >360 µmol/L for girls. Multivariate logistic regression analyses were performed to identify risk factors for HUA. Results: The highest proportion of hospitalized obese children was aged 10-13 years comprising 677 (50.9%) followed by those aged 6-9 years comprising 348 (26.2%) whereas the least proportion was aged 2-5 years comprising 76 (5.7%). The above differences in age distribution were still present in subgroup analyses according to weight status. Most hospitalized obese children were boys (64.7%), especially in the severe obesity group (75.0%). The overall estimated prevalence of HUA in obese children was 54.8%. It presented a gradual increase trend over the last 7 years, with more rapidly in boys than in girls. Subgroup analysis by weight status showed that the prevalence of HUA was higher in children with moderate obesity (64.3%) and severe obesity (64.2%) when compared with mild obesity (48.2%) (P all<0.01). Boys reached a relatively high HUA incidence level (≥60%) at age 12, which occurred about 2 years later than in girls (age 10). With 12 years as the cut-off point, a high prevalence of HUA (≥60%) was observed in both genders. Multivariable logistic regression analyses showed that boy (OR=2.844, 95% CI 2.024-3.998), age (OR=1.253, 95% CI 1.155-1.360), BMI-Z score (OR=2.132, 95% CI 1.438-3.162), fasting blood glucose (OR=0.907, 95% CI 0.860-0.956), phosphorus (OR=4.123, 95% CI 2.349-7.239), alkaline phosphatase (OR=1.002, 95% CI 1.001-1.004), creatinine (OR=1.067, 95% CI 1.037-1.098), urea nitrogen (OR=1.193, 95% CI 1.032-1.378), aspartate aminotransferase (OR=1.016, 95% CI 1.002-1.030), triglycerides (OR=1.339, 95% CI 1.075-1.667), and high-density lipoprotein cholesterol (OR=0.381, 95% CI 0.160-0.910) were independently associated with odds of HUA (P all<0.05). Conclusion: The prevalence of HUA in Chinese obese children and adolescents is unexpectedly high. Childhood HUA was significantly associated with obesity. Gender and age differences were observed in the association between childhood obesity and HUA. Obese children aged ≥12 years should be focused on screening the risk of HUA.

Medical Prospect of Melatonin in the Intervertebral Disc Degeneration through Inhibiting M1-Type Macrophage Polarization via SIRT1/Notch Signaling Pathway.

The study aims to explore the medical prospect of melatonin (MLT) and the underlying therapeutic mechanism of MLT-mediated macrophage (Mφ) polarization on the function of nucleus pulposus (NP) in intervertebral disc degeneration (IDD). RAW 264.7 Mφs were induced by lipopolysaccharide (LPS) to simulate Mφ polarization and the inflammatory reaction of Mφs with or without MLT were detected. Conditioned medium (CM) collected from these activated Mφs with or without MLT treatment were further used to incubate NP cells. The oxidative stress, inflammation and extracellular matrix (ECM) metabolism in NP cells were determined. Then, the changes in SIRT1/Notch signaling were detected. The agonist (SRT1720) and inhibitor (EX527) of SIRT1 were used to further explore the association among MLT. The interaction between SIRT1 and NICD was detected by immunoprecipitation (IP). Finally, puncture-induced rat IDD models were established and IDD degrees were clarified by X-ray, MRI, H&E staining and immunofluorescence (IF). The results of flow cytometry and inflammation detection indicated that LPS could induce M1-type Mφ polarization with pro-inflammatory properties. MLT significantly inhibited the aforementioned process and inhibited M1-type Mφ polarization, accompanied by the alleviation of inflammation. Compared with those without MLT, the levels of oxidative stress, pro-inflammatory cytokines and ECM catabolism in NP cells exposed to CM with MLT were markedly downregulated in a dose-dependent manner. The inhibition of SIRT1 and the enhancement of Notch were observed in activated Mφs and they can be reversed after MLT treatment. This prediction was further confirmed by using the SRT1720 and EX527 to activate or inhibit the signaling. The interaction between SIRT1 and NICD was verified by IP. In vivo study, the results of MRI, Pfirrmann grade scores and H&E staining demonstrated the degree of disc degeneration was significantly lower in the MLT-treated groups when compared with the IDD control group. The IF data showed M1-type Mφ polarization decreased after MLT treatment. MLT could inhibit M1-type Mφ polarization and ameliorate the NP cell injury caused by inflammation in vitro and vivo, which is of great significance for the remission of IDD. The SIRT1/Notch signaling pathway is a promising target for MLT to mediate Mφ polarization.

Dorsal root ganglion pulsed radiofrequency using bipolar technology in patients with lumbosacral radicular pain duration ≥ 2 years.

Background: Transforaminal epidural steroid injection (TFESI) or dorsal root ganglion pulsed radiofrequency (PRF) are alternative treatments for lumbosacral radicular pain (LSRP). This study aimed to investigate the clinical efficacy of TFESI combined with dorsal root ganglion PRF using bipolar technology to treat LSRP in patients with pain duration ≥ 2 years. Methods: This prospective single-armed cohort study included 20 patients with LSRP duration ≥ 2 years, who underwent treatment of TFESI combined with bipolar PRF. The primary outcomes included numerical rating scale (NRS) and successful treatment rate (pain relief ≥50%). The secondary outcomes included Oswestry Disability Index (ODI), patient satisfaction using the modified MacNab criteria, severe complications, hospital stay and total costs. The final follow-up was 6 months postoperatively. Results: The successful treatment rate and average pain relief at 6 months postoperatively were 80% and 73.0% ± 17.5%, respectively. The successful treatment rates in patients with and without prior intervention history at 6 months postoperatively were 77.8% and 81.8%, respectively. The mean NRS score significantly decreased from 6.5 ± 0.8 to 1.1 ± 0.7 at 2 weeks postoperatively, to 1.3 ± 0.7 at 3 months postoperatively, and to 1.7 ± 1.0 at 6 months postoperatively (all P < 0.001), while the mean ODI score significantly decreased from 43.5 ± 2.5 to 22.5 ± 4.3 at 2 weeks postoperatively, to 20.0 ± 3.5 at 3 months postoperatively, and to 19.5 ± 3.6 at 6 months postoperatively (all P < 0.001). The excellent and good patient satisfaction at 6 months postoperatively was 85%. No severe complications were observed in this cohort. The average hospital stay and total costs were 3.0 ± 0.5 days and 3.36 ± 0.77 thousand dollars, respectively. Conclusion: The treatment of TFESI combined with PRF using bipolar technology might be an alternative option to treat chronic LSRP in patients with pain duration ≥ 2 years after a failure of conservative treatments, with a favorable 6-month efficacy and inexpensive total costs. However, long-term outcomes and superiority of bipolar procedure over monopolar procedure in patients with longer pain duration should be further investigated in future studies.

Persistent Liver Dysfunction in Pediatric Patients After Total Cavopulmonary Connection Surgery.

Background: Studies have reported early liver dysfunction (LD) after cardiac surgery is associated with short and long-term mortality. In this study, we aimed to investigate risk factors for persistent LD after total cavopulmonary connection (TCPC) surgery. Methods: This is a retrospective case-control study. We defined persistent LD as LDs occurring between postoperative day 1 (POD1) and POD7 and sustaining at least on POD7, while transient LD as LDs occurring between POD1 and POD7 and recovering at least on POD7. Multivariable logistic regression analysis was applied and central venous pressure (CVP) was considered continuously or in quantiles. Results: Postoperative LD occurred in 111 (27.1%) patients. Transient and persistent LD occurred in 65 (15.9%) and 46 (11.2%) patients, respectively. Aortic cross-clamping (ACC) (odds ratio [OR] 2.55, 95% CI 1.26-5.14) and postoperative CVP (OR 1.34, 95% CI 1.18-1.51) were risk factors for persistent LD, also identified for postoperative any LD and transient LD. Adding postoperative CVP to the model only including ACC significantly improved persistent LD prediction (△AUC 0.15, p = 0.002). Compared with CVP ≤ 14 mmHg, adjusted ORs and 95% CI of persistent LD for CVP of 14-16 and >16 mmHg were 3.11 (1.24, 7.81) and 10.55 (3.72, 29.93), respectively. Patients with persistent LD might have a longer length of mechanical ventilation (mean difference, 13.5 h) and postoperative hospital stay (mean difference, 7 days), and higher postoperative costs (mean difference, 6.7 thousand dollars) compared to those with transient LD. Conclusions: Intra-operative application of ACC and postoperative elevated CVP were independent risk factors for persistent LD in pediatric patients following TCPC surgery. Compared to patients with transient LD, patients with persistent LD might have a longer length of mechanical ventilation and postoperative hospital stay, and higher postoperative costs. We should pay more attention to patients with high postoperative CVP to prevent their persistent LD occurrence.

The Effect of BMI, Age, Gender, and Pubertal Stage on Bone Turnover Markers in Chinese Children and Adolescents.

Objectives: To ascertain the associations of serum bone turnover markers (BTMs) levels with body mass index (BMI) in Chinese children and adolescents, and whether the influence of BMI, age, pubertal stage on BTMs varied by gender. Methods: A total of 500 students (180 controls and 320 children and adolescents with overweight/obesity) aged 9-14 years were randomly selected from the Chinese National Survey on Students Constitution and Health Cohort. Serum levels of BTMs, including bone formation marker bone alkaline phosphatase (BAP), collagen type 1 C-terminal propeptide (CICP), and bone resorption markers C-terminal telopeptide of type-I collagen (CTX) were determined by commercial enzyme-linked immunosorbent assay kits. The associations among BMI, age, gender, pubertal stage, and BTMs were analyzed. Results: Serum levels of CICP and CTX in overweight/obese children and adolescents were lower than those in controls (p<0.05). Moreover, after subgroup analysis stratified by gender, the decreased serum CICP and CTX levels in overweight/obese children and adolescents were observed only in boys (p<0.05). After adjustment of age and pubertal stage, there was a negative correlation between serum BAP and BMI in both boys and girls (p<0.05). However, the correlations between serum CICP, CTX levels, and BMI were significant in boys but not in girls. Serum BAP and CICP levels were independently correlated with BMI, age, gender, and pubertal stage, while CTX levels were independently correlated with BMI, age, and gender (p<0.05). BAP, CICP, and CTX levels showed a clear age, gender, and pubertal stage dependence with significantly higher values in boys (p<0.05). Conclusions: Our findings support the associations between serum BTMs levels and BMI in Chinese children and adolescents, and suggest age, gender, and pubertal stage differences in this relationship that warrant future studies.

Effect of preoperative pulse oximeter oxygen saturation on postoperative prolonged mechanical ventilation in patients with tetralogy of Fallot.

Background: As an easily accessible and intervened clinical indicator, preoperative pulse oximeter oxygen saturation (SpO2) is an important factor affecting the prognosis of patients with tetralogy of Fallot (TOF). However, whether SpO2 is associated with postoperative mechanical ventilation (MV) time remains unknown. Therefore, this study aimed to investigate the impact of preoperative SpO2 on postoperative prolonged mechanical ventilation (PMV) in children with TOF. Materials and methods: The study included children younger than 18 years who underwent corrective operations for TOF between January 2016 and December 2018 in Fuwai Hospital, China. Univariate and multivariate logistic regression analyses were used to evaluate the influence of preoperative SpO2 on postoperative PMV. After identifying SpO2 as an independent risk factor for PMV, patients were further divided into two groups according to the cutoff value of SpO2, and propensity score matching (PSM) analysis was used to eliminate the effect of confounding factors. The logistic regression was used to compare the outcomes between the two groups after PSM. Results: A total of 617 patients were finally enrolled in this study. By the univariable and multivariate logistic analysis, four independent risk factors for PMV were determined, namely, SpO2, surgical technique, aortic cross-clamp time, and intraoperative minimum temperature. According to the outcomes of 219 paired patients after PSM, the incidence of PMV was significantly higher in patients with lower preoperative SpO2 (P = 0.022). Also, there was significant increase in mechanical ventilation time (P = 0.019), length of intensive care unit stay (P = 0.044), postoperative hospital stay (P = 0.006), hospital stay (P = 0.039), and hospitalization cost (P = 0.019) at the lower preoperative SpO2 level. Conclusion: Low preoperative SpO2 represents an independent risk factor of postoperative PMV in children with TOF.

The critical BMI hypothesis for puberty initiation and the gender prevalence difference: Evidence from an epidemiological survey in Beijing, China.

Background: Although previous studies suggested that there is a certain level of body fat mass before puberty can be initiated, most studies have focused on girls. Objective: To investigate the relationship between precocious puberty and physical growth in school-aged children in Beijing, China. Methods: 7590 Chinese children (3591 girls and 3999 boys) aged 6-11 years were recruited in Beijing, China. Body mass index (BMI) categories were defined by WHO Child Growth Standards and central obesity were defined by sex-specific waist-to-height ratio cut-offs (≥0.46 for girls, ≥0.48 for boys). Sexual development was assessed using Tanner criteria. Results: The prevalence of general obesity and central obesity among boys was higher than that in girls. Girls had a significantly higher precocious puberty rate than boys (5.93% vs. 0.87%), particularly in those aged 7 years old (9.20%). Children in the general obesity and central obesity groups have a higher prevalence of precocious puberty and earlier median ages for the attainment of Tanner B2/T2. For girls with Tanner stages≥II at 6-year-old and 7-year-old, the mean BMI was equivalent to the 50th centile of a normal 9.9-year-old and 11.9-year-old girl, respectively. The mean BMI of boys with Tanner stages≥II at 7-year-old and 8-year-old was correspondent to the 50th centile of a normal 14-year-old and 15.3-year-old boy, respectively. For girls, general obesity appears to contribute to the risk of the development of precocious puberty to a greater extent than central obesity does. For boys, central obesity, but not general obesity, was an independent risk factor for precocious puberty. Conclusions: The prevalence of childhood obesity and precocious puberty was high in China. Precocious puberty was correlated with a large BMI. Boys had a higher threshold of BMI for puberty development than girls. Children with precocious puberty, particularly those with central obesity, should be aware of adverse cardiovascular events.

Optimal Degree of Hypothermia in Total Arch Replacement for Type A Aortic Dissection.

Background: We sought to investigate the best degree of hypothermic cardiac arrest (HCA) in type A aortic dissection (TAAD) with a cohort of 1,018 cases receiving total arch replacement from 2013 to 2018 in Fuwai Hospital. Method: The cohort was divided by DHCA (≤24°C, n = 580) vs. MHCA (>24°C, n = 438), and interquartile range (Q1-Q4). Primary endpoints included mortality, stroke, paraplegia, and continuous renal replacement therapy (CRRT), which were summarized as composite major outcomes (CMO). Results: The Odds Ratio (OR) of CMO for MHCA was 0.7 (95% CI: 0.5-1.0, p = 0.06) (unadjusted) and 0.6 (95% CI: 0.4-1.0, p = 0.055) (adjusted). DHCA group tended to have a significantly longer CPB time (175.6 ± 45.6 vs. 166.8 ± 49.8 min, p = 0.003), longer hospital stay (16.0 ± 13.6 vs. 13.5 ± 6.8 days, p < 0.001), and ICU stay [5.0 (3.9-6.6) vs. 3.8 (2.0-5.6) days]. A significantly greater blood loss was observed in DHCA group, with a greater requirement for RBC and platelet transfusion. Of note, MHCA showed a significant protective effect (60% risk reduction) for older patients (above 60 years) (OR 0.4; 95% CI: 0.2-0.8; p = 0.009). By quartering, Q1 had significantly higher mortality (10.9%) than Q4 (5.2%) (p = 0.035). For other comparisons, the gap was significantly widened in quartering between Q1 and Q4, i.e., the lower the temperature, the worse the outcomes, and vice versa. Propensity score matching and sensitivity analyses confirmed the above findings. Conclusions: A paradigm change from DHCA to MHCA may be encouraged in TAAD arch operation, especially for the elderly.

Prognostic Value of Preoperative Absolute Lymphocyte Count in Children With Tetralogy of Fallot.

Background Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Absolute lymphocyte count (ALC) is a low-cost and easy-to-obtain inflammatory indicator; however, its association with the prognosis of patients with TOF remains unknown. This study aimed to determine the prognostic value of preoperative ALC in children with TOF. Methods and Results This retrospective study included 707 patients aged <6 years who underwent corrective operations for TOF between January 2016 and December 2018 in Fuwai Hospital, China. The end points were mortality, extracorporeal membrane oxygenation placement, postoperative hospital stay >30 days, and severe postoperative complications; patients were grouped on the basis of prognosis: poor prognosis (n=76) and good prognosis (n=631). Univariable and multivariable logistic regression analyses were performed to identify the independent risk factors for poor prognosis, on which a risk scoring system was based. The receiver operating characteristic curve was used to assess model performance. Using another model without ALC, the effect of the addition of ALC was assessed. Results suggested that ALC was an independent factor with a cutoff point of 4.36×109/L. The addition of ALC improved the area under the curve from 0.771 to 0.781 (P<0.001). To avoid reverse causality and further control for confounding factors, the patients were further divided on the basis of ALC level, and a propensity score matching was performed; 117 paired patients were identified for further analysis. Low ALC levels had an odds ratio of 3.500 (95% CI, 1.413-8.672). Conclusions Low preoperative ALC represents an independent predictor of poor prognosis in children with TOF.

Associations Between Sleep Duration, Wake-Up Time, Bedtime, and Abdominal Obesity: Results From 9559 Chinese Children Aged 7-18 Years.

Objective: To investigate the associations of sleep duration, wake-up time, bedtime, and childhood abdominal obesity, and to test whether there is a weekday/weekend difference and the potential modifying role of sex. Methods: This cross-sectional study was based on the Students' Constitution and Health Survey and included 9559 students (4840 boys and 4719 girls) aged 7-18 years (7227 aged 7-12 years, 2332 aged 13-18 years). They were divided into two groups (control group and group with abdominal obesity). The physical measurements included children and youth body height, body weight, and waist circumference (WC). A parent-report questionnaire was used to collect the information about parent characteristics as well as lifestyle and sleep patterns (sleep duration, bedtime, and wake-up time of weekdays and weekends) of children and youth. Results: The prevalence of abdominal obesity was 30.57% and the percentages of sleep duration <9 hours/day, wake-up time before 07:00 am on weekdays and weekends, bedtime after 10:00 pm on weekends were significantly higher in the group with abdominal obesity. After adjusting for confounders, sleep duration <9 hours/day on weekends was inversely related to abdominal obesity in the overall subjects, regardless of their sex and age, while bedtime after 10:00 pm on weekends was inversely related to abdominal obesity only in the overall subjects, boys, and children aged 7-12 years. Logistic regression models in all subjects showed that shorter hours of weekends sleep duration were associated with greater risks of abdominal obesity, even after adjusting for all confounders, including wake-up time and bedtime. The adjusted odds ratios and 95% confidence intervals of abdominal obesity (with ≥10 hours/day as the reference group) for children with 9-10 hours/day, 8-9 hours/day, and <8 hours/day of weekend sleep duration were 1.23 (1.04-1.46), 1.59 (1.32-1.91) and 1.83 (1.42-2.36), respectively. Specifically, after stratification by sex and age, this phenomenon was only observed in boys and children aged 7-12 years. Conclusions: Sleep duration and bedtime on weekends were independently associated with the risk of childhood abdominal obesity, particularly in boys and children aged 7-12 years.

Predictive value of heart rate in patients with acute type A aortic dissection: a retrospective cohort study.

OBJECTIVE: Heart rate (HR) is a risk factor of mortality in many cardiovascular diseases but no clinical studies have focused on the association between HR and prognosis in patients with acute type A aortic dissection (ATAAD). This study aimed to evaluate the association between HR and long-term mortality and establish the criteria of HR in patients with ATAAD who underwent total aortic arch replacement combined with the frozen elephant trunk (TAR+FET). DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study that studied all consecutive patients with ATAAD who underwent TAR+FET in the Fuwai Hospital between 2009 and 2015. MAIN OUTCOMES AND MEASURES: 30-day postoperative, and estimated long-term mortality. RESULTS: Overall, 707 patients with ATAAD who underwent TAR+FET were followed up for a median duration of 29 months (range, 5-77 months). In multivariate logistic analysis, HR (p<0.001), age (p<0.001), renal insufficiency (p=0.033), ejection fraction (p=0.005), cardiopulmonary bypass time (p<0.001) and intraoperative blood loss (p=0.002) were significantly associated with 30-day postoperative and estimated long-term mortalities. A hinge point with a sharp increase in estimated long-term mortality was identified at 80 beats/min (bpm), and compared with HR ≤80 bpm, HR >80 bpm was associated with an almost threefold higher long-term mortality. HRs ≤60, 60-70, 70-80, 80-90, 90-100, 100-110 and >110 bpm were associated with 3.9%, 4.0%, 3.8%, 7.2%, 9.5%, 10.1% and 14.4% yearly risks of death, respectively. CONCLUSIONS: HR is a powerful predictor of long-term mortality in patients with ATAAD undergoing TAR+FET. HR >80 bpm is independently associated with elevated long-term mortality for patients with ATAAD.