Biochemical and molecular analysis of pediatric patients with metachromatic leukodystrophy in South China: functional characterization of five novel ARSA variants.

Metachromatic leukodystrophy (MLD) is a rare hereditary neurodegenerative disease caused by deficiency of the lysosomal enzyme arylsulfatase A (ARSA). This study described the clinical and molecular characteristics of 24 Chinese children with MLD and investigated functional characterization of five novel ARSA variants. A retrospective analysis was performed in 24 patients diagnosed with MLD at Guangzhou Women and Children's Medical Center in South China. Five novel mutations were further characterized by transient expression studies. We recruited 17 late-infantile, 3 early-juvenile, 4 late-juvenile MLD patients. In late-infantile patients, motor developmental delay and gait disturbance were the most frequent symptoms at onset. In juvenile patients, cognitive regression and gait disturbance were the most frequent chief complaints. Overall, 25 different ARSA mutations were identified with 5 novel mutations.The most frequent alleles were p.W320* and p.G449Rfs. The mutation p.W320*, p.Q155=, p.P91L, p.G156D, p.H208Mfs*46 and p.G449Rfs may link to late-infantile type. The novel missense mutations were predicted damaging in silico. The bioinformatic structural analysis of the novel missense mutations showed that these amino acid replacements would cause severe impairment of protein structure and function. In vitro functional analysis of the six mutants, showing a low ARSA enzyme activity, clearly demonstrated their pathogenic nature. The mutation p.D413N linked to R alleles. In western blotting analysis of the ARSA protein, the examined mutations retained reduced amounts of ARSA protein compared to the wild type. This study expands the spectrum of genotype of MLD. It helps to the future studies of genotype-phenotype correlations to estimate prognosis and develop new therapeutic approach.

Clinical spectrum, over 12-year follow-up and experience of SGLT2 inhibitors treatment on patients with glycogen storage disease type Ib: a single-center retrospective study.

BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment. RESULTS: In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients. CONCLUSION: Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.

Predicting therapeutic efficacy of oral rehydration salts in children with vasovagal syncope.

Objective: This study was designed to develop an easy-to-perform and inexpensive measure to predict efficacy of the oral rehydration salts (ORS) in children with vasovagal syncope (VVS). Materials and methods: Children diagnosed with VVS and treated with ORS for a median of 3 months at the Peking University First Hospital, China, were enrolled and followed up. Demographic data, clinical hemodynamic parameters, and variables related to red blood cells were collected at the baseline. On the basis of changes in symptom scores after treatment, participants were divided into effective or ineffective groups at the end of the follow-up. Logistic regression analysis was used to investigate parameters related to therapeutic efficacy of ORS and a predictive model of ORS effectiveness was created. The predictive efficiency was evaluated using the receiver operating characteristic curve. The accuracy/consistency was evaluated by the Hosmer-Lemeshow test and calibration curve. Internal validation was done using the bootstrap approach. Results: Totally 97 pediatric participants were included in the study and 4 (4.1%) were lost during the follow-up. ORS therapy was effective in 46 children and ineffective in 47 children. Children in the effective group had higher baseline red blood cell count, hemoglobin, and hematocrit than those in the ineffective group (p < 0.01). Through logistic regression analysis, the baseline hematocrit and body mass index (BMI) were included in predictive model for the response to ORS treatment. The predictive efficacy of the model showed an area under the curve of 0.77 (p < 0.01). The predicted probability cut-off value of 0.5 was found to be optimal, with a resulting sensitivity of 67.4% and specificity of 80.9%. In the Hosmer-Lemeshow test, p-value was 0.75, and the calibration plot showed a good model fitness. Internal validation was performed using the bootstrap approach (n = 1,000), showing 95% confidence interval of 0.67-0.86. Conclusion: Hemoglobin combined with BMI was useful for predicting the therapeutic efficacy of ORS in children with VVS.

Effects of Nursing Care Using a Fast-Track Surgery Approach in 49 Patients with Early-Stage Hepatocellular Carcinoma Undergoing First-Line Treatment with Radiofrequency Ablation: A Retrospective Study.

BACKGROUND Fast-track surgery (FTS), also known as enhanced recovery after surgery (ERAS), includes a coordinated perioperative approach to patient care that aims to facilitate postoperative recovery. The role of nursing care is central to the concept of FTS. This retrospective study aimed to evaluate the effects of nursing care using an FTS approach in 49 patients with early-stage hepatocellular carcinoma (HCC) undergoing first-line treatment with radiofrequency ablation (RFA). MATERIAL AND METHODS A retrospective analysis was made of 49 patients with early-stage hepatocellular carcinoma who underwent first-line treatment with radiofrequency ablation in the Department of Hepatobiliary Surgery in our hospital from January 2020 to December 2021. The nurses have been nursing the patients in accordance with the requirements of FTS from 2021. Compared with the data of patients receiving traditional nursing, the detailed differences in postoperative recovery, pain score, complication rate, liver and kidney function, and nursing satisfaction were analyzed. RESULTS After applying the FTS nursing model, the patients had significantly shorter time to first flatus, infusion, postoperative hospital stay, and lower total hospitalization expenses (P<0.05). Moreover, the Numerical Pain Rating Scale score was lower than that in the control group, the postoperative complications in the 2021 group were lower than those in the 2020 group, and the nursing satisfaction was also better than that of the 2020 group (P<0.05). CONCLUSIONS Nursing care using a fast-track surgery approach with early-stage hepatocellular carcinoma patients undergoing first-line treatment with radiofrequency ablation is better than conventional nursing, and improves recovery of patients.

Plasma human growth cytokines in children with vasovagal syncope.

Purpose: The study was designed to investigate the profile of plasma human growth cytokines in pediatric vasovagal syncope (VVS). Materials and methods: In the discovery set of the study, plasma human growth cytokines were measured using a Quantiboby Human Growth Factor Array in 24 VVS children and 12 healthy controls. Scatter and principal component analysis (PCA) diagrams were used to describe the samples, an unsupervised hierarchical clustering analysis was used to categorize the samples. Subsequently, the cytokines obtained from the screening assays were verified with a suspension cytokine array in the validation set of the study including 53 VVS children and 24 controls. Finally, the factors associated with pediatric VVS and the predictive value for the diagnosis of VVS were determined. Results: In the discovery study, the differential protein screening revealed that the plasma hepatocyte growth factor (HGF), transforming growth factor b1 (TGF-b1), insulin-like growth factor binding protein (IGFBP)-4, and IGFBP-1 in children suffering from VVS were higher than those of the controls (all adjust P- value < 0.05). However, the plasma IGFBP-6, epidermal growth factor (EGF), and IGFBP-3 in pediatric VVS were lower than those of the controls (all adjust P- value < 0.01). Meanwhile, the changes of 7 differential proteins were analyzed by volcano plot. Unsupervised hierarchical cluster analysis demonstrated that patients in the VVS group could be successfully distinguished from controls based on the plasma level of seven differential proteins. Further validation experiments showed that VVS patients had significantly higher plasma concentrations of HGF, IGFBP-1, and IGFBP-6, but lower plasma concentrations of EGF and IGFBP-3 than controls. The logistics regression model showed that increased plasma concentration of HGF and IGFBP-1 and decreased plasma concentration of EGF were correlated with the development of pediatric VVS. ROC curve analysis showed that the abovementioned 3 proteins were useful for assisting the diagnosis of VVS. Conclusion: Plasma human growth cytokine profiling changed in pediatric VVS. Elevated plasma concentrations of HGF and IGFBP-1, and decreased EGF were associated factors in the development of pediatric VVS. The abovementioned three proteins are helpful for the diagnosis of pediatric VVS.

Twenty-Four-Hour Urinary Sodium Excretion Predicts Therapeutic Effectiveness of Oral Rehydration Saline in Pediatric Vasovagal Syncope.

The study was designed to explore whether 24-hour urinary sodium excretion could predict the therapeutic effectiveness of oral rehydration saline in pediatric cases of vasovagal syncope. Eighty children suffering from vasovagal syncope with oral rehydration saline treatment in Department of Pediatrics, Peking University First Hospital, China, were recruited into the study. They were followed up for 3 (2, 3) months after treatment. Pre-treatment demographic, clinical, head-up tilt test-based hemodynamic and laboratory variables were compared between responders and non-responders. After univariate analysis, variables with p value < 0.05 in the comparison between responders and non-responders were further analyzed by binary logistic regression analysis. Receiver operating characteristic (ROC) curve was conducted to assess the value in predicting effectiveness of oral rehydration saline treatment. The results showed that 33 cases were responders, and 47 were non-responders. Blood sodium (138 ± 2 mmol/L vs. 139 ± 2 mmol/L, p < 0.05) and pre-treatment 24-hour urinary sodium excretion (74 ± 29 mmol/24 h vs. 109 (93, 141) mmol/24 h, p < 0.001) were lower in responders than in non-responders. The baseline 24-hour urinary sodium excretion was positively correlated to the duration from tilting to the positive response appearance in head-up tilt test (r = 0.289, p < 0.01). The cut-off value of baseline 24-hour urinary sodium excretion of the therapeutic effectiveness of oral rehydration saline on vasovagal syncope cases was 83 mmol/24 h, yielding a sensitivity of 87% and a specificity of 73% with AUC of 0.842 (p < 0.001). In conclusion, 24-hour urinary sodium excretion could be a useful biomarker to predict the therapeutic response to oral rehydration saline in pediatric cases of vasovagal syncope.

Clinical Efficacy of Empirical Therapy in Children with Vasovagal Syncope.

(1) Background: This case-control study was designed to assess the efficacy of empiric treatment for vasovagal syncope in children; (2) Methods: We retrospectively enrolled 181 children with vasovagal syncope from the Department of Pediatrics of Peking University First Hospital. The participants were categorized into four groups, based on the empiric treatment received: conventional treatment, including health education and orthostatic training; conventional treatment plus oral rehydration salts; conventional treatment plus metoprolol; conventional treatment plus midodrine hydrochloride. Patients were followed up to evaluate the syncopal or presyncopal recurrence. Kaplan-Meier curves were drawn to explore the syncopal or presyncopal recurrence in children, and the differences were compared among the groups using a log-rank test; (3) Results: Among the 181 children with vasovagal syncope, 11 were lost to follow-up. The median time of follow-up was 20 (8, 42) months. The Kaplan-Meier survival curve showed no significant difference in syncopal or presyncopal recurrence in children treated with different empiric options according to a log-rank test (χ2 = 1.328, p = 0.723); (4) Conclusions: The efficacy of unselected empiric therapy of vasovagal syncope in children was limited, and the individualized therapies merit further studies.

Predictor of Syncopal Recurrence in Children With Vasovagal Syncope Treated With Metoprolol.

Objective: To explore the predictors for syncopal recurrence in a pediatric population with vasovagal syncope (VVS) treated with metoprolol. Study Design: This study was conducted retrospectively among children suffering from VVS with or without syncopal recurrence. Data on the detailed medical history and auxiliary examinations were obtained from the electronic medical records. The risk factors for syncopal recurrence were studied by cox regression analyses and the corresponding best cutoff values were determined using receiver operating characteristic analysis. Kaplan-Meier curves were plotted to determine the trends of the syncopal recurrence-free survival rate. Results: Forty-two consecutive VVS children were enrolled in the study. At the end of a median follow-up duration of 9.0 (4.8, 19.1) months, 12 patients (29%) experienced ≥1 syncopal episode. Cox regression analyses revealed that the number of previous syncopal episodes before treatment was a risk factor for syncopal recurrence (hazard ratio = 1.027, 95% confidence interval 1.009 - 1.045, P = 0.003). Moreover, 4 previous syncopal episodes were certified as the best cutoff value, and the Kaplan-Meier curves showed that the syncopal recurrence-free survival rate over time in patients with > 4 previous syncopal episodes was significantly lower than that in patients with ≤4 episodes (P = 0.019 at the log-rank test). Conclusion: In a pediatric population with VVS while on the treatment of metoprolol, the number of previous syncopal episodes before treatment played a significant role in predicting syncopal recurrence.

Poincaré Plot Can Be a Useful Tool to Select Potential Responders to Metoprolol Therapy in Children with Vasovagal Syncope.

Purpose: To explore the value of the longitudinal axis/transverse axis ratio (L/T) of Poincaré plot in selecting children with vasovagal syncope (VVS) who were suitable for metoprolol therapy. Patients and Methods: Children with VVS hospitalized in Peking University First Hospital between January 2012 and June 2019 and treated with metoprolol were retrospectively included as the training set, and children with VVS hospitalized between July 2019 and December 2020 were included as the validation set. The sex, age at admission, height, weight, body mass index, course of disease, syncope symptom score before metoprolol treatment, treatment duration, supine heart rate (HR), supine systolic pressure, supine diastolic pressure, peak HR during the head-up tilt test (HUTT), changes of HR during HUTT, hemodynamic response during HUTT, left ventricular ejection fraction, left ventricular fractional shortening and the L/T of Poincaré plot were compared between responders and nonresponders in the training set. Logistic regression analysis was conducted to explore predictors. Receiver operating characteristic curve was utilized to determine the value of the predictors for selecting potential responders. Finally, the value of the predictors was further verified. Results: In the training set including 105 children, the L/T in responders was distinctly higher than that in nonresponders (P < 0.001), and there was no apparent difference between the two groups in other indexes. The L/T was statistically related to the efficacy of metoprolol (P < 0.001). The L/T >2.7 yielded a sensitivity of 88.2% and a specificity of 82.8% for indicating responders to metoprolol. Taking L/T >2.7 to select potential responders in another 43 children with VVS in the validation set, the sensitivity was 96.6%, specificity 71.4%, and accuracy 88.4%. Conclusion: The L/T of Poincaré plot >2.7 can be a useful tool to select potential responders to metoprolol therapy in children with VVS.

Risk factors of sitting-induced tachycardia syndrome in children and adolescents.

BACKGROUND: The study was designed to explore the risk factors for sitting-induced tachycardia syndrome (STS) in children and adolescents. METHODS AND RESULTS: In this case-control study, 46 children with STS and 184 healthy children and adolescents were recruited. Demographic characteristics, lifestyle habits, allergy history, and family history were investigated using a questionnaire. The changes in heart rate and blood pressure from supine to sitting were monitored using a sitting test. The possible differences between STS patients and healthy children were analyzed using univariate analysis. Logistic regression analysis was used to explore the independent risk factors for STS. Univariate analysis showed that the daily sleeping time of the STS children were significantly shorter than that of the control group [(8.8 ± 1.2) hours/day vs. (9.3 ± 1.0) hours/day, P = 0.009], and the proportion of positive family history of syncope in the STS patients was higher than the controls (4/42 vs. 3/181, P = 0.044). Multivariate logistic regression studies showed that reduced daily sleeping time was an independent risk factor of STS in children (P = 0.006). Furthermore, when daily sleeping time was prolonged by 1 h, the risk of STS was decreased by 37.3%. CONCLUSION: Reduced daily sleeping was an independent risk factor for STS in children and adolescents.

Sitting-induced hemodynamic changes and association with sitting intolerance in children and adolescents: a cross-sectional study.

Hemodynamic alteration with postural change from supine to sitting has been unclear in the young. In the cross-sectional study, 686 participants (371 boys and 315 girls, aged 6-18 years) were recruited from 4 schools in Kaifeng city, the central area of China. The active sitting test was performed to obtain heart rate (HR) and blood pressure (BP) changes from supine to sitting in children and adolescents. Hemodynamic change-associated sitting intolerance was analyzed. In the study participants, the 95th percentile (P95) values of changes in HR and BP within 3 min from supine to sitting were 25 beats/min and 18/19 mm Hg, respectively. Sixty-six participants had sitting intolerance symptoms. Compared with participants without sitting intolerance symptoms, those with symptoms more frequently had HR increase ≥ P95 or BP increase ≥ P95 within 3 min from supine to sitting (P < 0.001). Risk factors for sitting intolerance were age (odds ratio 1.218, 95% confidence interval 1.072-1.384, P = 0.002) and changes in HR or BP ≥ P95 within 3 min after sitting (odds ratio 2.902, 95% confidence interval 1.572-5.357, P = 0.001). We firstly showed hemodynamic changing profiles from supine to sitting and their association with sitting intolerance in children and adolescents. Sitting tachycardia is likely suggested with a change in HR ≥ 25 beats/min and sitting hypertension with a change in BP ≥ 20/20 mm Hg when changing from supine to sitting within 3 min. The age and changes in HR or BP were independent risk factors for sitting intolerance.

Risk Factors for Orthostatic Hypertension in Children.

OBJECTIVE: To investigate the risk factors for orthostatic hypertension in children. STUDY DESIGN: Eighty children with orthostatic hypertension were enrolled in the group with orthostatic hypertension, and 51 healthy children served as the control group. Demographic characteristics, clinical history, daily water intake, nightly sleep duration, the results of the standing test, and complete blood count were recorded and compared between the 2 groups. The risk factors for pediatric orthostatic hypertension were determined by logistic regression analysis. RESULTS: Body mass index and red blood cell distribution width were higher in the group with orthostatic hypertension than in healthy children, whereas daily water intake and sleep duration were lower. Logistic regression analyses showed that, if a child suffered from overweight, suffered from obesity, had a daily water intake of less than 800 mL, or had a red blood cell distribution width that was increased by 1%, the risk of orthostatic hypertension would be increased by 6.069 times (95% CI, 1.375-26.783; P < .05), 7.482 times (95% CI, 1.835-30.515; P < .01), 4.027 times (95% CI, 1.443-11.241; P < .01), or 4.008 times (95% CI, 1.698-9.461; P < .01), respectively. However, if the sleep duration was increased by 1 hour, the risk of developing orthostatic hypertension would be decreased by 74.3% (95% CI, 54.6%-85.4%, P < .01). CONCLUSIONS: Increased body mass index, inadequate water intake and sleep duration, and elevated red blood cell distribution width were identified as risk factors for pediatric orthostatic hypertension.

Reduced 24-h Sodium Excretion Is Associated With a Disturbed Plasma Acylcarnitine Profile in Vasovagal Syncope Children: A Pilot Study.

Objective: To investigate if the low sodium intake is associated with the plasma carnitine and acylcarnitine profile in children with vasovagal syncope (VVS). Materials and Methods: Twenty-six children suffering from VVS were recruited in the present study and divided into a group of low urinary sodium excretion or a group of normal urinary sodium excretion according to the excretion of 24-h urinary sodium <3 or 3-6 g, respectively. The excretion of 24-h urinary sodium was detected with ion-selective electrode approach. Plasma carnitine and acylcarnitine concentrations were measured with tandem mass spectrometry. Each participant completed the head-up tilt test. The demographics, clinical characteristics, hemodynamic parameters and plasma carnitine and acylcarnitine concentrations were compared between the two groups. A bivariate correlation between plasma acylcarnitine profiles and the excretion of 24-h urinary sodium was conducted with Spearman's correlation coefficients. Results: Of the enrolled VVS patients, 14 patients were assigned to the group of low urinary sodium excretion and the remaining 12 patients were assigned to the group of normal urinary sodium excretion. Symptoms of fatigue were more prevalent in the group of low urinary sodium excretion than in the group of normal urinary sodium excretion (p = 0.009). Aside from fatigue, no other differences in the demographics, clinical characteristics or hemodynamic parameters during the head-up tilt test were found between the two groups (p > 0.05). Concentrations of plasma tiglylcarnitine (C5:1), hydroxyhexadecanoylcarnitine (C16OH), hydroxyoctadecanoylcarnitine (C18OH), and carnitine C22 were significantly higher in the group of low urinary sodium excretion than in the group of normal urinary sodium excretion (all p-values = 0.048); moreover, they were all negatively correlated with 24-h urinary sodium levels (all p-values = 0.016). There were no differences between the two groups in other acylcarnitines or free carnitine. Conclusions: Reduced excretion of 24-h urinary sodium is associated with a disturbed plasma acylcarnitine profile in children with VVS. The findings suggest that restricted sodium intake-induced disturbance of plasma acylcarnitines and related cellular energy metabolism might be involved in the pathogenesis of VVS in children.

Sympathetic Overactivation From Supine to Upright Is Associated With Orthostatic Hypertension in Children and Adolescents.

There are no prior publications or submissions with any overlapping information, including studies and patients. The study data have not been presented as an abstract or poster before the submission. Objectives: The study was conducted to analyze the changes of baroreflex sensitivity and heart rate variability from supine to upright standing in children and adolescents with orthostatic hypertension to explore whether and how the autonomic nerve regulation was involved in the development of pediatric orthostatic hypertension. Methods: This case-control study included twenty-five children with orthostatic hypertension (the patient group) and twenty-six healthy controls (the control group). All subjects underwent a standing test, during which their hemodynamic parameters were continuously monitored by a Finapres Medical System, and baroreflex sensitivity and heart rate variability were calculated. Results: The demographic characteristics, supine baroreflex sensitivity, and supine heart rate variability including time domain and frequency domain indices did not differ between the patients with orthostatic hypertension and healthy subjects (P > 0.05). However, a more obvious drop of baroreflex sensitivity and a greater increase of low frequency/high frequency ratio from supine to upright were observed in subjects with orthostatic hypertension compared with those in the healthy children (P < 0.001 and P < 0.01, respectively). Changes of baroreflex sensitivity were negatively related to mean arterial pressure changes from supine to upright in all subjects (P < 0.01), and the increases in low frequency/high frequency ratio from supine to standing were positively correlated with those in mean arterial pressure in the study subjects (P < 0.001). Conclusion: Upright sympathetic overactivation is associated with pediatric orthostatic hypertension.

Body mass index is a promising predictor of response to oral rehydration saline in children with vasovagal syncope.

BACKGROUND: Vasovagal syncope (VVS) greatly impairs quality of life. The therapeutic efficacy of oral rehydration saline (ORS) for unselected VVS patients is not satisfactory due to the diverse mechanisms of the disease. Body mass index (BMI) was demonstrated to reflect blood volume to a certain extent. Therefore, the present study explored the capability of BMI to predict the therapeutic response of children with VVS to ORS treatment. METHODS: Seventy-four children with VVS who visited the Syncope Unit of Pediatrics at Peking University First Hospital from November 2010 to June 2019 receiving ORS treatment were enrolled for this retrospective case-control study. A comparison of demographic, clinical, and hemodynamic characteristics was performed between responders and non-responders. The correlation between baseline BMI and response time was analyzed. To determine the value of baseline BMI in predicting the therapeutic efficacy of ORS in children with VVS, a receiver operating characteristic curve analysis was performed. RESULTS: Fifty-two children were identified as responders, and the remaining 22 children were identified as non-responders. The baseline BMI of the responders was much lower than that of the non-responders (16.4 [15.5, 17.8] kg/m2vs. 20.7 ±e6 kg/m2, P < 0.001), and baseline BMI was positively correlated with response time in the head-up tilt test after adjusting for sex (r = 0.256, 95% confidence interval [CI]: 0.067-0.439, P = 0.029). The area under the receiver operating characteristic curve of baseline BMI was 0.818 (95% CI: 0.704-0.932, P < 0.001), and an optimal cut-off value of 18.9 kg/m2 yielded a sensitivity of 83% and a specificity of 73% to predict the efficacy of ORS in VVS. CONCLUSION: Prior to treatment, baseline BMI is a promising predictor of response to ORS in children with VVS.

Long-Term Outcomes of Children and Adolescents With Postural Tachycardia Syndrome After Conventional Treatment.

Objectives: To explore the long-term outcomes of children and adolescents with postural tachycardia syndrome receiving conventional interventions. Materials and Methods: A total of 121 patients were recruited, but 6 (5.0%) of them were lost at follow-up. The detailed clinical data were collected, and the reoccurrence and frequency of orthostatic intolerance symptoms were evaluated with a mean followed-up period of 18.7 months (range, 14-74 months). The Kaplan-Meier curve was used to show the cumulative symptom-free rate of patients over time. Factors influencing the long-term outcomes were examined using the Cox's proportional hazards models. Results: The cumulative symptom-free rate was gradually increased over time. It was 48.4% at the 1-year follow-up and increased to 85.6% at the 6-year follow-up. The duration of symptoms before treatment and the maximum upright heart rate in standing-up test were identified as independent indicators for the long-term outcomes. Each 1-month prolongation in the duration of symptoms before treatment was associated with a 1.2% decrease in the cumulative symptom-free rate. However, each 1-bpm increase in the maximum upright heart rate in standing-up test was associated with a 2.1% increase in the cumulative symptom-free rate. Conclusions: The long-term outcomes of postural tachycardia syndrome patients who received conventional interventions are benign and the cumulative symptom-free rate was gradually increased over time. The prolonged duration of symptoms before treatment and the reduced maximum upright heart rate in standing-up test are the independent risk indicators.

Differential Diagnostic Models Between Vasovagal Syncope and Psychogenic Pseudosyncope in Children.

Objective: We aimed to establish useful models for the clinical differential diagnosis between vasovagal syncope (VVS) and psychogenic pseudosyncope (PPS). Methods: This bicentric study included 176 patients (150 VVS and 26 PPS cases) for model development. Based on the results of univariate and multivariate analyses, a logistic regression model and a scoring model were established and their abilities to differentiate VVS from PPS were tested. Another 78 patients (53 VVS and 25 PPS) were used for external validation. Results: In the logistic regression model, the outcome indicated that the QT-dispersion (QTd) (P < 0.001), syncope duration (P < 0.001), and upright posture (P < 0.001) acted as independent factors for the differentiation of VVS from PPS, which generated an area under the curve (AUC) of 0.892. A cutoff value of 0.234 yielded a sensitivity and specificity of 89.3 and 80.8%, respectively, for the differentiation between VVS and PPS in the logistic regression model. In the scoring model which consists of three variables, a cutoff score of three points yielded a sensitivity and specificity of 91.3 and 76.9%, respectively, with an AUC of 0.909. The external validation test indicated that the negative and positive predictive values of the scoring model were 78.8 and 91.7%, respectively, and the accuracy was 80.8%. Conclusion: The scoring model consisting of three variables is an easy-to-perform, inexpensive, and non-invasive measure for initial differential diagnosis between VVS and PPS.