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Abstract Objective Given the scarcity of studies analyzing the clinical predictors of pediatric septic cases that would progress to septic shock, this study aimed to determine strong predictors for pediatric emergency department (PED) patients with sepsis at risk for septic shock and mortality. Methods We conducted chart reviews of patients with ≥ 2 age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) criteria to recognize patients with an infectious disease in two tertiary PEDs between January 1, 2021, and April 30, 2022. The age range of included patients was 1 month to 18 years. The primary outcome was development of septic shock within 48 h of PED attendance. The secondary outcome was sepsis-related 28-day mortality. Initial important variables in the PED and hemodynamics with the highest and lowest values during the first 24 h of admission were also analyzed. Results Overall, 417 patients were admitted because of sepsis and met the eligibility criteria for the study. Forty-nine cases progressed to septic shock within 48 h after admission and 368 were discharged without progression. General demographics, laboratory data, and hemodynamics were analyzed by multivariate analysis. Only the minimum diastolic blood pressure/systolic blood pressure ratio (D/S ratio) during the first 24 h after admission remained as an independent predictor of progression to septic shock and 28-day mortality. The best cutoff values of the D/S ratio for predicting septic shock and 28-day mortality were 0.52 and 0.47, respectively. Conclusions The D/S ratio is a practical bedside scoring system in the PED and had good discriminative ability in predicting the progression of septic shock and in-hospital mortality in PED patients. Further validation is essential in other settings.

Background: Kawasaki disease (KD) is an acute febrile vasculitis. Patients with previous KD have increased risk of coronary arterial aneurysms (CAA) and early-onset arteriosclerosis. Endothelial dysfunction is the earliest manifestation of arteriosclerosis. We aimed to explore the endothelial function and clinical characteristics of patients with previous KD. Methods: In this case–control study, we investigated childhood KD patients, with and without CAA, and a group of healthy controls. We obtained the anthropometric measurements, metabolic markers, vascular ultrasonography evaluating arterial stiffness and flow-mediated dilatation (FMD), and clinical information obtained by reviewing the patients' charts. Continuous variables were compared using non-parametric analyses and categorical variables, using the chi-square or Fisher's exact tests. Results: Seventy KD patients (median current age, 12.95 years; median follow-up duration, 10.88 years) and 14 healthy controls were recruited. FMD was significantly lower in the CAA group (n = 15) than the control group (FMDs: 5.59% [interquartile range, 3.99–6.86%] vs. 7.49% [5.96–9.42%], p = 0.049; diastolic FMD: 6.48% [4.14–7.32%] vs. 7.87% [6.19–9.98%], p = 0.042). The CAA group had a higher percentage of impaired FMD and the significantly largest coronary segments of the three groups. Other parameters including metabolic markers, carotid intima-media thickness, and arterial stiffness were not statistically different. Conclusion: KD patients, especially those with CAAs, may have impaired endothelial function. FMD may be a good indicator of endothelial dysfunction for use in long-term follow-up of KD patients.

Background: Most previous studies reported there were higher survival rates if low birth weight babies were born in tertiary perinatal centers (inborn) than elsewhere (outborn). The objective of this study is to examine whether the number and ratio of outborn babies decrease and the neonatal mortality differs between inborn and outborn babies. Methods: We used the pooled data of the Taiwan Clinical Effectiveness Index for the years 2011–2016 obtained from the Joint Commission of Taiwan to study the outborn/inborn number and neonatal mortality rate. Results: We found that the number of outborn babies did not decrease year by year. The ratio of outborn to total babies was lower in the groups of birth body weight 750–999 g and ≧ 2500 g than the other groups. The neonatal mortality rate in outborns was significantly higher than the inborns in the groups of birth body weight 1000–1499 g, 2000–2499 g and ≧ 2500 g (6.9 ± 2.4 vs. 3.8 ± 0.9, P = 0.009, 2.6 ± 0.6 vs. 0.6 ± 0.3, P = 0.002 and 1.52 ± 0.67 vs. 0.08 ± 0.02, P = 0.002, respectively) in medical centers. Conclusion: Improved maternal transport which promotes in utero transfer of patients may further improve neonatal outcome.

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease associated with rapid clinical deterioration and the need for intensive care; therefore, it is essential to identify clinical parameters related to mortality and establish prognostic factors correlated with unfavorable outcome in high risk patients whose treatment may fail. Methods: Between January 2004 and December 2018, a total of 51 pediatric patients (less than 18 years old) who fulfilled the diagnostic criteria of HLH-2004 with documented results of bone marrow investigations at Kaohsiung Chang Gung Memorial Hospital were enrolled. The treatment protocol was based on hemophagocytic lymphohistiocytosis-94 (HLH-94) and HLH-2004. We retrospectively reviewed electronic medical records (EMR) including clinical features, length of intensive care unit (ICU) stay, serological tests, microscopic reports of bone marrow examination, and ultrasound examination reports at diagnosis to identify prognostic factors. The patients were divided into four groups based on etiology; these included infection associated hemophagocytic syndrome (IAHS), macrophage activation syndrome (MAS), malignancy associated hemophagocytic lymphohistiocytosis (MA-HLH), and idiopathic hemophagocytic lymphohistiocytosis (IHLH) to identify differences among the groups. Results: Out of 51 patients enrolled, 27 patients had IAHS, 12 MAS, 8 MA-HLH, and 4 IHLH. The median age at diagnosis was 7 years. The overall mortality rate was 15.7% (there was no mortality in the MA-HLH group); the mean length of ICU stay was 6 ± 20.8 days. Longer activated partial thromboplastin time (aPTT) (p = 0.007), lower sodium concentration (p = 0.0007), and higher creatinine (p = 0.032) and aspartate aminotransferase (AST) (p = 0.017) were significantly related to mortality. Multivariate Cox regression analysis demonstrated that aPTT (p = 0.045, HR = 1.03, 95% CI = 1.0–1.1) was an independent risk factor for mortality. The receiver operating characteristic (ROC) curve showed that aPTT longer than 44.35 s was the cutoff value predicting mortality, with a sensitivity and specificity of 72% and 66.7%, respectively. Conclusion: MA-HLH had the lowest mortality rate, as most children died from the underlying malignant disease and not from HLH. Impaired liver and renal functions were related to mortality. Prolonged aPTT > 44.35 s is a strong predictive factor for mortality.

Background: Infective endocarditis (IE) is an important cause of morbidity and mortality in pediatric patients with heart disease. Little literature has explored differences in the presentation of endocarditis in children with and without heart disease. This study aimed to compare the clinical outcomes and determine the risk of in-hospital death in the study population. Methods: Data were retrospectively collected from 2001 to 2019 from the Chang Gung Research Database (CGRD), which is the largest collection of multi-institutional electronic medical records in Taiwan. Children aged 0–20 years with IE were enrolled. We extracted and analyzed the demographic and clinical features, complications, microbiological information, and outcomes of each patient. Results: Of the 208 patients with IE, 114 had heart disease and 94 did not. Compared to those without heart disease, more streptococcal infections (19.3% vs. 2.1%, p < 0.001) and cardiac complications (29.8% vs. 6.4%, p < 0.001) were observed in patients with heart disease. Although patients with heart disease underwent valve surgery more frequently (43.9% vs. 8.5%, p < 0.001) and had longer hospital stays (28.5 vs. 12.5, p = 0.021), their mortality was lower than that of those without heart disease (3.5% vs. 10.6%, p = 0.041). Thrombocytopenia was independent risk factor for in-hospital mortality in pediatric patients with IE (OR = 6.56, 95% CI: 1.43–40.37). Conclusion: Among pediatric patients diagnosed with IE, microbiological and clinical features differed between those with and without heart disease. Platelet counts can be used as a risk factor for in-hospital mortality in pediatric patients with IE.

Systemic lupus erythematosus (SLE) is an autoimmune disease that may cause vital organ damage. Although not rare for child-onset SLE to have cardiovascular or pulmonary involvement, myocarditis, and pulmonary hypertension are infrequent features and can be life-threatening. In this case report, we describe an 11-year-old girl with SLE who initially presented with fulminant myocarditis pulmonary hypertension, and massive pericardial effusion. Initial immunosuppressive therapy with methylprednisolone pulse therapy, and IVIG were administered, followed by cyclophosphamide, which was ultimately successful, with no residual pulmonary hypertension and no recurrence of myocarditis for over 3 years after the initial episode. Our case highlights the need for clinicians to be aware of systemic lupus erythematosus as a possible diagnostic entity in pediatric patients with severe myocarditis or pulmonary hypertension. Aggressive immunosuppressive therapy should be strongly considered in such cases, as it may lead to good short-term and long-term outcomes.

BackgroundTranscranial Doppler ultrasound is a sensitive, real time tool used for monitoring cerebral blood flow; it could provide additional information for cerebral perfusion in cerebral resuscitation during post cardiac arrest care. The aim of the current study was to evaluate the utility of a point-of-care transcranial Doppler ultrasound management algorithm on outcomes in pediatric asphyxial out-of-hospital cardiac arrest.MethodsThis retrospective cohort study was conducted in two tertiary pediatric intensive care units between January 2013 and June 2018. All children between 1 month and 18 years of age with asphyxial out-of-hospital cardiac arrest and a history of at least 3 min of chest compressions, who were treated with therapeutic hypothermia and survived for 12 h or more after the return of circulation were eligible for inclusion.ResultsTwenty-one patients met the eligibility criteria for the study. Sixteen (76.2%) of the 21 children were male, and the mean age was 2.8 ± 4.1 years. Seven (33.3%) of the children had underlying disorders. The overall 1-month survival rate was 52.4%. Twelve (57.1%) of the children received point-of-care transcranial Doppler ultrasound. The 1-month survival rate was significantly higher (p = 0.03) in the point-of-care transcranial Doppler ultrasound group (9/12, 75%) than in the non-point-of-care transcranial Doppler ultrasound group (2/9, 22.2%).ConclusionsPoint-of-care transcranial Doppler ultrasound group was associated with a significantly better 1-month survival rate compared with no point-of-care transcranial Doppler ultrasound group in pediatric asphyxial out-of-hospital cardiac arrest.

Background: To compare the clinical characteristics and outcomes of pediatric patients with refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) who received therapeutic hypothermia (TH) plus anticonvulsants or anticonvulsants alone. Methods: Two-medical referral centers, retrospective cohort study. Pediatric Intensive Care Unit (PICU) at Taoyuan Chang Gung Children's hospital and Kaohsiung Chang Gung Memorial Hospital. We reviewed the medical records of 23 patients with RSE/SRSE who were admitted to PICU from January 2014 to December 2017. Of these, 11 patients received TH (TH group) and 12 patients did not (control group). Results: The selective endpoints were RSE/SRSE duration, length of PICU stay, and Glasgow Outcome Scale (GOS) score. We applied TH using the Artic Sun® temperature management system (target temperature, 34–35 °C; duration, 48–72 h). Of the 11 patients who received TH, 7 had febrile infection-related epilepsy syndrome (FIRSE), one had Dravet syndrome, and three had traumatic brain injury. The TH group had significantly shortern seizure durations than did the control group (hrs; median (IQR) 24(40) vs. 96(90), p

Background: The objective of this research was to evaluate the fertility of Taiwanese women with diagnoses of congenital heart diseases (CHDs). The study also investigated how different forms of CHDs may have variously influenced fertility.Methods: We directed this nationwide, population-based and retrospective matched-cohort research by using data from the Taiwan National Health Insurance Research Database. The CHD group (n = 6602) included women with congenital structural heart diseases, aged 16–45 years in 2000. The non-CHD group (n = 6602) was matched according to urbanization and income. The outcomes, involving live birth, abortion, and fertility rates, were followed until the end of 2013. Poisson regression was used to evaluate the incidence rate ratios (IRRs).Results: The CHDs had an inferior rate of live births (IRR 0.74 [95% CI 0.71–0.78]) than the non-CHD group. There was also a lower fertility rate in the CHD group (IRR 0.81 [95% CI 0.78–0.84]) than the non-CHD group. Abortion rates between the two groups were similar.Conclusion: Congenital structural heart disease compromises female fertility, even among patients with simple forms of CHDs. It is suggested that pregnant patients with CHDs are early appeared to and advised personally with multidisciplinary care to improve their outcomes.

Aim: The aim of the current study was to identify early clinical predictors of neurologic outcome in children with asphyxial out-of-hospital cardiac arrest (OHCA) treated with therapeutic hypothermia.Methods: The present retrospective cohort study of comatose children treated with therapeutic hypothermia or normothermia after asphyxial OHCA was conducted between January 2010 and June 2018. All children aged between 1 month and 18 years of age, with a history of at least 3 min of chest compressions were eligible for inclusion. Their 6-month neurological outcomes were evaluated using the Pediatric Cerebral Performance Category (PCPC) score and early clinical predictors were determined.Results: A total of 100 patients met the eligibility criteria for the study. Sixty-four (64%) of the children were male, and the mean age of participants was 4.59 ± 5.45 years. Forty (40%) of the children had underlying disorders. The overall 1-month survival rate was 36%. Only 12 (12%) of the patients had favorable outcomes (PCPC ≤ 2). Thirty-four (34%) of the 100 children were receiving therapeutic hypothermia. In the univariate analysis, an initial lactate level of ≤ 80 mg/dL, a Glasgow coma scale (GCS) score of 5–8, a GCS motor score ≥4 and a present pupil reflex before therapeutic hypothermia, were significantly associated with favorable 6-month neurological outcomes. However, after the multivariate logistic analysis, only initial serum lactate level and GCS before therapeutic hypothermia were significantly associated with favorable 6-month neurological outcomes.Conclusion: Initial serum lactate level and GCS before therapeutic hypothermia were significantly associated with 6-month favorable neurological outcomes in pediatric asphyxial OHCA patients who were treated with therapeutic hypothermia. Therefore, these early clinical predictors could be helpful to facilitate future clinical research in children with asphyxial OHCA treated with therapeutic hypothermia.

To investigate whether a palm-held ultrasonocardiographic scanner would be useful for screening and follow-up in congenital heart disease (CHD). Methods: We retrospectively reviewed the echocardiographic images from June 1, 2014 to November 1, 2014. All patients underwent two ultrasonographic examinations including palm-held scanner examination and standard echocardiography. To compare the quality of the two instruments, we developed a diagnostic scoring system ranging from 1 point to 10 points, with 10 points indicating the best quality. Two experienced echocardiographers retrospectively reviewed all recorded images blindedly and gave each examination a score. Comparisons of diagnostic score between two equipments were performed. Results: A total of 262 patients’ images were reviewed. All cardiac lesions could be detected with both instruments. The mean diagnostic score of palm-held scanner and standard echocardiography were 8.20±0.53 versus 9.64±0.37 (p

Ketogenic diet therapies (KDTs) are widely used treatments for epilepsy, but the factors influencing their responsiveness remain unknown. This study aimed to explore the predictors or associated factors for KDTs effectiveness by evaluating the subtle changes in brain functional connectivity (FC) before and after KDTs. Segments of interictal sleep electroencephalography (EEG) were acquired before and after six months of KDTs. Analyses of FC were based on network-based statistics and graph theory, with a focus on different frequency bands. Seventeen responders and 14 non-responders were enrolled. After six months of KDTs, the responders exhibited a significant functional connectivity strength decrease compared with the non-responders; reductions in global efficiency, clustering coefficient, and nodal strength in the beta frequency band for a consecutive range of weighted proportional thresholds were observed in the responders. The alteration of betweenness centrality was significantly and positively correlated with seizure reduction rate in alpha, beta, and theta frequency bands in weighted adjacency matrices with densities of 90%. We conclude that KDTs tended to modify minor-to-moderate-intensity brain connections; the reduction of global connectivity and the increment of betweenness centrality after six months of KDTs were associated with better KD effectiveness.

Acute fulminant myocarditis (AFM) commonly presents as abrupt cardiogenic shock with or without dysrhythmia. This study evaluated the impact of extracorporeal membrane oxygenation (ECMO) on AFM-related hemodynamic compromise dysrhythmias. We also reported the clinical experience of AFM at our hospital. Methods: Eighteen children diagnosed with AFM were enrolled. Demographic variables, laboratory data, and clinical courses were reviewed. Thirteen surviving patients with hemodynamic compromise arrhythmia [complete atrioventricular block (CAVB) or ventricular tachycardia (VT)] during hospitalization were divided into Group A (ECMO group; n = 7) and Group B (non-ECMO group; n = 6). Results: The overall survival rate was 78% (14/18). There were no cases of mortality after ECMO was introduced at our hospital. Common symptoms at diagnosis included general malaise (94%), gastrointestinal symptoms (89%), chest pain (56%), shortness of breath (56%), and seizure/syncope (56%). In addition to abnormal cardiac enzyme levels, all patients displayed elevated alanine aminotransferase levels during early disease stages. Electrocardiography at diagnosis revealed dysrhythmia in 15 patients, namely, CAVB in 11 patients (61%) and VT in four patients (22%). During hospitalization, the dysrhythmia shifted from CAVB to VT in 10 patients and from sinus tachycardia to VT in one patient. New episodes of VT were common (overall occurrence rate, 83%). Although myocardial damage and dysfunction were more severe in Group A, the time to rhythm recovery in this group was shorter than that in Group B (median time, 1.7 days vs. 7.35 days, p = 0.045). All surviving patients had normal ventricular function at 6-month follow-up. Conclusion: Hemodynamic compromise arrhythmia is common in AFM patients and may cause rapid deterioration. Simply correcting sinus rhythm is not always sufficient because of myocardium instability. Timely use of ECMO can improve the survival rate and shorten the time to recapture sinus rhythm in AFM patients with CAVB or VT.

We aimed to evaluate the occurrence, treatment, and outcomes of neurological complications after bacterial meningitis in young infants. A case series study from a retrospective cohort from two tertiary-level medical centers in Taiwan between 2007 and 2016 was conducted. Eighty-five young infants aged < 90 days with bacterial meningitis were identified. 25 (29.4%) were born at preterm. Group B Streptococcus (GBS) and Escherichia coli caused 74.1% of identified cases. Despite the majority (90.6%) initially received microbiologically appropriate antibiotics, 65 (76.5%) had experienced at least one neurological complication identified at a median of 6 days (range: 1–173) after onset of bacterial meningitis. The most common neurological complication was seizure (58.8%), followed by subdural effusion (47.1%), ventriculomegaly (41.2%), subdural empyema (21.2%), hydrocephalus (18.8%), ventriculitis (15.3%), periventricular leukomalacia (11.8%), and encephalomalacia (10.6%). Nine patients (10.6%) died (including 4 had critical discharge on request) and 29/76 (38.2%) of the survivors had major neurological sequelae at discharge. Nighteen (22.4%) received surgical intervention due to these complications. After multivariate logistic regression, initial seizure (adjusted odds ratio [aOR]: 4.76, 95% confidence interval [CI]: 1.7–13.0, P = 0.002) and septic shock (aOR: 6.04; 95% CI: 1.35–27.0, P = 0.019) were independent predictors for final unfavorable outcomes.Conclusions: Neurological complications and sequelae are common in young infants after bacterial meningitis. Patients presented with early seizure or septic shock can be an early predictor of final unfavorable outcomes and require close monitoring. Further research regarding how to improve clinical management and outcomes is warranted.

Background: This study aimed to identify metabolic parameters at different time points of ketogenic diet therapy (KDT) and investigate their association with response to KDT in pediatric drug-resistant epilepsy (DRE). Methods: Prospectively, twenty-nine patients (0.67~20 years old) with DRE received classic ketogenic diet with non-fasting, gradual KD initiation protocol (GRAD-KD) for 1 year were enrolled. A total of 22 patients remaining in study received blood examinations at baseline, 3rd, 6th, 9th, and 12th months of KDT. β-hydroxybutyrate, free carnitine, acylcarnitines, and amino acids were compared between responders (seizure reduction rate ≥ 50%) and non-responders (seizure reduction rate < 50%) to identify the effectiveness of KDT. Results: The 12-month retention rate was 76%. The responders after 12 months of KDT were 59% (13/22). The free carnitine level decreased significantly at 9th months (p < 0.001) but increased toward baseline without symptoms. Propionyl carnitine (C3), Isovaleryl carnitine (C5), 3-Hydroxyisovalerylcarnitine (C5:OH) and methylmalonyl carnitine (C4-DC) decreased but 3-hydroxybutyrylcarnitine (C4:OH) increased significantly at 12th months of KDT. The glycine level was persistently higher than baseline after KDT. KDT responders had lower baseline C3 and long-chain acylcarnitines, C14 and C18, as well as lower C5, C18, and leucine/isoleucine. Conclusions: KDT should be avoided in patients with non-ketotic hyperglycemia. Routine carnitine supplementation is not recommended because hypocarnitinemia was transient and asymptomatic during KDT. Better mitochondrial βoxidation function associates with greater KDT response.

To investigate mid- to long-term outcomes in children with coronary artery fistula (CAF). Methods: We retrospectively reviewed the medical records of patients seen between September 1996 and August 2011. We enrolled those diagnosed with CAF via echocardiography (Philips SONOS 7500 system and Philips IE33) or angiography. The mean follow time was 42.58 ± 3.4 months (range, 1–166 months). For comparative purposes, participants were grouped as acquired versus congenital, and symptomatic versus asymptomatic. We also measured the size of the coronary artery (CA) in patients with CA dilatation (CAD). Results: Out of 122 CAF patients, spontaneous closure was detected in 37 patients at 21.59 ± 3.45 months after diagnosis. This timeframe did not differ between the acquired and congenital groups (21.64 ± 6.26 months vs. 21.57 ± 4.15 months; p = 0.991). Ninety patients were asymptomatic and remained so; their spontaneous closure rate was 28.89%. Moreover, 24 patients had CAD, including 17 with Kawasaki disease and seven with congenital CAF. The CAs of all congenital-CAF-plus-CAD patients were initially > 5 mm; these patients underwent percutaneous transcatheter intervention, and their CA sizes decreased significantly (6.11 ± 0.79 mm vs. 3.76 ± 0.36 mm; p = 0.002). Conclusion: With the advanced sensitivity of echocardiography, CAF can be detected more easily than ever before. Most patients with small CAFs are asymptomatic and may experience spontaneous closure. Therefore, management of CAF depends on symptoms; if patients are asymptomatic and have small CAFs, intervention may not be necessary, especially in acquired cases. However, if patients present with symptoms or persistent dilatation of the proximal CA, surgical or percutaneous closure should be performed.

The aim of this study was to determine the frequency, timing, and predictors of rewarming seizures in a cohort of children undergoing therapeutic hypothermia after resuscitation. We retrospectively reviewed consecutive pediatric patients undergoing therapeutic hypothermia after resuscitation admitted to our pediatric intensive care unit between January 2000 and December 2019. Continuous electroencephalographic monitoring was performed during hypothermia (24 h for cardiac aetiologies and 72 h for asphyxial aetiologies), rewarming (72 h), and then an additional 12 h of normothermia. Thirty comatose children undergoing therapeutic hypothermia after resuscitation were enrolled, of whom 10 (33.3%) had rewarming seizures. Two (20%) of these patients had their first seizure during the rewarming phase. Four (40%) patients had electroclinical seizures, and six (60%) had nonconvulsive seizures. The median time from starting rewarming to the onset of rewarming seizures was 37.3 h (range 6 to 65 h). The patients with interictal epileptiform activity and electrographic seizures during the hypothermia phase were more likely to have rewarming seizures compared to those without interictal epileptiform activity or electrographic seizures (p = 0.019 and 0.019, respectively). Therefore, in high-risk patients, continuous electroencephalographic monitoring for a longer duration may help to detect rewarming seizures and guide clinical management.

Objective: To evaluate and compare the clinical outcomes and development of children born between obstructive azoospermia (OA) couples and nonobstructive azoospermia couples (NOA) after testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). Materials and methods: Data were collected from infertile couples suffering from azoospermia who underwent TESE and ICSI from January 2001 to December 2009 at Chang Gung Memorial Hospital, Taiwan. A total of 154 ICSI cycles were performed using extracted testicular sperm from men with obstructive azoospermia (67 ICSI cycles) and men with nonobstructive azoospermia (87 ICSI cycles). Retrospective analysis of clinical outcomes and development of children born after TESE-ICSE between obstructive azoospermia couples and nonobstructive azoospermia couples. Results: The assisted reproductive technology (ART) result between OA and NOA groups, including age, E2 level on hCG day, number of oocytes retrieved, normal fertilization rate, zygote Grade 1 score distribution, number of top-quality embryos transferred, clinical pregnancy rate per transfer, chemical pregnancy rate per transfer, implantation rate, live birth rate per transfer, and abortion rate per transfer, were all similar. Thirty-one live births resulted from 67 ICSE cycles in the OA group and 33 live births from 87 ICSE cycles in the NOA group. The obstetric and perinatal outcomes were similar between the groups, and children conceived by using ICSI were generally healthy without raised tendency of major birth defect and development impairment. Conclusion: In our study, there were no differences in the fertility rate and clinic pregnancy rate between the OA and NOA groups using TESE-ICSI. Also, the clinical outcomes and development of children were similar between the OA and the NOA groups using TESE-ICSI.

Background: Conventional therapy against acute pediatric cardiopulmonary failure (APCPF) caused by a variety of disease entities remains unsatisfactory with extremely high morbidity and mortality. For refractory APCPF, extracorporeal membrane oxygenation (ECMO) is one of the last resorts. Methods: In this study, the in-hospital outcomes of pediatric patients with refractory APCPF receiving ECMO support were reviewed. Results: Between August 2006 and May 2011, a single-center cohort study was performed in pediatric patients who required ECMO support due to cardiogenic shock or severe hypoxemia. A total of 22 patients with mean age of 7.0 ± 6.3 years received ECMO (male = 11; female = 11). The indications included acute fulminant myocarditis (AFM) (n = 6), congenital diaphragmatic hernia (CDH) (n = 3), acute respiratory distress syndrome (ARDS) (n = 6), enterovirus 71 (n = 3), viral sepsis (n = 2), refractory ventricular fibrillation due to long QT syndrome (n = 1), and pulmonary edema with brain herniation (n = 1). Eighteen patients received veno-arterial (VA) mode ECMO, while another four patients undertook the veno-venous (VV) mode. The duration of ECMO use and hospitalization were 6.1 ± 3.1 and 24.4 ± 19.4 days, respectively. The survival rate in patients with AFM was 100% (n = 6). Successful ECMO weaning with uneventful discharge from hospital was noted in 14 (63.6%) patients, whereas in-hospital mortality despite successful ECMO weaning occurred in 5 patients (22.7%). Failure in ECMO weaning and in-hospital death was noted in 3 patients (13.6%). Conclusions: ECMO resuscitation is an effective strategy in the clinical setting of APCPF.

Pediatric patients with atrial septal defect (ASD) may have failure to thrive. This study aimed to investigate body weight changes in pediatric patients after transcatheter closure of ASD. Methods: From June 2003 to September 2008, we enrolled 60 pediatric patients who underwent transcatheter closure of ASD. Changes in body weight percentile, heart rate, and resolution of right ventricular hypertrophy were compared before and after ASD closure. Patients were divided into two groups according to initial weight percentile: group A,

Cartilage-hair hypoplasia (MIM 250250) is an autosomal recessive disease with diverse clinical manifestations. The clinical phenotypes include variable degrees of bone and hair dysplasia, deficient cellular and/or humoral immunity, and a predisposition to malignancy. Methods: We performed genetic studies of a patient with disproportionate short stature and brittle scalp hair. Genetic studies were also carried out in the patient's parents. Results: A novel maternal mutation that consisted of a duplication of 14 nucleotides at position −13 of the RNA component of the RNA component of mitochondrial RNA processing endoribonuclease gene (RMRP; g. −26 to −13 dupTACTACTCTGTGAA, promoter region) and a paternal mutation base substitution of C to T at nucleotide + 230 (designated as + 1 in the transcription initiation site) in the coding sequence of RMRP were detected in this patient. Conclusion: A novel maternal RMRP mutation was found in a Chinese boy with typical cartilage-hair hypoplasia.

Pandemic (H1N1) 2009 virus causes severe illness, including pneumonia, which leads to hospitalization and even death. To characterize the kinetic changes in viral load and identify factors of influence, we analyzed variables that could potentially influence the viral shedding time in a hospital-based cohort of 1,052 patients. Viral load was inversely correlated with number of days after the onset of fever and was maintained at a high level over the first 3 days. Patients with pneumonia had higher viral loads than those with bronchitis or upper respiratory tract infection. Median viral shedding time after the onset of symptoms was 9 days. Patients 13 years of age (11 days vs. 7 days). These results suggest that younger children may require a longer isolation period and that patients with pneumonia may require treatment that is more aggressive than standard therapy for pandemic (H1N1) 2009 virus.

To evaluate the feasibility of echocardiography after transcatheter closure of patent ductus arteriosus (PDA) with coils. Methods: Between April 1998 and December 2006, 131 patients had transcatheter coil occlusion of their PDA using Gianturco coils. We hypothesized that post-procedural hemolysis would not occur if a residual shunt < 1 mm or if no continuous waveform was detected by echocardiography. Immediately after coil implantation, patients without and with a residual shunt as detected by echocardiography were designated to groups A and B, respectively. The clinical presentations, laboratory data and outcomes were compared between the two groups. Results: There were 101 patients in group A and 30 patients in group B. Patients in group B had larger ductal diameter (2.8 ± 0.9 mm vs. 1.6 ± 0.8 mm; p < 0.001), larger Qp/Qs (1.9 ± 0.9 vs. 1.3 ± 0.4; p = 0.001), higher frequency of more than one coil used (14/30 vs. 11/101; p < 0.001), and female predominance (22/30 vs. 53/101; p = 0.043) compared with group A. Trivial residual shunt was noted in 6 patients in group A and 20 patients in group B on the day after embolization. All shunts spontaneously closed within 6 months in patients of group A, while five patients in group B had a persistent shunt at the 1-year follow-up and thereafter. Although the patients in group B had higher residual shunt rate than group A during follow-up (p < 0.001), none of these patients suffered from hemolysis. Conclusion: Echocardiography is a feasible tool to assess residual shunt after PDA closure. If a residual shunt < 1 mm or if no continuous waveform is detected by echocardiography, the risk of developing hemolysis is low.

Balloon angioplasty (BA) is an alternative to surgical repair for coarctation of the aorta (CoA) in children. However, its role in the treatment of native CoA in neonates and infants remains controversial. The purpose of this study was to report the midterm outcomes of BA for native CoA in neonates and infants with congestive heart failure (CHF). Methods: Between July 2000 and March 2007, 18 neonates and infants with native CoA and CHF who underwent BA were enrolled. Patients without recoarctation were designated as group A, while those with recoarctation or CHF were designated as group B. The clinical presentations, laboratory data, and outcomes were compared between groups. Results: There were 10 patients in group A and eight in group B. The mean age was 2.8 ± 3.1 months (range, 0.7–11 months). Mean body weight was 4.0 ± 1.9 kg (range, 2.1–8.0 kg). CHF improved markedly in all patients immediately after BA, with a reduction in systolic pressure gradient from 36.4 ± 12.0 to 5.6 ± 6.0 mmHg (p < 0.001). The recoarctation rate was 44% (8/18). The risk factors for restenosis were post-BA systolic pressure gradient > 10 mmHg (p = 0.007) and CoA diameter < 3 mm (p = 0.013). Conclusions: The outcomes of BA for native CoA in neonates and infants with CHF remain poor. The incidence of recoarctation is high in neonates and patients whose post-BA systolic pressure gradient is > 10 mmHg or whose CoA diameter is < 3 mm.

Myocarditis complicated with complete atrioventricular block (CAVB) is rare in children. The purpose of this study was to report the outcome of myocarditis with CAVB in our institution. Methods: Between June 1998 and June 2007, nine pediatric patients (aged from 1.5 to 16 years) were admitted, presenting with acute myocarditis with CAVB. We analyzed their clinical presentations, biochemistry and serology studies, chest X-rays, electrocardiograms, echocardiography, complications and outcomes. Results: Hypotension and Stokes-Adams seizures occurred in five and four of our patients, respectively. Cardiomegaly of chest X-ray was common in eight (89%) of our patients. Echocardiography revealed impaired left ventricular performance in three patients. Six patients suffered ventricular tachycardia (VT). Three cases of VT occurred before pacemaker implantation and the others occurred afterwards. Eight patients survived. Six of them regained sinus rhythm within 12 days (range 1−12 days), and two had a right bundle branch block at follow-up. Two patients had persistent CAVB, and one received permanent pacemaker implantation; the other received supportive care. One patient died due to persistent low cardiac output and a new onset of VT on the 4th admission day. During a follow-up period of 56 ± 27 months, all eight surviving patients remained asymptomatic. Conclusion: The outcome of CAVB complicated with myocarditis is variable. Most of our patients resumed normal heart function. The incidence of persistent CAVB was 22%. VT is a common and serious complication, but it can be effectively treated medically. Persistent low cardiac output after pacemaker implantation and late onset VT should be considered as risk factors of mortality.

To evaluate the outcome of transcatheter closure of atrial septal defects (ASD) with superior-anterior (SA) rim deficiency using Amplatzer septal occluder (ASO). Methods: Between June 2003 and March 2007, 84 patients with secundum type ASD attempted transcatheter insertion of ASO in our institution. According to the transesophageal echocardiographic findings, patients were divided into two groups: group A, with deficient SA rim (< 3 mm); group B, with sufficient SA rim (≥ 3 mm). There were 43 children and 41 adults (age range, 2.0–79.4 years; mean age, 22.0 ± 20.2 years). The failure rate, complications and the presence of residual shunt were compared between the two groups. Results: There were 34 patients in group A and 50 patients in group B. Failure of ASO implantation occurred in six patients, three in each group. One patient had two ASOs implanted for two separate ASDs. Therefore, the study cohort consisted of 78 patients with 79 ASO placed. Among 78 patients with successful implantation, five (6.4%) had persistent small residual shunt during follow-up (range, 1–46 months; mean, 21.6 ± 12.0 months). There was no statistically significant difference between group A and group B in the procedure's failure rate (p = 0.682), complications (p = 1.0) and the presence of residual shunt (p = 0.381) during the follow-up period. Conclusion: ASD with deficient SA rim is a common variation. Similar to ASD with sufficient rims, transcatheter closure of secundum type ASD is also effective for ASD with SA rim deficiency.

Kawasaki disease (KD) is an acute febrile vasculitic syndrome of early childhood often complicated by coronary artery lesion that drastically reduces the quality of life. The study aimed to identify a reliable marker for predicting nonresponsiveness to the first course of intravenous immunoglobulin (IVIG) in KD patients. A total of 63 patients with KD were enrolled in the study (IVIG response, 58; IVIG resistance, 5). Plasma samples were collected before and after IVIG infusion for measurement of biomarkers. Patients’ clinical characteristics and laboratory data were also analyzed. A receiver operating characteristic curve was generated to identify a cut-off value for predicting IVIG resistance. Among the biomarkers, the difference in plasma clusterin concentrations before and after IVIG infusion (CLUSTER 12) was significantly related to IVIG resistance (P=0.040; 95% confidence interval (CI): −25.8% to −6.0%). Using a CLUSTER 12 cut-off value of 8.52 mg/L had a much higher risk of IVIG resistance than those with CLUSTER 12 concentrations

BackgroundKawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis.MethodsRecruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14.ResultsBoth human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment.ConclusionThis result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2-mediated immune activation on CD14+ monocytes.

Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. High-dose intravenous immunoglobulin (IVIG) is the most effective therapy for KD to reduce the prevalence of coronary artery lesion (CAL) formation. Recently, the α2, 6 sialylated IgG was reported to interact with a lectin receptor, specific intracellular adhesion molecule-3 grabbing nonintegrin homolog-related 1 (SIGN-R1) in mice and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) in human, and to trigger an anti-inflammatory cascade. This study was conducted to investigate whether the polymorphism of DC-SIGN (CD209) promoter −336 A/G (rs4804803) is responsible for susceptibility and CAL formation in KD patients using Custom TaqMan SNP Genotyping Assays. A total of 521 subjects (278 KD patients and 243 controls) were investigated to identify an SNP of rs4804803, and they were studied and showed a significant association between the genotypes and allele frequency of rs4804803 in control subjects and KD patients (P=0.004 under the dominant model). However, the promoter variant of DC-SIGN gene was not associated with the occurrence of IVIG resistance, CAL formation in KD. The G allele of DC-SIGN promoter −336 (rs4804803) is a risk allele in the development of KD.