Risk Factors of Long-Term Sequelae After Transcatheter Closure of Perimembranous Ventricular Septal Defect in Young Children.

BACKGROUND: Complications arising from transcatheter closure of perimembranous ventricular septal defects (pmVSD) in children, such as residual shunts and aortic regurgitation (AR), have been observed. However, the associated risk factors remain unclear. This study identified risk factors linked with residual shunts and AR following transcatheter closure of pmVSD in children aged 2-12 years.Methods and Results: The medical records of 63 children with pmVSD and a pulmonary-to-systemic blood flow ratio <2.0 who underwent transcatheter closure between 2011 and 2018 were analyzed with a minimum 3-year follow-up. The success rate of transcatheter closure was 98.4%, with no emergency surgery, permanent high-degree atrioventricular block, or mortality. Defects ≥4.5 mm had significantly higher odds of persistent residual shunt (odds ratio [OR] 6.85; P=0.03). The use of an oversize device (≥1.5 mm) showed a trend towards reducing residual shunts (OR 0.23; P=0.06). Age <4 years (OR 27.38; 95% confidence interval [CI] 2.33-321.68) and perimembranous outlet-type VSD (OR 11.94, 95% CI 1.10-129.81) were independent risk factors for AR progression after closure. CONCLUSIONS: Careful attention is crucial for pmVSDs ≥4.5 mm to prevent persistent residual shunts in transcatheter closure. Assessing AR risk, particularly in children aged <4 years, is essential while considering the benefits of pmVSD closure.

Perioperative outcomes of Fontan operation: Impact of heterotaxy syndrome.

BACKGROUND/PURPOSE: Fontan operation is the standard surgical procedure for achieving long-term survival in single-ventricular complex congenital heart diseases (SV-CHD). We aim to identify the perioperative outcomes and impact of heterotaxy syndrome (HS) after Fontan operation in a tertiary pediatric cardiology center. METHODS: Medical records were reviewed for all patients who received Fontan operation and who were born between 1997 and 2017 in our institution. Preoperative, operative, and postoperative risk factors for perioperative mortality and morbidity were analyzed. RESULTS: Totally, 154 patients were enrolled (103 SV-CHD and 51 HS), and the male to female ratio was 92:62. The mean age of Fontan operation was 5.1 years, and extracardiac conduit comprised the majority (90.9%) of Fontan operation. Overall perioperative event-free survival to discharge was 91.6% (84.3% in HS and 95.1% in other SV-CHD, P = 0.032). For secondary outcomes, length of intensive care stay and duration of pleural effusion drainage were not significantly different between patients with HS and other SV-CHD, but postoperative arrhythmia was more common in HS group (31.4% vs. 12.6%, P = 0.005). In multivariable regression analysis, preoperative risk factors including operation year before 2007 and high PAP and postoperative factors of elevated postoperative CVP were associated with worse outcomes. HS was not a predictor of worse outcome after adjusting for preoperative PAP and operation era. CONCLUSION: Surgical outcome has improved much in current era. Perioperative outcome is poorer in patients with HS than other SV-CHD, but HS is not a predictor of perioperative mortality after adjusting for hemodynamic factors.

Safety and efficacy of transcatheter closure of outlet-type ventricular septal defects in children and adults with Amplatzer Duct Occluder II.

BACKGROUND/PURPOSE: Outlet-type VSD is frequently associated with aortic valve prolapse that surgery is frequently required. The literature regarding outcomes of transcatheter closure of outlet-type VSDs is scant. This study was conducted to know the safety and efficacy of transcatheter closure of outlet-type ventricular septal defects (VSDs) with Amplatzer Duct Occluder II (ADO II). METHODS: Medical records of patients underwent attempted transcatheter closure of outlet-type VSD with ADO II between October 2013 and August 2019 were retrospectively reviewed. RESULTS: Among 49 patients, transcatheter closure was successful in 45 (91.8%; 33 males and 12 females; mean [± standard deviation] age and body weight: 15.8 (±17.7) years and 36.6 (±23.3) kg, respectively). The median VSD diameter was 4.0 mm (range: 1.2-6.0 mm). Device closure failed in four because the sheath could not be advanced through a prograde or retrograde route in one patient, occluder embolization in the two patients, and failed right ventricular disc anchoring in one patient. After a mean follow-up of 22.7 months (range: 0.3-51.1 months), only nine (20.0%) patients had increased severity in aortic regurgitation (AR) on the echocardiography. Preprocedural AR decreased in severity or even disappeared in 11 (24.4%) patients. No heart block or device failure occurred during follow-up. A trivial-to-small residual shunt was detected in 19 patients (42.2%) in the most recent echocardiography. CONCLUSION: Transcatheter closure of outlet-type VSDs with ADO II is feasible. Although no significant aggravation of AR was observed in the short-to-mid-term follow-up, long-term follow-up is mandatory.

Clinical behavior and management of three types of renal angiomyolipomas.

OBJECTIVES: To analyze and present the demography, clinical behavior, especially the risk factors of tumor hemorrhage and management of sporadic angiomyolipoma (SAML), tuberous sclerosis complex associated angiomyolipoma (TSCAML) and epithelioid angiomyolipoma (EAML) in our institution. METHODS: A retrospective study of 587 patients who were diagnosed with renal angiomyolipoma in our institution between January 2000 and May 2015 was done. The AMLs were diagnosed by ultrasonography, CT, or MRI. EAML was confirmed by histopathology. Medical records and follow-up results were analyzed using the SPSS version 22 software. RESULTS: Out of 587 cases of renal AMLs, 87.4% were SAMLs, 8.7% were TSCAMLs and 3.9% were EAMLs. Most of the AML patients were asymptomatic. The most common presenting symptoms included flank pain and abdominal pain. The median tumor size of SAML, TSCAML, EAML were 4.7, 2.7, 10.5 cm respectively. Approximately half of SAMLs were conservatively treated, almost all TSCAMLs were treated conservatively, while all EAMLs were surgically treated. The median tumor size of hemorrhagic SAML cases was 8 cm versus non-hemorrhagic cases of 4.1 cm. The optimal cut-off point on the ROC curve for predicting SAML tumor hemorrhage was 7.35 cm. CONCLUSION: A larger tumor size, younger patient's age and higher BMI value correlated with a higher risk of tumor hemorrhage. For tumor sizes less than 7.35 cm, we recommend active surveillance or TAE for hemorrhage prevention. We also suggest that surgical management should be considered for patients with tumors larger than 7.35 cm, symptomatic and progressive AML, or suspicious EAML.

Gastric IgG4-related disease mimicking a gastrointestinal stromal tumor in a child: A case report.

BACKGROUND: Gastric IgG4-related disease (IgG4-RD) is rarely encountered in clinical practice, and especially more so among pediatric patients. To our knowledge, this is the first report of IgG4-RD presenting as a calcifying gastric mass in a child. We describe how this entity was difficult to differentiate from a gastrointestinal stromal tumor (GIST) imaging-based approaches. Therefore, this case highlights the importance of considering IgG4-RD in the differential diagnosis of gastric tumor before performing surgical resection, especially to distinguish it from malignancy to avoid unnecessary surgery. CASE SUMMARY: The patient suffered from epigastric pain for several days. Panendoscopy and computed tomography scan revealed a submucosal tumor. Differential diagnoses included GIST, leiomyoma, teratoma, and mucinous adenocarcinoma. However, laparoscopic proximal gastrectomy allowed for the definitive diagnosis of IgG4-related stomach disease. CONCLUSION: We emphasize the importance of considering IgG4-RD in the differential diagnosis of gastric submucosal tumors before performing surgical resection.

Self-Nanoemulsifying Drug Delivery System-Containing the Poorly Absorbed Drug - Valsartan in Post-Bariatric Surgery.

Purpose: Morbid obesity and its related metabolic syndrome are an important health issue. Recently, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) have accounted for the most popular bariatric surgeries. Valsartan (VST) is a common hypertension drug, and nano-carriers can increase its solubility and bioavailability. This study aims to explore the nano-VST formula in bariatric surgery subjects. Methods: High-fat fed animals were used as obese models. Operations were performed according to a standardized protocol. The drug was administrated by gavage, and blood samples were taken by serial tail vein sampling. Caco-2 cells were used for examining cell viability and drug uptake. A self-nano-emusifying drug delivery system (SNEDDS) formula was composed of sefsol-218, RH-40 and propylene glycol by a specified ratio, while high-performance liquid chromatography (HPLC) was used for determining drug concentrations. Results: Post-operatively, subjects that underwent RYGB lost more body weight compared to the SG group. The SNEDDS did not exhibit cytotoxicity after adequate dilution, and the cytotoxicity was not related to VST dose. A better cellular uptake of SNEDDS was observed in vitro. The SNEDDS formula achieved a diameter of 84 nm in distilled water and 140 nm in simulated gastric fluid. In obese animals, the maximum serum concentration (Cmax) of VST was increased 1.68-folds by SNEDDS. In RYGB with SUS, the Cmax was reduced to less than 50% of the obese group. SNEDDS increased the Cmax to 3.5 folds higher than SUS and resulted in 3.28-folds higher AUC0-24 in the RYGB group. Fluorescence imaging also confirmed a stronger signal of SNEDDS in the gastrointestinal mucosa. SNEDDS accumulated a higher drug concentration than suspension alone in the liver of the obese group. Conclusion: SNEDDS could reverse the VST malabsorption in RYGB. Further studies are mandatory to clarify post-SG change of drug absorption.

Preoperative N-terminal pro-brain natriuretic peptide is associated with Fontan outcomes.

OBJECTIVE: The role of preoperative N-terminal pro-brain natriuretic peptide level in patient outcomes after the Fontan operation remains unclear. METHODS: The medical records of all patients who underwent their first Fontan operation from June 2011 to October 2019 in our tertiary referral pediatric cardiac center were retrospectively reviewed. Preoperative hemodynamic factors and N-terminal pro-brain natriuretic peptide were analyzed to test the association of mortality and morbidity. RESULTS: We enrolled 110 patients (men/women 62/48; median age, 4.1 [3.4, 5.8] years; median follow-up period, 4.28 [2.31, 6.71] years). Almost all operations were extracardiac conduits (98.2%). Primary outcomes of death, Fontan takedown, and heart transplantation were observed in 9 patients (8.2%). Abnormal ventricular contractility, elevated preoperative pulmonary artery pressure, high pulmonary vascular resistance index, and high log10 N-terminal pro-brain natriuretic peptide level were associated with poor outcomes. SECONDARY OUTCOMES: atrioventricular valve regurgitation moderate or greater, elevated pulmonary artery pressure, high pulmonary vascular resistance index, and high log10 N-terminal pro-brain natriuretic peptide level were associated with rehospitalization due to heart failure. Multivariable Cox regression analysis revealed that log10 N-terminal pro-brain natriuretic peptide was the only significant predictor of all primary and secondary outcomes. A scoring system including factors of pulmonary artery pressure, pulmonary vascular resistance index, and N-terminal pro-brain natriuretic peptide was established, and the risk stratification is associated with outcomes after the Fontan operation. CONCLUSIONS: High preoperative N-terminal pro-brain natriuretic peptide was associated with poor outcomes after the Fontan operation.

Twin atrioventricular nodes, arrhythmias, and survival in pediatric and adult patients with heterotaxy syndrome.

BACKGROUND: Heterotaxy syndrome is likely to involve arrhythmias from associated conduction system abnormalities, which are distinct in different subtypes of isomerism and may change further after interventions and remodeling. OBJECTIVE: The purpose of this study was to understand the risk of arrhythmias and its relation to isomerism subtypes. METHODS: Patients diagnosed between 1980 and 2019 as having heterotaxy syndrome were enrolled and grouped as right atrial isomerism (RAI), left atrial isomerism (LAI), or indeterminate isomerism. RESULTS: Of the 366 patients enrolled, 326 (89.1%) had RAI, 35 (9.6%) LAI, and 5 (1.4%) indeterminate isomerism; 71 (19.4%) patients were adults. Arrhythmias occurred in 37.2% of patients (109 supraventricular tachycardia [SVT], 8 atrial fibrillation/flutter, 12 ventricular tachycardia, and 14 paced bradycardia). Freedom from arrhythmias by the age of 1, 5, 10, 20, and 40 years was 0.849, 0.680, 0.550, 0.413, and 0.053, respectively. Twin atrioventricular nodes were identified in 51.5% of patients with RAI, 8.7% of patients with LAI, and 40.0% of patients with indeterminate isomerism and were the key predictors of SVT. Indeterminate isomerism was also a risk factor for SVT. Other forms of tachycardia appeared relatively late. Sinus bradycardia with junctional rhythm was common in LAI (48.7%) and less in indeterminate isomerism (20.0%), with none occurring in RAI. Only in patients with RAI who showed the poorest survival, ventricular tachycardia worsened the long-term survival. CONCLUSION: RAI was the predominant subtype of heterotaxy in this cohort. Collectively, the median RAI/LAI ratio was 0.731 and 5.450 in Western and East Asian studies, respectively. Arrhythmias, tachycardia, or paced bradycardia were common, but the spectrum was distinct among subtypes.

Device deformation and left pulmonary artery obstruction after transcatheter patent ductus arteriosus closure in preterm infants.

BACKGROUND: Transcatheter closure of patent ductus arteriosus (PDA) is an effective alternative to surgical ligation in preterm infants. However, data on device deformation and risk of left pulmonary artery (LPA) obstruction remain scant. This study describes the outcomes and complications of transcatheter closure of PDA in preterm infants weighing <2500 g. METHODS: Amplatzer Piccolo Occluder and Amplatzer Vascular Plug were used. Echocardiography was repeated at prespecified intervals. The device waist and length were assessed through lateral fluoroscopy immediately and at least 3 months after deployment. RESULTS: Fourteen infants were prospectively enrolled (mean procedural weight 1335 g, procedural age 24 days), and all procedures were successful. There was no obstruction of adjacent vessels immediately after deployment. At follow-up, three infants developed aortic coarctation, all of which resolved gradually. Obstruction of the LPA occurred in eight infants, with five being severe cases. Compared with the shape immediately after deployment, the devices became significantly more flattened and lengthened at follow-up in patients with LPA obstruction. This deformation was nonsignificant in infants without any LPA obstruction. The ratio of the device waist after deployment to the nominal waist (<0.75) was highly predictive of LPA obstruction and late device deformation. The cannulated femoral vein was patent compared with the contralateral side. CONCLUSIONS: Device deformation occurring late at follow-up is common and may be associated with LPA obstruction in preterm infants after transcatheter PDA closure. Meticulous device selection and implantation technique are crucial for minimizing the associated risks.

Airway Delivery of Bone Marrow-Derived Mesenchymal Stem Cells Reverses Bronchopulmonary Dysplasia Superimposed with Acute Respiratory Distress Syndrome in an Infant.

Bronchopulmonary dysplasia (BPD), a disease affecting extremely premature infants, results from the disruption of normal pulmonary vascular and alveolar growth. Currently, there is no specific effective treatment. We report a case of a 10-mo-old female infant with BPD, who was admitted because of adenovirus pneumonia and acute respiratory distress syndrome (ARDS) with prolonged venovenous and arteriovenous extracorporeal membrane oxygenation (ECMO) support (total 125 d). The respiratory condition dramatically improved, and ECMO was removed 25 d after intratracheal delivery of maternal bone marrow-derived mesenchymal stem cells (BM-MSCs). Short tandem repeat examinations revealed that there was no maternal cells in the bronchial wash fluid. To our knowledge, this is the first human report of BM-MSC therapy reversal of the course of BPD superimposed with ARDS. We also suggest that BM-MSC therapy may not only be effective in the newborn stage but also works in infants and children with BPD.

Tai-Chi-Chuan Exercise Improves Pulmonary Function and Decreases Exhaled Nitric Oxide Level in Both Asthmatic and Nonasthmatic Children and Improves Quality of Life in Children with Asthma.

Tai-Chi-Chuan (TCC) is an exercise of low-to-moderate intensity which is suitable for asthmatic patients. The aim of our study is to investigate improvements of the lung function, airway inflammation, and quality of life of asthmatic children after TCC. Participants included sixty-one elementary school students and they were divided into asthmatic (n = 29) and nonasthmatic (n = 32) groups by the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Among them, 20 asthmatic and 18 nonasthmatic children volunteered to participate in a 60-minute TCC exercise weekly for 12 weeks. Baseline and postintervention assessments included forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), fractional exhaled nitric oxide (FeNO) level, and Standardised Pediatric Asthma Quality of Life Questionnaire (PAQLQ(S)). After intervention, the level of FeNO decreased significantly; PEFR and the FEV1/FVC also improved significantly in both asthmatic group and nonasthmatic group after TCC. The asthmatic children also had improved quality of life after TCC. The results indicated that TCC could improve the pulmonary function and decrease airway inflammation in both children with mild asthma and those without asthma. It also improves quality of life in mild asthmatic children. Nevertheless, further studies are required to determine the effect of TCC on children with moderate-to-severe asthma.

Clinical presentations and molecular studies of invasive renal epithelioid angiomyolipoma.

PURPOSE: Epithelioid angiomyolipoma (EAML) is a rare variant of renal angiomyolipoma with malignant potential, and the cytogenetic and clinical behavior of EAML remains a challenging issue. METHODS: We retrospectively analyze the clinical courses of five EAML, the use of everolimus on metastatic EAML, and next-generation sequencing (NGS) and polymerase chain reaction (PCR) studies to investigate the gene mutation of TSC and the impact of PI3K/Akt/mTOR signaling pathway in metastatic EAML. RESULTS: The mean age was 37.8 years, mean tumor size was 13 cm, all patients received radical nephrectomy, one stage IV patient received neoadjuvant mTOR inhibitor management, and one patient with high mitotic activity developed metastasis 1 year after nephrectomy. NGS assay showed a frameshift gene mutation of TSC2 in chromosome 16. PCR array for the mRNA alterations in PI3K/Akt/mTOR signaling pathway of EAML showed high expression of PIP3, AKT, TSC1, mTOR, PDK1, P70, 4E-BP1 and elF4E. CONCLUSION: EAML of the kidney is a specific type of renal AML with malignant potentials, where around 22% of the patients present with invasion or metastasis. Higher mitotic activities indicate a greater metastatic potential, with radical nephrectomy as the treatment of choice, and mTOR inhibitors such as everolimus either as neoadjuvant or adjuvant targeted therapy can lead to a better clinical outcome. NGS to explore the mTOR signaling pathway may help us to better understand the pathogenesis and progression of EAML.