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Background Tuberous Sclerosis Complex (TSC) is a rare multisystem disorder. In 2012 diagnostic criteria for TSC were revised. However, data on the incidence of TSC are limited. Methods Prospective, national surveillance study in Germany over a 2-year-period (03/2015–02/2017) using current revised criteria for TSC. Patients up to the age of 18 years with a new diagnosis of definite or possible TSC (clinical and/or genetic) were included. The aims of this study were 1) to generate up-to-date data on the incidence of definite or possible TSC, 2) to assess age at first diagnosis, and 3) to compare these data with previous epidemiologic data. Results In total, 86 patients met inclusion criteria (definite or possible TSC) with a median age at diagnosis of 6 months (range: 5 months before birth – 197 months of age). Among patients identified with features of TSC, 73.3% met criteria for definite diagnosis (median age: 7 months) and 26.7% met criteria for a possible diagnosis (median age: 3 months). 55.8% of patients were male. When excluding prenatally diagnosed patients, median age at diagnosis was 11 months with a range of 0 to 197 months. The 3 most common clinical features at diagnosis of TSC were central nervous system involvement in 73.3% patients (of these 95.2% experienced seizures), cutaneous involvement in 58.1% patients (with the most common lesion being hypomelanotic macules in 92%) and cardiac rhabdomyoma in half of the patients. Cardiac rhabdomyoma were detected by prenatal ultrasonography in 22.1% of patients. The presence of cardiac rhabdomyoma was associated with cardiac arrhythmias in 25.6% (about 13% of all diagnosed patients) in our cohort. The overall prevalence of seizure disorders was 69.8%. The annual incidence rate of TSC is estimated at a minimum of 1:17.785 live births. However correcting for underreporting, the estimated incidence rate of definite or possible TSC is approximately 1:6.760–1:13.520 live births in Germany. Conclusions This is the first study that assessed prospectively the incidence rate of TSC in children and adolescents using the updated diagnostic criteria of 2012. This prospective surveillance study demonstrates a low age at first diagnosis (median: 6 months), likely due to antenatal detection of cardiac rhabdomyoma. Early diagnosis bears the potential for implementing effective therapies at an earlier stage.

We report on a 6-year-old boy with underlying hypoplastic left heart syndrome and a total cavopulmonary connection (Fontan circulation) with a diagnosis of plastic bronchitis. After an initial good response to therapy, his productive cough became significantly stronger again. Four months later, the patient’s mother brought a preserving jar containing an extensive bronchial cast to the clinic, the size of which is rarely seen in small children. Plastic bronchitis is a rare but dreaded complication in patients with Fontan circulation as well as in infectious or inflammatory diseases; its treatment is challenging.

Objective: The objective of this study is to evaluate the clinical application and primary outcome of transcatheter embolization using Amplatzer™ Vascular Plug (AVP) Type 2 and Type 4 in different congenital cardiovascular malformations.Design: This is a single-center retrospective observational cohort study.Methods: We analyzed clinical and imaging data of 36 patients retrospectively who received transcatheter embolizations of the following malformations using AVP: systemic-to-pulmonary collateral arteries (SPCA), patent ductus arteriosus (PDA), ventricular septal defects (VSD), and aberrant pulmonary sequestration arteries (PSA). We included all patients treated in our institution from January 2010 to July 2023.Results: In 36 patients (median age 40.0 months, range 0.5 months–42.0 years; 56.8% male), 44 AVPs were implanted in 37 procedures. The target lesions were SPCA in n=15 procedures, PDA in n=9, VSD in n=9, and PSA in n=4. Thirty-four AVP Type 2 and 10 AVP Type 4 were applied, the latter only in SPCA and PSA. SPCA was most common in complex congenital heart disease with univentricular physiology (75.0%). VSD were associated with additional cardiac malformations in 33.3%, PDA were associated with prematurity (55.6%), and all pulmonary sequestrations occurred in scimitar syndrome. Primary total or subtotal occlusion succeeded in n38/44 (86.3%). For residual PDA, an additional occluder was implanted in one patient. In one case, pulmonary sequestration had to be treated surgically. One premature infant with PDA closure sustained a relevant obstruction of the left pulmonary artery by the outer AVP disc which required surgical correction 4 months later.Conclusion: Embolization using AVP is a suitable approach for closure of various cardiovascular malformations with a high primary success rate and low complication rate. It should be considered in treatment of different irregular vessel anomalies and in selected VSD.

Congenital critical aortic valve stenosis (CAVS) is a life-threatening disease requiring urgent treatment. First-line therapy is still controversial. The aim of our study was (1) to analyze retrospectively the patients of our institution who underwent balloon aortic valvuloplasty (BAV) due to CAVS and (2) describe the techniques for improved feasibility of intervention using microcatheters and retrieval loops. Twelve patients underwent 23 BAVs: 1 BAV was performed in 3 patients, 2 BAVs were performed in 7 patients, and 3 BAVs were performed in 2 patients. The peak trans-valvular pressure gradient (Δp) and left ventricular shortening fraction (LVSF) improved significantly in the first two interventions. In the first BAV, Δp decreased from 73.7 ± 34.5 mmHg to 39.8 ± 11.9 mmHg (p = 0.003), and the LVSF improved from 22.3 ± 13.5% to 31.6 ± 10.2% (p = 0.001). In the second BAV, Δp decreased from 73.2 ± 33.3 mmHg to 35.0 ± 20.2 mmHg (p < 0.001), and the LVSF increased from 26.7 ± 9.6% to 33.3 ± 7.4% (p = 0.004). Cardiac surgery during the neonatal period was avoided for all children. The median time to valve surgery was 5.75 years. Few complications occurred, namely mild-to-moderate aortic regurgitation, one remediable air embolism, and one intimal injury to the ascending aorta. We conclude that BAV is a successful emergency treatment for CAVS, resulting in left ventricular relief, clinical stabilization, and a time gain until cardiac surgery.

MicroRNAs (miRNAs) are small RNAs regulating gene expression post-transcriptionally. Recent studies demonstrated that miRNAs are involved in the development of congenital heart defects (CHD). In this study, we aimed at identifying the specific patterns of miRNAs in blood of monozygotic twin pairs discordant for CHD and to assess whether miRNAs might be involved in the development or reflect the consequences of CHD. miRNA microarray analysis and Real-Time Quantitative PCR (RT-qPCR) were employed to determine the miRNA abundance level from 12 monozygotic twins discordant for CHD and their non-CHD co-twins (n = 12). Enrichment analyses of altered miRNAs were performed using bioinformatics tools. Compared with non-CHD co-twins, profiling analysis indicated 34 miRNAs with a significant difference in abundance level (p<0.05, fold change ≥ 1.3), of which 11 miRNAs were up-regulated and 23 miRNAs were down-regulated. Seven miRNAs were validated with RT-qPCR including miR-511-3p, miR-1306-5p, miR-421, miR-4707-3p, miR-4732-3p, miR-5189-3p, and miR-890, and the results were consistent with microarray analysis. Five miRNAs namely miR-511-3p, miR-1306-5p, miR-4732-3p, miR-5189-3p, and miR-890 were found to be significantly up-regulated in twins < 10 years old. Bioinformatics analysis showed that the 7 validated miRNAs were involved in phosphatidylinositol signaling, gap junction signaling, and adrenergic signaling in cardiomyocytes. Our data show deregulated miRNA abundance levels in the peripheral blood of monozygotic twins discordant for CHD, and identify new candidates for further analysis, which may contribute to understanding the development of CHD in the future. Bioinformatics analysis indicated that the target genes of these miRNAs are likely involved in signaling and communication of cardiomyocytes.

Objectives: The purpose of this study was to analyze image quality and radiation exposure of thoracic computed tomography angiography (CTA) in children with congenital heart diseases (CHDs) using either manual contrast medium (CM) injection or automated power injectors with bolus tracking. Methods: A total of 137 thoracic CTAs of 120 consecutive pediatric patients were included in this retrospective study. We analyzed the method of CM administration (power injection with bolus tracking (PI) or manual injection (MI)), injection routes, volumes and flow rates of CM. For the evaluation of objective image quality, attenuation values in the heart chambers and great thoracic vessels were determined by region-of-interest (ROI) analysis and signal-to-noise (SNR) and contrast-to-noise (CNR) ratios calculated thereof. Visual image quality was assessed by two blinded readers (four-point Likert-scale) analyzing the presence of artifacts and the depiction of relevant anatomical structures. Effective radiation doses were calculated with dose length products and specific conversion factors. Results: CM administration was performed using PI in 119/137 CTAs, whereas MI was conducted in 18/137. The smallest size of peripheral venous cannulas was 24 gauge in 36/137 (26.3%) cases. Overall mean CM volume was 17 mL ± 16 mL (mean ± SD). In PI, the mean flow rate of CM was 1.52 ± 0.90 mL/s with a range between 0.5 and 5.0 mL/s. When comparing the overall PI population and an age-, size- and weight-matched PI subpopulation (18 cases) with the MI population, attenuation values in Hounsfield units (HU) and CNR values were significantly higher in the PI groups than in the MI group for each relevant cardiac structure (left ventricle, right ventricle, ascending aorta and pulmonary trunk, p = 0.02–0.001). Overall image quality and depiction of cardiac structures were rated significantly better in CTAs with PI (interquartile ranges: “good” to “excellent” (Likert 3–4)) in PI compared with CTAs acquired with MI (interquartile ranges: “fair” to “good” (2–3)) in MI by both readers (p < 0.001). The inter-observer reliability was strong, with a Kendall’s Tau-b correlation coefficient of τ = 0.802 (p < 0.001). The mean effective radiation dose (E) did not differ significantly when comparing the stratified samples (i.e., the matched PI subgroup and the MI group; 0.5 (±0.3) mSv in both, p = 0.76). There were no complications associated with the CM injections for both application approaches. Conclusions: Automated contrast agent applications with power injectors and bolus tracking ensure better image quality in pediatric CTA, even when low volumes and flow rates need to be applied. There is a slight increase in radiation associated with bolus tracking. This approach represents a suitable imaging technique for the work-up of congenital heart disease.

The pleural cavity represents a unique immunological compartment that can mount inflammatory reactions during infections, after surgery and in chronic immunological diseases. The connection between systemic immune reactions in the blood and local immune reactions in pleural effusions remains unclear. This study provides the first comprehensive immunological characterization of paired blood and pleural effusion samples, utilizing combined cell and cytokine analyses in pediatric patients undergoing cardiac surgery. In 30 pediatric patients (median age: 22 months) with pleural effusion after cardiac surgery for congenital heart defects, corresponding peripheral blood and pleural effusion samples were analyzed for their immune response. We used flow cytometry and multiplex immunoassays to quantify 14 T cell subpopulations and 12 T cell associated cytokines in each biosample. IL-6, IL-8, IL-10, TNF (p<0.0001) levels were significantly higher in pleural effusion compared to plasma. In contrast, IFN-γ, GM-CSF, IL-17A levels were lower in pleural effusion than in plasma (p ≤ 0.0005). In comparison to peripheral blood, there was a significantly higher proportion of T helper cells 1 (T 1, p=0.0023), T helper cells 17 (T 17, p=0.0334) and memory effector cytotoxic T cells (CD3 CD8 CD45RO CD62L , p=0.0449) in pleural effusion and the same trend was observed for memory effector T cells (CD3 CD4 CD45RO CD62L , p=0.0633) and double-negative T cells (CD3 CD4 CD8 ) (p=0.1085). Naïve T cells (CD3 CD4 CD45RO CD62L ) and naïve cytotoxic T cells (CD3 CD8 CD45RO CD62L ) were slightly reduced in pleural effusion compared to peripheral blood (not significant). Immunological factors in pleural effusions differed significantly from the corresponding blood samples in pediatric patients after cardiac surgery. The results suggest localized production of specific cytokines within the pleural space, while the distribution of other cytokines in pleural effusions appears to be more reflective of the systemic immune response. We found evidence that on the cellular level, the surface marker CD62L may play a key role in navigating T cells between the blood and pleural effusion. This study confirms that the pleural cavity harbors a unique lymphatic compartment, the analysis of which may be useful for both diagnostic and therapeutic purposes.

Background and Objectives: Patients with congenital heart disease (CHD), especially as a concomitant syndromal disease of trisomy 21 (T21), are at risk for impaired neurodevelopment. This can also affect these patients’ education. However, there continues to be a research gap in the educational development of CHD patients and T21 CHD patients. Materials and Methods: In total, data from 2873 patients from the German National Register for Congenital Heart Defects were analyzed. The data are based on two online education surveys conducted among patients registered in the National Register for Congenital Heart Defects (2017, 2020). Results: Of 2873 patients included (mean age: 14.1 ± 4.7 years, 50.5% female), 109 (3.8%) were identified with T21 (mean age: 12.9 ± 4.4 years, 49.5% female). T21 CHD participants had a high demand for early specific interventions (overall cohort 49.1%; T21 cohort 100%). T21 CHD children more frequently attended special schools and, compared to non-trisomy 21 (nT21) CHD patients, the probability of attending a grammar school was reduced. In total, 87.1% of nT21 CHD patients but 11% of T21 CHD patients were enrolled in a regular elementary school, and 12.8% of T21 CHD patients could transfer to a secondary school in contrast to 35.5% of nT21 CHD patients. Most of the T21 CHD patients were diagnosed with psychiatric disorders, e.g., learning, emotional, or behavioral disorders (T21 CHD patients: 82.6%; nT21 CHD patients: 31.4%; p < 0.001). Conclusions: CHD patients are at risk for impaired academic development, and the presence of T21 is an aggravating factor. Routine follow-up examinations should be established to identify developmental deficits and to provide targeted interventions.

Objective The aim of this study was to provide seizure etiology, semiology, underlying conditions, and out‐of‐ and in‐hospital diagnostics, treatment, and outcome data on children with out‐of‐ or in‐hospital‐onset status epilepticus (SE) according to the International League Against Epilepsy definition that required admission to the pediatric intensive care unit (PICU) for ≥4 hours. Methods This prospective national surveillance study on SE in childhood and adolescence was conducted over 2 years (07/2019‐06/2021). Results This study examined 481 SE episodes in 481 children with a median age of 43 months (1 month to 17 years 11 months), of which 46.2% were female and 50.7% had a previous seizure history. The most frequent acute SE cause was a prolonged, complicated febrile seizure (20.6%). The most common initial seizure types were generalized seizures (49.9%), focal seizures (18.0%), and unknown types (12.1%); 40.5% of patients suffered from refractory SE and 5.0% from super‐refractory SE. The three most common medications administered by nonmedically trained individuals were diazepam, midazolam, and antipyretics. The three most frequent anti‐seizure medications (ASMs) administered by the emergency physician were midazolam, diazepam, and propofol. The three most common ASMs used in the clinical setting were midazolam, levetiracetam, and phenobarbital. New ASMs administered included lacosamide, brivaracetam, perampanel, stiripentol, and eslicarbazepine. Status epilepticus terminated in 16.0% in the preclinical setting, 19.1% in the emergency department, and 58.0% in the PICU; the outcome was unknown for 6.9%. The median PICU stay length was 2 (1–121) days. The median modified Rankin scale was 1 (0–5) on admission and 2 (0–6) at discharge. New neurological deficits after SE were observed in 6.2%. The mortality rate was 3.5%. Significance This study provides current real‐world out‐of‐ and in‐hospital data on pediatric SE requiring PICU admission. New ASMs are more frequently used in this population. This knowledge may help generate a more standardized approach.