Objective
Despite advances in hematopoietic stem cell transplantation (HSCT), a considerable number of pediatric HSCT patients develops post-transplant complications requiring admission to the ...pediatric intensive care unit (PICU). The objective of this study was to evaluate clinical findings, PICU supportive therapy and outcome as well as predictive factors for 6-months survival after discharge of HSCT patients from PICU.
Study design
This retrospective single-center analysis investigated patient characteristics, microbiological findings, reasons for admission and death of 54 cases accounting for 94 admissions to the PICU of the University Children’s Hospital Tuebingen from 2002 to 2017. We compared clinical characteristics between children with and without 6-months survival after discharge from PICU following HSCT. Finally, we assessed the potential prognostic value of the oncological Pediatric Risk of Mortality Score (O-PRISM), the Pediatric Sequential Organ Failure Assessment Score (pSOFA) and the pRIFLE Criteria for Acute Kidney Injury for 6-months survival using Generalized Estimating Equations (GEE) and Receiver Operating Characteristic curves.
Results
Respiratory insufficiency, gastroenterological problems and sepsis were the most common reasons for PICU admission. Out of 54 patients, 38 (70%) died during or after their last PICU admission, 30% survived for at least six months. When considering only first PICU admissions, we could not determine prognostic factors for 6-months mortality. In contrast, under consideration of all PICU admissions in the GEE model, ventilation (p=0.03) and dialysis (p=0.007) were prognostic factors for 6-months mortality. Furthermore, pSOFA (p=0.04) and O-PRISM (p=0.02) were independent risk factors for 6-months mortality considering all PICU admissions.
Conclusion
Admission of HSCT patients to PICU is still associated with poor outcome and 69% of patients died within 6 months. Need for respiratory support and dialysis are associated with poor outcome. Prediction of 6-months survival is difficult, especially during a first PICU admission. However, on subsequent PICU admissions pSOFA and O-PRISM scores might be useful to predict mortality. These scores should be prospectively evaluated in further studies to verify whether they can identify pediatric HSCT recipients profiting most from transferal to the PICU.
Delirium represents the most common form of acute cerebral dysfunction in critical illness. The prevention, recognition, and treatment of delirium must become the focus of modern pediatric intensive ...care, as delirium can lead to increased morbidity and mortality. The aim of this study is to evaluate the impact of a delirium bundle consisting of mainly non-pharmacological measures.
This is a pre-/post-implementation study in an interdisciplinary pediatric intensive care unit of a tertiary care university hospital. In the pre-implementation period, pediatric intensive care delirium was monitored using the Sophia Observation withdrawal Symptoms and Pediatric Delirium scale. After introduction of a delirium bundle consisting of non-pharmacological prevention and treatment measures a period of 4 months was interposed to train the PICU staff and ensure that the delirium bundle was implemented consistently before evaluating the effects in the post-implementation period. Data collection included prevalence of delirium and withdrawal, length of PICU stay, duration of mechanical ventilation, and cumulative dose of sedatives and analgesics.
A total of 792 critically ill children aged 0-18 years were included in this study. An overall delirium prevalence of 30% was recorded in the pre-implementation group and 26% in the post-implementation group (
= 0.13). A significant reduction in the prevalence of pediatric delirium from was achieved in the subgroup of patients under 5 years of age (27.9 vs. 35.8%,
= 0.04) and in patients after surgery for congenital heart disease (28.2 vs. 39.5%,
= 0.04). Young age, length of PICU stay, and iatrogenic withdrawal syndrome were found to be risk factors for developing delirium.
Based on a validated delirium monitoring, our study gives new information regarding the prevalence of pediatric delirium and the characteristics of intensive care patients at risk for this significant complication. Especially young patients and patients after surgery for congenital heart disease seem to benefit from the implementation of non-pharmacological delirium bundles. Based on our findings, it is important to promote change in pediatric intensive care-toward a comprehensive approach to prevent delirium in critically ill children as best as possible.
Bronchopleural fistula (BPF) is a severe complication following pneumonia or pulmonary surgery, resulting in persistent air leakage (PAL) and pneumothorax. Surgical options include resection, ...coverage of the fistula by video-assisted thoracoscopic surgery (VATS), or pleurodesis. Interventional bronchoscopy is preferred in complex cases and involves the use of sclerosants, sealants and occlusive valve devices.
A 2.5-year-old girl was admitted to our hospital with persistent fever, cough and dyspnoea. Clinical and radiological examination revealed right-sided pneumonia and pleural effusion. The child was started on antibiotics, and the effusion was drained by pleural drainage. Following removal of the chest tube, the child developed tension pneumothorax. Despite insertion of a new drain, the air leak persisted. Thoracoscopic debridement with placement of another new drain was performed after 4 weeks, without abolishment of the air leak. Bronchoscopy with bronchography revealed a BPF in right lung segment 3 (right upper-lobe anterior bronchus). We opted for an interventional approach that was performed under general anaesthesia during repeat bronchoscopy. Following bronchographic visualisation of the fistula, a 2.7 French microcatheter was placed in right lung segment 3 (upper lobe), allowing occlusion of the fistula by successive implantation of 4 detachable high-density packing volume coils, which were placed into the fistula. Subsequent bronchography revealed no evidence of residual leakage, and the chest tube was removed 2 days later. The chest X-ray findings normalized, and follow-up over 4 years was uneventful.
Bronchoscopic superselective occlusion of BPF using detachable high-density packing large-volume coils was a successful minimally invasive therapeutic intervention performed with minimal trauma in this child and has not been reported thus far. In our small patient, the short interventional time, localized intervention and minimal damage in the lung seemed superior to the corresponding outcomes of surgical lobectomy or pleurodesis in a young growing lung, enabling normal development of the surrounding tissue. Follow-up over 4 years did not show any side effects and was uneventful, with normal lung-function test results to date.
Bone morphogenetic protein 2 (BMP2) in chromosomal region 20p12 belongs to a gene superfamily encoding TGF-β-signaling proteins involved in bone and cartilage biology. Monoallelic deletions of 20p12 ...are variably associated with cleft palate, short stature, and developmental delay. Here, we report a cranioskeletal phenotype due to monoallelic truncating and frameshift BMP2 variants and deletions in 12 individuals from eight unrelated families that share features of short stature, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease. De novo occurrence and autosomal-dominant inheritance of variants, including paternal mosaicism in two affected sisters who inherited a BMP2 splice-altering variant, were observed across all reported families. Additionally, we observed similarity to the human phenotype of short stature and skeletal anomalies in a heterozygous Bmp2-knockout mouse model, suggesting that haploinsufficiency of BMP2 could be the primary phenotypic determinant in individuals with predicted truncating variants and deletions encompassing BMP2. These findings demonstrate the important role of BMP2 in human craniofacial, skeletal, and cardiac development and confirm that individuals heterozygous for BMP2 truncating sequence variants or deletions display a consistent distinct phenotype characterized by short stature and skeletal and cardiac anomalies without neurological deficits.
Conventional catheter ablation of cardiac arrhythmias is associated with radiation risks for patients and laboratory personnel. However, nonfluoroscopic catheter guidance may increase the risk for ...inadvertent cardiac injury. A novel radiofrequency ablation catheter capable of real-time tissue-tip contact force measurements may compensate for nonfluoroscopic safety issues.
To investigate the feasibility of contact force-controlled zero-fluoroscopy catheter ablation.
In 30 patients (including 12 pediatric patients), zero-fluoroscopy catheter ablation of right-sided (right atrium, n = 20; right ventricle, n = 2) and left atrial (n = 8) arrhythmias was attempted. Inclusion criteria were symptomatic suspected atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, focal right atrial and ventricular arrhythmias, and lone atrial fibrillation. A novel irrigated-tip catheter with an integrated contact force sensor was used for nonfluoroscopic 3-dimensional electroanatomical mapping and radiofrequency ablation. Transseptal access was gained under transesophageal guidance for ablation of left-sided arrhythmias.
Procedural success without fluoroscopy was achieved in 29 of the 30 patients (97%). In 1 patient, endocardial nonfluoroscopic ablation failed because of an epicardial accessory pathway within a coronary sinus aneurysm. Mean total contact force and amplitude of force undulations were kept below 50 g during mapping and below 40 g during ablation to prevent contact force peaks (>100 g). Apart from a transient second-degree type I atrioventricular block, no complications occurred. The mean procedure time was 2.8 ± 0.9 hours. There were no arrhythmia recurrences during a mean follow-up of 6.2 ± 4.2 months.
Contact force-controlled zero-fluoroscopy catheter ablation is generally feasible in right-sided and left atrial cardiac arrhythmias.
Anomalous aortic origin of the left coronary artery (AAOLCA) from the right aortic sinus is a rare congenital anomaly associated with significantly increased risk of myocardial ischemia, arrhythmias ...and sudden cardiac death. This refers specifically to AAOLCA associated with interarterial and/or intramural course. Much less is known about anomalous origin of the left coronary artery from the right aortic sinus associated with a subpulmonic intramyocardial course.
We report a 12 year old girl who complained of recurrent episodes of chest pain lasting for some minutes and not associated to exercise. Echocardiography revealed AAOLCA from the right aortic sinus taking a subpulmonic course within the conal septum. The diagnosis was confirmed by CT-scan and selective coronary angiography. Treadmill test, Holter-ECG and bicycle-stress echocardiography revealed no evidence of myocardial ischemia reflecting unimpaired diastolic flow in the left coronary artery. According to the nature of the complaints and in the absence of signs of myocardial ischemia the episodes of chest pain were classified as idiopathic and not associated to the coronary anomaly. We opted for a conservative approach with regular follow-up visits. During a follow-up of 2 years without restriction of sports activities the patient has been asymptomatic.
According to the literature AAOLCA with subpulmonary intramyocardial course appears to be associated with significantly less clinical problems than AAOLCA taking an interarterial course. The diagnosis can be suspected based on echocardiography and confirmed by contrast-enhanced computed tomography. Until now there are only few data concerning the natural history and incidence of complications in this specific anomaly. Despite the probably benign nature we recommend regular follow-up examinations including stress-testing in these patients.
Uniatrial biventricular connection (UBC) is a rare cardiovascular anomaly characterized by absence of one atrioventricular connection and drainage of the other atrium via a solitary atrioventricular ...valve into both ventricles. The absent atrioventricular connection may affect either the left or right atrium. Because of the absence of one atrioventricular connection hearts with UBC have been classified among functionally univentricular hearts requiring palliative treatment according to the Fontan principle.
We report two further patients with UBC. In one of these patients careful echocardiographic examination of the atrioventricular junction in early infancy revealed the possibility of biventricular repair based on the favorable anatomy of the atrioventricular valve and balanced ventricles in the presence of an inlet ventricular septal defect (VSD).
Both patients presented in the neonatal period for evaluation of complex congenital heart disease. The anatomy of the atrioventricular valves in our patients was indistinguishable from atrioventricular septal defects exhibiting the morphology of a common valve with superior and inferior bridging leaflets. The common atrioventricular valve was connected exclusively to the right atrium draining into both ventricles while the left atrium drained into the right atrium via a secundum atrial septal defect. In one of our patients biventricular repair with good longterm-result was performed by reseptation of the atria, patch repair of the VSD and septation of the atrioventricular valve. The second patient underwent univentricular palliation according to the Fontan principle.
The echocardiographic findings in our patients suggest that at least some patients with UBC represent a variant of atrioventricular septal defects associated with extreme ventriculoatrial malalignment resulting in fusion of the deviated primary atrial septum with the lateral aspect of the atrioventricular junction. This offers the option of septation of the common atrioventricular valve and biventricular repair in patients with adequate size of both ventricles. Exact echocardiographic analysis of the morphology of the atrioventricular valve is essential to distinguish these patients with a morphologically common atrioventricular valve in early infancy from other variants of absent atrioventricular connection and to select those who are suitable for biventricular repair.
The closure of perimembranous ventricular septal defects (VSDs) is one of the most common surgeries performed in infancy. The technique of detachment of the anterior and septal leaflets of the ...tricuspid valve (TV) with subsequent leaflet augmentation is frequently used for isolated as well as non-isolated VSD closure. In this study, we compared the incidence of tricuspid regurgitation (TR) in patients who underwent a VSD repair with and without detachment of the TV in the short- and long-term follow-up.
A retrospective study that included 140 patients who underwent perimembranous VSD closure at our center from 2011-2016, where 102 of these patients underwent the procedure with detachment of the TV, was performed. The follow-up data were obtained from postoperative echocardiography performed in the follow-up visits. A total of 62 patients underwent follow-up at our center, where the follow-up time ranged from 1 to 9 years, with a mean of 71 ± 2.47 months.
Regarding patients who underwent a VSD repair with a detachment of the TV, 98.1% of the patients had none to mild TR, compared to 94.7% in patients without intraoperative TV detachment at the time of discharge. There were no reported cases of moderate to severe TR, atrioventricular blocks, aortic insufficiency, or deaths. A total of 98.1% of patients who underwent follow-up at our center with a TV detachment had none to mild TR compared to 94.7% in the group without TV detachment.
TV detachment with leaflet augmentation for VSD closure is safe and effective and does not increase the incidence of TR in the short- and long-term follow-up.
Recurrent rearrangements of chromosome 1q21.1 that occur via non-allelic homologous recombination have been associated with variable phenotypes exhibiting incomplete penetrance, including congenital ...heart disease (CHD). However, the gene or genes within the ∼1 Mb critical region responsible for each of the associated phenotypes remains unknown. We examined the 1q21.1 locus in 948 patients with tetralogy of Fallot (TOF), 1488 patients with other forms of CHD and 6760 ethnically matched controls using single nucleotide polymorphism genotyping arrays (Illumina 660W and Affymetrix 6.0) and multiplex ligation-dependent probe amplification. We found that duplication of 1q21.1 was more common in cases of TOF than in controls odds ratio (OR) 30.9, 95% confidence interval (CI) 8.9-107.6); P = 2.2 × 10−7, but deletion was not. In contrast, deletion of 1q21.1 was more common in cases of non-TOF CHD than in controls OR 5.5 (95% CI 1.4-22.0); P = 0.04 while duplication was not. We also detected rare (n = 3) 100-200 kb duplications within the critical region of 1q21.1 in cases of TOF. These small duplications encompassed a single gene in common, GJA5, and were enriched in cases of TOF in comparison to controls OR = 10.7 (95% CI 1.8-64.3), P = 0.01. These findings show that duplication and deletion at chromosome 1q21.1 exhibit a degree of phenotypic specificity in CHD, and implicate GJA5 as the gene responsible for the CHD phenotypes observed with copy number imbalances at this locus.
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