Administration of fibrinogen concentrate combined with prothrombin complex maintains hemostasis in children undergoing congenital heart repair (a long-term propensity score-matched study).

BACKGROUND: Bleeding is a common problem in children with congenital heart disease undergoing major cardiac surgery requiring cardiopulmonary bypass (CPB). Little is known about optimal management with blood products. OBJECTIVE: To investigate clinical outcome and hemostatic effects of fibrinogen concentrate (FC) in combination with prothrombin complex concentrate (PCC) versus standard treatment with fresh frozen plasma (FFP) in children undergoing cardiac surgery. METHODS: For this single-institution cohort study, data on 525 children were analyzed. Propensity score matching in 210 children was applied to reduce the impact of various baseline characteristics. RESULTS: Three children treated with FC/PCC developed surgical site bleeding requiring surgical revision. One child developed central venous line-related thrombosis. Blood loss through chest tube drainage was independent of FC/PCC. Coagulation abnormalities were not present in any of these children. Time to extubation and ICU stay did not differ. In the FC/PCC group, children received (median, Q1, Q3) 52 mg/kg (32, 83) FC and 28IU/kg (13, 44) PCC. Fibrinogen concentration was comparable at baseline. On admission to the ICU, fibrinogen was higher in children receiving FC/PCC, namely, 232 mg/dL (196, 280), than in children receiving FFP (186 mg/dL, 149, 224; P < .001). On discharge from the ICU, values did not differ ((FC/PCC 416 mg/dL (288, 501)), non-FC/PCC 418 mg/dL (272, 585; P = 1.000)). CONCLUSION: FC/PCC was well tolerated and permitted hemostasis to be maintained, even in the very young. We were not able to detect a signal for inferiority of this treatment. We conclude that FC/PCC can safely replace FFP.

Calcification or Not. This Is the Question. A 1-Year Study of Bovine Pericardial Vascular Patches (CardioCel) in Minipigs.

A main problem with bioprosthesis used for surgical correction of congenital cardiac malformation is its tendency to shrink and to calcify. Recently, a new material, that is, decellularized bovine pericardium (CardioCel), was introduced in clinics. It was proposed that this new patch material should not calcify and should be particularly suitable for the correction of vascular defects in inborn cardiac diseases. The aim of our chronic minipig study was to evaluate the performance of CardioCel patches implanted in aortic and pulmonary artery position, respectively. Ten minipigs aged 3 months were operated on. A CardioCel patch was implanted in the aorta ascendens and arteria pulmonalis, respectively. Seven minipigs completed the 12 months' follow-up. Angiography of both vessels, measurement of pressure gradients, and histologic evaluation of the implanted patches were carried out. Angiography of both great vessels revealed a good clinical outcome without stenosis. However, histologic examination of the patches showed calcification and neo-formation of hyaline cartilage in both vessel types. Staining of collagen and elastic fibers as well as α-smooth muscle actin demonstrated that the patches did not remodel into an anatomic vascular structure during the 1 year of implantation. In our chronic piglet model, CardioCel patches, when implanted in the ascending aorta and the pulmonary artery, led to calcification and neo-formation of hyaline cartilage in both vessel types 1 year after implantation. The present study indicates that the ideal patch biomaterial for repair of inborn cardiac diseases is still a goal not achieved yet.

Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study.

BACKGROUND: Stem-cell-based, tissue engineered transplants might offer new therapeutic options for patients, including children, with failing organs. The reported replacement of an adult airway using stem cells on a biological scaffold with good results at 6 months supports this view. We describe the case of a child who received a stem-cell-based tracheal replacement and report findings after 2 years of follow-up. METHODS: A 12-year-old boy was born with long-segment congenital tracheal stenosis and pulmonary sling. His airway had been maintained by metal stents, but, after failure, a cadaveric donor tracheal scaffold was decellularised. After a short course of granulocyte colony stimulating factor, bone marrow mesenchymal stem cells were retrieved preoperatively and seeded onto the scaffold, with patches of autologous epithelium. Topical human recombinant erythropoietin was applied to encourage angiogenesis, and transforming growth factor ß to support chondrogenesis. Intravenous human recombinant erythropoietin was continued postoperatively. Outcomes were survival, morbidity, endoscopic appearance, cytology and proteomics of brushings, and peripheral blood counts. FINDINGS: The graft revascularised within 1 week after surgery. A strong neutrophil response was noted locally for the first 8 weeks after surgery, which generated luminal DNA neutrophil extracellular traps. Cytological evidence of restoration of the epithelium was not evident until 1 year. The graft did not have biomechanical strength focally until 18 months, but the patient has not needed any medical intervention since then. 18 months after surgery, he had a normal chest CT scan and ventilation-perfusion scan and had grown 11 cm in height since the operation. At 2 years follow-up, he had a functional airway and had returned to school. INTERPRETATION: Follow-up of the first paediatric, stem-cell-based, tissue-engineered transplant shows potential for this technology but also highlights the need for further research. FUNDING: Great Ormond Street Hospital NHS Trust, The Royal Free Hampstead NHS Trust, University College Hospital NHS Foundation Trust, and Region of Tuscany.

Novel biodegradable polydioxanone stents in a rabbit airway model.

OBJECTIVE: This study was undertaken to evaluate safety and biocompatibility of a novel biodegradable polydioxanone stent in a rabbit tracheal model. Metallic and silicone stents represent standard therapeutic approaches for hollow organ stenosis, although complications have been reported repeatedly. Biodegradable stents could reduce the risks associated with this procedure while still achieving the purpose of maintaining lumen patency. METHODS: A commercially available polydioxanone suture strand with a long safety record was used to manufacture the self-expanding stents. The polydioxanone stents were then implanted bronchoscopically and under fluoroscopic guidance into the tracheas of white rabbits (N = 25). Periodic clinical examination was performed. Histopathologic examination concluded the study for the 5 experimental groups at 3, 4, 5, 10, and 15 weeks after implantation. RESULTS: There were no unexpected deaths and no stent displacements during the study. The animals remained in good condition, without stent debris expectoration. Macroscopic examination revealed that the tracheal lumen stayed open. Histologic examination showed that tracheal damage score was highest 5 weeks after stenting, including in-stent necrosis of the epithelium. Stent degradation was complete with no remnants after 10 weeks, leaving the trachea completely healed at 15 weeks after implantation. CONCLUSIONS: This animal airway model has demonstrated acceptable safety and biocompatibility of this novel biodegradable polydioxanone stent. We suggest that polydioxanone stenting be used for further clinical studies for cases in which complete stent degradation after temporary airway treatment is desirable.

First experience with biodegradable airway stents in children.

PURPOSE: We here report our experience with biodegradable polydioxanone stents for tracheal narrowing in children. DESCRIPTION: Eleven custom-made polydioxanone stents were implanted in 4 patients with airway narrowing due to external compression or intrinsic collapse. The median stent diameter was 9 mm (range, 6 to 14 mm) and median length was 15 mm (range, 13 to 70 mm). EVALUATION: Narrowing was relieved initially in all cases. There was no bleeding or perforation after polydioxanone stent implantation. Size mismatching was a problem in 2 cases. Three patients needed repeat stenting after stent absorption. There was 1 death, unrelated to the stent implantation. All 3 survivors are in good clinical condition up to 12 months after first stenting. CONCLUSIONS: This pilot study shows that polydioxanone stents offer an alternative to metallic or silastic stents for collapse or external compression of the trachea in children. They may avoid the need for permanent stenting and allow subsequent growth of the airway.

Novel biodegradable stents in the treatment of bronchial stenosis after lung transplantation.

OBJECTIVE: To evaluate the safety and effectiveness of novel biodegradable (BD) stents to treat bronchial anastomotic stenosis in patients after lung transplantation. METHODS: Twenty BD stents were implanted endoscopically in six patients (median age 41.5 years (range 35-57 years)) with post-transplant bronchial anastomotic stenoses, between 2006 and 2010. All stents were custom-made from bio-absorbable polydioxanone (PDS). The median stent diameter was 12 mm (8-17 mm) and median length was 20mm (12-30 mm). All patients were evaluated clinically, by bronchoscopy and high-definition computed tomography (CT). RESULTS: The stenosis was initially relieved in all cases. There was no bleeding, perforation or displacement after BD stent implantation. Four patients needed multiple stenting for anastomotic re-stenosis. Median time to any re-stenting was 5 months (2-15 months). There was one sudden death, 1 year after the last BD stent implantation, from a pulmonary embolus. All five survivors are in good clinical condition up to 4 years' follow-up (median 40 months, range 7-48 months) since first stenting and intervention-free up to 44 months (median 24 months, range 7-44 months). CONCLUSIONS: This small pilot study shows that BD stents are a safe, effective and reliable alternative to classical metallic stents in patients with anastomotic stenosis after lung transplantation, and may avoid the need for permanent stenting.

Aminoterminal brain natriuretic peptide levels in children and adolescents after Fontan operation correlate with congestive heart failure.

The aim of this study was to generate normal values of amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) in children and adolescents after Fontan operation without congestive heart failure (CHF) and to test the hypothesis that plasma levels of NT-pro-BNP correlate with the clinical severity of CHF. NT-pro-BNP plasma levels of 59 consecutive patients, with a median age of 8.4 years, after Fontan operation were measured using an automated enzyme immunoassay. The 97.5th percentile of NT-pro-BNP in patients without CHF was 282.3 pg/ml. The severity of heart failure was quantified by a pediatric cardiologist using the New York University Pediatric Heart Failure Index (NYUPHFI). NT-pro-BNP levels correlated with the NYUPHFI (p = 0.001). In patients with CHF (14/59) the NT-pro-BNP levels were significantly higher (median, 399 pg/ml; range, 140-5440 pg/ml) than in patients without CHF (median, 96 pg/ml; range, 11-376 pg/ml). NT-pro-BNP levels of patients with Fontan circulation without CHF are similar to those of healthy children. Plasma NT-pro-BNP concentrations correlate with the severity of CHF in children and adolescents after Fontan operation. Plasma NT-pro-BNP levels can help clinicians in the detection of CHF in pediatric patients with Fontan circulation.

Cardiac fibroma as an inherited manifestation of nevoid basal-cell carcinoma syndrome.

We report the case of an 8-month-old male infant presenting with life-threatening ventricular tachycardia. Echocardiography revealed a left ventricular tumor. The tumor was resected through a left ventriculotomy, and the left ventricle was reconstructed after a partial ventriculectomy Histologic investigation showed a completely resected benign fibroma. The 30-year-old mother was known to have nevoid basal-cell carcinoma syndrome, which can be associated with cardiac fibromas. We believe that this is an interesting addition to the medical literature.

Anomalous drainage of the inferior caval vein to the left atrium.

We report a girl, aged 11(7/12) years, who presented with cyanosis. Cardiac catheterization showed occlusion of the infrahepatic segment of the inferior caval vein, with drainage of the hepatic veins into the left atrium. Transoesophageal echocardiography revealed an anomalous Eustachian valve that baffled the vein to the left atrium. This lesion is an extremely rare cause of cyanosis.