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Background Tissue-engineered vascular grafts (TEVGs) have the potential to advance the surgical management of infants and children requiring congenital heart surgery by creating functional vascular conduits with growth capacity. Methods Herein, we used an integrative computational-experimental approach to elucidate the natural history of neovessel formation in a large animal preclinical model; combining an in vitro accelerated degradation study with mechanical testing, large animal implantation studies with in vivo imaging and histology, and data-informed computational growth and remodeling models. Results Our findings demonstrate that the structural integrity of the polymeric scaffold is lost over the first 26 weeks in vivo, while polymeric fragments persist for up to 52 weeks. Our models predict that early neotissue accumulation is driven primarily by inflammatory processes in response to the implanted polymeric scaffold, but that turnover becomes progressively mechano-mediated as the scaffold degrades. Using a lamb model, we confirm that early neotissue formation results primarily from the foreign body reaction induced by the scaffold, resulting in an early period of dynamic remodeling characterized by transient TEVG narrowing. As the scaffold degrades, mechano-mediated neotissue remodeling becomes dominant around 26 weeks. After the scaffold degrades completely, the resulting neovessel undergoes growth and remodeling that mimicks native vessel behavior, including biological growth capacity, further supported by fluid–structure interaction simulations providing detailed hemodynamic and wall stress information. Conclusions These findings provide insights into TEVG remodeling, and have important implications for clinical use and future development of TEVGs for children with congenital heart disease. Blum et al. combine computational and experimental methods to study the long-term development of tissue engineered vascular grafts in a lamb model. The authors demonstrate that the grafts undergo growth and remodeling, evolving to mimic the characteristics and function of a native blood vessel. Plain language summary Surgery to correct defects in the heart that are present at birth sometimes requires the use of artificial blood vessels called vascular grafts. Tissue-engineered vascular grafts (TEVGs) are scaffolds seeded with cells that can develop into functional blood vessels over time. We conducted a series of laboratory and computer-based experiments to investigate how TEVGs develop into functional blood vessels, and demonstrated two phases of changes to the TEVG after implantation: an early phase driven by inflammation, and a later phase driven by the mechanical properties of the tissue. At later time points, the resulting blood vessels demonstrated the ability to grow and respond to blood flow in similar ways to the body’s own blood vessels. These results provide insight into the processes by which TEVGs become functional blood vessels, with implications for future clinical use of this technology.

Primary pulmonary vein stenosis (PPVS) is an emerging problem among infants. In contrast to acquired disease, PPVS is the development of stenosis in the absence of preceding intervention. While optimal care approaches remain poorly characterized, over the past decade, understanding of potential pathophysiological mechanisms and development of novel therapeutic strategies are increasing. A multidisciplinary team of health care providers was assembled to review the available evidence and provide a common framework for the diagnosis, management, and treatment of PPVS during infancy. To address knowledge gaps, institutional and multi-institutional approaches must be employed to generate knowledge specific to ex-premature infants with PPVS. Within individual institutions, creation of a team comprised of dedicated health care providers from diverse backgrounds is critical to accelerate clinical learning and provide care for infants with PPVS. Multi-institutional collaborations, such as the PVS Network, provide the infrastructure and statistical power to advance knowledge for this rare disease.

Bioabsorbable materials made from polymeric compounds have been used in many fields of regenerative medicine to promote tissue regeneration. These materials replace autologous tissue and, due to their growth potential, make excellent substitutes for cardiovascular applications in the treatment of congenital heart disease. However, there remains a sizable gap between their theoretical advantages and actual clinical application within pediatric cardiovascular surgery. This review will focus on four areas of regenerative medicine in which bioabsorbable materials have the potential to alleviate the burden where current treatment options have been unable to within the field of pediatric cardiovascular surgery. These four areas include tissue-engineered pulmonary valves, tissue-engineered patches, regenerative medicine options for treatment of pulmonary vein stenosis and tissue-engineered vascular grafts. We will discuss the research and development of biocompatible materials reported to date, the evaluation of materials in vitro, and the results of studies that have progressed to clinical trials.

The aim of the study was to determine the variables associated with high-quality (HQ) versus low-quality (LQ) three-dimensional rotational angiography (3DRA) and create guides for optimization of approach to 3DRA in congenital cardiac catheterization (CCC). CCC has adopted 3DRA as a mainstay, but there has not been systematic analysis of approach to and factors associated with HQ 3DRA. This was a single-center, retrospective study of 3DRAs using Canon Infinix-I platform. Reconstructions were graded by 3 interventionalists. Quality was dichotomized into HQ and LQ. Univariable analyses and multivariable logistic regression models were performed. From 8/2016 to 12/2018, 208 3DRAs were performed in 195 CCCs; median age 7 years (2, 16), weight 23 kg (12, 57). The majority of 3DRAs were performed in patients with biventricular physiology ( N  = 137, 66%) and in pulsatile sites ( N  = 144, 69%). HQ 3DRA ( N  = 182, 88%) was associated with greater total injection volume [2.20 mL/kg (1.44, 3.29) vs. 1.62 mL/kg (1.10, 1.98), p  = 0.005] and more dilute contrast solution [60% (50, 100) vs. 100% (60, 100), p  = 0.007], but not with contrast volume administered ( p  = 0.2) on univariable analysis. On multivariable logistic regression, HQ 3DRA was significantly associated with patient weight [OR 0.97 (95% CI (0.94, 0.99), p  = 0.018], total injection volume [OR 1.04 (95% CI 1.01, 1.07) p  = 0.011], and percent contrast solution [OR 0.97 (95% CI 0.95, 1.00), p  = 0.022]. These data resulted in creation of scatter plots and a novel 3DRA Nomogram for estimating the probability of HQ 3DRA. This is the first study to create evidence-based contrast dose guides and nomogram for 3DRA in CCC. HQ 3DRA was associated with lower weight, higher total injection volumes, and more dilute contrast solution.

To evaluate short-term procedural outcomes and safety for infants < 2.5 kg who underwent catheterization with intended patent ductus arteriosus (PDA) device closure in a multi-center registry, as performance of this procedure becomes widespread. A multi-center retrospective review was performed using data from the Congenital Cardiac Catheterization Project on Outcomes (C3PO) registry. Data were collected for all intended cases of PDA closure in infants < 2.5 kg from April 2019 to December 2020 at 13 participating sites. Successful device closure was defined as device placement at the conclusion of the catheterization. Procedural outcomes and adverse events (AE) were described, and associations between patient characteristics, procedural outcomes and AEs were analyzed. During the study period, 300 cases were performed with a median weight of 1.0 kg (range 0.7–2.4). Successful device closure was achieved in 98.7% of cases with a 1.7% incidence of level 4/5 AEs, including one periprocedural mortality. Neither failed device placement nor adverse events were significantly associated with patient age, weight or institutional volume. Higher incidence of adverse events associated with patients who had non-cardiac problems ( p  = 0.017) and cases with multiple devices attempted ( p  = 0.064). Transcatheter PDA closure in small infants can be performed with excellent short-term outcomes and safety across institutions with variable case volume.

Three-dimensional printing is increasingly utilised for congenital heart defect procedural planning. CT or MR datasets are typically used for printing, but similar datasets can be obtained from three-dimensional rotational angiography. We sought to assess the feasibility and accuracy of printing three-dimensional models of CHD from rotational angiography datasets. Retrospective review of CHD catheterisations using rotational angiography was performed, and patient and procedural details were collected. Imaging data from rotational angiography were segmented, cleaned, and printed with polylactic acid on a Dremel® 3D Idea Builder (Dremel, Mount Prospect, IL, USA). Printing time and materials' costs were captured. CT scans of printed models were compared objectively to the original virtual models. Two independent, non-interventional paediatric cardiologists provided subjective ratings of the quality and accuracy of the printed models. Rotational angiography data from 15 catheterisations on vascular structures were printed. Median print time was 3.83 hours, and material costs were $2.84. The CT scans of the printed models highly matched with the original digital models (root mean square for Hausdorff distance 0.013 ± 0.003 mesh units). Independent reviewers correctly described 80 and 87% of the models (p = 0.334) and reported high quality and accuracy (5 versus 5, p = NS; κ = 0.615). Imaging data from rotational angiography can be converted into accurate three-dimensional-printed models of CHD. The cost of printing the models was negligible, but the print time was prohibitive for real-time use. As the speed of three-dimensional printing technology increases, novel future applications may allow for printing patient-specific devices based on rotational angiography datasets.

Recurrent laryngeal nerve injury leading to vocal cord paralysis is a known complication of cardiothoracic surgery. Its occurrence during interventional catheterisation procedures has been documented in case reports, but there have been no studies to determine an incidence. To establish the incidence of left recurrent laryngeal nerve injury leading to vocal cord paralysis after left pulmonary artery stenting, patent ductus arteriosus device closure and the combination of the procedures either consecutively or simultaneously. Members of the Congenital Cardiovascular Interventional Study Consortium were asked to perform a retrospective analysis to identify cases of recurrent laryngeal nerve injury after the aforementioned procedures. Twelve institutions participated in the analysis. They also contributed the total number of each procedure performed at their respective institutions for statistical purposes. Of the 1337 patients who underwent left pulmonary artery stent placement, six patients (0.45%) had confirmed vocal cord paralysis. 4001 patients underwent patent ductus arteriosus device closure, and two patients (0.05%) developed left vocal cord paralysis. Patients who underwent both left pulmonary artery stent placement and patent ductus arteriosus device closure had the highest incidence of vocal cord paralysis which occurred in 4 of the 26 patients (15.4%). Overall, 92% of affected patients in our study population had resolution of symptoms. Recurrent laryngeal nerve injury is a rare complication of left pulmonary artery stent placement or patent ductus arteriosus device closure. However, the incidence is highest in patients undergoing both procedures either consecutively or simultaneously. Additional research is necessary to determine contributing factors that might reduce the risk of recurrent laryngeal nerve injury.

Few data exist regarding outcomes after resection versus embolic treatment of symptomatic metastatic carcinoid and neuroendocrine tumors. The purpose of this study was to determine whether cytoreduction provides any benefit over embolic management of diffuse neuroendocrine tumors. A prospective database of 734 patients treated at our institution was retrospectively queried for symptomatic metastatic tumors treated with embolization or cytoreduction. Patients were compared with regard to pretreatment performance status, relief of symptoms, and survival. A total of 120 patients were identified: 59 undergoing embolization and 61 undergoing cytoreduction. Twenty-three patients had palliative cytoreduction (gross residual disease). Pretreatment performance status (Eastern Cooperative Oncology Group) was similar for both groups: .7+/-.70 (embolization) versus .8+/-.72 (cytoreduction; P=.27). Complete symptomatic relief was observed in 59% and partial relief in 32% of patients who underwent embolization, with a mean symptom-free interval of 22+/-13.6 months. A total of 69% of patients who underwent cytoreduction had complete symptomatic relief, and 23% had partial relief (P=.08 vs. embolization). The mean duration of relief was 35+/-22.0 months (P<.001 vs. embolization). The mean survival for the patients who underwent embolization was 24+/-15.8 months versus 43+/-26.1 months for those who underwent cytoreduction (P<.001). Survival in patients who underwent palliative cytoreduction was 32+/-18.9 months (P<.001 vs. embolization), whereas it was 50+/-27.6 months in patients who underwent curative resection (P<.001 vs. embolization; P<.001 vs. palliative). Cytoreduction for metastatic neuroendocrine tumors resulted in improved symptomatic relief and survival when compared with embolic therapy in this nonrandomized study. Cytoreduction should be pursued whenever possible even if complete resection may not be achievable.

Unlike Lie algebras, the finite dimensional complex representations of a simple Lie superalgebra are usually not semisimple. As a consequence, despite over thirty years of study, these remain mysterious objects. In this paper we introduce a new tool: the notion of cohomological support varieties for the finite dimensional supermodules for a classical Lie superalgebra g=g0¯⊕g1¯\\mathfrak {g} = \\mathfrak {g}_{\\bar 0} \\oplus \\mathfrak {g}_{\\bar 1} which are completely reducible over g0¯{\\mathfrak g}_{\\bar 0}. They allow us to provide a new, functorial description of the previously combinatorial notions of defect and atypicality. We also introduce the detecting subalgebra of g\\mathfrak {g}. Its role is analogous to the defect subgroup in the theory of finite groups in positive characteristic. Using invariant theory we prove that there are close connections between the cohomology and support varieties of g\\mathfrak {g} and the detecting subalgebra.