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Despite significant research efforts, clinical practice for arterial bypass surgery has been stagnant, and engineered grafts continue to face postimplantation challenges. Here, we describe the development and application of a durable small-diameter vascular graft with tailored regenerative capacity. We fabricated small-diameter vascular grafts by electrospinning fibrin tubes and poly(ε-caprolactone) fibrous sheaths, which improved suture retention strength and enabled long-term survival. Using surface topography in a hollow fibrin microfiber tube, we enable immediate, controlled perfusion and formation of a confluent endothelium within 3-4 days in vitro with human endothelial colony-forming cells, but a stable endothelium is noticeable at 4 weeks in vivo. Implantation of acellular or endothelialized fibrin grafts with an external ultrathin poly(ε-caprolactone) sheath as an interposition graft in the abdominal aorta of a severe combined immunodeficient Beige mouse model supports normal blood flow and vessel patency for 24 weeks. Mechanical properties of the implanted grafts closely approximate the native abdominal aorta properties after just 1 week in vivo. Fibrin mediated cellular remodeling, stable tunica intima and media formation, and abundant matrix deposition with organized collagen layers and wavy elastin lamellae. Endothelialized grafts evidenced controlled healthy remodeling with delayed and reduced macrophage infiltration alongside neo vasa vasorum-like structure formation, reduced calcification, and accelerated tunica media formation. Our studies establish a small-diameter graft that is fabricated in less than 1 week, mediates neotissue formation and incorporation into the native tissue, and matches the native vessel size and mechanical properties, overcoming main challenges in arterial bypass surgery., Competing Interests: Conflict of interest statement: M.B.E., B.G., H-Q.M., and S.G. have filed intellectual property related to this work through Johns Hopkins Technology Ventures.

Background: Given the shortage of donor organs in pediatric heart transplantation (HTx), pretransplant risk stratification may assist in organ allocation and recipient optimization. We sought to construct a scoring system to preoperatively stratify a patient's risk of one-year mortality after HTx., Methods: The United Network for Organ Sharing database was queried for pediatric (<18 years) patients undergoing HTx between 2000 and 2016. The population was randomly divided in a 4:1 fashion into derivation and validation cohorts. A multivariable logistic regression model for one-year mortality was constructed within the derivation cohort. Points were then assigned to independent predictors ( P < .05) based on relative odds ratios (ORs). Risk groups were established based on easily applicable, whole-integer score cutoffs., Results: A total of 5,700 patients underwent HTx; one-year mortality was 10.7%. There was a similar distribution of variables between derivation (n = 4,560) and validation (n = 1,140) cohorts. Of the 12 covariates included in the final model, nine were allotted point values. The low-risk (score 0-9), intermediate-risk (10-20), and high-risk (>20) groups had a 5.18%, 10%, and 28% risk of one-year mortality ( P < .001), respectively. Both intermediate-risk (OR = 2.46, 95% confidence interval [95% CI]: 1.93-3.15; P < .001) and high-risk (OR = 9.24, 95% CI: 6.92-12.35; P < .001) scores were associated with an increased risk of one-year mortality when compared to the low-risk group., Conclusions: The Children's Heart Assessment Tool for Transplantation score represents a pediatric-specific, recipient-based system to predict one-year mortality after HTx. Its use could assist providers in identification of patients at highest risk of poor outcomes and may aid in pretransplant optimization of these children.

Ischemic cardiomyopathy poses a significant public health burden due to the irreversible loss of functional cardiac tissue. Alternative treatment strategies include creation of three-dimensional (3D) cardiac tissues to both replace and augment injured native tissue. In this study, we utilize a net mold-based method to create a biomaterial-free 3D cardiac tissue and compare it to current methods using biomaterials. Cardiomyocytes, fibroblasts, and endothelial cells were combined using a hanging drop method to create spheroids. For the net mold patch method, spheroids were seeded into a net mold-based system to create biomaterial-free 3D cardiac patches. For the gel patch, spheroids were embedded in a collagen gel. Immunohistochemistry revealed increased alignment, vascularization, collagen I expression, cell viability, and higher density of cells in the net mold patch compared with the gel patch. Furthermore, in vivo testing in a left anterior descending artery ligation rat model found increased ejection fraction and smaller scar area following implantation of the net mold patch. We present a novel and simple reproducible method to create biomaterial-free 3D net mold patches that may potentially improve the treatment of heart failure in the future.

Impact Statement: We utilized innovative textile technology to create tissue-engineered vascular grafts (TEVGs) comprised exclusively of rapidly degrading material poly(glycolic acid). Our new technology led to robust neotissue formation in the TEVGs, especially extracellular matrix formation, such as elastin. In addition, the rapid degradation of the polymer significantly reduced complications, such as stenosis or calcification, as seen with the use of slow degrading polymers in the majority of previous studies for aortic small diameter TEVGs.

There has not been a multicenter investigation to elucidate the prevalence and impact of congenital diaphragmatic hernia (CDH) on children undergoing cardiac surgery. We investigated the prevalence of CDH across congenital cardiac diagnostic and procedural groups and its impact on outcomes. The STS Congenital Heart Surgery Database was queried to identify children undergoing cardiac surgery who also had CDH. Baseline perioperative characteristics and postoperative outcomes were compared between groups. Subgroup analyses were performed based on case complexity as determined by STAT Categories. Overall 426 of 157,419 (0.27%) pediatric patients undergoing an index cardiac operation had a diagnosis of CDH including 89 neonates (0.25% of all neonatal index operations), 217 infants (0.39%), and 120 children (0.18%). The frequency of concomitant CDH varied across diagnostic groups and, in neonates and infants, was highest for tetralogy of Fallot (0.45%, n = 41), coarctation (0.39%, n = 27) and complete atrioventricular septal defects (0.31%, n = 19). For neonates and infants outcomes were generally worse in CDH vs no-CDH patients across the various procedural strata. For example, STAT ≥3 operative mortality was 34.4% vs 10.3% ( P < 0.001) for neonates, and 24.2% vs 5.3% ( P < 0.001) for infants with vs without CDH, respectively. In older children, outcomes disparities were less clear cut with no significant differences in mortality, and variable differences for complication and length of stay outcomes. CDH occurs in a small percentage of patients born with congenital heart disease. Concomitant diagnosis of CDH portends increased morbidity and mortality in infants and neonates undergoing cardiac surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Valve-sparing root replacement is an attractive alternative to composite mechanical or biologic prostheses for aortic root aneurysms in children. Data on outcomes in pediatric patients are limited. We present our institutional experience with 100 consecutive pediatric valve-sparing aortic root procedures., Methods: All children who underwent valve-sparing root replacement at our institution from May 1997 to August 2017 were identified, and echocardiographic and clinical data were reviewed. The primary end point was mortality, and secondary end points included complications, further interventions, and subsequent valvular dysfunction., Results: Median age at operation was 13.6 years (interquartile range, 9.42-15.9); 51 patients (51%) had Marfan syndrome, and 39 patients (39%) had Loeys-Dietz syndrome. Mean preoperative maximum sinus diameter was 4.4 ± 0.71 cm (z score 7.3 [5.7-9.3]). Most patients (n = 80, 80%) underwent reimplantation procedures with a Valsalva graft. Four patients (4%) underwent David I reimplantation with a straight-tube graft, 13 patients (13%) underwent a Yacoub remodeling procedure, and 3 patients (3%) underwent a Florida sleeve procedure. Perioperative valve-sparing root replacement mortality was 2% (n = 2). Six patients required late reintervention for development of pseudoaneurysms. Eight patients underwent additional aortic surgery. Average time to reoperation was 7.23 ± 4.56 years. Of the 84 patients undergoing a reimplantation procedure, 5 (5.9%) underwent late valve replacement versus 5 (33.3%) of the 15 patients who received a remodeling procedure (P = .001)., Conclusions: Valve-sparing root replacement is a safe and effective option for children with aortic root aneurysms in children. The reimplantation procedure is preferred. Late aortic insufficiency and pseudoaneurysm formation remain late concerns., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

The distribution of periodic patterns of materials with radial or bilateral symmetry is a universal natural design principle. Among the many biological forms, tubular shapes are a common motif in many organisms, and they are also important for bioimplants and soft robots. However, the simple design principle of strategic placement of 3D printed segments of swelling and nonswelling materials to achieve widely different functionalities is yet to be demonstrated. Here, we report the design, fabrication, and characterization of segmented 3D printed gel tubes composed of an active thermally responsive swelling gel (poly N-isopropylacrylamide) and a passive thermally nonresponsive gel (polyacrylamide). Using finite element simulations and experiments, we report a variety of shape changes including uniaxial elongation, radial expansion, bending, and gripping based on two gels. Actualization and characterization of thermally induced shape changes are of key importance to robotics and biomedical engineering. Our studies present rational approaches to engineer complex parameters with a high level of customization and tunability for additive manufacturing of dynamic gel structures.

While pediatric HeartWare HVAD application has increased, determining candidacy and timing for initiation of pediatric VAD support has remained a challenge. We present our experience with a systematic approach to HVAD implantation as a bridge to pediatric heart transplantation. We performed a retrospective, single center review of pediatric patients (n = 11) who underwent HVAD implantation between September 2014 and January 2018. Primary endpoints evaluated were survival to heart transplantation, need for right ventricular assist device (RVAD) at any point, ongoing HVAD support, or death. Median patient age was 11 years (range: 3-16). Median BSA was 1.25 m 2 (range: 0.56-2.1). Heart failure etiologies requiring support were dilated cardiomyopathy (n = 8), myocarditis (n = 1), congenital mitral valve disease (n = 1), and single ventricle heart failure (n = 1). Median time from cardiac ICU admission for heart failure to HVAD placement was 15 days (range 3-55), based on standardized VAD implantation criteria involving imaging assessment and noncardiac organ evaluation. The majority of patients (91%) were INTERMACS Level 2 at time of implant. Three patients (27%) had CentriMag RVAD placement at time of HVAD implantation. Two of these three patients had successful RVAD explanation within 2 weeks. Median length of HVAD support was 60 days (range 6-405 days). Among the 11 patients, survival during HVAD therapy to date is 91% (10/11) with 9 (82%) bridged to heart transplantation and one (9%) continuing to receive support. Posttransplant survival has been 100%, with median follow-up of 573 days (range 152-1126). A systematic approach to HVAD implantation can provide excellent results in pediatric heart failure management for a variety of etiologies and broad BSA range., (© 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Cardiopulmonary bypass perfusion management significantly affects postoperative outcomes. In recent years, the principles of goal-directed therapy have been applied to the field of cardiothoracic surgery to improve patient outcomes. Goal-directed therapy involves continuous peri- and postoperative monitoring of vital clinical parameters to tailor perfusion to each patient's specific needs. Closely measured parameters include fibrinogen, platelet count, lactate, venous oxygen saturation, central venous oxygen saturation, mean arterial pressure, perfusion flow rate, and perfusion pulsatility. These parameters have been shown to influence postoperative fresh frozen plasma transfusion rate, coagulation state, end-organ perfusion, and mortality. In this review, we discuss the recent paradigm shift in pediatric perfusion management toward goal-directed perfusion.

This protocol describes a novel and easy net mold-based method to create three-dimensional (3-D) cardiac tissues without additional scaffold material. Human-induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs), human cardiac fibroblasts (HCFs), and human umbilical vein endothelial cells (HUVECs) are isolated and used to generate a cell suspension with 70% iPSC-CMs, 15% HCFs, and 15% HUVECs. They are co-cultured in an ultra-low attachment "hanging drop" system, which contains micropores for condensing hundreds of spheroids at one time. The cells aggregate and spontaneously form beating spheroids after 3 days of co-culture. The spheroids are harvested, seeded into a novel mold cavity, and cultured on a shaker in the incubator. The spheroids become a mature functional tissue approximately 7 days after seeding. The resultant multilayered tissues consist of fused spheroids with satisfactory structural integrity and synchronous beating behavior. This new method has promising potential as a reproducible and cost-effective method to create engineered tissues for the treatment of heart failure in the future.

Most tissue-engineered arterial grafts are complicated by aneurysmal dilation secondary to insufficient neotissue formation after scaffold degradation. The optimal graft would form an organized multilayered structure with a robust extracellular matrix that could withstand arterial pressure. The purpose of the current study was to determine how oversizing a biodegradable arterial scaffold affects long-term neotissue formation. Size-matched (1.0 mm, n = 11) and oversized (1.6 mm, n = 9) electrospun polycaprolactone/chitosan scaffolds were implanted as abdominal aortic interposition grafts in Lewis rats. The mean lumen diameter of the 1.6 mm grafts was initially greater compared with the native vessel, but matched the native aorta by 6 months. In contrast, the 1.0 mm grafts experienced stenosis at 6 and 9 months. Total neotissue area and calponin-positive neotissue area were significantly greater in the 1.6 mm grafts by 6 months and similar to the native aorta. Late-term biomechanical testing was dominated by remaining polymer, but graft oversizing did not adversely affect the biomechanics of the adjacent vessel. Oversizing tissue-engineered arterial grafts may represent a strategy to increase the formation of organized neotissue without thrombosis or adverse remodeling of the adjacent native vessel by harnessing a previously undescribed process of adaptive vascular remodeling.

Reconstruction is challenging in a patient with loss of a segment of Achilles tendon and infection in the overlying soft tissue. Here the authors describe one-stage tendon reconstruction, using an anterolateral thigh free flap incorporating a vascularized muscle flap and a strip of iliotibial tract in a patient with re-rupture of an Achilles tendon and soft tissue infection. Postoperative immobilization of the affected ankle using an external fixator enabled us to observe the flap directly and reduce pressure on the flap. The patient had a successful outcome, with no difficulty in walking, running, or climbing stairs and no limitation of range of motion at the ankle joint postoperatively. This is a promising technique for reconstruction of the Achilles tendon and treatment of infection as a one-step procedure.

Purpose: Patients with hypoplastic left heart syndrome (HLHS) present a diverse spectrum of aortic arch morphology. Suboptimal geometry of the reconstructed aortic arch may result from inappropriate size and shape of an implanted patch and may be associated with poor outcomes. Meanwhile, advances in diagnostic imaging, computer-aided design, and three-dimensional (3D) printing technology have enabled the creation of 3D models. The purpose of this study is to create a surgical simulation and training model for aortic arch reconstruction., Description: Specialized segmentation software was used to isolate aortic arch anatomy from HLHS computed tomography scan images to create digital 3D models. Three-dimensional modeling software was used to modify the exported segmented models and digitally design printable customized patches that were optimally sized for arch reconstruction., Evaluation: Life-sized models of HLHS aortic arch anatomy and a digitally derived customized patch were 3D printed to allow simulation of surgical suturing and reconstruction. The patient-specific customized patch was successfully used for surgical simulation., Conclusions: Feasibility of digital design and 3D printing of patient-specific patches for aortic arch reconstruction has been demonstrated. The technology facilitates surgical simulation. Surgical training that leads to an understanding of optimal aortic patch geometry is one element that may potentially influence outcomes for patients with HLHS.

Objective: The safety of surgical closure of patent ductus arteriosus (PDA) in very low birth weight premature neonates has been questioned because of associated morbidities. However, these studies are vulnerable to significant bias as surgical ligation has historically been utilized as "rescue" therapy. The objective of this study was to review our institutions' outcomes of surgical PDA ligation., Methods: All neonates with operative weight of ≤1.00 kg undergoing surgical PDA ligation from 2003 to 2015 were analyzed. Records were queried to identify surgical complications, perioperative morbidity, and mortality. Outcomes included pre- and postoperative ventilator requirements, pre- and postoperative inotropic support, acute kidney injury, surgical complications, and 30-day mortality., Results: One hundred sixty-six preterm neonates underwent surgical ligation. One hundred twenty-one (70.3%) had failed indomethacin closure. One hundred sixty-four (98.8%) patients required mechanical ventilation prior to surgery. At 17 postoperative days, freedom from the ventilator reached 50%. Of 109 (66.4%) patients requiring prolonged preoperative inotropic support, 59 (54.1%) were liberated from inotropes by postoperative day 1. Surgical morbidity was encountered in four neonates (2.4%): two (1.2%) patients had a postoperative pneumothorax requiring tube thoracostomy, one (0.6%) patient had a recurrent laryngeal nerve injury, and one (0.6%) patient had significant intraoperative bleeding. The 30-day all-cause mortality was 1.8% (n = 3); no deaths occurred intraoperatively., Conclusion: In this retrospective investigation, surgical PDA closure was associated with low 30-day mortality and minimal morbidity and resulted in rapid discontinuation of inotropic support and weaning from mechanical ventilation. Given the safety of this intervention, surgical PDA ligation merits consideration in the management strategy of the preterm neonate with a PDA.

Background: Although tricuspid valve detachment (TVD) facilitates improved exposure during transatrial ventricular septal defect (VSD) closure, few have analyzed the impact of TVD on long-term valve durability., Methods: Pediatric patients undergoing VSD closure at our institution from 1997 to 2013 were identified, and charts were retrospectively reviewed. Patients were separated into groups based on utilization of TVD. Propensity score matching was then performed using a nonparsimonious logistic regression model involving 7 variables. Primary outcome was residual TV dysfunction at long-term follow-up, defined as mild (2+) and moderate (3+) TV regurgitation (TR) on follow-up echocardiography. Secondary outcomes included postoperative atrioventricular dissociation, residual VSD, and reinterventions., Results: A total of 247 patients underwent VSD closure; 164 (66.4%) without TVD and 83 (33.6%) with TVD. Median follow-up time was 2,343 days (interquartile range, 1,237 to 3,963.5 days) in the group without TVD versus 1,606 days (interquartile range, 826 to 3,017 days) in those with TVD. After successfully matching 83 patients, 29 of 83 (34.9%) patients in the non-TVD group had mild TR versus 28 of 83 (33.7%) patients in the TVD group (p = 0.87). 2 patients in the non-TVD group had moderate TR versus 1 patient in the TVD group at long-term follow-up. One patient in each group suffered transient atrioventricular block, but neither required pacemaker insertion., Conclusions: TVD did not compromise long-term valve durability and did not impose increased morbidity. Patients who underwent TVD had a similar prevalence of mild TR to patients without TVD. Moderate TR was exceptionally rare in both groups. When exposure is difficult, TVD is a safe and effective technical adjunct., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder predisposing patients to aneurysm formation and arterial dissection. Aortic root replacement is often performed prophylactically and valve-sparing root replacement (VSRR) has become the procedure of choice. However, in these patients with connective tissue disorders, postoperative pseudoaneurysms may develop., Methods: All children with LDS undergoing VSRR at a single institution were retrospectively reviewed to identify patients who developed postoperative pseudoaneurysms., Results: Thirty-one children with LDS underwent VSRR; four of these developed pseudoaneurysms of their synthetic aortic root grafts requiring reoperation. These four children were reviewed to investigate the cause of pseudoaneurysm formation after VSRR. Each had severe subtypes of LDS. Each underwent reoperation for repair of their pseudoaneurysms and were found to have suffered pseudoaneurysms as a result of tearing of sutures from their reimplantation VSRR., Conclusions: Pseudoaneurysms following aortic root replacement with VSRR can occur in children with severe subtypes of LDS. Long-term surveillance is required to detect these potentially life-threatening lesions., (© 2018 Wiley Periodicals, Inc.)

We present seven cases of a relatively rare swan neck deformity resulting from chronic radial collateral ligament (RCL) injury of the proximal interphalangeal (PIP) joint in the little finger. All patients were middle-aged women (mean 51 years old, range 42-55), and the duration between the initial injury and surgery was 20 years (range 5-40). The chief complaint was painful snapping of the PIP joint. All patients had hyperextension and ulnar deviation of the PIP joint with mobile swan neck deformities that had not improved with conservative treatment. Radiographs revealed osteoarthritis and ulnar deviation of the PIP joints in all cases. We describe a method for reconstruction of both the palmar plate and the RCL of the affected PIP joint using a distally-based ulnar slip of flexor superficialis tendon. The prevention of PIP joint hyperextension was critical for successful resolution of symptoms; the aim of RCL augmentation was to prevent the recurrence of the deformity., Level of Evidence: IV.

Objectives: Virtual reality (VR) allows users to experience realistic, immersive 3D virtual environments with the depth perception and binocular field of view of real 3D settings. Newer VR technology has now allowed for interaction with 3D objects within these virtual environments through the use of VR controllers. This technical note describes our preliminary experience with VR as an adjunct tool to traditional angiographic imaging in the preprocedural workup of a patient with a complex pseudoaneurysm., Methods: Angiographic MRI data was imported and segmented to create 3D meshes of bilateral carotid vasculature. The 3D meshes were then projected into VR space, allowing the operator to inspect the carotid vasculature using a 3D VR headset as well as interact with the pseudoaneurysm (handling, rotation, magnification, and sectioning) using two VR controllers., Results: 3D segmentation of a complex pseudoaneurysm in the distal cervical segment of the right internal carotid artery was successfully performed and projected into VR. Conventional and VR visualization modes were equally effective in identifying and classifying the pathology. VR visualization allowed the operators to manipulate the dataset to achieve a greater understanding of the anatomy of the parent vessel, the angioarchitecture of the pseudoaneurysm, and the surface contours of all visualized structures., Conclusion: This preliminary study demonstrates the feasibility of utilizing VR for preprocedural evaluation in patients with anatomically complex neurovascular disorders. This novel visualization approach may serve as a valuable adjunct tool in deciding patient-specific treatment plans and selection of devices prior to intervention.

Objective: New platforms for patient imaging present opportunities for improved surgical planning in complex congenital heart disease (CHD). Virtual reality (VR) allows for interactive manipulation of high-resolution representations of patient-specific imaging data, as a supplement to traditional 2D visualizations and 3D printed heart models., Design: We present the novel use of VR for the presurgical planning of cardiac surgery in two infants with complex CHD to demonstrate interactive real-time views of complex intra and extracardiac anatomy., Results: The use of VR for cardiac presurgical planning is feasible using existing imaging data. The software was evaluated by both pediatric cardiac surgeons and pediatric cardiologists, and felt to be reliable and operated with a very short learning curve., Conclusions: VR with controller-based interactive capability allows for interactive viewing of 3D models with complex intra and extracardiac anatomy. This serves as a useful complement to traditional preoperative planning methods in terms of its potential for group based collaborative discussion, user defined illustrative views, cost-effectiveness, and facility of use., (© 2018 Wiley Periodicals, Inc.)

3D and 4D bioprinting of the heart are exciting notions in the modern era. However, myocardial bioprinting has proven to be challenging. This review outlines the methods, materials, cell types, issues, challenges, and future prospects in myocardial bioprinting. Advances in 3D bioprinting technology have significantly improved the manufacturing process. While scaffolds have traditionally been utilized, 3D bioprinters, which do not require scaffolds, are increasingly being employed. Improved understanding of the cardiac cellular composition and multiple strategies to tackle the issues of vascularization and viability had led to progress in this field. In vivo studies utilizing small animal models have been promising. 4D bioprinting is a new concept that has potential to advance the field of 3D bioprinting further by incorporating the fourth dimension of time. Clinical translation will require multidisciplinary collaboration to tackle the pertinent issues facing this field.

As the incidence of cardiovascular disease continues to climb worldwide, there is a corresponding increase in demand for surgical interventions involving vascular grafts. The current gold standard for vascular grafts is autologous vessels, an option often excluded due to disease circumstances. As a result, many patients must resort to prosthetic options. While widely available, prosthetic grafts have been demonstrated to have inferior patency rates compared with autologous grafts due to inflammation and thrombosis. In an attempt to overcome these limitations, many different materials for constructing vascular grafts, from modified synthetic nondegradable polymers to biodegradable polymers, have been explored, many of which have entered the translational stage of research. This article reviews these materials in the context of large animal models, providing an outlook on the preclinical potential of novel biomaterials as well as the future direction of vascular graft research.

Background: Despite advances in the Fontan procedure, there is an unmet clinical need for patient-specific graft designs that are optimized for variations in patient anatomy. The objective of this study is to design and produce patient-specific Fontan geometries, with the goal of improving hepatic flow distribution (HFD) and reducing power loss (P loss ), and manufacturing these designs by electrospinning., Methods: Cardiac magnetic resonance imaging data from patients who previously underwent a Fontan procedure (n = 2) was used to create 3-dimensional models of their native Fontan geometry using standard image segmentation and geometry reconstruction software. For each patient, alternative designs were explored in silico, including tube-shaped and bifurcated conduits, and their performance in terms of P loss and HFD probed by computational fluid dynamic (CFD) simulations. The best-performing options were then fabricated using electrospinning., Results: CFD simulations showed that the bifurcated conduit improved HFD between the left and right pulmonary arteries, whereas both types of conduits reduced P loss . In vitro testing with a flow-loop chamber supported the CFD results. The proposed designs were then successfully electrospun into tissue-engineered vascular grafts., Conclusions: Our unique virtual cardiac surgery approach has the potential to improve the quality of surgery by manufacturing patient-specific designs before surgery, that are also optimized with balanced HFD and minimal P loss , based on refinement of commercially available options for image segmentation, computer-aided design, and flow simulations., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Spheroids are increasingly being employed to answer a wide range of clinical and biomedical inquiries ranging from pharmacology to disease pathophysiology, with the ultimate goal of using spheroids for tissue engineering and regeneration. When compared to traditional two-dimensional cell culture, spheroids have the advantage of better replicating the 3D extracellular microenvironment and its associated growth factors and signaling cascades. As knowledge about the preparation and maintenance of spheroids has improved, there has been a plethora of translational experiments investigating in vivo implantation of spheroids into various animal models studying tissue regeneration. We review methods for spheroid delivery and how they have been utilized in tissue engineering experiments. We break down efforts in this field by organ systems, discussing applications of spheroids to various animal models of disease processes and their potential clinical implications. These breakthroughs have been made possible by advancements in spheroid formation, in vivo delivery and assessment. There is unexplored potential and room for further research and development in spheroid-based tissue engineering approaches. Regenerative medicine and other clinical applications ensure this exciting area of research remains relevant for patient care., (Copyright © 2018 Elsevier Inc. All rights reserved.)

To prevent bone metastasis, we developed polyethylene glycol (PEG)-conjugated aspartic acid (Asp)-modified liposomes (PEG-Asp-Lipo) as a bone-targeting carrier of paclitaxel (PTX) by using Asp-modified 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE-Asp). The affinity of Asp-modified liposomes to hydroxyapatite increased as the concentration of DPPE-Asp increased. The bone accumulation of [ 3 H]-labeled PEG(2)-Asp(33)-Lipo was approximately 24.6% 360 min after intravenous injection in mice, in contrast to 5.4% and 6.7% of [ 3 H]-labeled normal Lipo and PEG(2)-Lipo, respectively. Similarly, [ 14 C]-labeled PTX encapsulated into PEG(2)-Asp(33)-Lipo predominantly accumulated in the bone. Furthermore, using an in situ imaging experiment, we observed that near-infrared fluorescence-labeled PEG(2)-Asp(33)-Lipo selectively accumulated in the bone near the joint after intravenous injection in mice. We also found that FITC-labeled PEG(2)-Asp(33)-Lipo predominantly accumulated on eroded and quiescent bone surfaces. In a bone metastatic tumor mouse model, in which B16-BL6/Luc cells were injected into the left ventricle of female C57BL/6 mice, metastatic bone tumor growth was significantly inhibited by an intravenous injection of PEG(2)-Asp(33)-liposomal PTX. In contrast, PEGylated liposomal PTX hardly affected the growth of metastatic bone tumors. These findings indicate that PEG(2)-Asp(33)-Lipo is a promising bone-targeting carrier for the delivery of PTX and treatment of bone metastasis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Loeys-Deitz syndrome (LDS) is a connective tissue disorder characterized by aggressive aortopathy with a proclivity for aortic aneurysmal rupture and dissection. Prophylactic surgical intervention is often indicated to ameliorate risk of aneurysm rupture. Aortic root replacement involves excision of the coronary arteries from the aortic root with a button of surrounding aortic tissue and subsequent anastomosis of these buttons to the synthetic aortic graft. We report the case of a 16-year-old girl with LDS who developed pseudoaneurysms at the sites of previous coronary button implantation., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Electrospinning is a promising technology that provides biodegradable nanofiber scaffolds for cardiovascular tissue engineering. However, success with these materials has been limited, and the optimal combination of scaffold parameters for a tissue-engineered vascular graft (TEVG) remains elusive. The purpose of the present study is to evaluate the effect of bone marrow mononuclear cell (BM-MNC) seeding in electrospun scaffolds to support the rational design of optimized TEVGs., Methods: Nanofiber scaffolds were fabricated from co-electrospinning a solution of polyglycolic acid and a solution of poly(ι-lactide-co-ɛ-caprolactone) and characterized with scanning electron microscopy. Platelet activation and cell seeding efficiency were assessed by ATP secretion and DNA assays, respectively. Cell-free and BM-MNC seeded scaffolds were implanted in C57BL/6 mice (n = 15/group) as infrarenal inferior vena cava (IVC) interposition conduits. Animals were followed with serial ultrasonography for 6 months, after which grafts were harvested for evaluation of patency and neotissue formation by histology and immunohistochemistry (n = 10/group) and PCR (n = 5/group) analyses., Results: BM-MNC seeding of electrospun scaffolds prevented stenosis compared with unseeded scaffolds (seeded: 9/10 patent vs. unseeded: 1/10 patent, p = 0.0003). Seeded vascular grafts demonstrated concentric laminated smooth muscle cells, a confluent endothelial monolayer, and a collagen-rich extracellular matrix. Platelet-derived ATP, a marker of platelet activation, was significantly reduced after incubating thrombin-activated platelets in the presence of seeded scaffolds compared with unseeded scaffolds (p < 0.0001). In addition, reduced macrophage infiltration and a higher M2 macrophage percentage were observed in seeded grafts., Conclusions: The beneficial effects of BM-MNC seeding apply to electrospun TEVG scaffolds by attenuating stenosis through the regulation of platelet activation and inflammatory macrophage function, leading to well-organized neotissue formation. BM-MNC seeding is a valuable technique that can be used in the rational design of optimal TEVG scaffolds.

Recent advances have allowed for three-dimensional (3D) printing technologies to be applied to biocompatible materials, cells and supporting components, creating a field of 3D bioprinting that holds great promise for artificial organ printing and regenerative medicine. At the same time, stem cells, such as human induced pluripotent stem cells, have driven a paradigm shift in tissue regeneration and the modeling of human disease, and represent an unlimited cell source for tissue regeneration and the study of human disease. The ability to reprogram patient-specific cells holds the promise of an enhanced understanding of disease mechanisms and phenotypic variability. 3D bioprinting has been successfully performed using multiple stem cell types of different lineages and potency. The type of 3D bioprinting employed ranged from microextrusion bioprinting, inkjet bioprinting, laser-assisted bioprinting, to newer technologies such as scaffold-free spheroid-based bioprinting. This review discusses the current advances, applications, limitations and future of 3D bioprinting using stem cells, by organ systems.

In this report we present a case of re-stabilization of the proximal radius using vascularized free fibular graft combined with anconeus arthroplasty to stabilize the transplanted fibula in a patient with large loss of the proximal radius due to Ewing's sarcoma. A 20-year-old woman had Ewing's sarcoma in the proximal three-fourths of the radius. The resection of large part of the radius containing radial head were necessary for removal of the sarcoma. Reconstruction of the proximal radius was performed using vascularized free fibular graft and the transplanted fibula was stabilized by attaching the anconeus to the proximal edge of the fibula. 2 years after surgery, she had neither recurrence nor metastasis, and achieved functional recovery. The combination anconeus arthroplasty with vascularized free fibular graft can be a good technique for re-stabilization of the elbow and recovery of the forearm function.

There remains a need for large animal models to evaluate tissue-engineered vascular grafts (TEVGs) under arterial pressure to provide preclinical data for future potential human clinical trials. We present a comprehensive method for the interrogation of TEVGs, using an ovine bilateral arteriovenous (AV) shunt implantation model. Our results demonstrate that this method can be performed safely without complications, specifically acute heart failure, steal syndrome, and hypoxic brain injury, and it is a viable experimental paradigm. Our method allows for a non-invasive evaluation of TEVGs in terms of graft flow, graft diameter, and graft patency, while also allowing for graft needle puncture under ultrasound guidance. In addition, traditional pathological analysis, histology, and immunohistochemistry may be performed with the contralateral side providing paired control data to eliminate inter-subject variability while reducing the total number of animals. Further, we present a review of existing literature of preclinical evaluation of TEVGs in large animal models as AV conduits.

Objectives: Our goal was to evaluate the early and late results of the surgical management of congenital supravalvular aortic stenosis (SVAS)., Methods: We performed a retrospective, multicentre study using data from the European Congenital Heart Surgeons Association. Exclusion criteria were age >18 years, operation before 1990 and redo supravalvular aortic stenosis operations. Multivariate Cox regression analysis was performed to detect independent predictors of adverse events., Results: Of a total of 301 patients (male/female = 194/107; median age 3.9 years, range 13 days-17.9 years), 17.6% had a prior surgical or interventional procedure. Pulmonary artery stenosis was present in 41.5% and coronary anomalies in 13.6%. The operation consisted of a single patch repair in 36.7%, a pantaloon-shaped patch in 36.7%, a 3-patch technique in 14.3% and other techniques in 11.7%. Postoperative complications occurred in 14.9%, and the early mortality rate was 5%. At a median follow-up of 13 years (interquartile range 3.5-7.8; follow-up completed 79.1%), there were 10 late deaths (4.2%). A surgical reoperation or an interventional cardiology procedure occurred in 12.6% and 7.2%, respectively. No significant differences in outcomes between the techniques were found. Age at repair <12 months and pulmonary artery stenosis were associated with an increased risk of early (P = 0.0001) and overall mortality (P = 0.025), respectively. Having an operation after 2005 and co-existing pulmonary artery stenosis were significant predictors of late reintervention (P = 0.0110 and P = 0.001, respectively)., Conclusions: Surgical repair of congenital stenosis is an effective procedure with acceptable surgical risk and good late survival, but late morbidity is not negligible, especially in infants and when associated pulmonary artery stenosis is present., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Despite advances in surgical technique and postoperative care, long-term survival of children born with hypoplastic left heart syndrome (HLHS) remains limited, with cardiac transplantation as the only alternative for patients with failing single ventricle circulations. Maintenance of systemic right ventricular function is crucial for long-term survival, and interventions that improve ventricular function and avoid or defer transplantation in patients with HLHS are urgently needed. We hypothesize that the young myocardium of the HLHS patient is responsive to the biological cues delivered by bone marrow-derived mesenchymal stem cells (MSCs) to improve and preserve right ventricle function. The ELPIS trial (Allogeneic Human MEsenchymal Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome: An Open Label Pilot Study) is a phase I/IIb trial designed to test whether MSC injection will be both safe and feasible by monitoring the first 10 HLHS patients for new major adverse cardiac events. If our toxicity stopping rule is not activated, we will proceed to the phase IIb component of our study where we will test our efficacy hypothesis that MSC injection improves cardiac function compared with surgery alone. Twenty patients will be enrolled in a randomized phase II trial with a uniform allocation to MSC injection versus standard surgical care (no injection). The 2 trial arms will be compared with respect to improvement of right ventricular function, tricuspid valve annulus size, and regurgitation determined by cardiac magnetic resonance and reduced mortality, morbidity, and need for transplantation. This study will establish the safety and feasibility of allogeneic mesenchymal stem cell injection in HLHS patients and provide important insights in the emerging field of stem cell-based therapy for congenital heart disease patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In this study, we aimed to develop a polyethylene glycol (PEG)-conjugated third generation polyamidoamine (PAMAM) dendrimer with multiple carboxylic acids as a bone-targeting carrier for the treatment of bone diseases. We conjugated PAMAM backbones to various carboxylic acids [aspartic acid (Asp), glutamic acid (Glu), succinic acid (Suc), or aconitic acid (Aco)] to obtain four different types of carboxylic acid-modified PAMAMs. PEG was covalently bound to carboxylic acid-modified PAMAMs to obtain PEGylated carboxylic acid-modified PAMAMs. In a tissue distribution study, the amount of 111 In-labeled unmodified PAMAM taken up by the bone after intravenous injection in mice was 11.3%. In contrast, the dose of 111 In-labeled PEG(5)-Asp-PAMAM, PEG(5)-Glu-PAMAM, PEG(5)-Suc-PAMAM, or PEG(5)-Aco-PAMAM that accumulated in the bone after injection was approximately 46.0, 15.6, 22.6, and 24.5%, respectively. The bone clearance rates of 111 In-labeled PEGylated carboxylic acid-modified PAMAMs were proportional to their affinities to hydroxyapatite and Ca 2+ . An intra-bone distribution study showed that fluorescein isothiocyanate-labeled PEG(5)-Asp-PAMAM predominantly accumulated on eroded and quiescent surfaces, a pattern associated with the pathogenesis of bone diseases, such as rheumatoid arthritis and osteoporosis. Our findings indicate that PEG(5)-Asp-PAMAM is a promising drug carrier for efficient drug targeting to the bones., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We describe the use of veno-arterial extracorporeal membrane oxygenation (ECMO) in a 35-year-old female with severe fixed pulmonary hypertension who went into cardiogenic shock during a Cesarean section. Pregnancy in the presence of severe pulmonary hypertension is typically contraindicated due to high maternal mortality rates. This patient visited our hospital at 37 weeks of gestation after experiencing dyspnea and chest pain. Clinical evaluation revealed severe fixed pulmonary hypertension. At the time of the planned delivery, femoral lines were placed; in case of emergency, ECMO became necessary during the delivery. During delivery, the patient developed sudden hemodynamic collapse necessitating rapid cannulation and initiation of ECMO. She was stabilized pharmacologically and separated from ECMO after 2 days. The baby was delivered uneventfully, and the mother and child were discharged 1 month after delivery.

We have developed a novel method to deliver stem cells using 3D bioprinted cardiac patches, free of biomaterials. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), fibroblasts (FB) and endothelial cells (EC) were aggregated to create mixed cell spheroids. Cardiac patches were created from spheroids (CM:FB:EC = 70:15:15, 70:0:30, 45:40:15) using a 3D bioprinter. Cardiac patches were analyzed with light and video microscopy, immunohistochemistry, immunofluorescence, cell viability assays and optical electrical mapping. Cardiac tissue patches of all cell ratios beat spontaneously after 3D bioprinting. Patches exhibited ventricular-like action potential waveforms and uniform electrical conduction throughout the patch. Conduction velocities were higher and action potential durations were significantly longer in patches containing a lower percentage of FBs. Immunohistochemistry revealed staining for CM, FB and EC markers, with rudimentary CD31+ blood vessel formation. Immunofluorescence revealed the presence of Cx43, the main cardiac gap junction protein, localized to cell-cell borders. In vivo implantation suggests vascularization of 3D bioprinted cardiac patches with engraftment into native rat myocardium. This constitutes a significant step towards a new generation of stem cell-based treatment for heart failure.

This protocol describes 3D bioprinting of cardiac tissue without the use of biomaterials, using only cells. Cardiomyocytes, endothelial cells and fibroblasts are first isolated, counted and mixed at desired cell ratios. They are co-cultured in individual wells in ultra-low attachment 96-well plates. Within 3 days, beating spheroids form. These spheroids are then picked up by a nozzle using vacuum suction and assembled on a needle array using a 3D bioprinter. The spheroids are then allowed to fuse on the needle array. Three days after 3D bioprinting, the spheroids are removed as an intact patch, which is already spontaneously beating. 3D bioprinted cardiac patches exhibit mechanical integration of component spheroids and are highly promising in cardiac tissue regeneration and as 3D models of heart disease.

Bioprinting is a technology with the prospect to change the way many diseases are treated, by replacing the damaged tissues with live de novo created biosimilar constructs. However, after more than a decade of incubation and many proofs of concept, the field is still in its infancy. The current stagnation is the consequence of its early success: the first bioprinters, and most of those that followed, were modified versions of the three-dimensional printers used in additive manufacturing, redesigned for layer-by-layer dispersion of biomaterials. In all variants (inkjet, microextrusion, or laser assisted), this approach is material ("scaffold") dependent and energy intensive, making it hardly compatible with some of the intended biological applications. Instead, the future of bioprinting may benefit from the use of gentler scaffold-free bioassembling methods. A substantial body of evidence has accumulated, indicating this is possible by use of preformed cell spheroids, which have been assembled in cartilage, bone, and cardiac muscle-like constructs. However, a commercial instrument capable to directly and precisely "print" spheroids has not been available until the invention of the microneedles-based ("Kenzan") spheroid assembling and the launching in Japan of a bioprinter based on this method. This robotic platform laces spheroids into predesigned contiguous structures with micron-level precision, using stainless steel microneedles ("kenzans") as temporary support. These constructs are further cultivated until the spheroids fuse into cellular aggregates and synthesize their own extracellular matrix, thus attaining the needed structural organization and robustness. This novel technology opens wide opportunities for bioengineering of tissues and organs.

Traumatic lunate fractures are very rare and those treatments require an understanding of anatomical features. We present a case of an ulnolunate ligament avulsion fracture of the lunate that was successfully repaired by surgical fixation with open reduction and internal fixation. We believe that restoration of ulnolunate ligament function is important to prevent further deterioration of wrist function after this injury.

Purpose: Virtual surgery involves the planning and simulation of surgical reconstruction using three-dimensional (3D) modeling based upon individual patient data, augmented by simulation of planned surgical alterations including implantation of devices or grafts. Here we describe a case in which virtual cardiac surgery aided us in determining the optimal conduit size to use for the reconstruction of the right ventricular outflow tract., Description: The patient is a young adolescent male with a history of tetralogy of Fallot with pulmonary atresia, requiring right ventricle-to-pulmonary artery (RV-PA) conduit replacement. Utilizing preoperative magnetic resonance imaging data, virtual surgery was undertaken to construct his heart in 3D and to simulate the implantation of three different sizes of RV-PA conduit (18, 20, and 22 mm)., Evaluation: Virtual cardiac surgery allowed us to predict the ability to implant a conduit of a size that would likely remain adequate in the face of continued somatic growth and also allow for the possibility of transcatheter pulmonary valve implantation at some time in the future. Subsequently, the patient underwent uneventful conduit change surgery with implantation of a 22-mm Hancock valved conduit. As predicted, the intrathoracic space was sufficient to accommodate the relatively large conduit size without geometric distortion or sternal compression., Conclusion: Virtual cardiac surgery gives surgeons the ability to simulate the implantation of prostheses of different sizes in relation to the dimensions of a specific patient's own heart and thoracic cavity in 3D prior to surgery. This can be very helpful in predicting optimal conduit size, determining appropriate timing of surgery, and patient education.

Background: Loeys-Dietz syndrome (LDS) is an aggressive aortopathy with a proclivity for aortic aneurysm rupture and dissection at smaller diameters than other connective tissue disorders. We reviewed our surgical experience of children with LDS to validate our guidelines for prophylactic aortic root replacement (ARR)., Methods: We reviewed all children (younger than 18 years) with a diagnosis of LDS who underwent ARR at our institution. The primary endpoint was mortality, and secondary endpoints included complications and the need for further interventions., Results: Thirty-four children with LDS underwent ARR. Mean age at operation was 10 years, and 15 (44%) were female. Mean preoperative root diameter was 4 cm. Three children (9%) had composite ARR with a mechanical prosthesis, and 31 (91%) underwent valve-sparing ARR. Concomitant procedures included arch replacement in 2 (6%), aortic valve repair in 1 (3%), and patent foramen ovale closure in 16 (47%). There was no operative mortality. Two children (6%) required late replacement of the ascending aorta, 5 (15%) required arch replacement, 1 (3%) required mitral valve replacement, and 2 (6%) had coronary button aneurysms/pseudoaneurysms requiring repair. Three children required redo valve-sparing ARR after a Florida sleeve procedure, and 2 had progressive aortic insufficiency requiring aortic valve replacement after a valve-sparing procedure. There were 2 late deaths (6%)., Conclusions: These data confirm the aggressive aortopathy of LDS. Valve-sparing ARR should be performed when feasible to avoid the risks of prostheses. Serial imaging of the arterial tree is critical, given the rate of subsequent intervention., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background  The low-profile dorsal locking plating (DLP) technique is useful for treating dorsally comminuted intra-articular distal radius fractures; however, due to the complications associated with DLP, the technique is not widely used. Methods  A retrospective review of 24 consecutive cases treated with DLP were done. Results  All cases were classified into two types by surgical strategy according to the fracture pattern. In type 1, there is a volar fracture line distal to the watershed line in the dorsally displaced fragment, and this type is treated by H-framed DLP. In type 2, the displaced dorsal die-punch fragment is associated with a minimally displaced styloid shearing fracture or a transverse volar fracture line. We found that the die-punch fragment was reduced by the buttress effect of small l-shaped DLP after stabilization of the styloid shearing for the volar segment by cannulated screws from radial styloid processes. At 6 months after surgery, outcomes were good or excellent based on the modified Mayo wrist scores with no serious complications except one case. The mean range of motion of each type was as follows: the palmar flexion was 50, 65 degrees, dorsiflexion was 70, 75 degrees, supination was 85, 85 degrees, and pronation was 80, 80 degrees; in type 1 and 2, respectively. Conclusion  DLP is a useful technique for the treatment of selected cases of dorsally displaced, comminuted intra-articular fractures of the distal radius with careful soft tissue coverage.

Introduction: Conventional synthetic vascular grafts are limited by the inability to remodel, as well as issues of patency at smaller diameters. Tissue-engineered vascular grafts (TEVGs), constructed from biologically active cells and biodegradable scaffolds have the potential to overcome these limitations, and provide growth capacity and self-repair. Areas covered: This article outlines the TEVG design, biodegradable scaffolds, TEVG fabrication methods, cell seeding, drug delivery, strategies to reduce wait times, clinical trials, as well as a 5-year view with expert commentary. Expert commentary: TEVG technology has progressed significantly with advances in scaffold material and design, graft design, cell seeding and drug delivery. Strategies have been put in place to reduce wait times and improve 'off-the-shelf' capability of TEVGs. More recently, clinical trials have been conducted to investigate the clinical applications of TEVGs.

We describe the use of a pedicled unipolar latissimus dorsi flap to restore finger extension. The patient had large defects in the radial nerve and extensor musculature. A long-tailed, 50-cm-long flap was prepared, which enabled the end of the flap to be sutured to the extensor digitorum.

Background: Tissue-engineered vascular grafts (TEVGs) offer potential to overcome limitations of current approaches for reconstruction in congenital heart disease by providing biodegradable scaffolds on which autologous cells proliferate and provide physiologic functionality. However, current TEVGs do not address the diverse anatomic requirements of individual patients. This study explores the feasibility of creating patient-specific TEVGs by combining 3-dimensional (3D) printing and electrospinning technology., Methods: An electrospinning mandrel was 3D-printed after computer-aided design based on preoperative imaging of the ovine thoracic inferior vena cava (IVC). TEVG scaffolds were then electrospun around the 3D-printed mandrel. Six patient-specific TEVGs were implanted as cell-free IVC interposition conduits in a sheep model and explanted after 6 months for histologic, biochemical, and biomechanical evaluation., Results: All sheep survived without complications, and all grafts were patent without aneurysm formation or ectopic calcification. Serial angiography revealed significant decreases in TEVG pressure gradients between 3 and 6 months as the grafts remodeled. At explant, the nanofiber scaffold was nearly completely resorbed and the TEVG showed similar mechanical properties to that of native IVC. Histological analysis demonstrated an organized smooth muscle cell layer, extracellular matrix deposition, and endothelialization. No significant difference in elastin and collagen content between the TEVG and native IVC was identified. There was a significant positive correlation between wall thickness and CD68 + macrophage infiltration into the TEVG., Conclusions: Creation of patient-specific nanofiber TEVGs by combining electrospinning and 3D printing is a feasible technology as future clinical option. Further preclinical studies involving more complex anatomical shapes are warranted., (Copyright © 2016. Published by Elsevier Inc.)

Objectives: Early experience with Loeys-Dietz syndrome (LDS) suggested an aggressive aortopathy with high risk of aneurysm dissection and rupture at young ages and at smaller aortic diameters than in other connective tissue disorders. We reviewed our experience with LDS to re-examine our indications and outcomes of surgical management., Methods: We reviewed all patients with a diagnosis of LDS who underwent cardiovascular surgery at our institution. The primary endpoint was mortality, and secondary endpoints included postoperative complications and need for reintervention., Results: Seventy-nine operated patients with LDS were identified. Mean age at first operation was 25 years, 39 (49%) were female, and 38 (48%) were children (age <18 years). Six (8%) patients presented with acute dissection. Five (6%) patients had a bicuspid aortic valve, and all presented with an ascending aortic aneurysm with a mean root diameter of 3.5cm. Twenty (25%) patients had a previous sternotomy. Sixty-five (82%) patients underwent aortic root replacement, of whom 52 underwent a valve-sparing operation and 4 had concomitant arch replacement. Mean aortic root diameter in this group was 4.2 cm. Nine (11%) patients underwent aortic arch replacement, 2 (3%) had isolated ascending aorta replacement, and 3 (4%) underwent open thoracoabdominal repair. There were 2 (3%) operative and 8 late deaths. Nineteen patients underwent subsequent operations for late aneurysm and/or dissection. Mean follow-up was 6 years (range 0-24 years). Kaplan-Meier survival was 88% at 10 years., Conclusions: Growing experience with LDS has confirmed early impressions of its aggressive nature and proclivity toward aortic catastrophe. Surgical outcomes are favorable, but reintervention rates are high. Meticulous follow-up with cardiovascular surveillance imaging remain important for management, particularly as clinical LDS subtypes are characterized and more tailored treatment is developed., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: In pediatric patients with connective tissue disorders (CTDs), early cardiac presentation often involves severe mitral regurgitation (MR) associated with severe bileaflet prolapse and, less frequently, aortic root enlargement. We adopted a simplified repair to address MR and prevent systolic anterior motion (SAM) in this unique group of patients., Materials and Methods: Retrospective review of clinical and echocardiographic data of all pediatric patients (age < 18 years) with CTD and MR undergoing simplified repair at 3 institutions (2000-2014)., Results: Eighteen children who underwent surgery for severe MR and bileaflet prolapse were identified. All were treated with ring annuloplasty and Alfieri edge-to-edge repair. Median age and weight were 8.2 years (range, 0.4-17.2 years) and 24.9 kg (5.6-63.3 kg), respectively. Median left ventricular end diastolic dimension median z score was 4.9 (2.1-11.9). One patient died (5.6%), and there were no other major complications. Among survivors, 94.4% had mild regurgitation or less, with no stenosis or SAM at median clinical follow-up of 2.4 years (range, 0-13.9 years). Median left ventricular end-diastolic dimension z score regressed to 1.3 (-0.5 to 4.3)., Conclusions: In pediatric patients with CTD and severe MR, a simplified approach is associated with intermediate-term competence, absence of SAM or significant stenosis, and regression of left ventricular enlargement., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)