Failure of Limb Salvage in a Patient with Chronic Limb-Threatening Ischemia due to Persistent Sciatic Artery Stenosis: Direct Therapeutic Intervention is Important.

A 79-year-old woman presented to our hospital with a complaint of feeling a cold sensation in her right foot. After performing a contrast-enhanced computed tomography angiography, severe stenosis in the right persistent sciatic artery (PSA) was identified. However, stenting was considered inadvisable due to compression issues when sitting. Following anticoagulant therapy, the patient's symptoms improved. However, after seventeen months, she experienced recurrent severe pain in her right foot. Catheter angiography revealed occlusions in both the anterior and posterior tibial arteries. To address the issue, we conducted endovascular therapy, followed by a femoro-popliteal artery bypass and ligation of the PSA. Unfortunately, despite these efforts, a below-knee amputation was eventually performed. Limited experience with the PSA and delayed intervention may have led to the need for amputation. Therefore, it is crucial to emphasize the importance of prompt therapeutic intervention following the onset of initial symptoms.

Nanofiber-coated, tacrolimus-eluting sutures inhibit post-operative neointimal hyperplasia in rats.

Post-operative complications of vascular anastomosis procedures remain a significant clinical challenge and health burden globally. Each year, millions of anastomosis procedures connect arteries and/or veins in vascular bypass, vascular access, organ transplant, and reconstructive surgeries, generally via suturing. Dysfunction of these anastomoses, primarily due to neointimal hyperplasia and the resulting narrowing of the vessel lumen, results in failure rates of up to 50% and billions of dollars in costs to the healthcare system. Non-absorbable sutures are the gold standard for vessel anastomosis; however, damage from the surgical procedure and closure itself causes an inflammatory cascade that leads to neointimal hyperplasia at the anastomosis site. Here, we demonstrate the development of a novel, scalable manufacturing system for fabrication of high strength sutures with nanofiber-based coatings composed of generally regarded as safe (GRAS) polymers and either sirolimus, tacrolimus, everolimus, or pimecrolimus. These sutures provided sufficient tensile strength for maintenance of the vascular anastomosis and sustained drug delivery at the site of the anastomosis. Tacrolimus-eluting sutures provided a significant reduction in neointimal hyperplasia in rats over a period of 14 days with similar vessel endothelialization in comparison to conventional nylon sutures. In contrast, systemically delivered tacrolimus caused significant weight loss and mortality due to toxicity. Thus, drug-eluting sutures provide a promising platform to improve the outcomes of vascular interventions without modifying the clinical workflow and without the risks associated with systemic drug delivery.

Extruded poly (glycerol sebacate) and polyglycolic acid vascular graft forms a neoartery.

In the ongoing search for the optimal biomaterial for tissue engineered vascular grafts (TEVGs), poly (glycerol sebacate) (PGS) has emerged as a new potential candidate. We have utilized a novel method to create unique, pore-free, extruded PGS grafts with and without a supportive exterior layer of polyglycolic acid (PGA). The 1 mm diameter by 5 mm length TEVGs were implanted in a rat model of infrarenal abdominal aorta interposition grafting. Three months after implantation, TEVGs comprised of extruded PGS with an external PGA braid demonstrated a patency rate of 9/10 (90%) with no signs of dilatation, dehiscence, or rupture. The PGS/PGA graft was remodeled into a neoartery with complete endothelialization of the neoartery lumen and formation of smooth muscle actinin multilayers as demonstrated via immunohistochemistry. Formation and maturation of extracellular matrix material were also observed, with amounts of elastin and collagen comparable to native rat aorta. No significant host inflammatory response was observed. These findings suggest the combination of an extruded PGS tube with an external reinforcing PGA braid is a promising material for small diameter TEVGs.

Mycotic abdominal aortic aneurysm in a patient with systemic lupus erythematosus: A case of critical antinomy.

Mycotic abdominal aortic aneurysms (MAAAs) are rare but life-threatening, and no standard therapy has yet been established. Effective surgery with intensive antimicrobial therapy is crucial; however, this can be fatal in immunocompromised patients. Only a few reports of MAAA with concomitant autoimmune disease exist; therefore, we were concerned about our lack of experience and knowledge about appropriate treatment. We report a 69-year-old male with an MAAA secondary to septic shock after spinal fusion surgery. He had also been on long-term oral immunosuppressants for systemic lupus erythematosus (SLE). After preoperative cephazolin, we performed debridement of infected tissue, graft replacement with a rifampicin-bonded prosthesis, and omentopexy. On the 52nd post-operative day, he was transferred back to the previous attending hospital under oral antibiotics and prednisolone. MAAA in patients with SLE should be treated with in situ replacement using an antimicrobial prosthetic or biological graft with thorough debridement and omentopexy, followed by antimicrobials and immunosuppressants, as needed.

Near-infrared spectroscopy device selection affects intervention management for cerebral desaturation during cardiopulmonary bypass surgery.

OBJECTIVE: Currently, several near-infrared spectroscopy oximetry devices are used for detecting cerebral ischemia during cardiopulmonary bypass (CPB) surgery. We investigated whether two different models of near-infrared spectroscopy oximetry devices affect the assessment of cerebral ischemia and its management during CPB. METHODS: From January 2017 to August 2017, 70 adult cardiovascular surgery cases were randomly assigned to 1 of 2 different near-infrared spectroscopy oximetry devices. The devices were INVOS 5100C (Medtronic, Minneapolis, MN, USA) (group I; n = 35) and FORE-SIGHT ELITE (CAS Medical Systems, Branford, CT, USA) (group F; n = 35). RESULTS: There were no significant differences in patient characteristics. The rSO2 values were significantly higher for patients in group F than for patients in group I. Scalp-Cortex distance showed negative correlations with the mean rSO2 values in group I (P = 0.01). Interventions for low rSO2 during CPB for groups I and F were increase perfusion flow (13:5; P = 0.03), blood transfusion (7:1; P = 0.02), and both (6:1; P = 0.04), respectively. The Scalp-Cortex distance in group I was significantly longer in patients who required intervention than in patients who did not (17.1 ± 2.5 vs 15.1 ± 1.6 mm; P = 0.007). CONCLUSIONS: It is inappropriate to use the same intervention criteria for different near-infrared spectroscopy oximetry devices. Moreover, brain atrophy influence rSO2 values depending on device selection. It is important to note that inappropriate device selection may misguide perfusionists into performing unnecessary or excessive intervention during CPB.

[Extraction of a 36-year-old Pacemaker Lead Using Cardiopulmonary Bypass].

A 78-year-old man underwent pacemaker implantation via the left internal jugular vein 36 years ago. After 30 years, a new device was implanted via the right subclavian vein and the old lead was cut and buried underneath the skin due to infection. This time, the patient presented with persistent lead infection of the left side. We chose open heart surgery to excise the old lead because of severe adhesion and surrounding calcification. The infected lead was completely removed using cardiopulmonary bypass without complication. Old pacemaker leads tend to develop adhesion and calcification within the innominate vein and superior vena cava, and therefore, it is often difficult to remove it with percutaneous technique. It was considered that open heart surgery was useful to excise a very old pacemaker lead.

Venous Properties in a Fontan Patient with Successful Remission of Protein-Losing Enteropathy.

We present the case of a 1-year-old boy who developed protein-losing enteropathy (PLE) within 2 months of a fenestrated Fontan procedure. His fenestration rapidly closed despite bilateral pulmonary stenosis (BPS). Subsequent to PLE onset, both fenestration and the bilateral pulmonary artery were reconstructed, and the patient's PLE had been in remission, with additive use of medications, for more than 2 years. Notably, although fenestration closed again and central venous pressure (CVP) reduction was minimal, the surrogates of venous return resistance were markedly suppressed as shown by increased blood volume, reduced estimated mean circulatory filling pressure, and suppressed CVP augmentation against a contrast agent. Taken together, dynamic characteristics of venous stagnation, rather than the absolute value of CVP, were ameliorated by the pulmonary reconstruction and use of medications, suggesting a significant role of venous property in the physiology of PLE. In addition, simultaneous measures of CVP and ventricular end-diastolic pressure during the abdominal compression procedure suggested a limited therapeutic role of fenestration against PLE in this patient.

Echocardiogram Unmasked Hemodynamic Advantage of Atrial Pacing in Securing Ventricular Preload in a Fontan Patient with Junctional Rhythm.

While the advancement of perioperative management has expanded Fontan candidacy, not all patients have a successful postoperative course. Our case was a right isomerism patient who could not leave the ICU due to high central venous pressure and low output syndrome. Initial observation of the monitor ECG showed his rhythm to be supraventricular, however, an echocardiogram indicated simultaneous contraction of the atrium and ventricle, implying a junctional rhythm. While neither central venous pressure nor blood pressure improved with temporary pacing, better central venous and pulmonary venous blood flow patterns during pacing unraveled its positive impact. The patient successfully left the ICU after permanent pacing implantation. Hemodynamic study revealed a beneficial impact of atrial pacing in securing cardiac output and ventricular preload, lowering central venous pressure, and shortening blood transit time, which is partly attributed to the optimization of the fenestration function in reservation of the preload. Our case emphasizes the significant advantage of atrial pacing in a failing Fontan patient with junctional rhythm by reducing venous congestion and maximizing the benefit of fenestration.

Fast-Degrading Tissue-Engineered Vascular Grafts Lead to Increased Extracellular Matrix Cross-Linking Enzyme Expression.

Tissue-engineered vascular grafts (TEVGs) require adequate extracellular matrix (ECM) to withstand arterial pressure. Tissue transglutaminase (TG2) and lysyl oxidase (LOX) are enzymes that cross-link ECM proteins and play a pivotal role in the development of vascular stiffness associated with aging. The purpose of this study is to investigate the expression of ECM cross-linking enzymes and mechanisms of scaffold degeneration leading to vascular stiffness in TEVG remodeling. Fast- and slow-degrading electrospun TEVGs were fabricated using polydioxanone (PDO) and poly(L-lactide-co-caprolactone) (PLCL) copolymer, with a PDO/PLCL ratio of 9:1 for fast-degrading and 1:1 for slow-degrading graft. These grafts were implanted in rats (n = 5/group) as abdominal aortic interposition conduits. The grafts were harvested at 1 month to evaluate patency, mechanical properties, vascular neotissue formation, and the expression of ECM cross-linking enzymes. All TEVGs were patent without any aneurysmal formation at 1 month. ECM area, TG2-positive area, and LOX-positive area were significantly greater in fast-degrading TEVGs compared to slow-degrading TEVGs, with significantly less remaining scaffold. The mechanical properties of fast-degrading TEVGs were similar to that of native aorta, as demonstrated by strain-stress curve. In conclusion, at 1 month, fast-degrading TEVGs had rapid and well-organized ECM with greater TG2 and LOX expression and native-like mechanical properties, compared to slow-degrading TEVGs. Impact statement Around 1.4 million patients in the United States require arterial prostheses each year due to cardiovascular diseases. Current synthetic vascular grafts suffer from increased risk of infection, thrombosis, a lack of endothelialization, and compliance mismatch to the native vasculature. Tissue-engineered vascular graft (TEVGs) presented in this study exhibited tunable biodegradation profiles by controlling the polymer ratio of polydioxanone/poly(L-lactide-co-caprolactone). One month after implantation, the fast-degrading TEVGs exhibited mechanical properties similar to that of native aorta, formation of endothelium, and well-organized extracellular matrix (ECM) with increased expression of tissue transglutaminase and lysyl oxidases, which are critical to the ECM remodeling process.

Biomimetic Model of Contractile Cardiac Tissue with Endothelial Networks Stabilized by Adipose-Derived Stromal/Stem Cells.

Cardiac tissue engineering strategies have the potential to regenerate functional myocardium following myocardial infarction. In this study, we utilized novel electrospun fibrin microfiber sheets of different stiffnesses (50.0 ± 11.2 kPa and 90.0 ± 16.4 kPa) to engineer biomimetic models of vascularized cardiac tissues. We characterized tissue assembly, electrophysiology, and contractility of neonatal rat ventricular cardiomyocytes (NRVCMs) cultured on these sheets. NRVCMs cultured on the softer substrates displayed higher conduction velocities (CVs) and improved electrophysiological properties. Human umbilical vein endothelial cells (HUVECs) formed dense networks on the sheets when co-cultured with human adipose-derived stem/stromal cells (hASCs). To achieve vascularized cardiac tissues, we tested various tri-culture protocols of NRVCM:hASC:HUVEC and found that a ratio of 1,500,000:37,500:150,000 cells/cm2 enabled the formation of robust endothelial networks while retaining statistically identical electrophysiological characteristics to NRVCM-only cultures. Tri-cultures at this ratio on 90 kPa substrates exhibited average CVs of 14 ± 0.6 cm/s, Action Potential Duration (APD)80 and APD30 of 152 ± 11 ms and 71 ± 6 ms, respectively, and maximum capture rate (MCR) of 3.9 ± 0.7 Hz. These data indicate the significant potential of generating densely packed endothelial networks together with electrically integrated cardiac cells in vitro as a physiologic 3D cardiac model.

Aortic atresia with transposition of the great arteries.

We describe a rare case of newborn with aortic atresia and transposition of the great arteries who underwent successful surgical repair. To the best of our knowledge, no such case has been previously reported. We demonstrated that, even with a complex diagnosis, the patient could survive after rapid two-stage Norwood procedure.

Different degradation rates of nanofiber vascular grafts in small and large animal models.

Nanofiber vascular grafts have been shown to create neovessels made of autologous tissue, by in vivo scaffold biodegradation over time. However, many studies on graft materials and biodegradation have been conducted in vitro or in small animal models, instead of large animal models, which demonstrate different degradation profiles. In this study, we compared the degradation profiles of nanofiber vascular grafts in a rat model and a sheep model, while controlling for the type of graft material, the duration of implantation, fabrication method, type of circulation (arterial/venous), and type of surgery (interposition graft). We found that there was significantly less remaining scaffold (i.e., faster degradation) in nanofiber vascular grafts implanted in the sheep model compared with the rat model, in both the arterial and the venous circulations, at 6 months postimplantation. In addition, there was more extracellular matrix deposition, more elastin formation, more mature collagen, and no calcification in the sheep model compared with the rat model. In conclusion, studies comparing degradation of vascular grafts in large and small animal models remain limited. For clinical translation of nanofiber vascular grafts, it is important to understand these differences.

Cardiac regeneration using human-induced pluripotent stem cell-derived biomaterial-free 3D-bioprinted cardiac patch in vivo.

One of the leading causes of death worldwide is heart failure. Despite advances in the treatment and prevention of heart failure, the number of affected patients continues to increase. We have recently developed 3D-bioprinted biomaterial-free cardiac tissue that has the potential to improve cardiac function. This study aims to evaluate the in vivo regenerative potential of these 3D-bioprinted cardiac patches. The cardiac patches were generated using 3D-bioprinting technology in conjunction with cellular spheroids created from a coculture of human-induced pluripotent stem cell-derived cardiomyocytes, fibroblasts, and endothelial cells. Once printed and cultured, the cardiac patches were implanted into a rat myocardial infarction model (n = 6). A control group (n = 6) without the implantation of cardiac tissue patches was used for comparison. The potential for regeneration was measured 4 weeks after the surgery with histology and echocardiography. 4 weeks after surgery, the survival rates were 100% and 83% in the experimental and the control group, respectively. In the cardiac patch group, the average vessel counts within the infarcted area were higher than those within the control group. The scar area in the cardiac patch group was significantly smaller than that in the control group. (Figure S1) Echocardiography showed a trend of improvement of cardiac function for the experimental group, and this trend correlated with increased patch production of extracellular vesicles. 3D-bioprinted cardiac patches have the potential to improve the regeneration of cardiac tissue and promote angiogenesis in the infarcted tissues and reduce the scar tissue formation.

Regenerative and durable small-diameter graft as an arterial conduit.

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.

Formation of Neoarteries with Optimal Remodeling Using Rapidly Degrading Textile Vascular Grafts.

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.

[Omental Flap for the Device Infection of the HeartMate II].

Case 1:An 18-year-old male underwent emergent left extracorporeal ventricular assist device(eVAD) implantation for a cardiogenic shock because of dilated cardiomyopathy (DCM). After listing for heart transplant, he underwent a HeartMate II implantation as bridge-to-bridge(BTB) therapy. The omental flap was simultaneously used to prevent device infection that could have been induced by the infected malgranulation around the cannulas of the eVAD. Eventually, he was discharged and waiting for transplantation. Case 2:A 30-year-old male with DCM underwent emergent eVAD implantation for left ventricular support, centrifugal veno-pulmonary artery extracorporeal membrane oxygenation (ECMO) for right ventricular and respiratory support, and mitral valve replacement. After weaning of ECMO, he was listed for a heart transplant and underwent a HeartMate II implantation as BTB therapy. However, liver dysfunction and malnutrition prolonged wound healing. Despite applying vacuum assist closure device to promote wound healing, part of the driveline and pump housing were exposed. Therefore, radical debridement and omentopexy were performed for infection control. He was discharged after complete wound healing.

Correction to: Cerebral oximetry for cardiac surgery: a preoperative comparison of device characteristics and pitfalls in interpretation.

In the original publication, the length unit of the SCD in Table 1 and Fig. 2 has been incorrectly published as cm. The correct length unit is mm.

Cerebral oximetry for cardiac surgery: a preoperative comparison of device characteristics and pitfalls in interpretation.

Regional cerebral oximetry using near-infrared spectroscopy devices is commonly used for detecting cerebral ischemia during cardiopulmonary bypass, and aim to avoid poor cerebral perfusion which may result in perioperative neurological impairment. Today, several devices that can detect cerebral ischemia are commercially available. Although these devices operate on the same measurement principles, their algorithms for detecting and calculating cerebral ischemia are different and no criteria for directly comparing values measured by such different devices exist. From January 2017 to August 2017, 80 adult cardiovascular surgery patients were enrolled in the prospective study. In each patient, preoperative regional cerebral oxygen saturation values were measured by two different devices and their correlations with various preoperative factors were evaluated. Regional cerebral oxygen saturation levels were significantly higher for values of FORE-SIGHT ELITE (CAS Medical Systems, Branford, CT, USA) (F value) than those of the INVOS 5100C (Medtronic, Minneapolis, MN, USA) (I value). Scalp-cortex distance, hemoglobin concentration, and the presence or absence of hemodialysis showed significant correlations with ratios of measured values specific to each device (F/I). An appropriate device should be selected according to preoperative patient characteristics, and factors influencing regional cerebral oxygen saturation values should be considered to ensure the correct interpretation of measured values. This research was conducted with the approval of the ethics committee of our university (approval number: B16-96).

3D and 4D Bioprinting of the Myocardium: Current Approaches, Challenges, and Future Prospects.

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.

Oversized Biodegradable Arterial Grafts Promote Enhanced Neointimal Tissue Formation.

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.