Research

Induced pluripotent stem cell-derived endothelial cells promote angiogenesis and accelerate wound closure in a murine excisional wound healing model

Clayton ZE, Tan RP, Miravet MM, Lennartsson K, Cooke JP, Bursill CA, Wise SG, Patel S

Biosci. Rep. 2018 08;38(4)

PMID: 29976773

Abstract

Chronic wounds are a major complication in patients with cardiovascular diseases. Cell therapies have shown potential to stimulate wound healing, but clinical trials using adult stem cells have been tempered by limited numbers of cells and invasive procurement procedures. Induced pluripotent stem cells (iPSCs) have several advantages of other cell types, for example they can be generated in abundance from patients’ somatic cells (autologous) or those from a matched donor. iPSCs can be efficiently differentiated to functional endothelial cells (iPSC-ECs). Here, we used a murine excisional wound model to test the pro-angiogenic properties of iPSC-ECs in wound healing. Two full-thickness wounds were made on the dorsum of NOD-SCID mice and splinted. iPSC-ECs (5 × 10) were topically applied to one wound, with the other serving as a control. Treatment with iPSC-ECs significantly increased wound perfusion and accelerated wound closure. Expression of endothelial cell (EC) surface marker, platelet endothelial cell adhesion molecule (PECAM-1) (CD31), and pro-angiogenic EC receptor, Tie1, mRNA was up-regulated in iPSC-EC treated wounds at 7 days post-wounding. Histological analysis of wound sections showed increased capillary density in iPSC-EC wounds at days 7 and 14 post-wounding, and increased collagen content at day 14. Anti-GFP fluorescence confirmed presence of iPSC-ECs in the wounds. Bioluminescent imaging (BLI) showed progressive decline of iPSC-ECs over time, suggesting that iPSC-ECs are acting primarily through short-term paracrine effects. These results highlight the pro-regenerative effects of iPSC-ECs and demonstrate that they are a promising potential therapy for intractable wounds.

Sternal-Sparing Aortic Valve Replacement in a Patient with Osteogenesis Imperfecta: A Case Report

Joshi P, Thakur S, Finn C, Sadlier P

J. Heart Valve Dis. 2017 11;26(6):744-746

PMID: 30207130

Abstract

The case described here is the first reported case of successful isolated aortic valve replacement (AVR) via a right anterior thoracotomy (RAT) in a patient with osteogenesis imperfecta (OI). The most common reported complication in patients with OI undergoing AVR or other cardiac surgery is bleeding and sternal complications. By using a RAT approach, it was possible to replace the aortic valve without major bleeding, transfusion, or sternal complications.

Rapid Endothelialization of Off-the-Shelf Small Diameter Silk Vascular Grafts

Filipe EC, Santos M, Hung J, Lee BSL, Yang N, Chan AHP, Ng MKC, Rnjak-Kovacina J, Wise SG

JACC Basic Transl Sci 2018 Feb;3(1):38-53

PMID: 30062193

Abstract

Synthetic vascular grafts for small diameter revascularization are lacking. Clinically available conduits expanded polytetrafluorethylene and Dacron fail acutely due to thrombosis and in the longer term from neointimal hyperplasia. We report the bioengineering of a cell-free, silk-based vascular graft. In vitro we demonstrate strong, elastic silk conduits that support rapid endothelial cell attachment and spreading while simultaneously resisting blood clot and fibrin network formation. In vivo rat studies show complete graft patency at all time points, rapid endothelialization, and stabilization and contraction of neointimal hyperplasia. These studies show the potential of silk as an off-the-shelf small diameter vascular graft.

Apolipoprotein A-I Reduces In-Stent Restenosis and Platelet Activation and Alters Neointimal Cellular Phenotype

Vanags LZ, Tan JTM, Galougahi KK, Schaefer A, Wise SG, Murphy A, Ali ZA, Bursill CA

JACC Basic Transl Sci 2018 Apr;3(2):200-209

PMID: 30062205

Abstract

Even the most advanced drug-eluting stents evoke unresolved issues, including chronic inflammation, late thrombosis, and neoatherosclerosis. This highlights the need for novel strategies that improve stent biocompatibility. Our studies show that apolipoprotein A-I (apoA-I) reduces in-stent restenosis and platelet activation, and enhances endothelialization. These findings have therapeutic implications for improving stent biocompatibility.

Impact of serious mental illness on surgical patient outcomes

McBride KE, Solomon MJ, Young JM, Steffens D, Lambert TJ, Glozier N, Bannon PG

ANZ J Surg 2018 May;

PMID: 29756676

Abstract

BACKGROUND: People with comorbid mental illness have poorer health status and disparate access to healthcare. Several studies internationally have reported mixed findings regarding the association between mental illness and surgical patient outcomes. This study examines the surgical outcomes in people with decompensated serious mental illness (SMI) within the setting of the Australian universal healthcare system.

METHODS: Retrospective cohort study involving elective overnight surgical patients aged 18 years and above who attended a large public tertiary referral hospital in Sydney, Australia, between 2010 and 2014. Patients were identified using ICD-10-AM diagnosis codes. Outcomes measure including in-hospital mortality, post-operative complications, morbidity, admission and time in intensive care, length and cost of hospitalization, discharge destination and 28-day re-admission rates were examined.

RESULTS: Of 23 343 surgical patient admissions, 451 (2%) patients had decompensated comorbid SMI with a subset of 47 (0.2%) having a specific psychotic illness. Patients with SMI comorbidity had significantly higher in-hospital mortality (2% versus 0%), post-operative complications (22% versus 8%), total comorbidity (7.6 versus 3.4 secondary codes), admissions (29% versus 9%) and time in intensive care (34.6 h versus 5.0 h), stay in hospital (12.2 days versus 4.6 days), admission costs ($24 162 versus $12 336), re-admission within 28 days (14% versus 10%) and discharges to another facility (11% versus 3%).

CONCLUSION: Patients with comorbid SMI had significantly worse surgical outcomes and incur much higher costs compared with the general surgical population. These results strongly highlight that specific perioperative interventions are needed to proactively improve the identification, management and outcomes for these disadvantaged patients.

Concomitant thoracoscopic surgery for solitary pulmonary nodule and atrial fibrillation

Lu R, Mei J, Zhao D, Jiang Z, Xiao H, Wang M, Ma N

Interact Cardiovasc Thorac Surg 2018 03;26(3):402-406

PMID: 29136152

Abstract

OBJECTIVES: The incidence of both solitary pulmonary nodules (SPN) and non-valvular atrial fibrillation (NVAF) has increased over the past decade. We performed concomitant video-assisted thoracoscopic surgery with modified epicardial radiofrequency ablation procedure for NVAF and SPN resection.

METHODS: Sixteen patients (7 men, mean age 62.6 ± 11.2 years) with SPN and NVAF underwent this procedure. Of these patients, 10 had paroxysmal atrial fibrillation and 6 persistent atrial fibrillation. A modified epicardial radiofrequency ablation combined with pulmonary vein isolation, circumferential left atrial ablation, ganglionic plexus ablation and left atrial appendage resection was performed for all patients. Left pulmonary surgery was carried out subsequently.

RESULTS: The mean procedure duration was 203.1 ± 15.6 (range 177-224) min. All patients successfully underwent this procedure with no conversion to sternotomy or pacemaker implantation. Of the 16 included patients, 13 received lobectomy and 3 received wedge resection. No severe complications occurred postoperatively. The mean length of hospital stay was 9.1 ± 1.4 (range 7-11) days with a mean follow-up period of 18.7 ± 6.7 (range 8-32) months. One patient had AF recurrence 6 months postoperatively. No pulmonary vein stenosis was detected at the 3rd postoperative month. There were no deaths or thromboembolic events during follow-up.

CONCLUSIONS: This concomitant therapy proved to be safe and yielded good clinical outcomes. Therefore, it deserves to be considered as a treatment for patients with SPN and NVAF.

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