Marcin Maruszewski

Effectiveness of haemodialysis access with an autologous tissue-engineered vascular graft: a multicentre cohort study

BACKGROUND Application of a tissue-engineered vascular graft for small-diameter vascular reconstruction has been a long awaited and much anticipated advance for vascular surgery. We report results after a minimum of 6 months of follow-up for the first ten patients implanted with a completely biological and autologous tissue-engineered vascular graft. METHODS Ten patients with end-stage renal disease who had been receiving haemodialysis through an access graft that had a high probability of failure, and had had at least one previous access failure, were enrolled from centres in Argentina and Poland between September, 2004, and April, 2007. Completely autologous tissue-engineered vascular grafts were grown in culture supplemented with bovine serum, implanted as arteriovenous shunts, and assessed for both mechanical stability during the safety phase (0-3 months) and effectiveness after haemodialysis was started. FINDINGS Three grafts failed within the safety phase, which is consistent with failure rates expected for this high-risk patient population. One patient was withdrawn from the study because of severe gastrointestinal bleeding shortly before implantation, and another died of unrelated causes during the safety period with a patent graft. The remaining five patients had grafts functioning for haemodialysis 6-20 months after implantation, and a total of 68 patient-months of patency. In these five patients, only one intervention (surgical correction) was needed to maintain secondary patency. Overall, primary patency was maintained in seven (78%) of the remaining nine patients 1 month after implantation and five (60%) of the remaining eight patients 6 months after implantation. INTERPRETATION Our proportion of primary patency in this high-risk cohort approaches Dialysis Outcomes Quality Initiative objectives (76% of patients 3 months after implantation) for arteriovenous fistulas, averaged across all patient populations.

Mechanical properties of completely autologous human tissue engineered blood vessels compared to human saphenous vein and mammary artery.

We have previously reported the initial clinical feasibility with our small diameter tissue engineered blood vessel (TEBV). Here we present in vitro results of the mechanical properties of the TEBVs of the first 25 patients enrolled in an arterio-venous (A-V) shunt safety trial, and compare these properties with those of risk-matched human vein and artery. TEBV average burst pressures (3490+/-892 mmHg, n=230) were higher than native saphenous vein (SV) (1599+/-877 mmHg, n=7), and not significantly different from native internal mammary artery (IMA) (3196+/-1264 mmHg, n=16). Suture retention strength for the TEBVs (152+/-50 gmf) was also not significantly different than IMA (138+/-50 gmf). Compliance for the TEBVs prior to implantation (3.4+/-1.6%/100 mmHg) was lower than IMA (11.5+/-3.9%/100 mmHg). By 6 months post-implant, the TEBV compliance (8.8+/-4.2%/100 mmHg, n=5) had increased to values comparable to IMA, and showed no evidence of dilation or aneurysm formation. With clinical time points beyond 21 months as an A-V shunt without intervention, the mechanical tests and subsequent lot release criteria reported here would seem appropriate minimum standards for clinical use of tissue engineered vessels.

Cell-based therapeutics from an economic perspective: primed for a commercial success or a research sinkhole?

Despite widespread hype and significant investment through the late 1980s and 1990s, cell-based therapeutics have largely failed from both a clinical and financial perspective. While the early pioneers were able to create clinically efficacious products, small margins coupled with small initial indications made it impossible to produce a reasonable return on the huge initial investments that had been made to support widespread research activities. Even as US FDA clearance opened up larger markets, investor interest waned, and the crown jewels of cell-based therapeutics went bankrupt or were rescued by corporate bailout. Despite the hard lessons learned from these pioneering companies, many of todays regenerative medicine companies are supporting nearly identical strategies. It remains to be seen whether or not our proposed tenets for investment and commercialization strategy yield an economic success or whether the original model can produce a return on investment sufficient to justify the large up-front investments. Irrespective of which approach yields a success, it is critically important that more of the second-generation products establish profitability if the field is to enjoy continued investment from both public and private sectors.

Advanced Glycation End Products in the Development of Ischemic and Dilated Cardiomyopathy in Patients With Diabetes Mellitus Type 2

INTRODUCTION Hyperglycemia intensifies nonenzymatic glucose coupling to tissues, resulting in myocardial stiffness and formation of advanced glycation end products (AGE). The aim of this study was to assess seeking AGE in the myocardium from patients with type 2 diabetes (DM2) subjected to orthotopic heart transplantation (OHT), seeking to establish whether AGE play a role in the development of cardiomyopathies leading to OHT. MATERIAL The 2 studied groups consisted of 11 hearts explanted from patients with ischemic cardiomyopathy+DM2 (ICM+DM2, 55 +/- 6.5 years) and 8 from dilated cardiomyopathy+DM2 (DCM+DM2, 49.6 +/- 4.5 years). Comparative subgroups were composed of nondiabetic explanted hearts, 41 with ICM (52.8 +/- 5.8 years) and 41 with DCM (52.7 +/- 4.2 years). All patients were males. METHODS We examined immunohistochemical localization of AGE using a semiquantitative scale of reaction intensity in cardiomyocytes, fibroblasts, capillaries, arterioles, and arteries. Additionally, we calculated the scores for cardiocytes (AGE(Cardiocyte)) and all left ventricular components (AGE(LV)). RESULTS The cytoplasmic AGE deposits in cardiomyocytes were predominantly diffuse-granular in DM2 groups, whereas nondiabetic groups showed a lack of a reaction or a diffuse pattern. There were no differences in the reaction intensity between the 2 studied groups, or 2 comparative groups. All myocardial constituents showed higher AGE intensity in DM2 than nondiabetic groups. Only in the ICM+DM2 group did the DM2 duration correlate with AGE staining in selected myocardial layers and with AGE(Cardiocyte) and AGE(LV). CONCLUSIONS The presence of AGE in the hearts of patients requiring transplantation was related to the duration of DM2. The deposition of AGE in left ventricular myocardium was enhanced by DM2 particularly in patients with ICM.

Vascular abnormalities and cardiomyocyte lipofuscin deposits in endomyocardial biopsy specimens of heart transplant recipients: are they related to the development of cardiac allograft vasculopathy?

OBJECTIVE The aim of this study was to assess the predictive value of microvascular abnormalities and lipofuscin observed in endomyocardial biopsy samples for the development of cardiac allograft vasculopathy. METHODS The study group consisted of 68 cardiac allograft recipients (63 men and 5 women, 43 +/- 12 years old). We performed a re-evaluation of 1071 endomyocardial biopsy specimens to search for microvascular diseases and lipofuscin in cardiocytes. Endomyocardial biopsy specimens with an International Society for Heart and Lung Transplantation rejection grade of 2 or more and those without arterioles were excluded. Abnormalities found in the remaining 517 specimens were correlated with the grade of rejection. Biopsy specimens obtained 2 weeks, 12 months, and 36 months after transplantation were compared with coronary angiography results, clinical events of cardiac allograft vasculopathies, and survivals. Kaplan-Meier curves were constructed to compare the time to the development of cardiac allograft vasculopathy or death. RESULTS Enlarged endothelial cells, lymphocytes inside the arteriolar wall, occluded arteriolar lumen, endothelial vacuolization, and hypertrophy of the vascular muscle were significantly correlated with rejection grade. Although none of the vascular abnormalities predicted cardiac allograft vasculopathy, patients with lipofuscin deposits at the 12-month biopsy specimens were characterized by the rapid development of angiography-confirmed cardiac allograft vasculopathy (P < .08) and events related to cardiac allograft vasculopathy (P < .03, log-rank test). CONCLUSION Microvascular abnormalities correlate with mild cellular rejection, but they do not seem to be predictive for development of cardiac allograft vasculopathy detected by angiography. The presence of lipofuscin in 12-month endomyocardial biopsy specimens may be predictive of development of angiographically confirmed cardiac allograft vasculopathy.

Mechanical circulatory support is effective to treat pulmonary hypertension in heart transplant candidates disqualified due to unacceptable pulmonary vascular resistance

Introduction High pulmonary vascular resistance (PVR) in orthotopic heart transplantation (OHT) candidates is a risk factor of right ventricle failure after the procedure. However, the increase of PVR may be a consequence of the life-threatening deterioration of the left ventricle function. The use of mechanical circulatory support (MCS) seems to be the best solution, but it is reimbursed only in active OHT candidates. Aim We performed a retrospective analysis of MCS effectiveness in maintaining PVR at values accepted for OHT. Material and methods Starting from the year 2008 we identified 6 patients (all males, 42.8 ±17 years old) with dilated (n = 3), ischemic (n = 2), and restrictive cardiomyopathy (n = 1) in whom MCS – pulsatile left ventricle assist device (LVAD, n = 4), continuous flow LVAD (n = 1), and pulsatile biventricular assist device (BIVAD, n = 1) – was used at a time when PVR was unacceptable for OHT, and the reversibility test with nitroprusside was negative. After an average time of support of 261 ±129 days they were all transplanted. Results Right heart catheterization (RHC) results before MCS implantation were as follows: pulmonary artery systolic, diastolic, and mean pressure (PAPs/d/m) 60 ±20/28 ±7/40 ±11 mm Hg, pulmonary capillary wedge pressure (PCWP) 21 ±7 mm Hg, transpulmonary gradient (TPG) 19 ±7 mm Hg, cardiac output (CO) 3.6 ±0.8 l/min, PVR 5.7 ±2.1 Wood units (WU). Right heart catheterization results during MCS therapy were as follows: PAPs/d/s 27 ±11/12 ±4/17 ±6 mm Hg, PCWP 10 ±4 mm Hg, TPG 7 ±4 mm Hg, CO 5.1 ±0.7 l/min, PVR 1.4 ±0.6 WU. None of the patients experienced right ventricle failure after OHT with only one early loss due to multiorgan failure. Conclusions Mechanical circulatory support is an effective method of pulmonary hypertension treatment for patients disqualified for OHT due to high PVR.

Superficial herpes simplex virus wound infection following lung transplantation

Surgical site infections (SSIs) are infections of tissues, organs, or spaces exposed by surgeons during performance of an invasive procedure. SSIs are classified into superficial, which are limited to skin and subcutaneous tissues, and deep. The incidence of deep SSIs in lung transplant (LTx) patients is estimated at 5%. No reports have been published as to the incidence of superficial SSIs specifically in LTx patients. Common sense would dictate that the majority of superficial SSIs would be bacterial. Uncommonly, fungal SSIs may occur, and we believe that no reports exist as to the incidence of viral wound infections in LTx patients, or in any solid organ transplant patients. We report a de novo superficial wound infection with herpes simplex virus following lung transplantation, its possible source, treatment, and resolution.

Aortic cusp extension valvuloplasty: repair with an extracellular patch.

Introduction The proportion of valve repair procedures is increasing in experienced centers. The aim of the study was to assess the clinical and echocardiographic outcomes after aortic valve reconstruction with a novel surgical technique. Material and methods The study group consisted of 30 patients (23 male and 7 female) at a mean age of 35 ± 14 years. In patients with aortic root aneurysm the reimplantation or Florida sleeve technique was used. A sub-commissural annuloplasty, plication of the free edge of the cusp, shaving, and commissurotomy were performed. At this stage of surgery aortic repair was then attempted by cusp extension. Since 2013 the strips have been tailored from extracellular matrix. Results The mean aortic cross-clamp time was 90 ± 32 min. The mean cardiopulmonary bypass time was 126 ± 38 min. There was no in-hospital death. Re-exploration for bleeding was required in 1 patient. During follow-up, 1 patient needed reoperation at 1 year due to endocarditis. All patients remained alive in New York Heart Association (NYHA) functional class I. The echocardiographic findings remained unchanged in all cases during follow-up. Conclusions Our modification of aortic valve repair results in a good outcome.