Endovascular repair of traumatic axillosubclavian artery injuries.

Gun violence reached a 20-year peak in 2020, with the first-line treatment of axillosubclavian vascular injuries (SAVIs) remaining unknown. Traditional open exposure is difficult and exposes patients to iatrogenic venous and brachial plexus injury. The practice of endovascular treatment has been increasing. We performed a retrospective analysis of SAVIs at a level I trauma center. Seven patients were identified. Endovascular repair was performed in five patients. Technical success was 100%. The early results suggest that endovascular treatment of trauma-related SAVIs can be performed safely and effectively. However, complications such as stent thrombosis or occlusion can occur, demonstrating the need for surveillance.

Hepatorenal bypass resulting in dialysis independence in case of acute renal failure.

In the present case report, we have described a patient with bilateral renal artery occlusion resulting in the acute onset of refractory hypertension and renal failure requiring hemodialysis. Endovascular stenting of the renal arteries was not feasible owing to extensive aortic and renal orifice calcification. After consultation with nephrology and medical optimization, the patient underwent unilateral hepatorenal bypass, with subsequent improvement in renal function and sustained freedom from dialysis. Although percutaneous revascularization has become the preferred option for surgical management of renal artery occlusion, the findings from the present case have demonstrated that hepatorenal bypass remains a viable alternative for more complex cases.

Delayed delivery of endothelial progenitor cell-derived extracellular vesicles via shear thinning gel improves postinfarct hemodynamics.

BACKGROUND: Extracellular vesicles (EVs) are promising therapeutics for cardiovascular disease, but poorly-timed delivery might hinder efficacy. We characterized the time-dependent response to endothelial progenitor cell (EPC)-EVs within an injectable shear-thinning hydrogel (STG+EV) post-myocardial infarction (MI) to identify when an optimal response is achieved. METHODS: The angiogenic effects of prolonged hypoxia on cell response to EPC-EV therapy and EV uptake affinity were tested in vitro. A rat model of acute MI via left anterior descending artery ligation was created and STG+EV was delivered via intramyocardial injections into the infarct border zone at time points corresponding to phases of post-MI inflammation: 0 hours (immediate), 3 hours (acute inflammation), 4 days (proliferative), and 2 weeks (fibrosis). Hemodynamics 4 weeks post-treatment were compared across treatment and control groups (phosphate buffered saline [PBS], shear-thinning gel). Scar thickness and ventricular diameter were assessed histologically. The primary hemodynamic end point was end systolic elastance. The secondary end point was scar thickness. RESULTS: EPC-EVs incubated with chronically versus acutely hypoxic human umbilical vein endothelial cells resulted in a 2.56 ± 0.53 versus 1.65 ± 0.15-fold increase (P = .05) in a number of vascular meshes and higher uptake of EVs over 14 hours. End systolic elastance improved with STG+EV therapy at 4 days (0.54 ± 0.08) versus PBS or shear-thinning gel (0.26 ± 0.03 [P = .02]; 0.23 ± 0.02 [P = .01]). Preservation of ventricular diameter (6.20 ± 0.73 mm vs 8.58 ± 0.38 mm [P = .04]; 9.13 ± 0.25 mm [P = .01]) and scar thickness (0.89 ± 0.05 mm vs 0.62 ± 0.03 mm [P < .0001] and 0.58 ± 0.05 mm [P < .0001]) was significantly greater at 4 days, compared wit PBS and shear-thinning gel controls. CONCLUSIONS: Delivery of STG+EV 4 days post-MI improved left ventricular contractility and preserved global ventricular geometry, compared with controls and immediate therapy post-MI. These findings suggest other cell-derived therapies can be optimized by strategic timing of therapeutic intervention.

Delivery of progenitor cells with injectable shear-thinning hydrogel maintains geometry and normalizes strain to stabilize cardiac function after ischemia.

OBJECTIVES: The ventricle undergoes adverse remodeling after myocardial infarction, resulting in abnormal biomechanics and decreased function. We hypothesize that tissue-engineered therapy could minimize postischemic remodeling through mechanical stress reduction and retention of tensile myocardial properties due to improved endothelial progenitor cell retention and intrinsic biomechanical properties of the hyaluronic acid shear-thinning gel. METHODS: Endothelial progenitor cells were harvested from adult Wistar rats and resuspended in shear-thinning gel. The constructs were injected at the border zone of ischemic rat myocardium in an acute model of myocardial infarction. Myocardial remodeling, tensile properties, and hemodynamic function were analyzed: control (phosphate-buffered saline), endothelial progenitor cells, shear-thinning gel, and shear-thinning gel + endothelial progenitor cells. Novel high-resolution, high-sensitivity ultrasound with speckle tracking allowed for global strain analysis. Uniaxial testing assessed tensile biomechanical properties. RESULTS: Shear-thinning gel + endothelial progenitor cell injection significantly increased engraftment and retention of the endothelial progenitor cells within the myocardium compared with endothelial progenitor cells alone. With the use of strain echocardiography, a significant improvement in left ventricular ejection fraction was noted in the shear-thinning gel + endothelial progenitor cell cohort compared with control (69.5% ± 10.8% vs 40.1% ± 4.6%, P = .04). A significant normalization of myocardial longitudinal displacement with subsequent stabilization of myocardial velocity with shear-thinning gel + endothelial progenitor cell therapy compared with control was also evident (0.84 + 0.3 cm/s vs 0.11 ± 0.01 cm/s, P = .03). A significantly positive and higher myocardial strain was observed in shear-thinning gel + endothelial progenitor cell (4.5% ± 0.45%) compared with shear-thinning gel (3.7% ± 0.24%), endothelial progenitor cell (3.5% ± 0.97%), and control (8.6% ± 0.3%, P = .05). A resultant reduction in dynamic stiffness was noted in the shear-thinning gel + endothelial progenitor cell cohort. CONCLUSIONS: This novel injectable shear-thinning hyaluronic acid hydrogel demonstrates stabilization of border zone myocardium with reduction in adverse myocardial remodeling and preservation of myocardial biomechanics. The cellular construct provides a normalization of strain measurements and reduces left ventricular dilatation, thus resulting in improvement of left ventricular function.

Preoperative renal dysfunction does not affect outcomes of left ventricular assist device implantation.

OBJECTIVE: Selection criteria for durable left ventricular assist device (LVAD) implantation remain unclear. One such criterion is renal function. In this study we evaluated outcomes of LVAD implantation in patients with preoperative renal dysfunction. METHODS: Patients with implanted LVADs as destination therapy (DT) or bridge to transplantation (BTT) at a single institution between 2006 and 2015 were included. Primary stratification was according to pre-implantation glomerular filtration rate (GFR): >60 mL/min versus <60 mL/min or dialysis dependence. The primary outcome was post-LVAD implantation overall survival. RESULTS: Two hundred thirty-eight patients underwent LVAD implantation during the study period as DT (60%; n = 142) or BTT (40%; n = 96). Reduced GFR was present in 56% (n = 132), with 8% (n = 18) being dialysis-dependent. Normal versus reduced GFR cohorts were well matched except for a higher incidence of coronary artery disease in the patients with reduced GFR (61% vs 48%; P = .04). Mean follow-up was 13.5 ± 17.0 months. Unadjusted and risk-adjusted survival at 1, 3, 6, and 12 months after LVAD implantation were similar between the cohorts for DT and BTT. Rates of transplantation were comparable in BTT patients (61% normal vs 53% reduced GFR; P = .43). Recovery of renal function to a GFR >60 mL/min occurred in 43% (n = 17) and 57% (n = 42) of patients with reduced GFR in the BTT and DT cohorts, respectively, by 1 year post implantation. CONCLUSIONS: Well selected patients with preexisting renal dysfunction can undergo LVAD implantation with acceptable outcomes. Approximately half of LVAD recipients with preimplantation renal dysfunction will recover normal renal function within the first postoperative year. Renal dysfunction alone should not serve as an absolute contraindication to LVAD therapy.

Transplantation of "high-risk" donor hearts: Implications for infection.

BACKGROUND: Heart transplantation is the gold-standard treatment for end-stage heart failure. Short- and long-term outcomes have been excellent, but the shortage of organs persists. The number of potential recipients who die while awaiting orthotopic heart transplantation increases yearly. In 2004, the label "high-risk donor" (HRD) was applied, by the United Network for Organ Sharing (UNOS), to any organ donor who met the Centers for Disease Control (CDC) criteria for behavior that put them at high risk of infection. Despite organ shortages, grafts from HRD CDCs are often declined, because of concerns regarding infection. We undertook this study to analyze our extensive experience with orthotopic heart transplantation of grafts from HRD CDCs, and to determine the short- and long-term outcomes associated with recipients of hearts from HRD CDCs, particularly transmission of infection. METHODS: We performed 367 heart transplantations at our center from September 2008 to September 2014, a timeframe during which the HRD CDC labeling had been implemented. Of the total number of orthotopic heart transplantations performed, 55 patients (15%) received organs from HRD CDCs that had known negative serology for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. We reviewed demographic, perioperative, and short- and long-term outcomes. The recipients of grafts from HRD CDCs were followed closely, with 3- and 12-month surveillance laboratory testing of viral load for HIV, for hepatitis B, and for hepatitis C core- and surface-antigen serology. RESULTS: All 55 patients (72.7% were men) underwent a successful transplantation procedure. One patient was excluded from follow-up analysis because he was re-transplanted within 4 days owing to the posttransplant finding of metastatic lung adenocarcinoma within the donor. Primary etiology of heart failure was ischemic in 18 of the patients. The most common blood type was O positive, in 20 patients (37.1%), followed by A positive, in 19 patients (35.2%). A total of 19 (35.2%) patients were supported with a mechanical assist device before the transplantation. The average allograft ischemic time was 173 ± 96 minutes. The median length of hospital stay was 19.5 days. A low incidence was observed of the postoperative complications of stroke (1.9%), dialysis (3.9%), and complete heart block (3.9%). Kaplan-Meier analysis demonstrated excellent survival, both short-term (1 year; 94%) and long-term (3 years; 80%). Allograft function was excellent at time of discharge with a left ejection fraction of 67.8% ± 7.3%. Only one patient (1.9%) was noted to have hepatitis C seroconversion at 105 days after receiving the transplant. After antiviral treatment, the patient has had undetectable viral loads to date. All other patients had undetectable plasma viral loads of HIV, hepatitis C, and hepatitis B, determined using rigorous testing. CONCLUSIONS: We present the only single-center series on recipients of heart transplants from HRD CDCs. This potential source of suitable donor organs is shown to lead to excellent survival, without an increased incidence of perioperative or postoperative complications. Furthermore, the risk of transmission of infection from donors in this subgroup seems to be minimal.

Injectable shear-thinning hydrogels used to deliver endothelial progenitor cells, enhance cell engraftment, and improve ischemic myocardium.

OBJECTIVES: The clinical translation of cell-based therapies for ischemic heart disease has been limited because of low cell retention (<1%) within, and poor targeting to, ischemic myocardium. To address these issues, we developed an injectable hyaluronic acid (HA) shear-thinning hydrogel (STG) and endothelial progenitor cell (EPC) construct (STG-EPC). The STG assembles as a result of interactions of adamantine- and ß-cyclodextrin-modified HA. It is shear-thinning to permit delivery via a syringe, and self-heals upon injection within the ischemic myocardium. This directed therapy to the ischemic myocardial border zone enables direct cell delivery to address adverse remodeling after myocardial infarction. We hypothesize that this system will enhance vasculogenesis to improve myocardial stabilization in the context of a clinically translatable therapy. METHODS: Endothelial progenitor cells (DiLDL(+) VEGFR2(+) CD34(+)) were harvested from adult male rats, cultured, and suspended in the STG. In vitro viability was quantified using a live-dead stain of EPCs. The STG-EPC constructs were injected at the border zone of ischemic rat myocardium after acute myocardial infarction (left anterior descending coronary artery ligation). The migration of the enhanced green fluorescent proteins from the construct to ischemic myocardium was analyzed using fluorescent microscopy. Vasculogenesis, myocardial remodeling, and hemodynamic function were analyzed in 4 groups: control (phosphate buffered saline injection); intramyocardial injection of EPCs alone; injection of the STG alone; and treatment with the STG-EPC construct. Hemodynamics and ventricular geometry were quantified using echocardiography and Doppler flow analysis. RESULTS: Endothelial progenitor cells demonstrated viability within the STG. A marked increase in EPC engraftment was observed 1-week postinjection within the treated myocardium with gel delivery, compared with EPC injection alone (17.2 ± 0.8 cells per high power field (HPF) vs 3.5 cells ± 1.3 cells per HPF, P = .0002). A statistically significant increase in vasculogenesis was noted with the STG-EPC construct (15.3 ± 5.8 vessels per HPF), compared with the control (P < .0001), EPC (P < .0001), and STG (P < .0001) groups. Statistically significant improvements in ventricular function, scar fraction, and geometry were noted after STG-EPC treatment compared with the control. CONCLUSIONS: A novel injectable shear-thinning HA hydrogel seeded with EPCs enhanced cell retention and vasculogenesis after delivery to ischemic myocardium. This therapy limited adverse myocardial remodeling while preserving contractility.

Tissue-engineered, hydrogel-based endothelial progenitor cell therapy robustly revascularizes ischemic myocardium and preserves ventricular function.

OBJECTIVES: Cell-based angiogenic therapy for ischemic heart failure has had limited clinical impact, likely related to low cell retention (<1%) and dispersion. We developed a novel, tissue-engineered, hydrogel-based cell-delivery strategy to overcome these limitations and provide prolonged regional retention of myocardial endothelial progenitor cells at high cell dosage. METHODS: Endothelial progenitor cells were isolated from Wistar rats and encapsulated in fibrin gels. In vitro viability was quantified using a fluorescent live-dead stain of transgenic enhanced green fluorescent protein(+) endothelial progenitor cells. Endothelial progenitor cell-laden constructs were implanted onto ischemic rat myocardium in a model of acute myocardial infarction (left anterior descending ligation) for 4 weeks. Intramyocardial cell injection (2 × 10(6) endothelial progenitor cells), empty fibrin, and isolated left anterior descending ligation groups served as controls. Hemodynamics were quantified using echocardiography, Doppler flow analysis, and intraventricular pressure-volume analysis. Vasculogenesis and ventricular geometry were quantified. Endothelial progenitor cell migration was analyzed by using endothelial progenitor cells from transgenic enhanced green fluorescent protein(+) rodents. RESULTS: Endothelial progenitor cells demonstrated an overall 88.7% viability for all matrix and cell conditions investigated after 48 hours. Histologic assessment of 1-week implants demonstrated significant migration of transgenic enhanced green fluorescent protein(+) endothelial progenitor cells from the fibrin matrix to the infarcted myocardium compared with intramyocardial cell injection (28 ± 12.3 cells/high power field vs 2.4 ± 2.1 cells/high power field, P = .0001). We also observed a marked increase in vasculogenesis at the implant site. Significant improvements in ventricular hemodynamics and geometry were present after endothelial progenitor cell-hydrogel therapy compared with control. CONCLUSIONS: We present a tissue-engineered, hydrogel-based endothelial progenitor cell-mediated therapy to enhance cell delivery, cell retention, vasculogenesis, and preservation of myocardial structure and function.