Darwin Eton

The University of Chicago Medical Center, Department of Surgery, Retired

University of Chicago, Surgery, Retired Professor of Surgery

Northshore University HealthSystem, Surgery, Faculty Member

Loyola University Chicago, Surgery, Adjunct

University of Southern California, Surgery, Associate Professor 1995-1999

University of Illinois at Chicago, Surgery, Voluntary Professor Of Surgery

West Virginia University, Surgery, Faculty Member

Rush University Medical Center, Surgery, Adjunct

University of Miami Miller School of Medicine, Division of Vascular Surgery, Retired Professor and Chief Vascular Surgery

University of Miami Miller School of Medicine, Division of Surgical Oncology, Dewitt Daughtry Family Department of Surgery, Retired Professor and Chief Vascular Surgery

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I seek to advance a cell therapy that promotes neovascularization around occlusive vascular disease, while simultaneously promoting safe fibrinolysis of chronic occlusive thrombus in patients with chronic vascular disease. I was trained at MIT (Cambridge MA) and I am a Distinguished Fellow of the Society of Vascular Surgery and of the American College of Surgeons. My research won the 2016 Cures Within Reach Competition, and led to the formation of a start up company: Vasogenesis Inc (Boston MA). We have human clinical data showing efficacy. The clinical data obtained were substantiated by hemodynamic and angiographic data, and most importantly, was corroborated by proteomic and cytometry data.

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Gregory Dusting

University of Melbourne

Johannes Van Lieshout

Academic Medical Centre/ Universiteit van Amsterdam

Université de Sherbrooke (University of Sherbrooke)

Shou-dong Lee

Sergio Lorenzo

T. Scheeren

University of Groningen

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Papers by Darwin Eton

Effect of prostacyclin on vascular capacity in the dog

Journal of Clinical Investigation, Sep 1, 1985

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Immediate Repair Compared with Surveillance of Small Abdominal Aortic Aneurysms

The New England Journal of Medicine, May 9, 2002

Background-There is an ongoing debate as to whether the gastrointestinal safety of COX-2 inhibiti... more Background-There is an ongoing debate as to whether the gastrointestinal safety of COX-2 inhibition compared with nonsteroidal antiinflammatory drugs (NSAIDs) may come at the cost of increased cardiovascular events. In view of the large number of patients at cardiovascular risk requiring chronic analgesic therapy with COX-2 inhibitors for arthritic and other inflammatory conditions, the effects of selective COX-2 inhibition on clinically useful surrogates for cardiovascular disease, particularly endothelial function, need to be determined. Methods and Results-Fourteen male patients (mean age, 66Ϯ3 years) with severe coronary artery disease (average of 2.6 vessels with stenosis Ͼ75%) undergoing stable background therapy with aspirin and statins were included. The patients received celecoxib (200 mg BID) or placebo for a duration of 2 weeks in a double-blind, placebo-controlled, crossover fashion. After each treatment period, flow-mediated dilation of the brachial artery, high-sensitivity C-reactive protein, oxidized LDL, and prostaglandins were measured. Celecoxib significantly improved endothelium-dependent vasodilation compared with placebo (3.3Ϯ0.4% versus 2.0Ϯ0.5%, Pϭ0.026), whereas endothelium-independent vasodilation, as assessed by nitroglycerin, remained unchanged (9.0Ϯ1.6% versus 9.5Ϯ1.3%, Pϭ0.75). High-sensitivity C-reactive protein was significantly lower after celecoxib (1.3Ϯ0.4 mg/L) than after placebo (1.8Ϯ0.5 mg/L, Pϭ0.019), as was oxidized LDL (43.6Ϯ2.4 versus 47.6Ϯ2.6 U/L, Pϭ0.028), whereas prostaglandins did not change. Conclusions-This is the first study to demonstrate that selective COX-2 inhibition improves endothelium-dependent vasodilation and reduces low-grade chronic inflammation and oxidative stress in coronary artery disease. Thus, selective COX-2 inhibition holds the potential to beneficially impact outcome in patients with cardiovascular disease. (Circulation. 2003;107:405-409.

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Combined carotid endarterectomy and coronary artery bypass grafting in asymptomatic carotid artery stenosis

PubMed, Oct 1, 1998

The role of combined carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) in p... more The role of combined carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) in patients with severe asymptomatic carotid artery disease and concurrent symptomatic coronary artery disease is controversial. The objective of this report is to investigate the safety of combined CEA/CABG. The medical records of 30 patients who underwent combined CEA/CABG for coexistent asymptomatic carotid and symptomatic coronary artery occlusive disease were reviewed. All patients were scheduled for either elective or urgent myocardial revascularization due to their symptomatic coronary artery disease. Color-flow duplex scanning identified internal carotid artery stenosis of 80 to 99 per cent in 28 patients (93%) and 50 to 79 per cent in 2 patients (7%). Seventeen patients (57%) were male. The mean age was 64 +/- 10 years (range, 42-84 years). Contralateral internal carotid artery occlusion was present in four patients. Severe left main coronary artery disease was present in 12 patients (40%) and 7 patients (23%) had an ejection fraction of less than 50 per cent. There were no perioperative deaths or strokes. One patient suffered a myocardial infarction on postoperative day 1. This study demonstrates the safety of combined CEA/CABG for coexistent coronary and asymptomatic carotid disease. Using this surgical approach for critical coexistent disease may minimize the incidence of perioperative cerebrovascular complications in patients undergoing CABG.

Photodynamic Therapy

Archives of Surgery, Oct 1, 1995

OBJECTIVE To study the cytotoxic effect of photodynamic therapy (PDT) on myointimal hyperplasia (... more OBJECTIVE To study the cytotoxic effect of photodynamic therapy (PDT) on myointimal hyperplasia (MIH) in 120 New Zealand white rabbits using the chromophore chloroaluminum phthalocyanine tetrasulfonate (APtS). DESIGN A common carotid artery (CCA) injury model was used to initiate MIH. Photodynamic therapy was administered 1 week after injury (inhibition arm) or 6 weeks after injury (treatment arm). The inhibition arm CCAs were harvested 6 weeks after therapy. The treatment arm CCAs were harvested 1 week or 6 weeks after therapy. Each evaluation included four subgroups (n = 10 each): control, drug only, laser only, and drug plus laser. INTERVENTIONS An established CCA balloon injury model was used. Photodynamic therapy was administered by exposing CCAs to continuous external laser irradiation 30 minutes after treatment with a 2.5-mg/kg intravenous dose of APtS (fluence = 25 J/cm2, lambda = 672 nm). The control and drug-only subgroups received sham reoperations without laser exposure. MAIN OUTCOME MEASURES Following harvest, the CCAs were evaluated for area of stenosis and cell density. RESULTS In the inhibition arm, no PDT effect was seen on intimal cell density or area stenosis. In the treatment arm, intimal cell density was markedly diminished (P < .05) in the rabbits in the drug-laser group that were killed 1 week but not 6 weeks after PDT compared with rabbits in the control, drug-only, and laser-only groups. Area stenosis was not significantly affected by PDT. CONCLUSIONS Marked acute cytotoxicity of PDT on MIH was verified in vivo in the treatment arm. No sustained benefit of PDT was seen in the inhibition or the treatment arms. Refinements in dosimetry will be necessary to achieve long-term benefit of PDT for MIH.

Endograft design concerns for retrohepatic caval hemorrhage

Journal of Vascular Surgery: Venous and Lymphatic Disorders, 2020

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Stent-assisted vascular anastomoses

Seminars in vascular surgery, 2000

A stent can be used to rapidly create a laminar end-to-end vascular anastomosis. To construct a s... more A stent can be used to rapidly create a laminar end-to-end vascular anastomosis. To construct a stent-assisted vascular anastomosis (SAVA), 2 traction sutures 180 degrees apart are used to pull 1 conduit into another so that they overlap. A stent is balloon expanded to create a seal in the area of overlap. A SAVA takes 5 to 15 minutes to create. Essential to the procedure is proper sizing of the graft, stent, and balloon. The SAVA becomes reinforced internally by a neointima and externally by periadventitial scar tissue. No anastomotic leaks or pseudoaneurysms were observed in 13 patients (1 to 2.5 years; mean, 14 months), 6 adult mongrel dogs (6 months), and 5 growing pigs (5.5 months). Three of 9 upper-extremity basilic vein SAVAs (dialysis shunts) occluded (3, 9, and 13 months). Stent deformation was seen in all 3 despite protection by external graft rings. Within our follow-up interval, a balloon-expandable stent is an effective tool to use to rapidly join a vessel to a graft. B...

Filgrastim, fibrinolysis, and neovascularization

by Darwin Eton and Rachana Patil

Tissue Engineering and Regenerative Medicine, 2022

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Omental transfer for salvage of the moribund lower extremity

The American surgeon, 1998

Use of omental flaps is well documented in soft tissue reconstruction of the head and neck, chest... more Use of omental flaps is well documented in soft tissue reconstruction of the head and neck, chest wall, and abdomen. Three cases of omental transfer for soft tissue reconstruction of the lower extremities are presented. In two patients, free vascularized omental flaps were used to cover deep soft tissue defects over the lower leg and in one patient, a pedicle flap was used to cover a deep groin defect extending into the hip joint. In all patients, use of an omental graft allowed revascularization and subsequent wound healing with good cosmetic results.

Filgrastim, fibrinolysis, and neovascularization

Journal of Tissue Engineering and Regenerative Medicine, 2022

Segmental recanalization of chronically occluded arteries was observed in patients with chronic l... more Segmental recanalization of chronically occluded arteries was observed in patients with chronic limb-threatening ischemia (CLTI) treated with Filgrastim, a granulocyte colony stimulating factor, every 72 h for up to a month, and an infra-geniculate programmed compression pump (PCP) for 3 h daily. Molecular evidence for fibrinolysis and neovascularization was sought. CLTI patients were treated with PCP alone (N = 19), or with Filgrastim and PCP (N = 8 and N = 6, at two institutions). Enzyme-Linked Immunosorbent Assay was used to measure the plasma concentration of plasmin and of fibrin degradation products (FDP), and the serum concentration of proteins associated with neovascularization. In the PCP-alone group, blood was sampled on Day 1 (baseline) and after 30 days of daily PCP. In the Filgrastim and PCP group, blood was drawn on Day 1, and 1 day after the 5th and the 10th Filgrastim doses. Each blood draw occurred before and after 2 h of supervised PCP. Significant (p < 0.01) PCP independent increases in the plasma concentration of plasmin (>10-fold) and FDP (>5-fold) were observed 1 day after both the 5th and the 10th Filgrastim doses, compared to Day 1. Significant (p < 0.05) increases in the concentration of pro-angiogenic proteins (e.g., HGF, MMP-9, VEGF A) were also observed. Filgrastim at this novel dosimetry induced fibrinolysis without causing acute hemorrhage, in addition to inducing a pro-angiogenic milieu conducive to NV. Further clinical testing is warranted at this novel dosimetry in CLTI, as well as in other chronically ischemic tissue beds. Trial registration. https://clinicaltrials.gov/ct2/show/NCT02802852.

Results Peripheral Rotary Early and Late Clinical

Résultats précoces et tardifs de l'athérectomie rotative des artères des membres inférieurs

Annales De Chirurgie Vasculaire, 1992

Volume Guarantee High-Frequency Oscillatory Ventilation in Preterm Infants With RDS: Tidal Volume and DCO2 Levels for Optimal Ventilation Using Open-Lung Strategies

Frontiers in Pediatrics, 2020

High frequency oscillatory ventilation with volume-guarantee (HFOV-VG) is a promising lung protec... more High frequency oscillatory ventilation with volume-guarantee (HFOV-VG) is a promising lung protective ventilator mode for the treatment of respiratory failure in newborns. However, indicators of optimal ventilation during HFOV-VG mode are not identified yet. In this study, we aimed to evaluate optimal high-frequency tidal volume (VThf) and the dissociation coefficient of CO 2 (DCO 2) levels to achieve normocapnia during HFOV-VG after lung recruitment in very low birthweight infants with respiratory distress syndrome (RDS). Preterm babies under the 32nd postmenstrual week with severe RDS that received HFOV-VG using open-lung strategy between January 2014 and January 2019 were retrospectively evaluated. All included patients were treated with the Dräger Babylog VN500 ventilator in the HFOV-VG mode. In total, 53 infants with a mean gestational age of 26.8 ± 2.3 weeks were evaluated. HFOV mean optimal airway pressure (MAPhf) level after lung recruitment was found to be 10.2 ± 1.7 mbar. Overall, the mean applied VThf per kg was 1.64 ± 0.25 mL/kg in the study sample. To provide normocapnia, the mean VThf was 1.61 ± 0.25 mL/kg and the mean DCO 2 corr was 29.84 ± 7.88 [mL/kg] 2 /s. No significant correlation was found between pCO 2 levels with VThf (per kg) or DCO 2 corr levels. VThf levels to maintain normocarbia were significantly lower with 12 Hz frequency compared to 10 Hz frequency (1.50 ± 0.24 vs. 1.65 ± 0.25 mL/ kg, p < 0.001, respectively). A weak but significant positive correlation was found between mean airway pressure (MAPhf) and VThf levels. To our knowledge, this is the largest study to evaluate the optimal HFOV-VG settings in premature infants with RDS, using the open-lung strategy. According to the results, a specific set of numbers could not be recommended to achieve normocarbia. Following the trend of each patient and small adjustments according to the closely monitored pCO 2 levels seems logical.

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Stromal cell-derived factor-1 enhances pro-angiogenic effect of granulocyte-colony stimulating factor

Cardiovascular Research, 2007

Objective: Granulocyte colony-stimulating factor (G-CSF) mobilizes bone marrow mononuclear cells ... more Objective: Granulocyte colony-stimulating factor (G-CSF) mobilizes bone marrow mononuclear cells into the peripheral circulation. Stromal cell-derived factor-1 (SDF-1) enhances the homing of progenitor cells mobilized from the bone marrow and augments neovascularization in ischemic tissue. We hypothesize that SDF-1 will boost the pro-angiogenic effect of G-CSF. Methods and results: NIH 3T3 cells retrovirally transduced with SDF-1α gene (NIH 3T3/SDF-1) were used to deliver SDF-1 in vitro and in vivo. Endothelial progenitor cells (EPCs) co-cultured with NIH 3T3/SDF-1 cells using cell culture inserts migrated faster and were less apoptotic compared to those not exposed to SDF-1. NIH 3T3/SDF-1 (10 6 cells) were injected into the ischemic muscles immediately after resection of the left femoral artery and vein of C57BL/6J mice. G-CSF (25 μg/kg/day) was injected intraperitioneally daily for 3 days after surgery. Blood perfusion was examined using a laser Doppler perfusion imaging system. The perfusion ratio of ischemic/non-ischemic limb increased to 0.57 ± 0.03 and 0.50 ± 0.06 with the treatment of either SDF-1 or G-CSF only, respectively, 3 weeks after surgery, which was significantly higher than the saline-injected control group (0.41 ± 0.01, P b 0.05). Combined treatment with both SDF-1 and G-CSF resulted in an even better perfusion ratio of 0.69 ± 0.08 (P b 0.05 versus the single treatment groups). Mice were sacrificed 21 days after surgery. Immunostaining and Western blot assay of the tissue lysates showed that the injected NIH 3T3/SDF-1 survived and expressed SDF-1. CD34 + cells were detected with immunostaining, capillary density was assessed with alkaline phosphatase staining, and the apoptosis of muscle cells was viewed using an in situ cell death detection kit. More CD34 + cells, increased capillary density, and less apoptotic muscle cells were found in both G-CSF and SDF-1 treated group (P b 0.05 versus other groups). Conclusion: Combination of G-CSF-mediated progenitor cell mobilization and SDF-1-mediated homing of EPCs promotes neovascularization in the ischemic limb and increases the recovery of blood perfusion.

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Combined carotid endarterectomy and coronary revascularization operation

The Annals of Thoracic Surgery, 1998

The increasing risk of perioperative stroke after coronary artery bypass grafting can in part be ... more The increasing risk of perioperative stroke after coronary artery bypass grafting can in part be attributed to the increased incidence of carotid stenosis with increasing patient age. The efficacy of carotid endarterectomy has been demonstrated for both symptomatic and asymptomatic patients. Combined operations yield acceptable mortality and stroke risks, provide good freedom from late events, and cost less than staged operations.

Combination Cell and Gene Therapy for Peripheral Ischemia Using Myoblasts and Stem Cells Engineered with Conditionally Silenced Genes

Peripheral limb ischemia Peripheral arterial disease (PAD) impairs end-organ perfusion (reviewed ... more Peripheral limb ischemia Peripheral arterial disease (PAD) impairs end-organ perfusion (reviewed in 1, 2) and afflicts more than 300,000 new patients annually. Intermittent claudication (muscle pain) is a common early manifestation, affecting more than 10 % of people over 50 years of age. Claudication is associated with an 8-12 % annual mortality. Progression to pain at rest and

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Abstract 4932: CXCR4 Expression on Bone Marrow-derived Cells Was Regulated Positively by Calcium and Negatively by Aging

Cell surface receptors play major roles in the mobilization and homing of progenitor cells from t... more

Venous Anti-Reflux Implant

Splenic artery as a conduit to facilitate visceral arterial reconstruction

Journal of Vascular Surgery Cases

Magnetic device to assist transcorporeal guidewire placement

Thoracic aortic endograft

Effect of prostacyclin on vascular capacity in the dog

Journal of Clinical Investigation, Sep 1, 1985

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Immediate Repair Compared with Surveillance of Small Abdominal Aortic Aneurysms