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Showing papers by "Mark D. Iafrati published in 2016"


Journal ArticleDOI
TL;DR: There is no difference in the incidence of REVAS for EVA vs L&S, but the causes of REvAS are different with L &S, which has important implications for treatment.
Abstract: Background Recurrence of varicose veins after surgery (REVAS) for saphenous incompetence has been well described after ligation and stripping (LS 40 of 125 limbs), followed by the development of anterior accessory saphenous vein incompetence (19%; 23 of 125 limbs). In contrast to other reports, incompetent calf perforating veins were an infrequent cause of REVAS (7%; eight of 125). Conclusions There is no difference in the incidence of REVAS for EVA vs L&S, but the causes of REVAS are different with L&S, which has important implications for treatment.

84 citations


Journal ArticleDOI
TL;DR: Comb1 and UN3 stimulate wound resolution in diabetic Yorkshire swine through upregulation of multiple reparative growth factors and cytokines, especially matrix metalloproteinases and inhibitors that may aid in reversing the proteolytic imbalance characteristic of chronically inflamed non-healing wounds.
Abstract: Non-healing wounds are a major global health concern and account for the majority of non-traumatic limb amputations worldwide. However, compared to standard care practices, few advanced therapeutics effectively resolve these injuries stemming from cardiovascular disease, aging, and diabetes-related vasculopathies. While matrix turnover is disrupted in these injuries, debriding enzymes may promote healing by releasing matrix fragments that induce cell migration, proliferation, and morphogenesis, and plasma products may also stimulate these processes. Thus, we created matrix- and plasma-derived peptides, Comb1 and UN3, which induce cellular injury responses in vitro, and accelerate healing in rodent models of non-healing wounds. However, the effects of these peptides in non-healing wounds in diabetes are not known. Here, we interrogated whether these peptides stimulate healing in a diabetic porcine model highly reminiscent of human healing impairments in type 1 and type 2-diabetes. After 3–6 weeks of streptozotocin-induced diabetes, full-thickness wounds were surgically created on the backs of adult female Yorkshire swine under general anesthesia. Comb1 and UN3 peptides or sterile saline (negative control) were administered to wounds daily for 3–7 days. Following sacrifice, wound tissues were harvested, and quantitative histological and immunohistochemical analyses were performed for wound closure, angiogenesis and granulation tissue deposition, along with quantitative molecular analyses of factors critical for angiogenesis, epithelialization, and dermal matrix remodeling. Comb1 and UN3 significantly increase re-epithelialization and angiogenesis in diabetic porcine wounds, compared to saline-treated controls. Additionally, fluorescein-conjugated Comb1 labels keratinocytes, fibroblasts, and vascular endothelial cells in porcine wounds, and Far western blotting reveals these cell populations express multiple fluorescein-Comb1-interacting proteins in vitro. Further, peptide treatment increases mRNA expression of several pro-angiogenic, epithelializing, and matrix-remodeling factors, importantly including balanced inductions in matrix metalloproteinase-2, -9, and tissue inhibitor of metalloproteinases-1, lending further insight into their mechanisms. Comb1 and UN3 stimulate wound resolution in diabetic Yorkshire swine through upregulation of multiple reparative growth factors and cytokines, especially matrix metalloproteinases and inhibitors that may aid in reversing the proteolytic imbalance characteristic of chronically inflamed non-healing wounds. Together, these peptides should have great therapeutic potential for all patients in need of healing, regardless of injury etiology.

18 citations


Journal ArticleDOI
TL;DR: A procedure for noninvasively measuring the flow-induced wall pressure distribution in both effectively rigid, thick-wall and flexible, thin-wall phantoms under perfusion conditions dynamically simulating the in vivo abdominal aorta is described.
Abstract: Abdominal aortic aneurysms (AAAs) represent permanent, localized dilations of the abdominal aorta. Here, we describe a procedure for noninvasively measuring the flow-induced wall pressure distribution in both effectively rigid, thick-wall and flexible, thin-wall phantoms under perfusion conditions dynamically simulating the in vivo abdominal aorta. Both phantoms accurately replicated the shape of patient AAAs including the renal and iliac arteries, and the flexible phantoms reflected patient tissue mechanical properties as well. As an example of their use, wall pressure distributions measured in rigid and flexible phantoms derived from one representative patient under flow conditions emulating the aorta at rest are presented. In both phantoms, there was a net pressure decrease from the upstream end of the bulge to the downstream end. However, there was a five times larger variation of wall pressure magnitude along the bulge region of the flexible phantom than along the rigid phantom, 6–7 mmHg versus more than 30 mmHg. In addition, in the rigid phantom, pressure signal fluctuations were of the same order of magnitude as the pressure transducer inherent noise level. In the flexible phantom, they were approximately 10 times the noise level in the absence of flow, suggesting that flow in the flexible phantom was unstable even at Reynolds number 500.

6 citations



Journal ArticleDOI
TL;DR: This study prospectively compare the diagnostic performance of con ventional multiplanar venography vs intravascular ultrasound (IVUS) for diagnosing and treating ICFVO and to characterize the patient response to iliofemoral vein intervention (ie, clinical improvement, quality of life] over 6 months of follow up.
Abstract: s from the 2016 American Venous Forum Annual Meeting Venogram Versus Intravascular Ultrasound for Diagnosing and Treating Iliofemoral Vein Obstruction (VIDIO): Report From a Multicenter, Prospective Study of Iliofemoral Vein Interventions Table. Significant iliofemoral vein stenosis/obstruction Lesion detection (N 1⁄4 100 patients) IVUS Multiplanar venography No. of lesions detected, total 124 66 No. of patients with: 0 lesions detected 19 48 1 lesion detected 46 40 2 lesions detected 27 10 3 lesions detected 8 2 P. J. Gagne, R. Tahara, C. Fastabend, L. Dzieciuchowicz, W. Marston, S. Vedantham, W. Ting, M. Iafrati, M. Lugli, A. Gasparis, S. Black, P. Thorpe, M. Passman. Norwalk Hospital; Allegheny Vein & Vascular Bradford, Pa; Imperial Health, Lake Charles, La; Szpital Kli niczny Przemienienia Panskiego Uniwersytetu Medycznego w Poznaniu, Poznan, Poland; University of North Carolina, Chapel Hill, NC; Wash ington University, St. Louis, Mo; Mt. Sinai Hospital, New York, NY; Tufts Medical Center, Boston, Mass; Hesperia Hospital Clinic, Modena, Italy; Stony Brook Medicine, Stony Brook, NY; St. Thomas Hospital, London, UK; Arizona Heart, Phoenix, Ariz; University of Alabama, Birmingham, Ala Background: Iliac/common femoral vein obstruction (ICFVO) can cause both severe venous insufficiency and significant patient morbidity. When identified, treatment with percutaneous angioplasty and stent can be life changing. Both multiplanar venography and intravascular ultrasound are used to diagnose ICFVO and to guide intervention. This study was designed to (1) prospectively compare the diagnostic performance of con ventional multiplanar venography vs intravascular ultrasound (IVUS) for diagnosing and treating ICFVO; and (2) to characterize the patient response to iliofemoral vein intervention (ie, clinical improvement, quality of life [QoL]) over 6 months of follow up. Methods: In a prospective, multicenter, single arm study, patients (clinical class CEAP C4 C6) underwent invasive assessment for ICFVO and possible endovascular intervention. In patients with bilateral disease, the more severely affected leg was designated the study limb. Exclusion criteria were prior venous stents, venovenous bypass surgery, known chronic total occlusion; severe superficial venous reflux; acute deep vein thrombosis, history of thrombophilia; and elevated serum creatinine. All patients under went multiplanar (ie, AP, RAO, LAO) venography of the study leg, and a treatment strategy based on the venograms was documented. All patients then underwent IVUS evaluation of the study leg, and the final treatment strategy was documented. Completion multiplanar venography and IVUS was performed after any intervention. Significant ICFVO was (1) 50% diam eter stenosis on venogram, (2) 50% cross sectional area stenosis on IVUS, (3) webs or collaterals. Duplex ultrasound, CEAP class, Venous Clinical Severity Score (VCSS), QoL questionnaires (ie, SF 36v2, CIVIQ 14), and ulcer measurements were performed at baseline, 1 month and 6 month follow up visits. Results: Between July, 2014 and July, 2015, 100 patients were enrolled at 11 U.S. and three European centers. Median age was 63 years (range, 30 85 years); 43% were women; left right study leg distribution was 63:37. Baseline parameters were CEAP: C4 (35%), C5 (15%), C6 (50%); VCSS (scale 0 30) 14.5 6 4.8 (mean 6 SD); CIVIQ 14 (scale 0 100) 54.9 6 23.9 (mean 6 SD). The Table summarizes lesion detection by modality. IVUS detected significantly more lesions than multiplanar venography (P 0.05), * (<0.05), ** (<0.01), *** (<0.001). 136 (P < .0001) in a cohort of patients with advanced venous insufficiency. Data regarding lesion characteristics, stent sizing, treatment plan changes based on venogram vs IVUS, and clinical/QoL response to intervention will be available for report at the end of 2015. Author Disclosures: P. J. Gagne: Speaker/honoraria, grants, consultant/ advisory board, collaborator for Volcano Corporation; R. Tahara: Nothing to disclose; C. Fastabend: Nothing to disclose; L. Dzieciuchowicz: Nothing to disclose; W. Marston: Nothing to disclose; S. Vedantham: Nothing to disclose; W. Ting: Nothing to disclose; M. Iafrati: Nothing to disclose; M. Lugli: Nothing to disclose; A. Gasparis: Nothing to disclose; S. Black: Nothing to disclose; P. Thorpe: Nothing to disclose; M. Passman: Nothing to disclose. Deep Venous Thrombosis Associated With Caval Extension of Iliac Stent E. Murphy, B. Johns, M. Alias, W. Crim, S. Raju. The RANE Center, Jackson, Miss Background: It is generally difficult to place an iliac vein stent “pre cisely” at the iliac caval junction with venographic control or even with IVUS guidance. This is because the anatomic junction is not circular but a tilted oval and the lesion whether primary or post thrombotic may variably encroach on the vena cava. We have advocated extending the stent 3 to 5 cm into the cava to prevent the lesion squeezing the stent distally or com pressing the end into a cone. This suggestion has met with resistance due to concerns of jailing contralateral iliac flow and subsequent deep venous throm bosis (DVT). We analyzed DVT incidence following placement of Wallstent with caval extension as well as a modification where a Z stent on top of the Wallstent stack was used for the extension. With widely spaced struts, contra lateral jailing was less likely to occur in addition to other technical benefits. Methods: A total of 755 limbs with consecutive Wallstent caval ex tensions (2007 to 2011) and 982 limbs with Z stent extensions (2011 to 2015) were analyzed for DVT incidence. Fisher exact test was used for sta tistical comparison. Results: Patient demographics were similar for both groups. The mean age was 58 years old; 68% female and 32% male; 61% of patients left side, and 39% right side. Patient pathology: 52% PTS only, 35% MTS only, 13% had both MTS and PTS. DVT incidence is shown in the Table. Left sided DVT was more common overall and in either group (P < .003). l teral s Ipsilateral DVT (<30 days) Ipsilateral DVT ($30 days) Total Ipsilateral DVTs Total DVTs 9 26 12 38 57 * 6*** 3** 9*** 12***

5 citations