Risk Factors for Delayed Healing and Recurrence of Chronic Venous Leg Ulcers—An Analysis of 1324 Legs

Gohel, Manjit; Taylor, M.; Earnshaw, J. J.; Heather, B. P.; Poskitt, K. R.; Whyman, M. R.

doi:10.1016/j.ejvs.2004.10.002

Cited by 146 publications

(138 citation statements)

References 26 publications

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“…2,4,5 Regardless of the clinical strategy used, evident variations in the outcome in patients with similar disease pattern and treatment are observed. 6 Therefore, apart from CVD, increasing age and female gender, irrefutable evidence of predisposition to VLU is still limited and elusive. As regards to genetics, candidate genes could potentially be those involved in inflammatory processes, fibroblast growth factors, angiogenesis, or apoptosis.…”

mentioning

confidence: 99%

DNA-array of gene variants in venous leg ulcers: Detection of prognostic indicators

Gemmati

Federici

Catozzi

et al. 2009

Journal of Vascular Surgery

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By analyzing simultaneously selected SNPs, it might be possible to glean precious information in predicting VLU onset or in stratifying patients according to their potential to heal. Although significant, our findings must be considered preliminary and the proposed prognostic indicators considered with caution, before ulterior more extensive studies in different populations can eventually confirm the present findings.

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mentioning

confidence: 99%

DNA-array of gene variants in venous leg ulcers: Detection of prognostic indicators

Gemmati

Federici

Catozzi

et al. 2009

Journal of Vascular Surgery

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“…Over 500 000 patients are treated for venous ulcers annually (Margolis and Cohen, 1994) and this treatment constitutes approximately 1% of total health care costs in the western world (Nelzen, 2000). Multiple factors contribute to the delayed healing of venous ulcers including ambulatory venous hypertension often associated with venous reflux, poor nutrition, advancing age, smoking, and medical compliance (i.e., following physician's guidelines and recommendations) (Gohel et al, 2005). The direct wound care cost associated with venous ulcers exceeds $2400 per month, but also is associated with indirect costs due to limited productivity and quality of life issues related to pain and depression (Olin et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Low-frequency (<100 kHz), low-intensity (<100 mW/cm2) ultrasound to treat venous ulcers: A human study and in vitro experiments

Samuels

Weingarten

Margolis

et al. 2013

The Journal of the Acoustical Society of America

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The purpose of this study was to examine whether low frequency (<100 kHz), low intensity (<100 mW/cm 2 , spatial peak temporal peak) ultrasound can be an effective treatment of venous stasis ulcers, which affect 500 000 patients annually costing over $1 billion per year. Twenty subjects were treated with either 20 or 100 kHz ultrasound for between 15 and 45 min per session for a maximum of four treatments. Healing was monitored by changes in wound area. Additionally, two in vitro studies were conducted using fibroblasts exposed to 20 kHz ultrasound to confirm the ultrasound's effects on proliferation and cellular metabolism. Subjects receiving 20 kHz ultrasound for 15 min showed statistically faster (p < 0.03) rate of wound closure. All five of these subjects fully healed by the fourth treatment session. The in vitro results indicated that 20 kHz ultrasound at 100 mW/cm 2 caused an average of 32% increased metabolism (p < 0.05) and 40% increased cell proliferation (p < 0.01) after 24 h when compared to the control, non-treated cells. Although statistically limited, this work supports the notion that low-intensity, low-frequency ultrasound is beneficial for treating venous ulcers.

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“…2 Age is a recognized risk factor for complications after surgery including delayed and incomplete wound healing and tissue loss and accounts for significant morbidity and mortality in this group. [3][4][5][6] Animal studies have confirmed the impact of aging on wound healing. [7][8][9] Tissue perfusion is regulated through the control of blood vessel diameter, which itself is controlled by the contractile state of vascular smooth muscle cells (VSMCs).…”

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confidence: 99%

Blocking Thrombospondin-1/CD47 Signaling Alleviates Deleterious Effects of Aging on Tissue Responses to Ischemia

Isenberg

Hyodo

Pappan

et al. 2007

ATVB

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Objective-Decreased blood flow secondary to peripheral vascular disease underlies a significant number of chronic diseases that account for the majority of morbidity and mortality among the elderly. Blood vessel diameter and blood flow are limited by the matricellular protein thrombospondin-1 (TSP1) through its ability to block responses to the endogenous vasodilator nitric oxide (NO). In this study we investigate the role TSP1 plays in regulating blood flow in the presence of advanced age and atherosclerotic vascular disease. Methods and Results-Mice lacking TSP1 or CD47 show minimal loss of their resistance to ischemic injury with age and increased preservation of tissue perfusion immediately after injury. Treatment of WT and apolipoprotein E-null mice using therapeutic agents that decrease CD47 or enhance NO levels reverses the deleterious effects of age-and diet-induced vasculopathy and results in significantly increased tissue survival in models of ischemia. Conclusion-With increasing age and diet-induced atherosclerotic vascular disease, TSP1 and its receptor CD47 become more limiting for blood flow and tissue survival after ischemic injury. Drugs that limit TSP1/CD47 regulation of blood flow could improve outcomes from surgical interventions in the elderly and ameliorate vascular complications attendant to aging. Key Words: nitric oxide Ⅲ thrombospondin-1 Ⅲ perfusion Ⅲ ischemia Ⅲ wound healing C omplications from peripheral vascular disease, including coronary artery disease and myocardial infarction, stroke, and ischemic vascular disease affect some 80% of people over the age of 65. The elderly have significant alterations in vascular anatomy including a loss of vascular networks 1 and alterations in vascular response to injury. 2 Age is a recognized risk factor for complications after surgery including delayed and incomplete wound healing and tissue loss and accounts for significant morbidity and mortality in this group. [3][4][5][6] Animal studies have confirmed the impact of aging on wound healing. [7][8][9] Tissue perfusion is regulated through the control of blood vessel diameter, which itself is controlled by the contractile state of vascular smooth muscle cells (VSMCs). Nitric oxide (NO) is a primary and ubiquitous dilator of blood vessels. 10 NO is constitutively produced in blood vessels by endothelial nitric oxide synthase (eNOS). NO activates soluble guanylate cyclase (sGC) leading to cGMP production and vasodilation. In aged vascular cells, 11 animals, and people, both eNOS expression and NO production 12 are decreased.We recently reported that thrombospondin-1 (TSP1) blocks NO-driven VSMC relaxation in a CD47-dependent manner. 13-15 NO-driven alterations in blood flow are substantially greater in the absence of TSP1 or CD47. Given the deleterious effects of aging on the cardiovascular system, we wanted to determine whether blocking of TSP1 inhibition of NO signaling would provide significant tissue protection in senescent animals. Aged WT and apolipoprotein E (apoE)-null mice (with diet-driv...

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Risk Factors for Delayed Healing and Recurrence of Chronic Venous Leg Ulcers—An Analysis of 1324 Legs

Abstract: Elderly patients with longstanding ulcers should be targeted for further research and may benefit from adjunctive treatments to improve clinical outcomes. Patients not treated with superficial venous surgery were at increased risk of leg ulcer recurrence.

Cited by 146 publications

References 26 publications

DNA-array of gene variants in venous leg ulcers: Detection of prognostic indicators

DNA-array of gene variants in venous leg ulcers: Detection of prognostic indicators

Low-frequency (<100 kHz), low-intensity (<100 mW/cm2) ultrasound to treat venous ulcers: A human study and in vitro experiments

Blocking Thrombospondin-1/CD47 Signaling Alleviates Deleterious Effects of Aging on Tissue Responses to Ischemia

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Risk Factors for Delayed Healing and Recurrence of Chronic Venous Leg Ulcers—An Analysis of 1324 Legs

Abstract: Elderly patients with longstanding ulcers should be targeted for further research and may benefit from adjunctive treatments to improve clinical outcomes. Patients not treated with superficial venous surgery were at increased risk of leg ulcer recurrence.

Cited by 146 publications

References 26 publications

DNA-array of gene variants in venous leg ulcers: Detection of prognostic indicators

DNA-array of gene variants in venous leg ulcers: Detection of prognostic indicators

Low-frequency (&lt;100 kHz), low-intensity (&lt;100 mW/cm2) ultrasound to treat venous ulcers: A human study and in vitro experiments

Blocking Thrombospondin-1/CD47 Signaling Alleviates Deleterious Effects of Aging on Tissue Responses to Ischemia

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Low-frequency (<100 kHz), low-intensity (<100 mW/cm2) ultrasound to treat venous ulcers: A human study and in vitro experiments