Effects of Non-thermal, Non-cavitational Ultrasound Exposure on Human Diabetic Ulcer Healing and Inflammatory Gene Expression in a Pilot Study.

Effects of Non-thermal, Non-cavitational Ultrasound Exposure on Human Diabetic Ulcer Healing and Inflammatory Gene Expression in a Pilot Study.
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DOI:
10.1016/j.ultrasmedbio.2018.05.011
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发表时间:
2018-09
影响因子:
2.9
通讯作者:
Spiller KL
Spiller KL
中科院分区:
医学3区
文献类型:
--
作者:
Bajpai A;Nadkarni S;Neidrauer M;Weingarten MS;Lewin PA;Spiller KL

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本临床研究的目的是在有限的患者人群中评估基于低强度低频超声(LFLI-US)的新型高级伤口护理治疗影响人类糖尿病足溃疡(DFU)伤口闭合率以及影响促炎和抗炎基因相对表达变化的潜力。这些基因的表达比率(称为M1/M2评分,因为它受到随着伤口愈合进展巨噬细胞从促炎(M1)表型向抗炎(M2)表型转变的启发),先前被认为是用标准护理治疗的DFU的潜在愈合指标。我们还在20例慢性静脉溃疡患者的初步研究中表明,以25 Hz脉冲重复频率(PRF)输送的非空化、非热、低频(20 kHz)、低强度(空间峰值时间峰值强度<100 mW/cm 2;即压力振幅为55 kPa)超声(LFLI-US)可有效改善伤口愈合。在本研究中,我们评估了每周LFLI-US暴露影响糖尿病溃疡患者伤口愈合的可能性,并分析了清创糖尿病伤口组织中M1/M2评分的时间变化。尽管这是仅8名患者的有限患者群体,但与假手术治疗的患者相比,用LFLI-US治疗的伤口显示出伤口尺寸的显著更快减小(p<0.001)。此外,所有愈合的糖尿病溃疡的M1/M2评分值降低,所有未愈合的糖尿病溃疡的M1/M2评分值增加,表明M1/M2评分可用作晚期DFU治疗的疗效指标。该指标将有助于临床决策,确保最佳伤口管理,从而有助于降低医疗费用。此外,所呈现的结果可能有助于了解超声辅助慢性伤口愈合的机制。这些机制的知识可以导致个性化或患者量身定制的治疗。
The purpose of this clinical study was to assess, in a limited patient population, the potential for a novel advanced wound care treatment based on low intensity, low frequency ultrasound (LFLI-US) to affect wound closure rate in human diabetic foot ulcers (DFU) and to effect changes in the relative expression of pro-inflammatory and anti-inflammatory genes. The ratio of expression of these genes, termed the M1/M2 score because it was inspired by the transition of macrophages from pro-inflammatory (M1) to anti-inflammatory (M2) phenotypes as wound healing progresses, was previously presented as a potential healing indicator for DFUs treated with the standard of care. We have also shown that noncavitational, nonthermal, low frequency (20 kHz), low intensity (spatial peak temporal peak intensity <100mW/cm2; i.e. pressure amplitude of 55 kPa) ultrasound (LFLI-US) delivered with a pulse repetition frequency (PRF) of 25 Hz was effective at improving wound healing in a pilot study of 20 patients with chronic venous ulcers. In this study, we assessed the potential for weekly LFLI-US exposures to affect wound healing in patients with diabetic ulcers, and we analyzed temporal changes in the M1/M2 score in debrided diabetic wound tissue. Although this was a limited patient population of only 8 patients, wounds treated with LFLI-US showed a significantly faster reduction in wound size compared to sham-treated patients (p<0.001). In addition, the value of the M1/M2 score decreased for all healing diabetic ulcers and increased for all non-healing diabetic ulcers, suggesting that the M1/M2 score could be useful as an indicator of treatment efficacy for advanced DFU treatments. Such indicator would facilitate clinical decision making, ensuring optimal wound management and thus contributing to reduction of healthcare expenses. Moreover, the results presented may contribute to understanding of the mechanisms underlying ultrasonically assisted chronic wound healing. The knowledge of these mechanisms could lead to personalized or patient-tailored treatment.
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