Thomas H. Leung,1,2 Lillian F. Zhang,1 Jing Wang,1 Shoucheng Ning,3 Susan J. Knox,3 and Seung K. Kim1,4,5
1Department of Developmental Biology, 2Department of Dermatology, 3Department of Radiation Oncology, 4Howard Hughes Medical Institute, and 5Department of Medicine, Oncology Division, Stanford University School of Medicine, Stanford, California, USA.
Nuclear factor-κB (NF-κB) regulates cellular responses to inflammation and aging, and alterations in NF-κB signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of CCL2 and SOD2, two NF-κB–dependent genes. In cultured cells, HOCl inhibited the activity of inhibitor of NF-κB kinase (IKK), a key regulator of NF-κB activation, by oxidizing cysteine residues Cys114 and Cys115. In NF-κB reporter mice, topical HOCl reduced LPS-induced NF-κB signaling in skin. We further evaluated topical HOCl use in two mouse models of NF-κB–driven epidermal disease. For mice with acute radiation dermatitis, topical HOCl inhibited the expression of NF-κB–dependent genes, decreased disease severity, and prevented skin ulceration. In aged mice, topical HOCl attenuated age-dependent production of p16INK4a and expression of the DNA repair gene Rad50. Additionally, skin of aged HOCl-treated mice acquired enhanced epidermal thickness and proliferation, comparable to skin in juvenile animals. These data suggest that topical HOCl reduces NF-κB–mediated epidermal pathology in radiation dermatitis and skin aging through IKK modulation and motivate the exploration of HOCl use for clinical aims.
Eric Clayman, MD; Zackery Beauchamp, BS; Jared Troy, MD
Abstract
Background. Orthopedic hardware infections often require hardware removal or replacement. In some situations, hardware removal is not possible or would require amputation. Thus, a method of in-situ hardware salvage could significantly improve patient outcomes. Hypochlorous acid is a broad-spectrum antimicrobial solution with rapid effectiveness in biofilm impairment.
Methods. This article presents 2 patients with orthopedic hardware infection. Patient A had recurrent draining sinuses from an intramedullary nail in the femur. The orthopedic surgery team recommended above-knee amputation if hardware salvage was not possible. Patient B had a degloving injury of the right upper extremity with radius and ulna fractures that required revascularization and free flap coverage; when hardware infection developed, hardware removal would have required external fixator placement. In both patients, hypochlorous acid was used intraoperatively during debridement to soak the hardware for 5 minutes. Closed suction drains were placed along the hardware, and postoperative instillations of hypochlorous acid were placed through the drains for 5 minutes 1 to 2 times a day for 4 days for Patient A and 7 days for Patient
Results. On follow-up at 10 months for Patient A and at 9 months for Patient B, there was no evidence of recurrent hardware infection. Hardware was successfully salvaged in both patients.
Conclusions. Hypochlorous acid is an effective and safe topical antimicrobial agent for recurrent infections due to hardware-associated biofilm. Postoperative instillations of 0.025% hypochlorous acid through closed suctions drains may improve hardware salvage rates and optimize
Keywords PhaseOne Hypochlorous Acid Hardware Salvage Infected Hardware Biofilm
现任中华医学会创伤分会创面学组全国委员、中国医师学会烧伤分会全国委员、中华医学会烧伤分会青年委员、全军烧伤专业委员会委员、重庆市烧伤专业委员会委员、西南五省一巿烧伤整形学术委员会常委、中华烧伤杂志通讯编委、国家自然基金及SFDA新药评审专家、国外SCI杂志BURNS及Military Medicine等杂志审稿人等。
教授,烧伤科主任,博士生导师,国家级首批新世纪百千万人才工程人选、省烧伤外科专业委员会常委等。享受国务院特殊津贴。
管理治疗了大量烧烫伤、冻伤、电击伤、压疮及瘢痕患者,多次参与成批危重烧伤患者的救治工作。曾于国内外多所权威激光及整形治疗机构进修学习。
擅长: 各种烧伤治疗、表皮肿物去除和皮瓣成形、体表瘢痕防治,糖尿病足、褥疮、慢性难愈性创面的治疗;面部、胸部整形,自体脂肪移植。
从事整形、烧伤临床、教学、科研10年。2016年在中国科学院整形外科医院进修整1年,系统的学习了整形美容理论知识和临床手术技能。在国内第一作者发表论文6篇,参与发表论文20余篇,多篇为核心期刊。
伤口世界平台生态圈,以“关爱人间所有伤口患者”为愿景,连接、整合和拓展线上和线下的管理慢性伤口的资源,倡导远程、就近和居家管理慢性伤口,解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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