A Possible Contribution of Altered Cathepsin B Expression to the Development of Skin Sclerosis and Vasculopathy in Systemic Sclerosis

Cathepsin B (CTSB) is a proteolytic enzyme potentially modulating angiogenic processes and extracellular matrix remodeling. While matrix metalloproteinases are shown to be implicated in tissue fibrosis and vasculopathy associated with systemic sclerosis (SSc), the role of cathepsins in this disease has not been well studied. The aim of this study is to evaluate the roles of CTSB in SSc. Serum pro-CTSB levels were determined by enzyme-linked immunosorbent assay in 55 SSc patients and 19 normal controls. Since the deficiency of transcription factor Fli1 in endothelial cells is potentially associated with the development of SSc vasculopathy, cutaneous CTSB expression was evaluated by immunostaining in Fli1+/− and wild type mice as well as in SSc and control subjects. The effects of Fli1 gene silencing and transforming growth factor-β (TGF-β) on CTSB expression were determined by real-time PCR in human dermal microvascular endothelial cells (HDMECs) and dermal fibroblasts, respectively. Serum pro-CTSB levels were significantly higher in limited cutaneous SSc (lcSSc) and late-stage diffuse cutaneous SSc (dcSSc) patients than in healthy controls. In dcSSc, patients with increased serum pro-CTSB levels showed a significantly higher frequency of digital ulcers than those with normal levels. CTSB expression in dermal blood vessels was increased in Fli1+/− mice compared with wild type mice and in SSc patients compared with healthy controls. Consistently, Fli1 gene silencing increased CTSB expression in HDMECs. In cultured dermal fibroblasts from early dcSSc, CTSB expression was decreased compared with normal fibroblasts and significantly reversed by TGF-β1 antisense oligonucleotide. In conclusion, up-regulation of endothelial CTSB due to Fli1 deficiency may contribute to the development of SSc vasculopathy, especially digital ulcers, while reduced expression of CTSB in lesional dermal fibroblasts is likely to be associated with skin sclerosis in early dcSSc

The combination of high bacterial count and positive biofilm formation is associated with the inflammation of pressure ulcers

Mao Kunimitsu,1 Gojiro Nakagami,1,2 Aya Kitamura,1 Yuko Mugita,1 Kaname Akamata,3 Sanae Sasaki,4 Chieko Hayashi,4 Yukie Mori,1 Hiromi Sanada1,2 1Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 2Global Nursing Research Center, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 3Department of Dermatology, The University of Tokyo Hospital, Tokyo, Japan; 4Department of Nursing, The University of Tokyo Hospital, Tokyo, Japan Objective: Evaluating the bacterial bioburden of pressure ulcers through bacterial count and pathogenicity is important but is currently difficult to perform in the clinical setting. In order to address this problem, we proposed two methods: 1) measurement of bacterial count using a quantitative device and 2) detection of biofilm formation by wound blotting. The purpose of this study was to investigate the relationship between the bacterial bioburden, assessed by combining these two methods, and the presence of wound inflammation.Patients and methods: The participants of this cross-sectional study were patients aged >20years with category II, III, IV, or unstageable pressure ulcers examined during a routine round in an interdisciplinary pressure ulcer team between July 2014 and April 2018. Relevant clinical information, including bacterial count, biofilm formation, and presence of inflammation, was collected from the pressure ulcer round record. The relationship between the bacterial bioburden and the presence of inflammation was analyzed using multilevel logistic regression analysis.Results: We included 273 samples obtained from 98 patients. High bacterial count was significantly associated with wound inflammation (P=0.009) and positive biofilm formation tended to be associated with wound inflammation (P=0.076). In terms of combining these parameters, high bacterial count and positive biofilm formation were significantly associated with wound inflammation (OR: 4.61, 95% CI: 1.37–15.46, P=0.013).Conclusion: Assessment using both bacterial count and biofilm detection parameters may provide more accurate evaluation of the bacterial bioburden of the wound and contribute to appropriate wound care. Keywords: wound infection, wound assessment, critical colonization, wound blotting, thermograph

Utility of a three-dimensional wound measurement device in pressure ulcers

Taichi Goto,1–3 Gojiro Nakagami,1,4 Ayano Nakai,1 Shuhei Noyori,1,5 Sanae Sasaki,6 Chieko Hayashi,6 Tomomitsu Miyagaki,7 Kaname Akamata,7 Hiromi Sanada1,4 1Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 2Global Leadership Initiative for an Age-Friendly Society, The University of Tokyo, Bunkyo-ku, 3Japan Society for the Promotion of Science, Chiyoda-ku, Japan; 4Global Nursing Research Center, Graduate School of Medicine, The University of Tokyo, 5Graduate Program for Social ICT Global Creative Leaders, The University of Tokyo, 6Department of Nursing, 7Department of Dermatology, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan Introduction: Depth assessment is important for severe pressure ulcers (PUs); however, a device for the metric measurement of wounds, including depth, is lacking in clinical settings. Recent technological advancements have enabled the evaluation of the depth of wounds, and three-dimensional measurements are now available. The aim of this study was to test the utility of a newly developed three-dimensional wound measurement device in the clinical setting.Methods: We recruited three patients, each with a PU, who were being treated by a PU team at a university hospital. We measured the length, width, area, and maximal depth of the ulcers by using the device and with the conventional method. The ulcer volume was measured only with the device. The difference in measurement results of the device before and after debridement was compared in the first patient. The difference in measurement results between the conventional method and the device was compared in the second patient. Correlation coefficients between the conventional method and the device obtained from longitudinal data were calculated in the third patient.Results: The changes in measurements between before and after debridement were easily detected by the device in the first patient. Although the maximal depth was different, the length, width, and area were consistent between the conventional method and the device in the second patient. The correlation coefficients of the length, width, and area between the conventional method and the device were 0.35, 0.48, and 0.59, respectively, in the third patient whose PU exhibited a vague wound edge.Conclusion: Although two-dimensional measurements were comparable between the conventional method and the device, there were some challenges to performing three-dimensional measurement more precisely. A further study is needed to determine the specific characteristics of wounds that result in poor measurement accuracy. Keywords: three-dimensional wound measurement device, wound depth, wound volum