Outcome Analysis Of Hyperbaric Oxygen Therapy In Diabetic Wounds And Related Gene Expression Analysis
Vikram G. Mookerjee, Xiao Tian Wang, Mariska Raglow-Defranco, Solomon Swartz, Bielinsky Brea, Deborah Ciombor, Paul Y. Liu.
Rhode Island Hospital, Providence, RI, USA.
BACKGROUND Hyperbaric oxygen therapy (HBOT) is used to treat diabetic wounds. However, not all patients have a positive response to HBOT. We aimed to analyze the outcomes of HBOT in diabetic wounds and identify a molecular signature that differentiates HBOT-responsive from non-responsive patients to enable more cost-effective utilization of HBOT.
METHODS The medical records of patients with diabetic wounds and ≥10 HBOT treatments from September 2013 to August 2017 were reviewed. 6mm punch-biopsies were obtained from the wound beds pre-HBOT (T0) and after 7 treatments (T7). At the end of HBOT, total 7 biopsied patients were divided into responders (wound size reduction of ≥30%) and non-responders. Total RNA was extracted and RT-qPCR was performed to analyze 37 genes related to angiogenesis, inflammation, and oxidative stress. 6 housekeeping genes were selected to normalize gene expression. The threshold for changes in gene expression was set at 3-fold.
RESULTS Outcome of HBOT: 37 of 51 wounds (72.5%) were responders. Among these, 30 wounds (81.1%) completely closed. Among 14 non-responders, 6 wounds (42.9%) required amputation. Gene Expression: At T0, responders had lower relative expressions of 5 genes compared to non-responders: HSPA1A, ICAM1, TGFB1, TIMP2, and TNXB. However, at T7, these 5 genes plus TNF were up-regulated in responders compared to T0. In non-responders, CCL2 was down-regulated and TXN was up-regulated. CONCLUSIONS A 30% reduction in wound size during HBOT is a critical threshold to distinguish HBOT-responsive wounds, with significant differences in both complete wound closure and amputation rates. The responders exhibited lower gene expressions of HSPA1A, ICAM1, TGFB1, TIMP2, and TNXB before HBOT compared to non-responders, but presented notably up-regulated expression of these genes after 7 HBOT treatments; in contrast, non-responders failed to up-regulate these genes in response to HBOT. These genes could be candidates for predicting HBOT-responsiveness in future studies.
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