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What Next-Generation Sequencing Reveals About TCC And Chronic DFUs

Total contact casting (TCC) is the gold standard for offloading diabetic foot ulcers. Period. Yet, it remains far too seldomly used by wound care practitioners of all specialties, including podiatric physicians. There are many reasons for this, including the time it takes to remove and apply casts in a busy clinical setting, the cost of materials and issues with reimbursement. Patients can also be apprehensive about TCC due to past (negative) experiences, fear of infection from an inability to inspect the wound frequently and mobility limitations/restrictions. Additionally, casts can crack, get wet or dirty, and need replacement at unpredictable times (usually on a Friday afternoon).

Of course, it is well-established that the success of TCC in healing DFUs revolves around a combination of pressure reduction and forced adherence.1-2 Patients cannot remove the offloading device. Therefore, the wound remains protected for the duration of therapy. However, another explanation may lie deep within the microbiome.  

We recently started investigating the effect of TCC on the microbiome of chronic diabetic foot ulcers (DFUs) using next-generation sequencing (NGS). Next-generation sequencing is a diagnostic assay that can detect known pathogens comprising the microbiome, including fungi, viruses, protists and bacteria with a rapid turnaround time (less than 48 hours). Collecting samples from wounds on a weekly basis from patients utilizing TCC and employing next-generation sequencing with bioinformatics analysis, we have observed some interesting, albeit very preliminary, findings.  

First, chronic ulcers not exhibiting clinical signs of infection still show colonization by a large variety of microorganisms. Second, the microbiological makeup of ulcers in patients with TCC seems to change from week to week. This is not unlike the findings by Gardner and team, who analyzed the microbiome of neuropathic, non-ischemic DFUs using high-throughput sequencing of the bacterial 16S ribosomal RNA gene.3 In this study, the authors found that traditional culture methods significantly underrepresented microbial load, the presence and diversity of potential pathogens, and that ulcer duration positively correlated with bacterial diversity.

Loesche and colleagues also studied the microbiome of DFUs using high throughput sequencing of the 16S ribosomal RNA gene, and reported a faster rate of healing in wounds with a more dynamic microbiota.4 Perhaps most interesting and worthy of further study will be the potential change in the microbiome that occurs in the days and weeks leading up to wound closure.

Although it bears repeating that the work involving TCC and next-generation sequencing remains in the very early stages, this combination of “old meets new” treatment may offer clues for solving the puzzle of healing chronic DFUs. More importantly, it may provide substantial evidence that TCC is more complex than previously understood.

Dr. Isaac is the Director of Research with Foot & Ankle Specialists of the Mid-Atlantic (FASMA). He is a Diplomate of the American Board of Foot and Ankle Surgery.

References
1.    Lavery LA, Vela SA, Lavery DC, Quebedeaux TL. Reducing dynamic foot pressures in high-risk diabetic subjects with foot ulcerations. A comparison of treatments. Diabetes Care. 1996;19(8):818-821.
2.    Armstrong DG, Lavery LA, Kimbriel HR, Nixon BP, Boulton AJ. Activity patterns of patients with diabetic foot ulceration: patients with active ulceration may not adhere to a standard pressure off-loading regimen. Diabetes Care. 2003;26(9):2595-2597.
3.    Gardner SE, Hillis SL, Heilmann K, Segre JA, Grice EA. The neuropathic diabetic foot ulcer microbiome is associated with clinical factors. Diabetes. 2013;62(3):923-930.
4.    Loesche M, Gardner SE, Kalan L, et al. Temporal stability in chronic wound microbiota is associated with poor healing. J Invest Dermatol. 2017;137(1):237-244.

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