Recognizing The Utility Of Biomarkers In Podiatric Practice And Future Applications

Lecturers recently discussed “biomarkers” at the Symposium on Advanced Wound Care Fall (SAWC Fall) 2019 in Las Vegas last month. Attending different lectures, I started to realize that although the term biomarker seems new, biomarkers are actually well-known to most of us taking care of patients. 

We often think of biomarkers as indicators of disease or severity of the disease state. However, in general terms, a biomarker is “anything that can be used as an indicator of a particular disease state or some other physiological state of an organism.”¹ 

There are some common existing markers that are not directly referred to as biomarkers. Body temperature is a well-known biomarker for fever. One uses blood pressure to determine the risk of stroke. It is also widely known that cholesterol levels are biomarkers and risk indicators for coronary and vascular disease, and that C-reactive protein (CRP) is a marker for inflammation. In essence, we have used biomarkers from the beginning of time to diagnose, evaluate and treat our patients. 

Biomarkers can be specific cells, molecules, genes, enzymes or hormones. A biomarker can serve as a predictive tool for a disease state, assist in early diagnosis, serve as a monitoring tool to indicate improvement or resolution of a disease state or process, or serve as a diagnostic tool to help assess the progress of a condition. Now with new technologies emerging, a biomarker can be something that helps us to design personalized therapies or individualized treatment plans. This can be specific to a particular condition or patient, determining the most effective therapeutic regimes or determining response to drug therapy.

A predictive biomarker helps to assess the most likely response to a particular treatment while a prognostic marker shows the progression of disease with or without treatment.² Early in the process of new drug development studies, researchers often use molecular biomarkers. For instance, a researcher would apply molecular biomarkers in a phase I study for establishing doses and dosing regimens for future phase II studies. 

In podiatric medicine, we are well aware of HbA1c, which serves as a biomarker for monitoring the clinical response to antidiabetic treatment. One may cite matrix metalloproteinases (MMPs) as a reason for non-healing wounds. Three-phase bone scans or those with Indium-111- and/or Technetium-99m-phosphate-labelled leukocytes evaluate for presence of infection in bone or fractures. This imaging can serve as a biomarker to assist in diagnosis. I suggest that podiatrists review what the best biomarkers may be for many of the procedures and treatment plans we provide, and publish on these biomarkers for ongoing recognition in the field of foot and ankle care.

During the SAWC Fall meeting, I started to think about two new technologies that I have been using for the past year in clinical trials. While these technologies are not specifically referred to as biomarkers, I feel that they meet the definition of a biomarker. 

The Snapshot NIR device (Kent Imaging) uses light in the near-infrared spectrum to determine tissue oxygen saturation, a key indicator of tissue health. Near-infrared light is very useful in detecting oxygenated and deoxygenated blood, which conveys not only tissue health but the healing capacity of wounds or tissue transplants as well. Oxygen saturation levels serve as biomarkers for wound healing potential and the viability of tissue substitutes, skin grafts or flaps.^3-6   

The other device I am currently enrolling patients for in an ongoing institutional review board-approved clinical trial is MolecuLight i:X Wound Imaging Device (MolecuLight). One can use this handheld fluorescence imaging device to assess wounds and surrounding skin.⁷ The MolecuLight i:X is precisely calibrated to detect bacteria at levels of ≥ 104 CFU/g on a quantitative scale or predominantly moderate-to-heavy growth on a semi-quantitative scale.⁸

There are many other biomarkers. In molecular terms, biomarker is "the subset of markers that might be discovered using genomics, proteomics technologies or imaging technologies.”⁹ Biomarkers play major roles in medicinal biology. Biomarkers are also seen as the key to personalized medicine with treatments individually tailored to specific patients for highly efficient intervention in disease processes such as in cancer treatment.⁹

Where are biomarkers already at work in your practice and where do you see them emerging in the future?

Dr. Aung is Chief of the Podiatry Section of the Tenet Health System/St. Joseph’s Hospital and a Panel Physician at Tenet Health System/St. Mary’s Hospital Outpatient Wound and Hyperbaric Center in Tucson, Ariz. She is a member of the APMA Coding Committee, the APMA MACRA/MIPS Task Force and is on the Exam Committee of the American Board of Wound Management. Her website is www.healthy-feet.com.

References

1. The Biomarkers Consortium. Foundation for the National Institutes of Health. Available at: https://fnih.org/what-we-do/biomarkers-consortium. Accessed 11/4/2019. 
2. Tevak Z, Kondratovich M, Mansfield E. US FDA and personalized medicine: in vitro diagnostic regulatory perspective. Per Med. 2010;7(5): 517–530. 
3. Bowen RE, Treadwell G, Goodwin M. Correlation of near infrared spectroscopy measurements of tissue oxygen saturation with transcutaneous pO₂ in patients with chronic wounds. SM Vasc Med. 2016;1(2):1006.
4. Landsman A, Barnhart D. Predicting wound closure and flap viability using near infrared spectroscopy (NIRS). Poster presented at: APWCA 17^th Annual National Clinical Conference; September 6-8, 2018; Baltimore. 
5. Livingston M. Multispectral oximetry imaging readings with associated healing trajectory. Kent Imaging Website. Available at: https://www.kentimaging.com/wp-content/uploads/2017/10/Kent_Wounds_6-Page_LD_final.pdf. Accessed 11/4/2019. 
6. Abdulrauf M, Stranc MF, Sowa MG, Germscheid SL, Mantsch HH. Novel approach in the evaluation of flap failure using near infrared spectroscopy and imaging. Can J Plast Surg. 2000;8:68-72. 
7. DaCosta RS, Kulbatski I, Lindvere-Teene L, et al. Point-of-care autofluorescence imaging for real-time sampling and treatment guidance of bioburden in chronic wounds: first-in-human results. PLOS ONE. 2015;10(2):e0116623. doi: 10.1371/journal.pone.0116623.
8. Rennie MY, Lindvere-Teene L, Tapang K, Linden R. Point-of-care fluorescence imaging predicts the presence of pathogenic bacteria in wounds: a clinical study. J Wound Care. 2017;26(8):452-460. 
9. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95.