Introduction

Compared to areas not considered to be in the “diabetes belt,” or part of a “diabetic cluster,” there are several factors that contribute to the higher prevalence of diabetes that lead to significant downstream implications such as the development of diabetic foot ulcers (DFUs) and amputations. These include cigarette smoking, dyslipidemia, obesity, physical inactivity, insulin resistance, high blood pressure, inadequate glycemic control [10], preventative care nonadherence, and lack of comprehensive insurance coverage, among others.

In addition, Peripheral Artery Disease (PAD) is considered a major risk factor for morbidity and mortality [11], and studies have shown an increased prevalence of PAD in lower-income areas [11]. Nearly 100,000 major leg amputations are performed every year in the US. Of these, over half are attributable to a combination of diabetes and PAD [4,12,13].  For patients with diabetes and PAD, especially in minority communities where there is a significant higher risk of amputation and poor survival, preventative care and care coordination are critical to avoid progression to Chronic Limb-Threatening Ischemia (CLTI), ulceration, amputation, and death. Integrating routine diabetic foot care and examinations and leveraging inexpensive tests, including hemoglobin A1c testing, and non-invasive vascular assessments have been shown to help limit amputation [14-16].

Inequities in healthcare outcomes exist when there are variations in the distribution of resources based on the geographic location of a population that contributes to the lack of opportunity and leads to the unavoidable differences in health outcomes. Recent community-based efforts to improve access to care, affordability, peer practices, community education, and adherence to treatment plans have been a focus of clinicians and patient advocacy groups alike [17]. The development of DFUs is a highly morbid consequence of longstanding and poorly managed diabetes. Of those patients with  diabetes, close to 35% will develop a DFU in their lifetime, with 20% of those  resulting in a lower-extremity amputation, either below or above the ankle, or both [18]. Additionally, 10% will die within 1 year of their DFU diagnosis [19,20]. Differences in practice patterns and insurance directives have been shown to contribute to unequal outcomes in minority populations [3,21-24]. For example, patients with DFUs that lack health insurance are less likely to undergo revascularization or wound debridement and more likely to have an amputation than those with private insurance [12,17,25]. These higher rates of amputation and increased mortality are much larger in low income and minority communities [26]. Since 2014, the incidence of lower-extremity amputation among these communities is growing, with some areas showing a 50% increase [27-29]. The combined effects of the socioeconomic differences, limited accessibility to proper healthcare, the disparities in levels of care and amputation rates by race and ethnicity cannot be and should not be ignored [30,31].

Emerging Botanical Based Treatments

Most commercially available treatments address only one component of a DFU at a time, such as inflammation, resulting in a significantly higher cost with little or no guarantee of success. Other treatments concentrate on addressing tissue bacterial loads while others promote improved vascularization.

Emerging, and novel botanical therapies that are safe, effective and low-cost could be a solution in overcoming gaps in care and providing alternatives to conventional treatments in this at-risk population (Figure 1). A botanical-based supercharged hydrogel, LAVIOR Diabetic Wound Gel (LAVIOR Pharma Inc., Miami, Florida), was developed to address many barriers to wound healing including  inflammation, bacteria, vascularization, and  hypoxia to support expedited wound healing. The product has been approved for reimbursement by Medicare -Part B and endorsed by the American Diabetes Association’s Better Choices For Life Program that provide consumers a simple way to identify products and services that are suitable for people with diabetes or at-risk for diabetes. National retail chains, such as Walmart, have also made this affordable over-the-counter treatment available, allowing easy access to this patient population in need of care, especially those with no insurance or those with high deductibles.

Figure 1: Reference: Yadav, J.P., Singh, A.K., Grishina, M. et al. Insights into the mechanisms of diabetic wounds: pathophysiology, molecular targets, and treatment strategies through conventional and alternative therapies. Inflammopharmacol (2024). Reprinted with permission.

Many diabetic foot ulcers therapies can  be cost prohibitive and vary in efficacy. One area of concentration and research has been identifying natural, non-synthetic treatment options, including those derived from botanicals. These well-researched botanicals, including Inula Viscosa and Inula Viscosa AGS RIED (Figure 2) are flowering plants native to the Middle East.

Figure 2: Inula Viscosa AGS RIED.

Inula viscosa (compositae) is known in traditional medicine for a large range of biological activities including antipyretic, anti-bacterial and antifungal activity [32]. It has been used to treat diabetes, bronchitis, diarrhea, rheumatism, and injuries, among other ailments. Inula Viscosa has been shown to elicit several responses in the body, including antimicrobial, antioxidant, antiulcerogenic, anthelmintic, and complications resulting from diabetes [33-38]. After over a decade of research, a new species of Inula Viscosa, AGS-RIED, has been incorporated into an Over the Counter (OTC) supercharged wound hydrogel (LAVIOR Diabetic Wound Gel®, LAVIOR Pharma Inc., Miami, FL) yielding a wide array of sesquiterpenoids, especially Sesquiterpene Lactones (SLs) [39-44]. SLs and have been shown to exhibit antimicrobial, antitumor, anti-inflammatory, antifungal, and antimalarial activity [40].  LAVIOR’s Diabetic Wound Gel specializes in addressing chronic wounds mired in the prolonged inflammatory stage, impeding proper healing. The gel is designed to be a vasodilator by encouraging oxygen to the wound. With their advanced technology, patient case reports have illustrated expedited healing, contributing to a better quality of life, reduced healthcare costs, reduced hospitalizations, and a lowering of the risk and necessity of limb amputation [45].

Case Reports

Herein the authors present two patient case reports reviewing the successful treatment with a supercharged hydrogel. Both patients had significant comorbidities and diabetes-related complications and were facing amputation. The patients have given consent for the use of their photos in this manuscript.

Patient 1 - History and Presentation:

A 46-year-old Haitian American male with a history of AIDS, sickle cell anemia, blood glucose abnormalities, chronic pain syndrome, deep vein thrombosis (DVT), and deficiency of nutrients. Patient presented with a 4 cm x 3 cm chronic medial malleolus ulcer (venous ulcer) with 100% fibrotic tissue and severe pain (Figure 3).

Prior Treatments: The patient did not receive any prior treatment before seeing the clinician.

Treatment Algorithm

The wound bed was rinsed with normal saline and the supercharged wound hydrogel was applied to entire wound surface and covered with a nonadherent dressing, 4x4 gauze and wrapped with Kling. Patients were instructed to apply the wound gel 2x/week with nonadherent dressing as daily changes causes maceration.

Figure 3: Treatment and healing progression of 46-year-old Haitian American male with a history of AIDS, sickle cell anemia, blood glucose abnormalities, chronic pain syndrome, Deep Vein Thrombosis (DVT), and deficiency of nutrients with Lavior Diabetic Wound Gel.

Results

After 7 days of treatment, the wound size reduced to 3 cm x 3 cm and there was 100% granulation, no pain on palpation, no drainage, and no sign of local infection. After 51 days of treatment with the hydrogel, the wound had 98% closure.  After 3 months from initial treatment, the wound had complete closure.         

Patient 2 - History and Presentation:

History: A 46-year-old Haitian American female with a history of diabetes and obesity who presented with a dry distal gangrenous 4th digit with necrotic changes, local edema, and erythema (Figure 4).

Prior Treatments: Previous treatment included Augmentin 500mg p.o every 12h x 10 days and Bactroban dressing on daily basis with no improvement.

Treatment Algorithm

The wound bed was rinsed with normal saline and the supercharged wound hydrogel was applied to entire wound surface and covered with a nonadherent dressing, 4x4 gauze and wrapped with Kling. Patients were instructed to apply the wound gel 2x/week with nonadherent dressing as daily changes causes maceration.

Figure 4: Treatment and healing progression of 46-year-old Haitian American female with a history of diabetes and obesity who presented with a dry distal gangrenous 4th digit with necrotic changes, local edema, and erythema with Lavior Diabetic Wound Gel.