Comments on “Non-classical monocytes frequency and serum vitamin D3 levels are linked to diabetic foot ulcer associated with peripheral artery disease”

We read with great interest the article titled “Non-classical Monocyte Frequency and Serum Vitamin D3 Levels are Linked to Diabetic Foot Ulcer Associated with Peripheral Artery Disease,” published in your esteemed journal¹. The research highlights the reduced frequency of non-classical monocytes and low vitamin D3 levels in patients with diabetic foot ulcers (DFUs) associated with peripheral artery disease (PAD), shedding light on the potential role of these factors in DFU pathogenesis. We commend the authors for this valuable contribution, but we believe several methodological improvements could further enhance the study's impact.

The study's focus on limited laboratory markers may have overlooked other potential indicators. Additional biomarkers, such as calcium, potassium, uric acid, liver function tests, and indices like the systemic immune-inflammation index (SII) and the systemic inflammation response index (SIRI), could provide deeper insights into the inflammatory processes at play in DFU patients². This might help better predict poor outcomes.

Although the Meggitt–Wagner classification provided useful data, it lacks a clear focus on vascular involvement. Other classification systems, such as the PEDIS and SINBAD systems, which evaluate factors like perfusion, depth, infection, and ischemia, could offer a more comprehensive assessment of DFUs and their correlation with PAD³.

The study did not explore other medications beyond antidiabetic drugs that patients might have been using, nor did it address the impact of conditions like cancer, hematologic disorders, or autoimmune diseases. These factors can influence immune function and thus alter the study outcomes.

Alcohol consumption was not investigated, despite its known role in DFU outcomes. Additionally, categorizing smoking status into non-smokers, former smokers, and current smokers could provide a clearer picture of its impact on DFU development and progression.

Classifying PAD into mild, moderate, and severe categories and comparing the frequency of non-classical monocytes and vitamin D3 levels across these groups would enrich the analysis, offering more nuanced insights into the relationship between PAD severity and immune response.

The relatively small sample size of the study could limit its statistical power, leading to wider margins of error. A larger cohort would increase the robustness of the findings, ensuring better generalizability and precision⁴.

In conclusion, while this study makes a significant contribution to our understanding of the relationship between non-classical monocytes, vitamin D3, and DFUs associated with PAD, addressing the outlined limitations would strengthen the findings and their implications. We believe that future studies incorporating these factors could further advance research in this critical area.

The authors declare no conflict of interest.

Approval of the research protocol: N/A.

Informed consent: N/A.

Registry and the registration no. of the study/trial: N/A.

Animal studies: N/A.