Comments on ‘The impact of inflammatory biomarkers on amputation rates in patients with diabetic foot ulcers’

I have read with great interest the article titled ‘The impact of inflammatory biomarkers on amputation rates in patients with diabetic foot ulcers’, recently published in your esteemed journal.¹ The study's exploration of the association between hematological inflammatory markers and the likelihood of amputation in patients with diabetic foot ulcers (DFUs) is both timely and relevant, especially given the increasing prevalence of diabetes-related complications. However, while the study offers valuable insights, several methodological limitations warrant further consideration to enhance the findings' robustness and applicability in clinical practice.

Firstly, the selection of inflammatory biomarkers appears somewhat limited. Expanding the scope to include additional markers, such as the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammatory Response Index (SIRI), could provide a more comprehensive understanding of the inflammatory processes driving amputation risk in DFU patients.² Recent studies have demonstrated that these indices are robust predictors of poor outcomes in various inflammatory conditions, including DFUs.³ Their inclusion could yield a more thorough analysis of the correlation between inflammation and amputation rates.

Moreover, when assessing the relationship with inflammatory biomarkers, the study does not distinguish between major and minor amputations. Differentiating between these categories could reveal essential distinctions in the inflammatory response associated with varying levels of limb loss, providing more nuanced insights into the severity of DFUs and the corresponding inflammatory response.

Another critical aspect that could have been better addressed is determining optimal cut-off values for biomarkers like C-reactive protein (CRP). Establishing precise thresholds is crucial for translating research findings into clinical practice, where they can guide decision-making and help identify patients at the highest risk of adverse outcomes. The lack of such data in the study limits the clinical utility of these biomarkers in predicting amputation risk.

Additionally, while the article acknowledges the role of inflammation in peripheral arterial disease (PAD), it stops short of fully elucidating the connection between vascular involvement and inflammatory biomarkers in the context of DFU-related amputations.^{4, 5} Given that PAD is implicated in a significant proportion of lower limb amputations, a more in-depth exploration of this relationship could provide a more holistic understanding of the factors influencing amputation risk in DFU patients.

A more detailed statistical analysis could further enhance the study's credibility. For instance, utilizing advanced statistical models that account for confounding variables or conducting a power analysis to ensure the study is adequately powered would strengthen the findings. It would also be beneficial to explore whether patient diversity—such as differences in age, gender or comorbidities—was sufficiently accounted for, as these factors could significantly influence inflammation and subsequent amputation risk.

Finally, considering the practical implications of these findings in clinical settings could further enrich the study. For example, discussing how including additional biomarkers or determining optimal cut-off values might improve patient stratification, enable earlier interventions or lead to more tailored treatment strategies would provide a more straightforward path from research to clinical practice.

In conclusion, while the article makes a valuable contribution to the field, addressing these methodological and analytical limitations would significantly strengthen the study's impact and applicability in clinical practice. I encourage the authors to consider these suggestions for future research, as they hold the potential to improve patient outcomes and advance our understanding of DFU management.

The authors declare no conflicts of interest.

Written informed consent was obtained from the patient to publish the current case report.