[Response to Letter] “Association Between the Systemic Inflammatory Response Index and Severe Infection in Patients with Diabetic Foot”

Dear editor

Thank you very much for recognizing the advantages of this manuscript, as well as for your careful reading and constructive ideas. We will briefly summarize and respond to the issues mentioned in the previous letter.¹

Firstly, according to the guidelines of the International Diabetes Federation (IDF) and the International Working Group on the Diabetic Foot (IWGDF), the severity of diabetic foot infection (DFI) was defined as follows. 1) Moderate infection: an ulcer extending to bone and fascia, erythema >2 cm in diameter, and no systemic symptoms. 2) Severe infection: the presence of two or more systemic symptoms, such as temperature >38°C or <36°C, heart rate >90 beats/min, respiratory rate >20 breaths/min, partial pressure of carbon dioxide <4.3 kPa (32 mmHg), white blood cell count >12,000 or <4,000 cells/mm³, or the presence of >10% immature (band) neutrophils. The Systemic Inflammatory Response Index (SIRI) was calculated as follows: SIRI = (neutrophil count × monocyte count)/lymphocyte count. Considering that SIRI and severe DFI each have some other important components besides neutrophils, we believe that the abnormality of neutrophil count alone cannot fully represent SIRI or the severity of DFI, which is why the guidelines have combined other indicators to diagnose the severity of DFI. For this reason, we believe that the potential relationship between SIRI and severe DFI in neutrophils does not affect the consideration of SIRI as an evaluation indicator for severe DFI. On the contrary, we aim to find a clinically accessible and efficient indicator that may reflect severe infection through the definition of severe infection, and the situation of the same source allows SIRI to balance accessibility and correlation. In addition, precisely because the area under the ROC curve is an exploratory preliminary analysis, we continued to conduct multi factor analysis and subgroup analysis in our manuscript to further demonstrate that our conclusion is robust. However, we also believe that it is an interesting and clinically valuable viewpoint to perform a sensitivity analysis excluding the leukocyte and neutrophil components from the severity definition, which will be analyzed in future prospective studies in our plan. Our readers’ innovative and highly valuable comments may also be considered as an internal consistency validation of the diagnostic criteria for severe DFI. We are currently conducting data collection for a large sample prospective study. Thank you once again sincerely for your valuable suggestions. Please look forward to our future manuscripts.

Secondly, based on the suggestion on the multivariable logistic regression model, we have recently conducted the bootstrap validation, and the calibration curve can further support our model (Figure 1). At the same time, we analyzed the variance inflation factors (VIF) of our final model and found that all VIFs were less than 5, which further suggested that the final model was reliable. This result also further supports that an events-per-variable (EPV) ratio in our manuscript is acceptable in the range of 5–10.²

Figure 1.

The calibration curve of our final model.

Notes: The red arrow emphasizes the apparent curve, bias-corrected curve, and ideal curve (Bootstrap=2000).

Thirdly, regarding the remaining suggestions, as mentioned in the limitations section of our manuscript, it is essential that prospective studies with larger sample sizes should be conducted. As emphasized in the title of our manuscript, our core conclusion is still aimed at the association. A prospective study is something we are currently working on. The issue of stronger evidence for causal relationships will be further demonstrated in our prospective research. Unfortunately, as the data for our future research has not yet been made public, we are temporarily unable to share it with readers. The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Thank you once again sincerely for your valuable suggestions. Please look forward to our future manuscripts.

Fourthly, we highly appreciate the valuable comments from our readers and welcome you to further message us for cooperation.

Funding Statement

This communication was supported by the Changzhou Science and Technology Program (CJ20242025) and the Major Science and Technology Projects of Changzhou Health Commission (ZD202425).

Data Sharing Statement

The data that support the supplementary findings of this communication are available from the corresponding author upon reasonable request.

Author Contributions

Ping Wu: Conceptualization, Funding acquisition, Writing – original draft. Wendong Xu: Writing – original draft. Rui Chen: Writing – original draft. Zhenghui Xu: Conceptualization, Writing – review and editing. All authors have agreed on the journal to which the article will be submitted. All authors reviewed and agreed on all versions of the article before submission, during revision, the final version accepted for publication, and any significant changes introduced at the proofing stage. All authors agree to take responsibility and be accountable for the contents of the article.

Disclosure

The authors report no conflicts of interest in this work.