Abstract
To the Editor:
W
Regarding the aspects mentioned by the authors, we would like to make some comments and clarifications. First, regarding the post-surgical missing variables (such as the presence of leukocytosis or clinical signs of infection), we agree on their relevance for the present investigation. If in the future a strong correlation is established between serum interleukin-6 (IL-6) values and other more cost-effective and available markers of systemic inflammation derived from the hemogram (such as the systemic immune-inflammation index), this could result in a rapid, inexpensive, and applicable test that could be used routinely in the postoperative period of patients who have undergone surgery for pediatric acute appendicitis (PAA). Similarly, if a greater number of post-surgical variables are rigorously collected, adjusted multivariable analyses can provide evidence on different aspects of the pathology in prognostic terms, which is a field of great interest.
Second and concerning the sample size of our work, our analysis was effectively limited by the sample size. Obtaining serum IL-6 samples 12 hours after surgery invariably implied obtaining samples at untimely hours, and in many cases, the patient's peripheral venous accesses did not reflux so a new venipuncture was required to obtain them. These factors had an important influence on the loss of samples during our investigation and we believe that they should be considered by future authors. In our case, we opted to obtain the serum IL-6 measurement 12 hours after surgery to avoid potential losses in patients who were discharged early. However, it would be of great interest to obtain serial measurements at other points (for example, at 24 and 48 hours) to establish marker curves and determine the moment of greatest diagnostic and prognostic yield for post-surgical serum IL-6. We agree with the authors on the existence of a potentially high interindividual variability and add as a nuance the potential usefulness of age-stratified analyses, given the behavior shown by other biomarkers in children depending on the age range in which they are determined (such as leukocytosis).
Finally, we believe that the wide analytical ranges of the molecule that we obtained, with significant outliers, corresponds to the nature of IL-6 and we do not believe that they are conditioned by the sample size of our analysis. The preceding literature supports this fact.3,4 Other markers such as serum calprotectin have previously demonstrated this behavior in the context of PAA. 5
Our research group is currently developing a prospective multicenter study (BIDIAP 2), which is expected to provide new insights into the diagnostic and prognostic role of serum IL-6 in PAA. We look forward to sharing our results soon.