Is procalcitonin to cortisol ratio really the right combination?

Dear editor,

We read with great interest the article by Liu H et al.[1] The authors proposed to explore the value of the procalcitonin-to-cortisol ratio (P/C ratio) in predicting the prognosis of patients with abdominal sepsis. However, we have some concerns.

First, when developing a ratio with two parameters, one of the parameters should have a positive linear relationship with the disease severity, and the other should have a negative linear relationship. The neutrophil-to-lymphocyte ratio (NLR) is a classic ratio developed in this format, which includes neutrophil counts that increase as an inflammatory disease worsens and lymphocyte counts that normally decrease as an inflammatory disease worsens.[2] The issue is that serum cortisol levels and illness severity have a U-shaped relationship rather than a linear one,[3] which means that either low or high serum cortisol levels indicate a poor prognosis.

Second, according to a systematic review and meta-analysis, procalcitonin is only moderately effective as a postoperative sepsis diagnostic test in major abdominal surgery.[4] In addition, procalcitonin is not very good at predicting the prognosis of sepsis.[5]

Third, according to this study, there was a statistically significant difference in serum cortisol levels (8 a.m.) between the survival and non-survival groups, with a P-value of 0.045. Furthermore, receiver operator characteristic curve analysis was used to compare procalcitonin and P/C ratio, and the result showed no differences (P=0.087). These results may not be convincing.

Therefore, we consider that the combination of procalcitonin and cortisol might not be the optimal one.

REFERENCES

• 1 Liu H, Hu J, Xiao JG, Kang HJ, Zhou FH. The procalcitonin-to-cortisol ratio is a potential prognostic predictor in sepsis with abdominal source: a retrospective observational study. World J Emerg Med. 2022;13(6):441-7.

• 2 Huang Z, Fu Z, Huang W, Huang K. Prognostic value of neutrophil-to-lymphocyte ratio in sepsis: a meta-analysis. Am J Emerg Med. 2020;38(3):641-7.

• 3 Qin F, Sun Y, Hu W, Wei X, Li Z, Zhou J, et al. The relationship between preoperative serum cortisol level and the stability of plaque in carotid artery stenosis patients undergoing carotid endarterectomy. J Thorac Dis. 2016;8(7):1611-7.

• 4 Jerome E, McPhail MJ, Menon K. Diagnostic accuracy of procalcitonin and interleukin-6 for postoperative infection in major gastrointestinal surgery: a systematic review and meta-analysis. Ann R Coll Surg Engl. 2022;104(8):561-70.

• 5 Lee S, Song J, Park DW, Seok H, Ahn S, Kim J, et al. Diagnostic and prognostic value of presepsin and procalcitonin in non-infectious organ failure, sepsis, and septic shock: a prospective observational study according to the Sepsis-3 definitions. BMC Infect Dis. 2022;22(1):8.

Author’s reply

Thanks for your interest in our article about the predictive value of the procalcitonin-to-cortisol ratio (P/C ratio).

It is critical to develop a ratio to predict the prognosis in the clinical study. However, there are plenty of confounding factors, especially when more than one parameter is involved in the predictive model. In fact, there are still some debate about the role of neutrophil-to-lymphocyte ratio (NLR) as a predictor of prognosis. A previous study found no significant relationship between NLR and prognosis of mortality in critically ill patients with sepsis.[1] Another study reported that the non-survivors had a relatively lower NLR, with a 0.1-fold reduction in mortality for every 10-unit increase in sepsis.[2] Another study reported that a low NLR was associated with early death (< 5 d after the onset of septic shock) in septic shock patients, the NLR of the early-death patients at admission was significantly lower than that of late-death patients and survivors. However, an increase in NLR was associated with late death (> 5 d after the onset of septic shock) in septic shock patients.[3] On the other hand, the cut-off value of NLR varied dramatically from 4.36 to 23.8,[4] indicating the extent of uncertainty of NLR. NLR is possibly affected by the disease severity, corticosteroid treatment, different stages of sepsis and so on.

There are also some combinations of parameters that have the same tendency according to the severity of the disease. The ratio of creatine kinase MB isoenzyme (CK-MB) to CK is a classic index for predicting the occurrence of myocardial infarction. CK-MB/CK increases to more than 5%–8% when myocardial infarction occurs.[5] In the other example, severe fever with thrombocytopenia syndrome (SFTS), a common infectious disease caused by the severe fever with thrombocytopenia syndrome virus, has emerged as a public health concern due to its high mortality rate. AST and ALT are two regular liver enzymes that increase simultaneously during liver injury. The AST/ALT ratio has been shown to be an independent risk factor for the prognosis of patients with SFTS. AST/ALT-ratio >2.683 was associated with a shorter median survival time, indicating an unfavourable prognosis.[6]

In our study, although there is no significant difference between the P/C ratio and PCT, the P/C ratio is an effective prognostic index with a high AUC (0.919). This was a single-center retrospective cohort study. Therefore, bias could not be avoided. The sample size was relatively small, with only 132 participants enrolled. The age range was wide, from 18 to 90 years old. Elderly patients have a higher risk of critical illness-related corticosteroid insufficiency (CIRCI). The study was an attempt to find out more about CIRCI. Further research is needed to confirm this.

Thank you again for your concern.