The Role of NLR in the Diagnosis and Prognosis of Sepsis

Neutrophil-lymphocyte ratio (NLR), as an inflammatory index, is cheap and easy to obtain, and could be widely used in hospitals at all levels. NLR is a valuable biomarker that is significantly correlated with the status of immune and inflammatory responses. In the past few years, NLR has been continuously and extensively explored in various diseases, and the research progress is considerable. In cardiovascular disease, NLR can predict arrhythmia and short - and long-term mortality in patients with acute coronary syndrome. NLR may be associated with heart failure and valvular heart disease. Moreover, NLR has been shown to be associated with respiratory diseases (such as chronic obstructive pulmonary disease), immune diseases (rheumatoid arthritis and systemic lupus erythematosus), and digestive diseases (acute appendicitis, hepatocellular carcinoma, liver fibrosis, and cirrhosis).

Importantly, the study of NLR in sepsis has received much attention in recent years. A 2019 meta-analysis concluded that peripheral white blood cell ratios, including NLR, lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), are associated with clinical outcomes in sepsis and are useful biomarkers of infection. They recommended that NLR be evaluated in future hierarchical models, To clarify its relationship with NLR and clinical outcome and the prognostic value of NLR, it is worth mentioning that NLR has also been found to have the ability to predict the outcome of sepsis. It has been shown that NLR, together with other inflammatory parameters, might be a marker for early detection of sepsis in the intensive care unit. However, a large body of evidence demonstrating the association between NLR and adverse clinical outcomes in sepsis remains controversial. Another study concluded that "no association was found between NLR and 28-day in-hospital mortality in patients with sepsis". In addition, the reliability of NLR on admission in predicting the prognosis of critical illness was also lower than that of traditional markers (including CRP, PCT, serum lactic acid and APACHEⅡ score).

This study aimed to retrospectively investigate the early predictive value of inflammation-related parameters in-hospital mortality of septic patients.

Sepsis is defined as a life-threatening organ dysfunction caused by the host's malfunctioning response to infection, which has become one of the major problems in the world's public health. The development of effective biomarkers for the diagnosis of sepsis is undoubtedly helpful for us to timely and accurately understand the diagnosis, progression, and prognosis of sepsis.

The neutrophil-to-lymphocyte ratio (NLR), as an inflammatory indicator, is inexpensive and easily accessible parameter and could be widely used. In severe infectious diseases, particularly in sepsis, a substantial increase in peripheral blood neutrophils has been discovered, which reflects the severity of the inflammatory response. Neutrophil reverse migration following the initial neutrophil infiltration into inflammatory scenarios may further exacerbate the increase in the peripheral blood neutrophils. Lymphocyte apoptosis-induced reduction of peripheral blood lymphocytes is a significant feature of sepsis that could lead to adaptive immunosuppression. NLR is a cheap and rapidly available predictor of sepsis and has shown a significant correlation with other relatively expensive and non-rapidly existing markers of inflammation and sepsis.

Importantly, research on NLR in sepsis has received wide attention in recent years. NLR within 24 hours before intensive care unit (ICU) admission could be used as a marker for early diagnosis of sepsis. In addition to the diagnostic value of NLR, it is worth mentioning that NLR has also been found to have the ability of predicting the prognosis of sepsis. A meta-analysis in 2019 indicates that peripheral blood leucocyte ratios, including NLR, lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratios (PLR), could be useful infection biomarkers and associated with clinical prognosis of sepsis. A meta-analysis in 2020 also indicates that the higher NLR was linked to poor prognosis in patients with sepsis (n = 10,685) (hazard ratio (HR) = 1.75). NLR at admission is shown to be an independent predictor of in-hospital mortality of septic patients (n = 174). NLR, PLR and LMR can be useful predictors for early identification of post-percutaneous nephrolithotomy (PNL) sepsis. However, the exact role of NLR in the early prediction of the prognosis of septic patients remain controversial. No correlation was found between NLR at admission of emergency department and 28-day hospital mortality of septic patients. NLR at admission is less suitable than conventional inflammatory markers C-reactive protein (CRP) and procalcitonin (PCT) to detect the presence of sepsis in ICU patients. NLR at ICU admission is also less reliable than CRP, PCT, lactic acid and acute physiology and chronic health evaluation (APACHE Ⅱ) score in assessing the severity and in predicting 28-day mortality of critical illness.

In this study, the investigators enrolled septic patients to determine the role of NLR in the early prediction of in-hospital mortality of patients with sepsis. In addition, considering that PLR, neutrophil percentage (NE%) and monocyte to lymphocyte ratio (MLR) have been confirmed to be also associated with the mortality of patients with sepsis, while retrospectively analyzing the role of NLR, the investigators also studied the roles of PLR, MLR, neutrophil percentage, and other inflammation-related parameters on the first, second, third, and seventh days after hospitilization in the in-hospital mortality of septic patients.

Eligibility Criteria:
Inclusion Criteria:

* 1.Patients with sepsis
* 2.ICU stay time ≥3 days;

Exclusion Criteria:

* 1. History of solid organ or bone marrow transplantation;
* 2. Diseases that may affect immune-related indicators, such as autoimmune diseases such as rheumatoid arthritis and SLE, or hematological malignancies such as leukemia and lymphoma;
* 3. Have received radiotherapy or chemotherapy within the past 30 days, or have received immunosuppressive drugs (tripterygium, mycophenolate, cyclophosphamide, FK506, etc.), or have received continuous treatment with more than 10mg of prednisolone/day (or the same dose of other hormones);
* 4. Pregnancy or lactation;c