Method Article
The prognostic utility of neutrophil-lymphocyte ratio in spinal surgery: systematic review protocol
https://doi.org/10.21203/rs.3.rs-1593367/v1
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Neutrophil-lymphocyte ratio has been extensively reported to predict patients' outcomes in fields such as cancer, cardiac surgery, infection, and stroke medicine. However, there is no consensus on the prognostic utility of NLR in spinal surgery patients. Hence, this systematic review aims to analyse existing evidence and evaluate the relationship between NLR and outcome measures in spinal surgery patients.
This is a study protocol describing our systematic review methods.
Due to the ageing population, spine-related conditions have become one of the most common presentations in healthcare and are the leading causes of disability and low quality of life worldwide [1–4]. Various spine surgery procedures have been associated with significant functional improvements in some patients with spinal pathologies such as trauma, degenerative disc disease, spondylolisthesis, and deformity [2, 5, 6]. However, complications that increase morbidity and mortality, reportedly occur in 7 to 20% of spinal surgery cases [7]. There is a need for an effective prognostic tool that would facilitate risk-benefit considerations for surgery, prompt postoperative surveillance of high-risk patients and consequentially enable early recognition and timely management of complications.
Neutrophil-lymphocyte ratio (NLR), the ratio of the absolute neutrophil count and absolute lymphocyte count in peripheral blood, is a routinely available and inexpensive marker of systemic inflammation [8]. In the last decade, NLR has been widely reported as an effective prognostic tool in cancer, cardiac surgery, infection, stroke, subarachnoid haemorrhage, gliomas, and brain metastasis [9–15]. However, the association between NLR and clinical prognosis in spinal surgery has not been established. Hence, this systematic review aims to analyse existing evidence and evaluate the relationship between NLR and outcome measures in spinal surgery patients.
Literature search
We will perform a comprehensive literature search using the PubMed, SCOPUS and EMBASE databases from inception till April 22, 2022. We will search the abstracts/titles/ keywords on these databases as follows: ((neutrophil to lymphocyte ratio) OR (neutrophil lymphocyte ratio) OR (neutrophil-to-lymphocyte ratio) OR (NLR)) AND ((spin*) OR (cervical) OR (thorac*) OR (lumb*) OR (decompression) OR (fusion) or (vertebroplasty) OR (kyphoplasty) OR (laminectomy) OR (foraminotomy) OR (nucleoplasty) OR (corpectomy)) NOT ((cervical-cancer) OR (cervical-dysplasia)).
A study will be included if it meets the following criteria: (1) Included patients with any spine-related non-neurodegenerative condition and/or those that underwent spine surgery; (2) evaluates the associations between baseline and/or post-treatment NLR and patients' outcomes; and (3) English language and full text available. A study will be excluded if it meets any of these criteria: (1) review articles, expert opinions, letters, conference abstracts, case reports, or editorials; or (2) non-human subjects; (3) neurodegenerative conditions (4) did not report the events ratio or area-under-curve (AUC) while evaluating the prognostic utility of NLR; or (5) NLR used for diagnostic purposes and/or assessment of disease severity only.
Literature search duplicates will be excluded in Mendeley (Elsevier, London, UK). The title/abstracts will be divided into four sets, and each set will be screened independently by two reviewers using Rayyan software. The eligible full texts will also be divided into four sets. Two reviewers will independently screen a set of full texts articles and subsequently perform data extraction using a predesigned data extraction proforma. Discrepancies will be resolved through discussion between the reviewers until mutual agreement is reached
Data to be extracted:
Title
Author
Year of publication
Study design: prospective versus retrospective; cohort study versus case-control study versus other.
Country of study
Procedure(s) included
Spinal condition(s) included
Exclusion criteria
Number of patients
Age (mean + SD/ median (IQR))
Sex (number of Male/ number of Female)
Day blood sample was obtained: Preoperative or postoperative. If postoperative, the day(s) the blood sample was taken will be extracted.
Average NLR value
Outcome measure: The nature of the outcome measured that will be identified is uncertain, therefore there will be no prior criteria. It is anticipated outcomes, such as the following, will be identified, and used as inclusion criteria:
Complications
Pain outcomes
Functional outcomes
Length of stay
Overall survival /mortality.
For each outcome measure, we will extract the following data: Length of follow-up, number of patients with event/ number without event, NLR threshold, the method used for threshold selection, AUC, sensitivity, specificity, event ratio with 95% confidence interval, conclusion (association between NLR and outcome measure)
Multivariate data is preferred to univariate data if both are provided. However, univariate data will be deemed acceptable if no multivariate results is presented.
Using the Synthesis without meta-analysis (SWiM) in systematic reviews reporting guideline [16], we will conduct a narrative synthesis describing the association between NLR and patient outcomes reported in the spine surgery. Studies will be primarily grouped based on outcome measures and secondarily by the time the blood samples were taken (baseline versus postoperative).
For the studies reporting event ratio, the direction of effect will be categorised as significantly positive, significantly negative, or not significant. For studies reporting AUC, the direction of effect will be categorised as excellent (AUC > 0.9), good (AUC = 0.8–0.9), acceptable (AUC = 0.7–0.8), poor (AUC = 0.6–0.7), and failed (AUC = 0.5–0.6) [17].
Subsequently, for each outcome measure, the prognostic utility of baseline and post-treatment NLR will be summarised by vote counting the direction of effect reported in each study. Also, we will summarise the effect estimates by reporting the median and interquartile range of the effect estimates for each outcome measure. Heterogeneity in reported effects will be investigated by structuring tables and figures around the outcomes assessed.
The quality assessment of selected articles will be assessed by two independent reviewers using the Newcastle–Ottawa scale (NOS) criteria. Studies with NOS scores 0–3, 4–5, 6–7 and 8–9 will be considered as unsatisfactory, satisfactory, good quality and very good quality, respectively. We will conduct sensitivity analysis by repeating our primary analysis after: (i) excluding the studies considered as unsatisfactory (NOS scores: 0–3) and (ii) excluding the studies considered as unsatisfactory or satisfactory (NOS scores: 0–5).
The certainty of evidence of the synthesis findings for each outcome measure will be evaluated by using the GRADE framework for prognostic factor research [18].
We will not perform more advanced meta-analyses because we are considering a wide range of associations with NLR and a high level of heterogeneity is expected across the selected studies.
Conflicts of interest:
None
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