Method Article
The prognostic utility of neutrophil-lymphocyte ratio in spinal surgery: systematic review protocol.
https://doi.org/10.21203/rs.3.rs-1593367/v2
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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 for a systematic review.
Neutrophil
Lymphocyte
spine surgery
prognosis
outcomes
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 conduct a 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)).
Inclusion/exclusion criteria
A study will be included if it meets the following criteria: (1) Includes patients with any spine-related condition and/or those that underwent spine surgery; (2) evaluates the associations between baseline and/or post-treatment NLR and patients' outcomes; (3) reports the events ratio and/or area-under-curve (AUC) and/or provides raw rata from which these parameters can be calculated; and (4) English language and full text available. Exclusion criteria: (1) review articles, expert opinions, letters, conference abstracts, case reports, or editorials; or (2) non-human subjects; or (3) NLR used for diagnostic purposes and/or severity assessment of spine disease only.
Data extraction
Literature search duplicates will be excluded in Mendeley (Elsevier, London, UK). The titles/abstracts will be screened independently by two reviewers using Rayyan software. We will conduct a reference check of the selected articles to identify any additional studies. Two reviewers will independently screen full texts articles for eligibility and perform data extraction using a predesigned proforma. Discrepancies will be resolved through discussion between the reviewers until mutual agreement is reached.
Data to be extracted:
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.
Data analysis
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
1. Kepler CK, Vaccaro AR, Hilibrand AS, et al (2014) National trends in the use of fusion techniques to treat degenerative spondylolisthesis. Spine (Phila Pa 1976) 39:1584–1589. https://doi.org/10.1097/BRS.0000000000000486
2. Grotle M, Småstuen MC, Fjeld O, et al (2019) Lumbar spine surgery across 15 years: Trends, complications and reoperations in a longitudinal observational study from Norway. BMJ Open 9:e028743. https://doi.org/10.1136/bmjopen-2018-028743
3. Todd AG (2011) Cervical spine: Degenerative conditions. Current Reviews in Musculoskeletal Medicine 4:. https://doi.org/10.1007/s12178-011-9099-2
4. Fehlings MG, Arvin B (2009) Surgical management of cervical degenerative disease: The evidence related to indications, impact, and outcome. Journal of Neurosurgery: Spine 11
5. Kang CN, Kim CW, Moon JK (2016) The outcomes of instrumented posterolateral lumbar fusion in patients with rheumatoid arthritis. Bone and Joint Journal 98B:102–108. https://doi.org/10.1302/0301-620X.98B1.36247
6. Bible JE, Kang JD (2016) Anterior cervical discectomy and fusion: Surgical indications and outcomes. Seminars in Spine Surgery 28:. https://doi.org/10.1053/j.semss.2015.11.002
7. Barbanti-Brodano G, Griffoni C, Halme J, et al (2020) Spinal surgery complications: an unsolved problem—Is the World Health Organization Safety Surgical Checklist an useful tool to reduce them? European Spine Journal 29:. https://doi.org/10.1007/s00586-019-06203-x
8. Zahorec R (2001) Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratislavské lekárske listy 102:5–14
9. Russell CD, Parajuli A, Gale HJ, et al (2019) The utility of peripheral blood leucocyte ratios as biomarkers in infectious diseases: A systematic review and meta-analysis. Journal of Infection 78:. https://doi.org/10.1016/j.jinf.2019.02.006
10. Lin S, Hu S, Ran Y, Wu F (2021) Neutrophil-to-lymphocyte ratio predicts prognosis of patients with hepatocellular carcinoma: A systematic review and meta-analysis. Translational Cancer Research 10
11. Perry LA, Liu Z, Loth J, et al (2022) Perioperative Neutrophil-Lymphocyte Ratio Predicts Mortality After Cardiac Surgery: Systematic Review and Meta-Analysis. Journal of Cardiothoracic and Vascular Anesthesia 36:. https://doi.org/10.1053/j.jvca.2021.07.001
12. Li W, Hou M, Ding Z, et al (2021) Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Stroke: A Systematic Review and Meta-Analysis. Frontiers in Neurology 12
13. Gomes dos Santos A, de Carvalho RF, de Morais ANLR, et al (2021) Role of neutrophil-lymphocyte ratio as a predictive factor of glioma tumor grade: A systematic review. Critical Reviews in Oncology/Hematology 163
14. Mitsuya K, Nakasu Y, Kurakane T, et al (2017) Elevated preoperative neutrophil-to-lymphocyte ratio as a predictor of worse survival after resection in patients with brain metastasis. Journal of Neurosurgery 127:. https://doi.org/10.3171/2016.8.JNS16899
15. Nóbrega Lima Rodrigues de Morais A, Ribeiro Baylão VM, Martins Silva T, et al (2021) Is neutrophil-lymphocyte ratio a useful tool for predicting outcome in subarachnoid hemorrhage? A systematic review. Neurosurgical Review 44
16. Campbell M, McKenzie JE, Sowden A, et al (2020) Synthesis without meta-analysis (SWiM) in systematic reviews: Reporting guideline. The BMJ 368:. https://doi.org/10.1136/bmj.l6890
17. Mandrekar JN (2010) Receiver operating characteristic curve in diagnostic test assessment. Journal of Thoracic Oncology 5:1315–1316. https://doi.org/10.1097/JTO.0b013e3181ec173d
18. Huguet A, Hayden JA, Stinson J, et al (2013) Judging the quality of evidence in reviews of prognostic factor research: adapting the GRADE framework. Systematic reviews 2, 71:. https://doi.org/10.1186/2046-4053-2-71
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