Protocol registration

This study will be performed based on Preferred Reporting Items for Systematic Review and Meta-Analyses Protocol (PRISMA-P) guideline [16] (S1 Table). The protocol was registered on the website of https://www.crd.york.ac.uk/prospero/ on June 13, 2021 (Registration number: CRD42021260459). We plan to conduct this study between May 2021 and December 2021.

Data sources and search strategies

The literature search was conducted using PubMed, Embase and Cochrane Library databases from inception to May 10, 2021 to determine eligible observational studies on the impact of sarcopenia on postoperative outcomes in patients undergoing spinal surgery. The search will apply Medical Subject Headings and free-text words related to the following three elements: sarcopenia, spinal surgery, and clinical outcomes (S2 Table). We will not include grey literature such as unpublished conference proceedings or abstracts from relevant conference meetings due to potential high risk of bias. In addition, we will also manually screen the reference list of included studies to identify additional studies that meet the inclusion criteria, with the aim to minimize the missing literatures. If the related data provided in the original articles are unclear or insufficient, we will contact the corresponding authors to obtain detailed information.

Study selection and eligibility criteria

Relevant observational studies that describe the clinical outcomes in sarcopenia patients undergoing spinal surgery are identified by T.W. and Z.X. The titles, abstracts and full texts (if necessary) will be reviewed to determine eligibility of the study on the basis of inclusion and exclusion criteria. Any discrepancy will be resolved through discussion; otherwise, a senior author (Z.M.) will be consulted.

The inclusion criteria of this study are summarised using the PECOS (participants, exposure, comparison, outcome, study design) framework according to Cochrane handbook [17].

Participants

Surgically treated patients (over 18 years of age) with an established diagnosis of spine diseases including spinal injury, scoliosis, intervertebral disc herniation, a variety of spinal degenerative diseases or malignant spinal metastases based on accepted criteria (such as clinical symptoms and imaging examinations) will be included.

Exposure

Sarcopenia is the primary exposure of interest. Therefore, studies will be included in the systematic review if their exposed participants have a confirmed diagnosis of sarcopenia.

Studies in which the exposure status (both primary and secondary sarcopenia) is mainly determined according to the European Working Group on Sarcopenia in Older People (EWGSOP) (2010), EWGSOP2 (2018), the Foundation for the National Institutes of Health Sarcopenia Project (FNIH) (2014) and Asian Working Group for Sarcopenia (AWGS) algorithm [18, 19]. Sarcopenia can also be measured by low muscle mass, low skeletal muscle strength, and poor physical performance. A non-sarcopenia cohort is defined as the non-exposure (comparison) group.

Outcomes

Studies will be included in this systematic review if one of the outcomes will be involved (1) major adverse outcomes of spinal surgery; (2) length of stay; (3) adverse events.

Major adverse outcomes of spinal surgery will include:

• Lower back pain, lower extremity pain, and lower extremity numbness, assessed using Japanese Orthopaedic Association (JOA) and visual analogue scale (VAS) scores [20].
• Postoperative complications, commonly including postoperative visual loss, peripheral nerve injury, skin damage, postoperative nausea and vomiting and deep vein thrombosis collected according to Clavien-Dindosystem [21].
• Morbidity rate, which is calculated and assessed by the Charlson Comorbidity Index [22]
• Mortality, including in-hospital mortality, 30-day postoperative mortality, 90-day postoperative mortality and overall mortality.

Length of stay refers to duration between admission and discharging.

Adverse events include anemia requiring blood transfusion, cardiac arrest, septicemia, wound complications (rupture, infection), confusion, intraoperative dural tear, acute renal injury, pneumonia, urinary tract infection, urinary retention, epidural hematoma, deep venous thrombosis, etc. [8]. Adverse events will be collected using spinal event severity system version 2 (SAV2.0) [23].

Data extraction

Two reviewers will independently extract the date using a piloted standardized data extraction form. Any discrepancies will be resolved through discussion and, if necessary, the corresponding authors of the original text will be contacted to obtain correct and complete information. The following information will be extracted from each study:

• First author
• Year of publication
• Study design
• Study region or country
• Observation period
• Sample size of the involved participants
• Sex ratio
• Preoperative diagnosis
• Comorbidity
• Surgical methods
• Surgical site
• Surgical acuity
• Definition and measurement of sarcopenia
• Outcomes with their definitions
• Follow-up period
• Adjusted variables

Methodological quality assessment

Methodological quality (risk of bias) will be assessed using Newcastle-Ottawa Scale (NOS) tool [24]. Any discrepancies will be resolved through consensus. For each eligible observational study, the following domains will be assessed: the representativeness of the exposed cohort, the selection of the control (non-exposed) cohort, the determination of exposure factors, whether the outcome events occur before the start of follow-up, the comparability of the cohort, the assessment of the outcome events that occurred, the duration of follow-up, and report on the levels of loss to follow-up [25]. A score of NOS 7 or less corresponds to low study quality (a high risk of bias), and a score greater than 7 corresponds to high study quality (a low risk of bias).

Data synthesis

Stata statistical software (version 15.0; STATA, College Station, TX) will be used for all meta-analysis. We will abstract directly or calculate odds radio (OR) and 95% CI as the effect measure for dichotomous variables. While for continuous outcome variables, weighted mean difference (WMD) (if all the studies use the same measurement tool and the same unit) or standardized mean difference (SMD) (if studies use various measurement tools or different units) will be abstracted along with their corresponding 95% CIs for meta-analysis. Dichotomous outcome variables will be pooled using the Mantel Haenszel method and continuous outcome variables will be pooled using the inverse variance method [26]. Between-study heterogeneity will be evaluated by Cochrane Q test with a P value more than 0.10 indicating no heterogeneity or slight heterogeneity, while P more than 0.10 implying significant heterogeneity. Besides, heterogeneity will also be assessed by the I² statistics with I² values more than 50% considering significant heterogeneity [27, 28]. A summary of exposure effect estimates will be calculated using the more conservative approach of a random effects model. In addition, sensitivity analysis will be performed to test the robustness of pooled estimates. Multiple subgroup analyses will also be performed to further explore the source of between-study heterogeneity stratified by disease type (degenerative spinal disease vs. traumatic spinal injury vs. spinal metastatic disease), sarcopenia definition (EWGSOP vs. AWGS) and other variables. When a sufficient number of studies (≥10 studies) are included for meta-analysis, publication bias will be assessed by visual inspection of the funnel plot symmetry and further by Egger’s linear regression test [29]. We will only provide a narrative description instead of meta-analysing the study outcome data if significant heterogeneity exists. If a publication bias is suggested, we will utilize the Duvall and Tweedle trim-and-fill model to adjust the effect estimates [30].