Prognostic value of the CALLY index for functional outcomes in acute ischemic stroke: a systematic review and exploratory quantitative synthesis

Background The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel composite biomarker reflecting systemic inflammation, nutritional status, and immune function. Emerging evidence suggests its potential prognostic value in acute ischemic stroke (AIS). However, no systematic analysis has been conducted to evaluate its association with functional outcomes in AIS patients. This systematic review with exploratory quantitative synthesis aimed to assess the prognostic value of the CALLY index for functional outcomes in AIS. Methods We systematically searched the Cochrane Library, EMBASE, PubMed, and Web of Science databases from inception to March 2026. The search was initially conducted in February 2025 and updated in March 2026 prior to submission. Observational studies evaluating the association between the CALLY index and functional outcomes in AIS patients were included. The primary outcome was poor functional outcome defined by the modified Rankin Scale (mRS), with poor outcome defined as mRS ≥ 2, mRS > 2, or mRS ≥ 3 at 3 months. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Heterogeneity was evaluated using Cochran’s Q test and I 2 statistic. Results Three studies involving 1,161 AIS patients were included. The exploratory quantitative synthesis revealed that a higher CALLY index was significantly associated with a lower risk of poor functional outcome (pooled OR = 0.766, 95% CI: 0.695–0.845, p < 0.001), with no significant heterogeneity across studies ( I 2 = 0.0%, Q = 1.33, p = 0.516). All included studies were of high quality (NOS scores 8-9). Publication bias could not be reliably assessed due to the limited number of included studies. Conclusion This systematic review with exploratory quantitative synthesis provides preliminary pooled evidence suggesting that the CALLY index may be a potential predictor of functional outcome in AIS patients. A higher CALLY index was associated with a lower risk of poor functional outcomes. However, given the limited number of included studies (only three retrospective studies from China), these findings should be considered hypothesis-generating rather than confirmatory and require validation in large-scale, multicenter, prospective studies across diverse populations before clinical application. Systematic review registration The review was registered in PROSPERO: CRD420261350196 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261350196 .