Transparent qualitative model-building in high-stakes digital governance: a methods protocol for tracing institutional mechanisms.

Kawasaki disease (KD), first described by Dr. Kawasaki in Japan in 1967, is a febrile systemic illness characterized by vasculitis affecting small- and medium-sized arteries. Its primary complication is coronary artery lesion (CAL) (). Although the exact etiology of KD remains incompletely elucidated, it is widely considered to arise from inflammatory cascades in genetically vulnerable hosts triggered by excessive immune responses to infectious or environmental stimuli (). Several studies have suggested an association between KD and (MP) infection (–). Relevant literature () indicates that MP infection exacerbates the progression of CAL and myocardial injury during the subacute phase of KD. Serum complement C3 and C4 concentrations serve as biomarkers of immune function and immune-mediated pathological injury. In KD patients, the peripheral blood CD4 T cell counts and the CD4/CD8 ratio are elevated, while the CD8 T cell numbers are reduced (). Previous reports have documented that serum C3 concentrations in children with MP pneumonia are higher in the acute phase than the convalescent phase and remain elevated relative to those of healthy controls across both phases (). Activation of the complement system caused by MP infection may be one of the triggering factors for MP-KD. In addition, MP can secrete superantigens that directly bind to MHC class II (MHC-II) molecules, driving the polyclonal activation of CD4+ T cells, robust cytokine release, and subsequent vascular inflammation (, ). Lu et al. demonstrated that IVIG effectively inhibits cytokine production, yet immune cell activation persists in KD patients with concurrent MP infection; these activated immune cells directly promote myocardial injury. This mechanism may account for the more protracted inflammation and heightened risk of cardiac sequelae observed in MP-associated KD (). Given that concurrent MP infection markedly exacerbates long-term cardiac damage in KD patients, identifying modifiable protective interventions to reduce CAL risk in this high-risk subgroup carries important clinical implications. A Chinese case–control study reported an inverse association between exclusive breastfeeding and KD onset, implying that breastfeeding acts as a protective factor against KD (). Furthermore, studies have shown that breastfeeding for ≥6 months significantly reduces the risk of coronary artery injury () and is associated with a decreased risk of KD (, ). Several mechanistic pathways have been proposed to account for this inverse association between breastfeeding and KD risk (). First, breast milk contains bioactive protective factors such as immunoglobulins, nucleotides, lactoferrin, and lymphocytes, which counteract pathogenic invasion and suppress dysregulated immune responses to lower the risk of KD. Second, breastfeeding promotes infant immune maturation and confers indirect protection via reshaping intestinal microbiome composition and boosting commensal bacterial proliferation. Moreover, breastfeeding mothers typically demonstrate higher health literacy, and their infants tend to adopt healthier daily routines with lower vulnerability to infection, which further reduces KD incidence. Accordingly, breastfeeding substantially modifies the risk of immune-mediated vasculitic disorders such as KD (). Cross-national epidemiological studies have validated breastfeeding’s protective role against KD (–). Nevertheless, prior systematic reviews only summarized studies verifying breastfeeding’s cardiac protective benefits among unselected KD patients (, , ); to date, no published research has evaluated whether breastfeeding modifies CAL risk specifically in KD children co-infected with MP. Accordingly, we performed this retrospective cohort study to compare CAL risk between exclusively breastfed and formula-fed children with KD complicated by MP co-infection. Partially breastfed infants were also incorporated into analyses to characterize the full spectrum of infant feeding exposures. We consecutively screened all children admitted to our hospital with KD between January 2020 and January 2025 and retrospectively enrolled 388 eligible participants, consisting of 232 boys and 156 girls. All participants received standardized treatment (2 g/kg IVIG + aspirin) and consistent routine clinical management. This retrospective cohort study obtained ethical approval from the Ethics Committee of Anqing Municipal Hospital; informed consent was waived given the anonymized retrospective data collection design. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki. KD was diagnosed when patients presented with fever lasting ≥5 days plus at least four of the five core clinical manifestations (complete Kawasaki disease [cKD]), namely: (1) bilateral conjunctival congestion, (2) changes in the lips and mouth: dry and red lips, strawberry tongue, and diffuse congestion of the oropharyngeal mucosa, (3) rash, including isolated red