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In addition, in vitro studies have shown that recombinant TTR amyloid aggregates are internalized by human cardiac fibroblasts, which subsequently secrete IL-6 and IL-8, providing mechanistic evidence that TTR aggregates can trigger inflammatory responses in cardiac cells [77]

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However, postoperative improvement after shunt placement is variable, and reliable preoperative predictors are lacking, leaving patients exposed to uncertain surgical benefit and procedural risk