In Reply: Use of Antibacterial Envelopes in Neuromodulation Surgeries With Implantable Device Insertion: A Systematic Review and Meta-Analysis

To the Editor: We appreciate Drs Liu and Xiong's thoughtful reading of our systematic review and the opportunity to clarify two key points they raised.1,2 Their letter highlights exactly the sort of constructive dialogue that advances the science of infection prevention in neuromodulation. Regarding their first comment about late-onset infections, we fully agree that clinically significant events can occur well beyond the perioperative window. Unfortunately, the individual studies available to us reported relatively short follow-up periods—typically under 1 year and no longer than 3 years.3-6 Our analysis could not look further than the horizons these primary data allowed, so any limitation on detecting very late infections reflects the design of the underlying studies rather than the scope of our review. We therefore see their observation as a welcome prompt for future investigators to design retrospective cohorts and prospective registries with surveillance extending at least 2 years, if not longer. Their second comment concerns the possibility of noninfectious adverse effects related to antibacterial envelopes. During protocol development, we searched specifically for neuromodulation studies that quantified perielectrode fibrosis, trace-metal accumulation, or other envelope-related sequelae. We found none that met our inclusion criteria. Regulatory summaries for the TYRX™ Neuro absorbable envelope likewise list no neuromodulation-specific fibrotic or toxicological concerns in premarket testing.7 While cardiovascular data suggest that the mesh is generally well-tolerated, we agree that extrapolation is imperfect. We deliberately flagged this paucity in the Discussion section and recommended dedicated biocompatibility work in future trials. Because both points raised by the correspondents stem from gaps in the literature rather than errors in our analysis, we believe our reply can stand on a concise description of those gaps and of why longer, safety-oriented research is essential. We hope this clarification helps readers interpret our findings within their proper limits and encourages the rigorous long-term investigations still needed to define the envelope's role in neuromodulation.