Ito, Kenyu

Background and Objectives: Mitigating post-operative complications is a key metric of success following interbody fusion. LLIF is associated with a unique complication profile when compared to other approaches, and while numerous studies have attempted to report the incidence of post-operative complications, there is currently no consensus regarding their definitions or reporting structure. The aim of this study was to standardize the classification of complications specific to lateral lumbar interbody fusion (LLIF). Materials and Methods: A search algorithm was employed to identify all the articles that described complications following LLIF. A modified Delphi technique was then used to perform three rounds of consensus among twenty-six anonymized experts across seven countries. Published complications were classified as major, minor, or non-complications using a 60% agreement threshold for consensus. Results: A total of 23 articles were extracted, describing 52 individual complications associated with LLIF. In Round 1, forty-one of the fifty-two events were identified as a complication, while seven were considered to be approach-related occurrences. In Round 2, 36 of the 41 events with complication consensus were classified as major or minor. In Round 3, forty-nine of the fifty-two events were ultimately classified into major or minor complications with consensus, while three events remained without agreement. Vascular injuries, long-term neurologic deficits, and return to the operating room for various etiologies were identified as important consensus complications following LLIF. Non-union did not reach significance and was not classified as a complication. Conclusions: These data provide the first, systematic classification scheme of complications following LLIF. These findings may improve the consistency in the future reporting and analysis of surgical outcomes following LLIF.

Abstract Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. Using Sanger and exome sequencing in a CMS patient, we identified two heteroallelic mutations, p.Glu1233Lys and p.Arg1277His, in LRP4 coding for the postsynaptic low-density lipoprotein receptor-related protein 4. LRP4, expressed on the surface of the postsynaptic membrane of the neuromuscular junction, is a receptor for neurally secreted agrin, and LRP4 bound by agrin activates MuSK. Activated MuSK in concert with Dok-7 stimulates rapsyn to concentrate and anchor AChR on the postsynaptic membrane and interacts with other proteins implicated in the assembly and maintenance of the neuromuscular junction. LRP4 also functions as an inhibitor of Wnt/beta-catenin signaling. The identified mutations in LRP4 are located at the edge of its 3rd beta-propeller domain and decrease binding affinity of LRP4 for both MuSK and agrin. Mutations in the LRP4 3rd beta-propeller domain were previously reported to impair Wnt signaling and cause bone diseases including Cenani–Lenz syndactyly syndrome and sclerosteosis-2. By analyzing naturally occurring and artificially introduced mutations in the LRP4 3rd beta-propeller domain, we show that the edge of the domain regulates the MuSK signaling whereas its central cavity governs Wnt signaling. We conclude that LRP4 is a new CMS disease gene and that the 3rd beta propeller domain of LRP4 mediates the two signaling pathways in a position-specific manner.