Reverse shoulder arthroplasty glenoid lateralization influences scapular spine strains.

BACKGROUND: Scapular spine insufficiency fractures following reverse shoulder arthroplasty are poorly understood. There exists limited literature regarding the role of reverse shoulder arthroplasty lateralization on scapular spine strains and fractures. The purpose of this cadaveric biomechanical simulator study was to evaluate the role of glenoid lateralization on scapular spine strain. METHODS: Eight cadaveric shoulders were tested using an in-vitro simulator. A custom modular reverse shoulder arthroplasty was implanted that allowed for in-situ glenoid lateralization adjustment. Scapular spine strain was measured by strain gauges placed in clinically relevant Levy zones along the scapular spine. All specimens were tested in loaded forward elevation and abduction. RESULTS: Glenoid lateralization from 0 to 5 mm caused negligible changes in scapular spine strains. Lateralization from 5 to 10 mm, however, caused significant increases in strain at 0° forward elevation in all strain gauges (p < 0.026). Strains measured in Levy zone 2 were significantly higher than all other locations (p < 0.039). Additionally, forward elevation resulted in significantly higher strain values than abduction (p = 0.001). CONCLUSIONS: Glenoid lateralization is an important parameter in reverse shoulder arthroplasty; however, our results demonstrate higher degrees of lateralization may place higher strains on the scapular spine. An understanding of reverse shoulder arthroplasty lateralization and scapular spine strains is important to optimize parameters and to mitigate negative effects. LEVEL OF EVIDENCE: Basic Sciences Study, Cadaveric Model, Biomechanics.

Modulation of toll-like receptor 4. Insights from x-ray crystallography and molecular modeling.

Toll-like receptors (TLRs) are a family of proteins with a key role in the innate immune system. They are specialized in the recognition of molecular patterns present in microbial components, through mechanisms not yet unraveled at atomic level. Improvement in the understanding of the molecular mechanisms that drive TLR signaling is of paramount importance to grasp key aspects of immunity, potentially leading to the design of new molecules able to modulate their functions. Toll-like receptor 4 (TLR4), along with its accessory protein myeloid differentiation factor 2 (MD-2), builds a heterodimeric complex that specifically recognizes lipopolysaccharides (LPS), which are present on the cell wall of gramnegative bacteria, activating the immune response. Some TLR4 modulators are undergoing preclinical and clinical evaluation for the treatment of sepsis, inflammatory diseases, cancer, and rheumatoid arthritis. Reported X-ray crystal structures together with molecular modeling studies, not reviewed before in the literature, have recently contributed to the elucidation of key interactions at atomic level of the binding between the TLR4/MD-2 system and different TLR4/MD-2 ligands. The purpose of this review is to summarize these reported studies which may account for the SAR rationalization of natural/ synthetic agonist/antagonist TLR4 binders and may also guide further design of novel TLR4 modulators.