Introduction: Surgical Site Infection (SSI) is a rare but serious complication following Posterior Spinal Fusion (PSF) for pediatric scoliosis. Several studies have identified patient risk factors for SSI following PSF, including high Body Mass Index (BMI). The purpose of this study was to determine whether Radiographic Skin-to-spine Distance (RSD) can be used as a surrogate for BMI when evaluating the pediatric patient’s risk of developing a SSI after PSF. Methods: This study was performed retrospectively and included patients ages 0-18 who underwent PSF for scoliosis over a four-year period. RSD, defined as the distance from the L5 spinous process to the skin, was measured using preoperative lateral radiographs. Results: Of the 176 included patients, we identified eight (4.5%) who suffered from surgical site infection following PSF. Logistic regression analysis revealed no statistically significant predictors for SSI. However, there was a strong, statistically significant linear regression prediction between RSD and BMI (r = 0.71, p=0.001). Discussion: RSD was not shown to be predictive of SSI in this patient cohort. However, the strong correlation found between RSD and BMI suggests that when assessing risk of SSI, RSD may be useful as a substitute for BMI when BMI cannot be easily ascertained.
The skin has a pronounced ability to adapt to physical changes in the environment by exhibiting plasticity at the cellular level. Transient mechanical deformations applied to the skin are accommodated without permanent changes to tissue structure. However, sustained physical stress induces long-lasting alterations in the skin, which are mediated by shifts in the fates of epidermal stem cells. To investigate this phenomenon, we implemented two-photon intravital imaging to capture the responses of epidermal cells when an acute mechanical force is applied to the live skin. We show that mechanical stress induces the formation of intracellular vesicles in epidermal stem cells, which are filled with extracellular fluid and gradually enlarge causing the deformation of the cell nucleus. By lineage tracing analysis we demonstrate that the degree of nuclear deformation is linked to cell fate. Utilizing a fluorescent in vivo reporter, to capture intracellular calcium dynamics, we show that mechanical force induces a sustained increase in intracellular calcium within basal epidermal stem cells. Conditional deletion of Piezo1, a mechanosensitive ion channel, alters intracellular calcium dynamics and increases the number of stress vesicles in epidermal stem cells. Using a human skin xenograft model, we show that stress vesicles are a conserved phenomenon in mammalian skin. This study uncovers stress vesicles as key manifestations of the mechanism that regulates the fate of epidermal stem cells under conditions of mechanical stress, in which Piezo1 and calcium dynamics are also involved.
Loss of vision due to corneal endothelial dysfunction affects millions worldwide and has limited treatment options. Here we present a proof-of-concept for a therapeutic approach that aims to enhance regeneration of the corneal endothelium by inducing proliferation of quiescent cells in vivo, using modified mRNA technology. To test the efficacy of this strategy we developed a mouse model to analyze corneal endothelial regeneration by longitudinal live imaging, using two-photon microscopy. The mouse corneal endothelium displayed complete cellular quiescence and a decline in cell density with aging, consistent with human data. Limited proliferation of corneal endothelial cells was observed during injury repair but was insufficient to restore the tissue to pre-injury levels. Treatment via intracameral injection of five modified mRNAs, encoding for proteins involved in cell cycle activation, induced transient proliferation in corneal endothelial cells in the absence of injury and led to an increase in tissue cell density. This approach may offer a paradigm for enhancing the regenerative response in organs with limited endogenous ability.
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