Abstract Introduction: Saddle syndrome is caused by post-traumatic adhesions between the interosseous and lumbrical tendons and the intermetacarpal ligament in the webspaces of the hand. Diagnosis can be challenging, requiring a high index of suspicion with inadequately defined diagnostic criteria. Case Report: We present a case of saddle syndrome secondary to repetitive motorcycle use in a 56-year-old female to highlight the pathoanatomy, workup, diagnostic magnetic resonance imaging findings, and a new surgical approach for this disorder. Given persistent symptoms, surgical intervention was pursued using a commissural approach that provided superior en face visualization of the pathological anatomy. The adhesions between the intrinsic tendons and the intermetacarpal ligament were released with partial ligament resection. Conclusion: Immediate post-operative mobilization led to complete pain resolution and return to full function by 3 months. This report provides the first high-quality in vivo photographs correlating with advanced imaging findings and demonstrates how a commissural surgical approach offers improved anatomical visualization for treating this condition. Level of Evidence: V.
Olivia A. Swaim, S. Luchsinger, Edward J. Wu· Journal of Orthopaedic Case...· 0 citations
Lineage plasticity, or transdifferentiation, is increasingly recognized as a resistance mechanism to androgen receptor (AR) inhibition in prostate cancer. Lineage plasticity is characterized by loss of AR signaling and epithelial differentiation, along with activation of stemness-associated pathways, epithelial-mesenchymal transition (EMT), or alternative differentiation programs such as neuroendocrine prostate cancer (NEPC). Loss of the tumor suppressors TP53 and RB1 is common in tumors exhibiting lineage plasticity; however, mechanisms by which TP53/RB1 loss promotes this phenotype remain poorly understood, and effective treatments are limited. Using multi-omic profiling of TP53/RB1 loss prostate cancer models, we identified alterations in chromatin accessibility, DNA methylation, and gene expression associated with lineage plasticity. Importantly, many pathways activated upon TP53/RB1 loss could be blocked through BET bromodomain inhibition. TP53/RB1-deficient cells also harbored widespread DNA methylation changes that silenced pathways linked with restraining lineage plasticity. Combined BET bromodomain and DNA methyltransferase (DNMT) inhibition was more effective than single agent treatment in suppressing growth of TP53/RB1 loss models exhibiting a stem-like or NEPC program. This was partly explained by abrogation of discrete lineage plasticity pathways modulated by each agent. Altogether, our work suggests combined BET bromodomain and DNMT inhibition is a promising therapeutic approach for prostate tumors exhibiting lineage plasticity.
W. Storck, Diana Flores, A. Kumaraswamy et al.· JCI Insight· 0 citations
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