RESUMEN
PURPOSE OF REVIEW: Spinal cord stimulation (SCS) is an increasingly utilized therapy for the treatment of neuropathic pain conditions. Though minimally invasive and reversable, there are several important device-related complications that physicians should be aware of before offering this therapy to patients. The aim of this review is to synthesize recent studies in device-related SCS complications pertaining to cylindrical lead implantation and to discuss etiologies, symptoms and presentations, diagnostic evaluation, clinical implications, and treatment options. RECENT FINDINGS: Device-related complications are more common than biologic complications. Device-related complications covered in this review include lead migration, lead fracture, lead disconnection, generator failure, loss of charge, generator flipping, hardware related pain, and paresthesia intolerance. The use of SCS continues to be an effective option for neuropathic pain conditions. Consideration of complications prior to moving forward with SCS trials and implantation is a vital part of patient management and device selection. Knowledge of these complications can provide physicians and other healthcare professionals the ability to maximize patient outcomes.
RESUMEN
Women with germline BRCA1 mutations (BRCA1+/mut) have increased risk for hereditary breast cancer. Cancer initiation in BRCA1+/mut is associated with premalignant changes in breast epithelium; however, the role of the epithelium-associated stromal niche during BRCA1-driven tumor initiation remains unclear. Here we show that the premalignant stromal niche promotes epithelial proliferation and mutant BRCA1-driven tumorigenesis in trans. Using single-cell RNA sequencing analysis of human preneoplastic BRCA1+/mut and noncarrier breast tissues, we show distinct changes in epithelial homeostasis including increased proliferation and expansion of basal-luminal intermediate progenitor cells. Additionally, BRCA1+/mut stromal cells show increased expression of pro-proliferative paracrine signals. In particular, we identify pre-cancer-associated fibroblasts (pre-CAFs) that produce protumorigenic factors including matrix metalloproteinase 3 (MMP3), which promotes BRCA1-driven tumorigenesis in vivo. Together, our findings demonstrate that precancerous stroma in BRCA1+/mut may elevate breast cancer risk through the promotion of epithelial proliferation and an accumulation of luminal progenitor cells with altered differentiation.