Highlights d A scRNA-seq study reveals shared and distinct features of human MMRd and MMRp CRC d Co-variation of single-cell transcriptional programs across specimens predicts immune hubs d A myeloid-rich inflammatory hub is identified below the colonic lumen in human CRC d CXCR3-ligand+ cells form foci with activated T cells in human MMRd CRC
Statement of Translational RelevanceDetection of persistent circulating tumor DNA (ctDNA) after curative-intent surgery to identify patients with minimal residual disease (MRD) who will ultimately recur has emerged as a potentially transformative approach in oncology. Early identification of patients with MRD through ctDNA detection could identify patients in whom additional therapy might salvage the chance of cure. To date, ctDNA MRD assays have employed a tumor-informed approach, requiring initial sequencing of tumor tissue to guide ctDNA detection, and thus cannot be used when a patient has insufficient tumor tissue for analysis. Here, we evaluate the first tumoruninformed, plasma-only ctDNA assay integrating genomic and epigenomic signatures to detect MRD in post-operative colorectal cancer (CRC) patients, without requiring parallel tumor sequencing, which produced favorable sensitivity and specificity, comparable to tumor-informed approaches. These data highlight the feasibility and potential clinical utility of plasma-only ctDNA-guided MRD detection.
To analyze use of combined liver and kidney transplantation (CLKT) for patients with chronic primary diseases of both organs and for patients with hepatorenal syndrome. Design: Retrospective case series. Setting: Multiorgan transplantation service in a large university medical center. Patients: A total of 98 patients underwent 99 CLKTs during a 16-year period; 76 had primary renal diseases, and 22 had hepatorenal syndrome. Patients receiving isolated liver and kidney transplants were analyzed for comparison. Main Outcome Measures: Patient and graft survival, rejection rates, and need for hemodialysis before and after transplantation.
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