Urinary Cell Transcriptome Profiling and Identification of ITM2A, SLAMF6, and IKZF3 as Biomarkers of Acute Rejection in Human Kidney Allografts.

Identification of a shared gene expression pattern between T cell-mediated rejection (TCMR) and antibody-mediated rejection (AMR) in human kidney allografts may help prioritize targets for the treatment of both types of acute rejection. METHODS: We performed RNA sequencing and bioinformatics of genome-wide transcriptome profiles of urinary cells to identify novel mRNAs shared between TCMR and AMR and of mechanistic relevance. Customized RT-QPCR assays were then used to validate their abundance in urinary cells. Urinary cell transcriptome profiles and mRNA abundance were assessed in 22 urine samples matched to 22 TCMR biopsies, 7 samples matched to 7 AMR biopsies, and 24 samples matched to 24 No Rejection (NR) biopsies and correlated with biopsy diagnosis. RESULTS: RNA sequencing data and bioinformatics identified 127 genes in urine to be shared between TCMR and AMR. We selected 3 novel mRNAs-ITM2A, SLAMF6, and IKZF3-for absolute quantification and validation by customized RT-QPCR assays. The abundance of all 3 mRNAs was significantly higher in urine matched to TCMR or AMR than in urine matched to NR biopsies. Receiver-operating-characteristic curve analysis showed that all 3 mRNAs distinguished TCMR or AMR from NR. Their abundance was similar in patients with TCMR and those with AMR. CONCLUSIONS: State-of-the-art antirejection therapies are mostly effective to treat TCMR but not AMR. Our identification of mRNAs shared between TCMR and AMR and contributing to T cell-B cell interactions may help prioritize therapeutic targets for the simultaneous treatment of TCMR and AMR.

Intraoperative and postanesthesia care unit fluid administration as risk factors for postoperative complications in patients with head and neck cancer undergoing free tissue transfer.

BACKGROUND: This study aims to evaluate the impact of perioperative fluid administration, defined as fluid delivered intraoperatively and in the postanesthesia care unit, on postoperative outcomes. METHODS: Medical records of 102 patients with oral cavity squamous cell carcinoma undergoing free flap reconstruction between January 2011 and December 2015 were reviewed. The primary endpoint was development of a postoperative complication according to the Clavien-Dindo classification. Perioperative factors recorded were Washington University Head and Neck Comorbidity Index, operating time, vasopressor use, blood loss, intraoperative fluid, and perioperative fluid. RESULTS: Greater perioperative fluid administration was independently associated with surgical complications, flap complications, overall incidence of any complication, and increased length of stay. Greater intraoperative fluid administration was independently associated with higher rates of surgical complications. Intraoperative delivery of vasopressors was not associated with flap or surgical complications. CONCLUSION: Receiving less perioperative fluid was associated with fewer complications and decreased length of stay.