Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver

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Robotic kidney transplantation in the obese patient: 10‐year experience from a single center

Despite increasing obesity rates in the dialysis population, obese kidney transplant candidates are still denied transplantation by many centers. We performed a single‐center retrospective analysis of a robotic‐assisted kidney transplant (RAKT) cohort from January 2009 to December 2018. A total of 239 patients were included in this analysis. The median BMI was 41.4 kg/m², with the majority (53.1%) of patients being African American and 69.4% of organs sourced from living donors. The median surgery duration and warm ischemia times were 4.8 hours and 45 minutes respectively. Wound complications (mostly seromas and hematomas) occurred in 3.8% of patients, with 1 patient developing a surgical site infection (SSI). Seventeen (7.1%) graft failures, mostly due to acute rejection, were reported during follow‐up. Patient survival was 98% and 95%, whereas graft survival was 98% and 93%, at 1 and 3 years respectively. Similar survival statistics were obtained from patients undergoing open transplant over the same time period from the UNOS database. In conclusion, RAKT can be safely performed in obese patients with minimal SSI risk, excellent graft function, and patient outcomes comparable to national data. RAKT could improve access to kidney transplantation in obese patients due to the low surgical complication rate.     

Quantification of cellular viability by automated microscopy and flow cytometry

Cellular viability is usually determined by measuring the capacity of cells to exclude vital dyes such as 4′,6-diamidino-2-phenylindole (DAPI), or by assessing nuclear morphology with chromatinophilic plasma membrane-permeant dyes, such as Hoechst 33342. However, a fraction of cells that exclude DAPI or exhibit normal nuclear morphology have already lost mitochondrial functions and/or manifest massive activation of apoptotic caspases, and hence are irremediably committed to death. Here, we developed a protocol for the simultaneous detection of plasma membrane integrity (based on DAPI) or nuclear morphology (based on Hoechst 33342), mitochondrial functions (based on the mitochondrial transmembrane potential probe DiOC₆(3)) and caspase activation (based on YO-PRO^®-3, which can enter cells exclusively upon the caspase-mediated activation of pannexin 1 channels). This method, which allows for the precise quantification of dead, dying and healthy cells, can be implemented on epifluorescence microscopy or flow cytometry platforms and is compatible with a robotized, high-throughput workflow.     

The Use of Bortezomib as a Rescue Treatment for Acute Antibody-Mediated Rejection: Report of Three Cases and Review of Literature

Antibody-mediated rejection (AMR) typically occurs early after transplantation in approximately 5%–7% of recipients. The literature reports suggest that 12%–37% of kidney transplant recipients with acute AMR do not respond to treatment and eventually lose their grafts. The proteasome inhibitor bortezomib is currently approved by the Food and Drug Administration for the treatment of multiple myeloma. It has been demonstrated both in vitro and in vivo to possess apoptotic properties against mature plasma cells. Herein we have described a series of 3 patients with positive cross-matches who developed early AMR after kidney transplantation. Bortezomib rescue treatment was administered after the patients failed to respond to plasmapheresis/intravenous immunoglobulin and splenectomy. All 3 patients responded with full, durable recovery of renal function. In conclusion, bortezomib is useful to treat refractory AMR after kidney transplantation.