Anti-CD47 monoclonal antibody therapy reduces ischemia-reperfusion injury of renal allografts in a porcine model of donation after cardiac death.

We investigated whether blockade of the CD47 signaling pathway could reduce ischemia-reperfusion injury (IRI) of renal allografts donated after cardiac death (DCD) in a porcine animal model of transplantation. Renal allografts were subjected to 30 minutes of warm ischemia, 3.5 hours of cold ischemia, and then perfused with a humanized anti-CD47 monoclonal antibody (CD47mAb) in the treatment group or HTK solution in the control group (n = 4/group). The animals were euthanized five days after transplantation. At the time of reperfusion, indocyanine green-based in vivo imaging showed that CD47mAb-treated organs had greater and more uniform reperfusion. On post-transplant days 3-5, the treatment group had lower values compared to the control for creatinine and blood urea nitrogen. Histological examination of allograft tissues showed a significant decrease of acute tubular injury in the CD47mAb-treated group compared to control. Compared to the control group, CD47mAb treatment significantly decreased genes expression related to oxidative stress (sod-1, gpx-1, and txn), the inflammatory response (il-2, il-6, inf-g, and tgf-b), as well as reduced protein levels of BAX, Caspase-3, MMP2, and MMP9. These data demonstrate that CD47mAb blockade decreases IRI and subsequent tissue injury in DCD renal allografts in a large animal transplant model.

Pharmacologic venous thromboembolism prophylaxis for preterm prelabor rupture of membranes.

BACKGROUND: Pregnant patients with preterm prelabor rupture of membranes (PPROM) may experience prolonged hospitalization, which is an indication for pharmacologic venous thromboembolism (VTE) prophylaxis according to certain international guidelines. The proportion of patients who deliver unexpectedly and within a period during which pharmacologic prophylaxis would be expected to impact coagulation is unknown. OBJECTIVE: To estimate the proportion of patients with PPROM who would deliver within 12 hours of typical dosing of pharmacologic VTE prophylaxis if administered routinely for antepartum admissions >72 hours. STUDY DESIGN: This is a retrospective cohort study from a database including patients admitted for expectant management of PPROM January 2011 to September 2020. The outcome of the study was the proportion of patients who remained undelivered 72 hours after admission and experienced an unplanned delivery potentially within 12 hours of enoxaparin administration. We evaluated patients undelivered after 72 hours due to international recommendations to initiate VTE prophylaxis in hospitalized patients after 72 hours. Unplanned delivery was defined as onset of spontaneous labor or other indication for immediate delivery. Timing of delivery was analyzed based on usual timing of enoxaparin administration daily at approximately 8 am and the recommendation to withhold regional anesthesia until 12 hours after a prophylactic dose. RESULTS: 1381 deliveries were identified as PPROM out of the 49,322 deliveries in our database. 139 cases were included after the following exclusions: delivery >35 weeks (N=641), rupture of membranes >34 weeks (N=145), delivery <72 hours after admission (N=409), insufficient data (N=35), and duplicates (N=12). Sixty of the 139 (43%) had an unplanned delivery, while 33 of these (24% of total) occurred within 12 hours of enoxaparin administration. CONCLUSION: A quarter of patients admitted for PPROM had an unplanned delivery within 12 hours of typical enoxaparin dosing. This cohort may experience harm (ineligibility for regional anesthesia, risks of general anesthesia, increased risk of bleeding) if given routine pharmacologic VTE prophylaxis. Risk/benefit considerations should be discussed with patients in considering pharmacologic versus mechanical prophylaxis during prolonged hospitalization for PPROM.