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C ytomegalovirus (CMV) infection after transplantation in immunosuppressed recipients is common 1 and is often associated with an increased risk for acute and chronic allograft rejection. 2 The risk of CMV diseases is known to be the highest amongst CMV seronegative recipients (RÀ) receiving an organ from CMV seropositive donors (Dþ). 3,4 However, the mechanism of CMV reactivation and subsequent dissemination in such Dþ to RÀ combination is poorly understood. 5 Previously, it has been shown that after transplantation a multitude of systemically released inflammatory cytokines can promote CMV viral reactivation. 6-9 In addition, in vitro studies demonstrate that inflammatory mediators such as interleukins-6, tumor necrosis factor-a, or prostaglandin E2 can activate nuclear factor kB and

Xenogeneic porcine islet transplantation is a promising potential therapy for type 1 diabetes (T1D). Understanding human immune responses against porcine islets is crucial for the design of optimal immunomodulatory regimens for effective control of xenogeneic rejection of porcine islets in humans. Humanized mice are a valuable tool for studying human immune responses and therefore present an attractive alternative to human subject research. Here, by using a pig‐to‐humanized mouse model of xenogeneic islet transplantation, we described the human immune response to transplanted porcine islets, a process characterized by dense islet xenograft infiltration of human CD45+ cells comprising activated human B cells, CD4+CD44+IL‐17+ Th17 cells, and CD68+ macrophages. In addition, we tested an experimental immunomodulatory regimen in promoting long‐term islet xenograft survival, a triple therapy consisting of donor splenocytes treated with ethylcarbodiimide (ECDI‐SP), and peri‐transplant rituximab and rapamycin. We observed that the triple therapy effectively inhibited graft infiltration of T and B cells as well as macrophages, promoted transitional B cells both in the periphery and in the islet xenografts, and provided a superior islet xenograft protection. Our study therefore indicates an advantage of donor ECDI‐SP treatment in controlling human immune cells in promoting long‐term islet xenograft survival.

Recipient allosensitization is a potential barrier to transplantation. 1 Blood transfusions, prior transplantation, and pregnancies may all result in allospecific memory T and B cells as well as antibodies. 2 In contrast to naïve T cells, memory T cells have a low activation threshold and thus are capable of mounting a rapid and exaggerated immune response when restimulated. 3,4 Additionally, memory B cells and preformed alloantibodies can also mediate allograft rejection. 5,6 Memory B cell differentiation has been associated with a rapid recall antibody

Background: Surgical debulking of neuroendocrine tumor (NET) is used as a therapeutic approach for metastatic NETs in selected centers. Reported outcomes after parenchymal-sparing liver resections (PSR) in NET patients with high numbers of liver metastases are sparse. Methods: NET patients that underwent surgical debulking from 2019 to 2021 were reviewed. Trends in perioperative liver function was examined, as well as symptom response, complications, and progression free survival. Results: 1069 liver lesions (median=17) were debulked from 53 patients with a combination of PSR (45%) and ultrasound-guided microwave ablations (MWA) (55%). Post-operative transaminitis was proportional to the number of lesions debulked: Median POD1 AST was 681 IU/L for 1-15 lesions vs. 1396 IU/L for >15 lesions, p=0.01 (R2=0.271, p<0.001) and ALT was 596 IU/L vs 1149 IU/L, respectively, p=0.01 (R2=0.221, p<0.001). Thrombocytopenia occurred in 75% of patients and severity correlated with increasing number of lesions (median POD2 platelets 157 x 109/L for 1-15 lesions vs. 109 x 109/L for >15 lesions, p=0.04; R2=0.163, p=0.003). Synthetic liver function measured by postoperative INR (median POD1 INR 1.3 vs 1.4, p=0.21) and total bilirubin (median POD 2 TB 1.35 vs 0.95 mg/dL; p=0.67) did not differ according to number of lesions debulked. 13% of patients sustained a Clavien-Dindo grade 3/4 complication which was not associated with the number of lesions targeted. All patients with preoperative symptoms had improvement after surgery. Median time to recurrence was 10.9 months. Conclusions: PSR with MWA for large numbers of NET liver metastases is safe and effective for symptom control and does not affect synthetic liver function. Transaminitis and thrombocytopenia are proportionate to the amount of liver lesions debulked.