Blockade of the CD40-CD154 costimulatory signal is an attractive strategy for immunosuppression and tolerance induction in organ transplantation. Treatment with anti-CD154 monoclonal antibodies (mAbs) results in potent immunosuppression in nonhuman primates (NHPs). Despite plans for future clinical use, further development of these treatments was halted by complications. As an alternative approach, we have been focusing on the inhibition of the counter receptor, CD40 and have shown that a novel human anti-CD40 mAb, ASKP1240, markedly prolongs renal allograft survival in NHPs, although allografts eventually underwent chronic allograft nephropathy. On the basis of our previous findings that a CD40-CD154 costimulation blockade induces tolerance to hepatic, but not cardiac, allografts in rodents, we tested here our hypothesis that a blockade of CD40 by ASKP1240 allows acceptance of hepatic allografts in NHPs. A 2-week ASKP1240 induction treatment prolonged liver allograft survival in NHPs; however, the graft function deteriorated due to chronic rejection. In contrast, a 6-month ASKP1240 maintenance monotherapy efficiently suppressed both cellular and humoral alloimmune responses and prevented rejection on the hepatic allograft. No serious side effects, including thromboembolic complications, were noted in the ASKP1240-treated monkeys. We conclude that CD40 blockade by ASKP1240 would be a desirable immunosuppressant for clinical liver transplantation.

PV size strongly influences PV complications. Other factors such as younger age, low portal venous flow, and high hepatic arterial flow may be risk factors for PV complications.

The novel piperidine compound, DTCM-glutarimide, was found to be a new inhibitor of macrophage activation, inhibiting AP-1 activity. It also inhibited graft rejection in mice, and thus may be a candidate for an anti-inflammatory agent.

Background: A reduction in complications and mortality can be observed over the last few decades among elderly patients in the early postoperative period for colorectal cancer (CRC) surgery, but long-term outcomes are largely unknown. This study aimed to investigate the long-term outcomes of elderly patients 80 years and older after CRC surgery in comparison with younger age groups. The influence of clinical, oncological, and physical parameters on outcome were retrospectively analyzed.Methods: A total of 346 patients underwent CRC surgery with curative intent between January 2013 and December 2017. Patients were divided into three age groups: younger than 60 (n=47), between 60 and 79 (n=218), and 80 and older (n=81). Clinicopathological variables including comorbidity, modified frailty index, prognostic nutrition index (PNI), operative/postoperative data, and outcome including cause of death were compared among age groups. To identify factors associated with death from CRC and other causes, univariate and multivariate analyses using the Cox proportional hazards model were performed.Results: Immediate postoperative morbidity of patients with Clavien-Dindo grades of III or greater (16.0%) and the 30-day mortality rate (2.5%) of patients 80 years and older were not statistically different from those of younger age groups. Long-term disease-free survival was also similar among age groups, suggesting CRC surgery provides oncological benefit to patients irrespective of age. Multivariate analysis revealed that R1 resection, advanced tumor stage, carcinoembryonic antigen (CEA) level of >5 ng/mL, undifferentiated tumor, and longer postoperative hospital stay were risk factors for CRC death. Long-term overall survival was significantly reduced in comparison to younger age groups. Seventy percent of deaths in elderly patients during follow-up were primarily from respiratory failure and cardiovascular disease. Multivariate analysis demonstrated that advanced age, frailty, low PNI, and open procedure were risk factors for other causes of mortality.Conclusions: Elderly patients undergoing CRC surgery appeared to enjoy similar oncological benefits as younger age groups. Since both modified frailty index and PNI were correlated with mortality unrelated to CRC, preoperative assessment of these factors can be important for predicting outcome and selecting patients for prehabilitation.

Summary Since prolonged cold preservation of the heart deteriorates the outcome of heart transplantation, a more protective preservation solution is required. We therefore developed a new solution, named Dsol, and examined whether Dsol, in comparison to UW, could better inhibit myocardial injury resulting from prolonged cold preservation. Syngeneic heterotopic heart transplantation in Lewis rats was performed after cold preservation with UW or Dsol for 24 or 36 h. In addition to graft survival, myocardial injury, ATP content, and Ca2+ ‐dependent proteases activity were assessed in the 24‐h preservation group. The cytosolic Ca2+ concentration of H9c2 cardiomyocytes after 24‐h cold preservation was assessed. Dsol significantly improved 7‐day graft survival after 36‐h preservation. After 24‐h preservation, Dsol was associated with significantly faster recovery of ATP content and less activation of calpain and caspase‐3 after reperfusion. Dsol diminished graft injury significantly, as revealed by the lower levels of infarction, apoptosis, serum LDH and AST release, and graft fibrosis at 7‐day. Dsol significantly inhibited Ca2+ overload during cold preservation. Dsol inhibited myocardial injury and improved graft survival by suppressing Ca2+ overload during the preservation and the activation of Ca2+ ‐dependent proteases. Dsol is therefore considered a better alternative to UW to ameliorate the outcome of heart transplantation.