A nonspecific inflammatory and thrombotic reaction termed instant blood-mediated inflammatory reaction (IBMIR) has been reported when allogenic or xenogenic islets come into contact with blood. This reaction is known to cause significant loss of transplanted islets. We hypothesized that IBMIR occurs in patients undergoing total pancreatectomy followed by autologous islet transplantation (TP-AIT) and tested this hypothesis in 24 patients and in an in vitro model. Blood samples drawn during the peritransplant period showed a significant and rapid increase of thrombin-anti-thrombin III complex (TAT) and C-peptide during islet infusion, which persisted for up to 3 h, along with a decreased platelet count. A concomitant increase in levels of inflammatory proteins IL-6, IL-8 and interferon-inducible protein-10 was observed. An in vitro model composed of pure islets plus autologous blood also demonstrated significantly increased levels of TAT (p<0.05), C-peptide (p<0.05), tumor necrosis factor-alpha (p<0.05) and MCP-1 (p<0.05), as well as strong tissue factor expression in islets. Islet viability decreased significantly but was rescued by the presence of low-molecular-weight dextran sulfate. In conclusion, AIT-induced elevation of TAT and destruction of islets suggests that IBMIR might occur during AIT. Modulating this process may help improve islet engraftment and the insulin independence rate in TP-AIT patients.

Islet cell transplantation is a promising beta cell replacement therapy for patients with brittle type 1 diabetes as well as refractory chronic pancreatitis. Despite the vast advancements made in this field, challenges still remain in achieving high frequency and long-term successful transplant outcomes. Here we review recent advances in understanding the role of inflammation in islet transplantation and development of strategies to prevent damage to islets from inflammation. The inflammatory response associated with islets has been recognized as the primary cause of early damage to islets and graft loss after transplantation. Details on cell signaling pathways in islets triggered by cytokines and harmful inflammatory events during pancreas procurement, pancreas preservation, islet isolation, and islet infusion are presented. Robust control of pre- and peritransplant islet inflammation could improve posttransplant islet survival and in turn enhance the benefits of islet cell transplantation for patients who are insulin dependent. We discuss several potent anti-inflammatory strategies that show promise for improving islet engraftment. Further understanding of molecular mechanisms involved in the inflammatory response will provide the basis for developing potent therapeutic strategies for enhancing the quality and success of islet transplantation.

Poor efficacy is one of the issues for clinical islet transplantation. Recently, we demonstrated that pancreatic ductal preservation significantly improved the success rate of islet isolation; however, two transplants were necessary to achieve insulin independence. In this study, we introduced iodixanol-based purification, thymoglobulin induction, and double blockage of IL-1β and TNF-α as well as sirolimus-free immunosuppression to improve the efficacy of clinical islet transplantation. Nine clinical-grade human pancreata were procured. Pancreatic ductal preservation was performed using ET-Kyoto solution in all cases. When the isolated islets met the clinical criteria, they were transplanted. We utilized two methods of immunosuppression and anti-inflammation. The first protocol prescribed daclizumab for induction, then sirolimus and tacrolimus to maintain immunosuppression. The second protocol used thymoglobulin for induction and tacrolimus and mycophenolate mofetil to maintain immunosuppression. Eternacept and anakinra were administered as anti-inflammatory drugs. The total amount of insulin required, HbA1c, and the SUITO index were determined to analyze and compare the results of transplantation. All isolated islet preparations (9/9) met the criteria for clinical transplantation, and they were transplanted into six type 1 diabetic patients. All patients achieved insulin independence with normal HbA1c levels; however, the first protocol required two islet infusions ( N = 3) and the second protocol only required a single infusion ( N = 3). The average SUITO index, at 1 month after a single-donor islet transplantation, was significantly higher in the second protocol (49.6 ± 8.3 vs. 19.3 ± 6.3, p < 0.05). Pancreatic ductal preservation, iodixanol-based purification combined with thymoglobulin induction, and blockage of IL-1β and TNF-α as well as sirolimus-free immunosuppression dramatically improved the efficacy of clinical islet transplantations. This protocol enabled us to perform successful single-donor islet transplantations. Further large-scale studies are necessary to confirm these results and clarify the mechanism of each component.

This was a retrospective cohort study, which aimed to investigate the factors associated with hesitancy to receive a third dose of a coronavirus disease 2019 (COVID-19) vaccine. A paper-based questionnaire survey was administered to all participants. This study included participants who provided answers in the questionnaire about whether they had an intent to receive a third dose of a vaccine. Data on sex, age, area of residence, adverse reactions after the second vaccination, whether the third vaccination was desired, and reasons to accept or hesitate over the booster vaccination were retrieved. Among the 2439 participants, with a mean (±SD) age of 52.6 ± 18.9 years, and a median IgG-S antibody titer of 324.9 (AU/mL), 97.9% of participants indicated their intent to accept a third vaccination dose. The logistic regression revealed that participants of a younger age (OR = 0.98; 95% CI: 0.96–1.00) and with a higher antibody level (OR = 2.52; 95% CI: 1.27–4.99) were positively associated with hesitancy over the third vaccine. The efficacy of the COVID-19 vaccine and concerns about adverse reactions had a significant impact on behavior regarding the third vaccination. A rapid increase in the booster dose rate is needed to control the pandemic, and specific approaches should be taken with these groups that are likely to hesitate over the third vaccine, subsequently increasing booster contact rate.

A magnitude 9.0 earthquake struck off eastern Japan in March 2011. Many survivors have been living in temporary houses provided by the local government since they lost their houses as a result of the great tsunami (tsunami group) or the expected high-dose radiation resulting from the nuclear accident at the Fukushima Daiichi Nuclear Power Plant (radiation group). The tsunami was more than 9 m high in Soma, Fukushima, which is located 30 km north of the Fukushima Daiichi Nuclear Power Plant and adjacent to the mandatory evacuation area. A health screening program was held for the evacuees in Soma in September 2011. The aim of this study was to compare the metabolic profiles of the evacuees before and after the disaster. We hypothesized that the evacuees would experience deteriorated metabolic status based on previous reports of natural disasters.

Inconsistent islet isolation is one of the issues of clinical islet transplantation. In the current study, we applied ductal injection to improve the consistency of islet isolation. Seven islet isolations were performed with the ductal injection of ET-Kyoto solution (DI group) and eight islet isolations were performed without the ductal injection (standard group) using brain-dead donor pancreata. Isolated islets were evaluated based on the Edmonton protocol for transplantation. The DI group had significantly higher islet yields (588,566 ± 64,319 vs. 354,836 ± 89,649 IE, p < 0.01) and viability (97.3 ± 1.2% vs. 92.6 ± 1.2%, p < 0.02) compared with the standard group. All seven isolated islet preparations in the DI group (100%), versus only three out of eight isolated islet preparations (38%) in the standard group met transplantation criteria. The islets from the DI group were transplanted into three type 1 diabetic patients and all three patients became insulin independent. Ductal injection significantly improved quantity and quality of isolated islets and resulted in high success rate of clinical islet transplantation. This simple modification will reduce the risk of failure of clinical islet isolation.