Abstract Introduction A quarter of UK SPK transplants are from Deceased Cardiac Donors(DCD), with an increasing number recovered following in-situ normothermic regional perfusion(NRP). The aim of this study was to review the UK experience of SPK transplantation following NRP in DCD. Methods Data were collected on all first DCD SPKTs(n=360) performed during 2013–2021 from the UK Transplant Registry. Non-NRP DCD SPK were compared to NRP DCD SPKs. Kaplan Meier plots and cox regression analyses were performed. Results Some 198 pancreas were offered from NRP donors with 83 being retrieved. The majority of SPK grafts were from nonNRP donors n=324(90.0%) with n=36(10.0%) from NRP donors. The median cold ischaemic time (CIT) from NRP donors (9.7 hours) was significantly less than nonNRP donors (10.2 hours) (p=0.013). For all other parameters, donors were well matched. Recipients who received a graft from an NRP donor were also well matched with the recipients who received a graft from a nonNRP donor. Univariate analysis showed no statistically significant difference in one-year pancreas graft (NRP 97.2%, non-NRP 89.2%, p=0.145), kidney graft (NRP 100%, nonNRP 95.9%, p=0.221) or patient survival (NRP 100%, nonNRP 98.3%, p=0.442) despite an increasing trend in favour of NRP SPK. Conclusions This is the largest reported analysis of NRP for SPK transplants to date. NRP has previously been shown to be beneficial for liver transplants. Despite some concerns that NRP may preferentially benefit the liver at the expense of other organs our study has shown no adverse effects. Larger studies are needed to evaluate whether NRP improves graft utilisation rates for SPK.

Abstract Introduction This study aimed to assess if the use of kidneys from donors with a decreased eGFR had an adverse effect on patient and graft survival. Methods Data on all UK SPKT's from 2001-2021 were obtained from the NHSBT UK Transplant Registry (n=2,631). Cases with missing information were removed, leaving a final cohort of 1,819 (69.1%). eGFR was calculated using the CKD-EPI equation. Pancreas Graft (PGS), Kidney Graft (KGS) and patient survival analyses were conducted using Kaplan-Meier plots and Cox-regression models. Results 71% (n=1,292) of grafts were from donors with an eGFR>90 and 29%(n=530) were from donors with an eGFR<90. Donors with an eGFR<90 were statistically significantly more likely to be older (p<0.0001), a DBD donor (p=0.0086**) and have a higher BMI(p<0.0001). Recipients who received a graft from a donor with an eGFR<90 were well matched with those who received a graft from a donor with an eGFR>90. Univariate analysis showed a statistically significant decreased KGS(p=0.007**) when the donor had an eGFR<90. This trend was not seen when comparing patient or pancreas survival. Conclusion We accept a lower GFR could be indicative of either an AKI or a sign of early chronic kidney disease. In this current data analysis, we have been unable to successfully distinguish between the two however we have shown poorer KGS in those with a lower eGFR (<90). This had no impact on pancreas or patient survival. Further analysis is needed to explain the precise reasons for the lower eGFRs at the time of organ donation.

Abstract Introduction The genotypes HLA DR3/DR4, DR3/DR3, DR4/DR4 are associated with a predisposition to diabetes. This study evaluated UK recipient outcomes after pancreas transplantation from donors with a diabetes-associated genotypes. Methods Data on all UK pancreas transplants from 2004–2019 was obtained from the NHSBT-UK Registry, n=2,938. HLA-DR type was recorded for all organ donors. Re-transplants and those missing patient (PS) or graft (GS) survival were excluded, resulting in a final cohort of n=2,661. We further delineated our categories into SPK, PTA and PAK as a previous study suggested different recipient categories may be adversely affected. Univariate analyses were conducted using Kaplan-Meier plots and multi-variate analysis using Cox-regression models. Complications were analysed using chi-squared analyses. Results The majority of grafts were from donors not associated with diabetes genotypes (90.1%, n=2397) whereas 5.4%(n=145) came from HLA DR3/DR4 donors, 1.6%(n=43) from DR3/DR3 and (n=76)2.9% from DR4/DR4. Comparable outcomes for GS at 1yr (SPK p=0.980, PTA p=0.759, PAK p=0.244) and 3yrs (SPK p=0.708, PTA p=0.744, PAK p=0.275) and PS at 1yr (SPK p=0.553, PTA p=0.527, PAK p=0.756) and 3yrs (SPK p=0.728, PTA p=0.928, PAK p=0.424) were seen. Multivariate analysis also showed no statistically significant difference in GS (p=0.604, HR 1.041, 95%CI 0.895, 1.211) or PS (p=0.623, HR 1.045, 95%CI 0.876, 1.248). There were comparable complication rates. Conclusion This multicentre UK study has found comparable survival outcomes and complication rates within our donor-HLA-genotype groups. We do not believe that the presence or absence of a diabetes associated HLA-genotype influences outcomes for any category of pancreas transplant. Take-home message We do not believe that the presence or absence of a diabetes-associated HLA-genotype influences outcomes for any category of pancreas transplant.

Abstract Introduction WHO declared a pandemic of COVID-19 in March 2020. This study analyses the impact of COVID-19 on beta-cell replacement therapy in the UK. Methods Pancreas and islet donation and transplant activity in the period March 2020/2021 was compared with the same period the previous year. Results 2,180 patients had a functioning graft during March 2020/2021. 5.8%(n=126) tested positive for COVID-19 and two died (1%). In this period there was a 43% reduction in solid organ donors n=1,615, compared with the previous year, n=2,840. Of the 625 solid organ donors with a pancreas offered, 32% had the pancreas retrieved compared with 51% the previous period. 97 whole pancreas and islet transplants were performed in the UK down 54% from the prior period. Of the 84 pancreas transplant recipients; four tested positive for COVID-19 but none died, and two grafts failed within the first week from vascular thrombosis (neither were COVID-19 positive). Of the 13 SIK and islet alone transplant recipients, two tested positive for COVID-19 but neither died. Of these SIK transplants, one is known to have failed within a month and this is equivalent to that seen in the previous time period. To our knowledge, no patient receiving beta cell replacement therapy died of COVID during the first year of the pandemic despite immunosuppression. Conclusion In the UK, pancreas, and islet transplantation have continued during the pandemic at a lower rate. Outcomes following transplantation within the COVID era are, so far, similar to those in the period prior. Take-home message Outcomes following transplantation within the COVID era are, so far, similar to those in the period prior.

Abstract Introduction Only 3.4% of simultaneous pancreas and kidney transplants (SPKT) in the UK are performed for recipients with T2DM. The aim of this study was to compare outcomes after SPKT for recipients with either T1DM or T2DM. Methods Data on all UK SPKTs from 2003–2019 were obtained from the NHSBT UK Transplant Registry (n=2,236). Current SPKT selection criteria for T2DM requires insulin treatment and recipient BMI<30kg/m2 at listing. Cases where the aetiology of diabetes was missing and recipients who had received a re-transplant were excluded, resulting in a final cohort of n=2,154. Graft (GS) and patient (PS) survival analyses were conducted using Kaplan-Meier plots and Cox regression models. Complications were compared using chi-squared analyses. Results The majority of SPKTs were performed in recipients with T1DM (95.6%, n=2,060), and 3.4% (n=94) were performed in T2DM recipients. Recipients with T2DM were statistically significantly more likely to be older (p<0.0001), male (p<0.0001), with a higher BMI (p=0.0191), and not requiring dialysis (p<0.0001). Univariate analysis showed comparable outcomes for GS and PS at 1yr (GS p=0.120; PS p=0.886) and 3yrs (GS p=0.316; PS p=0.237). Multi-variate analysis also showed comparable outcomes in GS (p=0.564, HR 1.221, 95%CI 0.619, 2.406) and PS (p=0.556, HR 1.280, 95%CI 0.563, 2.911). Common complications after SPKT were analysed and no statistically significant differences were seen between recipients. Conclusion This is the largest European study evaluating outcomes after SPKT comparing recipients with T1DM or T2DM. Carefully selected recipients with T2DM were shown to have comparable graft survival, patient survival and rates of complications. Take-home message Carefully selected recipients with T2DM were shown to have comparable graft survival, patient survival and rates of complications.

Background Inherited epidermolysis bullosa (EB) encompasses 4 major types and at least 23 clinically distinctive phenotypes. Although considerable variability in cutaneous disease activity is known to exist within each, severity and anatomic distribution of skin lesions remain the major criteria used for subclassification. Objective We sought to generate accurate anatomic "density" diagrams depicting the relative extent and location of skin lesions within each major EB subtype. Methods Diagrams were created for each major EB type, on the basis of medical history and physical examination findings obtained from 1986 to 2002 from 3280 consecutive enrollees in the National EB Registry. Results An anatomic diagram was created for each of the major EB subtypes, representing a prototypic composite photograph of cutaneous disease activity. Conclusions Marked variability exists in the extent of skin involvement within each major EB subtype. The use of these diagrams, generated from the world's largest cohort of patients with EB, should assist the clinician in more accurately subclassifying newly encountered patients.

Despite major advances in structured education, insulin delivery and glucose monitoring, diabetes self-management remains an unremitting challenge. Insulin therapy is inextricably linked to risk of dangerous hypoglycaemia and sustained hyperglycaemia remains a leading cause of renal failure. This review sets out to demystify transplantation for diabetes multidisciplinary teams, facilitating consideration and incorporation within holistic overall person-centred management. Deceased and living donor kidney, whole pancreas and isolated islet transplant procedures, indications and potential benefits are described, in addition to outcomes within the integrated UK transplant programme.

Patients dying from primary intracranial malignancy are a potential source of organs for transplantation. However, a perceived risk of tumor transfer to the organ recipient has limited their use. We evaluated the risk of tumor transmission by reviewing the incidence in patients transplanted in the UK. Information from the UK Transplant Registry was combined with that from the national cancer registries of England, Wales and Northern Ireland to identify all organ donors between 1985 and 2001 inclusive with a primary intracranial malignancy and to identify the occurrence of posttransplant malignancy in the recipients of the organs transplanted. Of 11,799 organ donors in the study period, 179 were identified as having had a primary intracranial malignancy, including 33 with high-grade malignancy (24 grade IV gliomas and 9 medulloblastomas). A total of 448 recipients of 495 organs from 177 of these donors were identified. No transmission of donor intracranial malignancy occurred. Organs from patients dying from primary intracranial malignancy, including those with high-grade tumors, should be considered for transplantation and the small risk of tumor transmission should be balanced against the likely mortality for potential recipients who remain on the transplant waiting list.

Transforming growth factor-beta (TGF-beta)can induce the cyclin-dependent kinase inhibitors p21 and p15 in a variety of cell types. We have shown previously that Smad3 is required for the growth inhibitory activity of TGF-beta, whereas overexpression of Smads is not sufficient to activate the expression of p21 in HaCaT cells. These data suggest that an additional signaling pathway may be involved in stimulating p21 in HaCaT cells. Given the recent finding that the mitogen-activated protein kinase (MAPK) pathway can cause p21 induction and arrest cells, we examined the involvement of this pathway for p21 and p15 induction by TGF-beta, We found that TGF-beta can regulate the MAPK pathway, leading to the increased transactivation ability of transcription factor Elk, Constitutively active components in the MAPK pathway activate pal expression, and inhibitors or dominant negative constructs for the MAPK pathway significantly decrease p21 induction by TGF-beta, Both constitutively active MEK and inhibitors for MEK have no effect on Smad activity, including DNA binding, localization, and interaction with coactivator p800/CBP, These findings suggest that the MAPK pathway may be an independent pathway that is involved in p21 and p15 induction by TGF-beta.