BACKGROUND:Islet transplantation has the potential to cure type 1 diabetes by restoring endogenous insulin production. However, its success relies on balancing improved glycaemic control with the risks of immunosuppressive therapy. This study aimed to evaluate long-term outcomes of islet transplantation alone for type 1 diabetes, focusing on the effects of islet mass and immunosuppressive regimens on graft survival and insulin independence, and weighing glycaemic control benefits against the risks of immunosuppressive therapy. METHODS:This cohort study retrospectively analysed individuals aged 18-67 years with type 1 diabetes who received intraportal islet transplantation alone at IRCCS Ospedale San Raffaele, Milan, Italy. Inclusion criteria comprised adults with type 1 diabetes diagnosed before the age of 55 years with severe recurrent hypoglycaemia or glycaemic instability. Major exclusion criteria included a HbA1c of more than 12·5%, a BMI of more than 30 kg/m2, and insulin requirements exceeding 1·2 IU/kg per day, along with contraindications to immunosuppressive therapy. Participants were recruited from the hospital's islet transplant registry. Follow-up was conducted through regular clinical visits, with data collected retrospectively. Outcomes assessed included patient survival, graft survival, insulin independence, glycaemic control, and adverse events. Data were analysed using an intention-to-treat method, mixed-effects models, Kaplan-Meier estimates, and Cox and logistic regression to identify factors linked to metabolic success and reduced risks. FINDINGS:79 patients underwent intrahepatic or intraportal islet transplantation alone between Feb 16, 2001, and June 1, 2023, and received a total of 159 islet infusions, with a median total islet mass of 9637 islet equivalents (IEQ) per kg. Complications were infrequent and mostly involved minor bleeding, with only 3% (two of 79) of patients requiring surgical intervention. Glycaemic control improved significantly after infusion, with a reduction of HbA1c by -10·04 mmol/mol (-13·63 to -6·46), and a decrease in daily insulin requirements by -13·35 units per day (-17·04 to -9·65). The intention-to-treat analysis showed a median graft survival (fasting C peptide ≥0·3 ng/mL) of 3·9 years (95% CI 1·6 to 6·2) and 44% (35/79) insulin independence for a median of 6 years (95% CI 2·88 to 9·08). Patients receiving more than 10 000 IEQ/kg with BAS, FK506, and Rapa therapy had a median graft survival of 9·7 years (3·1-16·0) and 73% (16 of 22) insulin independence. Kaplan-Meier estimates indicated graft survival rates of 86% at 1 year, 65% at 5 years, 47% at 10 years, 47% at 15 years, and 40% at 20 years. Overall survival was 92% (73 of 79) over a median follow-up of 13·1 years, with a 20-year survival probability of 84%. Adverse events related to immunosuppressive therapy were reported in 44% (35 of 79) of patients, with allosensitisation rates increasing from 6% at baseline to 42% after therapy discontinuation. INTERPRETATION:This analysis of a large islet transplantation alone cohort provides valuable insights into factors influencing outcomes and highlights potential risks, supporting informed clinical decision making and the optimisation of future β-cell replacement strategies. FUNDING:None.
Predicting clinical deterioration in COVID-19 patients remains a challenging task in the Emergency Department (ED). To address this aim, we developed an artificial neural network using textual (e.g. patient history) and tabular (e.g. laboratory values) data from ED electronic medical reports. The predicted outcomes were 30-day mortality and ICU admission. We included consecutive patients from Humanitas Research Hospital and San Raffaele Hospital in the Milan area between February 20 and May 5, 2020. We included 1296 COVID-19 patients. Textual predictors consisted of patient history, physical exam, and radiological reports. Tabular predictors included age, creatinine, C-reactive protein, hemoglobin, and platelet count. TensorFlow tabular-textual model performance indices were compared to those of models implementing only tabular data. For 30-day mortality, the combined model yielded slightly better performances than the tabular fastai and XGBoost models, with AUC 0.87 ± 0.02, F1 score 0.62 ± 0.10 and an MCC 0.52 ± 0.04 ( p < 0.32). As for ICU admission, the combined model MCC was superior ( p < 0.024) to the tabular models. Our results suggest that a combined textual and tabular model can effectively predict COVID-19 prognosis which may assist ED physicians in their decision-making process.
BACKGROUND: lung damage leading to gas-exchange deficit and sepsis leading to systemic hypoperfusion are well-known features of severe pneumonia. Although frequently described in COVID-19, their prognostic impact in COVID-19-related pneumonia vs COVID-19-urelated pneumonia has never been compared. This study assesses fundamental gas-exchange and hemodynamic parameters and explores their prognostic impact in COVID-19 pneumonia and non-COVID-19 pneumonia.METHODS: we prospectively evaluated arterial pO2/FiO2, alveolar to arterial O2 gradient, shock index, and serum lactate in 126 COVID-19 pneumonia patients, aged 18-65, presenting to the emergency department with acute, non-hypercapnic respiratory failure. As a control group we identified 1:1 age-, sex-, and pO2/FiO2-matched COVID-19-urelated pneumonia patients. Univariate and multivariable predictors of 30-day survival were identified in both groups.RESULTS: COVID-19 patients showed lower arterial serum lactate concentration (p<0.001) and shock index (p<0.001) values as compared to non-COVID-19 patients. While we did not observe differences in lactate concentration or in shock index values in deceased vs surviving COVID-19 patients (respectively, p=0.7 and p=0.6), non-COVID-19 deceased patients showed significantly higher lactate and shock index than non-COVID-19 survivors (p<0.001 and p=0.03). The pO2/FiO2 was the most powerful determinant of survival by Cox regression multivariate analysis in COVID-19 patients (p=0.006), while it was lactate in non-COVID-19 patients (p=0.001).CONCLUSIONS: as compared to COVID19-unrelated pneumonia, COVID-19 pneumonia outcome seems more strictly correlated to the extent of lung damage, rather than to the systemic circulatory and metabolic derangements typical of sepsis.
Pancreatic surgery still remains burdened by high levels of morbidity and mortality with a relevant incidence of complications, even in high volume centers. This review highlights the interventional radiological management of complications after pancreatic surgery. The current literature regarding the percutaneous drainage of fluid collections due to pancreatic fistulas, percutaneous transhepatic biliary drainage due to biliary leaks and transcatheter embolization (or stent–graft) due to arterial bleeding is analyzed. Moreover, also, percutaneous intra-portal islet auto-transplantation for the prevention of pancreatogenic diabetes in case of extended pancreatic resection is also examined. Moreover, a topic not usually treated in other similar reviewsas percutaneous intra-portal islet auto-transplantation for the prevention of pancreatogenic diabetes in case of extended pancreatic resection is also one of our areas of focus. In islet auto-transplantation, the patient is simultaneously donor and recipient. Differently from islet allo-transplantation, it does not require immunosuppression, has no risk of rejection and is usually efficient with a small number of transplanted islets.
Aims Abnormalities in the oculomotor system may represent an early sign of diabetic neuropathy and are currently poorly studied. We designed an eye-tracking-based test to evaluate oculomotor function in patients with type 1 diabetes. Methods We used the SRLab—Tobii TX300 Eye tracker® , an eye-tracking device, coupled with software that we developed to test abnormalities in the oculomotor system. The software consists of a series of eye-tracking tasks divided into 4 classes of parameters (Resistance, Wideness, Pursuit and Velocity) to evaluate both smooth and saccadic movement in different directions. We analyzed the oculomotor system in 34 healthy volunteers and in 34 patients with long-standing type 1 diabetes. Results Among the 474 parameters analyzed with the eye-tracking-based system, 11% were significantly altered in patients with type 1 diabetes ( p < 0.05), with a higher proportion of abnormalities observed in the Wideness (24%) and Resistance (10%) parameters. Patients with type 1 diabetes without diabetic neuropathy showed more frequently anomalous measurements in the Resistance class ( p = 0.02). The classes of Velocity and Pursuit were less frequently altered in patients with type 1 diabetes as compared to healthy subjects, with anomalous measurements mainly observed in patients with diabetic neuropathy. Conclusions Abnormalities in oculomotor system function can be detected in patients with type 1 diabetes using a novel eye-tracking-based test. A larger cohort study may further determine thresholds of normality and validate whether eye-tracking can be used to non-invasively characterize early signs of diabetic neuropathy. Trial: NCT04608890.
Background: Obesity may negatively impact clinical outcomes in kidney transplant (KT) recipients. Limited information is available on the prevalence of obesity in this population, and on the lifestyle habits associated with obesity. Methods: we conducted an online, anonymous survey to assess of the proportion of KT recipients with obesity, adherence to the Mediterranean diet (i.e., a dietary regimen with proven renal and cardiovascular outcomes) using the MEDI-Lite questionnaire, and level of physical activity using the International Physical Activity Questionnaire (IPAQ) short form among KT recipients. Results: 255 KT recipients participated. Median (25th–75th quartile) age was 56.0 (48.0; 62.0) years, 43.9% female, median BMI 23.9 (21.6; 26.5) kg/m2. The proportion of KT recipients with obesity was 9.8% (95% confidence interval, 6.4 to 14.1%). Adequate adherence to the Mediterranean diet (Medi-Lite score >9) was overall low (44.7%; 40.0 vs. 45.2% in those with or without obesity, respectively; p = 0.618). In participants with obesity the Medi-Lite score inversely correlated with BMI (R = −0.45; p < 0.025). Overall, 30.6% of participants had a low level of physical activity (44.0 vs. 29.1% of those with or without obesity, respectively; p = 0.125). The amount of energy expended walking was significantly lower among participants with obesity (462 (0.0; 1436) vs. 1056 (433; 2005) METs/week, p = 0.017). Conclusions: the burden of obesity among KT recipients is similar to that of the general population. Adherence to the Mediterranean diet was generally low, and nearly one-third of participants had a low level of physical activity. Building specialized multidisciplinary teams to manage obesity in KT recipients is urgently needed.
Background: Solid organ transplant (SOT) recipients may be at increased risk for severe disease and mortality from COVID-19 because of immunosuppression and prolonged end-stage organ disease. As a transplant center serving a diverse patient population, we report the cumulative incidence and outcomes of SARS-CoV-2 infection in our cohort of SOT recipients. Methods: We prospectively included in this observational study SOT recipients with a functioning kidney (n = 201), pancreas ± kidney (n = 66) or islet transplant (n = 24), attending outpatient regular follow-up at the San Raffaele Hospital from February 2020 to April 2021. Antibodies to SARS-CoV-2 were tested in all patients by a luciferase immunoprecipitation system assay. Results: Of the 291 SOT recipients, 30 (10.3%) tested positive for SARS-CoV-2 during the study period and prevalence was not different among different transplants. The SARS-CoV-2 antibody frequency was around 2.6-fold higher than the incidence of cases who tested positive for SARS-CoV-2 RT-PCR. As for the WHO COVID-19 severity classification, 19 (63.3%) SOT recipients were mild, nine (30%) were moderate, and two were critical and died yielding a crude mortality rate in our patient population of 6.7%. Kidney transplant (OR 12.9 (1.1–150) p = 0.041) was associated with an increased risk for moderate/critical disease, while statin therapy (OR 0.116 (0.015–0.926) p = 0.042) and pancreas/islet transplant (OR 0.077 (0.007–0.906) p = 0.041) were protective. Conclusions: The incidence of SARS-CoV-2 infection in SOT recipients may be higher than previously described. Due to the relative high crude mortality, symptomatic SOT recipients must be considered at high risk in case of SARS-CoV-2 infection.
Background and aims: Obesity-related cardiometabolic risk factors associate with COVID-19 severity and outcomes. Epicardial adipose tissue (EAT) is associated with cardiometabolic disturbances, is a source of proinflammatory cytokines and a marker of visceral adiposity. We investigated the relation between EAT characteristics and outcomes in COVID-19 patients. Methods and results: This post-hoc analysis of a large prospective investigation included all adult patients (>= 18 years) admitted to San Raffaele University Hospital in Milan, Italy, from February 25th to April 19th, 2020 with confirmed SARS-CoV-2 infection who underwent a chest computed tomography (CT) scan for COVID-19 pneumonia and had anthropometric data available for analyses. EAT volume and attenuation (EAT-At, a marker of EAT inflammation) were measured on CT scan. Primary outcome was critical illness, defined as admission to intensive care unit (ICU), invasive ventilation or death. Cox regression and regression tree analyses were used to assess the relationship between clinical variables, EAT characteristics and critical illness. One-hundred and ninety-two patients were included (median [25th-75th percentile] age 60 years [53-70], 76% men). Co-morbidities included overweight/obesity (70%), arterial hypertension (40%), and diabetes (16%). At multivariable Cox regression analysis, EAT-At (HR 1.12 [1.04-1.21]) independently predicted critical illness, while increasing PaO2/FiO(2) was protective (HR 0.996 [95% CI 0.993; 1.00]). CRP, plasma glucose on admission, EAT-At and PaO2/FiO(2) identified five risk groups that significantly differed with respect to time to death or admission to ICU (log-rank p < 0.0001). Conclusion: Increased EAT attenuation, a marker of EAT inflammation, but not obesity or EAT volume, predicts critical COVID-19. (C) 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Background. Graft quality from extended criteria donors (ECDs) is extremely wide, and a reliable evaluation parameter is required. So far, biopsy is widely used to evaluate ECD organs and to decide whether double (DKT) or single (SKT) kidney transplantation should be performed. The aim of this study is to compare renal resistance (RR) trend during hypothermic machine perfusion (HMP) with a preimplantation biopsy score. Methods. From December 2014 to April 2020, HMP has been systematically applied to all organs from ECDs for at least 3 hours. All grafts underwent a preimplantation biopsy histologic assessment with Karpinski's score. SKTs or DKTs were performed accordingly. RR trend during the first 180 minutes of HMP was compared with the biopsy score. Results. Eighty-three kidneys were used to perform 57 transplantations (31 SKTs and 26 DKTs). A biopsy confirmed suitability for transplantation in all cases, and the median score was 4 (range, 2-7). Kidneys with a score of 5 to 7 had significantly higher RR value than kidneys with a score of 0 to 4 at basal time (3.35 vs 2.71; P = .074), at 60 minutes (1.24 vs 0.94; P = .031), at 120 minutes (1.10 vs 0.81; P = .010), and at 180 minutes (1.00 vs 0.77; P = .022). A cutoff value of RR >0.88 at 120 minutes of perfusion had the best sensibility and specificity (0.71 and 0.75, respectively) to discriminate kidneys with a score of 5 to 7 from kidneys with a score of 0 to 4. No differences were found in postoperative outcomes between SKT and DKT recipients. Conclusions. RR trend during HMP correlates with the histologic score in ECD kidneys and can be used as a reliable parameter to evaluate graft quality.
The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.
ObjectivesCoronavirus disease 2019 (COVID‐19) is a viral illness caused by severe acute respiratory syndrome coronavirus 2. With the increasing number of improved and discharged patients with COVID‐19, the definition of an adequate follow‐up strategy is needed. The purpose of this study was to assess whether lung ultrasound (LUS) is an effective indicator of subclinical residual lung damage in patients with COVID‐19 who meet discharge criteria.MethodsWe prospectively enrolled 70 consecutive patients with COVID‐19 who had a prolonged hospitalization with inpatient rehabilitation between April 6 and May 22, 2020. All of the patients underwent an LUS evaluation at discharge. Data of patients with more severe disease during the acute phase (ie, required ventilatory support) were compared to those of patients with milder disease.ResultsAmong the 70 patients with COVID‐19 (22 women and 48 men; mean age ± SD, 68 ± 13 years), the LUS score before discharge was still frankly pathologic and higher in patients who had more severe disease during the acute phase compared to patients with milder disease (median [interquartile range], 8.0 [5.5–13.5] versus 2.0 [1.0–7.0]; P < .001), even when both categories met internationally defined discharge criteria.ConclusionsLung ultrasound can identify the persistence of subclinical residual lung damage in patients with severe COVID‐19 even if they meet discharge criteria. Considering the low cost, easy application, and lack of radiation exposure, LUS seems the ideal tool to be adopted in outpatient and primary care settings for the follow‐up of patients with COVID‐19.
OBJECTIVE:Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients.RESEARCH DESIGN AND METHODS:A phase 3, multicenter, randomized, double-blind, parallel-assignment study (NCT01817959) was conducted in recipients of islet allotransplants randomized (2:1) to reparixin or placebo in addition to immunosuppression. Primary outcome was the area under the curve (AUC) for C-peptide during the mixed-meal tolerance test at day 75 ± 5 after the first and day 365 ± 14 after the last transplant. Secondary end points included insulin independence and standard measures of glycemic control.RESULTS:The intention-to-treat analysis did not show a significant difference in C-peptide AUC at both day 75 (27 on reparixin vs. 18 on placebo, P = 0.99) and day 365 (24 on reparixin vs. 15 on placebo, P = 0.71). There was no statistically significant difference between treatment groups at any time point for any secondary variable. Analysis of patient subsets showed a trend for a higher percentage of subjects retaining insulin independence for 1 year after a single islet infusion in patients receiving reparixin as compared with patients receiving placebo (26.7% vs. 0%, P = 0.09) when antithymocyte globulin was used as induction immunosuppression.CONCLUSIONS:In this first double-blind randomized trial, islet transplantation data obtained with reparixin do not support a role of CXCR1/2 inhibition in preventing islet inflammation-mediated damage.
Background Use of cell-based medicinal products (CBMPs) represents a state-of-the-art approach for reducing general immunosuppression in organ transplantation. We tested multiple regulatory CBMPs in kidney transplant trials to establish the safety of regulatory CBMPs when combined with reduced immunosuppressive treatment. Methods The ONE Study consisted of seven investigator-led, single-arm trials done internationally at eight hospitals in France, Germany, Italy, the UK, and the USA (60 week follow-up). Included patients were living-donor kidney transplant recipients aged 18 years and older. The reference group trial (RGT) was a standard-of-care group given basiliximab, tapered steroids, mycophenolate mofetil, and tacrolimus. Six non-randomised phase 1/2A cell therapy group (CTG) trials were pooled and analysed, in which patients received one of six CBMPs containing regulatory T cells, dendritic cells, or macrophages; patient selection and immunosuppression mirrored the RGT, except basiliximab induction was substituted with CBMPs and mycophenolate mofetil tapering was allowed. None of the trials were randomised and none of the individuals involved were masked. The primary endpoint was biopsy-confirmed acute rejection (BCAR) within 60 weeks after transplantation; adverse event coding was centralised. The RTG and CTG trials are registered with ClinicalTrials.gov, NCT01656135, NCT02252055, NCT02085629, NCT02244801, NCT02371434, NCT02129881, and NCT02091232. Findings The seven trials took place between Dec 11, 2012, and Nov 14, 2018. Of 782 patients assessed for eligibility, 130 (17%) patients were enrolled and 104 were treated and included in the analysis. The 66 patients who were treated in the RGT were 73% male and had a median age of 47 years. The 38 patients who were treated across six CTG trials were 71% male and had a median age of 45 years. Standard-of-care immunosuppression in the recipients in the RGT resulted in a 12% BCAR rate (expected range 3.2-18.0). The overall BCAR rate for the six parallel CTG trials was 16%. 15 (40%) patients given CBMPs were successfully weaned from mycophenolate mofetil and maintained on tacrolimus monotherapy. Combined adverse event data and BCAR episodes from all six CTG trials revealed no safety concerns when compared with the RGT. Fewer episodes of infections were registered in CTG trials versus the RGT. Interpretation Regulatory cell therapy is achievable and safe in living-donor kidney transplant recipients, and is associated with fewer infectious complications, but similar rejection rates in the first year. Therefore, immune cell therapy is a potentially useful therapeutic approach in recipients of kidney transplant to minimise the burden of general immunosuppression. Copyright (C) 2020 Elsevier Ltd. All rights reserved.
Abstract Background The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated the immunogenicity and safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy. Methods In this phase 3, randomized (1:1), observer-blind, multicenter trial, RT recipients were enrolled and received 2 doses of RZV or placebo 1–2 months (M) apart 4–18M posttransplant. Anti–glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post–dose 1, and 1M and 12M post–dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post–dose 2. Results Two hundred sixty-four participants (RZV: 132; placebo: 132) were enrolled between March 2014 and April 2017. gE-specific humoral and cell-mediated immune responses were higher in RZV than placebo recipients across postvaccination time points and persisted above prevaccination baseline 12M post–dose 2. Local AEs were reported more frequently by RZV than placebo recipients. Overall occurrences of renal function changes, rejections, unsolicited AEs, serious AEs, and pIMDs were similar between groups. Conclusions RZV was immunogenic in chronically immunosuppressed RT recipients. Immunogenicity persisted through 12M postvaccination. No safety concerns arose. Clinical Trials Registration NCT02058589.
Hyperglycemia is the main pathogenic factor underlying the development of secondary complications of diabetes. Pancreas transplantation (PTx), either alone or combined with kidney transplantation, rapidly restores euglycemia in insulin-dependent diabetic individuals. This chapter will review the effects of PTx on the main microvascular and macrovascular secondary complications of diabetes, namely nephropathy, neuropathy, retinopathy, and cardiomyopathy. Although PTx provides some early benefits and halts the progression of certain complications, long-term euglycemia after PTx alone is needed to improve several outcomes.
A combined kidney and pancreas transplant is a therapeutic option for patients with type 1 diabetes and end-stage renal disease. After successful transplantation, fertility is rapidly restored, allowing women of childbearing age to have spontaneous pregnancies and men to father pregnancies. These pregnancies are at increased risk for maternal and neonatal adverse outcomes due to immunosuppressive therapy, comorbidities, previous type 1 diabetes and previous transplant surgery, although the majority ends with the birth of a live and healthy offspring. Hypertension, miscarriages, diabetes, infections, graft rejections, preterm delivery and low birth weight may complicate pregnancies after pancreas-kidney transplantation. Since not all immunosuppressive drugs can be safely used in pregnancy, it is important to review immunosuppressive treatment before conception. Adequate pre-conception counseling is important to inform women and their partners about potential risks for the pregnancy and the grafts and the advantages of pregnancy planning. These pregnancies should be managed within a multidisciplinary team, comprising a transplant physician, an endocrinologist, a nephrologist, an obstetrician and a neonatologist. Last but not least, it is very important to continue collecting data on the pregnancies in pancreas-kidney transplantation with the aim to improve knowledge and to generate evidence-based guidelines for the care of women after pancreas-kidney transplants who are considering a pregnancy.
Curing type 1 diabetes means replacing the lost insulin secretion with a perpetual, autonomous, and self-regulating source of insulin delivery able to correct all the metabolic abnormalities and prevent the long-term chronic complications of the disease. In Milan, substantial experience in islet transplantation and beta-cell replacement has been gained and maintained during the last three decades, thereby achieving a leading position in the production of human islets for transplantation and its establishment as one of the most experienced centers in the world with more than 370 islet infusions performed and high-level scientific production. During this long period the field of islet transplantation has evolved significantly from the breakthrough of the first cases in early 1990s, since significant advances in islet isolation and engraftment, together with improved immunosuppressive strategies, have been reported. A major effort is now being focused on a special multidisciplinary and integrated project aiming at bringing islet transplantation and beta-cell replacement to the level of a successful clinical routine procedure.
Background: Pancreas transplants (PTx) from pediatric donors (PDs, age <18 years) might expose to greater technical difficulties and provide less insulin independence in the long-term due to smaller beta cells mass. Most available data on pancreas transplants from PDs relate to simultaneous pancreas-kidney transplants, whereas little is known on pancreas transplant alone (PTA) from PDs. Methods: We retrospectively analyzed perioperative surgical complications and graft survival in T1D recipients of PTA or pancreas after kidney (PAK) transplant from PDs or adult donors (ADs) between Jan 2010 and May 2018. Data were collected through electronic medical record review. Results: A total of 43 PTx recipients (35 PTA) had data available for analyses. Age at PTx was 40.0±8.3 years, T1D duration 25±10 years, 46.5% female, BMI 23±3 k/m2. Nearly half (49%) pancreas grafts were from PDs. Median donor age was 18 [IQR: 16] years (min. 2, max 45 years). Donor characteristics (age, BMI, body surface area [BSA]) significantly differed between groups (all p<0.05), but recipient characteristics (age at PTx, T1D duration, BMI) were similar. Median length of stay was similar in the AD and PD groups (17.5 [8.5] vs. 14 [7.0] days, p=NS). Rates of any perioperative surgical complications (55% vs. 33%), re-laparotomy (41% vs. 19%) and explanation (36% vs. 10%) were numerically lower and early graft thrombosis was significantly lower (55% vs. 10%, p<0.01) in the PD group. Median graft survival was numerically greater in the AD vs. the PD group (8.5 vs. 5.7 years, p=0.34). However, rejection rate was significantly higher in the PD group (4.5% vs. 52%, p<0.01). We found no correlation between donor characteristics (age, BMI, BSA and donor/recipient BSA ratio) and graft survival. Conclusions: PTx from PDs tended to be associated with less surgical complications vs. PTx from ADs. Graft survival was similar. Expanding selection criteria to include PDs would increase the availability of pancreas grafts and possibly improve clinical outcomes. Disclosure C. Conte: None. C. Socci: None. A. Secchi: None. P. Maffi: None.