Pancreatic islet transplantation: current advances and challenges.

Diabetes is a prevalent chronic disease that traditionally requires severe reliance on medication for treatment. Oral medication and exogenous insulin can only temporarily maintain blood glucose levels and do not cure the disease. Most patients need life-long injections of exogenous insulin. In recent years, advances in islet transplantation have significantly advanced the treatment of diabetes, allowing patients to discontinue exogenous insulin and avoid complications.Long-term follow-up results from recent reports on islet transplantation suggest that they provide significant therapeutic benefit although patients still require immunotherapy, suggesting the importance of future transplantation strategies. Although organ shortage remains the primary obstacle for the development of islet transplantation, new sources of islet cells, such as stem cells and porcine islet cells, have been proposed, and are gradually being incorporated into clinical research. Further research on new transplantation sites, such as the subcutaneous space and mesenteric fat, may eventually replace the traditional portal vein intra-islet cell infusion. Additionally, the immunological rejection reaction in islet transplantation will be resolved through the combined application of immunosuppressant agents, islet encapsulation technology, and the most promising mesenchymal stem cells/regulatory T cell and islet cell combined transplantation cell therapy. This review summarizes the progress achieved in islet transplantation, and discusses the research progress and potential solutions to the challenges faced.

Skeletal Myoblast Cells Enhance the Function of Transplanted Islets in Diabetic Mice.

Islet transplantation (ITx) is an established and safe alternative to pancreas transplantation for type 1 diabetes mellitus (T1DM) patients. However, most ITx recipients lose insulin independence by 3 years after ITx due to early graft loss, such that multiple donors are required to achieve insulin independence. In the present study, we investigated whether skeletal myoblast cells could be beneficial for promoting angiogenesis and maintaining the differentiated phenotypes of islets. In vitro experiments showed that the myoblast cells secreted angiogenesis-related cytokines (vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and stromal-derived factor-1α (SDF-1α)), contributed to maintenance of differentiated islet phenotypes, and enhanced islet cell insulin secretion capacity. To verify these findings in vivo, we transplanted islets alone or with myoblast cells under the kidney capsule of streptozotocin-induced diabetic mice. Compared with islets alone, the group bearing islets with myoblast cells had a significantly lower average blood glucose level. Histological examination revealed that transplants with islets plus myoblast cells were associated with a significantly larger insulin-positive area and significantly higher number of CD31-positive microvessels compared to islets alone. Furthermore, islets cotransplanted with myoblast cells showed JAK-STAT signaling activation. Our results suggest two possible mechanisms underlying enhancement of islet graft function with myoblast cells cotransplantation: "indirect effects" mediated by angiogenesis and "direct effects" of myoblast cells on islets via the JAK-STAT cascade. Overall, these findings suggest that skeletal myoblast cells enhance the function of transplanted islets, implying clinical potential for a novel ITx procedure involving myoblast cells for patients with diabetes.

Impact of Pretransplant C-Reactive Protein, Neutrophiles, Platelets, and Albumin Levels on Recipient Survival After Simultaneous Pancreas and Kidney Transplantation.

BACKGROUND: Long-lasting diabetes mellitus type 1 and end-stage renal disease induce severe metabolic and immunologic deterioration. Pretransplant C-reactive protein (CRP) and albumin (ALB) levels impact kidney transplantation. We evaluated the effects of preoperative CRP, ALB, neutrophils (NEU), and platelet (PLT) counts on 1- and 5-year recipient survival after simultaneous pancreas and kidney transplantation (SPK). METHODS: Among 103 SPK recipients, the parameters were as follows: CRP (mean: 4.5 ± 4.97 mg/L); NEU (mean: 5.12 ± 2.13 × 103/mm3); PLT (mean: 244 ± 84 × 103/mm3); ALB (mean 4.5 ± 0.75 g/dL) were obtained before transplantation. Cox regression, uni-, multivariate analysis for 1- and 5-year survivals were performed with 95% CIs, and the area under the receiver operating characteristic (ROC) curve (AUC) was assessed. RESULTS: In Cox regression, ALB <3.65 g/dL significantly affected 1- and 5-year survivors with hazard ratios of 8 (95% CI, 1.5-38.28; P < .05) and 3.13 (95% CI, 1.45-6.73; P < .05), respectively. In univariate analysis, we found significantly decreased 1-year survival when PLT <180×103/mm3, ALB <3.65 g/dL, NEU >5.8×103/mm3 and CRP >2.25 mg/L with odds ratios (OR) of 6.75 (95% CI, 2.12-21.15); 4.05 (95% CI, 1.3-12.09); 2.97 (95% CI, 1.02-8.64) and 5.51 (95% CI, 1.67-18.19), respectively. Independent factors for 5-year survival were CRP, ALB, and PLT with OR of 4.72 (95% CI, 1.67-13.29), 3.31 (95% CI, 1.18-9.25), and 4.2 (95% CI, 1.39-12.68), respectively. In multivariate analysis, we built 2 models for 1-year survival. Model 1 (ALB+PLT) with ORs of 3.12 (95% CI, 0.97-10.07) and 5.55 (95% CI, 1.67-18.4); and model 2 (CRP+PLT) with ORs of 5.51 (95% CI, 1.5-17.3) and 4.3 (95% CI, 1.2-15.06), respectively. The AUC for models 1 and 2 were 0.74 and 0.759, respectively. CONCLUSIONS: NEU, PLT, ALB, and CRP levels assessed before transplantation are independent factors for 1- and 5-year SPK recipient survival.

Combined Liver-Pancreas Transplantation as Novel Treatment for Patient With Cystic Fibrosis: A Case Report.

BACKGROUND: A 21-year-old woman diagnosed with cystic fibrosis developed cirrhosis, exocrine pancreatic insufficiency, and insulin-dependent diabetes mellitus. The patient qualified for double organ liver-pancreas transplantation beyond typical indications. The respiratory symptoms of cystic fibrosis were moderate and well-treated. The patient was endangered mainly by liver insufficiency and recurrent hypoglycemia, which was due to the treatment of diabetes with high doses of insulin. Computed tomography showed mild bronchiectasis, cirrhotic liver, splenomegaly, and atrophy of the pancreas. Pseudomonas aeruginosa colonized the upper respiratory tract. Gastrointestinal complications were sufficient for the patient to be qualified for combined liver-pancreas transplantation. METHODS: First, a standard hepatectomy was performed. The liver was transplanted orthotopically. Subsequently, the team performed pancreas transplantation through a separate incision. The donor's duodenum was anastomosed to the recipient's jejunum, close to the ligament of Treitz. RESULTS: No serious complications were noted during the postoperative period. Transplanted organs started functioning without delay. The patient was discharged after 6 weeks in general good condition. Twenty months later, the patient felt well, and the grafts kept functioning properly. CONCLUSION: Combined liver-pancreas transplantation in patients with CF restores exocrine and endocrine pancreatic function and minimizes the risk of life-threatening complications associated with liver insufficiency. Improvement of life quality coincides with the possibility of discontinuing insulin and pancreatic enzyme supplementation. The combination of liver and pancreas transplantation may prevent advanced pulmonary complications, extend the prognosis of survival, and improve the long-term life quality.

Clinical Islet Xenotransplantation: Development of Isolation Protocol, Anti-Rejection Strategies, and Clinical Outcomes.

Allogeneic islet transplantation has become a standard therapy for unstable type 1 diabetes. However, considering the large number of type 1 diabetic patients, the shortage of donors is a serious issue. To address this issue, clinical islet xenotransplantation is conducted. The first clinical islet xenotransplantation was performed by a Swedish team using fetal pancreatic tissue. Thereafter, clinical trials of islet xenotransplantation were conducted in New Zealand, Russia, Mexico, Argentina, and China using neonatal pig islets. In clinical trials, fetal or neonatal pancreata are used because of the established reliable islet isolation methods. These trials demonstrate the method's safety and efficacy. Currently, the limited number of source animal facilities is a problem in terms of promoting islet xenotransplantation. This limitation is due to the high cost of source animal facilities and the uncertain future of xenotransplantation. In the United States, the first xenogeneic heart transplantation has been performed, which could promote xenotransplantation. In Japan, to enhance xenotransplantation, the 'Medical Porcine Development Association' has been established. We hope that xenogeneic transplantation will become a clinical reality, serving to address the shortage of donors.

Surgery for carpal tunnel syndrome in patients with and without diabetes-Is there a difference in the frequency of surgical procedures?

Carpal tunnel syndrome (CTS) occurs more often among individuals with diabetes. The aim of this retrospective observational registry study was to examine whether individuals with diabetes and CTS are treated surgically to the same extent as individuals with CTS but without diabetes. Data on CTS diagnosis and surgery were collected from the Skåne Healthcare Register (SHR). A total of 35,105 individuals (age ≥ 18 years) diagnosed with CTS from 2004-2019 were included. Data were matched to the Swedish National Diabetes Register (NDR. Cox regression models were used to calculate the risk of the use of surgical treatment. Of the 35,105 included individuals with a CTS diagnosis, 17,662 (50%) were treated surgically, and 4,966 (14%) had diabetes. A higher number of individuals with diabetes were treated surgically (2,935/4,966, 59%) than individuals without diabetes (14,727/30,139, 49%). In the Cox regression model, diabetes remained a significant risk factor for surgical treatment (PR 1.14 (95% CI 1.11-1.17)). Individuals with type 1 diabetes were more frequently treated surgically (490/757, 65%) than individuals with type 2 diabetes (2,445/4,209, 58%). There was no difference between the sexes and their treatment. The duration of diabetes was also a risk factor for surgical treatment in diabetes type 2, but high HbA1c levels were not. Individuals with diabetes are more likely to be treated surgically for CTS than individuals without diabetes. Individuals with type 1 diabetes are more likely to be treated surgically for CTS than individuals with type 2 diabetes.

Surgical complications and technical failure of simultaneous pancreas-kidney transplantation: A 22-year experience from a single center.

Simultaneous pancreas-kidney transplantation (SPKT) is the best treatment for selected individuals with type 1 diabetes mellitus and end-stage renal disease. Despite advances in surgical techniques, donor and recipient selection, and immunosuppressive therapies, SPKT remains a complex procedure with associated surgical complications and adverse consequences. We conducted a retrospective study that included 263 SPKT procedures performed between May 2000, and December 2022. A total of 65 patients (25%) required at least one relaparotomy, resulting in an all-cause relaparotomy rate of 2.04 events per 100 in-hospital days. Lower donor body mass index was identified as an independent factor associated with reoperation (OR .815; 95% CI:  .725-.917, p = .001). Technical failure (TF) occurred in 9.9% of cases, primarily attributed to pancreas graft thrombosis, intra-abdominal infections, bleeding, and anastomotic leaks. Independent predictors of TF at 90 days included donor age above 36 years (HR 2.513; 95% CI 1.162-5.434), previous peritoneal dialysis (HR 2.503; 95% CI 1.149-5.451), and specific pancreas graft reinterventions. The findings highlight the importance of carefully considering donor and recipient factors in SPKT. The incidence of TF in our study population aligns with the recent series. Continuous efforts should focus on identifying and mitigating potential risk factors to enhance SPKT outcomes, thereby reducing post-transplant complications.

Impact of a Public Health Emergency on Behavior, Stress, Anxiety and Glycemic Control in Patients With Pancreas or Islet Transplantation for Type 1 Diabetes.

A public health emergency such as the COVID-19 pandemic has behavioral, mental and physical implications in patients with type 1 diabetes (T1D). To what extent the presence of a transplant further increases this burden is not known. Therefore, we compared T1D patients with an islet or pancreas transplant (ß-cell Tx; n = 51) to control T1D patients (n = 272). Fear of coronavirus infection was higher in those with ß-cell Tx than without (Visual Analogue Scale 5.0 (3.0-7.0) vs. 3.0 (2.0-5.0), p = 0.004) and social isolation behavior was more stringent (45.8% vs. 14.0% reported not leaving the house, p < 0.001). A previous ß-cell Tx was the most important predictor of at-home isolation. Glycemic control worsened in patients with ß-cell Tx, but improved in control patients (ΔHbA1c +1.67 ± 8.74 vs. -1.72 ± 6.15 mmol/mol, p = 0.006; ΔTime-In-Range during continuous glucose monitoring -4.5% (-6.0%-1.5%) vs. +3.0% (-2.0%-6.0%), p = 0.038). Fewer patients with ß-cell Tx reported easier glycemic control during lockdown (10.4% vs. 22.6%, p = 0.015). All T1D patients, regardless of transplantation status, experienced stress (33.4%), anxiety (27.9%), decreased physical activity (42.0%), weight gain (40.5%), and increased insulin requirements (29.7%). In conclusion, T1D patients with ß-cell Tx are increasingly affected by a viral pandemic lockdown with higher fear of infection, more stringent social isolation behavior and deterioration of glycemic control. This trial has been registered in the clinicaltrials.gov registry under identifying number NCT05977205 (URL: https://clinicaltrials.gov/study/NCT05977205).

Revolutionizing pancreatic islet organoid transplants: Improving engraftment and exploring future frontiers.

Type-1 Diabetes Mellitus (T1DM) manifests due to pancreatic beta cell destruction, causing insulin deficiency and hyperglycaemia. Current therapies are inadequate for brittle diabetics, necessitating pancreatic islet transplants, which however, introduces its own set of challenges such as paucity of donors, rigorous immunosuppression and autoimmune rejection. Organoid technology represents a significant stride in the field of regenerative medicine and bypasses donor-based approaches. Hence this article focuses on strategies enhancing the in vivo engraftment of islet organoids (IOs), namely vascularization, encapsulation, immune evasion, alternative extra-hepatic transplant sites and 3D bioprinting. Hypoxia-induced necrosis and delayed revascularization attenuate organoid viability and functional capacity, alleviated by the integration of diverse cell types e.g., human amniotic epithelial cells (hAECs) and human umbilical vein endothelial cells (HUVECs) to boost vascularization. Encapsulation with biocompatible materials and genetic modifications counters immune damage, while extra-hepatic sites avoid surgical complications and immediate blood-mediated inflammatory reactions (IBMIR). Customizable 3D bioprinting may help augment the viability and functionality of IOs. While the clinical translation of IOs faces hurdles, preliminary results show promise. This article underscores the importance of addressing challenges in IO transplantation to advance their use in treating type 1 diabetes effectively.

Assessing the influence of graft loss on 4-year patient survival after simultaneous pancreas-kidney transplantation: Kaplan-Meier versus Competing Risk Analysis model.

BACKGROUND: Graft loss increases the risk of patient death after simultaneous pancreas-kidney (SPK) transplantation. The relative risk of each graft failure is complex due to the influence of several competing events. METHODS: This retrospective, single-center study compared 4-year patient survival according to the graft status using Kaplan-Meier (KM) and Competing Risk Analysis (CRA). Patient survival was also assessed according to five eras (Era 1: 2001-2003; Era 2: 2004-2006; Era 3: 2007-2009; Era 4: 2010-2012; Era 5: 2012-2015). RESULTS: Between 2000 and 2015, 432 SPK transplants were performed. Using KM, patient survival was 86.5% for patients without graft loss (n = 333), 93.4% for patients with pancreas graft loss (n = 46), 43.7% for patients with kidney graft loss (n = 16), and 25.4% for patients with pancreas and kidney graft loss (n = 37). Patient survival was underestimated using KM versus CRA methods in patients with pancreas and kidney graft losses (25.4% vs. 36.2%), respectively. Induction with lymphocyte depleting antibodies was associated with 81% reduced risk (HR.19, 95% CI.38-.98, p = .0048), while delayed kidney function (HR 2.94, 95% CI 1.09-7.95, p = .033) and surgical complications (HR 2.94, 95% CI 1.22-7.08, p = .016) were associated with higher risk of death. Four-year patient survival increased from Era 1 to Era 5 (79% vs. 87.9%, p = .047). CONCLUSION: In this cohort of patients, kidney graft loss, with or without pancreas graft loss, was associated with higher mortality after SPK transplantation. Compared to CRA, the KM model underestimated survival only among patients with pancreas and kidney graft losses. Patient survival increased over time.

Inflammatory and hypoxic stress-induced islet exosomes released during isolation are associated with poor transplant outcomes in islet autotransplantation.

Islets experience enormous stress during the isolation process, leading to suboptimal endocrine function after total pancreatectomy with islet autotransplantation (TPIAT). Our investigation focused on inducing isolation stress in islets ex vivo, where proinflammatory cytokines and hypoxia prompted the release of stress exosomes (exoS) sized between 50 and 200 nm. Mass spectrometry analysis revealed 3 distinct subgroups of immunogenic proteins within these exoS: damage-associated molecular patterns (DAMPs), chaperones, and autoantigens. The involvement of endosomal-sorting complex required for transport proteins including ras-associated binding proteins7A, ras-associated binding protein GGTA, vacuolar protein sorting associated protein 45, vacuolar protein sorting associated protein 26B, and the tetraspanins CD9 and CD63, in exoS biogenesis was confirmed through immunoblotting. Next, we isolated similar exoS from the islet infusion bags of TPIAT recipients (N = 20). The exosomes from infusion bags exhibited higher DAMP (heat shock protein family A [Hsp70] member 1B and histone H2B) levels, particularly in the insulin-dependent TPIAT group. Additionally, elevated DAMP protein levels in islet infusion bag exosomes correlated with increased insulin requirements (P = .010) and higher hemoglobin A1c levels 1-year posttransplant. A deeper exploration into exoS functionality revealed their potential to activate monocytes via the toll-like receptor 3/7: DAMP axis. This stimulation resulted in the induction of inflammatory phenotypes marked by increased levels of CD68, CD80, inducible nitric oxide synthase, and cyclooxygenase-2. This activation mechanism may impact the successful engraftment of transplanted islets.

[Diabetes and pancreas or islet transplantation: psychological issues]. / Diabète et transplantation du pancréas ou d'îlots de Langerhans : enjeux psychologiques.

Diabetes is a chronic and progressive disease that affects an increasing number of patients. The prevalence of associated psychological comorbidities is high and often requires the implementation of targeted psychological interventions. Pancreas or islet transplantation remains a therapeutic option to consider, for a part of patients with type 1 diabetes unstable disease or established complications. From the clinical indication to the waiting period for a transplantation, then to the postoperative and long-term care, the diabetic patient is found to experience perpetual changes that may test his adaptability. In this article, the psychological aspects of the pancreas or islet transplantation, as well as the role of a liaison psychiatrist in a transplantation unit will be discussed.

Le diabète est une maladie chronique et évolutive atteignant un nombre croissant de patients. La prévalence des comorbidités psychiques associées est élevée et nécessite souvent l'implémentation d'interventions psychologiques ciblées. La transplantation du pancréas ou d'îlots de Langerhans est une option thérapeutique à considérer pour certains patients avec un diabète de type 1 instable ou des complications installées. De l'indication clinique à la période d'attente pour une greffe, puis des suites postopératoires jusqu'à la vie d'après la greffe, le patient diabétique vit des transitions multiples le mettant à l'épreuve. Dans cet article, nous discutons les aspects psychologiques de ces transplantations ainsi que les interventions du psychiatre de liaison au sein d'un service de transplantation.

Dynamics of Sex Hormones in Men with Diabetes Mellitus After Autologous Mesenchymal Stem Cell Transplant.

OBJECTIVES: Our goal was to determine levels of sex hormones in men with type 1 diabetes mellitus and type 2 diabetes mellitus after autologous mesenchymal stem cell transplant. MATERIALS AND METHODS: We examined 10 male patients (32-56 years old) with type 1 diabetes mellitus and type 2 diabetes mellitus, whom we subsequently divided into 2 groups and examined. Group 1 comprised 5 male patients who received autologous mesenchymal stem cell transplant (cells were obtained from patient's iliac crest and cultured for 3-4 weeks) by intravenous infusion. Group 2 comprised 5 male patients (control group) who were on hypoglycemic tablet therapy or insulin therapy. The quantity of autologous mesenchymal stem cells infused was 95 × 106 to 97 × 106 cells. We analyzed levels of testosterone, luteinizing hormone, estradiol, and glycated hemoglobin in patients both before and 3 months after the autologous mesenchymal stem cell transplant procedure. RESULTS: In men with type 1 diabetes mellitus and type 2 diabetes mellitus, autologous mesenchymal stem cell transplant led to an increase in testosterone levels from 5.31 ± 2.12 to 6.33 ± 2.12 ng/mL (P = .82), a decrease in luteinizing hormone from 8.43 ± 1.25 to 5.94 ± 1.57 mIU/mL (P = .04), and a decrease in glycated hemoglobin from 9.45 ± 1.24% to 8.53 ± 1.08% (P = .25) after 3 months. The increase in testosterone in men with autologous mesenchymal stem cell transplant group of 6.33 ± 2.12 ng/mL was significant compared with men in the control group (3.9 ± 1.18 ng/mL; P = .01). CONCLUSIONS: Testosterone level increased and luteinizing hormone level decreased within 3 months after autologous mesenchymal stem cell transplant in men with diabetes mellitus.

Biomaterial-assisted strategies to improve islet graft revascularization and transplant outcomes.

Islet transplantation holds significant promise as a curative approach for type 1 diabetes (T1D). However, the transition of islet transplantation from the experimental phase to widespread clinical implementation has not occurred yet. One major hurdle in this field is the challenge of insufficient vascularization and subsequent early loss of transplanted islets, especially in non-intraportal transplantation sites. The establishment of a fully functional vascular system following transplantation is crucial for the survival and secretion function of islet grafts. This vascular network not only ensures the delivery of oxygen and nutrients, but also plays a critical role in insulin release and the timely removal of metabolic waste from the grafts. This review summarizes recent advances in effective strategies to improve graft revascularization and enhance islet survival. These advancements include the local release and regulation of angiogenic factors (e.g., vascular endothelial growth factor, VEGF), co-transplantation of vascular fragments, and pre-vascularization of the graft site. These innovative approaches pave the way for the development of effective islet transplantation therapies for individuals with T1D.

Closed-Loop Insulin Delivery May Help Prevent Metabolic Complications During Bariatric Surgery in Patients with Type 1 Diabetes: A Case Report.

Introduction: Obesity in patients with type 1 diabetes (T1D) may worsen their prognosis. Bariatric surgery in these patients can be associated with complications such as diabetic ketoacidosis and severe hypoglycemic episodes. Closed-loop insulin delivery could be a solution to avoid them. Case Report: A 45-year-old woman with T1D and obesity (body mass index of 38.4 kg/m2) was included in our preoperative course of bariatric surgery. Three months before surgery, a closed-loop insulin delivery was instituted due to one prior severe hypoglycemia. Patient did not have immediate or late postoperative hypoglycemia despite consuming a weak amount of carbohydrate. Three months after surgery glycemic control was on target with 86% of time in range 70-180 mg/dL and no time below 70 mg/dL. Conclusion: This case report shows that the use of a closed-loop insulin delivery made it possible to perform bariatric surgery in complete safety for our patient.

Insulin independence following islet transplantation improves long-term metabolic outcomes.

AIMS: Pancreatic islet allotransplantation is an effective therapy for type 1 diabetes mellitus, restoring glycaemic control and hypoglycaemic awareness in patients with recurrent severe hypoglycaemia. Insulin independence following transplant is being increasingly reported; however, this is not a primary endpoint in the UK. Having surpassed 10 years of islet transplantation in Scotland, we aimed to evaluate the impact of insulin independence following transplant on metabolic outcomes and graft survival. METHODS: We conducted a retrospective analysis on data collected prospectively between 2011 and 2022. Patients who underwent islet transplantation in Scotland up to the 31st January 2020 were included. Primary endpoint was graft survival (stimulated C-peptide >50 pmol/L). Secondary endpoints included GOLD score, HbA1c, C-peptide and insulin requirement. Outcomes were compared between patients who achieved insulin independence at any point following transplant versus those who did not. RESULTS: 60 patients were included. 74.5% experienced >50 severe hypoglycaemic episodes in the year preceding transplant. There was a 55.0% decrease in insulin requirement following transplant and 30.0% achieved insulin independence. Mean graft survival time was 9.0 years (95% CI 7.2-10.9) in patients who achieved insulin independence versus 4.4 years (95% CI 3.4-5.3) in patients who did not. Insulin independence was associated with significantly improved graft function, glycaemic control and hypoglycaemic awareness at 1 year. CONCLUSIONS: This is the largest UK single-centre study on islet transplant to date. Our findings demonstrate significantly improved outcomes in patients who achieved insulin independence following islet transplantation.

Impact of pancreas transplantation alone on kidney function: A multicenter clinical cohort study.

Pancreas transplantation alone (PTA) is a ß cell replacement option for selected patients with type 1 diabetes mellitus; concerns have been raised regarding deterioration in kidney function (KF) after PTA. This retrospective multicenter study assessed actual impact of transplantation and immunosuppression on KF in PTA recipients at three Transplant Centers. The primary composite endpoint 10 years after PTA was >50% eGFR decline, eGFR < 30 mL/min/1.73 m2 , and/or receiving a kidney transplant (KT). Overall, 822 PTA recipients met eligibility. Median baseline and 10-year eGFR (mL/min/1.73 m2 ) were 76.3 (58.1-100.8) and 51.3 (35.3-65.9), respectively. Primary composite endpoint occurred in 98 patients (53.5%) with 45 experiencing a >50% decrease in eGFR by 10 years post-transplant, 38 eGFR < 30 mL/min/1.73 m2 and 49 requiring KT. KF declined most significantly within 6 months post-PTA, more often in females and patients with better preserved GFR up to 5 years with 11.6% kidney failure at 10 years. Patient survival and death-censored graft survival were both 68% at 10 years with overall graft thrombosis rate 8%. KF declined initially after PTA but stabilized with further slow progression. In conclusion, prospective intervention studies are needed to test renal sparing interventions while gathering more granular data.

Could Transplantation into the Thyroid Gland Benefit Pancreatic Islet Grafting in Unstable Type 1 Diabetes (T1DM), Complicated Type 2 Diabetes (T2DM), and Patients with Total Pancreatectomy?

BACKGROUND: Insular allograft for unstable type 1 diabetes and autograft in pancreatectomy patients are nowadays considered established procedures with precise indications and predictable outcomes. The clinical outcome of islet transplantation is similar to that of pancreas transplantation, avoiding the complications associated with organ transplantation. OBJECTIVE: We hypothesised that transplantation of islets of Langerhans within an endocrine organ could better promote their engraftment and function. This could help to resolve or ameliorate known pathological conditions such as unstable type 1 diabetes and complicated type 2 diabetes. RATIONALE: Pancreatic islet transplantation is currently performed almost exclusively in the liver. The liver provides a sufficiently favourable environment, although not entirely. The hepatic parenchyma has a lower oxygen tension than the pancreatic parenchyma and the vascular structure of the liver is not typical of an exclusively endocrine organ. Moreover, islet transplantation into the liver is not without complications, including hematoma or portal vein thrombosis. PROPOSED PROJECT: The thyroid gland is the endocrine gland proposed as a 'container'. In fact, it has all the characteristics of 'physio-compatibility' which can address the objectives assumed. It is indeed an ideal site because it is an easily accessible anatomical site that allows islets to be implanted using ultrasound-guided transcutaneous inoculation technique. Moreover, it has physiological and anatomical endocrine affinities with pancreatic islets and, if necessary, it can be removed, using hormone supplementation or replacement therapy. CONCLUSIONS: The thyroid gland may be proposed as an ideal site for islet implantation due to its anatomical and physiocompatibility characteristics.

[Simultaneous living donor pancreas-kidney transplantation in a patient with type 1 diabetes mellitus after program hemodialysis. Case report].

Simultaneous pancreas-kidney transplantation is an effective treatment option for end-stage renal disease with diabetes mellitus. Successful simultaneous pancreas-kidney transplantation allows achieving euglycemia, stabilizing existing microvascular complications and slowing their progression, improving the patient's quality of life, lipid and calcium-phosphorus metabolism, reducing the risks of cardiovascular events. Therefore, in view of the patient's severe general condition due to prolonged intoxication, hyperglycemia and other complications of chronic kidney disease, the earliest possible surgical treatment with minimization of the patient's stay on dialysis therapy is crucial to improve the outcome of transplantation.