procurement-parathyroid-glands-from-living-donor-pigs-ex-vivo

Procurement of Parathyroid Glands from Living Donor Pigs and <em>Ex Vivo</em> Identification

Hypoparathyroidism, often resulting from surgical complications, severely disrupts calcium homeostasis, leading to disabling symptoms. Current treatments ...

UNIVERSITY OF LILLE

Human islet transplantation is a viable treatment option for type 1 diabetes mellitus (T1DM). However, pancreatic islet inflammation after transplantation induced by innate immune responses is likely to hinder graft function. This is mediated by incompatibility between islets and the blood interface, known as instant blood-mediated inflammatory reaction (IBMIR). Herein we hypothesized that portal venous administration of islet cells with human recombinant antithrombin (ATryn®), a serine protease inhibitor (serpin), which plays a central role in the physiological regulation of coagulation and exerts indirect anti-inflammatory activities, may offset coagulation abnormalities such as disseminated intravascular coagulation (DIC) and IBMIR. The current prospective, randomized experiment was conducted using an established preclinical pig model. Three groups were constituted for digested pancreatic tissue transplantation (0.15 ml/kg): control, NaCl 0.9% (n = 7); gold standard, heparin (25 UI/kg) (n = 7); and human recombinant ATryn® (500 UI/kg) (n = 7). Blood samples were collected over time (T0 to 24 h), and biochemical, coagulation, and inflammatory parameters were evaluated. In both the control and heparin groups, one animal died after a portal thrombosis, while no deaths occurred in the ATryn®-treated group. As expected, islet transplantation was associated with an increase in plasma IL-6 or TNF-α levels in all three groups. However, DIC was only observed in the control group, an effect that was suppressed after ATryn® administration. ATryn® administration increased antithrombin activity by 800%, which remained at 200% for the remaining period of the study, without any hemorrhagic complications. These studies suggest that coadministration of ATryn® and pancreatic islets via intraportal transplantation may be a valuable therapeutic approach for DIC without risk for islets and subjects.

Human Recombinant Antithrombin (ATryn) Administration Improves Survival and Prevents Intravascular Coagulation After Intraportal Islet Transplantation in a Piglet Model.

Several devices are available for liver parenchyma transection (LPT). The aim of this study was to compare the Ultracision Harmonic scalpel (UHS) with the Cavitron Ultrasonic Surgical Aspirator (CUSA) among patients who underwent hemi-right hepatectomies (RH) to homogenize transection areas.

Comparative Study With Propensity Score Matching Analysis of Two Different Methods of Transection During Hemi-Right Hepatectomy: Ultracision Harmonic Scalpel Versus Cavitron Ultrasonic Surgical Aspirator.

The long-term outcome of allogenic islet transplantation is unknown. The aim of this study was to evaluate the 10-year outcome of islet transplantation in patients with type 1 diabetes and hypoglycemia unawareness and/or a functioning kidney graft.

Ten-Year Outcome of Islet Alone or Islet After Kidney Transplantation in Type 1 Diabetes: A Prospective Parallel-Arm Cohort Study.

The COVID-19 pandemic is rapidly spreading worldwide, notably in Europe and North America where obesity is highly prevalent. The relation between obesity and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has not been fully documented.

High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Requiring Invasive Mechanical Ventilation.

Anticoagulation practices in total pancreatectomy with autologous islet cell transplant patients: an international survey of clinical programs.

One century after the discovery of insulin, the French Health regulations have just authorized the reimbursement for islet transplantation. Intraportal islet allotransplantation from a pancreatic donor is indicated in patients with type 1 diabetes (T1D) complicated with lability or hypoglycemia unawareness, or in case of a functioning kidney graft; islet auto-transplantation may be indicated after pancreatic surgery.Compared with insulin even administered in closed-loop pumps, the specificity of islet allotransplantation is the restoration of C-peptide secretion. Long-term insulin-independence is observed when the engrafted islet mass is sufficient, at the cost of immunosuppression. Fewer low-glucose events and less glucose variability, are observed even with minimal functional islet graft, after islet transplantation as at onset of T1D, when a residual C-peptide secretion is maintained, an objective currently approached with less aggressive immuno-modulating therapies than in the past. Therefore, restoration or preservation of endogen insulin secretion is an important goal, allowing to maintain a long-term glucose balance with more than 70% of time in range 3.9-10mmol/L and less than 3% of time <3.9mmol/L, thus reducing the occurrence of diabetic complications. In the clinical setting, - the preservation of C-peptide at early stage of T1D, - the use of technological ressources (multi-injections, sensors, insulin pump, closed-loop systems) at later stages, - and islet transplantation when hypoglycemia awareness becomes impaired are complementary for a personalized care all along the life of T1D patients.

1921-2021: From insulin discovery to islet transplantation in type 1 diabetes.

The value of non-invasive tests for monitoring the resolution of significant liver fibrosis after treatment is poorly investigated. We compared the performances of six non-invasive tests to predict the resolution of significant fibrosis after bariatric surgery.

Performance of non-invasive tests for liver fibrosis resolution after bariatric surgery.

Islet transplantation has been associated with better metabolic control and quality of life than insulin treatment alone, but direct evidence of its effect on hard clinical endpoints is scarce. We aimed to assess the effect of islet transplantation on patient-graft survival in kidney transplant recipients with type 1 diabetes.

Islet-after-kidney transplantation versus kidney alone in kidney transplant recipients with type 1 diabetes (KAIAK): a population-based target trial emulation in France.

Metabolic dysfunction-associated steatotic liver disease (MASLD) exhibits considerable variability in clinical outcomes. Identifying specific phenotypic profiles within MASLD is essential for developing targeted therapeutic strategies. Here we investigated the heterogeneity of MASLD using partitioning around medoids clustering based on six simple clinical variables in a cohort of 1,389 individuals living with obesity. The identified clusters were applied across three independent MASLD cohorts with liver biopsy (totaling 1,099 participants), and in the UK Biobank to assess the incidence of chronic liver disease, cardiovascular disease and type 2 diabetes. Results unveiled two distinct types of MASLD associated with steatohepatitis on histology and liver imaging. The first cluster, liver-specific, was genetically linked and showed rapid progression of chronic liver disease but limited risk of cardiovascular disease. The second cluster, cardiometabolic, was primarily associated with dysglycemia and high levels of triglycerides, leading to a similar incidence of chronic liver disease but a higher risk of cardiovascular disease and type 2 diabetes. Analyses of samples from 831 individuals with available liver transcriptomics and 1,322 with available plasma metabolomics highlighted that these two types of MASLD exhibited distinct liver transcriptomic profiles and plasma metabolomic signatures, respectively. In conclusion, these data provide preliminary evidence of the existence of two distinct types of clinically relevant MASLD with similar liver phenotypes at baseline, but each with specific underlying biological profiles and different clinical trajectories, suggesting the need for tailored therapeutic strategies.

Data-driven cluster analysis identifies distinct types of metabolic dysfunction-associated steatotic liver disease.

The aim of this study was to investigate the consequences of the histological progression of metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis on long-term survival after bariatric surgery.

Resolution of Metabolic Dysfunction-associated Steatohepatitis With No Worsening of Fibrosis After Bariatric Surgery Improves 15-year Survival: A Prospective Cohort Study.

Type 2 diabetes (T2D) is a common comorbidity in kidney transplant recipients, representing a significant proportion of the candidate pool. Post-kidney transplantation management of T2D remains challenging, leading to inferior long-term outcomes compared to non-diabetic recipients. This study aimed to assess the association between Homeostatic Model Assessment 2 (HOMA2) derived insulin resistance and beta-cell function on kidney graft outcomes in T2D kidney transplant recipients. We conducted a monocentric retrospective study at the University Hospital of Lille, including all consecutive adult T2D patients who underwent kidney transplantation between January 2007 and December 2018. HOMA2 indexes (HOMA2 IR for insulin resistance and HOMA2 B for beta-cell function) were calculated at one-year post-transplantation. Primary endpoint was graft survival and secondary endpoints were death-censored graft survival, patient survival and post-transplant metabolic control. Among 1620 kidney transplant recipients, 138 patients with T2D were included, with a median follow-up of 1837 days [1283-2726]. HOMA2 IR was significantly associated with an increased risk of kidney graft failure or death (HR per unit = 1.11 (1.02-1.21). Beta-cell function was not associated with graft prognosis, but decreased beta-cell function was associated with poorer metabolic control over time. This study highlights the significance of insulin resistance as a potential determinant of long-term outcomes in T2D kidney transplant recipients.

Article	Year
Human Recombinant Antithrombin (ATryn) Administration Improves Survival and Prevents Intravascular Coagulation After Intraportal Islet Transplantation in a Piglet Model. Cell transplantation\| PubMed ID: 27938471	2017
Comparative Study With Propensity Score Matching Analysis of Two Different Methods of Transection During Hemi-Right Hepatectomy: Ultracision Harmonic Scalpel Versus Cavitron Ultrasonic Surgi... Surgical innovation\| PubMed ID: 28799459	2017
Ten-Year Outcome of Islet Alone or Islet After Kidney Transplantation in Type 1 Diabetes: A Prospective Parallel-Arm Cohort Study. Diabetes care\| PubMed ID: 31615852	2019
High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Requiring Invasive Mechanical Ventilation. Obesity (Silver Spring, Md.)\| PubMed ID: 32271993	2020
Anticoagulation practices in total pancreatectomy with autologous islet cell transplant patients: an international survey of clinical programs. Transplant international : official journal of the European Society for Organ Transplantation\| PubMed ID: 33452835	2021
1921-2021: From insulin discovery to islet transplantation in type 1 diabetes. Annales d'endocrinologie\| PubMed ID: 33839122	2021
Performance of non-invasive tests for liver fibrosis resolution after bariatric surgery. Metabolism: clinical and experimental\| PubMed ID: 38219973	2024
Islet-after-kidney transplantation versus kidney alone in kidney transplant recipients with type 1 diabetes (KAIAK): a population-based target trial emulation in France. The lancet. Diabetes & endocrinology\| PubMed ID: 39250921	2024
Data-driven cluster analysis identifies distinct types of metabolic dysfunction-associated steatotic liver disease. Nature medicine\| PubMed ID: 39653777	2024
Resolution of Metabolic Dysfunction-associated Steatohepatitis With No Worsening of Fibrosis After Bariatric Surgery Improves 15-year Survival: A Prospective Cohort Study. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association\| PubMed ID: 39709138	2025
Association between HOMA2 based beta-cell function or insulin resistance and long-term outcomes in kidney transplant recipients with type 2 diabetes. Scientific reports\| PubMed ID: 39738741	2024

Mikael Chetboun

Biography

JoVE Journal Publications

Other Publications