The Seattle Heart Failure Model in Kidney Transplant Recipients.

Cardiovascular disease is the leading cause of mortality following kidney transplantation. Heart failure affects 17-21% of patients with chronic kidney disease and increases along with time receiving dialysis. The Seattle Heart Failure Model (SHFM) is a validated mortality risk model for heart failure patients that incorporates clinical, therapeutic, and laboratory parameters but does not include measures of kidney function.

Persistence of long-term insulin independence after islet transplantation and two subsequent pregnancies.

Pregnancy increases metabolic demand for insulin and may lead to the exhaustion of intraportally transplanted islets and post-gestational hyperglycemia. To prevent these complications, we implemented preemptive insulin supplementation during two subsequent pregnancies in an insulin-independent islet transplant recipient. This strategy resulted in optimal blood glucose control during the pregnancies, the preservation of the optimal islet graft function and the postpartum maintenance of long-term insulin independence.

Islets Transplantation at a Crossroads - Need for Urgent Regulatory Update in the United States: Perspective Presented During the Scientific Sessions 2021 at the American Diabetes Association Congress.

Clinical islet allotransplantation has been successfully regulated as tissue/organ for transplantation in number of countries and is recognized as a safe and efficacious therapy for selected patients with type 1 diabetes mellitus. However, in the United States, the FDA considers pancreatic islets as a biologic drug, and islet transplantation has not yet shifted from the experimental to the clinical arena for last 20 years. In order to transplant islets, the FDA requires a valid Biological License Application (BLA) in place.

Pain resolution and glucose control in pediatric patients with chronic pancreatitis after total pancreatectomy with islet auto-transplantation.

Background: Chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) in pediatric patients are strongly associated with genetic mutations and lead to pan-parenchymal disease refractory to medical and endoscopic treatment. Our aim was to assess pain resolution and glucose control in patients with CP and ARP following total pancreatectomy with islet auto-transplantation (TPIAT).

Methods: We retrospectively analyzed prospectively collected clinical data of 12 children who developed CP and ARP and underwent TPIAT when 21 years old or younger at the University of Chicago between December 2009 and June 2020.

Arguments against the Requirement of a Biological License Application for Human Pancreatic Islets: The Position Statement of the Islets for US Collaborative Presented during the FDA Advisory Committee Meeting.

The Food and Drug Administration (FDA) has been regulating human islets for allotransplantation as a biologic drug in the US. Consequently, the requirement of a biological license application (BLA) approval before clinical use of islet transplantation as a standard of care procedure has stalled the development of the field for the last 20 years. Herein, we provide our commentary to the multiple FDA's position papers and guidance for industry arguing that BLA requirement has been inappropriately applied to allogeneic islets, which was delivered to the FDA Cellular, Tissue and Gene Therapies Advisory Committee on 15 April 2021.

Evaluating the Prognostic Value of Islet Autoantibody Monitoring in Islet Transplant Recipients with Long-Standing Type 1 Diabetes Mellitus.

(1) Background: The correlation between titers of islet autoantibodies (IAbs) and the loss of transplanted islets remains controversial. We sought to evaluate the prognostic utility of monitoring IAbs in diabetic patients after islet transplantation (ITx); (2) Methods: Twelve patients with Type 1 diabetes mellitus and severe hypoglycemia underwent ITx. Serum concentration of glutamic acid decarboxylase (GAD), insulinoma antigen 2 (IA-2), and zinc transport 8 (ZnT8) autoantibodies was assessed before ITx and 0, 7, and 75 days and every 3 months post-operatively; (3) Results: IA-2A (IA-2 antibody) and ZnT8A (ZnT8 antibody) levels were not detectable before or after ITx in all patients (median follow-up of 53 months (range 24-61)).

Targeting CXCR1/2 in the first multicenter, double-blinded, randomized trial in autologous islet transplant recipients.

Several cytokines and chemokines are elevated after islet infusion in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT), including CXCL8 (also known as interleukin-8), leading to islet loss. We investigated whether use of reparixin for blockade of the CXCL8 pathway would improve islet engraftment and insulin independence after TPIAT. Adults without diabetes scheduled for TPIAT at nine academic centers were randomized to a continuous infusion of reparixin or placebo (double-blinded) for 7 days in the peri-transplant period.

Post-Hoc Analysis of a Randomized, Double Blind, Prospective Study at the University of Chicago: Additional Standardizations of Trial Protocol are Needed to Evaluate the Effect of a CXCR1/2 Inhibitor in Islet Allotransplantation.

A recent randomized, multicenter trial did not show benefit of a CXCR1/2 receptor inhibitor (Reparixin) when analysis included marginal islet mass (>3,000 IEQ/kg) for allotransplantation and when immunosuppression regimens were not standardized among participating centers. We present a post-hoc analysis of trial patients from our center at the University of Chicago who received an islet mass of over 5,000 IEQ/kg and a standardized immunosuppression regimen of anti-thymocyte globulin (ATG) for induction. Twelve islet allotransplantation (ITx) recipients were randomized (2:1) to receive Reparixin ( = 8) or placebo ( = 4) in accordance with the multicenter trial protocol.

COVID-19 in hospitalized liver transplant recipients: An early systematic review and meta-analysis.

Adverse clinical outcomes related to SARS-CoV-2 infection among liver transplant (LTx) recipients remain undefined. We performed a meta-analysis to determine the pooled prevalence of outcomes among hospitalized LTx recipients with COVID-19. A database search of literature published between December 1, 2019, and November 20, 2020, was performed per PRISMA guidelines.

Arterial Intimal Fibrosis in Reperfusion Biopsy Correlates with Graft Function after Kidney Transplant.

Introduction: Alterations to the procurement biopsy are one of the main reasons that kidneys are not suitable for transplant and are discarded. The literature on procurement and reperfusion biopsy is inconsistent and heterogeneous. The objective of this study is to describe the correlation of the different histological characteristics detected by the procurement and reperfusion biopsies in relation to graft function.

En bloc liver and pancreas transplantation after total pancreatectomy with autologous islet transplantation.

We present a patient with intractable and debilitating pain secondary to chronic pancreatitis who was effectively treated with total pancreatectomy with islet autotransplantation (TPIAT). Islets engrafted into his liver significantly contributed to improved blood glucose control and quality of life. Subsequently, the patient developed alcohol related acute liver failure and en bloc liver and pancreas transplantation was performed to replace the failing liver with engrafted islets.

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update.

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices.

Total pancreatectomy with islet autotransplantation in diabetic and pre-diabetic patients with intractable chronic pancreatitis.

Total pancreatectomy with islet autotransplantation (TPIAT) is an effective treatment option for non-diabetic patients with intractable chronic pancreatitis. The outcome and potential benefits for pre-diabetic and diabetic patients are less well established. Thirty-four patients underwent TPIAT were retrospectively divided into 3 groups according to pre-operative glycemic control: diabetes mellitus (DM) (n=5, 15%), pre-DM (n=11, 32%) and non-DM (n=18, 54%).

BETA-2 score is an early predictor of graft decline and loss of insulin independence after pancreatic islet allotransplantation.

This study aimed to evaluate whether the BETA-2 score is a reliable early predictor of graft decline and loss of insulin independence after islet allotransplantation. Islet transplant procedures were stratified into 3 groups according to clinical outcome: long-term insulin independence without islet graft decline (group 1, N = 9), initial insulin independence with subsequent islet graft decline and loss of insulin independence (group 2, N = 13), and no insulin independence (group 3, N = 13). BETA-2 was calculated on day 75 and multiple times afterwards for up to 145 months posttransplantation.

The impact of full-spectrum endoscopy on pathological lesion detection in different regions of the colon: a randomised, controlled trial.

Introduction: Colonoscopy is crucial for detecting and localising pathological lesions within the colon. Colonoscopy quality is defined by the caecal intubation rate, withdrawal time, adenoma detection rate, and polyp detection rate. The newly introduced full-spectrum endoscope (FUSE) provides a 330° field of view, allowing endoscopists to observe more colonic anatomy.

Early Infectious Complications After Total Pancreatectomy with Islet Autotransplantation: a Single Center Experience.

Introduction: We assessed whether positive microbiological cultures from the islet preparation had any effect on the risk of infectious complications (IC) after total pancreatectomy with islet autotransplantation (TPIAT) in our center.

Methods: We analyzed preservation fluid and final islet product surveillance cultures with reference to clinical data of patients undergoing TPIAT. All patients received routine prophylactic broad-spectrum antibiotics.

Pancreatic beta cell/islet mass and body mass index.

Body mass index (BMI) is widely used to define obesity. In studies of pancreatic beta-cell/islet mass, BMI is also a common standard for matching control subjects in comparative studies along with age and sex, based on the existing dogma of their significant positive correlation reported in the literature. We aimed to test the feasibility of BMI and BSA to assess obesity and predict beta-cell/islet mass.

Validation of a New North American Islet Donor Score for Donor Pancreas Selection and Successful Islet Isolation in a Medium-Volume Islet Transplant Center.

The selection of optimal pancreas donors is one of the key factors in determining the ultimate outcome of clinical islet isolation. North American Islet Donor Score (NAIDS) allows for estimating the chance of the success of islet isolation. It was developed based on the data from over 1000 donors from 11 islet isolation centers and validated in the University of Alberta, Edmonton, on the cohort from the most active islet transplant center.

Assessment of simple indices based on a single fasting blood sample as a tool to estimate beta-cell function after total pancreatectomy with islet autotransplantation - a prospective study.

We investigated six indices based on a single fasting blood sample for evaluation of the beta-cell function after total pancreatectomy with islet autotransplantation (TP-IAT). The Secretory Unit of Islet Transplant Objects (SUITO), transplant estimated function (TEF), homeostasis model assessment (HOMA-2B%), C-peptide/glucose ratio (CP/G), C-peptide/glucose creatinine ratio (CP/GCr) and BETA-2 score were compared against a 90-min serum glucose level, weighted mean C-peptide in mixed meal tolerance test (MMTT), beta score and the Igls score adjusted for islet function in the setting of IAT. We analyzed values from 32 MMTTs in 15 patients after TP-IAT with a follow-up of up to 3 years.

Classification system of the tibiofibular syndesmosis blood supply and its clinical relevance.

Due to the lack of anatomical studies concerning complexity of the tibiofibular syndesmosis blood supply, density of blood vessels with further organization of syndesmotic vascular variations is presented in clinically relevant classification system. The material for the study was obtained from cadaveric dissections. We dissected 50 human ankles observing different types of arterial blood supply.