Piotr J. Bachul

BETA-2 Score Allows for Convenient and Precise Monitoring of Islet Function and Early Detection of Islet Dysfunction

Introduction BETA-2 was developed to more conveniently and precisely assess islet graft function than commonly used beta-score, which requires a stimulation test. After validation of BETA-2 in our cohort of patients in relation to 90-min glucose in a mixed meal tolerance test and beta-score, we decided to assess the practical utility of BETA-2 in monitoring islet allograft function in individual patients. Methods We retrospectively analyzed BETA-2 calculations during clinical evaluations in islet allotransplantation (ITx) recipients with up to 3 islet infusions. We specifically looked in reference to previously established BETA-2 cut-offs for the detection of glucose intolerance <18 and insulin independence >13. Results We analyzed 298 BETA-2 scores calculated in 14 patients (7 women and 7 men) with an average age of 42.9 ± 9.5 years. In these patients, BETA-2 correlated well with islets function. Four patients, who experienced stable, long-term insulin independence after only one transplant, had a BETA-2 continuously over 18 (Fig 1). Figure. No caption available. Another 3 patients required a second transplant to reach the same outcome with the same BETA-2 characteristic (Fig 2). Figure. No caption available. In those patients, despite only discrete changes in fasting glucose level, the BETA-2 decreased to below 18 and continued gradually declining. This drop in BETA-2 always predicted islet dysfunction, the need for insulin support and subsequent transplant, which became clinically obvious as BETA-2 dropped below 13 (Fig 3 and 4). Figure. No caption available. Figure. No caption available. In the remaining patients, even when BETA-2 eventually reached peak above 18 after subsequent transplant, islet function gradually declined without obvious reason within a year or 2 with BETA-2 below 13 requiring re-introduction of insulin support. (Fig 4). One of these patients has not been able to stop insulin completely despite 3 subsequent transplants but BETA-2 has never increased above 18, which confirms utility of BETA-2. 12% (14/121) of BETA-2 measurements above 18 were made during the early period after iTx, when insulin was administered irrespectively of beta-cell function, in order to facilitate islet engraftment. In 80.2% of cases (142/177) where BETA-2 value was above the cut-off of 13, patients were off-insulin. The remaining 19.8% were on insulin due to failing islet function with dropping BETA-2 or supporting post infusion islet engraftment as described above. BETA-2 calculations below 13 were in 94.4% (113/121) in patients receiving insulin. Remaining 6.6% of BETA-2 calculations (8/121) were below the cut-off of 13, yet patients were still off insulin due to their non-compliance to the recommendation to resume insulin therapy based on clinically evident suboptimal glucose control. Conclusion BETA-2 score, based on only a single fasting blood sample is a very reliable tool for islet function assessment and allows early detection of islet graft decline before obvious clinical symptoms. This work was supported by the Illinois Department 370 of Public Health Grant “Pancreatic Islet Transplantation” US Public Health Service Grant DK-020595 to the University of Chicago Diabetes Research Training 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. Four (27%) individuals had discontinued insulin completely prior to day 75, while 6 out of 12 patients (50%) did not require insulin support at 1‐year follow‐up with HbA1c 6.0% (5.5–6.8). BETA‐2 was the most consistent among indices strongly correlating with all reference measures of beta‐cell function (r = 0.62–0.68). In addition, it identified insulin independence (cut‐off = 16.2) and optimal/good versus marginal islet function in the Igls score well, with AUROC of 0.85 and 0.96, respectively. Based on a single fasting blood sample, BETA‐2 score has the most reliable discriminant value for the assessment of graft function in patients undergoing TP‐IAT.

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. Our classification system is based on the vascular variations of the anterior aspect of tibiofibular syndesmosis and corresponds with vascular density. According to our study the mean vascular density of tibiofibular syndesmosis is relatively low (4.4%) and depends on the type of blood supply. The highest density was observed among ankles with complete vasculature and the lowest when lateral anterior malleolar artery was absent (5.8% vs. 3.5%, respectively). Awareness of various types of tibiofibular syndesmosis arterial blood supply is essential for orthopedic surgeons who operate in the ankle region and radiologists for the anatomic evaluation of this area. Knowledge about possible variations along with relatively low density of vessels may contribute to modification of treatment approach by the increase of the recommended time of syndesmotic screw stabilization in order to prevent healing complications.

Pain Control, Glucose Control, and Quality of Life in Patients With Chronic Pancreatitis After Total Pancreatectomy With Islet Autotransplantation: A Preliminary Report

BACKGROUNDnTotal pancreatectomy (TP) is offered as a last treatment option for pain relief in patients with chronic pancreatitis. Concurrent islets autotransplantation (TP-IAT) may improve glucose control.nnnMETHODSnWe analyzed results in 20 recent patients who underwent TP-IAT at The University of Chicago. The median observation period was 28 months (2-38). Data were collected prospectively then analyzed retrospectively.nnnRESULTSnThe number of patients requiring opioids daily for pain control decreased from 16 (80%) prior to surgery to 2 (13%) 1 year after, with only 1 (6.5%) patient experiencing persistent phantom pancreatic pain. Opioid requirements decreased from a median 56.3 (0-240) morphine equivalent dose to 5 (0-130) on day 75 and to 0 (0-30) at 1-year follow up. Five patients (25%) completely stopped insulin support prior to day 75 while maintaining hemoglobin A1c of 5.9% (5-6.3). Eight (53%) patients were insulin free at 1 year with A1c of 6% (5.5-6.8) and a similar rate persisted in next 2 years. For the remaining patients, the more islet function that was preserved, the less insulin they required and A1c was closer to optimal. Quality of Life (QoL) measured by SF36 Physical (PCS) and Mental (MCS) Component Score improved on day 75 (Pxa0< .001) and maintained improvement later on. Both PCS and MCS improved regardless of whether patient requires insulin support or not.nnnCONCLUSIONSnImprovements of QoL with pain resolution and good glucose control can be achieved after TP-IAT in properly selected patients with CP and intractable pain, regardless of patient insulin support status.

External Validation of the Newly Developed BETA-2 Scoring System for Pancreatic Islet Graft Function Assessment

BACKGROUNDnBETA-2 score using a single fasting blood sample was developed to estimate beta-cell function after islet transplantation (ITx) and was validated internally by a high ITx volume center (Edmonton). The goal was to validate BETA-2 externally, in our center.nnnMETHODSnAreas under receiver operating characteristic curves (AUROCs) were obtained to see if beta score or BETA-2 would better detect insulin independence and glucose intolerance.nnnRESULTSnWe analyzed values from 48 mixed meal tolerance tests (MMTTs) in 4 ITx recipients with a long-term follow-up to 140 months (LT group) and from 54 MMTTs in 13 short-term group patients (ST group). AUROC for no need for insulin support was 0.776 (95% confidence interval [CI] 0.539-1, Pxa0= .02) and 0.922 (95% CI 0.848-0.996, Pxa0< .001) for beta score and 0.79 (95% CI 0.596-0.983, Pxa0= .003) and 0.941 (95% CI 0.86-1, Pxa0<xa0.001) for BETA-2, in LT and ST groups, respectively, and did not differ significantly. In LT group BETA-2 scorexa0≥ 13.03 predicted no need for insulin supplementation with sensitivity of 98%, specificity of 50%, positive predictive value (PPV) of 93%, and negative predictive value (NPV) of 75%. In ST group the optimal cutoff wasxa0≥13.63 with sensitivity of 92% and specificity, PPV, and NPV 82% to 95%. For the detection of glucose intolerance BETA-2 cutoffs werexa0<19.43 in LT group andxa0<17.23 in ST group with sensitivity > 76% and specificity, PPV, and NPV > 80% in both groups.nnnCONCLUSIONnBETA-2 score was successfully validated externally and is a practical tool allowing for frequent and reliable assessments of islet graft function based on a single fasting blood sample.

Crossing Anatomic Barriers—Transplantation of a Kidney with 5 Arteries, Duplication of the Pyelocalyceal System, and Double Ureter

During the time of organ harvest, it is crucial for the kidney procurement team to consider significant vascular anatomical variations. Multiple renal arteries are not uncommon, and unintentional injury can result in an irreversibly damaged kidney graft that needs to be discarded. We present a kidney graft with 5 renal arteries and a single vein that was successfully procured and implanted with good graft function at discharge and at 4-yr follow-up. According to the literature, additional renal arteries can be found in about 33% of kidneys. This is the first study on a kidney with 5 arteries in the published literature, especially in the context of transplantation.