[Show abstract][Hide abstract] ABSTRACT: The detection and management of potential donor-derived infections is challenging, in part due to the complexity of communications between diverse labs, organ procurement organizations (OPOs), and recipient transplant centers. We sought to determine if communication delays or errors occur in the reporting and management of donor-derived infections and if these are associated with preventable adverse events in recipients. All reported potential donor-derived transmission events reviewed by the Organ Procurement and Transplantation Network Ad Hoc Disease Transmission Advisory Committee from January 2008 to June 2010 were evaluated for communication gaps between the donor center, OPO and transplant centers. The impact on recipient outcomes was then determined. Fifty-six infection events (IEs; involving 168 recipients) were evaluated. Eighteen IEs (48 recipients) were associated with communication gaps, of which 12 resulted in adverse effects in 69% of recipients (20/29), including six deaths. When IEs and test results were reported without delay, appropriate interventions were taken, subsequently minimizing or averting recipient infection (23 IEs, 72 recipients). Communication gaps in reported IEs are frequent, occur at multiple levels in the communication process, and contribute to adverse outcomes among affected transplant recipients. Conversely, effective communication minimized or averted infection in transplant recipients.
American Journal of Transplantation 11/2014; · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We utilized intravenous arginine with measurements of insulin, C-peptide, and glucagon to examine β-cell and α-cell survival and function in a group of 10 chronic pancreatitis recipients 1-8 years after total pancreatectomy and autoislet transplantation (TP/IAT). Insulin and C-peptide responses correlated robustly with the number of islets transplanted (correlation coefficients range = 0.81-0.91; p<0.01- 0.001). Since a wide range of islets were transplanted, we normalized the insulin and C-peptide responses to the number of islets transplanted in each recipient for comparison with responses in normal subjects. No significant differences were observed in terms of magnitude and timing of hormone release in the two groups. Three recipients had a portion of the autoislets placed within their peritoneal cavities, which appeared to be functioning normally up to 7 years post-transplant. Glucagon responses to arginine were normally timed and normally suppressed by intravenous glucose infusion. These findings indicate that arginine stimulation testing may be a means of assessing the numbers of native islets available in autologous islet transplant candidates and is a means of following post-transplant α- and β- cell function and survival.
[Show abstract][Hide abstract] ABSTRACT: Defective glucagon secretion during hypoglycemia after islet transplantation has been reported in animals and humans with type 1 diabetes. To ascertain whether this is true of islets from nondiabetic humans, subjects with autoislet transplantation in the intrahepatic site only (TP/IAT-H) or in intrahepatic plus nonhepatic (TP/IAT-H+NH) sites were studied. Glucagon responses were examined during stepped hypoglycemic clamps. Glucagon and symptom responses during hypoglycemia were virtually absent in subjects who received islets in the hepatic site only (glucagon increment over baseline = 1 ± 6, pg/mL, mean ± SE, n = 9, p = ns; symptom score = 1 ± 1, p = ns). When islets were transplanted in both intrahepatic + nonhepatic sites, glucagon and symptom responses were not significantly different than Control Subjects (TP/IAT-H + NH: glucagon increment = 54 ± 14, n = 5; symptom score = 7 ± 3; control glucagon increment = 67 ± 15, n = 5; symptom score = 8 ± 1). In contrast, glucagon responses to intravenous arginine were present in TP/IAT-H recipients (TP/IAT: glucagon response = 37 ± 8, n = 7). Transplantation of a portion of the islets into a nonhepatic site should be seriously considered in TP/IAT to avoid posttransplant abnormalities in glucagon and symptom responses to hypoglycemia.
American Journal of Transplantation 07/2014; · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The islet size distribution in a preparation may contribute to islet transplant outcomes. At the same islet equivalent (IE) dose, larger islets may exhibit poorer therapeutic value and this may be because of oxygen diffusion limitations that worsen in proportion to islet size.
To test this hypothesis, we studied the impact of islet size index (ISI) and other islet product characteristics on outcomes after islet autotransplant (IAT) in recipients receiving a marginal islet dose (2000-4999 IEs per kg body weight) from January 1, 2009 to June 11, 2012, at the University of Minnesota (n=58). ISI was defined as the number of IE divided by the number of islet particles (IPs) in a preparation; an ISI less than 1 indicates a mean islet diameter that is less than 150 μm. The primary post-IAT outcome was 6-month insulin use status.
Logistic regression analysis indicate that IPs/kg (P=0.001), IEs/kg (P=0.019), total IPs transplanted (P=0.040), and ISI (P=0.074) were most strongly correlated with the primary outcome. The ISI (mean±standard error) was lower for recipients achieving insulin independence at 6 months (0.71±0.05) versus those partially (0.83±0.05) or completely (1.00±0.07) insulin dependent. The combination of islet dose (expressed as units IPs/kg) and ISI exhibited a sensitivity of 75% and specificity of 74% in predicting insulin independence in this population of patients.
Islet autotransplant recipients of a marginal islet doses were more likely to achieve insulin independence when transplanted with a greater number of smaller islets.
[Show abstract][Hide abstract] ABSTRACT: Describe the surgical technique, complications, and long-term outcomes of total pancreatectomy and islet autotransplantation (TP-IAT) in a large series of pediatric patients.
Surgical management of childhood pancreatitis is not clear; partial resection or drainage procedures often provide transient pain relief, but long-term recurrence is common due to the diffuse involvement of the pancreas. Total pancreatectomy (TP) removes the source of the pain, whereas islet autotransplantation (IAT) potentially can prevent or minimize TP-related diabetes.
Retrospective review of 75 children undergoing TP-IAT for chronic pancreatitis who had failed medical, endoscopic, or surgical treatment between 1989 and 2012.
Pancreatitis pain and the severity of pain statistically improved in 90% of patients after TP-IAT (P < 0.001). The relief from narcotics was sustained. Of the 75 patients undergoing TP-IAT, 31 (41.3%) achieved insulin independence. Younger age (P = 0.032), lack of prior Puestow procedure (P = 0.018), lower body surface area (P = 0.048), higher islet equivalents (IEQ) per kilogram body weight (P = 0.001), and total IEQ (100,000) (P = 0.004) were associated with insulin independence. By multivariate analysis, 3 factors were associated with insulin independence after TP-IAT: (1) male sex, (2) lower body surface area, and (3) higher total IEQ per kilogram body weight. Total IEQ (100,000) was the single factor most strongly associated with insulin independence (odds ratio = 2.62; P < 0.001).
Total pancreatectomy and islet autotransplantation provides sustained pain relief and improved quality of life. The β-cell function is dependent on islet yield. Total pancreatectomy and islet autotransplantation is an effective therapy for children with painful pancreatitis that failed medical and/or endoscopic management.
[Show abstract][Hide abstract] ABSTRACT: Background
Chronic-pancreatitis is a debilitating-disease resulting from many etiologies. The-subset with hereditary/genetic defects (HGP) not only has chronic-pain, but also an increased-risk for pancreatic-cancer. The long-term-outcomes of TP-IAT for chronic pancreatitis due-to-HGP are not clear.
Review of a prospectively-maintained-database of 484 TP-IAT-from-1977-2012 at a single-center. The-outcomes (pain-relief, narcotic-use, β cell-function, health-related quality of-life-measures of patients-that-received TP-IAT for hereditary/genetic-defects (PRSS1 (n=38), SPINK1 (n=9), CFTR (n=14) and Familial (n=19) were-evaluated-and-compared to those with non-hereditary/genetic-etiology.
All 80 patients with HGP were narcotic-dependent and failed-endoscopic-management or direct-pancreatic-surgery. Post TP-IAT, 90% of the patients-were-pancreatitis-pain-free with sustained-pain-relief; over 65% had partial or full β-cell-function. Compared to non-hereditary etiologies, HGP were-younger (22 yrs vs.38 yrs p=<0.001), had-pancreatitis-pain of longer-duration (11.6±1.1 vs. 9.0±0.4 yrs p=0.016) , had a higher-pancreas-fibrosis-score (7±0.2 vs. 4.8±0.1 p=<0.001), and-trended-toward-lower-Islet-yield (3,435 ± 361 IEQ vs. 3850± 128 IEQ p=0.28). Using-multivariate-logistic-regression, (1) non-HGP-etiology (p value=0.019) (2) lower severity-of-pancreas-fibrosis (p value < 0.001), (3) shorter-duration-of-years with pancreatitis (p value = 0.008) and (4) higher-transplant IEQ per KG body-weight (p value =<0.001) were-more likely-to-achieve-insulin-independence (p value < 0.001). There was a significant-improvement in HRQoL from-baseline, by SF-36, in physical-and-mental-component HRQoL scores (p <0.001). None-of-the-patients in the entire-cohort-developed-cancer of pancreatic-origin in the liver or elsewhere during 2,936 person-years of follow-up.
TP-IAT in patients with chronic pancreatitis due to HGP etiology provides long- term pain relief (90%) and preservation-of-beta-cell-function. Patients with chronic-painful pancreatitis due to HGP with a high-life-time-risk of pancreatic-cancer should be considered earlier for TP-IAT before pancreatic-inflammation results in higher-degree of pancreatic-fibrosis and islet-cell-function-loss.
Journal of the American College of Surgeons 01/2014; · 4.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the role of sex on cytokine expression and mortality in critically ill patients.
A cohort of patients admitted to were enrolled and followed over a 5-year period.
Two university-affiliated hospital surgical and trauma ICUs.
Patients 18 years old and older admitted for at least 48 hours to the surgical or trauma ICU.
Major outcomes included admission cytokine levels, prevalence of ICU-acquired infection, and mortality during hospitalization conditioned on trauma status and sex. The final cohort included 2,291 patients (1,407 trauma and 884 nontrauma). The prevalence of ICU-acquired infection was similar for men (46.5%) and women (44.5%). All-cause in-hospital mortality was 12.7% for trauma male patient and 9.1% for trauma female patient (p = 0.065) and 22.9% for nontrauma male patients and 20.6% for nontrauma female patients (p = 0.40). Among trauma patients, logistic regression analysis identified female sex as protective for all-cause mortality (odds ratio, 0.57). Among trauma patients, men had significantly higher admission serum levels of interleukin-2, interleukin-12, interferon-γ, and tumor necrosis factor-α, and among nontrauma patients, men had higher admission levels of interleukin-8 and tumor necrosis factor-α.
The relationship between sex and outcomes in critically ill patients is complex and depends on underlying illness. Women appear to be better adapted to survive traumatic events, while sex may be less important in other forms of critical illness. The mechanisms accounting for this gender dimorphism may, in part, involve differential cytokine responses to injury, with men expressing a more robust proinflammatory profile.
Critical care medicine 12/2013; · 6.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The simple question of how much tissue volume (TV) is really safe to infuse in total pancreatectomy-islet autotransplantation (TP-IAT) for chronic pancreatitis (CP) precipitated this analysis. We examined a large cohort of CP patients (n = 233) to determine major risk factors for elevated portal pressure (PP) during islet infusion, using bivariate and multivariate regression modeling. Rates of bleeding requiring operative intervention and portal venous thrombosis (PVT) were evaluated. The total TV per kilogram body weight infused intraportally was the best independent predictor of change in PP (ΔPP) (p < 0.0001; R(2) = 0.566). Rates of bleeding and PVT were 7.73% and 3.43%, respectively. Both TV/kg and ΔPP are associated with increased complication rates, although ΔPP appears to be more directly relevant. Receiver operating characteristic analysis identified an increased risk of PVT above a suggested cut-point of 26 cmH2 O (area under the curve = 0.759), which was also dependent on age. This ΔPP threshold was more likely to be exceeded in cases where the total TV was >0.25 cm(3) /kg. Based on this analysis, we have recommended targeting a TV of <0.25 cm(3) /kg during islet manufacturing and to halt intraportal infusion, at least temporarily, if the ΔPP exceeds 25 cmH2 O. These models can be used to guide islet manufacturing and clinical decision making to minimize risks in TP-IAT recipients.
American Journal of Transplantation 10/2013; · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Islet autotransplant (IAT) may ameliorate postsurgical diabetes following total pancreatectomy (TP), but outcomes are dependent upon islet mass, which is unknown prior to pancreatectomy. We evaluated whether preoperative metabolic testing could predict islet isolation outcomes and thus improve assessment of TPIAT candidates. We examined the relationship between measures from frequent sample IV glucose tolerance tests (FSIVGTT) and mixed meal tolerance tests (MMTT) and islet mass in 60 adult patients, with multivariate logistic regression modeling to identify predictors of islet mass ≥2500 IEQ/kg. The acute C-peptide response to glucose (ACRglu) and disposition index from FSIVGTT correlated modestly with the islet equivalents per kilogram body weight (IEQ/kg). Fasting and MMTT glucose levels and HbA1c correlated inversely with IEQ/kg (r values -0.33 to -0.40, p ≤ 0.05). In multivariate logistic regression modeling, normal fasting glucose (<100 mg/dL) and stimulated C-peptide on MMTT ≥4 ng/mL were associated with greater odds of receiving an islet mass ≥2500 IEQ/kg (OR 0.93 for fasting glucose, CI 0.87-1.0; OR 7.9 for C-peptide, CI 1.75-35.6). In conclusion, parameters obtained from FSIVGTT correlate modestly with islet isolation outcomes. Stimulated C-peptide ≥4 ng/mL on MMTT conveyed eight times the odds of receiving ≥2500 IEQ/kg, a threshold associated with reasonable metabolic control postoperatively.
American Journal of Transplantation 08/2013; · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: y The findings and conclusions in this report are those of the authors and do not represent the official position of AST, ASTS, NATCO, or UNOS. Participation by representatives of the CDC, CMS, HRSA, HHS and the FDA was primarily to serve as a technical resource and not to represent the official position of the federal government. In 2011, live donor transmission events involving Human Immunodeficiency Virus (HIV) and Hepatitis C virus (HCV) prompted consideration of changing the process of live donor testing and evaluation in the United States. Following CDC recommendations for screening all live donors with nucleic acid testing for HIV, HCV and Hepatitis B (HBV), a consensus confer-ence was convened to evaluate this recommendation. Workgroups focused on determining whether there was an evidence based rationale for identifying live donors at increased risk for HIV, HBV and HCV, testing options and timing for diagnosing these infections in potential donors and consent issues specific to poten-tial increased risk donor utilization. Strategies for donor assessment were proposed. Based on review of the limited available evidence as well as guidance documents and policies currently in place in the United States and other countries, the conference participants recommended that HIV, HBV and HCV NAT should not be required for live donor evaluation; the optimal timing of live donor testing for these blood borne pathogens has not been determined.
American Journal of Transplantation 06/2013; 13:1405-1415. · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Technical failure (TF) continues to have a significant impact on the success of pancreas transplantation. We assessed risk factors for TF in 1115 pancreas transplants performed at a single center between 1998 and 2011. The overall TF rate was 10.2%. In a multivariable model, donor BMI ≥30 (HR 1.87, p = 0.005), donor Cr ≥2.5 (HR 3.16, p = 0.007), donor age >50 (HR 1.73, p = 0.082) and preservation time >20 h (HR 2.17, p < 0.001) were associated with TF. Bladder drainage of exocrine secretions was protective (HR 0.54, p = 0.002). We incorporated these factors in a Composite Risk Model. In this model the presence of one risk factor did not significantly increase risk of TF (HR 1.35, p = 0.346). Two risk factors in combination increased risk greater than threefold (HR 3.65, p < 0.001) and three risk factors increased risk greater than sevenfold (HR 7.66, p = <0.001). The analysis also identified many factors that were not predictive of TF, including previous transplants, immunosuppressive agent selection, and almost all recipient demographic parameters. While the model suggests that two or more risk factors predict TF, strategies to reduce preservation time may mitigate some of this risk.
American Journal of Transplantation 05/2013; · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rapid discontinuation of prednisone (RDP) has minimized steroid-related complications following kidney transplant (KT). This trial compares long-term (10-year) outcomes with three different maintenance immunosuppressive protocols following RDP in adult KT. Recipients (n = 440; 73% living donor) from March 2001 to April 2006 were randomized into one of three arms: cyclosporine (CSA) and mycophenolate mofetil (MMF) (CSA/MMF, n = 151); high-level tacrolimus (TAC, 8-12 μg/L) and low-level sirolimus (SIR, 3-7 μg/L) (TAC(H) /SIR(L) , n = 149) or low-level TAC (3-7 μg/L) and high-level SIR (8-12 μg/L) (TAC(L) /SIR(H) , n = 140). Median follow-up was ∼7 years. There were no differences between arms in 10-year actuarial patient, graft and death-censored graft survival or in allograft function. There were no differences in the 10-year actuarial rates of biopsy-proven acute rejection (30%, 26% and 20% in CSA/MMF, TAC(H) /SIR(L) and TAC(L) /SIR(H) ) and chronic rejection (38%, 35% and 31% in CSA/MMF, TAC(H) /SIR(L) and TAC(L) /SIR(H) ). Rates of new-onset diabetes mellitus were higher with TAC(H) /SIR(L) (p = 0.04), and rates of anemia were higher with TAC(H) /SIR(L) and TAC(L) /SIR(H) (p = 0.04). No differences were found in the overall rates of 16 other post-KT complications. These data indicate that RDP-based protocol yield acceptable 10-year outcomes, but side effects differ based on the maintenance regimen used and should be considered when optimizing immunosuppression following RDP.
American Journal of Transplantation 02/2013; · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: the A2ALL Study Group. Computerized assessment of competence-related abilities in living liver donors: the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Abstract: Background: Despite its importance, determination of competence to consent to organ donation varies widely based on local standards. We piloted a new tool to aid transplant centers in donor assessment. Methods: We assessed competence-related abilities among potential living liver donors (LDs) in the nine-center A2ALL study. Prospective LDs viewed an educational video and were queried to assess Understanding, Appreciation, Reasoning, and ability to express a Final Choice using the MacArthur Competence Assessment Tool for Clinical Research, adapted for computerized administration in LDs ("MacLiver"). Videotaped responses were scored by a clinical neuropsychologist (JF). Results: Ninety-three LDs were assessed. Mean (standard deviation; domain maximum) scores were as follows: Understanding: 18.1 (2.6; max = 22), Appreciation: 5.1 (1.0; max = 6), Reasoning: 3.1 (0.8; max = 4), and Final Choice: 3.8 (0.5; max = 4). Scores did not differ by demographics, relationship to the recipient, eligibility to donate, or eventual donation (p > 0.4). Higher education was associated with greater Understanding (p = 0.004) and Reasoning (p = 0.03). Conclusion: Standardized, computerized education with independent ratings of responses may (1) alert the clinical staff to potential donors who may not be competent to donate and (2) highlight areas needing further assessment and education, leading to better informed decision making.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: Islet autotransplantation (IAT) is performed in nondiabetic patients with chronic pancreatitis at the time of total pancreatectomy (TP) to minimize risk of postoperative diabetes. The role of TP-IAT in patients with chronic pancreatitis and C-peptide-positive diabetes is not established. We postulate that IAT can preserve beta cell mass and thereby benefit patients with preexisting diabetes undergoing TP. METHODS: Preoperative metabolic testing, islet isolation outcomes, and subsequent islet graft function were reviewed for 27 patients with diabetes mellitus and chronic pancreatitis undergoing TP-IAT. The relationships between the results of preoperative metabolic testing and islet isolation outcomes were explored using regression analysis. RESULTS: Mean islet yield was 2060 (SD, 2408) islet equivalents/kg. Peak C-peptide (from mixed meal tolerance testing) was the strongest predictor of islet yield, with higher stimulated C-peptide levels associated with greater islet mass. Half of the patients who had C-peptide levels measured after transplantation demonstrated C-peptide production at a level that conveys protective benefit in type 1 diabetes (≥0.6 ng/mL). CONCLUSIONS: These findings provide proof of concept that significant islet mass can be isolated in patients with chronic pancreatitis and C-peptide-positive diabetes mellitus undergoing TP-IAT. Stimulated C-peptide may be a useful marker of islet mass before transplantation in these patients.
[Show abstract][Hide abstract] ABSTRACT: Mycobacterium tuberculosis is a ubiquitous organism that infects one-third of the world's population. In previous decades, access to organ transplantation was restricted to academic medical centers in more developed, low tuberculosis (TB) incidence countries. Globalization, changing immigration patterns, and the expansion of sophisticated medical procedures to medium and high TB incidence countries have made tuberculosis an increasingly important posttransplant infectious disease. Tuberculosis is now one of the most common bacterial causes of solid-organ transplant donor-derived infection reported in transplant recipients in the United States. Recognition of latent or undiagnosed active TB in the potential organ donor is critical to prevent emergence of disease in the recipient posttransplant. Donor-derived tuberculosis after transplantation is associated with significant morbidity and mortality, which can best be prevented through careful screening and targeted treatment. To address this growing challenge and provide recommendations, an expert international working group was assembled including specialists in transplant infectious diseases, transplant surgery, organ procurement and TB epidemiology, diagnostics and management. This working group reviewed the currently available data to formulate consensus recommendations for screening and management of TB in organ donors.
American Journal of Transplantation 08/2012; 12(9):2288-300. · 6.19 Impact Factor