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This retrospective study analyzed glycemic trends, incidence of post-transplant diabetes mellitus (PTDM) incidence and associated risk factors in a cohort of patients who underwent first-time heart transplantation (HT). Univariate analyses compared patient with and without pretransplant diabetes mellitus (DM). Multivariate regression analyses were conducted to determine association between PTDM and different risk factors. Finally, trends in glucometrics and other outcomes are described across follow-up time points. There were 152 patients who underwent HT between 2010 and 2015, 109 of whom had no pretransplant history of DM. PTDM incidence was 38% by the 1-year follow-up. Pretransplant body mass index (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.01 to 1.23, p = 0.03), insulin use during the final 24 hours of inpatient stay (OR 4.26, 95% CI 1.72 to 10.56, p <0.01), mean inpatient glucose (OR 2.21, 95% CI 1.33 to 3.69, p <0.01), and mean glucose in the final 24 hours before discharge (OR 1.29, 95% CI 1.03 to 1.60, p = 0.03) were associated with increased odds of PTDM at 1 year. In patients on insulin before discharge, blood glucose values were significantly higher compared with those who were not (136 mg/dl vs 114 mg/dl at 1 to 3 months, 112 vs 100 at 4 to 6 months, 109 vs 98 at 8 to 12 months, all p <0.01). This analysis improves understanding of PTDM incidence, glucometric trends, and risk differences by DM status in the HT population. Similar to liver and kidney patients, inpatient glucometrics may be informative of PTDM risk in HT patients. Guidelines for this population should be developed to account for risk heterogeneity and need for differential management., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Vascularized pancreas transplantation is the only treatment that establishes normal glucose levels and normalizes glycosylated hemoglobin levels in type 1 diabetic patients. The first vascularized pancreas transplant was performed by William Kelly and Richard Lillehei, to treat a type 1 diabetes patient, in December 1966. In Brazil, Edison Teixeira performed the first isolated segmental pancreas transplant in 1968. Until the 1980s, pancreas transplants were restricted to a few centers of the United States and Europe. The introduction of tacrolimus and mycophenolate mofetil in 1994, led to a significant outcome improvement and consequently, an increase in pancreas transplants in several countries. According to the International Pancreas Transplant Registry, until December 31st, 2010, more than 35 thousand pancreas transplants had been performed. The one-year survival of patients and pancreatic grafts exceeds 95 and 83%, respectively. The better survival of pancreatic (86%) and renal (93%) grafts in the first year after transplantation is in the simultaneous pancreas-kidney transplant group of patients. Immunological loss in the first year after transplant for simultaneous pancreas-kidney, pancreas after kidney, and pancreas alone are 1.8, 3.7, and 6%, respectively. Pancreas transplant has 10 to 20% surgical complications requiring laparotomy. Besides enhancing quality of life, pancreatic transplant increases survival of uremic diabetic patient as compared to uremic diabetic patients on dialysis or with kidney transplantation alone.

Background: Previous studies have found no association between graft ischemic time (IT) and survival in pediatric heart transplant (HTx) recipients. However, previous studies were small or analyzed risk only at the extremes of IT, where observations are few. We sought to determine whether graft IT is independently associated with graft survival in a large cohort of children with no a priori assumptions about where the risk threshold may lie., Methods: All children aged <18 years in the U.S. undergoing primary HTx (1987 to 2008) were included. The primary end point was graft loss (death or retransplant) within 6 months. Multivariate analysis was performed to analyze the association between graft IT and graft loss within 6 months after transplant. A secondary end point of longer-term graft loss was assessed among recipients who survived the first 6 months after transplant., Results: Of 4,716 pediatric HTxs performed, the median IT was 3.5 hours (interquartile range, 2.7-4.3 hours). Adjusted analysis showed that children with an IT > 3.5 hours were at increased risk of graft loss within 6 months after transplant (hazard ratio, 1.3; 95% confidence interval, 1.1-1.5; p = 0.002). Among 6-month survivors, IT was not associated with longer-term graft loss., Conclusions: IT beyond 3.5 hours is associated with a 30% increase in risk of graft loss within 6 months in pediatric HT recipients. Although the magnitude of risk associated with IT is small compared with the risk associated with recipient factors, these findings may be important during donor assessment for high-risk transplant candidates., (2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Early pancreas graft failure after simultaneous pancreas and kidney (SPK) transplantation is common. We studied the impact of early pancreas graft failure on long-term kidney and patient survival., Methods: We included all primary SPK transplants performed in the United States between January 1, 2000, and December 31, 2007, who had maintained kidney graft function at 90 days posttransplantation. Kaplan-Meier and Cox multivariate analyses were performed. The causes of death between the two cohorts were compared., Results: A total of 6282 SPK recipients were included in the analyses. Of those, 470 had lost pancreas graft within the first 90 days largely related to pancreas graft thrombosis. Early pancreas graft failure was associated with lower subsequent kidney graft and patient survival (log-rank, P=0.02 and P<0.001, respectively). Multivariate regression analyses demonstrated a 70% higher risk of kidney graft failure after 3 years (adjusted hazard ratio 1.69; 95% CI 1.08, 2.66; P=0.022) and more than doubled the risk for death (adjusted hazard ratio 2.18; 95% CI 1.67, 2.85; P<0.001) among SPK recipients with early pancreas graft failure. The causes of death were similar between the two cohorts., Conclusion: Early pancreas graft failure in SPK transplant recipients is associated with an increased risk for subsequent kidney failure and death. Optimization of therapeutic interventions after early pancreas graft failure is needed.

Rationale: Obesity is considered a relative contraindication to lung transplantation, based on studies that have not accounted for key confounders. Little is known about the risk of death for underweight candidates after transplantation., Objectives: To examine the associations of pretransplant obesity and underweight with the risk of death after lung transplantation., Methods: We examined 5,978 adults with cystic fibrosis, chronic obstructive pulmonary disease, and diffuse parenchymal lung disease who underwent lung transplantation in the United States between 1995 and 2003. We used Cox models and generalized additive models to examine the association between pretransplant body mass index and the risk of death after lung transplantation with adjustment for donor and recipient factors., Measurements and Main Results: The median follow-up time was 4.2 years. Compared with normal weight recipients, the multivariable-adjusted rates of death were 15% higher for underweight recipients (95% confidence interval, 3 to 28%), 15% higher for overweight recipients (95% confidence interval, 6 to 26%), and 22% higher for obese recipients (95% confidence interval, 8 to 39%). These relationships persisted when stratified by diagnosis. The multivariable-adjusted population attributable fraction was 12% at 1 year and 8% at 5 years., Conclusions: Both obesity and underweight are independent risk factors for death after lung transplantation, contributing to up to 12% of deaths in the first year after transplantation. Primary care providers and pulmonologists should promote a healthy weight for patients with lung disease long before transplantation is considered.

The relationship between corticosteroids and osteonecrosis is well known. Limited data suggest that statins modulate cholesterol metabolism and may protect against osteonecrosis. The authors analyzed their prospective renal transplant database to determine if statin usage reduces the incidence of corticosteroid-related osteonecrosis and identified 2,881 renal transplantation patients who met the entry criteria. Among 338 patients on statins, 15 (4.4%) developed osteonecrosis, versus 180 of 2,543 (7%) patients who were not on statins. Osteonecrosis-free survival was similar in patients with and without statin exposure.

Background and Objectives: This study examined the risks, predictors, and mortality implications of cerebrovascular disease events after kidney transplantation in a national cohort., Design, Setting, Participants, & Measurements: This analysis used United States Renal Data System registry data to study retrospectively Medicare-insured kidney transplant candidates (n = 51,504), recipients (n = 29,614), and recipients with allograft failure (n = 2954) in 1995 through 2002. New-onset cerebrovascular disease events including ischemic stroke, hemorrhagic stroke, and transient ischemic attacks were ascertained from billing records, and participants were followed until Medicare-end or December 31, 2002. Multivariable survival analysis was used to compare cerebrovascular disease event incidence and risk profiles among the study samples., Results: The cumulative, 3-yr incidence of de novo cerebrovascular disease events after transplantation was 6.8% and was lower than adjusted 3-yr estimates of 11.8% on the waiting list and 11.2% after graft loss. In time-dependent regression, transplantation predicted a 34% reduction in subsequent, overall cerebrovascular disease events risk compared with remaining on the waiting list, whereas risk for cerebrovascular disease events increased >150% after graft failure. Similar relationships with transplantation and graft loss were observed for each type of cerebrovascular disease event. Smoking was a potentially preventable correlate of posttransplantation cerebrovascular disease events. Women were not protected. All forms of cerebrovascular disease event diagnoses after transplantation predicted increased mortality., Conclusions: Along with known benefits for cardiac complications, transplantation with sustained graft function seems to reduce risk for vascular disease events involving the cerebral circulation.

Background: Monitoring cyclosporine microemulsion (CsA-ME; Neoral) exposure 2 hours postdose (C2) has been reported to optimize the efficacy and safety of CsA-ME therapy. The addition of induction therapy to a maintenance regimen including CsA-ME C2 monitoring has not been evaluated., Methods: In all, 123 adult renal transplant recipients were recruited at 14 U.S. centers for this 6-month study. CsA-ME dose was to be titrated to attain C2 targets of 1700 and 1500 ng/ml during posttransplant months 1 and 2, respectively. After 2 months, patients were randomized to one of two groups with different, decreasing C2 targets. Basiliximab, mycophenolate mofetil, and corticosteroids completed the study immunosuppression., Results: Of the 119 evaluable patients, 76% were male, 22% African American, and 66% deceased donor recipients. Biopsy-proven acute rejection occurred in 10 patients (9.3%); there were two failed grafts and one death. Serum creatinine and calculated GFR values suggest good renal function, with month 6 medians of 1.5 ng/ml and 67 ml/min/1.73 m. Safety and tolerability assessments revealed no unexpected outcomes. Observed C2 levels were generally lower than protocol targets, particularly in the first weeks posttransplantation., Conclusions: The striking efficacy and outcomes may have been achieved in this study with lower C2 levels of CsA-ME because of the addition of basiliximab induction.

The impact of graft loss on acute coronary syndromes (ACS) after renal transplantation has not been studied in a national population. It was hypothesized that ACS might be more frequent after graft loss, as many of the benefits of a functioning allograft on metabolism and volume regulation would be lost. Data from the 2000 United States Renal Data System (USRDS) was used to conduct an historical cohort study of ACS in 14,237 patients who received renal transplants between April 1, 1995, and June 30, 1998, (followed until April 28, 2000) with valid information from CMS Form 2728, excluding patients with hospitalized ACS before renal transplant. Cox nonproportional regression models were used to calculate the time-dependent adjusted hazard ratio (AHR) of graft loss (censored for death) for time-to-first hospitalization for ACS (International Classification of Diseases 9th Modification Diagnosis Codes [ICD9] code 410.x or 411.x) occurring after transplant. The incidence of ACS was 12.1 per 1000 patient-years (PY) in patients after graft loss versus 6.5 per 1000 PY after transplantation (excluding patients with graft loss). As a time-dependent variable, graft loss had an AHR of 2.54 (95% confidence interval, 1.09 to 5.96; P = 0.031 by Cox regression). Other risk factors associated with ACS included diabetes, older recipient, and male recipient. Allograft rejection was NS. Renal transplant recipients share some of the risk factors for ACS with the general population. In addition, graft loss was identified as a unique risk factor for ACS in this population.

The aims of this analysis are to characterize the incidence and types of malignancies and tumor-specific mortality in our institution. Retransplantation, rejection episodes, and OKT3 use were evaluated. Our single-institution prospective database of 1,570 liver transplantations in 1,421 patients was analyzed. Data were statistically analyzed regarding sex, age at transplantation, time from transplantation to diagnosis of tumor, tumor type, and follow-up time. One hundred twenty-five patients (8.8%) developed de novo tumors; 69 patients were men, 56 patients were women. Seventeen patients received more than one allograft. De novo tumors were as follows: skin, 41; lymphomas, 35; lung, 11; colon, 6; anal, 2; rectal, 1; breast, 7; thyroid, 3; oropharyngeal squamous cell, 3; metastatic without primary tumor identified, 4; renal cell, 3; Kaposi's sarcoma, 1; angiosarcoma, 1; uterine, 1; ovarian, 1; pituitary, 1; pancreatic, 2; cholangiocarcinoma, 1; and esophageal, 1. These tumors developed in a statistically significant chronological sequence. Lung cancers and lymphomas showed shorter mean survival times, as well as greater mortality. OKT3 use and rejection did not show significance in tumor development. De novo tumors post-liver transplantation affected our population in a distribution similar to that of the general non-transplantation population. Intense short courses of immunosuppression for rejection were not as important as chronic immunosuppression in the development of tumors. The risk for development was not enough to preclude transplantation. We found that tumors developed in chronological fashion. Therefore, directed surveillance, patient education, and early detection may facilitate earlier treatment.

Obesity is a concern in the long-term management of patients following liver transplantation, yet the risk of obesity and the factors that influence its development have not been well defined. We evaluated posttransplantation weight change among a cohort of 774 adults who had their height and weight recorded before liver transplantation at three major centers. Obesity was defined as a body mass index (BMI) of at least 30 kg/m2. Weight at transplantation was adjusted by the amount of ascites removed. Mean BMI increased from 24.8 kg/m2 pretransplantation to 27.0 kg/m2 in the first posttransplantation year, to 28.1 kg/m2 in the second year, and very little with subsequent observation. Among 320 patients who were not obese before transplantation, 21.6% became obese within 2 years after transplantation. On evaluation of numerous potential donor and pretransplantation risk factors, greater recipient BMI, greater donor BMI, and being married were found to be predictors of subsequent obesity (P < .05). Posttransplantation predictors of obesity included absence of acute cellular rejection, higher cumulative prednisone dose in the second year, and cyclosporine-based immunosuppression, although only rejection and prednisone dose remained predictors on multivariate analysis. Despite the marked weight gain after transplantation, prevalence of obesity at 2 years was only slightly greater than in the general US population. Obesity occurred commonly after liver transplantation, sometimes with a striking gain in weight. In addition to BMI at transplantation, donor BMI, marital status, occurrence of acute rejection, and prednisone dose affected the incidence of obesity., (Copyright 1998 W.B. Saunders Company.)