Long-term results in diabetic patients undergoing heart transplantation.

We conducted a retrospective study of 305 nondiabetic patients and 37 diabetic patients who underwent heart transplantation from July 1982 to May 1990. Actuarial survival was similar for both groups of patients at 1 year (76.4% versus 81.3%) and at 2 years (69.6% versus 73.0%). Because we were interested in long-term results, we further analyzed only those patients surviving more than 1 year after transplantation (214 nondiabetic patients and 29 diabetic patients). Mean follow-up for the nondiabetic patients was 31.8 +/- 16.2 months and for the diabetic patients, 32.9 +/- 4.1 months. The respective mean age in each group was 50.4 +/- 10.3 years and 51.6 +/- 9.1 years. No difference was observed between the nondiabetic patients and diabetic patients regarding the rejection rate per patient-month (0.040 +/- 0.041 versus 0.045 +/- 0.051 episodes per patient-month), the infection rate per patient-month (0.056 +/- 0.081 versus 0.081 +/- 0.102 episodes per patient-month), or renal function as evidenced by mean creatinine levels at 1, 2, and 3 years. Twelve patients were insulin-dependent before transplantation; and 1 year after transplantation, they required an insulin dose 2.12 times greater than the dose before operation. Coronary artery disease developed in 32.8% of the nondiabetic patients, compared with 31.0% of the diabetic patients by the fourth year of follow-up. Despite the need for increased insulin doses, the diabetic patients had similar long-term survival to that of the nondiabetic patients, without an increased risk of rejection, infection, renal dysfunction, or coronary artery disease. Our experience supports the feasibility of heart transplantation in selected diabetic recipients.     

Long-term survival after kidney and kidney-pancreas transplantation in diabetic patients

PURPOSE: To investigate the influence of diabetes mellitus on patient and graft survival among renal versus renal-pancreatic recipients. METHODS: Among 270 renal transplants performed from 1985 to 2002, a total of 204 (75%) were in diabetic patients and 66 (25%) in nondiabetic patients. Among the 204 diabetic patients 161 (60%) kidneys were transplanted simultaneously with a pancreatic graft (SKPT group). The overall group of patient included 164 (61%) men and 106 (39%) women with mean time on dialysis of 31 +/- 21 months (range 0 to 126 months). The mean duration of diabetes was 24 +/- 7 years (range 5 to 51 years). Ninety-nine percent of the patients were on renal replacement therapy (79% hemodialysis and 20% peritoneal dialysis). RESULTS: The overall rejection rate was similar (NS). Both patient and kidney graft survival rates were worse in diabetics. Patient survival was 82% at 5 years among patients undergoing SKPT, 60% in diabetics receiving only a kidney, and 88% in nondiabetic transplanted patients. Kidney graft survival at 5 years was 77% in diabetics receiving SKPT, 68% in diabetics receiving a kidney alone, and 82% in nondiabetic patients. Overall patient survival was significantly greater among nondiabetics (P =.002) or in diabetics who received SKPT compared with diabetics who only had a kidney transplant (P =.001). CONCLUSIONS: This retrospective clinical evaluation confirms that combined pancreas and kidney transplantation should be the first choice to insulin-dependent diabetes mellitus (IDDM) patients with end-stage diabetic nephropathy.     

Long-term survival after cardiac retransplantation: a twenty-year single-center experience

OBJECTIVE: To identify risk factors for survival after cardiac retransplantation and compare the survival after retransplantation with that after primary cardiac transplantation. METHODS: A retrospective analysis of 952 patients undergoing cardiac transplantation for the treatment of end-stage heart disease at a single center between 1977 and October 1997. Of these, 43 patients (4.5%) underwent cardiac retransplantation for cardiac failure resulting from transplant-related coronary artery disease, rejection, and early graft failure. RESULTS: No significant difference in actuarial patient survival was found by Kaplan-Meier analysis at 1, 2, and 5 years between patients undergoing primary transplantation and those undergoing retransplantation 76%, 71%, and 60% versus 66%, 66%, and 51%, respectively (P =.2). Multivariable analysis identified a shorter interval between transplants and an initial diagnosis of ischemic cardiomyopathy as significant risk factors for death after retransplantation (P =.04 and.03, respectively). Since 1993, when our criteria for patient selection for retransplantation were revised on the basis of earlier experience to exclude patients with allograft dysfunction as a result of primary graft failure and those with intractable acute rejection occurring less than 6 months after transplantation, the survival has been significantly better (<1993 = 45%, 45%, and 33% versus >/=1993 = 94%, 94%, and 94% at 1, 2, and 4 years, respectively, P =.003). CONCLUSION: The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation, especially in patients with transplant-related coronary artery disease. Patient characteristics and other preoperative variables should assist in the rational application of retransplantation to ensure optimal use of donor organs.     

Long-term survival in lung transplant recipients after successful preoperative coronary revascularization

OBJECTIVE: Coronary artery disease is considered a contraindication to lung transplantation. We studied effect of pre-lung transplantation nonobstructive coronary artery disease and revascularized coronary artery disease on long-term lung transplant survival. METHODS: Clinical courses of 172 lung transplant recipients from December 1990 to May 2003 were reviewed. Significant coronary artery disease, defined as left main stenosis of greater than 50% or other epicardial vessel stenosis of greater than 70%, was present in 7 patients; 6 received percutaneous coronary intervention and 1 received coronary artery bypass grafting before transplantation. RESULTS: Groups were similar with regard to sex, race, or length of intensive care days. The group with normal coronary arteries was significantly younger than the groups with coronary artery disease. The revascularized group had a significant increase in dysrhythmias (P < .003) and 1-, 3-, and 5-year survivals of 85%, 85%, and 69%, respectively. Those with insignificant coronary artery disease (14 patients) demonstrated a 1-, 3-, and 5-year survival of 64%, 40%, and 32%, respectively. The normal coronary group (151 patients) had a 1-, 3-, and 5-year survival of 75%, 58%, and 40%, respectively. The revascularized group had a significant survival advantage compared with that of the insignificant coronary artery disease group (P < .04, log-rank test). CONCLUSION: Long-term survival of lung transplant recipients with revascularized coronary arteries is similar to that of subjects with normal coronary arteries, despite an increased incidence of dysrhythmias. Lung transplant recipients with insignificant coronary artery disease had a worse survival than the revascularized group. More studies are needed to ascertain the cause and determine the optimal management for lung transplant recipients with insignificant coronary artery disease.     

The influence of donor age on transplant coronary artery disease and survival post heart transplantation: is it safe to extend donor age?

BACKGROUND: Due to the increasing demand for suitable cardiac donor organs, acceptance criteria need to be re-evaluated. We retrospectively analyzed the effect of donor age on survival following cardiac transplantation. METHOD: Three hundred thirty-five cardiac transplant recipients and corresponding donor data were reviewed using SPSS. RESULTS: Seventy-two recipients had early posttransplant angiography or postmortem data available. The mean donor age of recipients with evidence of graft coronary artery disease (32.5 +/- 11.7 years) was significantly higher than that of recipients free of transplant coronary artery disease (TCAD) (24.8 +/- 9.4 years; P=.003). Recipient of organs from donors aged less than 50 years were less likely to develop TCAD than those of donors aged over 50 years (odds ratio 0.333; 95% CI 0.239-0.465; P=.044). TCAD also occurred much earlier posttransplantation in recipients of organ from donors over 50 years (mean time 6.5 years; median 5.0 years) than those of donors under 50 years (mean time 12.7 years; median 14.0 years). CONCLUSION: We observed no increase in mortality associated with cardiac donors over 50 years. However, increased donor age was associated with an increased incidence of TCAD.     

Survival benefits of heart and lung transplantation.

OBJECTIVE: Heart and lung transplantation has gained acceptance as therapy for end-stage cardiac and pulmonary failure. The early and intermediate survival benefits of one center's 10-year experience with 177 patients undergoing thoracic transplantation were examined. SUMMARY BACKGROUND DATA: As experience in cardiac and pulmonary transplantation has increased, improvements in patient selection, organ preservation, preoperative support, and perioperative care have significantly reduced the early threats to patient survival. Graft dysfunction due to chronic rejection appears to be the main risk for longer-term survival, and data compiled by the United Network for Organ Sharing (UNOS) indicate a 70% 5-year survival for heart transplants and a 50% 5-year survival for lung transplant recipients. METHODS: The medical records of 120 heart recipients, 52 lung transplant recipients, and 5 heart-lung recipients were reviewed. Cumulative survival estimates were made using Kaplan-Meier analysis. The etiologies of operative and long-term mortality in each transplant population were identified. A comparison of long-term survival after heart transplantation versus coronary revascularization in a group of patients with ischemic cardiomyopathy was performed. RESULTS: Operative mortality in both the cardiac and pulmonary transplant recipients was 8%. From 1990 to 1995, 70 consecutive adult cardiac transplant procedures were performed without an operative mortality. Three of five patients survived heart-lung transplantation. The extended actuarial survival rate at 5 years was 80% for the cardiac transplant recipients. The 2-year actuarial survival rate for the lung transplant recipients was 88%. Graft dysfunction was the most common cause of operative mortality in the heart transplant group whereas infection was responsible for most of the operative mortality after lung transplantation. CONCLUSIONS: Cardiac and pulmonary transplantation can be applied to morbidly ill patients with excellent operative and intermediate-term survival.     

Bilateral skeletonized internal thoracic artery grafts in patients with diabetes mellitus

OBJECTIVE: Increased risk of deep sternal infections has prohibited routine bilateral internal thoracic artery grafting in diabetic patients. The technique for harvesting the skeletonized internal thoracic artery provides the potential to minimize this risk. The purpose of this study was to compare the outcome of bypass grafting with bilateral skeletonized internal thoracic arteries in diabetic and nondiabetic patients. METHODS: From May 1996 to April 1998, 231 consecutive diabetic and 534 nondiabetic patients underwent bilateral skeletonized internal thoracic artery grafting. Mean age was 66 years. Compared with the nondiabetic group, the diabetic group comprised more women (29% vs 18%, P =.001), had a greater prevalence of hypertension (53% vs 44%, P =.019) and congestive heart failure (20% vs 14%, P =.016), but a lower prevalence of preoperative acute myocardial infarction (26% vs 34%, P =.027). RESULTS: Operative mortality of diabetic patients was comparable with that of nondiabetic patients (3% vs 2.6%). The two groups also had similar occurrences of deep sternal infection (2.6% vs 1.7%, respectively, P =.40). Deep sternal infection was significantly more prevalent in obese, diabetic women (3/20 = 15%) than in diabetic patients without this combination of risk factors (3/211 = 1.4%, P <.0001) (odds ratio 11.1, confidence interval 2.1-59.4). Diabetic patients also had a higher incidence of stroke (3.5% vs 0.9%, P =.014). Three-year actuarial survival of diabetic patients was lower (91.3% vs 94.7%, P =.083). CONCLUSIONS: Bilateral skeletonized internal thoracic artery grafting is a good surgical revascularization option in diabetic patients. Operative mortality and prevalence of sternal infection are comparable with those of nondiabetic patients. However, the risk of sternal infection in obese diabetic women is high, and for them we advocate the use of a single artery instead of bilateral internal thoracic arteries.     

Clinical course of hepatitis C virus infection in renal transplant recipients

Patients with end-stage renal disease are at high risk for exposure to hepatitis C virus (HCV) infection. Although both viral replication and liver disease progression are accelerated after renal transplantation, the long-term impact of chronic HCV infection is unclear. Our aim was to analyze the course of HCV infection in renal transplant recipients and the effects of HCV reactivation on patient and graft survival. METHODS: We retrospectively examined the 21-year (1985-2006) data of 1274 renal transplant recipients, 43 of whom were anti-HCV positive at the time of transplantation. RESULTS: The mean posttransplant follow-up of 43 patients was 62.0 +/- 7.3 months. At the time of transplantation, HCV RNA was positive in 11 (25.6%) patients and negative in 32 (74.4%) patients. HCV reactivation was seen in 19 (45.2%) patients at a mean time of 20.8 +/- 5.7 months. In 31 (72%) patients, acute rejection occurred, whereas graft loss occurred in 10 (23%) patients. Three (7%) patients died. Among 43 patients, 22 (51.2%) were treated with interferon before transplantation. There was a statistically significant association between pretransplant interferon therapy and pretransplant HCVRNA level (P=.024), but no significant association of HCV reactivation and graft rejection, mortality, or kidney survival. CONCLUSION: HCV reactivation occurred in nearly half of the renal transplant recipients, mostly in the second year. Patient survival and graft survival were not affected by HCV reactivation. Anti-HCV positivity should not preclude chronic renal failure patients from renal transplantation.     

Midterm results of a prospective randomized comparison of two different rabbit-antithymocyte globulin induction therapies after heart transplantation

This prospective randomized study compared the effects in heart transplant recipients of thymoglobulin and ATG, two rabbit polyclonal antithymocyte antibodies available for induction therapy. Among 40 patients (29 men and 11 women, mean age: 40.7 +/- 14 years) undergoing orthotopic heart transplantation, 20 were randomly allocated to receive induction with thymoglobulin (group A) and 20 to ATG-fresenius (group B). Comparisons between the two groups included early posttransplant (6 months) incidence of acute rejection episodes (grade >/= 1B), bouts of steroid-resistant rejection, time to first rejection, survival, graft atherosclerosis, infections, and malignancies. The study groups displayed similar preoperative and demographic variables. No significant difference was found with regard to actuarial survival (P =.98), freedom from rejection (P =.68), number of early rejections > 1B (P =.67), mean time to first early cardiac rejection (P =.13), number of steroid-resistant rejections (P =.69). Cytomegalovirus reactivations were more frequent among group A (65%) than group B (30%; P =.028). New infections due to cytomegalovirus occurred only in group A (four patients; 20%; P =.05). No cases of malignancies were observed at a mean follow-up of 32.8 +/- 8.9 months. Although thymoglobulin and ATG showed equivalent efficacy for rejection prevention, they have different immunological properties. In particular, thymoglobulin seems to be associated with a significantly higher incidence of cytomegalovirus disease/reactivation.     

Clinical outcome after coronary artery revascularization and lung transplantation

BACKGROUND: Presence of coronary artery disease (CAD) in otherwise eligible lung transplant candidates is considered a contraindication to lung transplantation. We reviewed the clinical outcome of our experience in lung transplant recipients with operable coronary artery disease and normal left ventricular function. METHODS: Medical records of all transplant recipients with coronary artery disease were reviewed. Data analyzed include demographics, coronary angiograms, coronary artery revascularization procedure, and clinical outcome after lung transplantation. RESULTS: Between April 1992 and August 2001, 354 lung transplant procedures were performed. Eighteen patients (5%) had significant CAD (greater than 50% stenoses). Six male patients (mean age 59 years) underwent percutaneous transluminal coronary angioplasty/stent and after lung transplantation all were discharged after a median hospital stay of 8.5 days. All recipients are alive at a median follow-up time of 14.5 months after their transplant. Twelve male patients (mean age 58 years) had combined coronary artery bypass grafting and lung transplantation. All recipients were discharged after a median hospital stay of 16 days. Nine recipients are alive at a median follow-up time of 7.5 months after transplant. One-year survival by the Kaplan-Meier method is 88% for the 18 patients with coronary artery disease who underwent revascularization and lung transplantation. CONCLUSIONS: Despite the traditional criteria of excluding all eligible transplant candidates due to coronary artery disease, coronary revascularization in select candidates with favorable anatomy and normal left ventricular function can allow patients to undergo lung transplantation with acceptable outcomes.     

Impact of cytomegalovirus hyperimmune globulin on outcome after cardiothoracic transplantation: a comparative study of combined prophylaxis with CMV hyperimmune globulin plus ganciclovir versus ganciclovir alone.

BACKGROUND: Cytomegalovirus (CMV) disease was previously shown to be unaltered by a 28-day course of ganciclovir compared with placebo in seronegative recipients of hearts from seropositive donors (D+/R-). This study tests the hypothesis that a combination of ganciclovir plus CMV hyperimmune globulin (CMVIG) is more effective than ganciclovir alone for preventing acute CMV illness and its long-term sequelae. METHODS: The study population receiving CMVIG (n=80) included 27 heart transplant recipients (D+/R-) and 53 heart-lung and lung transplant recipients (R+ and/or D+). Each group was matched with historical controls who underwent transplantation within the preceding 2-3 years. Outcome measures compared were as follows: 3-year incidence of CMV disease; fungal infection; acute rejection; survival; rates and severity of transplant coronary artery disease (in heart patients) defined by intimal thickness (ultrasound) and coronary artery stenosis (angiographic); and incidence and death from obliterative bronchiolitis defined by pathological criteria on endobronchial biopsy specimens (in heart-lung/lung patients). RESULTS: Patients treated with CMVIG had a higher disease-free incidence of CMV, lower rejection incidence, and higher survival rate compared with the patients treated with ganciclovir alone. The coronary artery intimal thickness and the prevalence of intimal thickening were lower in the patients receiving CMVIG. Heart-lung and lung transplant patients treated with CMVIG had lower incidences of obliterative bronchiolitis and death from obliterative bronchiolitis and longer survival compared with the patients treated with ganciclovir alone. CONCLUSIONS: CMVIG plus ganciclovir seems to be more effective that ganciclovir alone for preventing the sequelae of CMV infection. A prospective randomized study is required to confirm these observations.     

Reduced acute rejection and superior 1-year renal allograft survival with basiliximab in patients with diabetes mellitus. The Global Simulect Study Group

BACKGROUND: Renal allograft recipients with diabetes mellitus often demonstrate poorer clinical outcomes than nondiabetic patients. Basiliximab (Simulect), a chimeric anti-interleukin-2 receptor monoclonal antibody, reduced the incidence of acute rejection in renal allograft recipients in 2 multicenter, placebo-controlled, phase III trials. METHODS: An analysis of pooled results from the 2 trials was conducted to compare the efficacy and safety of basiliximab with placebo in renal transplant recipients with and without prior diabetes. Patients received either basiliximab (20 mg on day 0 and day 4 posttransplantation) or placebo in combination with cyclosporine for microemulsion (Neoral) and steroids. RESULTS: A total of 722 patients (150 diabetic, 572 nondiabetic) were eligible for intent-to-treat analysis. At 12 months, basiliximab as compared with placebo reduced the proportion of patients experiencing first acute rejection by 41% in diabetics (P<0.01) and by 29% in nondiabetics (P<0.001). Biopsy-confirmed rejection was reduced by 44% in diabetics (P<0.01) and by 26% in nondiabetics (P<0.01). The first acute rejection episode requiring augmented immunosuppression other than steroids was reduced by 49% in diabetics (P<0.01) and by 41% in nondiabetics (P<0.001); death, graft loss, or first rejection episode was reduced by 43% in diabetics (P=0.001) and by 22% in nondiabetics (P<0.01). Superior graft survival was maintained in diabetic recipients treated with basiliximab versus placebo (96% vs. 86%; P=0.022). There were no significant differences in safety between basiliximab and placebo in both diabetic and nondiabetic patients. CONCLUSIONS: Basiliximab is associated with a significant reduction in acute rejection and an excellent safety profile in renal transplant recipients with and without diabetes mellitus. Superior graft survival was evident in diabetic patients.     

A comparative analysis of outcome after heart transplantation in patients aged 60 years and older: the University of Alberta experience

BACKGROUND: The Registry of the International Society for Heart and Lung Transplantation (ISHLT) 2001 Annual Report indicated that the vast majority of heart transplant recipients are between 50 and 64 years of age. However, patient age beyond 60 years may have higher long-term mortality compared to younger patients. The purpose of this study was to compare short- and intermediate-term results including rates of acute rejection, transplant coronary artery disease, infections, malignancy, and mortality in cardiac transplant recipients 60 years or older with those below the age of 60 years. METHODS: We retrospectively analyzed the results of 50 patients aged 60 years and older who underwent heart transplantation at the University of Alberta from January 1990 to December 2000 and compared them with the results of 225 younger patients undergoing heart transplantation in the same time period. RESULTS: The older and younger groups had similar rates for treated acute rejection episodes (20.0% vs. 12.6%), transplant coronary artery disease (4.0% vs. 1.1%), and mortality (10.5% vs. 14.3%), respectively. No differences were noted with regards to quality and quantity of infection or malignancy rates. Five-year actuarial survival between the older and younger patients was also comparable at 89.5% vs.86.9% (p > 0.05). CONCLUSIONS: Heart transplantation in patients 60 years of age and older can be performed as successfully as in younger patients (< 60 years) with comparable morbidity and mortality, suggesting that patient age per se should not be an exclusion criterion for heart transplantation.     

De novo immunosuppression with sirolimus and tacrolimus in heart transplant recipients compared with cyclosporine and mycophenolate mofetil: a one-year follow-up analysis

BACKGROUND: Limited data exist regarding the safety and efficacy of sirolimus in combination with a calcineurin inhibitor in heart transplant recipients. METHODS: From January 2001 to June 2002, 31 de novo heart transplant recipients (treatment group) received a combination of sirolimus, tacrolimus, low-dose rabbit antithymocyte globulin, and glucocorticoids. Outcomes, such as actuarial survival, rate of rejection, incidence of infection, probability of developing diabetes mellitus, renal function, platelet and white blood cell counts, and incidence of coronary artery disease at 1 year, were compared with a cohort of 25 patients (control group) who underwent transplantation primarily in 2000 and in early 2002 treated with cyclosporine, mycophenolate mofetil, and glucocorticoids. All patients were followed up for at least 12 months. RESULTS: Kaplan-Meier actuarial 1-year survival rates were equivalent between groups (97% for the treatment group and 88% for the control group), as was freedom from allograft rejection (48% and 42% for treatment and control groups, respectively). No cases of transplant arteriopathy were noted within the first posttransplantation year. Renal function was not significantly affected in either group. There was a striking increased incidence of mediastinitis in the treatment group (19%) versus 0% in the control group (P = .02). Tacrolimus-sirolimus therapy was associated with a nearly 11-fold increased incidence of new-onset diabetes mellitus as well (P = .004). CONCLUSION: Tacrolimus, sirolimus, and steroids (following low-dose rabbit antithymocyte globulin) were associated with an increased incidence of mediastinitis and posttransplantation diabetes mellitus. No obvious long-term benefit on survival, arteriopathy, or renal function was noted.     

Long-term results of cardiac transplantation in patients 65 years of age and older: a comparative analysis

BACKGROUND: Advanced age is viewed by some transplant centers as a contraindication for heart transplantation secondary to concerns regarding decreased survival. METHODS: Between January 1992 and June 2002, 63 of 881 (7.2%) orthotopic heart transplants were performed in patients above 65 years. These patients were compared to 63 recipients below age 65 who were matched for sex, etiology of heart failure, United Network for Organ Sharing status, and immunosuppression therapy era. RESULTS: Mean age was 67.1 +/- 2.3 years (range, 65.0 to 74.8) for the older group and 48.1 +/- 14.5 years (range, 18.3 to 64.4) for the younger group (p < 0.001). There was no significant difference in the incidence of diabetes, hypertension, chronic obstructive pulmonary disease, or peripheral vascular disease between the groups (p = not significant) although there were more patients with prior myocardial infarctions in the older group (p < 0.001). There was no significant difference in overall survival between the groups, with 1-, 3-, 5-, and 10-year actuarial survival of 85.8%, 80.3%, 73.1%, and 49.9% for the older group; and 86.9%, 83.4%, 75.0%, and 57.0% for the younger group (p = 0.597). Postoperative intensive care unit stay and overall hospital stay were similar for the two groups (p = not significant). There was no significant difference between the groups in freedom from infection or rejection at 1, 3, or 5 years after transplant (p = not significant) although the incidence of transplant coronary artery disease was higher in the older group (p = 0.025). CONCLUSIONS: These data demonstrate similar short-term and long-term results for elderly and young recipients undergoing cardiac transplantation. This supports proceeding with transplantation in carefully selected elderly patients.     

Human herpesvirus-6 in liver transplant recipients: role in pathogenesis of fungal infections, neurologic complications, and outcome

BACKGROUND: The clinical impact and relevance of human herpesvirus-6 (HHV-6) infection in liver transplant recipients, has not been fully discerned. METHODS: A prospective study of 80 consecutive liver transplant recipients was performed using surveillance cultures for HHV-6 at weeks 2, 3, 4, and 6 after transplantation. Viral isolation was used for the detection of HHV-6. RESULTS: HHV-6 infection occurred in 39% (31 of 80) of the patients. Patients with HHV-6 infection were more likely to have hepatocellular carcinoma as underlying liver disease (P=.09). Mental status changes of unidentifiable etiology were significantly more likely to occur in patients with HHV-6 compared with those without (26%, 9 of 31 vs. 6%, 3 of 49, P=.008). HHV-6 infection was an independent predictor of invasive fungal infections (odds ratio 8.3, 95% confidence interval, 1.2-58.0, P=.03). A significant association between HHV-6 infection and CMV infection after transplantation, CMV recipient and donor serostatus, rejection, or fever of unknown origin, could not be documented. Mortality at last follow-up in patients with HHV-6 infection (29%, 9 of 31) was significantly greater than those without HHV-6 (6%, 3 of 49, P=.008). CONCLUSIONS: Central nervous system complications of unknown etiology after liver transplantation may be related to HHV-6 infection. HHV-6 viremia was an independently significant predictor of invasive fungal infections and was associated with late mortality in liver transplantation recipients.     

Heart transplant coronary artery disease in Chinese recipients

BACKGROUND: Transplant coronary artery disease is the principle limiting factor for long-term survival of heart transplantation (HTx) recipients. We reviewed our data to assess the incidence of this disorder among Chinese HTx recipients and to compare it with the results of Western studies. MATERIAL AND METHODS: From July 1988 to May 2002, 182 patients received 184 orthotopic HTx. One hundred sixty-three recipients survived for at least 1 year with available SPECT scans or coronary angiogram studies. The data set included donor characteristics, recipient characteristics, active cytomegalovirus (CMV) infection rate, rejection episodes, immunosuppressants, and human leukocyte antigen (HLA) mismatches. RESULTS: Surgical mortality in our program was 4.3% and the actuarial freedom from coronary artery disease at 1, 3, and 5 years was 99%, 95%, and 92%, respectively. Angiogram results were stratified into coronary artery disease (n = 15) or absence of the disorder (n = 148) groups. Only older donor age showed statistical significance between the groups. Compared with the Western series, the present data show higher actuarial survival rates and freedom from coronary artery disease. There were statistically significant differences in regard to graft ischemia time, proportion of male recipients, ischemic heart disease, rejection episodes during the first year, and incidence of CMV infection. CONCLUSIONS: SPECT scan can detect coronary artery disease before there is significant stenosis of the coronary artery with acceptable survival rates. Chinese HTx recipients show a lower incidence of the disorder, lower rates of ischemia heart disease, lower proportion of male gender, lower incidence of CMV infection, fewer rejection episodes during the first year, and less ischemic time than Western recipients, which maybe the contributing factors to their better survival.     

Comparison of hepatitis C histological recurrence rates and patient survival between split and deceased donor liver transplantation

INTRODUCTION: Controversy exists as to whether there is an increased severity or frequency of recurrent hepatitis C viral (HCV) infection in recipients of adult living donor liver transplantation (LDLT) grafts. We sought to examine the time to histological recurrence and survival in HCV (+) patients who underwent split liver transplantation (SLT), which is technically similar to what occurs in the LDLT procedure. METHODS: Twenty four HCV (+) adult recipients were identified through the UNOS database as having had SLT procedures at three centers: Mount Sinai Medical Center, University of Chicago, and University of California at Los Angeles. Of these, 17 patients with comprehensive data were matched to 32 HCV (+) patients who underwent whole deceased donor liver transplantation (DDLT) during the same time period. Outcome and time to initial HCV recurrence as documented by liver biopsy were assessed. Liver biopsy was performed when clinically indicated. RESULTS: Patients who had SLT were significantly older (P=.01). There was no difference in number of rejection episodes (P=.40). Fifteen of 17 SLT (88%) versus 24/32 DDLT (75%) patients had documented HCV recurrence by biopsy (P=.46). The time to median cumulative incidence of recurrence of HCV post-liver transplantation was 12.6 months (SLT) versus 39.8 months (DDLT) patients. There was no difference in survival between SLT and DDLT patients (47 vs 70 months, P=.62) nor in cumulative incidence of histological HCV recurrence at 1, 2, and 3 years (P=.198, .919, and .806, respectively). CONCLUSION: There is no difference in the cumulative incidence of histological recurrence of HCV post-liver transplant or in survival between recipients of deceased donor and split liver transplants.     

Simultaneous pancreas-kidney transplantation reduces excess mortality in type 1 diabetic patients with end-stage renal disease

BACKGROUND: Diabetic renal disease continues to be the most significant cause of end-stage renal disease (ESRD) in the United States. Renal transplantation improves diabetic ESRD patient survival; however, the diabetic state remains associated with poor patient survival. Simultaneous pancreas-kidney (SPK) transplantation can restore normoglycemia and thus may improve outcomes. METHODS: We assessed the impact of SPK on age-range-matched type 1 diabetic patients who underwent renal transplantation at a single center. The observed/expected life span and annual mortality rates (AMRs) were used as measures of survival. A Cox proportional hazards analysis was used to analyze the impact of potential variables on mortality in SPK recipients. RESULTS: SPK transplantation (N = 335) increased the observed/expected life span compared with diabetic cadaveric (DM-Cad, N = 147) and live-donor (DM-Live, N = 160) transplant recipients (P = 0.004) and significantly reduced the AMRs (SPK, 1. 5%; DM-Cad, 6.27%; DM-Live, 3.65%, P = 0.008, SPK vs. other DM). Moreover, the SPK observed/expected life span and AMR were not significantly different from that of age-range-matched nondiabetic transplant recipients (N = 492). The only variable that was significantly associated with patient survival was discharge serum creatinine (relative risk 1.16, P < or = 0.0154). CONCLUSION: These data demonstrate that SPK improves the ability for type 1 diabetic patients to live more of their expected life span. This suggests that glycemic control, even as a late intervention in a diabetic patient's lifetime, may beneficially affect survival.     

Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease.

BACKGROUND: Acute cellular rejection is the mechanism of most immune-related injury in cardiac transplant recipients. However, antibody-mediated humoral rejection (HR) has also been implicated as an important clinical entity following orthotopic heart transplantation. Humoral rejection has been reported to play a role in graft dysfunction in the early post-transplant period, and to be a risk factor for the development of transplant coronary artery disease. Some involved in transplantation pathology doubt the existence of clinically significant humoral rejection in cardiac allografts. Those who recognize its existence disagree on its possible role in graft dysfunction or graft coronary artery disease. In this study, we report clinical features of patients with the pathologic diagnosis of HR at our institution since July 1997, when we began systematic surveillance for humoral rejection. METHODS: We reviewed medical records of patients with the pathologic diagnosis of HR without concurrent cellular rejection between July 1997 and January 2001. Diagnosis was based on routine histology ("swollen cells" distending capillaries, interstitial edema and hemorrhage) and immunofluorescence (capillary deposition of immunoglobulin and complement with HLA-DR positivity), or immunoperoxidase staining of paraffin-embedded tissue (numerous CD68-positive macrophages and fewer swollen endothelial cells distending capillaries). RESULTS: A total of 44 patients (4 to 74 years old) showed evidence of HR without concurrent cellular rejection at autopsy or on one or more biopsies. Although females comprised only 26% of our transplant population, 23 patients (52%) with HR were female. A positive peri-operative flow cytometry T-cell crossmatch was observed in 32% of HR patients compared with 12% of controls (p = 0.02). Hemodynamic compromise consisting of shock, hypotension, decreased cardiac output/index and/or a rise in capillary wedge or pulmonary artery pressure was observed in 47% of patients at the time of diagnosis of HR. Six patients (5 females) died (14% mortality) with evidence of HR at or just before autopsy, 6 days to 16 months after transplantation. The incidence of transplant coronary artery disease was 10% greater at 1 year, and 36% greater at 5 years, in patients with HR when compared with non-HR patients. CONCLUSIONS: Humoral rejection was associated with acute hemodynamic compromise in 47% of patients, and was the direct cause of death in 6 patients (13%). Humoral rejection is a clinicopathologic entity with a high incidence in women and is associated with acute hemodynamic compromise, accelerated transplant coronary artery disease and death.