The impact and outcome of transplant coronary artery disease in a pediatric population: a 9-year multi-institutional study.

BACKGROUND: Transplant coronary artery disease (TCAD) limits survival in heart transplant recipients; however, its incidence in children is unknown. The purpose of this study was to determine the angiographic incidence of TCAD, potential risk factors, and outcomes in a large pediatric cohort. METHODS: From January 1993 to December 1, a total of 1,222 children, aged newborn to 17 years, underwent primary cardiac transplantation at 20 institutions. A total of 2,049 coronary angiograms were performed in 751 patients. All angiograms were graded for coronary disease and results were submitted to the Pediatric Heart Transplant Study database. We analyzed time-related freedom from graded severity and events from coronary disease, and we examined risk factors. RESULTS: The incidence of angiographic abnormalities at 1, 3, and 5 years was 2%, 9%, and 17%, respectively; however, moderate-to-severe disease occurred in only 6% at 5 years, compared with 15% in the adult transplant database (p <0.0001). The major risk factors were older recipient and donor age. Two or more episodes of rejection in the 1st year correlated with coronary disease (p = 0.05). Overall freedom from graft loss caused by primary TCAD was 99%, 96%, and 91% at 1, 5, and 9 years after heart transplantation, respectively. Death or graft loss occurred within 2 years of diagnosis in patients with severe disease; 24% of patients with any coronary disease died within 2 years. CONCLUSIONS: The incidence of TCAD in children is smaller than the incidence in adults, but increases with age. Graft loss is infrequent in children; however, severe coronary disease correlates with poor prognosis.     

The urgency of diagnosis and surgical treatment of acute suppurative cholangitis.

Twenty patients with suppurative cholangitis were seen at the Massachusetts General Hospital over a nine year period. Fifteen patients had acute obstructive suppurative cholangitis due to complete obstruction of the common duct, many with coma, hypotension, and positive blood cultures. Sixty per cent of patients were older than seventy years, and most had a history of biliary tract disease. Although most had jaundice, abdominal pain, and fever, clinical symptoms were variable. The diagnosis of cholangitis was made in only 30 per cent of patients before autopsy or surgery. Eighteen patients had calculi in the common duct, and two had primary fibrosis of the ampulla. Patients explored less than 24 hours after admission or deterioration died less often than those operated on after some delay. Most patients underwent common duct exploration and four had a concomitant sphincterotomy. In one instance, cholecystostomy only was performed and this patient died because of ongoing sepsis. The overall mortality was 40 per cent; of those subjected to operation, 25 per cent died in the hospital. Recovery was dramatic among most survivors, and calculous disease did not recur, except for two patients with retained stones. Prophylactic cholecystectomy is recommended to prevent the occurrence of this subtle and highly dangerous syndrome.     

Causes of late mortality in pediatric liver transplant recipients.

OBJECTIVE: This study was undertaken to review the incidence and causes of death in children who have survived long-term (more than 1 year) after liver transplantation (LT). SUMMARY BACKGROUND DATA: No studies of the causes of late mortality in pediatric LT recipients are currently available in the literature. METHODS: The study group consists of 212 pediatric patients who survived more than 1 year after LT. Twenty-three of these patients subsequently died (mean follow-up = 5.3 yr). Hospital records, office charts, and autopsy records were reviewed retrospectively to identify the causes of death. The patients who died were further evaluated by age, gender, length of survival, primary diagnosis, immunosuppression, and retransplantation. RESULTS: The most common cause of death was graft failure, followed closely by infection. In patients dying from graft failure, eight of the nine patients underwent retransplantation and no child survived more than three liver transplants. Overwhelming infections occurred suddenly in eight children who had been previously healthy. Noncompliance was the third most common cause of death, primarily in older children. One child died from a posttransplant lymphoproliferative disorder (PTLD). Actuarial survival at 10 years is 83.7% (based on 100% survival at 1 year). There was no difference in survival based on primary disease. Retransplantation was far more prevalent in the nonsurvivors (47.8%) compared with survivors (13.7%) (p < 0.05). There were no significant differences in survival based on age, gender, or immunosuppression. CONCLUSIONS: Late mortality in children continues to be directly related to complications of LT and immunosuppression, even after the first year of transplantation. This is in contrast to adult liver transplant recipients, where approximately 50% of late deaths were related to LT and the remainder were because of unrelated illnesses.     

Deferred versus prophylactic therapy with gancyclovir for cytomegalovirus in allograft liver transplantation

OBJECTIVE: The aim of this study was to assess the efficacy of deferred versus prophylactic therapy with gancyclovir to prevent cytomegalovirus (CMV) infection or disease in liver transplantation recipients, and to alter the timing of infection or the incidences of acute rejection, chronic rejection, or death. METHODS: We retrospectively studied 89 consecutive liver transplant recipients with a minimum of 1 year follow-up. CMV early antigen detection (pp65) was performed weekly for the first 2 months and thereafter monthly for an additional 10 months. Forty-one recipients were administered prophylactic treatment and (48 recipients) deferred therapy for positive antigenemia. RESULTS: During the first year after transplantation, CMV infection or disease developed in 61% or 12.2% of those treated with prophylactic therapy and 54.1% or 31.3% of those treated with deferred therapy (P = 0.51 or P = 0.032, respectively). The mean time to CMV disease in the prophylactic group was 161 +/- 33 days compared with 82 +/- 27 days for the deferred therapy arm (P < 0.001). Subgroup analysis based on CMV serological status also showed prophylactic treatment significantly diminished CMV disease in the CMV IgG antibody negative group. No patients died in the prophylactic group, and one died in the deferred group (P = 0.54). The incidence of acute rejection episodes was 34% in the prophylactic and 46% in the deferred group (P = 0.26). Chronic rejection was observed in two recipients in the prophylactic group versus one recipient in the deferred arm (P = 0.35). CONCLUSION: Compared with deferred therapy prophylactic therapy with gancyclovir decreased CMV disease and delayed the onset of CMV disease after liver transplantation.     

Immunosuppressive Treatment of Primary Cadaveric Renal Transplant Patients Receiving Kidneys from Non-Heart Beating Donors

Abstract: Since November 1982, 276 primary cadaveric kidney transplants have been performed using kidneys from non-heart beating donors. Between November 1982 and December 1986, 49 transplant patients were treated with cyclosporine and steroid immunosuppressive therapy (CSA regimen). Twenty-seven patients were treated with low dose cyclosporine (initial dosage, 4 mg/kg/day), steroid therapy, and a 21-day course of 500 mg/day anti-lymphocyte globulin (ALG 1 regimen) between January 1987 and December 1987. Seventy-nine patients were treated with low dose cyclosporine (initial dosage, 6 mg/ kg/day), steroid therapy, and a 14-day course of 1,000 mg/day antilymphocyte globulin (ALG 2 regimen) between January 1988 and June 1990, and 85 patients were treated with low dose cyclosporine (initial dosage, 6 mg/ kg/day), steroid therapy, and a 14-day course of 1,000 mg/day antilymphocyte globulin followed by 2 mg/kg/day mizoribine (ALG 3 regimen) between July 1990 and May 1995. Ten patients, who showed hypersensitivity to antilymphocyte globulin therapy, were treated with low dose cyclosporine, steroid therapy, and mizoribine. Finally, 26 patients were treated with FK506 and steroid therapy (FK.506 regimen) between June 1990 and February 1992. Graft survival was 78% at 1 year, 69% at 3 years, 63% at 5 years, and 51% at 10 years in the CSA regimen group and 67% at 1 year, 52% at 3 years, and 48% at 5 years in the ALG 1 regimen group. It was 85% at 1 year, 70% at 3 years, and 62% at 5 years in the ALG 2 regimen group and 87% at 1 year and 67% at 3 years in the ALG 3 regimen group. In the FK506 regimen group, graft survival was 92% at 1 year and 80% at 3–5 years. Never-functioning grafts were observed in 3 CSA patients (6%), I ALG 1 patient (4%), 3 ALG 2 patients (4%), 3 ALG 3 patients (4%), and I FK506 patient (4%). These results indicate that low dose cyclosporine (initial dosage, 6 mg/kg/day), steroid therapy, and a 14 day course of antilymphocyte globulin therapy is beneficial for cadaveric renal transplant patients receiving kidneys from non-heart beating donors; FK506 and steroid therapy might be more effective than cyclosporine based immunosuppressive therapies even in such patients.     

Relationship among epicardial coronary disease, tissue myocardial perfusion, and survival in heart transplantation.

BACKGROUND: Cardiac allograft vasculopathy continues to represent the major limitation to long-term cardiac allograft survival. Routine angiography and intravascular ultrasound fall short in their ability to detect microcirculatory aberrations. Thrombolysis in myocardial infarction (TIMI) myocardial perfusion grades (TMPG) have been used as a measure of microvascular circulation in patients treated for acute myocardial infarction. We studied the correlation of epicardial coronary anatomy with microvascular flow as determined by TMPG and correlated it with patient outcome. METHODS: We enrolled 66 consecutive cardiac transplant recipients (49 men; mean age 52 +/- 13 years; range 15-70 years) undergoing surveillance coronary angiogram during a 9-month period. All angiograms were interpreted for epicardial coronary anatomy by an independent investigator. Another investigator, blinded for clinical data and angiogram interpretation, interpreted TMPGs. TMPG 0 was defined as no apparent tissue-level perfusion; TMPG 1 indicated presence of myocardial blush but no clearance from the microvasculature; TMPG 2 blush cleared slowly; and TMPG 3 indicated that blush began to clear during washout (blush is minimally persistent after 3 cardiac cycles of washout). Cardiac deaths served as the primary outcome variable. RESULTS: Fifty-eight of 66 patients had an abnormal TMPG. Mean TMPG in all these patients was 4.2 +/- 3 (normal is 9). Forty-four patients (Group A) with no angiographic coronary narrowing had TMPG 4.81 +/- 3.1, and 22 patients (Group B) with epicardial coronary narrowing 40% of lumen diameter had TMPG 3.0 +/- 2.5 (p = 0.007). There was no difference in TMPG related to the coronary territory involved. At a mean follow-up of 30 +/- 2.5 months, 6 (13.6%) of 44 patients in Group A had died, and 7 (31.8%) of 22 in Group B had died (p < 0.03). CONCLUSIONS: Microcirculatory aberrations as assessed by tissue TMPG is abnormal across all coronary territories in cardiac transplant recipients and associated with poor survival, suggesting a generalized microvascular involvement even in the presence of a normal angiogram. Patients with focal epicardial coronary narrowing have significantly greater decline in tissue perfusion, independent of the coronary territory involved, and exhibit poor survival compared with patients without epicardial coronary disease.     

Efficacy of pyrimethamine for the prevention of donor-acquired Toxoplasma gondii infection in heart and heart-lung transplant patients

Seven (11%) of the first 65 patients who received heart transplants at Papworth Hospital were mismatched for Toxoplasma gondii. Of these, four (57%) experienced T. gondii infection and two died. The remaining two had severe symptoms and received anti-T-gondii chemotherapy for a year after transplantation. In an attempt to reduce the impact of donor-acquired T. gondii in our heart transplant recipients, we decided in April 1984 to give prophylactic pyrimethamine to all T. gondii-mismatched patients. In this study, 7 years later, we review the efficacy of this policy. Five of 37 (14%) patients given prophylactic pyrimethamine acquired T. gondii infection; only one was symptomatic, and none died. This compares with 100% symptomatic infection in the pre-1984 patients, who did not receive prophylactic pyrimethamine. We believe that our experience has shown that pyrimethamine is effective in reducing the incidence and severity of primary donor-acquired T. gondii infection in mismatched heart and heart-lung transplant recipients.     

Prognosis of moderate coronary artery lesions in heart transplant patients.

BACKGROUND: Despite recent advances in our understanding of allograft vasculopathy, little is known about the evolution of moderate coronary lesions in heart transplant recipients. METHODS: We retrospectively analyzed 58 heart transplant patients undergoing annual coronary angiography who demonstrated a moderate lesion (>30% and <60% diameter stenosis) on any routine annual study. In an attempt to find criteria that could distinguish such patients who were at high risk of disease progression from those at low risk, we reviewed the clinical and biologic features and angiographic and clinical outcomes of patients with and without lesion progression at 1 year. RESULTS: Of the 58 patients who had an initially moderate coronary lesion, 28 (48%) showed progression of the lesion at angiography 1 year later (occlusion of the culprit vessel or progression to a severe lesion >60%) that required revascularization (angioplasty or bypass surgery). The 30 remaining patients showed no lesion progression. At the time of the first angiogram the only criterion which could predict lesion progression at 1 year was the presence of multi-vessel disease (p < 0.0001). Prognosis for these patients was poorer than in those with no disease progression, with a higher proportion of revascularization and sudden death (p < 0.001). Patients without lesion progression at 1 year had neither clinical events nor significant subsequent lesion progression during a mean follow-up of 6 years. CONCLUSIONS: The presence of a moderate coronary stenosis in heart transplant patients justifies a repeat angiogram 1 year later. The use of percutaneous coronary angioplasty in such patients has not been validated, but may be an option to delay or prevent progression to coronary occlusion.     

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.     

Outcome of patients with secondary amyloidosis in dialysis treatment.

Between the years 1974 and 1987, 37 patients with secondary amyloidosis entered dialysis treatment at our department. All had amyloidosis secondary to chronic arthritic disease (35) or to other chronic inflammatory causes (2). Only two patients were maintained on CAPD throughout follow-up; 12 patients (32%) received a kidney transplant. Survival in dialysis at 1 year was 82%, at 2 years 46%, and at 3 years 37%. Survival of amyloidosis patients transplanted at the Finnish transplant centre within the same period was worse at 1 year, but better at 2 and 3 years, 70%, 62%, and 62% respectively, but the difference was not significant. Populations are not compatible, since patients were selected for transplantation. Infection was a common cause of death, 7/18 (39%) deaths; cardiac deaths were less common, only two myocardial infarctions and one cardiac arrhythmia (17%). Symptoms of cardiac amyloid infiltration indicated a poor prognosis, although it did not necessarily predict death of a cardiac cause. Cardiac infiltration of amyloid was more common in autopsy than previously reported (10 of 13 patients), probably indicating longer duration of amyloidosis in patients treated with renal replacement therapy. Patients who died within follow-up had a shorter interval between the start of primary disease and the development of amyloidosis than those who survived, 11.8 versus 17.7 years (P = 0.041), and also a slightly shorter period between diagnosis of amyloidosis and start of dialysis, 3.0 versus 4.4 years (P = 0.129). This indicates that the rate of progression of amyloidosis determines the development of disease-associated complications, and fast progression may predict serious outcome.     

Causes of mortality beyond 1 year after primary pediatric liver transplant under tacrolimus

BACKGROUND: Success of pediatric liver transplantation has improved significantly. Most posttransplant deaths occur early and are related to surgical complications or recipient status at the time of transplantation. The causes of mortality beyond the first year have not been well described. METHODS: Three hundred twenty-six pediatric liver transplants were performed between November 1989 and April 1998 using tacrolimus-based immunosuppression. Patients were followed until March 2002. Mean follow-up was 9.2+/-2.4 years. RESULTS: At 1 year, 279 patients (85.5%) were alive. In the subsequent 12.5 years, 10 of the remaining children died (3.58%) at a mean interval of 3.68+/-1.69 years after transplant. The mean age at transplant was 5.62+/-6.3 years. Six patients had infections as a major contributor to mortality, including two patients with posttransplant lymphoproliferative disorder (PTLD) and one patient that died after retransplantation for hepatitis. Two patients had recurrent malignancy. Other deaths were attributable to chronic rejection, liver failure after being lost to follow-up, and complications of cystic fibrosis. CONCLUSIONS: Pediatric liver transplantation using tacrolimus-based immunosuppression has demonstrated excellent success, with 1- and 10-year survival rates of 85.5% and 82.9%, respectively. Late mortality after pediatric liver transplantation overall remains low, with a rate of 0.32% per year. The most common cause of death was infection (60%), including PTLD-related disease (20%). However, in the recent cohort of patients who underwent transplantation after September 1995, there were no fatal cases of Epstein-Barr virus or PTLD or late mortality thus far, suggesting a benefit from improved infectious disease surveillance using currently available modalities. Mortality from chronic rejection and noncompliance under tacrolimus has been exceedingly rare.     

Antilymphocyte globulin versus OKT3 induction therapy in cadaveric kidney transplantation: a prospective randomized study.

Different induction therapies have been used in renal transplantation to avoid cyclosporine (CsA) nephrotoxicity and early acute graft rejection. This study compares the efficacy of a short course of prophylactic OKT3 to that of antilymphocyte globulin (ALG) in preventing acute renal allograft rejection when administered concomitantly with CsA and steroids. Between March 1988 and December 1990, 140 first-cadaver renal transplant recipients were randomly allocated to two immunosuppression groups--ALG group (n = 68): ALG 15 mg/kg just before transplant surgery, ALG 12 mg/kg the first day after transplant, followed by four doses of 10 mg/kg on alternate days; and OKT3 group (n = 72): OKT3 5 mg just before transplant, followed by four doses of 5 mg/d. Both groups included low-dose CsA and steroids. The incidence of rejection during the first 3 months after transplantation was 15% in the ALG group and 19% in the OKT3 group (NS). Kaplan-Meier estimates of patients free of rejection at 2 years was 85% in the ALG group and 77% in the OKT3 group (NS). The 3-year actuarial graft survival was 82% and 85% (NS), and 3-year patient survival was 97% and 98% (NS), in the ALG and OKT3 groups, respectively. These results indicate that the concomitant association of CsA and ALG or OKT3 constitutes a safe and effective therapeutic strategy that provides a low incidence of rejection and gives good results for patient and graft survival.     

Role of ultrasound screening for gallbladder disease in pretransplant patients

There is no uniform data regarding prophylactic cholecystectomy in patients undergoing renal transplantation with gallbladder disease. Data analyses suggest that posttransplant patients on cyclosporine have a higher incidence of gallbladder calcifications compared with nonimmunosuppressed patients. Laparoscopic cholecystectomy is a relatively safe procedure in modern-day surgery. Taking these facts into consideration, we attempted to compare risks and complications associated with gallbladder disease and eventual cholecystectomy in pretransplant versus posttransplant patients. Between June 1999 and December 2005, 210 renal transplants were performed at our institution. One hundred four patients who had transplants before April 2003 were not screened for gallbladder disease and nine of these patients developed gallbladder disease. These patients form our control group. One hundred six patients who had transplants after April 2003 had pretransplant screening for gallbladder disease and 11 patients were identified with gallbladder disease. These patients form our study group. Nine patients who developed gallbladder disease after renal transplant underwent laparoscopic cholecystectomy with three resulting morbidities (33%), two graft losses (22%), and one mortality (11%). There was one mortality (11%) in this group. One patient in the study group died of acute gallstone pancreatitis. Of the 11 patients who were found to have gallbladder disease on screening, nine patients underwent laparoscopic cholecystectomy with one morbidity and no mortality or graft loss. Given the relative rarity of the critical events in this study (morbidity, mortality, and graft loss), the definitive statistical value of prescreening for gallbladder disease cannot be established. However, our results are suggestive of clinical value and thus we tentatively recommend ultrasound screening for gallbladder disease for all pretransplant patients and laparoscopic cholecystectomy for those identified to have gallbladder disease.     

Less Maintenance Immunosuppression in Lung Transplantation Following Hematopoietic Stem Cell Transplantation From the Same Living Donor

Living‐donor lobar lung transplantation (LDLLT) is one of the final options for saving patients with pulmonary complications after hematopoietic stem cell transplantation (HSCT). We retrospectively investigated 19 patients who had undergone LDLLT after HSCT in Japan. Eight patients underwent LDLLT after HSCT in which one of the donors was the same living donor as in HSCT (SD group), while 11 received LDLLT from relatives who were not the HSCT donors (non‐SD group). In the SD group, three patients underwent single LDLLT. The 5‐year survival rate was 100% and 58% in the SD and non‐SD groups, respectively. In the SD group, postoperative immunosuppression was significantly lower than in the non‐SD group. Two patients died of infection and one died of post‐transplant lymphoproliferative disease (PTLD) in the non‐SD group, while only one patient died of PTLD 7 years after LDLLT in the SD group. Hematologic malignancy relapsed in two patients in the non‐SD group. For the three single LDLLTs in the SD group, immunosuppression was carefully tapered. In our study, LDLLT involving the same donor as for HSCT appeared to have advantages related to lower immunosuppression compared to LDLLT from relatives who were not the HSCT donors.     

Antilymphocyte globulins versus OKT3 as prophylactic treatment in highly sensitized renal transplant recipients

Abstract Monoclonal antibodies were proposed as an effective prophylactic immunosuppressive treatment in highly sensitized patients (HSP). In this study we compared the results obtained in HSP treated with OKT3 or antilymphocyte globulins (ALG). From January 1989 to January 1993, 38 transplantations were performed in patients with high panel reactive antibodies (PRA>50%). The group comprised 22 women and 16 men, mean age 45 ± 2 (23–67) years; ten were second grafts and two were third grafts. Peak PR A was ≥ 80% in 24 sensitized patients and 50–80% in 14 sensitized patients. Patients were randomly assigned to either prophylactic OKT3 ( n = 15) or ALG ( n = 23). Oral cyclosporin A (10 mg/kg) was started at day 8 in the OKT3 group and when the serum creatinine level decreased to 200 μymol/l in the ALG group. OKT3 was systematically withdrawn on day 10 but ALG was stopped only when total blood cyclosporin A concentration reached 150–200 ng/ml. In both groups, azathioprine (150 mg/day) and prednisolone were given. During the first months, 6/15 grafts were lost in the OKT3 group (three hyperacute rejections, one renal vein thrombosis, one steroid-resistant rejection, one death); in the ALG group 4/23 grafts were lost (one hyperacute rejection, two steroid-resistant rejections, one death). Side effects were significantly more frequent in the OKT3 group than in the ALG group. After 12 months of follow up, the graft survival was 71% (27/38) and did not significantly differ (log-rank test, NS) between the OKT3 (60%, 9/15) and the ALG group (78%, 18/23). We conclude that the use of the monoclonal antibody OKT3 as a prophylactic agent in HSP does not improve the early graft survival when compared with prophylactic ALG. Polyclonal antibodies, which react with many epitopes and are much better tolerated seem to offer a good strategy for induction therapy in this population.     

Pulmonary nocardiosis in heart transplant recipients: treatment and outcome

BACKGROUND: Nocardial infections typically affect patients receiving immunosuppressants, occurring early after surgery in 3% to 40% of heart transplant (HTx) recipients. The emergence of antibiotic resistance and occurrence of disease recurrences in AIDS population has engendered controversy about the treatment for immunodepressed HTx patients. METHODS: We present a retrospective study of the diagnosis, treatment and outcome of 560 HTx recipients between 1984 and 2002. RESULTS: Among the five cases of Nocardia infection (0.9%), three cases developed late after HTx (between 3.1 and 11 years follow-up). All patients had pulmonary disease and one in addition had subcutaneous nodules. Microbiological diagnosis required open lung biopsy in one case. All patients were treated primarily with trimethoprim-sulphamethoxazole, but evidence of resistance to sulfonamides led us to change the antimicrobial combination in two cases. Four patients who received one year of antibiogram-guided therapy showed complete healing without recidivism. Three patients died, all due to non-related causes, at follow-ups between 1 and 5 years. In one case a cutaneous recurrence of disease was attributed to noncompliance. CONCLUSIONS: Nocardiosis in current HTx is less common than previously reported. Its incidence seems to be delayed in time with modern immunosuppressants. Given the high incidence of sulfamide resistance, treatment must be guided by antibiotic sensitivity. We believe that maintenance therapy for a whole year is the appropriate option in order to avoid recidivism in this population.     

Paget's sarcoma: limb salvage by custom mega prosthesis: four case reports

Of 4 Paget's sarcoma patients (age range, 55-68 years) underwent limb salvage surgery by custom mega prosthesis, 3 had lesions in the upper extremity and one in the proximal femur. Three of the patients were at stage IIB of the disease, according to Enneking's system of staging musculoskeletal tumours. All 4 patients underwent wide resection with a mean length of 152.5 mm. The defects were reconstructed with custom-made prostheses: proximal humeral prostheses in 2 of the patients, total elbow prosthesis in one, and total hip prosthesis in one. During a mean postoperative follow-up period of 40 months, one died of disseminated disease 14 months after surgery; one remained disease-free; 2 had local recurrence and required amputation, of whom one died of disseminated disease one year after amputation, the other had no further evidence of the disease. We report the functional outcomes of the 2 patients who were alive at the latest follow-up. The 2-year patient survival rate was 50%.     

Impact of proximal or midvessel discrete coronary artery stenoses on survival after heart transplantation.

To assess survival after the development of transplant coronary artery disease, annual angiography reports from 353 heart transplant recipients were reviewed. Fifty-four patients who survived beyond 1 year and in whom moderate-to-severe proximal or midvessel coronary artery disease developed were identified. Moderate-to-severe proximal or midvessel coronary disease was defined for this study as a 40% or more stenosis in 1 or more primary or secondary epicardial arteries. Actuarial survival (Kaplan-Meier) from the time of disease detection in those 54 patients was 67% at 1 year, 44% at 2 years, and 17% at 5 years. Actuarial survival was reduced proportionate to disease severity. Survival for single-vessel disease (> or = 40% stenosis) was 64% at 1 year, 36% at 2 years, and 22% at 5 years. Survival was significantly worse with triple-vessel disease (13% at 2 years; p = 0.01) and intermediate for double-vessel disease (41% at 2 years; p = 0.01). Of 19 patients who underwent retransplantation for coronary artery disease, 13 patients (68%) died at a mean of 24 +/- 20 months (range, 1 to 59), and of 15 patients from whom postmortem or angiographic data were available, 11 patients (73%) showed recurrence of significant coronary artery disease in the new graft. Identification of moderate or severe proximal or midvessel coronary disease at angiography predicts an overall mortality rate of more than 50% at 2 years. The poor survival rate in those who underwent retransplantation (around 50% at 4 years) and the high rate of redevelopment of coronary disease suggest that retransplantation should be reserved for selected candidates with angiographically severe disease, if used at all.     

The Prognostic Significance of Iliac Vessel Calcification in Renal Transplantation

BackgroundPeripheral vascular disease and major extremity amputation are common in patients with established renal failure and are associated with considerable morbidity. Several studies have shown high rates of amputation following simultaneous pancreas-kidney transplantation, but there is minimal literature on the incidence of amputation following renal transplantation. Furthermore, there is little evidence regarding the best method of predicting which patients might be at risk of developing peripheral vascular complications after transplantation.MethodsWe undertook a 5 year follow-up on the cohort of patients who were on our renal transplant waiting list 5 years ago (January 2007). At this time, it was standard practice within our unit for all patients to have routine pelvic x-rays to assess for vascular calcification of the iliac vessels at the time of activation onto the transplant waiting list. Any patients with moderate/severe calcification on x-ray, which may complicate transplantation, were referred for computed tomography angiogram (CTA) of their aorto-iliac vessels. Mortality, transplantation outcomes, and amputation rates at 5 years were correlated with the severity of calcification on preoperative imaging.ResultsOne hundred eighty-seven patients were on the waiting list for renal transplantation in January 2007 (92 men; mean age, 58.3 +/? 6.2 years). Ninety-three patients received a transplant during the subsequent 5 years. By January 2012, 82 patients had a functioning transplant, 45 remained on the waiting list (5 suspended), 40 patients had died, and 20 were alive but no longer on the waiting list. Seventy-three (39.5%) had moderate or severe calcification on plain x-ray and went on to have CTA. Of these patients, 16 (21.9%) had extensive calcification affecting all the iliac vessels and were removed from the waiting list as a result. Preoperative imaging was useful in determining the side for surgery in a further 18 patients (24.3%). Twenty-two patients developed vascular complications. Nineteen (86.4%) had moderate-severe vascular calcification on imaging. Four of the patients with vascular complications (18.2%) underwent transplantation (2 had below knee amputation (BKA) prior to transplantation; 1 developed distal ischemia on the same side as the transplantation 2 years postoperatively; 1 had bilateral above knee amputation (AKA) approximately 2 years after transplantation). Eleven (50%) of the patients with vascular complications were dead at 5 years of follow-up. Mortality and amputation rates were higher in patients with moderate-severe calcification than minimal calcification (30.1% vs 16.6%; P = .02 and 10.9% vs 1.8%; P = .003, respectively). There was no difference in rates of delayed graft function (DGF), biopsy-proven acute rejection (BPAR), or creatinine at 1 year between patients who underwent transplantation with moderate-severe calcification and those without, however, intraoperative vascular complications (26.7% vs 3%; P < .001), graft loss (28.1% vs 3.4%; P = .01), and death with a functioning transplant (9.7% vs 1.6%; P = .04) rates were higher in patients with extensive calcification compared with those without.ConclusionsPlain x-ray of the pelvis is a useful screening tool to identify those patients who may require further detailed vascular imaging prior to transplantation. Amputation rates following renal transplantation are low and peripheral vascular disease (PVD) in isolation should not preclude transplantation. Nevertheless, significant vascular calcification is predictive of mortality both with and without transplantation and graft loss in patients with a renal transplant.     

Cardiac Risk Assessment in Kidney Transplant Candidates: Clinical Usefulness of Different Guidelines

Although cardiovascular (CV) assessment is recommended to minimize perioperative risk in all potential kidney transplant recipients, the utility and reliability of various assessment methods are not well established. In this study, we investigated the CV evaluations and outcomes of standardized CV assessment protocols (Lisbon and American Society of Transplantation [AST]) in potential kidney transplant recipients. Data were analyzed for 266 end-stage renal disease patients (mean age 45.4 ± 13 years, female-to-male ratio 126:140) accepted for kidney transplantation wait-listing. Patients were classified as low and high cardiac risk according to their first cardiac evaluation. Major cardiovascular events (CVEs) and deaths were recorded. At the end of follow-up (median 639 days), 72 (27.1%) patients underwent kidney transplantation. A total of 49 patients (18.4%) had CVEs and 42 (15.8%) patients died. Being over 45 years of age and having dialysis vintage over 1 year were found to be independent risk factors for CVEs. Forty-eight out of 60 high-risk patients evaluated with noninvasive tests had negative results. Twelve out of these 48 patients had a CVE in due course. Among 10 patients who underwent coronary angiography, 1 had a CVE and 1 died. The sensitivity and specificity of the AST guidelines (area under the curve = 0.647, P = .005, sensitivity 83%, specificity 54%) were higher than Lisbon. In conclusion, the predictive risk factors for CVEs were age over 45 years and dialysis vintage over a year. Our results also suggest that exercise electrocardiography and myocardial perfusion scintigraphy for cardiac evaluation are less sensitive in CVE prediction. We recommend clinicians to use the AST guidelines and to prioritize coronary angiography in pretransplant CV assessment.