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PubMed1989

[Present status of lung transplantation and heart-lung transplantation].

On the basis of development of the immunosuppressive drugs such as cyclosporine since 1981, many successful cases have been reported on clinical lung and heart-lung transplantations. A principal disease for a single lung transplantation is pulmonary fibrosis. Obstructive lung disease and bilateral pulmonary sepsis such as cystic fibrosis and bronchiectasis are now considered to be done double lung transplantation. On the other hand, heart-lung transplantations have been performed not only on primary pulmonary hypertension and Eisenmenger's syndrome but also on restrictive and/or obstructive lung disease. Today's subjects on lung and heart-lung transplantations are as follows 1) The establishment of preservation method of transplant organs. 2) Development of an appropriate technique of monitoring for the rejected lungs. 3) Assessment and improvement of bronchial anastomotic healing. 4) Investigation of the causal factors on reimplantation response and obliterative bronchitis. Long-term survivals have been reported in both lung and heart-lung transplantation. Therefore, many attempts have been increasingly made in order to obtain the heart beating cadaver donors in Japan. But experimental study on the unsolved problems of transplantation should be continuously carried out for successful clinical lung and heart-lung transplantation.

Graft Rejection↗
PubMed2001

Allogenic stem cell transplantation as salvage therapy for patients relapsing after autologous transplantation: experience from a single institution.

The prognosis of patients relapsing after an autologous transplant (autoSCT) is very poor. Allogenic stem cell transplantation (alloSCT) offers the possibility of curing some of these patients, at the cost, however, of a high transplant related mortality (TRM). The aim of this study was to analyze the outcome of 14 consecutive patients with hematologic malignancies, from a single institution, who underwent alloSCT for progressive disease after autoSCT. Patients had relapsed at a median of 11.5 months (range 2-72) after autoSCT and they underwent alloSCT at a median of 25.5 months (range 7-73) from the first transplant. Ten patients received HLA-identical related peripheral blood progenitor cells, three patients underwent matched-unrelated donor marrow transplants, and one patient received a mismatched related transplant. Conditioning regimens consisted of total body irradiation plus cyclophosphamide (n=5) or melphalan (n=1), or high-dose combination chemotherapy (n=8). Cyclosporin A and methotrexate were administered as graft-versus-host disease (GVHD) prophylaxis. Eight patients (57%) developed grade II-IV acute GVHD. All evaluable patients (n=6) presented extensive chronic GVHD. Overall survival at 1 year was 16% (median 3.5 months, 95% CI 0.7-10.3). Ten patients (71%) died from transplant related complications at a median of 3.5 months (range 0.7-11). Only one patient died of recurrent disease. Three patients remain alive and in complete remission at the time of this report (4, 20 and 20 months, respectively). In conclusion, alloSCT offers the possibility of a sustained control of the disease in some patients who relapse after an autoSCT. However, the procedure is associated with a high transplant-related mortality. Better results might be obtained by carefully selecting patients and by reducing the intensity of the preparative regimen.

Adult↗
PubMed1997

Combined liver-total bowel transplantation has no immunologic advantage over total bowel transplantation alone. A prospective study in a porcine model.

BACKGROUND: Rejection remains a major obstacle to successful bowel transplantation in humans. It has been suggested that a simultaneous liver transplant would shield the bowel graft from immunologic attack, but the liver shortage would be aggravated. In a preclinical model, we studied the influence of simultaneous liver grafting by comparing the incidence of early bowel rejection after combined liver-total (small- and large-) bowel transplants vs total bowel transplants alone. METHODS: We assessed the incidence of early post-transplant rejection, graft-vs-host disease, and infection after combined liver-total bowel transplants (group 1, n = 10) and total bowel transplants alone (group 2, n = 9) in outbred Yorkshire Landrace pigs. Liver and bowel grafts were transplanted orthotopically with portal vein drainage after recipient hepatectomy (group 1) and total enterectomy (groups 1 and 2). Posttransplant immunosuppression was performed with intravenous tacrolimus (whole blood levels, 15 to 30 ng/mL) and prednisolone. In groups 1 and 2, bowel biopsy specimens from the ileostomy were obtained daily. In group 1, liver biopsy specimens were obtained weekly. Rejection was graded according to a 4-point scoring system (none, mild, moderate, and severe). RESULTS: Overall graft survival at days 7, 14, and 21 was 89%, 44%, and 11%, respectively, in group 1 vs 100%, 100%, and 86%, respectively, in group 2 (P < .001). Death rates owing to (irreversible) rejection at days 7, 14, and 21 were 0% in groups 1 and 2 (P = .48). Grading of bowel rejection episodes, based on the results of daily biopsy specimens, was not significantly different between the groups whether on individual days or overall. In group 1, the incidence of liver rejection episodes was as high as 66% (day 14 and at autopsy). At autopsy, generalized graft-vs-host disease (skin, native intestine, and native liver) was noted in 55% of group 1 and 43% of group 2 pigs (P = .55). Graft-vs-host disease was noted concurrently with rejection episodes of the liver or bowel grafts. CONCLUSIONS: Simultaneous liver grafting did not further reduce the incidence of early bowel rejection or graft-vs-host disease when compared with total bowel transplants alone. Based on the results of this preclinical study, simultaneous liver grafting is not indicated for patients with short-bowel syndrome and normal liver function.

Animals↗
PubMed1997

Hepatitis G virus infection before and after liver transplantation. Liver Transplantation Database.

The hepatitis G virus is a newly discovered flavivirus that has been linked to acute and chronic hepatitis of unknown cause. We determined the prevalence of hepatitis G virus infection in 179 selected patients undergoing liver transplantation at three centers participating in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Liver Transplantation Database. Pretransplantation and posttransplantation specimens were tested for hepatitis G virus RNA by polymerase chain reaction. Before transplantation, 9 of 38 (24%) patients with fulminant hepatic failure, 9 of 62 (15%) with cryptogenic cirrhosis, 3 of 35 (9%) with cholestatic liver disease, and 5 of 44 (11%) with chronic hepatitis C were positive for hepatitis G virus RNA (P = .27). Patients with and without viral RNA were similar in clinical features, liver test abnormalities, and survival after transplantation. Posttransplantation serum specimens were tested from 73 patients; 9 of 11 (82%) who were positive for viral RNA before transplantation remained positive, but 35 of 62 (56%) patients who were initially negative became positive after transplantation, a rate consistent with that predicted from the number of blood products administered. Only 5% of de novo HGV infections could be attributed to preexisting hepatitis G virus RNA in the donor. Comparison of patients with and without hepatitis G virus infection showed no difference in incidence of hepatitis after transplantation. Thus, hepatitis G virus infection was present in 15% of patients before and appeared de novo in half of patients after liver transplantation. Although hepatitis G virus infection was not associated with poor outcome, the frequency of this infection after transplantation calls for further long-term evaluation.

Adult↗
PubMed1993

Renal transplantation in children and adolescents: the 1992 annual report of the North American Pediatric Renal Transplant Cooperative Study.

From January 1987 to January 1992 the North American Pediatric Renal Transplant Cooperative Study registered and followed 2,037 children and adolescents 17 years of age or less who received 2,197 renal transplants at 75 participating centers in the United States and Canada. The cumulative experience over 5 years of data collection demonstrated trends in renal transplantation practice for pediatric patients. The percentage of live donor organ recipients receiving donor-specific blood transfusions decreased from 40% in 1987 to less than 12% in 1991; random blood transfusions also were used less frequently during the most recent 2 years of the study. Immunosuppressive therapy on posttransplant day 0 or 1 with polyclonal and monoclonal antilymphocyte agents was used in over 40% of transplants. There was also a notable preference for the combined use of prednisone, azathioprine and cyclosporine as maintenance immunosuppression. The percentage of live donor source graft recipients receiving cyclosporine increased from 78% in 1987 to 90% in the most recent year, and considered together, nearly 90% of live donor and cadaver organ recipients received cyclosporine. The observed graft survival probabilities for live donor grafts were 88%, 83%, 81% and 76% at years 1-4 post transplantation, respectively. The 1st through 4th year graft survival probabilities for cadaver grafts were 74%, 68%, 63% and 58%, respectively. The five most common causes of pediatric end-stage renal disease have remained as: hypoplastic-dysplastic kidney, obstructive uropathy, focal segmental glomerulosclerosis, reflux nephropathy and systemic immunological diseases throughout the 5 years of this study. There has been a decrease in children 2 years of age or less undergoing transplant surgery. On average, 50% of graft failures were due to the various forms of rejection. Vascular thrombosis (14%) and recurrence of primary renal disease (7%) were the next most frequently encountered causes of graft failure. Poor linear growth was identified as a problem affecting the majority of children both before and after transplantation. Post transplant linear growth was best among recipients less than 6 years of age at transplantation and recipients of all ages who received alternate-day prednisone. A total of 16 malignancies were reported during the 5 years of study. A total of 105 deaths were reported, with infection (41%) the most common primary cause of death. The 2-year patient survival probabilities were 95.5% and 93% for recipients of live donor and cadaver grafts, respectively.

Adolescent↗
PubMed2004

[Organ transplantation in human immunodeficiency virus-infected patients. Results of a survey in German transplantation centres].

BACKGROUND: Despite considerable advances following the introduction of highly active antiretroviral therapy, organ transplantation is usually denied categorically for human immunodeficiency virus (HIV) patients, and it is presented in German transplantation law as a contraindication. Today, this should be questioned critically. METHOD: A survey at all 87 German transplant centres was done concerning (1) how many HIV-positive patients were transplanted before and after February 2000, (2) willingness of the centres to transplant HIV-infected patients in the future, and (3) course of transplanted HIV patients so far. RESULTS: With a response rate of 78%, 39% of the questioned centres were accepting HIV patients in the future for transplantation, and 39% rejected this. Twenty percent voted for individual case decision. Three centres had practiced liver transplantation in 11 patients. CONCLUSION: The decision to transplant HIV-positive patients in Germany is mostly based on individual cases and not refused in general. However, prospective studies on this issue are justified and needed.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Pediatric liver transplantation: from the full-size liver graft to reduced, split, and living related liver transplantation.

Between 1984 and 1996, the authors performed 499 liver transplants in 416 children less than 15 years old. The overall patient survival at 10 years was 76.5%. It was 71.3% for the 209 children grafted in 1984-1990; 78.5% for biliary atresia (n = 286), 87.3% for metabolic diseases (n = 59), and 72.7% for acute liver failure (n = 22). The 5-year survival was 73.6% for the 209 children grafted in 1984-1990 and 85% for the 206 grafted in 1991-1996. Scarcity of size-matched donors led to the development of innovative techniques: 174 children who electively received a reduced liver as a first graft in our center had a 5-year survival of 76% while 168 who received a full-size graft had a survival of 85% (NS). Results of the European Split Liver Registry showed 6-month graft survival similar to results obtained with full-size grafts collected by the European Liver Transplant Registry. Extensive use of these techniques allowed the mortality while waiting to be reduced from 16.5% in 1984-1990 to 10% in 1991-1992. It rose again to 17% in 1993, leading the authors to develop a program of living related liver transplantation (LRLT). The legal and ethical aspects are analyzed. Between July 1993 and October 1997, the authors performed 53 LRLTs with 90% survival. In elective cases, a detailed analysis was made of the 45 children listed for LRLT between July 1993 and March 1997 and the 79 registered on the cadaveric waiting list during the same period. Mortality while waiting was 2% and 14.5% for the LRLT and cadaveric lists, respectively. The retransplantation rate was 4.6% and 16.1% for LRLT and cadaveric transplants, respectively. Overall post-transplant survival was 88% and 82% for children who received a LRLT or a cadaveric graft, respectively. Overall survival from the date of registration was 86% and 70% (P < 0.05) for LRLT or cadaveric LT respectively. The 2-year post-transplant survival in children less than 1 year of age at transplantation was 88.8% and 80. 3% with a LRLT or cadaveric graft, respectively; patient survival after 3 months post-transplant was 95.8% and 91.9% for stable children waiting at home, 93.7% and 93.7% in children hospitalized for complications of their disease, and 89.5% and 77.7% for children hospitalized in an intensive care unit at the time of transplantation for children who received a LRLT or cadaveric graft, respectively. It is concluded that LRLT seems to be justified for multidisciplinary teams having a large experience with reduced and split liver grafting.

Child↗
PubMed1991

Survival of DNA HLA-DR typed and matched cadaver kidney transplants. The Collaborative Transplant Study.

The clinical value of serological HLA matching for cadaver kidney transplantation remains uncertain because the success rate for HLA-matched cadaver transplants is lower than that of HLA-matched sibling grafts. Up to 25% of serological HLA-DR typings may be incorrect when compared with a more accurate DNA-RFLP method, and we have now examined whether incorrect HLA-DR typings account for the lower than expected success rates of HLA-matched cadaver transplants. 58 transplant centres took part in this study and DNA was extracted from over 4000 samples of frozen tissue at the study centre. 8 laboratories then completed blind RFLP typing for HLA-DR. Serological typing data were reported by individual transplant laboratories. 29 of 107 transplants (27%) that were reported as HLA A, B, DR compatible and 76 of 273 (28%) transplants that were reported as HLA B, DR compatible according to serological typing were found to be HLA-DR mismatched by DNA typing. The one-year transplant success rate for DNA-matched HLA, A, B, DR grafts was 87% compared with 69% for mismatched grafts (p less than 0.02); the corresponding success rate for DNA-matched HLA B, DR grafts was 85% compared with 72% for mismatched grafts (p less than 0.01). Many transplants that were previously thought to be HLA matched are mismatched, and this finding may account for previously unexplained graft failures.

Cadaver↗
PubMed2005

Utility of post-transplant anti-HLA antibody measurements in pediatric cardiac transplant recipients.

BACKGROUND: Studies have associated anti-HLA antibodies detected by panel-reactive antibody (PRA) with increased risk for rejection and transplant coronary artery disease (TCAD) in adults, but the role of PRAs in monitoring immunologic status after pediatric cardiac transplantation has not been described. METHODS: We reviewed post-transplant PRAs in 96 pediatric heart recipients. PRAs were performed concurrently with endomyocardial biopsy and if rejection was suspected. The presence of anti-HLA IgG antibodies was defined as >10% reactivity. Pre-transplant variables, including age, race, gender, pre-transplant PRAs and presence of a mechanical assist device, were correlated with post-transplant PRAs. Outcome variables included rejection history, TCAD incidence and survival. RESULTS: The mean age of patients was 9.0 +/- 6.8 years. A mean of 8.1 +/- 5.3 PRAs were measured over a follow-up period of 4.8 +/- 2.7 years. There was a mean of 0.55 +/- 0.71 rejection events per patient-year, and TCAD was detected in 19 (22%) patients. Nineteen patients (20%) had anti-HLA Class I antibodies and 37 (39%) had Class II antibodies detected after transplant. There was no association between Class I antibodies and survival, TCAD or rejection. Class II antibodies were associated with worse survival and a decreased time-free of TCAD. Class II antibodies were also associated with rejection at the time of measurement (sensitivity 17%, specificity 94%) and for the ensuing 3 months (sensitivity 12%, specificity 94%). CONCLUSIONS: Class II anti-HLA antibodies correlate with worse patient outcomes and rejection episodes after pediatric cardiac transplant. A low sensitivity precludes use as a sole diagnostic tool, but post-transplant PRAs may be an important adjunct in a multi-faceted algorithm to assess immunologic status.

Adolescent↗
PubMed2004

Successful listing of patients for liver transplant was related to participation of referring doctor in the transplant program.

INTRODUCTION: Experience with liver transplantation is limited in many parts of Asia. Therefore, patients from nontransplant centers may not be referred in a timely fashion for transplants. Our aim was to evaluate the pattern of referral for liver transplantation and their outcomes in Singapore. METHODS: Consecutive patients referred from 1990 to 2001 were reviewed. Patients from any hospital in Singapore (or the region) could be referred to the program. They were discussed at the weekly meetings. Appropriate patients were placed on the waiting list. "Pending" indicated that the disease was early or there were unsettled medical or social issues. Unsuitable patients were "rejected" for transplant. RESULTS: There were 385 patients referred over a 12-year period. Hepatitis B cirrhosis and hepatocellular carcinoma (HCC) were the most common indications among adults, whereas biliary atresia was the most common for children. Pediatric patients were more likely than adult patients to be listed for transplant (53/76 vs 106/309, P < .001). Patients referred by regular attendees of the program were more likely to be accepted than nonattendees (38% vs 25%, P = .04). "Disease too early", "advanced HCC", and "refusal by family members" were the most common reasons for rejection. CONCLUSION: Members of the Liver Transplant Program were more likely to refer suitable patients for transplant at the appropriate time. Better interaction between gastroenterologists inside and outside the transplant program would help to improve the timing of referrals for liver transplantation, and hence, patient survival.

Adult↗
PubMed1997

The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg, Maryland.

PURPOSE: To assess impact of cytomegalovirus (CMV) donor-recipient serostatus, infection, or disease on development of invasive fungal infection in orthotopic liver transplant recipients. PATIENTS AND METHODS: An analysis of prospectively collected data in 146 liver transplant recipients (intention to treat cohort) from 4 tertiary care, university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). Patients were observed for 1 year after transplantation for the development of CMV infection, CMV disease, CMV pneumonia, as well as for the development of opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine and throat and every other week of buffy coat for CMV for 2 months, then monthly for 6 months, at 1 year, and at the time of any clinical illness. Pre- and posttransplant variables including CMV-serostatus of donor and recipient, fungal isolation from sterile body sites, fungemia, bacteremia, antibiotic use, immunosuppression, treatment for rejection, and volumes of blood products were measured. RESULTS: Survival analysis demonstrated that 36% of patients with CMV disease developed invasive fungal disease within the first year post-transplant compared with 8% of those without CMV disease (P < 0.0001). One-year mortality in patients with invasive fungal disease was 15 of 22 (68%) compared with 23 of 124 (19%) in those without invasive fungal disease (P < 0.001). A multivariable, time-dependent analysis demonstrated that being a CMV-seronegative recipient of a CMV-seropositive donor organ (P < 0.001), having bacteremia (P = 0.001), UNOS (United Network for Organ Sharing) status 4 (need for life support measures) at transplant (P = 0.002), and volume of platelets (P = 0.002) were independently associated with invasive fungal disease. Restriction of cases of invasive fungal disease to those that occurred more than 2 weeks after transplant demonstrated an association with CMV disease (P = 0.003), bacteremia (P = 0.003), need for life support (P = 0.03), and volume of blood products transfused (P = 0.02). CONCLUSION: CMV disease or being a CMV-seronegative recipient of a CMV-seropositive donor organ is an important predictor for invasive fungal disease following orthotopic liver transplantation.

Adolescent↗
PubMed2002

[Post-transplantation vaccination of bone-marrow transplant recipients].

BACKGROUND: Patients subject to bone marrow transplantation (BMT) and other blood stem cell transplantations are severely immunocompromised after transplantation. Some studies have suggested that post-transplantation loss of acquired immunity may play a role. The objective of this study was to determine the susceptibility to vaccine-preventable diseases in people subject to BMT and the serologic response after vaccination. PATIENTS AND METHOD: Study population was people subject to transplantation at least 6 months before initiating vaccination and without immunosuppressive treatment at that time. A prevaccination serologic analysis was carried out, and the hepatitis B, the adult tetanus-diphtheria (Td), the IPV, the influenza and the pneumococccal vaccines were administered in accordance with standard guidelines Depending on the immune status of the patient according to the serologic analysis, the MMR vaccine was administered no sooner than 18 months after transplantation. After vaccination, a serologic analysis was carried out to determine the response. RESULTS: The mean time SD between transplant and the initiation of vaccination was 3.2 2.9 years. Of the 122 recipients of BMT (average age 35.8 13 years; 54.2% male), 51.7% received an allogenic and 48.3% an autologous transplant. Before vaccination, the susceptibility was 48.2% for tetanus, 66.7% for diphtheria, 74.1% for pertussis, 85.9% for hepatitis B, 13.4% for measles, 36.7% for rubella and 9.2% for mumps. The rates of seroconversion with protective titers after vaccination for tetanus, diphtheria and hepatitis B were 94%, 67% and 75% respectively. The response to the MMR vaccine was greater than 70%, with a second dose of the vaccine being needed in 26% of patients. CONCLUSIONS: Susceptibility to vaccine-preventable diseases in transplanted patients is high. The acceptable response to vaccination justifies the development of specific programs. Given the special characteristics of this group of patients, vaccination programs must be simple and flexible.

Adolescent↗
PubMed1997

Epstein-Barr virus-associated post-transplant lympho-proliferative disease of donor origin in liver transplant recipients.

BACKGROUND/AIMS: Post-transplant lymphoproliferative disease, a potential complication of solid organ transplantation, occurs in about 3% of orthotopic liver transplant recipients. We report the genetic and virological characterization of two cases of post-transplant lymphoproliferative disease that occurred early (4 and 6 months) after orthotopic liver transplant as large-cell non-Hodgkin's lymphomas located at the hepatic hilum. METHODS: Lymphomatous tissues were analyzed for clonality and presence of Epstein-Barr virus (EBV) sequences by Southern blot, polymerase chain reaction, and in situ hybridization techniques. RESULTS: The tumors in both cases were sustained by a clonal proliferation of B lymphocytes containing type A EBV DNA. Moreover, in situ hybridization with a digoxigenin-labeled EBV-specific probe evidenced a strong nuclear signal in most of the neoplastic cells. DNA microsatellite analysis at three different loci detected alleles of donor origin in both tumor samples, suggesting that the neoplastic B cells were of donor origin. CONCLUSIONS: EBV-infected donor B lymphocytes might be responsible for intragraft post-transplant lymphoproliferative disease in orthotopic liver transplant recipients. As 20 to 30% of post-transplant lymphomas involve the graft itself, donor-derived post-transplant lymphoproliferative disease might be more frequent than presently appreciated. Prospective studies are needed to assess its real incidence and identify possible risk factors.

B-Lymphocytes↗
PubMed2002

[Persistence of oxidative stress after heart transplantation: a comparative study of patients with heart transplant versus chronic stable heart failure].

INTRODUCTION AND OBJECTIVE: Chronic heart failure (CHF) is associated with oxidative stress. Heart transplantation, an important therapeutic alternative in these patients, could reduce oxidative stress by improving cardiac function. Our aim was to evaluate post-heart transplantation oxidative stress. PATIENTS AND METHOD: We studied three experimental groups: a) heart transplant recipients without evidence of rejection (n = 11); b) NYHA class III CHF patients (n = 19), and c) healthy control subjects (n = 14). Oxidative stress was assessed by measuring plasma malondialdehyde levels (MDA), and determining the enzymatic activities of glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD). RESULTS: The demographic characteristics of the three groups were similar. Mean time from transplantation was 20.0 4.8 months. Mean MDA plasma levels in heart transplantation and CHF patients were significantly higher than in normal subjects (3.35 0.8; 3.27 1.7 y 0.9 0.3 microM, respectively). GSH-Px activity increased after transplantation compared to control subjects (0.40 0.06 and 0.33 0.05 U/g Hb, respectively), but not the CHF group. A significant decrease in SOD activity was found in the heart transplant vs. CHF group (0.44 0.1 vs. 0.87 0.6 U/mg Hb). There were no differences in CAT values between heart transplant and CHF patients. CONCLUSION: These findings demonstrated the presence of permanent oxidative stress in patients who have undergone heart transplantation, characterized by an increase in MDA and a decrease in SOD activity, despite an increase in GSH-Px activity.

Adult↗
PubMed2001

Pre-transplant corticosteroid use and outcome in lung transplantation.

BACKGROUND: The early experience of lung transplantation was plagued with airway anastomotic complications. The use of corticosteroids in the pre-transplant period has been implicated as a major contributing factor in bronchial dehiscence, and many patients have been denied transplantation on the basis of corticosteroid use. We conducted the current study to assess the risks associated with pre-transplant corticosteroid use. METHODS: We analyzed records of 73 single- and bilateral-single lung transplant recipients who had chronic obstructive pulmonary disease or alpha(1)-antitrypsin deficiency as their underlying disease from 1986 to 1996. Twenty-six patients (steroid group) received daily corticosteroid therapy (prednisone, 1.5 to 40 mg/day) up to the time of transplantation, whereas 47 patients did not receive chronic corticosteroids and had no corticosteroid therapy within 3 months of transplantation (non-steroid group). RESULTS: The demographic profiles of the 2 groups were comparable. We noted no statistical significances in length of hospital stay, duration of intensive care, and post-operative pulmonary function. The rates of cytomegalovirus infection, acute rejection, bronchiolitis obliterans syndrome, and survival were also similar. The non-steroid group seemed to have a higher rate of bronchial stenosis at 3 years (29% vs 6%, p = 0.03). Bronchial dehiscence did not occur in either study group. CONCLUSIONS: Pre-transplant use of corticosteroids does not adversely affect outcome following lung transplantation.

Adult↗
PubMed2003

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.

Adult↗
PubMed2003

A comparison of intravascular ultrasound with coronary angiography for evaluation of transplant coronary disease in pediatric heart transplant recipients.

BACKGROUND: The purpose of this study was to assess the sensitivity of coronary angiography versus intravascular ultrasound for detecting significant transplant coronary artery disease in children. We also examined associations between potential risk factors for transplant coronary artery disease and intravascular ultrasound findings, and evaluated the safety of intravascular ultrasound. METHODS: All pediatric heart transplant patients who had intravascular ultrasound following routine coronary angiography were included. Transplant coronary artery disease was quantified by assigning Stanford classes and calculating intimal indices for intravascular ultrasound images. These findings were compared with qualitative coronary angiography findings. Risk factors for transplant coronary artery disease, cardiac events and complications were recorded. RESULTS: Sixteen patients had 27 intravascular ultrasound procedures during the study period. All patients had evidence of transplant coronary artery disease at their latest intravascular ultrasound study. Of the patients whose most severely afflicted coronary artery underwent both imaging modalities at the latest study, 50% had significant transplant coronary artery disease (Stanford Class >/=II) by intravascular ultrasound and normal coronary angiography. A higher mean first-year biopsy score may be associated with significant transplant coronary artery disease by intravascular ultrasound, but a large number of patients will be required to determine this with statistical certainty. One major complication occurred early in the experience. CONCLUSIONS: In children, intravascular ultrasound is more sensitive for detecting significant transplant coronary artery disease than coronary angiography, but may add cost, time and potential morbidity to screening protocols. Prospective, multicenter studies are needed to best utilize intravascular ultrasound in this patient population.

Adolescent↗
PubMed1999

Early post-transplant medical compliance and mental health predict physical morbidity and mortality one to three years after heart transplantation.

BACKGROUND: Poor medical compliance has been held responsible for a large proportion of deaths occurring subsequent to initial postoperative recovery. However, beyond clinical reports, there has been little empirical examination of this issue, or of the extent to which major psychiatric disorder and failure to adjust to the transplant predict long-term physical morbidity and mortality. We prospectively examined whether a full range of compliance behaviors and psychiatric outcomes during the first year post-transplant predicted subsequent mortality and physical morbidity through 3 years post-transplant. METHODS: A total of 145 heart recipients who had received detailed compliance and mental health assessments during the first year post-transplant were followed up at 3 years post-transplant. Interview data and corroborative information from family members were used to determine compliance in multiple domains, psychiatric diagnoses, and psychiatric symptomatology during the first year post-surgery. Medical record reviews were performed to abstract data on acute graft rejection episodes, incident cardiac allograft disease (CAD) and mortality from 1 to 3 years post-transplant. RESULTS: After controlling for known transplant-related predictors of outcome, multivariate analyses yielded the following significant (p < 0.05) results: (a) risk of acute graft rejection was 4.17 times greater among recipients who were not compliant with medications; (b) risk of incident CAD was elevated by persistent depression (Odds Ratio, OR = 4.67), persistent anger-hostility (OR = 8.00), medication noncompliance (OR = 6.91), and obesity (OR = 9.92); and (c) risk of mortality was increased if recipients met criteria for Post-Traumatic Stress Disorder related to the transplant (OR = 13.74). CONCLUSIONS: The findings, plus data we have previously reported that showed which patients are most likely to have compliance and psychiatric problems early post-transplant, suggest that interventions focused on maximizing patients' psychosocial status in these areas may further improve long-term physical health outcomes in this population.

Adult↗