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Pre-transplant reversible pulmonary hypertension predicts higher risk for mortality after cardiac transplantation.

BACKGROUND: Pre-transplant fixed pulmonary hypertension is associated with higher post-transplant mortality. In this study, we assessed the significance of pre-transplant reversible pulmonary hypertension in patients undergoing cardiac transplantation. METHODS: Overall, we studied 182 patients with baseline normal pulmonary pressures or reversible pulmonary hypertension, defined as a decrease in pulmonary vascular resistance (PVR) to < or =2.5 Wood units (WU), who underwent cardiac transplantation. Multiple recipient and donor characteristics were assessed to identify independent predictors of mortality. RESULTS: The average duration of follow-up was 42 +/- 28 months. Forty patients (22%) died during the follow-up period. Baseline hemodynamics for alive vs dead patients were as follows: pulmonary artery systolic (PAS) 42 +/- 15 vs 52 +/- 15 mm Hg; PA diastolic 21 +/- 9 vs 25 +/- 9 mm Hg; PA mean 28 +/- 11 vs 35 +/- 10 mm Hg; transpulmonary gradient (TPG) 9 +/- 4 vs 11 +/- 7 mm Hg (all p < 0.05); total pulmonary resistance 7.7 +/- 4.8 vs 8.8 +/- 3.2 WU (p = 0.08); and PVR 2.3 +/- 1.5 vs 2.9 +/- 1.6 WU (p = 0.06). In an unadjusted analysis, patients with PAS >50 mm Hg had a higher risk of death (odds ratio [OR] 5.96, 95% confidence interval [CI] 1.46 to 19.84 as compared with PAS < or =30 mm Hg). There was no significant difference in survival among patients with baseline PVR <2.5, 2.5 to 4.0 or >4.0 WU, but patients with TPG > or =16 had a higher risk of mortality (OR 4.93, 95% CI 1.84 to 13.17). PAS pressure was an independent predictor of mortality (OR 1.04, 95% CI 1.02 to 1.06). Recipient body mass index, history of sternotomy; and donor ischemic time were the other independent predictors of mortality. CONCLUSION: Pre-transplant pulmonary hypertension, even when reversible to a PVR of < or =2.5 WU, is associated with a higher mortality post-transplant.

Adult↗

Detection of anti-MICA antibodies in patients awaiting kidney transplantation, during the post-transplant course, and in eluates from rejected kidney allografts by Luminex flow cytometry.

Previously we have reported on the development of antibodies against MICA alleles in kidney transplant recipients. These alloantibodies have now been determined using a new assay using Luminex beads bound to soluble recombinant MICA antigens produced in insect cells. In the present study we have analyzed sera from 85 kidney transplant recipients on the waiting list and 66 patients transplanted within the last 4 years and 59 acid eluates obtained from allograft nephrectomy specimens. Many of the patients in those groups were sensitized and some had previous transplants (waiting list: 15%; post-tx: 7.6%; eluates 22%) and their sera were found to contain anti-human leukocyte antigen (HLA) and anti-MICA antibodies. Anti-MICA antibodies were detected in 21/85 (24.7%) of the waiting list patients and in 15/66 (22.7%) of the transplanted recipients; 11 of the eluates (18.6%) were found to have MICA-specific antibodies (6 of them also had anti-HLA antibodies and 5 did not). These data suggested that immunization against mismatched MICA alleles induces development of anti-MICA antibodies. The finding of MICA allele-specific antibodies in eluates of kidney transplants suggests that anti-MICA antibodies can be involved in the pathogenesis of kidney allograft rejection. Further studies will be required to determine whether patients who produce alloantibodies against MICA alleles are at risk for transplant rejection even when no HLA antibodies are detected.

Adult↗

Outcome after pediatric liver transplantation impact of living donor transplantation on cost.

OBJECTIVE: To compare the direct health care cost of living donor liver transplantation (LDLT) with that of cadaver donor liver transplantation (CDLT) in children and identify predictors of cost. STUDY DESIGN: All 16 children who underwent LDLT from January 1997 through January 2002 at Cincinnati Children's Hospital Medical Center comprised the study population. They were matched for age, diagnosis, and nutritional status with 31 children who received CDLT during the same era. A historic cohort analysis was performed. RESULTS: There was no difference in the 1-year mortality rates between both groups. Costs associated with graft retrieval contributed 15.3% and 31% of the initial transplant cost for LDLT and CDLT, respectively. Mean cost of care in the first year was 60.3% higher for LDLT than CDLT (P=.01). Multivariate analysis identified biliary complications and insurance status as predictors of cost for initial transplantation (R(2)=0.57), whereas biliary complications and pediatric end stage liver disease scores were identified as predictors of cost of care in the first year after transplantation (R(2)=0.77). CONCLUSIONS: The comprehensive cost of LDLT in the first year after transplantation is higher than cadaveric transplantation. This must be balanced against the time spent and care needs of patients on the waiting list.

Cadaver↗

Pulmonary tailoring and lobar transplantation to overcome size disparities in lung transplantation.

Size matching between donors and recipients represents one of the organ distribution criteria widely accepted by lung transplant teams. However, in some cases it is not possible to allocate a donor to the corresponding size-compatible recipient. To avoid possible complications derived from the implantation of oversized lungs into smaller recipients, surgical procedures such as pulmonary tailoring and lobar transplantation have been advocated. We review our experience in 13 patients undergoing volume reduction of the lung graft at the time of transplantation, either by nonanatomical lung volume reduction or by lobar transplantation. There were no significant differences between lung-downsized patients and standard lung transplantation patients in terms of donor characteristics, surgical and postoperative complications, functional outcome, and survival. We conclude that downsizing the lung graft either by nonanatomical resection or lobar transplantation is safe and reliable to overcome size disparities between donor and recipients, with no additional morbidity and with similar early and midterm outcomes to those in standard lung transplants.

ABO Blood-Group System↗

Innovative strategies to expand cadaveric donor pool for liver transplantation (SITF project): a network between Italian transplantation centers supported by the Ministry of Health.

In 2002, the Italian Ministry of Health (IMH) launched a formal call for health research programs within the Research and Development (R&D) Policy. In this context, the research program "Innovative Strategies to Expand Cadaveric Donor Pool for Liver Transplantation" (SITF Project) has been proposed. The SITF Project has been formally approved by IMH as a 2-year research program included in the R&D Policy. The main goals of the SITF Project are to improve matching criteria for split liver transplantation (SLT) in both pediatric and adult recipients, to promote an increase of the SLT/full- size liver transplantation ratio at the national level, and, especially, to establish shared criteria for SLT in 2 adult recipients. The original executive plan of the SITF Project prefigured the participation of both the Italian transplantation centers with more advanced experience in the field of SLT, and institutional partnership, such as Nord Italia Transplant (NITp) and Italian National Transplant Center. A first Web public area concerning the SITF Project has been activated, as well as a reserved Web area with the aim to share cadaveric donors and patients in the waiting lists between Operative Units involved in the research program. For this objective, the first version Oracle-based database able to perform an automatic matching between a single cadaveric donor and 2 potential adult recipients has been released at the beginning of 2005. The SITF Project represents a new approach in the management of SLT for 2 adult recipients in Italy and a model for a functional network between Italian transplantation centers.

Cadaver↗

Clinical status of patients removed from a transplant waiting list rivals that of transplant recipients at significant cost savings.

We retrospectively contrasted the medical outcome of patients removed from the heart transplant consideration list because of clinical improvement with that of transplant recipients. Of 60 patients awaiting transplantation, 18 were removed from the list (group A), and 42 required transplant or died (group B). Group A significantly improved regarding exercise oxygen uptake, ejection fraction, and hemodynamics. For more than 2 years after transplantation or "delisting," both groups had comparable symptoms (New York Heart Association class I to II) and cardiovascular mortality (1 of 18 for group A vs 3 of 32 for group B) but lower hospitalizations for group A (0.5 +/- 0.6 of 27 months per patient) versus group B (2.8 +/- 2.1 of 23 months per patient) (p = 0.0002). Despite two patients who had been removed from the list requiring transplantation, savings for delisting exceeded $2.2 million. Thus medical therapy allows transplant recipient list removal with clinical improvements sustained for 1 to 3 years at significant cost savings.

Cardiac Output, Low↗

Lung transplantation with cardiopulmonary bypass exaggerates pulmonary vasomotor dysfunction in the transplanted lung.

Pulmonary vascular resistance is significantly increased in the transplanted lung. If cardiopulmonary bypass is required, the transplanted lung is reperfused with activated blood elements, which might exacerbate the reperfusion injury. The purpose of this study was to examine the influence of cardiopulmonary bypass on the following mechanisms of pulmonary vasomotor control in a dog model of autologous lung transplantation: (1) endothelium-dependent cyclic guanosine monophosphate-mediated relaxation (response to acetylcholine), (2) endothelium-independent cyclic guanosine monophosphate-mediated relaxation (response to nitroprusside), and (3) beta-adrenergic cyclic adenosine monophosphate-mediated relaxation (response to isoproterenol). Autologous right lung transplants were performed with (n = 4 dogs) and without (n = 5 dogs) bypass. Lungs were stored in cold saline solution (4 degrees C, 3 hours) before reimplantation. Pulmonary vasomotor control mechanisms were studied in isolated pulmonary arterial rings immediately after harvest and 1 hour after reimplantation. Ten rings were studied in each group at each time. Statistical analysis was by analysis of variance. Without bypass, endothelium-dependent cyclic guanosine monophosphate-mediated relaxation and beta-adrenergic cyclic adenosine monophosphate-mediated relaxation were significantly impaired, although endothelium-independent cyclic guanosine monophosphate-mediated relaxation was not. Use of bypass produced significantly greater impairment of both endothelium-dependent cyclic guanosine monophosphate-mediated relaxation and beta-adrenergic cyclic adenosine monophosphate-mediated relaxation. In addition, use of bypass produced significant dysfunction of endothelium-independent cyclic guanosine monophosphate-mediated relaxation as well. We conclude that using cardiopulmonary bypass to perform lung transplantation greatly exaggerates pulmonary vasomotor dysfunction in the transplanted lung. This dysfunction may contribute to significantly higher pulmonary vascular resistance in the transplanted lung if cardiopulmonary bypass is used.

Acetylcholine↗

Lasting beneficial effect of short-term inhaled nitric oxide on graft function after lung transplantation. Paris-Sud University Lung Transplantation Group.

The combination of ischemia and reperfusion after lung transplantation is characterized by endothelial damage, neutrophil sequestration, and decreased release of endothelial nitric oxide. Because nitric oxide has been shown to selectively dilate the pulmonary vasculature, abrogate neutrophil adherence, and restore endothelial dysfunction, we hypothesized that inhaled nitric oxide given for 4 hours during initial reperfusion might attenuate reperfusion injury in a porcine model of left single-lung transplantation. We tested hemodynamic and gas exchange data, lung neutrophil sequestration, and pulmonary artery endothelial dysfunction after 4 and 24 hours of reperfusion in 12 pigs randomly assigned to nitric oxide and control groups. Harvested lungs were preserved in normal saline solution for 24 hours at 4 degrees C. During transplantation, inflatable cuffs were placed around each pulmonary artery to allow separate evaluation of each lung by occluding flow. Compared with the transplanted lungs in the control group, transplanted lungs in pigs treated with inhaled nitric oxide significantly improved gas exchange, pulmonary vascular resistance, shunt fraction, and oxygen delivery at 4 and 24 hours after reperfusion. Neutrophil sequestration, as measured by the neutrophil-specific enzyme myeloperoxidase and the alveolar leukocyte count per light microscopic field, was significantly lower at 24 hours after reperfusion in the transplanted lungs of the nitric oxide group. The nitric oxide-treated native right lungs exhibited significantly reduced increase in neutrophil accumulation compared with that in control native right lungs. After 24 hours of reperfusion, endothelium-dependent relaxation to acetylcholine was similarly and severely altered in both groups. We conclude that short-term inhaled nitric oxide given during the first 4 hours of reperfusion after lung transplantation significantly attenuates reperfusion injury, improving graft function as long as 24 hours after operation. This effect is probably mediated by a decrease in neutrophil sequestration. A protective effect on the contralateral lung was also observed. Inhaled nitric oxide may be a suitable agent when an acute reperfusion phenomenon is anticipated.

Administration, Inhalation↗

Kidney transplantation from living-unrelated donors: comparison of outcome with living-related and cadaveric transplants under current immunosuppressive protocols.

OBJECTIVES: Living-unrelated donors may become an additional organ source for patients on the kidney waiting list. We studied the impact of a combination of calcineurin inhibitors and mycophenolate-mofetil together with steroids on the outcomes of living-related (LRD), unrelated (LUR), and cadaver transplantation. METHODS: Between September 1997 and January 2000, 129 patients underwent LRD (n = 80) or LUR (n = 49) kidney transplantation, and another 173 patients received a cadaveric kidney. Immunosuppressive protocols consisted of mycophenolate-mofetil with cyclosporine-Neoral (41%) or tacrolimus (59%) plus steroids. We compared the patient and graft survival data, rejection rate, and graft functional parameters. RESULTS: LRD recipients were younger (33.6 years) than LUR (47.8 years) and cadaver (43.7 years) donor recipients (P <0.001). HLA matching was higher in LRD patients (P <0.001). Acute rejection developed in 28.6% of LUR versus 27.5% of LRD transplants and 29.7% of cadaver kidney recipients (P = not significant). The creatinine level at 1, 2, and 3 years after transplant was 1.63, 1.73, and 1.70 mg% for LRD patients; 1.48, 1.48, and 1.32 mg% for LUR patients; and 1.75, 1.68, and 1.67 mg% for cadaver kidney recipients (P = not significant), respectively. No difference in patient survival rates was found among the groups. The 1, 2, and 3-year graft survival rates were significantly better in recipients of LRD (91.3%, 90.0%, and 87.5%, respectively) and LUR transplants (89.8%, 87.8%, and 87.8%, respectively) than in cadaver kidney recipients (81.5%, 78.6%, 76.3%, respectively; P <0.01). CONCLUSIONS: Despite HLA disparity, the rejection and survival rates of LUR transplants under current immunosuppressive protocols are comparable to those of LRD and better than those of cadaveric transplants.

Adult↗

Analysis of factors that affect outcome of primary cadaveric renal transplantation in the UK. HLA Task Force of the Kidney Advisory Group of the United Kingdom Transplant Support Service Authority (UKTSSA)

BACKGROUND: In the UK, kidneys are exchanged between centres on the basis of matching for HLA. We analysed various factors that might affect graft outcome to establish whether exchange of kidneys on this basis remains valid. METHODS: 6363 primary cadaveric renal transplants carried out in 23 centres in the UK between 1986 and 1993 were used in the analysis. 6338 (99.6%) patients who underwent transplantation were followed up at 1 year. 5-year follow-up data were available for 2907 (97.8%) of the 2972 patients who survived to 5 years. We made random checks to validate the data. A multifactorial analysis with Cox's proportional hazards models was used to analyse factors that had a possible effect on graft outcome. To ensure that the analysis of matching was constant during the 8-year study, our analysis was based on the HLA antigens used for organ exchange (11 A locus antigens, 27 B locus antigens, and 12 DR locus antigens). We assessed overall outcome at 5 years and during three periods after transplantation at: 0-3 months, 3-36 months, and after 36 months. FINDINGS: The following factors were significantly associated with graft outcome in the multifactorial analysis: year of graft, age of donor, age of recipient, whether the recipient had diabetes, cause of donor's death, cold ischaemic time, transport of kidneys, transplant centre, and matching for HLA. The best outcome was achieved with kidneys that had no mismatches at HLA-A, HLA-B, and HLA-DR loci (000 mismatches). The next most favourable outcome was achieved with one mismatch at either A or B loci or one mismatch at both the A and B , but no mismatch at the DR locus (100, 010, or 110 mismatches). Age of the donor and recipient had a significant effect on transplant outcome: older age was associated with increased risk of graft failure. INTERPRETATION: Various factors affect the outcome of primary cadaveric renal transplantation, particularly the age of the donor and the recipient. However, the effect of matching for HLA remains a strong one and fully justifies the continuing policy in the UK of exchanging kidneys on the basis of HLA matching, especially to recipients when there is a 000 mismatch for HLA between donor and recipient. On the basis of this analysis, a new allocation scheme for kidneys was introduced in the UK in 1998. During the first 9 months of the scheme, there has been a doubling of the number of HLA-000 mismatched kidneys transplanted.

Adolescent↗

Examination of parameters influencing the benefit:detriment ratio of cyclosporine in renal transplantation. The Canadian Transplant Study Group.

The benefit:detriment ratio of Cyclosporine (CsA) in renal transplantation was examined by analysis of the data accumulated within the Canadian Transplant Study Group (CTSG). Transplantation was performed according to commonly defined protocols, and 496 patients were analysed following cadaveric or live-related transplantation. One-year patient and graft survival were 96% and 86%, respectively, following living-related HLA nonidentical transplantation, 92% and 75% following primary cadaveric transplantation, and 97% and 58% following cadaveric retransplantation. A clear beneficial effect of blood transfusion was observed following primary cadaveric renal transplantation (P = 0.04), with a trend towards improved graft survival in donor/recipient pairs matched at the B or Dr locus (89% v 73%, P = NS). Prolonged machine preservation (greater than 24 hours) of the kidney or long (greater than than 45 minutes) surgical anastomosis time, and an elevated serum CsA level adversely influenced allograft function. Graft function in patients receiving CsA stabilized by approximately 6 months posttransplant, and subsequently remained constant as determined by both serum creatinine and calculation of creatinine clearance. Hypertension was more common (P = 0.003) in patients receiving CsA, and vascular complications were more frequent although this difference was not statistically significant. Infectious complications were comparable between the two groups. Two lymphomas were confirmed in patients receiving CsA. The mean cost of CsA throughout the first 12 months posttransplant based on a 60 kg patient weight was $4,490, and reduced by $3,397 each subsequent year of maintenance treatment.

Adolescent↗

[Sequential double-lung transplantation. Technique and results in the first 3 cases. Pulmonary Transplant Group].

Patients who suffer advanced lung disease associated to respiratory infection and who are candidates for transplantation must have both lungs replaced. Until recently, this procedure was accomplished by transplanting a heart-lung block, a procedure of questionable merit if the heart is healthy, or by carrying out a double-lung transplant requiring extracorporeal circulation and involving a high percentage of complications the tracheal anastomosis. The year 1990 saw publication of the first descriptions of a simpler procedure, sequential double-lung transplantation. After brief experience with good results in single-lung transplantation, we present the first three cases of sequential double-lung replacement carried out in Spain. We describe the consecutive substitution of both lungs, with no need for extracorporeal circulation in most cases. Sequential bilateral lung transplantation combines the advantages of single-lung transplantation with the use of anterior thoracoesternotomy to provide good access to both pleural cavities, facilitating the procedure when pleural adhesion is present.

Adolescent↗

How many myeloid post-progenitor cells have to be transplanted to completely abrogate neutropenia after peripheral blood progenitor cell transplantation? Results of a computer simulation.

Although hematopoietic recovery following high-dose chemotherapy (HD-CT) and peripheral blood progenitor cell (PBPC) transplantation is rapid, there is still a 5- to 7-day period of severe neutropenia which, theoretically, might be abrogated by an additional transplantation of more differentiated myeloid post-progenitor cells (MPPC). However, both the number of MPPC required to abrogate neutropenia as well as the optimum scheduling of MPPC infusions are currently unknown. Therefore, these questions were addressed by applying a computer model of human granulopoiesis. First, model calculations simulating varying levels of chemotherapy dose intensity were performed and compared with typical clinical neutrophil recovery curves. Using this approach, the data for HD-CT without PBPC transplantation could be reproduced by assuming a reduction of stem cells, committed granulopoietic progenitors and proliferating precursors to about 0.001% of normal. PBPC-supported HD-CT was reproduced by increasing the starting values to at least 0.1%, which corresponded to about 1 to 2 x 10(5)/kg transplanted CFU-GM. Interestingly, reproduction of PBPC-supported HD-CT data could be observed for a wide range of starting values (0.1%-10% of normal), thus confirming the clinical observation that hematopoietic recovery after PBPCT cannot be improved by increasing the dose of transplanted cells over a certain threshold. Using the same simulation model, we then studied the effects of an additional MPPC transplantation. The results showed, that at least 5.7 X 10(8) MPPC/kg have to be provided in addition to the normal PBPC graft to avoid neutropenia <100/microL, and that MPPC are best transplanted on days 0 and 6 after HD-CT. Assuming a 100- to 120-fold cellular ex-vivo expansion rate and MPPC representing about 70% of total expanded cells, 5.7 X 10(8) MPPC/kg could be generated starting from 1 to 2 leukapheresis preparations with about 7 to 8 x 10(6) CD34+ PBPC/kg. Considering furthermore, that only a fraction of ex-vivo generated cells will seed and effectively produce neutrophils in-vivo, the required number of MPPC is most likely even higher and, therefore, might be difficult to be achieved clinically. However, the validity of the model results remains to be proven in appropriate clinical studies.

Antineoplastic Combined Chemotherapy Protocols↗

To transplant or not to transplant recurrent hepatitis C and liver failure.

In summary, re-OLT accounts for 10% of all OLTs performed and is associated with significantly increased resource use, and decreased survival compared with primary OLT. After transplantation into an HCV-infected recipient, infection of the allograft by HCV is invariable. As patients survive longer after liver transplantation, it is likely that allograft failure related to HCV recurrence will occur. Results of re-OLT for HCV are inferior to those of primary grafting, paralleling the results for retransplantation for other indications. Many studies have demonstrated that HCV infection significantly impairs patient and allograft survival after liver retransplantation, regardless of etiology of allograft failure. Patient survival rates with HCV infection are 57% to 65% at 1 year, as compared with 65% to 82% among patients without HCV infection. Experience with retransplantation is limited, however, and studies are difficult to interpret because of small sample sizes and lack of uniform definitions of survival, HCV recurrence, and allograft failure. Similar to outcomes after retransplantation for non-HCV related indications, the most common causes of death are sepsis and multi-organ failure. The high mortality associated with retransplantation has not universally been caused by recurrent disease, however recent studies have demonstrated that re-recurrent HCV occurs and the natural history is similar, if not more accelerated, after the second transplant. HCV infection may, in fact, increase mortality in a group of patients already predisposed to an inferior outcome. Preoperative serum creatinine and bilirubin have been consistently associated with survival after retransplantation and favorable results are attainable with strict selection criteria. The increasing use of expanded donor criteria, in particular, LRLT, raises important practical and ethical issues with regards to the HCV-positive transplant recipient and will become a challenge to the transplant community as a whole. With the donor morbidity and mortality associated with LRLT currently estimated at 32% and 0.3%, respectively, one must determine how much risk is acceptable to the donor in relation to the outcome in the recipient. This is especially true in HCV-infected recipients, in whom HCV re-recurrence may occur in the second allograft and lead to accelerated failure. LRLT, however, would not deplete the organ pool and would lead to the use of scarce cadaveric organs to patients who are awaiting primary liver transplantation. Despite inferior outcomes, a better tactic may be to consider retransplantation for recurrent HCV in those whose primary transplant was a LDLT, as the initial allograft did not deplete the donor pool. Given the shortage of donor organs and the increasing number of patients with HCV-induced allograft cirrhosis, identifying ways to improve allograft survival in HCV-infected patients represents an important focus for further research. Additional studies are needed to further explore the mechanisms underlying the reduction in survival and to identify which HCV-positive individuals are at greatest risk for poor survival. Studies are beginning to emerge that demonstrate that HCV recurrence can be modified with combination antiviral therapy and that the HCV virus can be eliminated. Additional longitudinal prospective studies are needed to assess the exact impact of HCV on survival after retransplantation, the effects of the newer immunosuppressive agents such as sirolimus and mycophenolate mofetil on HCV, the use of preemptive antiviral therapy on HCV eradication and fibrosis modification, and the appropriateness of expanded donor criteria. Until we have longer follow-up and greater experience with the HCV-positive recipient with allograft failure, retransplantation should be considered a viable option for highly selected patients, particularly in patients in whom renal failure and severe hyperbilirubinemia have not occurred.

Graft Rejection↗

Liver transplantation in Italy: current status. Study Group on Liver Transplantation of the Italian Association for the Study of the Liver (A.I.S.F.).

The first liver transplant in Italy was performed in 1982. With the improvement in results, the number of patients followed, in recent years, has substantially increased in all centres. In parallel, the indications for liver transplantation have expanded and have raised the need for more organized structures where patients can be referred for evaluation and transplantation. Indications and contraindications to liver transplantation in Italy, the role of retransplantation, paediatric liver transplantation, waiting list management, liver transplantation outside Italy and the new Italian laws on organ donation are discussed. The multidisciplinary Study Group on Liver Transplantation of the Italian Association for the Study of the Liver (AISF) has collected information from all the Italian centres to ascertain the degree of consistency in their methods.

Humans↗

Hyperhomocysteinemia and transplant coronary artery disease in cardiac transplant recipients.

BACKGROUND: In cardiac transplant recipients, long-term survival may be limited by transplant coronary artery disease (TxCAD). Hyperhomocysteinemia (Hhcy) has been associated with vascular disease and is common in transplant recipients. The objective of this study was to determine the relationship between fasting homocysteine (Hcy) concentrations and TxCAD in a cohort of cardiac transplant recipients. METHODS: Forty-eight patients more than 5 yr after transplant were recruited from a cohort of 72 consecutive patients with in-depth analysis of homocysteine levels from the Cardiac Transplant Clinic. Early morning fasting blood was obtained, and the plasma separated and frozen within 30 min. Hcy concentrations were determined by high-performance liquid chromatography (HPLC) with pulsed integrated amperometry. Coronary angiograms were reviewed in a blinded fashion. TxCAD was diagnosed, using the most recent angiogram, when a >25% lesion was present anywhere in the coronary tree. RESULTS: Forty-eight patients transplanted between 1985 and 1994 were studied. The mean Hcy concentration for the cohort was 23.5+/-5.0 micromol/L, all patients had homocysteine levels above the upper range of normal (5-15 micromol/L). Hcy concentrations were significantly higher in patients with angiographic evidence of TxCAD: 25.0+/-5.9 vs. 21.9+/-3.4 micromol/L, p=0.03. This effect persisted when covariates were taken into account using logistic regression analysis. CONCLUSIONS: Hhcy is associated with TxCAD. Prospective studies are required to confirm this association and to assess the efficacy of Hcy-lowering therapy in this patient population.

Adult↗

Rescue of acute portal vein thrombosis after liver transplantation using a cavoportal shunt at re-transplantation.

BACKGROUND: Portal vein thrombosis is a rare but devastating complication following orthotopic liver transplantation. Fulminant liver failure ensues with acute portal vein thrombosis after transplantation limiting the treatment options. METHODS: We successfully re-transplanted a 46-year-old female patient who developed acute portal vein thrombosis 19 d after orthotopic liver transplantation. Vascular reconstruction included a cavoportal shunt to augment portal blood flow. RESULTS: Twelve months after re-transplantation this patient lives independently and enjoys excellent liver allograft function. CONCLUSIONS: Cavoportal shunt can augment portal blood flow in adult recipients of orthotopic liver transplants. This technique can be successfully employed during re-transplantation when portal blood flow is inadequate to maintain patency.

Female↗

Transplantation of kidneys from donors with hepatitis C antibody into recipients with pre-transplantation anti-HCV.

Hepatitis C virus (HCV) is transmitted by organ transplantation. Consequently, several organ procurement organizations have imposed a moratorium on use of organs from anti-HCV positive donors. Because of the inadequate supply of cadaver kidneys for transplantation, we adopted a policy to transplant kidneys from anti-HCV donors into anti-HCV positive recipients. During the period between March 1990 and December 1992, 24 anti-HCV positive dialysis patients received a kidney from anti-HCV positive donors (group I) and 40 anti-HCV positive patients received a kidney from anti-HCV negative donors (group II). We compared the prevalence of liver disease, anti-HCV, HCV RNA, graft and patient survival between groups. Pre-transplantation 17 of 24 (71%) patients in group I and 31 of 40 (79%) of patients in group II had serum HCV RNA. Post-transplantation follow-up was 26 +/- 8 months and 30 +/- 10 months in groups I and II, respectively. During follow-up, elevated ALT levels were present in 7 of 24 (29%) and 16 of 40 (40%) of patients in groups I and II, respectively (P > 0.05). Post-transplantation, all patients in both groups retained anti-HCV. The prevalence of HCV RNA post-transplantation was 22 of 23 (96%) patients in group I and 30 of 39 (77%) of patients in group II (P > 0.05). Graft and patient survival in group I (96% and 100%, respectively) were not significantly different from those in group II (93% and 98%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗