Combined liver-kidney transplantation: Analysis of patients with preformed lymphocytotoxic antibody

In this report, we address combined liver-kidney transplantation, with particular attention to the apparent phenomenon of protection of kidney allografts to antibody mediated destruction by liver allografts. Four patients were found to have positive crossmatch before the liver phase of the combined transplant (pre-OT/KT samples). These positive crossmatches were due entirely to anti-HLA class I antibodies, as demonstrated by their removal by immunoabsorption on pololed platelets. In three of these patients, post-OT/pre-KT samples showed a conversion to a negative crossmatch (in the fourth patient this was not done). A kidney allograft, harveted from the same donor, was then placed into the recipient, and in patients no. 3, 7, and 12, good initial function was noted. In one of these patients was there evidence of hyperacute rejection. Post-OT/KT samples were collected in patients no. 3, 7, and 8, and then analyzed for the reappearance of donor specific lymphocytotoxic antibodies in the posttransplant period (data on patient no. 12 was not available at time of preparation). Lymphocytotoxic antibodies with donor specificity could not be detected in any of the samples during the first week posttransplant. The decrease in %PRA and conversion of a positive to negative crossmatch following liver transplantation was correlated to the HLA specificty of the antibody found in the pretransplant serum and the HLA type of the tranplanted organs. In the two instances where an HLA specificity could be determined by panel analysis, transplantation with donor organs bearing these HLA specificities led to a specific disppearance of these antibodies during the postransplant phase

Combined liver-kidney transplantation and the effect of preformed lymphocytotoxic antibodies

Thirty-eight sequentially placed liver and kidney allografts were evaluated with respect to patient and graft survival, and the influence of preformed lymphocytotoxic antibodies was analysed. The results suggest that the survival rate of combined liver and kidney transplantation is similar to the survival rate of liver transplantation alone. Sequentially placed kidney allografts may be protected from hyperacute rejection in the presence of donor specific lymphocytotoxic antibodies, but not in all instances. Both patient and kidney allograft survival was lower in positive crossmatch patients (33% and 17% respectively) than in negative crossmatch patients (78% and 75%). High levels of panel reactive antibodies (>10%) also appeared to have a deleterious effect on survival, although the majority of the patients who failed also had a positive crossmatch. Although preformed lymphocytotoxic antibodies are not an absolute contraindication to combined liver-kidney transplantation, they do appear to have a deleterious effect on long-term graft survival. However, more correlation with clinical parameters is needed. © 1994

Heart Rate Variability Measured Early in Patients with Evolving Acute Coronary Syndrome and 1-year Outcomes of Rehospitalization and Mortality

Objective: This study sought to examine the prognostic value of heart rate variability (HRV) measurement initiated immediately after emergency department presentation for patients with acute coronary syndrome (ACS). Background: Altered HRV has been associated with adverse outcomes in heart disease, but the value of HRV measured during the earliest phases of ACS related to risk of 1-year rehospitalization and death has not been established. Methods: Twenty-four-hour Holter recordings of 279 patients with ACS were initiated within 45 minutes of emergency department arrival; recordings with �18 hours of sinus rhythm were selected for HRV analysis (number [N] �193). Time domain, frequency domain, and nonlinear HRV were examined. Survival analysis was performed. Results: During the 1-year follow-up, 94 patients were event-free, 82 were readmitted, and 17 died. HRV was altered in relation to outcomes. Predictors of rehospitalization included increased normalized high frequency power, decreased normalized low frequency power, and decreased low/high frequency ratio. Normalized high frequency �42 ms2 predicted rehospitalization while controlling for clinical variables (hazard ratio [HR] �2.3; 95% confidence interval [CI] �1.4–3.8, P�0.001). Variables significantly associated with death included natural logs of total power and ultra low frequency power. A model with ultra low frequency power �8 ms2 ( HR �3.8; 95% CI �1.5–10.1; P�0.007) and troponin �0.3 ng/mL (HR �4.0; 95% CI �1.3–12.1; P�0.016) revealed that each contributed independently in predicting mortality. Nonlinear HRV variables were significant predictors of both outcomes. Conclusion: HRV measured close to the ACS onset may assist in risk stratification. HRV cut-points may provide additional, incremental prognostic information to established assessment guidelines, and may be worthy of additional study

Heart Rate Variability Measurement and Clinical Depression in Acute Coronary Syndrome Patients: Narrative Review of Recent Literature

Aim: We aimed to explore links between heart rate variability (HRV) and clinical depression in patients with acute coronary syndrome (ACS), through a review of recent clinical research literature. Background: Patients with ACS are at risk for both cardiac autonomic dysfunction and clinical depression. Both conditions can negatively impact the ability to recover from an acute physiological insult, such as unstable angina or myocardial infarction, increasing the risk for adverse cardiovascular outcomes. HRV is recognized as a reflection of autonomic function. Methods: A narrative review was undertaken to evaluate state-of-the-art clinical research, using the PubMed database, January 2013. The search terms “heart rate variability” and “depression” were used in conjunction with “acute coronary syndrome”, “unstable angina”, or “myocardial infarction” to find clinical studies published within the past 10 years related to HRV and clinical depression, in patients with an ACS episode. Studies were included if HRV measurement and depression screening were undertaken during an ACS hospitalization or within 2 months of hospital discharge. Results: Nine clinical studies met the inclusion criteria. The studies’ results indicate that there may be a relationship between abnormal HRV and clinical depression when assessed early after an ACS event, offering the possibility that these risk factors play a modest role in patient outcomes. Conclusion: While a definitive conclusion about the relevance of HRV and clinical depression measurement in ACS patients would be premature, the literature suggests that these measures may provide additional information in risk assessment. Potential avenues for further research are proposed

OKT3 in the reversal of acute hepatic allograft rejection.

OKT3 was an effective immunosuppressant agent in patients with acute cell-mediated allograft rejection that had not responded to initial steroid therapy. OKT3 was also valuable for treating patients with early hepatic graft dysfunction caused by other factors than rejection. In such recipients, the doses of CyA can be greatly reduced, allowing recovery of frequently damaged kidneys while maintaining effective immunosuppression

The liver transplant waiting list—a single-center analysis

At this transplant center 1340 patients were entered on the liver transplant waiting list during the first 25 months (October 1987 to November 1989) after the initiation of the UNOS allocation system for liver grafts. Of these 972 (72.5%) of the patients received a graft, 120 (9.0%) died waiting for a graft, 109 (8.1%) remained on the active list as of the study endpoint of December 15, 1989, 123 (9.2%) were withdrawn from candidacy, and 16 (1.2%) received a transplant at another center. A total of 1201 patients were candidates for a first graft. Of the 812 primary candidates who received a graft, 64.8% received their graft within one month of entry on the waiting list. Of the 109 primary candidates who died before a graft could be found, 79.0% died within a month of entry onto the waiting list. At time of transplantation, 135 (16.6%) primary recipients of a graft were UNOS class 1, 326 (40.1%) were UNOS class 2, 190 (23.4%) were UNOS class 3, and 161 (19.8%) were UNOS class 4. Actuarial survival rates (percentage) at 6 months for recipients in UNOS class 1, class 2, class 3, and class 4 were 88.7±2.9, 82.6+2.1, 78.4±3.2, and 68.4±3.9, respectively (P<0.001). At the time of death of recipients who failed to get a graft, 6 (5.5%) were UNOS class 1, 14 (12.8%) were UNOS class 2, 23 (21.1%) were UNOS class 3, and 66 (60.6%) were UNOS class 4. These results indicate that a high proportion of liver transplant candidates are in urgent need of a graft and that the UNOS system succeeds in giving these patients high priority. However patient mortality on the waiting list and after transplantation would lessen significantly if more patients with end-stage liver disease were referred to the transplant center in a timely manner before their condition reaches the point where the probability of survival is diminished. © 1991 by Williams & Wilkins