PubMed Health⌕ Search

Biomedical subjects

Richard B Freeman

Publications and source records attributed to Richard B Freeman.

At least 37 records · Page 2Linked to original sources
PubMed2004

Summary report of a national conference: Evolving concepts in liver allocation in the MELD and PELD era. December 8, 2003, Washington, DC, USA.

A national conference was held to review and assess data gathered since implementation of MELD and PELD and determine future directions. The objectives of the conference were to review the current system of liver allocation with a critical analysis of its strengths and weaknesses. Conference participants used an evidence-based approach to consider whether predicted outcome after transplantation should influence allocation, to discuss the concept of minimal listing score, to revisit current and potential expansion of exception criteria, and to determine whether specific scores should be used for automatic removal of patients on the waiting list. After review of data from the first 18 months since implementation, association and society leaders, and surgeons and hepatologists with wide regional representation were invited to participate in small group discussions focusing on each of the main objectives. At the completion of the meeting, there was agreement that MELD has had a successful initial implementation, meeting the goal of providing a system of allocation that emphasizes the urgency of the candidate while diminishing the reliance on waiting time, and that it has proven to be a powerful tool for auditing the liver allocation system. It was also agreed that the data regarding the accuracy of PELD as a predictor of pretransplant mortality were less conclusive and that PELD should be considered in isolation. Recommendations for the transplant community, based on the analysis of the MELD data, were discussed and are presented in the summary document.

Adult↗
PubMed2004

Expanded criteria donor grafts for deceased donor liver transplantation under the MELD system: a decision analysis.

Expanded criteria donor (ECD) liver grafts have a higher likelihood of primary graft failure (PGF) compared with standard criteria donor (SCD) grafts. Given a choice between an available ECD graft versus waiting for an SCD graft that may not always become available, what should liver transplant candidates do? The study's aim was to estimate 1-year survival comparing immediate ECD liver grafting with waiting for an SCD organ. Using UNOS data, published literature estimates, and expert opinion, we constructed a Markov decision analytic model to estimate survival while waiting for an SCD transplant and survival with immediate ECD transplant. Sensitivity analyses were performed by varying model parameters individually and simultaneously with a second-order Monte Carlo simulation. For all patients with MELD scores >20, survival was higher with immediate ECD transplant despite the additional increased risk for PGF. Survival was better with an immediate ECD transplant unless the probability of PGF exceeded 23%, 72%, and 88% for recipients with MELD scores of 11-20, 21-25, and 26-30 respectively. For patients with MELD scores >30, the survival benefit with the immediate ECD strategy persisted at even higher rates of PGF. In conclusion, our results suggest that, despite the higher risk for PGF, transplantation with an available ECD graft should be preferred over waiting for an SCD organ for patients with advanced MELD scores. At less advanced MELD scores, the survival benefit depends on the risk of PGF associated with the ECD organ.

Cadaver↗
PubMed2004

Liver transplantation for hepatocellular cancer: the impact of the MELD allocation policy.

Recent reports suggest that selected patients undergoing liver transplantation for stage 1-2 hepatocellular cancer (HCC) have an excellent long-term survival and a low incidence of recurrence. In the past, over 45% of HCC patients on the United Network for Organ Sharing/Organ Procurement Transplantation Network waiting list did not receive a donor organ for up to 2 years. This resulted in not only a high mortality rate but a high rate of being removed from the waiting list because of progression of HCC to advanced stages. The introduction of the Model for End-Stage Liver Disease (MELD) allocation policy has had a positive effect on HCC liver transplant candidates with the number of patients transplanted for HCC significantly increasing over the past several years. In addition, waiting time for HCC patients to receive a deceased donor has decreased significantly and the number of patients dropping out from the waiting list because of advanced stage disease has also decreased. An early assessment of the MELD allocation policy suggests that posttransplant survival for HCC patients comparing pre-MELD to post-MELD eras is similar. Using the data we have collected on the MELD allocation policy, we have already made modifications to the MELD allocation policy for HCC patients. It is hoped that through continued data collection and assessment, a consensus can be reached to further optimize the use of deceased donors in HCC recipients.

Carcinoma, Hepatocellular↗
PubMed2004

Improving liver allocation: MELD and PELD.

On February 27, 2002, the liver allocation system changed from a status-based algorithm to one using a continuous MELD/PELD severity score to prioritize patients on the waiting list. Using data from the Scientific Registry of Transplant Recipients, we examine and discuss several aspects of the new allocation, including the development and evolution of MELD and PELD, the relationship between the two scoring systems, and the resulting effect on access to transplantation and waiting list mortality. Additional considerations, such as regional differences in MELD/PELD at transplantation and the predictive effects of rapidly changing MELD/PELD, are also addressed. Death or removal from the waiting list for being too sick for a transplant has decreased in the MELD/PELD era for both children and adults. Children younger than 2 years, however, still have a considerably higher rate of death on the waiting list than adults. A limited definition of ECD livers suggests that they are used more frequently for patients with lower MELD scores.

Adult↗
PubMed2004

Predicted lifetimes for adult and pediatric split liver versus adult whole liver transplant recipients.

Split liver transplantation allows 2 recipients to receive transplants from one organ. Comparisons of predicted lifetimes for two alternatives (split liver for an adult and pediatric recipient vs. whole liver for an adult recipient) can help guide the use of donor livers. We analyzed mortality risk for 48,888 waitlisted candidates, 907 split and 21,913 whole deceased donor liver transplant recipients between January 1, 1995 and February 26, 2002. Cox regression models for pediatric and adult patients assessed average relative wait list and post-transplant death risks, for split liver recipients. Life years gained compared with remaining on the waiting list over a 2-year period were calculated. Seventy-six splits (152 recipients) and 24 re-transplants resulted from every 100 livers (13.1% [adult] and 18.0% [pediatric] 2-year re-transplant rates, respectively). Whole livers used for 93 adults also utilized 100 livers (re-transplant rate 7.0%). Eleven extra life years and 59 incremental recipients accrued from each 100 livers used for split compared with whole organ transplants. Split liver transplantation could provide enough organs to satisfy the entire current demand for pediatric donor livers in the United States, provide more aggregate years of life than whole organ transplants and result in larger numbers of recipients.

Adult↗
PubMed2004

Valganciclovir: oral prevention and treatment of cytomegalovirus in the immunocompromised host.

Herpes virus infections, particularly those caused by cytomegalovirus (CMV), lead to significant and, sometimes severe, clinical problems for the immunocompromised host. As effective agents have become available, several treatment and prevention strategies have evolved over the past decade, first in intra-venous form and more recently, as oral preparations. Valganciclovir, the valine ester of ganciclovir, is an orally administered, potent, antiviral agent active against all herpes viruses. When taken orally, valganciclovir has much-improved bioavailability compared with oral ganciclovir and achieves ganciclovir exposures similar to intravenous ganciclovir. Clinical trials evaluating the safety and efficacy of valganciclovir for the treatment of new AIDS-associated CMV retinitis showed equivalency to intravenous ganciclovir and prevented progression of quiescent disease. In solid organ recipients, once-daily valganciclovir has been proven equivalent to oral ganciclovir for the prevention of CMV infection. The high bioavailability and convenient dosing formulation make valganciclovir an attractive option for these indications.

AIDS-Related Opportunistic Infections↗
PubMed2003

Impact of donor infections on outcome of orthotopic liver transplantation.

Infection occurs when microbial agents enter the host, either through airborne transmission or by direct contact of a substance carrying the infectious agent with the host. Human body fluids, solid organs, or other tissues often are ideal vectors to support microbial agents and can transmit infections efficiently from donor to recipient. In the case of blood transfusion and tissue transplantation, the main consequence of such a transmission is infection of the recipient. However, in the case of solid-organ transplantation, and particularly for liver transplantation, donor infections are not only transmitted to the recipient, the donor infection also may affect the donated liver's preservability and subsequent function in the recipient irrespective of the systemic consequences of the infection. In addition, solid organ recipients of infected organs are less able to respond to the infectious agent because of their immunosuppressive treatment. Thus, transmission of infections from organ donor to liver recipient represents serious potential risks that must be weighed against a candidate's mortality risk without the transplant. However, the ever-increasing gap between the number of donors and those waiting for liver grafts makes consideration of every potential donor, regardless of the infection status, essential to minimize waiting list mortality. In this review, we will focus on assessing the risk of transmission of bacterial, fungal, viral, and parasitic infectious agents from cadaveric liver donors to recipients and the effect such a transmission has on liver function, morbidity, and mortality. We will also discuss risk-benefit deliberations for using organs from infected donors for certain types of recipients. These issues are critically important to maximize the use of donated organs but also minimize recipient morbidity and graft dysfunction.

Chagas Disease↗
PubMed2002

The dispersal of mucosal memory B cells: evidence from persistent EBV infection.

We have used latent infection with the human herpesvirus Epstein-Barr virus to track the dispersal of memory B cells from the mucosal lymphoid tissue of Waldeyer's ring (tonsils/adenoids). EBV is evenly distributed between the memory compartments of Waldeyer's ring and the peripheral blood. However, it has an approximately 20-fold higher preference for Waldeyer's ring over the spleen or mesenteric lymph nodes. These observations are consistent with a model whereby the virus preferentially establishes persistent infection within memory B cells from Waldeyer's ring. The virus then colonizes the entire peripheral lymphoid system, at a low level, by trafficking with these memory B cells as they circulate through the body and back to Waldeyer's ring. This pathway may reflect that of normal memory B cells derived from nasopharyngeal and other mucosal lymph nodes.

Adenoids↗
PubMed2002

Predicting the probability of progression-free survival in patients with small hepatocellular carcinoma.

Allocation of cadaveric livers to patients based on such objective medical urgency data as the Model for End-Stage Liver Disease (MELD) score may not benefit patients with small hepatocellular carcinomas (HCCs). To ensure that these patients have a fair opportunity of receiving a cadaveric organ, the risk for death caused by HCC and tumor progression beyond 5 cm should be considered. Using a Markov model, two hypothetical cohorts of patients with small hepatomas were assumed to have either (1) Gompertzian tumor growth, in which initial exponential growth decreases as tumor size increases; or (2) rapid exponential growth. The model tracked the number of patients who either died or had tumor progression beyond 5 cm. These results were used to back-calculate an equivalent MELD score for patients with small HCCs. All probabilities in the model were varied simultaneously using a Monte Carlo simulation. The Gompertzian growth model predicted that patients with a 1- and 4-cm tumor have 1-year progression-free survival rates of 70% (HCC-specific MELD score 6) and 66% (HCC-specific MELD score 8), respectively. When assuming rapid exponential growth, patients with a 1- and 4-cm tumor have progression-free survival rates of 69% (HCC-specific MELD score 6) and 12% (HCC-specific MELD score 24), respectively. Our model predicted that the risk for death caused by HCC or tumor progression beyond 5 cm should increase with larger initial tumor size in patients with small hepatomas. To ensure that these patients have a fair opportunity to receive a cadaveric organ, HCC-specific scores predicted by our model could be added to MELD scores of patients with HCC.

Cadaver↗
PubMed2002

Redrawing organ distribution boundaries: results of a computer-simulated analysis for liver transplantation.

For several years, the Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) Liver and Intestinal Transplantation Committee has been examining effects of changes and proposed changes to the liver allocation system. The Institute of Medicine recently recommended that the size of liver distribution units be increased to improve the organ distribution system. Methods to achieve this and the potential impact on patients and transplant centers of such a change are evaluated in this study. In hypothetical scenarios, we combined geographically contiguous organ procurement organizations (OPOs) in seven different configurations to increase the size of liver distribution units to cover populations greater than 9 million persons. Using the UNOS Liver Allocation Model (ULAM), we examined the effect of 17 different organ allocation sequences in these proposed realignments and compared them with those predicted by ULAM for the current liver distribution system by using the following primary outcome variables: number of primary liver transplantations performed, total number of deaths, and total number of life-years saved. Every proposed new liver distribution unit plan resulted in fewer primary transplantations. Many policies increased the total number of deaths and reduced total life-years saved compared with the current system. Most of the proposed plans reduced interregional variation compared with the current plan, but no one plan consistently reduced variation for all outcome variables, and all reductions in variations were relatively small. All new liver distribution unit plans led to significant shifts in the number of transplantations performed in individual OPOs compared with the current system. The ULAM predicts that changing liver distribution units to larger geographic areas has little positive impact on overall results of liver transplantation in the United States compared with the current plan. Enlarging liver distribution units likely will result in significant shifts in organs across current OPO boundaries, which will have a significant impact on the activity of many transplant centers.

Computer Simulation↗
PubMed2002

Optimizing the use of donated cadaver livers: analysis and policy development to increase the application of split-liver transplantation.

The American Society of Transplant Surgeons and the American Society of Transplantation jointly sponsored a conference in Crystal City, Virginia, on March 28th and 29th, 2001, to explore mechanisms for maximizing the cadaver-organ donor pool. Participants from transplantation medicine, surgery, organ procurement organizations, the general public, and government convened to address expanding utilization of each organ type. The committee assigned to review liver organ utilization identified multiple practices that could expand the potential donor pool including non-heart beating donors, marginal grafts, efficient allocation of cadaver organs, and wider application of split-liver transplantation. This article details the data reviewed by the liver committee and their recommendations on policy development for the expanded application of split-liver transplantation.

Cadaver↗