Mount Sinai Journal of Medicine最新文献

Hepatitis C is a widespread problem, and the prevalence is higher in patients on hemodialysis than in the general population. In addition, hepatitis C reduces survival in dialysis patients and renal-transplant recipients. Kidney transplantation offers a survival advantage to those patients with chronic hepatitis C infection faced with the alternative of remaining on dialysis. Kidney transplantation should therefore be considered the treatment of choice for patients with end-stage renal disease and hepatitis C infection. However, these patients need to be chosen appropriately, and there are no well-established guidelines for the workup or selection of these of these patients. Liver biopsy is an essential tool to determine the degree of fibrosis in these patients and also will prove useful in the management of the patients after transplantation. Transplantation of kidneys from hepatitis C-positive donors to hepatitis C-positive recipients has been shown to be safe and confers a significant advantage in terms of waiting time in this population where death on the waiting list is significant. Treatment prior to transplantation should be considered by the hepatology team, although it is often more difficult to treat given the constraints of a patient in renal failure. Although interferon treatment in hepatitis C-positive kidney-transplant candidates is recommended, treatment posttransplant remains controversial. Simultaneous kidney/liver transplantation should be considered for those candidates with evidence of portal hypertension or decompensated cirrhosis.

Six decades after its first implementation, kidney transplantation remains the optimal therapy for end-stage renal disease requiring dialysis. Despite the incontrovertible mortality reduction and cost-effectiveness of kidney transplantation, the greatest remaining barrier to treatment of end-stage renal disease is organ availability. Although the waiting list of patients who stand to benefit from kidney transplantation grows at a rate proportional to the overall population and proliferation of diabetes and hypertension, the pool of deceased-donor organs available for transplantation experiences minimal to no growth. Because the kidney is uniquely suited as a paired organ, the transplant community's answer to this shortage is living donation of a healthy volunteer's kidney to a recipient with end-stage renal disease. This review details the history and evolution of living-donor kidney transplantation in the United States as well as advances the next decade promises. Laparoscopic donor nephrectomy has overcome many of the obstacles to living donation in terms of donor morbidity and volunteerism. Known donor risks in terms of surgical and medical morbidity are reviewed, as well as the ongoing efforts to delineate and mitigate donor risk in the context of accumulating recipient morbidity while on the waiting list.

Since its first performance in 1967, cardiac transplantation has emerged from a medical curiosity to become the treatment of choice for advanced heart failure. Refinements in surgical technique, development of a standardized endomyocardial biopsy grading system, and the discovery of newer immunosuppressive medications have improved the outlook for today's heart-transplant recipients. For the most recent era, median survival has increased to 10 years and median survival conditional upon surviving the first transplant year is now >14 years. Quality of life is excellent. This article will concisely review the major clinical outcomes following transplantation including survival, quality of life, immunosuppression, and short- and long-term complications.

This article reviews the field of donation after cardiac death, focusing on the history, ethicolegal issues, clinical outcomes, best practices, operative techniques, and emerging strategies to optimize utilization of this resource. Donation after cardiac death is one effective way to decrease the organ shortage and has contributed the largest recent increase in abdominal organ allografts. Currently, donation after cardiac death organs confer an increased risk of ischemic cholangiopathy after liver transplant and of delayed graft function after kidney transplant. As this field matures, risk factors for donation after cardiac death organ transplant will be further identified and clinical outcomes will improve as a result of protocol standardization and ongoing research.

Much has been written about the need for and barriers to achievement of greater diversity in the biomedical workforce from the perspectives of gender, race, and ethnicity; this is not a new topic. These discussions often center around a "pipeline" metaphor that imagines students flowing through a series of experiences to eventually arrive at a science career. Here we argue that diversity will only be achieved if the primary focus is on (1) what is happening within the pipeline, not just counting individuals entering and leaving it; (2) de-emphasizing the achievement of academic milestones by typical ages; and (3) adopting approaches that most effectively develop talent. Students may develop skills at different rates based on factors such as earlier access to educational resources, exposure to science (especially research experiences), and competing demands for time and attention during high school and college. Therefore, there is wide variety among students at any point along the pipeline. Taking this view requires letting go of imagining the pipeline as a sequence of age-dependent steps in favor of milestones of skill and talent development decoupled from age or educational stage. Emphasizing talent development opens up many new approaches for science training outside of traditional degree programs. This article provides examples of such approaches, including interventions at the postbaccalaureate and PhD levels, as well as a novel coaching model that incorporates well-established social science theories and complements traditional mentoring. These approaches could significantly impact diversity by developing scientific talent, especially among currently underrepresented minorities.

Transplantation is the treatment of choice for end-stage kidney, heart, lung, and liver disease. Short-term outcomes in solid-organ transplantation are excellent, but long-term outcomes remain suboptimal. Advances in immune suppression and human leukocyte antigen matching techniques have reduced the acute rejection rate to <10%. Chronic allograft injury remains problematic and is in part immune-mediated. This injury is orchestrated by a complex adaptive and innate immune system that has evolved to protect the organism from infection, but, in the context of transplantation, could result in allograft rejection. Such chronic injury is partially mediated by anti-human leukocyte antigen antibodies. Severe rejections have largely been avoided by the development of tissue-typing techniques and crossmatch testing, which are discussed in detail. Further advances in the understanding of T- and B-cell immunology have led to the development of new immunomodulatory therapies directed at prolonging allograft survival, including those that decrease antibody production as well as those that remove antibodies from circulation. Further application of these immunomodulatory therapies has allowed expansion of the donor pool in some cases by permitting ABO-incompatible transplantation and transplantation in patients with preformed antibodies. Although vast improvements have been made in allograft survival, patients must remain on lifetime immunosuppression. Withdrawal of immunosuppression almost always ultimately leads to allograft rejection. The ultimate dream of transplant biologists is the induction of tolerance, where immune function remains intact but the allograft is not rejected in the face of withdrawn immunosuppression. This, however, has remained a significant challenge in human studies.

The introduction of spiral computed tomography from the days of single-slice spiral to today's 64-row multidetector computed tomography and beyond creates datasets with unprecedented spatial and temporal resolution. The key to computed tomography imaging in the big picture is not in the acquisition of data, but in the use of the data acquired. By supplementing traditional axial interpretation with 3-dimensional rendering of the computed tomography volume, the greatest amount of information available is extracted. The information provided by a comprehensive postprocessed study, which includes multiplanar reconstruction in the coronal, sagittal, and oblique plane, as well as 3-dimensional maps of both the arterial and venous phase datasets using volume rendering and maximum intensity projection techniques, allows for key clinical decisions to be made with a high degree of accuracy. Postprocessing of computed tomography data is thus no longer an option, but a true requirement in this era of 64-row multidetector computed tomography and beyond.

The growing disparity between organ availability for transplantation and the number of patients in need has challenged the donation and transplantation community of practice to develop innovative processes, ideas, and techniques to bridge the gaps. Advances in the sharing of best practices in the donation community have contributed greatly over the last 8 years. Broader sharing of updated guidelines for declaration of brain death in conjunction with improvements in deceased donor management have increased opportunities for organ donation. New techniques for organ preservation and organ resuscitation have allowed for better utilization of the potential donor pool. This review will highlight processes, ideas, and techniques in organ donation.

Obesity is a worldwide epidemic leading to severe comorbidity that damages end-organ function. Overall transplant outcomes in this population are inferior to those in nonobese patients. Large population studies show decreased patient and graft survival in obese kidney transplant patients. Despite the poorer outcomes, kidney transplantation is considered because of the survival benefit as compared with the wait-listed dialysis patients. In liver transplantation, the benefit to transplantation as compared with remaining on the list is obvious, as there is no viable liver dialysis at this time. Obesity in potential organ donors impacts both medical and surgical issues. Obesity-related kidney disease affects both the remaining and transplanted kidney. Pancreas donor organs are associated with decreased early graft survival. Liver donor organs with significant steatosis lead to an increased risk for delayed or nonfunction of the organ. Immunosuppressive drugs with variable lipophilicity and altered volume of distribution can greatly affect the therapeutic usefulness of these drugs. Transplant candidates benefit from a multidisciplinary team approach to their care. As the epidemic progresses and less-invasive treatments for metabolic surgery evolve, we are likely to require more patients to lose weight prior to transplantation as we continue to strive for improved outcomes.

Most solid-organ transplants performed in the Western world are from deceased donors. In the last decade, deceased donation rates have reached a plateau as the number of patients with end-stage organ disease has steadily increased, resulting in a large discrepancy between organ supply and demand. Living donor transplantation is one way to decrease this discrepancy. However, living donation is not universally accepted. For instance, living donation rates vary geographically (eg, living donation is more accepted in Asia than in the Western world) and depend on the organ donated (eg, kidney versus liver donation). In this article we will review the ethical principles guiding living donor liver transplantation, with emphasis on justification and safeguards that support the practice of adult-to-adult living donor liver transplantation, the most clinically and ethically challenging type of living organ donation. Our ethical justification will include a presentation of triangular or tripartite equipoise, a framework that aims to balance donor safety, expected recipient outcomes, and need.