Immunosuppression and the Risk of Post-Transplant Malignancy Among Cadaveric First Kidney Transplant Recipients

The success of renal transplantation may be counterbalanced by serious adverse medical events. The effect of immunosuppression on the incidence of de novo neoplasms among kidney recipients should be monitored continuously. Using data from the Scientific Registry of Transplant Recipients, we studied the association of induction therapy by immunosuppression with antilymphocyte antibodies, with the development of de novo neoplasms. The study population included more than 41 000 recipients who received a cadaveric first kidney transplant after December 31, 1995, and were followed through February 28, 2002. Using Cox regression models, we estimated time to development of two types of malignancy: de novo solid tumors and post-transplant lymphoproliferative disorder (PTLD). We made adjustments for several patient demographic factors and comorbidities. Induction therapy was significantly associated with a higher relative risk (RR) of PTLD (RR = 1.78, p < 0.001), but not with a greater likelihood of de novo tumors (RR = 1.07, p = 0.42). Treatment with maintenance tacrolimus vs. cyclosporine showed a significantly different RR of developing de novo tumors for recipients with induction than for those not receiving induction (p = 0.024). These new estimates of the magnitude of malignancy risk associated with induction therapy may be useful for clinical practice.     

Clinical Outcomes after Traumatic Brain Injury

Traumatic brain injury (TBI) is a major cause of death and disability that often affects young people. After injury, the degree of recovery can be highly variable, with some people regaining near complete function while others remain severely disabled. Understanding what factors influence recovery is important for counseling patients and families in the acute period after injury and can help guide therapeutic decisions in the acute period following injury. In this review, prognostic algorithms useful for clinicians are discussed. Tools for grading patient outcomes, their role in clinical care and research studies, and their limitations are reviewed. Ongoing work focusing on the development of biomarkers to track TBI recovery and the refinement of clinical outcome metrics is summarized.     

History of deceased organ donation, transplantation, and organ procurement organizations

The historical development of deceased organ donation, transplantation, and organ procurement organizations is reviewed. The concept of transplantation, taking parts from one animal or person and putting them into another animal or person, is ancient. The development of organ transplantation brought on the need for a source of organs. Although many early kidney transplants used kidneys from living donors, these donors could not satisfy the ever-growing need for organs, and extrarenal organs were recovered only from deceased donors. This need for organs to satisfy the great demand led to specialized organizations to identify deceased donors, manage them until recovery occurred, and to notify transplant centers that organs were available for their patients. The functions of these organ procurement organizations expanded to include other required functions such as education, accounting, and compliance with state and federal requirements. Because of the shortage of organs relative to the demand, lack of a unified organ allocation system, the perception that organs are a national resource and should be governed by national regulations, and to improve results of organ procurement organizations and transplant centers, the federal government has regulated virtually all phases of organ procurement and transplantation.     

Patient perspective survey of total hip vs total knee arthroplasty surgery

A 42-item survey was developed and administered to determine patient perception of and satisfaction with total hip arthroplasty (THA) vs total knee arthroplasty (TKA). A total of 153 patients who had both primary THA and TKA for osteoarthritis with 1-year follow-up were identified. Survey response rate was 72%. Patients were more satisfied with THA meeting expectations for improvement in function and quality of life (P < .05), whereas pain relief expectations were equivalent. Most patients (70.9%) reported that TKA required more physiotherapy. One-year Oxford score and improvement in Oxford score from preoperative to 1 year were superior for THAs (P = .000). Despite equivalent pain relief, THAs trend toward higher satisfaction compared with TKAs. THA is more likely to "feel normal" with greater improvement in Oxford score. Recovery from TKA requires more physiotherapy and a longer time to achieve a satisfactory recovery status. Patients should be counseled accordingly.     

Permanent acceptance of both cardiac and skin allografts using a mild conditioning regimen for the induction of stable mixed chimerism in mice

Patients who are receiving an organ transplant nowadays are sentenced to the life-long administration of immunosuppressive drugs, which have serious side effects. The reliable induction of donor-specific tolerance therefore remains a major goal in organ transplantation. Previously, we have developed a sublethal, non-myeloablative murine model in which permanent mixed, multilineage chimerism and donor-specific tolerance are established. Our model involves engraftment of fully allogeneic T cell depleted donor bone marrow cells in low dose irradiated and anti-CD3 treated major histocompatibility complex (MHC)-disparate recipient mice. To investigate whether vascularized organ grafts are accepted in our model, we performed heterotopic heart transplantations in our mixed chimeric mice. Chimeric mice permanently accepted hearts from the bone marrow donor (>130 days) and rapidly rejected third party-type allografts (median survival time 9 days). Untreated control recipient mice rejected both donor- and third party-type allografts. In addition, mice that accepted their cardiac grafts, donor-specific acceptance of skin grafts was observed. In conclusion, the establishment of stable mixed chimerism with this low-toxicity regimen resulted in permanent donor-specific acceptance of vascularized organ as well as skin grafts across a full MHC barrier.     

18F-2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography Scanning Affects Surgical Management in Selected Patients With High-Risk, Operable Breast Carcinoma

Background The role of positron emission tomography (PET) scanning in determining the extent of disease in patients with breast cancer has not been defined. We investigated the utility of ¹⁸F-2-fluoro-2-deoxy-D-glucose (FDG)-PET scanning compared with conventional imaging with computed tomographic scanning and bone scanning in determining the extent of disease in patients with high-risk, operable breast cancer. Methods This was a prospective study of patients who presented to Memorial Sloan-Kettering Cancer Center for operative treatment of breast cancer. Eighty eligible patients were enrolled and underwent computed tomographic chest, abdomen, pelvis, and bone scans, followed by FDG-PET. Changes in treatment based on scan findings were recorded by the operating surgeons. Imaging findings were verified by biopsy or long-term follow-up. Results Eight (10%) of 80 patients were found to have metastatic disease that was seen on both conventional imaging and PET. Four additional patients (5%) had additional foci of disease on PET that affected treatment decisions. No patient had findings on conventional imaging alone. Conventional imaging studies resulted in a higher number of findings that generated additional tests and biopsies that ultimately had negative results (17% vs. 5% for PET). There was a statistically significant difference in specificity for PET compared with conventional imaging (P = .01). Conclusions Conventional imaging and PET were equally sensitive in detecting metastatic disease in patients with high-risk, operable breast cancer, but PET generated fewer false-positive results. FDG-PET scanning should be further studied in this setting and considered in the preoperative evaluation of selected patients with breast cancer.     

Report of a National Conference on Donation after Cardiac Death

A national conference on organ donation after cardiac death (DCD) was convened to expand the practice of DCD in the continuum of quality end-of-life care. This national conference affirmed the ethical propriety of DCD as not violating the dead donor rule. Further, by new developments not previously reported, the conference resolved controversy regarding the period of circulatory cessation that determines death and allows administration of pre-recovery pharmacologic agents, it established conditions of DCD eligibility, it presented current data regarding the successful transplantation of organs from DCD, it proposed a new framework of data reporting regarding ischemic events, it made specific recommendations to agencies and organizations to remove barriers to DCD, it brought guidance regarding organ allocation and the process of informed consent and it set an action plan to address media issues. When a consensual decision is made to withdraw life support by the attending physician and patient or by the attending physician and a family member or surrogate (particularly in an intensive care unit), a routine opportunity for DCD should be available to honor the deceased donor's wishes in every donor service area (DSA) of the United States.