Biomedical subjects

Maureen A McBride

Publications and source records attributed to Maureen A McBride.

At least 19 recordsLinked to original sources

PubMed2006

Trends over a decade of pediatric liver transplantation in the United States.

During the last 10 to 15 years, medical and surgical innovations have established pediatric liver transplantation as the optimal therapy for children suffering acute and chronic liver disease. We hypothesized that the profile of current pediatric liver transplant recipients would differ significantly from that of an earlier era. We collected and compared data regarding the characteristics of children undergoing liver transplantation alone in 2 eras separated by more than a decade from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Transplant recipients from March 1, 2002 to December 31, 2004, compared to those from January 1, 1990, to December 31, 1992, tended to be more evenly distributed across age, race/ethnicity, and disease etiology. There was a major shift toward utilization of partial grafts from both deceased and living donors to achieve transplantation for the youngest children (<1 and 1-5 yr) in particular. However, in spite of these innovative transplant strategies and only a modest increase in demand for pediatric liver transplantation, wait list times for both pediatric candidates and recipients have still increased between eras. In conclusion, the sobering reality that mortality on the waiting list remains highest for the youngest pediatric liver candidates frames our challenge for the next decade.

Adolescent↗

PubMed2006

Post-transplant de novo malignancies in renal transplant recipients: the past and present.

Post-transplant de novo malignancies are reviewed in three time periods: (i) the azathioprine (AZA) era from 1962 to 1980-1981, (ii) the cyclosporine (CYA) era (1980 to present) in which the calcineurin inhibitors, CYA and tacrolimus (TAC), were the mainstay of recipient immunosuppression, and (iii) the TOR inhibitor era starting in the year 2000. Both transplant registry and transplant center reports on malignancies occurring in the AZA era are reviewed. Reports from transplant centers and from the Cincinnati Transplant Tumor Registry (CTTR) in both the early CYA era (1980s) and the 1900-2000 CYA era are reported. Cancer incidence associated with AZA versus CYA, CYA versus TAC, and AZA versus mycophenolate mofetil (MMF) is compared in both transplant center and registry reports including new, unreported Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) data from 1998 to 2003. The malignancy incidence associated with lymphocyte-depleting antibody and corticosteroid immunosuppression is discussed. Reduced malignancy incidence recently reported with TOR inhibitors is compared with that of conventional immunosuppression. Important nondrug factors influencing the incidence of post-transplant malignancies from seven single and three registry reports are detailed. The substantial role that de novo malignancies play in post-transplant mortality is discussed. Finally, management recommendations for recipients who develop de novo post-transplant malignancies are briefly presented.

Antilymphocyte Serum↗

PubMed2005

Skin cancer in organ transplant recipients: effect of pretransplant end-organ disease.

BACKGROUND: Solid organ transplant recipients are at increased risk for posttransplant neoplasms. OBJECTIVE: Our purpose was to determine whether various diseases causing end-organ failure are associated with different degrees of risk of skin cancer development after transplantation. METHODS: The Organ Procurement and Transplantation Network/United Network for Organ Sharing Transplant Tumor Registry was searched for the incidence of skin cancer among kidney, liver, and heart transplant recipients in the United States between 1996 and 2001. Multivariate analysis was used to determine the association between disease diagnosis and posttransplant skin cancer. RESULTS: Transplant recipients with specific pretransplant diseases, such as polycystic kidney disease and cholestatic liver disease, were at increased risk for skin cancer. Patients with diabetes mellitus had a lower incidence of skin cancer after kidney transplantation. LIMITATIONS: The study had only a brief follow-up period, indirect assessment of photodamage, and possible underreporting. CONCLUSION: Transplant recipients with a history of certain diseases warrant intensive skin cancer surveillance and strict sun-protective practices.

Adolescent↗

PubMed2005

Impact of the expanded criteria donor allocation system on the use of expanded criteria donor kidneys.

BACKGROUND: The U.S. Organ Procurement and Transplantation Network recently implemented a policy allocating expanded criteria donor (ECD) kidneys by waiting time alone. ECD kidneys were defined as having a risk of graft failure > or = 1.7 times that of ideal donors. ECDs include any donor > or = 60 years old and donors 50 to 59 years old with at least two of the following: terminal creatinine >1.5 mg/dL, history of hypertension, or death by cerebrovascular accident. The impact of this policy on use of ECD kidneys is assessed. METHODS: The authors compared use of ECD kidneys recovered in the 18 months immediately before and after policy implementation. Differences were tested using t test and chi2 analyses. RESULTS: There was an 18.3% increase in ECD kidney recoveries and a 15.0% increase in ECD kidney transplants in the first 18 months after policy implementation. ECD kidneys made up 22.1% of all recovered kidneys and 16.8% of all transplants, compared with 18.8% (P<0.001) and 14.5% (P<0.001), respectively, in the prior period. The discard rate was unchanged. The median relative risk (RR) for graft failure for transplanted ECD kidneys was 2.07 versus 1.99 in the prepolicy period (P=not significant); the median RR for procured ECD kidneys was unchanged at 2.16. The percentage of transplanted ECD kidneys with cold ischemia times (CIT) <12 hr increased significantly; the corresponding percentage for CIT > or = 24 hr decreased significantly. CONCLUSIONS: The recent increase in ECD kidney recoveries and transplants appears to be related to implementation of the ECD allocation system.

Humans↗

PubMed2005

Laparoscopic live donor nephrectomy: a risk factor for delayed function and rejection in pediatric kidney recipients? A UNOS analysis.

The impact of laparoscopic (vs. open) donor nephrectomy on early graft function and survival in pediatric kidney recipients (< or =18 years) is unknown. We studied 995 pediatric live donor txs reported to UNOS from January 2000 to June 2002, in two recipient age groups: 0-5 years (n = 212, 44% laparoscopic donors [LapD]) and 6-18 years (n = 783, 50% LapD). Delayed graft function (DGF) rates were higher for LapD versus open donor (OpD) txs (0-5 years, 12.8% vs. 2.5% [p = 0.004]; 6-18 years, 5.9% vs. 2.8% [p = 0.03]). Acute rejection incidence for LapD versus OpD txs was higher at 6 months for recipients 0-5 years (18.6% vs. 5.9%, p = 0.01) and 6-18 years (22.5% vs. 15.6%, p = 0.03), and 1 year for recipients 0-5 years (24.3% vs. 7.9%, p = 0.004). In multivariate analyses, significant independent risk factors for rejection at 6 months and 1 year were recipient age 6-18 years, pretx dialysis, LapD nephrectomy and DGF. Graft survival was similar for LapD versus OpD txs. In this retrospective UNOS database analysis, LapD procurement was associated with increased DGF and an independent risk factor for rejection during the first year, particularly for recipients 0-5-years old. Future investigations must confirm these findings and identify strategies to optimize procurement and pediatric recipient outcome.

Adolescent↗

PubMed2004

Survival after pancreas transplantation in patients with diabetes and preserved kidney function.

CONTEXT: Solitary pancreas transplantation (ie, pancreas alone or pancreas-after-kidney) for diabetes mellitus remains controversial due to procedure-associated morbidity/mortality, toxicity of immunosuppression, expense, and unproven effects on the secondary complications of diabetes. Whether transplantation offers a survival advantage over conventional therapies for diabetes is unknown. OBJECTIVE: To determine the association between solitary pancreas transplantation and survival in patients with diabetes and preserved kidney function. DESIGN, SETTING, AND PATIENTS: Retrospective observational cohort study conducted at 124 transplant centers in the United States, in 11 572 patients with diabetes mellitus on the waiting list for pancreas transplantation (pancreas alone, pancreas-after-kidney, or simultaneous pancreas-kidney) at the United Network for Organ Sharing/Organ Procurement and Transplantation Network between January 1, 1995, and December 31, 2000. All patients receiving a multiorgan (other than simultaneous pancreas-kidney) transplant were excluded, as were those listed for solitary pancreas transplantation who had a serum creatinine level greater than 2 mg/dL (176.8 micromol/L) at time of listing, or who ultimately received a simultaneous pancreas-kidney transplant. MAIN OUTCOME MEASURE: All-cause mortality within 4 years following transplantation (or within a comparable time on the waiting list for the group not undergoing transplantation). RESULTS: Overall relative risk of all-cause mortality for transplant recipients (compared with patients awaiting the same procedure) over 4 years of follow-up was 1.57 (95% confidence interval [CI], 0.98-2.53; P =.06) for pancreas transplant alone, 1.42 (95% CI, 1.03-1.94; P =.03) for pancreas-after-kidney transplant, and 0.43 (95% CI, 0.39-0.48) for simultaneous pancreas-kidney transplant. Transplant patient 1- and 4-year survival rates were 96.5% and 85.2% for pancreas transplant alone, respectively, and 95.3% and 84.5% for pancreas-after-kidney transplant, while 1- and 4-year survival rates for patients on the waiting list were 97.6% and 92.1% for pancreas transplant alone, respectively, and 97.1% and 88.1% for pancreas-after-kidney transplant. CONCLUSION: From 1995-2000, survival for those with diabetes and preserved kidney function and receiving a solitary pancreas transplant was significantly worse compared with the survival of waiting-list patients receiving conventional therapy.

Adolescent↗

PubMed2003

Association of the type of induction immunosuppression with posttransplant lymphoproliferative disorder, graft survival, and patient survival after primary kidney transplantation.

BACKGROUND: The use of antilymphocyte antibodies for induction therapy or for treatment for rejection has been associated with an increased risk of posttransplant lymphoproliferative disorder (PTLD). The authors investigated the incidence of PTLD after monoclonal antilymphocyte, polyclonal antilymphocyte, interleukin (IL)-2 receptor antibody, or no induction therapy in primary kidney transplant recipients. METHODS: A multivariate Cox analysis of 38,519 primary kidney transplants from January 1, 1997, to December 31, 2000, was performed to compare the incidence of PTLD, graft survival, and patient survival among the induction groups. RESULTS: The actual incidence of PTLD was 0.85% in 2,713 recipients with monoclonal, 0.81% in 4,343 with polyclonal, 0.50% in 7,800 with IL-2, and 0.51% in 23,663 recipients with no induction therapy (P=0.02). The Cox model indicated that as compared with no induction, the increased risk of PTLD was 72% with monoclonal (P=0.03), 29% with polyclonal (P=0.27), and 14% with IL-2 induction (P=0.52). IL-2 receptor antibody was associated with a 17% reduced risk of graft loss (P=0.002) and a 21% reduced risk of mortality (P=0.005) compared with no induction. Monoclonal and polyclonal induction therapies were not associated with a reduced risk of graft loss or mortality. Mycophenolate mofetil discharge maintenance immunosuppression was associated with a significantly reduced risk of PTLD and graft loss compared with azathioprine. CONCLUSIONS: Among induction therapies, IL-2 receptor antibody induction was associated with the smallest risk of PTLD and improved graft and patient survival. Monoclonal or polyclonal induction was not associated with improved graft or patient survival, and monoclonal induction was associated with an increased risk of PTLD.

Adolescent↗

PubMed2003

Hormonal resuscitation yields more transplanted hearts, with improved early function.

BACKGROUND: Brain death results in cardiovascular instability and poor organ perfusion in many brain-dead donors. Hormonal resuscitation stabilizes certain brain-dead donors and is associated with significant increases in the numbers of organs transplanted per donor. The goal of this study was to examine the quality of hearts recovered from donors treated with hormonal resuscitation. METHODS: A retrospective analysis of 4,543 recipients of hearts recovered from brain-dead donors, reported to the United Network for Organ Sharing/Organ Procurement and Transplantation Network database between November 1, 1999, and December 31, 2001, was conducted. Hormonal resuscitation consisted of a methylprednisolone bolus and infusions of vasopressin and either triiodothyronine or l-thyroxine. Univariate and multivariate analyses were used to evaluate the quality of hearts from donors who received three-drug hormonal resuscitation (3HR) treatment versus donors who did not receive all three drugs (non-3HR). Death within 30 days and early graft dysfunction were used as endpoints. RESULTS: Hearts from 3HR donors demonstrated a 1-month survival rate of 96.2%, compared with a 92.1% survival rate for non-3HR donor hearts (P<0.01). Early graft dysfunction occurred in 5.6% of 3HR donor hearts and 11.6% of non-3HR donor hearts (P<0.01). Multivariate results demonstrated a 46% reduced odds of death within 30 days and a 48% reduced odds of early graft dysfunction. Steroids alone and steroids plus triiodothyronine/l-thyroxine also significantly reduced prolonged graft dysfunction. CONCLUSIONS: This study suggests that 3HR treatment of brain-dead donors results in increased numbers of transplanted hearts, with improved short-term graft function.

Adult↗

PubMed2003

Aggressive pharmacologic donor management results in more transplanted organs.

BACKGROUND: Brain death results in adverse pathophysiologic effects in many cadaveric donors, resulting in cardiovascular instability and poor organ perfusion. Hormonal resuscitation (HR) has been reported to stabilize and improve cardiac function in brain-dead donors. The goal of this study was to examine the effect of HR on the brain-dead donor on the number of organs transplanted per donor. METHODS: A retrospective analysis of all brain-dead donors recovered in the United States from January 1, 2000, to September 30, 2001, was conducted. HR consisted of a methylprednisolone bolus and infusions of vasopressin and either triiodothyronine or L-thyroxine. Univariate analyses and multivariate logistic regression analyses were used to detect differences between the HR group and those donors who did not receive HR. RESULTS: Of 10,292 consecutive brain-dead donors analyzed, 701 received three-drug HR. Univariate analysis showed the mean number of organs from HR donors (3.8) was 22.5% greater than that from nonhormonal resuscitation donors (3.1) (P <0.001). Multivariate analyses showed that HR was associated with the following statistically significant increased probabilities of an organ being transplanted from a donor: kidney 7.3%, heart 4.7%, liver 4.9%, lung 2.8%, and pancreas 6.0%. Extrapolation of these probabilities to the 5,921 brain-dead donors recovered in 2001 was calculated to yield a total increase of 2,053 organs. CONCLUSION: HR stabilizes certain brain-dead donors and is associated with significant increases in organs transplanted per donor.

Adult↗

PubMed2003

Evolution of endpoints for renal transplant outcome.

Progressive improvement in short-term kidney transplant survival and reduction in acute rejection rates have restricted our ability to assess newer therapy. Past and present conventional endpoints, such as short-term graft survival and acute rejection rates, are no longer practical. This has prompted investigators to search for alternative endpoints. Long-term graft survival is an ideal endpoint. However, this requires a large cohort of patients with longer follow-up. A simpler approach would be to identify short-term markers, which can predict long-term survival. Short-term potential markers that can predict long-term survival are: clinical (renal function), histological (renal pathological markers) and immunological (anti-donor antibody, blood and urine cytokines). Post-transplant renal function estimated by serum creatinine, cystatin C and creatinine clearance within 1 year, and histological indices, as the Banff chronicity score, have the potential to predict long-term graft survival. Serum creatinine is limited as a marker by its variability based on recipient age, body weight, race and sex. Histological indices are limited, due to the invasive nature of evaluation. Post-transplant renal function and histological indices can be used potentially as a composite endpoint, in combination with conventional endpoints, such as graft loss, death and acute rejection. A practical approach for assessing newer therapies in future studies is to use composite endpoints, which combine conventional endpoints (graft loss, death, acute rejection) with newer endpoints (renal function, histological indices).

Creatinine↗

PubMed2003

The OPTN waiting list, 1988-2002.

1. Additions to the OPTN waiting list decreased in 2002 for all organs except kidney and pancreas islets. 2. On November 30, 2003, there were 89,361 registrations on the combined UNOS waiting list. Of these, 67% were awaiting kidney transplantation, and 20% were awaiting liver transplantation. 3. The majority of patients on the UNOS waiting list on October 31, 2000 were of blood type O (52%), White (51%) and male (57%), and awaiting their first transplant (87%). 4. Despite lengthy waiting times, the percentage transplanted within one year following listing has increased over the past 2 years for all organs except kidney. A tremendous increase in the percentage of liver candidates transplanted within one year was observed in 2002. 5. Blood type and medical urgency have a significant impact upon the percent transplanted within one year of listing for most organ types. Patients awaiting heart, liver, pancreas, and intestinal transplants experience the highest probability of receiving a transplant within one year. 6. Death rates per patients waiting at risk have declined since 1988 for most patients awaiting life-saving organs and have remained relatively low for those awaiting a kidney, pancreas, or kidney-pancreas transplant.

Adolescent↗

PubMed2002

Organ donors with positive viral serology or malignancy: risk of disease transmission by transplantation.

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Hepatitis, Viral, Human↗

PubMed2002

Living kidney donors in need of kidney transplants: a report from the organ procurement and transplantation network.

BACKGROUND: Our aim was to use the Organ Procurement and Transplantation Network (OPTN) database to determine the number of renal waitlist candidates who previously had been living donors. METHODS: All living renal donors in the OPTN database were cross-checked against the renal waitlist history files. Additionally, renal transplant programs were contacted that had listed candidates as qualified for four additional allocation points available to patients who previously had donated an organ. Confirmatory phone calls to transplant programs yielded additional cases previously unreported to the United Network for Organ Sharing. RESULTS: A total of 56 previous living donors were identified as having been subsequently listed for cadaveric kidney transplantation. Forty-three have received transplants; 36 currently have functioning grafts. One died after transplantation. Two candidates died while waiting. CONCLUSIONS: Living renal donation has long-term risks that may not be apparent in the short term. The numbers here reported underestimate the actual number of living donors with renal failure, because they include only patients listed for a kidney transplant. To determine risk factors for postdonation renal failure, long-term living-donor follow-up data are needed.

Databases as Topic↗

PubMed2002

Survival of mandatorily shared cadaveric kidneys and their paybacks in the zero mismatch era.

BACKGROUND: The United Network for Organ Sharing has mandated the national sharing of well-matched cadaveric kidneys with payback to the national pool. On March 6, 1995, the policy was extended to include sharing of cadaveric kidneys for which there is a recipient with a 0-HLA mismatch (0-MM). However, the beneficial effects of this policy have been questioned. To address these concerns, we analyzed the effects of this system on graft survival, cold ischemia time, and the transplantation of highly sensitized patients during the 0-MM era. METHODS: We analyzed cadaveric solitary kidney transplant data in the OPTN/The United Network for Organ Sharing database. Cox proportional hazards analyses were conducted on 29,401 transplants performed between March 6, 1995 and December 31, 1998 to assess the effects of mandatory sharing and paybacks on graft outcome. We also compared the outcome of pairs of kidneys in which one was shared as either an 0-MM kidney (n=833) or as a payback (n=440) and the mate was transplanted locally. RESULTS: Overall, 36% of kidneys were shared, 15.6% as 0-MM and 20.4% as paybacks or other shares. Although the sharing of 0-MM kidneys significantly increased cold ischemia time, the risk of graft loss was significantly decreased. The survival of payback kidneys was not significantly different from other shared kidneys. Sharing 0-MM kidneys appeared to increase the chances of transplantation of sensitized patients and 47% of the kidneys transplanted in patients with a panel reactive antibody of more than 80% were from 0-MM donors. CONCLUSIONS: National sharing of 0-MM kidneys appears to lead to a small but significant improvement in intermediate-term graft survival despite increasing cold ischemia time. The current policy also increases access of highly sensitized patients to transplantation.

Adolescent↗

PubMed2002

Transplant tumor registry: donor related malignancies.

BACKGROUND: Transmission of donor malignancies has been intermittently reported since the early days of clinical transplantation. The incidence of United States donor related malignancies has not previously been documented. METHODS: All donor related malignancies reported to the Organ Procurement and Transplantation Network/United Network for Organ Sharing from 4/1/94-7/1/01 in a cohort of 34,933 cadaveric donors and 108,062 recipients were investigated by contacting the transplant centers to verify that the reported tumors were of donor origin. Time and mode of discovery, as well as graft and patient outcome, were determined. The status of other recipients from the donor was investigated. RESULTS: A total of 21 donor related malignancies from 14 cadaveric and 3 living donors were reported. Fifteen tumors were donor transmitted and 6 were donor derived. Transmitted tumors are malignancies that existed in the donor at the time of transplantation. Derived tumors are de novo tumors that develop in transplanted donor hematogenous or lymphoid cells after transplantation. The cadaveric donor related tumor rate is 0.04% (14 of 34,993). The donor related tumor rate among transplanted cadaveric organs is 0.017% (18 of 108,062). Among patients developing donor related malignancies, the overall mortality rate was 38%, with that of transmitted tumors being 46% and derived tumors being 33%. The cadaveric donor related tumor mortality rate is 0.007% (8 of 108,062). CONCLUSIONS: The United States incidence of donor related tumors is extremely small. The donor related tumor death rate is also extremely small, particularly when compared with waiting-list mortality.

Cadaver↗

PubMed2002

Transplant tumor registry: donors with central nervous system tumors1.

BACKGROUND: Despite 13,000 central nervous system (CNS) tumor deaths per year in the United States, CNS tumor donors comprise only 1% of cadaveric donors recovered per year. Concern about tumor transmission may be a possible reason for this very small percentage. Both the size of the candidate waiting list and the number of deaths on the waiting list are progressively increasing because of the donor shortage. METHODS: During a 96-month period, the United Network for Organ Sharing recorded 42,340 cadaver donors of whom 397 had a past history of a CNS tumor or the cause of death listed as a CNS tumor. A total of 1,220 organs were transplanted from these 397 donors. All recipients who reported a posttransplant malignancy during a mean follow-up of 36 months were identified. RESULTS: There was no difference in patient survival of organs from CNS tumor donors when compared to donors with no CNS tumors. CNS tumor donors were not used more often for either urgent or older recipients. A total of 39 patients reported posttransplant malignancies but none of these tumors were donor-derived. There is a wide variation in the number of CNS tumor donors utilized by individual organ procurement organizations. CONCLUSIONS: The risk of tumor transmission from donors with CNS malignancies seems to be small. Certain tumors, such as glioblastoma multiforme and medulloblastoma, carry a high risk of transmission and should be avoided. The risk of tumor transmission should be weighed against the risk of the patient dying on the waiting list without a transplant.

Cadaver↗

PubMed2002

Increased transplanted organs from the use of a standardized donor management protocol.

The organ shortage has resulted in increasing recipient waiting lists and waiting-list deaths. The increased use of expanded donors has been associated with increased discarding of procured organs because of poor organ function. A structured donor management algorithm or critical pathway was tested to determine its effect on the donor management and procurement process. A pilot study examined donors from 88 critical care units in 10 organ procurement organizations managed under the critical pathway and compared them to retrospective data collected at those same pilot sites. The total number of organs both procured and transplanted per 100 donors was significantly greater (p <0.01) in the critical pathway group when compared to the control group. There was no significant difference in 1-year graft survival for any of the organs recovered, and no significant difference in the rate of delayed graft function in the kidneys transplanted. Use of a structured donor management algorithm results in significant increases in organs procured and organs transplanted without any reduction in the quality of the organs being transplanted.

Clinical Protocols↗