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Biomedical subjects

A I Reed

Publications and source records attributed to A I Reed.

At least 19 recordsLinked to original sources

A "weight-listing" paradox for candidates of renal transplantation?

Research suggests that end-stage renal disease patients with elevated body mass index (BMI) have superior outcomes on dialysis. In contrast, low and high BMI patients represent the highest risk cohorts for kidney transplant recipients. The important question remains concerning how to manage transplant candidates given the potentially incommensurate impact of BMI by treatment modality. We conducted a retrospective analysis of waitlisted and transplanted patients in the United States from 1990 to 2003. We constructed Cox models to evaluate the effect of BMI on mortality of waitlisted candidates and identified risk factors for rapid weight change. We then assessed the impact of weight change during waitlisting on transplant outcomes. Decline in BMI on the waiting list was not protective for posttransplant mortality or graft loss across BMI strata. Substantial weight loss pretransplantation was associated with rapid gain posttransplantation. The highest risk for death was among listed patients with low BMI (13-20 kg/m(2), adjusted hazard ratio = 1.47, p < 0.01). Approximately one-third of candidates had a change in BMI category prior to transplantation. While observed declines in BMI may be volitional or markers of disease processes, there is no evidence that candidates have improved transplant outcomes attributable to weight loss. Prospective trials are needed to evaluate the efficacy of weight loss protocols for candidates of kidney transplantation.

Adolescent↗

Effect of early recurrence of hepatitis C on late biliary anastomotic stricture after liver transplantation.

The aim of the current study was to clarify whether recurrence of hepatitis C (HCV) infection affects biliary complications after liver transplantation (OLT), with special reference to late biliary anastomotic strictures (LBAS). We reviewed 665 consecutive adult OLT recipients with a choledochocholedochostomy without T-tube placement between 1990 and 2005. Biliary anastomotic stricture was confirmed by ERCP. The LBAS was defined as stricture that occurred 30 days or more after OLT. Recurrence of HCV was diagnosed by histological examination using liver biopsy specimen and confirmed by the presence of HCV-RNA. Early HCV recurrence was defined as recurrence that occurred within 6 months after OLT; LBAS occurred in 54 patients (8% of total). Mean duration from OLT to occurrence of LBAS was 6.9 months (1-44 months). Patients with HCV infection had higher occurrence of LBAS than did non-HCV patients (11% vs 5%, P = .0093). Among HCV patients, those with early HCV recurrence had exclusively high rate of LBAS (16%). In multivariate analyses, early recurrence of HCV (P < .001, relative risk [RR] 6.4), as well as occurrence of HAT (P = .0018, RR 8.0), and prolonged CIT (P = .034, RR 3.3) were independent risk factors affecting LBAS. In conclusion, patients with HCV infection have increased occurrence of LBAS after OLT. Additionally, early recurrence of HCV contributes to a higher rate of LBAS.

Adult↗

Clinical and financial impact of obesity on the outcome of liver transplantation.

The purpose of this study was to determine whether body mass index (BMI) influences the clinical outcomes and overall cost of transplantation in adult liver transplantation (OLT) using records of 700 adult OLT recipients. Patients were divided into BMI range groups over the range of 15 to 42 (mean = 26.7), namely: <25, n = 288 (41%); 25 to 30, n = 245 (35%); > or =30, n = 167 (24%). Only a small subset of this last group was morbidly obese (BMI > or = 35, n = 37, 5% of total). We did not detect an effect of BMI on patient or graft survival, the incidence of acute graft rejection, or major surgical complications. BMI was not related to length of hospital stay. There were no statistical differences between the three groups with respect to the ratio of overall hospital cost in a general linear model, corrected for age, gender, calculated Model for End-Stage Liver Disease score, retransplant status, or return to the operating room. In conclusion, obesity did not influence either the costs or the clinical outcomes following OLT. Further analysis of the morbidly obese population with respect to cost and outcome is warranted.

Adult↗

Liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the commonest malignancies worldwide, and accounts for more than 1 million deaths annually. Identification of tumors early in the course of disease appears to be important for treatment, yet remains difficult to accomplish. Without treatment the prognosis is dismal with a median survival of 6-9 months. Partial hepatic resection is generally accepted as the treatment of choice for HCC with reported survival rates of up to 50% at 5 years. Unfortunately poor underlying liver function as well as tumor number or location preclude traditional hepatic resection in many cases. Total hepatectomy with transplantation (LT) has been advocated such cases, but the results have been variable. LT offers the advantage of radical tumor removal even in patients with multifocal disease or severe cirrhosis. Additionally, LT removes the possibility of metachronous lesions developing in the liver remnant and restores normal liver function. The critical limitation to advocating LT as primary oncotherapy in patients with HCC is the severe shortage of donor livers. Until organ availability improves, transplantation for HCC can only be offered to patients whose survival is predicted to be similar to that in patients transplanted for benign disease. This report reviews the current role and indications for liver transplantation as therapy for hepatocellular carcinoma.

Asia↗

Outcome of kidney transplants in patients known to be flow cytometry crossmatch positive.

BACKGROUND: The clinical significance of the flow cytometry crossmatch has been addressed in several retrospective studies, but the results have been controversial. There are no prospective studies in which patients known to be antibody positive underwent transplantation. METHODS: The flow cytometry crossmatch was performed prospectively in 1130 renal transplant recipients. A decision to perform transplantation was based on whether the positive results were on T or B cells, in the current or peak specimen, and taking into account the presence or absence of other immunological risk factors. One hundred antibody-positive patients received a transplant. Graft survival and rejection episodes were analyzed in this group and compared with 100 crossmatch-negative patients matched for age, sex, race, and time of transplantation. RESULTS: The incidence of rejection at 1 month was higher in antibody-positive patients (26%) than in antibody-negative patients (12%, P<0.01). Early rejection seemed to be more frequent in antibody-positive patients regardless of whether the antibodies were current or historic, or against T or B cells. There were more steroid-resistant rejections in antibody-positive than in antibody-negative patients. However, biopsy specimens showed that vascular lesions that can be associated with humoral rejection were not more frequent in the antibody-positive patients than in the controls. There were no differences in graft survival between the two groups. CONCLUSIONS: Low-level preformed alloantibodies detected by flow cytometry represent a risk of rejection even for patients purposely selected for having no additional immunological risk factors. The risk seems to be due to donor-specific memory rather than to a direct effect of the antibodies. The results indicate that flow cytometry provides useful information to assess donor-recipient compatibility.

B-Lymphocytes↗

Susceptibility of liver allografts to high or low concentrations of preformed antibodies as measured by flow cytometry.

Liver grafts are more resistant to damage by HLA antibodies than other organ allografts, but it is not clear if the antibodies are associated with graft rejection or graft loss, or if different antibody concentrations have different effects. To explore potential associations between antibody concentrations and outcome, preformed IgG antibodies against donor cells were quantified by flow cytometry in 465 consecutive liver transplant recipients. Antibody-positive patients were classified according to whether they had high or low antibody concentrations and analyzed for possible correlation with graft rejection or graft loss. The results showed that the incidence of rejection was not significantly different between antibody-positive and negative patients. However, patients with high antibody concentrations had a higher incidence of steroid-resistant rejections (31% at 1 year) than patients with low antibody (4%) or no antibody (8%, p < 0.0004). These effects were mainly due to T-cell (HLA class 1) antibodies. The overall incidence of rejection at 1 year was 69% for high antibody patients, 51% for patients with low antibodies and 53% for patients with no antibodies (p not significant). In an apparent paradox, antibody-positive patients underwent fewer early graft losses. Thus, the associations of preformed antibodies and outcome depend, on the one hand, on antibody concentrations, and on the other hand on whether the outcome measured is steroid-sensitive rejection, steroid-resistant rejection or graft survival. These complex interactions may explain the controversial results observed in previous studies.

Adolescent↗

What happens to renal transplant recipients who lose their grafts?

Little attention has been given to the fate of patients who lose their grafts. We reviewed outcomes of 438 recipients of first renal allografts who underwent transplantation at our institution between January 1, 1988, and December 31, 1997, and lost their grafts or died with a functioning transplant. Of the 438 patients, 168 patients died with a functioning transplant. The most common causes of death were cardiac disease, infection, and cancer. Patients who died with a functioning graft were older (>49 years, 64.3%) than patients who died after returning to dialysis therapy or who are still alive (>49 years, 25.9%). Eighty-six patients (39%) who returned to dialysis therapy were again placed on a cadaveric waiting list. Only 44 patients received a second transplant, of which 30 transplants (68.2%) are still functioning. Our study shows that relatively few patients who lose kidney transplants are returned to the cadaveric waiting list and even fewer undergo retransplantation.

Adolescent↗

Graft survival in pediatric liver transplantation.

BACKGROUND/PURPOSE: Liver transplantation is standard therapy for children with a variety of liver diseases. The current shortage of organ donors has led to aggressive use of reduced or split grafts and living-related donors to provide timely liver transplants to these children. The purpose of this study is to examine the impact of these techniques on graft survival in children currently treated with liver transplantation. METHODS: Data were obtained on all patients less than 21 years of age treated with isolated liver transplants performed after January 1, 1996 in an integrated statewide pediatric liver transplant program, which encompasses 2 high-volume centers. Nonparametric tests of association and life table analysis were used to analyze these data (SAS v 6.12). RESULTS: One hundred twenty-three children received 147 grafts (62 at the University of Florida, 85 at the University of Miami). Fifty-two (36%) children were less than 1 year of age at time of transplant, and 80 (55%) were less than 2 years of age. Patient survival rate was identical in the 2 centers (1-year actuarial survival rate, 88.4% and 87.1%). Twenty-five (17%) grafts were reduced, 28 (19%) were split, 6 were from living donors (4%), and 88 (60%) were whole organs. One-year graft survival rate was 80% for whole grafts, 71.6% for reduced grafts, and 64.3% for split grafts (P =.06). Children who received whole organs (mean age, 6.1 years) were older than those who received segmental grafts (mean age, 2.5 years; P <.01). Multifactorial analysis suggested that patient age, gender, and use of the graft for retransplant did not influence graft survival, nor did the type of graft used influence patient survival. CONCLUSIONS: The survival rate of children after liver transplantation is excellent independent of graft type. Use of current techniques to split grafts between 2 recipients is associated with an increased graft loss and need for retransplantation. Improvement in graft survival of these organs could reduce the morbidity and cost of liver transplantation significantly in children.

Age Distribution↗

Liver transplantation for hepatocellular carcinoma.

OBJECTIVE: To analyze patient and tumor characteristics that influence patient survival to select patients who would most benefit from liver transplantation. SUMMARY BACKGROUND DATA: The selection of patients with hepatocellular carcinoma (HCC) for liver transplantation remains controversial. METHODS: One hundred twelve patients with nonfibrolamellar HCC who underwent a liver transplant from 1985 to 2000 were reviewed. Survival was calculated using the Kaplan-Meier method, with differences in outcome assessed using the log-rank procedure. Multivariate analysis was then performed using a Cox regression model. RESULTS: Overall patient survival rates were 78%, 63%, and 57% at 1, 3, and 5 years, respectively. Patients infected with the hepatitis B virus had a worse 5-year survival than those who were not (43% vs. 64%), with most deaths being attributed to recurrent hepatitis B. However, patients with hepatitis B virus who underwent more recent transplants using antiviral therapy fared as well as those who were negative for the virus, showing a 5-year survival rate of 77%. Patients with vascular invasion by tumor had a worse 5-year survival than patients without vascular invasion (33% vs. 68%). Vascular invasion, tumor size greater than 5 cm, and poorly differentiated tumor grade were predictors of tumor recurrence by univariate analysis; however, only vascular invasion remained significant on multivariate analysis: the rate of tumor recurrence at 5 years was 65% in patients with vascular invasion and only 4% for patients without vascular invasion. CONCLUSIONS: For well-selected patients with HCC, liver transplantation in the current era can achieve equivalent results to transplantation for nonmalignant indications. Vascular invasion is an indicator of high risk of tumor recurrence but is difficult to detect before transplantation.

Adolescent↗

Resection of the inferior vena cava for hepatic malignancy.

Involvement of the inferior vena cava (IVC) by hepatic tumors, although uncommon, is considered to be unresectable by standard surgical techniques. Recent advances in hepatic surgery have made combined hepatic and vena caval resection possible. The purpose of this study is to describe the surgical techniques and early results of combined resection of the liver and IVC. From 1997 to 2000, 11 patients underwent resection of the IVC along with four to seven liver segments. Resections were carried out for hepatocellular carcinoma (four); colorectal metastases (four); and hepatoblastoma, gastrointestinal stromal tumor metastases, and squamous cell carcinoma in one patient each. Ex vivo procedures were performed twice, and total vascular isolation was used in the nine other cases. The IVC was reconstructed with ringed Gore-Tex tube graft (five), primarily (five), or with Gore-Tex patches (one). There were two early deaths: one from liver failure at 3 weeks and one from sepsis secondary to a perforated segment of small bowel 4 months postresection. One patient with a gastrointestinal stromal tumor died at 32 months of recurrent tumor and one patient with hepatocellular carcinoma is alive with recurrent tumor at 16 months. The remaining patients are alive and disease free with follow-up ranging from 3 to 40 months without evidence of IVC occlusion. Combined resection of the liver and IVC is a formidable undertaking with substantial surgical risk. However, this aggressive surgical approach offers a chance for cure in patients with tumors involving the IVC that would otherwise have a dismal prognosis.

Adolescent↗

Infusion of donor spleen cells and rejection in liver transplant recipients.

Intact or inactivated donor lymphoid cells have been found to downregulate the alloimmune response in a number of experimental models. We conducted a randomized, prospective, double blind, and placebo-controlled trial to determine whether heat-treated donor spleen cells would affect early rejection after liver transplantation. Donor spleen was obtained during organ procurement for 40 patients undergoing liver transplantation. All patients were treated with cyclosporine, azathioprine and steroids. The patients were randomized after surgery to receive either heat-treated (45 degrees C for 1 h) spleen cells or placebo. Patients underwent protocol biopsies at 1 wk, 4 and 12 months, or as needed. Biopsies were reviewed in a blind fashion and scored according to the Banff consensus criteria. Randomization resulted in 19 patients in the spleen cell group and 21 in the placebo group. One-yr graft survival was 94 and 100%, respectively. Early rejection was more frequent in the spleen cell group (61 vs. 35%, p, not significant). The histopathological rejection activity index at 7 d was also higher for the patients in the spleen cell group: 39% of spleen cell treated patients had a score of 4 or higher as opposed to 5% in the placebo group (p < 0.01). The mean score was 2.9 +/- 2.8 for the spleen cell group versus 1.3 + 1.7 for the placebo group (p = 0.034). It is concluded that heat-treated donor spleen cells given within 24 h after liver transplantation were not clinically beneficial and increased the intensity of rejection in 7-d protocol liver biopsies.

Cell Transplantation↗

Delayed graft function after renal transplantation.

BACKGROUND: There is a strong association between delayed graft function (DGF) and reduced graft survival (GS) of cadaveric renal transplants. This study was performed to identify donor characteristics that might predict adverse outcomes. METHODS: We reviewed the folders of 509 consecutive organ donors for 586 renal transplant recipients receiving grafts between 1990 and 1995. A uniform immunosuppression protocol was employed. RESULTS: The factors that did not alter the rate of DGF were procurement year, local versus shared organs, donor gender, race, hypotension, serum creatinine level and trend, blood transfusions, and vasopressor use and dose. The factors that did alter the frequency of DGF were cause of death (P=0.0053), donor age (P=0.0017), cold ischemic time (P=0.0009), anastomotic time (P=0.0012), combined cold ischemic time and anastomotic time (P=0.00018), and body mass index (P=0.009). All of the factors with the exception of body mass index were of comparable import when analyzed by multiple logistic regression. One-year GS of patients without DGF was 93.2%, and the GS of those with DGF was 76.6% (P < 0.0001). However, none of the donor factors correlated with 1-year GS. Seventy-seven donors were the source of paired transplants performed by our program. Sixty percent were concordant for immediate function, 32% were discordant for DGF with equal numbers affecting the first or second graft, and in only 8% did DGF affect both grafts. CONCLUSIONS: Donor factors associated with DGF were increased ischemia, donor age, and cause of death. Although there is a close association between DGF and reduced GS, there is no association between these donor factors and GS. This seeming paradox suggests that unknown variables contribute heavily to early graft outcome.

Adolescent↗

Nonheartbeating cadaveric organ donation.

OBJECTIVE: The authors evaluated the potential use of nonheartbeating (NHB) cadaver donors as an additional source to the current supply of brain-dead cadaver donors. SUMMARY BACKGROUND DATA: The numbers of cadaveric donors has not increased significantly during the last 5 years, despite a rising need for transplantable organs. Any improvement in cadaveric organ procurement will depend on the use of previously unrecognized potential donors. METHODS: During a 2-year period, 24 kidneys were retrieved from 12 NHB donors. Nineteen kidneys were transplanted. RESULTS: These kidneys sustained a mean warm ischemia time of 26 minutes (range 20-35 min). A mean lowest creatinine level of 2.0 mg/dL, (range 1.1-3.0 mg/dL), the rate of postoperative dialysis (22%), and a 1-year graft survival rate of 76% for kidneys from NHB-donated kidneys compare favorably to expected results achieved nationally from brain-dead cadaveric donors. CONCLUSIONS: Nonheartbeating donor kidneys can yield acceptable graft function and be of no disadvantage to recipients of cadaver transplants.

Adolescent↗

Plasma pancreatic secretory trypsin inhibitor as a marker of pancreas graft rejection after combined pancreas-kidney transplantation.

One of the major problems in clinical pancreas transplantation is the lack of a simple and sensitive marker for detecting the early process of allograft rejection. Plasma pancreatic secretory trypsin inhibitor (p-PSTI) levels were measured in recipients of combined pancreas-kidney transplants (SPKT) and isolated cadaveric renal transplants (CRT) as controls. In the postoperative courses of SPKT recipients without acute rejection episodes and any other complications, high preoperative and immediate postoperative concentrations of p-PSTI gradually declined from the third day after transplantation and returned to the baseline level (less than 87.9 ng/ml) by the 6th day, and then remained unchanged. In this study, 11 out of 17 SPKT recipients experienced 13 acute rejection episodes. Early in the rejection course, p-PSTI levels increased significantly (P less than 0.05) 1 day before the initial day of diagnosed rejection (peak value; 232.7 +/- 99.3 ng/ml), and then they decreased following antirejection therapy. In the control group, p-PSTI elevation was less dramatic (peak value: 70.5 +/- 22.8 ng/ml, P less than 0.01) and did not precede the rise in serum creatinine. We conclude that p-PSTI may be an early, sensitive, and reliable marker of clinical pancreas graft rejection.

Adult↗