The impact of donor factors on the outcomes following liver transplantation.
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Publications and source records attributed to A Lo.
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We report the case of a pancreas-alone transplant recipient who developed Rhodococcus equi pneumonia after receiving multiple courses of antilymphocyte therapy for the treatment of recurrent acute pancreas allograft rejection. We also review and discuss the diagnosis, clinical course, and treatment of 18 cases of R. equi infection reported in solid organ transplant recipients. The lung is the most common primary site of infection, but R. equi infection is difficult to diagnose because of the pleomorphic, gram-positive, and partially acid-fast nature of the organism. Treatment usually involves a combination of antibiotics including rifampin, macrolides, vancomycin, and ciprofloxacin. The optimal duration of therapy is unknown, but relapse is common if the duration of treatment is less than 14 days. The duration of therapy should be guided by clinical recovery, culture results, and radiographic findings. Monitoring levels of immunosuppressive agents-such as tacrolimus and cyclosporine-is needed in order to avoid clinically significant drug interactions with rifampin or the macrolides when these agents are used in order to treat R. equi infection in the transplant population.
We report an experience with 71 simultaneous kidney-pancreas transplant (SKPT) recipients receiving daclizumab induction in combination with tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. The mean follow-up time was 5.9+/-2.5 (SD) months (range 0.5-11 months). The study population included 47 males (65%) and 24 females (35%) with a mean age of 40+/-8 years. The mean pretransplant duration of diabetes and dialysis were 25+/-8 and 1.5+/-0.9 years (34 hemodialysis, 16 peritoneal dialysis), respectively. Mean HLA match was 1.2+/-1.5, with one patient receiving a second transplant. The mean cold ischemic times for the kidney and the pancreas were 15+/-5 and 16+/-4 hr, respectively. Six-month patient, kidney, and pancreas graft survival and rejection rates were 97, 96, 93, and 35%, respectively. There were two deaths, one due to fungal infection and the other due to a cardiac event. There were three kidney graft losses, two immunological, and one death with function. Of the five pancreas graft losses, two were due to infection, one immunological, one thrombosis, and one death with function. The patient population was then stratified according to the number of daclizumab doses: 4-5 doses (n=45) or 1-3 doses (n=26). There were no differences in patient and kidney graft survival rates, 98 vs. 96%, and 92 vs. 92%, respectively. However, there was a trend toward improved pancreas graft survival in the group receiving 4-5 doses (96%) compared with 1-3 doses (85%), P=0.07. Although more patients receiving 1-3 doses had rejection (54%) than patients receiving 4-5 doses (24%), there was no dose response relationship between the total number of doses or the adjusted total mg/kg dose and time to rejection. All patients with functioning grafts have good renal and pancreas allograft function at 6 and 12 months. The overall incidence of major infection was 27% and there were no differences in the incidence of infection between the two groups. No major adverse events were attributed to daclizumab use. In conclusion, excellent short-term outcomes were noted in this retrospective, multicenter survey of initial experience with daclizumab induction in combination with TAC, MMF, and steroids in SKPT recipients. Optimal dosing strategies for SKPT recipients remain to be determined.
HYPOTHESIS: Although control of the hepatic vascular pedicle is commonly used during hepatic resection, the optimal method of vascular control continues to be debated. The utility of total or selective vascular isolation, pedicle inflow occlusion, or the absence of vascular isolation during minor and major hepatectomy needs to be examined. DESIGN: Retrospective review of hepatic resections performed for either isolated colorectal or noncolorectal hepatic metastases. SETTING: The University of Chicago Hospitals, Chicago, Ill, a tertiary-care referral center. PATIENTS: One hundred forty-one patients who underwent hepatic resection for isolated metastatic liver disease were identified through The University of Chicago Hospitals Tumor Registry. MAIN OUTCOME MEASURES: Intraoperative parameters, perioperative morbidity and mortality, and tumor recurrence. RESULTS: Four groups were compared with alternative methods of vascular management, including total vascular isolation, Longmire clamping, Pringle maneuver, or no vascular control. Tumor number and size were not significantly different between groups. Blood loss and transfusion requirements tended to be higher in the total vascular isolation group and were significantly higher compared with the Pringle group (P =.06) and the no vascular control group (P =.04), but this also correlated with a higher incidence of complexity of surgical resection. The highest incidence of postoperative complications occurred in the total vascular isolation group (P<.05). With similar permanent pathologic margins, the rates of intrahepatic recurrence were similar among all groups, with the no vascular control group having the lowest recurrence rate. CONCLUSIONS: All methods of vascular control appeared equivalent with respect to limiting blood loss and transfusion requirements while providing adequate surgical margins. The highest rates of blood requirements and complications were noted in the total vascular isolation group, which corresponded to the highest incidence of complex resections. The Longmire clamp group incurred the lowest incidence of complications and resulted in identical surgical margins. The application of vascular control is beneficial to surgeons during hepatic resection, but the method of control should be selected based on the location and complexity of resection required and preference of the individual surgeon.
Since 1996, our standard immunosuppressive protocol for simultaneous kidney-pancreas transplantation (SKPT) has been tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids without antibody induction. When basiliximab and daclizumab, monoclonal antibodies directed against the interleukin-2 receptor (IL-2R), became available, we selectively added these agents to our standard protocol. The purpose of this prospective, open-label study was to evaluate the safety and efficacy of IL-2 receptor antagonists in SKPT. From April 1998 to August 1999, 35 SKPTS were performed. One patient with delayed graft function received Thymoglobulin and was excluded; 17 received no induction, and 17 received IL-2R antagonists (9 basiliximab, 8 daclizumab) as induction. Demographic- and transplant characteristics were similar between the two groups. At 6 months, patient survival was 88 % (15/17) in the induction arm compared to 100 % (17/17) in the no-induction arm, P = NS. The 2 causes of death were sepsis and hemolytic uremic syndrome, and both patients died with functioning grafts. Death-censored pancreas and kidney graft survival rates in the induction and the no-induction groups were 88 % vs. 100 % respectively, in both groups. The incidence of acute rejection (kidney or pancreas) at 6 months did not differ between the two groups (35 % in both groups). Biopsy proven pancreas and kidney acute rejections were 35 % vs. 24 % and 12 % vs. 12 % in the induction- and no-induction groups, respectively. The incidences of major infection and readmission did not differ between groups. TAC trough levels and mean daily doses of TAC, MMF and steroids did not differ between the two groups at 1, 3, and 6 months. The incidence of event-free survival (no death, rejection, or graft loss) at 6 months was 59 % (10/17) in the induction and 65 % (11/17) in the no-induction group. Basiliximab and daclizumab appear to be safe in SKPT. However, the preliminary results of this study do not demonstrate a significant benefit in either reducing the incidence of acute rejection or improving outcomes at 6 months. Larger studies with longer follow-up are needed to confirm these findings.
BACKGROUND: The impact of tacrolimus (TAC), mycophenolate mofetil (MMF) and steroid immunosuppression on cytomegalovirus (CMV) infection in combination with ganciclovir prophylaxis in simultaneous kidney-pancreas transplantation (SKPT) has not been well studied. METHODS: A retrospective analysis was made of 75 SKPTs performed between 1 January 1996 and 7 January 1999. All patients received ganciclovir for 3 months, but CMV donor (D)+ / recipient (R)- patients received ganciclovir for 6 months. RESULTS: 16/74 (22%) were CMV D+/R-, 25 (33%) D+/R+, 16 (22%) D-/R+, and 17 (23%) D-/R- (1 patient with unknown donor serology was excluded). The mean time to CMV infection was 198 days post-transplant. The incidence of either CMV infection or tissue invasive CMV disease was 16/74 (22%), including 9 (12%) with CMV infection and 7 (10%) CMV disease. The one-year patient, kidney, and pancreas graft survival rates were 91%, 89%, and 83%, respectively. The mean follow-up was 29 months (minimum of 12 months). CMV infection was not associated with an increased incidence of graft failure or mortality. The D+/R- group had the highest incidence of CMV infection (44%) compared with the other serologic groups (17%, P=0.02). Concurrent CMV and rejection occurred more frequently in the D+/R- than the other serologic groups (25% vs. 7%, P=0.03). The D-/R- group had the best outcomes, with no CMV infection, improved kidney graft survival at the end of follow-up (82% vs. 72%, P=0.04) and the highest event-free survival (no CMV infection, rejection, or graft loss) when compared to the other groups (76% vs. 33%, P<0.01). CONCLUSIONS: Compared to previous studies, ganciclovir prophylaxis delayed the onset and reduced the severity of CMV infection in patients receiving TAC, MMF, and steroids. Despite ganciclovir prophylaxis, CMV seronegative patients receiving CMV D+ organs had worse outcomes than seronegative recipients receiving CMV D- organs.
BACKGROUND: It is important to assess the potential efficacy and safety of offering donation incentives as part of recruitment and retention programs. STUDY DESIGN AND METHODS: In 1995, 7489 allogeneic donors responded to an anonymous mail survey that inquired about demographics, donation history, infectious disease risks, and the potential appeal of incentives. RESULTS: The projected net effect of offering blood credits and medical testing would be to motivate, respectively, 58 percent and 46 percent of donors to return, whereas offering an item of limited value would motivate 20 percent to do so. First-time and younger donors reported more frequently than repeat or older donors that incentives would appeal to them. Donors attracted by cash were 60 percent more likely to have a risk for transfusion-transmissible infections (p = 0.03). Although not statistically significant, the odds of being an at-risk donor were higher among individuals attracted by tickets to events (OR 1.5) and extra time off work (OR 1.2). CONCLUSION: These findings suggest that offering blood credits and (though to a lesser extent) items of limited value could be safe and effective strategies for retaining donors. Although medical tests were found to have broad appeal, studies are needed to identify tests in which donors would be most interested.
BACKGROUND: With changing demographics of the United States population and the continuous need to recruit new donors, it is important to monitor the demographic profile of first-time donors and to evaluate changes in the donor pool to improve recruitment targeting. STUDY DESIGN AND METHODS: First-time whole blood (n = 901,862) donors at five United States blood centers between 1991 and 1996 were analyzed. RESULTS: The total number of first-time donors appears to be decreasing. Over the 6-year period, there was an overall increase in the proportion of Hispanic and other minority first-time donors and a concurrent decrease in the proportion of white donors at Retrovirus Epidemiology Donor Study centers. Other variables, including age, sex, and education, did not show a consistent trend. CONCLUSION: The demographic profile of first-time donors is changing. These data highlight the importance for blood centers to continuously monitor the donor population. A better understanding of the donor population may help blood centers adjust their donor outreach, recruitment, and retention programs. New recruitment efforts appear needed to counter general apathy toward donating blood, and minority groups appear to be receptive to becoming blood donors.
We retrospectively reviewed long-term outcomes in simultaneous kidney-pancreas transplant (SKPT) recipients with portal-enteric (P-E) versus systemic-bladder (S-B) drainage. Forty-five patients were alive with functioning grafts 1 year after SKPT and were followed up for a minimum of 3 years (mean, 5.9 years), including 26 patients with P-E drainage and 19 patients with S-B drainage. Recipient demographic and transplant characteristics were similar between the two groups. In both groups, hospital admissions decreased significantly with increasing time after SKPT, although significantly fewer readmissions occurred in the first year in the P-E than the S-B group. The most common reason for readmission in both groups was infection, followed by miscellaneous, surgical, and immunologic morbidity. The incidence of readmission for dehydration was significantly less in the P-E group (P < 0.01). Mean systolic and diastolic blood pressures were similar between groups, although the number of antihypertensive medications was significantly less in the S-B group. Although fasting C-peptide levels were significantly greater in the S-B group, the two groups were similar with regard to carbohydrate (fasting serum glucose, hemoglobin A(1c)) and lipid (total cholesterol) metabolism. Renal and pancreas allograft functions were similar between the two groups. At 1 year post-SKPT, stabilization in most diabetic complications was reported. Four quality-of-life surveys that provided 29 scores were completed 6 to 24 months (mean, 18.5 months) after SKPT. Improved quality of life was reported in all but one of the scales, with many dimensions showing significant improvements. At 3 years after SKPT, no activity limitation was reported in 76% of patients with P-E drainage versus 53% with S-B drainage (P = 0.11). Five-year actual patient, kidney, and pancreas graft survival rates after P-E versus S-B drainage are 92% and 84%, 81% and 79%, and 88% and 74%, respectively (P = not significant). SKPT with P-E drainage is a safe and effective method to treat advanced diabetic nephropathy and is associated with decreasing morbidity, improving rehabilitation and quality of life, and stablizing metabolic function over time. The long-term prognosis after the first year is excellent and at least similar to the results achieved with S-B drainage.
BACKGROUND: The demand for transplantable organs exceeds donor supply. Patients with central nervous system (CNS) or other tumors are controversial donors, and the donor cancer transmission rates in cardiothoracic transplant recipients have not been determined. The Israel Penn International Transplant Tumor Registry (IPITTR) was queried to define the risk of donor cancer transmission in cardiothoracic transplant recipients. METHODS: All heart, lung, or heart-lung recipients of organs from donors with a history of malignancy were reviewed. Donor and recipient demographics, histologic findings, and recurrence were reviewed. RESULTS: Twenty-two patients received 17 hearts, 3 lungs, and 2 heart-lung transplants from donors with known CNS or other malignancies. No malignancy transmissions were noted with astrocytomas (n = 3) or glioblastomas (n = 1), except a medulloblastoma that recurred at 6 months. The transmission rate for CNS tumors was 17% (1 of 6), and 1- and 3-year survivals were 67% and 50%, respectively. The most common non-CNS donor cancer was renal cell carcinoma (n = 5). Two renal cell cancer transmissions occurred, both when vascular extension was present. The most aggressive tumor transmission was choriocarcinoma (n = 2) and melanoma (n = 2). Two of 3 choriocarcinomas metastasized with 67% mortality, and both melanomas were transmitted and resulted in death. Other donor cancers included angiosarcoma (n = 2), cervical (n = 1), lung (n = 1), prostate (n = 1), and a liver adenocarcinoma. The transmission rate for all non-CNS groups was 56% (9 of 16) with a 2-year survival of 40%. CONCLUSIONS: The IPITTR experience indicates that tumor transmission is high (10 of 22, 45%) in cardiothoracic transplant recipients. Similar to intra-abdominal organ recipients in the IPITTR, (1) renal cell carcinomas without capsular invasion appear safe with no transmission, (2) vascular invasion in renal cell carcinoma appears to result in early tumor transmission, and (3) melanoma and choriocarcinoma have high rates of transmission with early and almost universal death.
1. An isolated perfused rat liver (IPRL) preparation was used to investigate separately the disposition of the non-steroidal anti-inflammatory drug (NSAID) naproxen (NAP), its reactive acyl glucuronide metabolite (NAG) and a mixture of NAG rearrangement isomers (isoNAG), each at 30 microg NAP equivalents ml perfusate (n = 4 each group). 2. Following administration to the IPRL, NAP was eliminated slowly in a log-linear manner with an apparent elimination half-life (t 1/2) of 13.4 +/- 4.4h. No metabolites were detected in perfusate, while NAG was the only metablolite present in bile in measurable amounts (3.9 +/- 0.8% of the dose). Following their administration to the IPRL, both NAG and isoNAG were rapidly hydrolysed (t 1/2 in perfusate = 57 +/- 3 and 75 +/- 14 min respectively). NAG also rearranged to isoNAG in the perfusate. Both NAG and isoNAG were excreted intact in bile (24.6 and 14.8% of the NAG and isoNAG doses, respectively). 3. Covalent NAP-protein adducts in the liver increased as the dose changed from NAP to NAG to isoNAG (0.20 to 0.34 to 0.48% of the doses, respectively). Similarly, formation of covalent NAP-protein adducts in perfusate were greater in isoNAG-dosed perfusions. The comparative results suggest that isoNAG is a better substrate for adduct formation with liver proteins than NAG.
Members of the steroid-thyroid-retinoid receptor superfamily regulate a spectrum of cellular functions, including metabolism and growth and differentiation. We sought to isolate novel members of this family by using degenerate oligonucleotide primers directed to sequences encoding the AF-2 domain of these molecules in a PCR-based approach. The AF-2 domain serves a critical function in recruiting coregulatory molecules and in transcriptional activation. We report the cloning and initial characterization of a novel gene, WDR10, which encodes a 140-kD protein that is highly expressed in pituitary and testis. This protein, WDR10p, contains an AF-2 domain as well as seven N-terminal WD repeats and is highly conserved through evolution. Chromosomal localization studies placed WDR10 at 3q21, near a locus for the Moebius syndrome, Hailey-Hailey disease, and rhodopsin, which is involved in several forms of retinitis pigmentosa. The expression pattern of WDR10 and its chromosomal location makes this novel gene a candidate gene for the hypogonadism associated with some forms of retinitis pigmentosa and the Moebius syndrome.
OBJECTIVE: This study sought to provide reference data for the Eating Disorder Inventory (EDI) with use of young adolescent black and white girls. Moreover, the study examined the relationship between race, age, socioeconomic status, and adiposity and each of the eight EDI scales. METHOD: To achieve these aims, data were used that had been collected in Years 3, 5, and 7 as part of the National Heart, Lung, and Blood Institute Growth and Health Study, a longitudinal cohort study of risk factors for obesity in black and white girls. For the present report, data were available from 2,228 girls in Year 3, 2,056 girls in Year 5, and 1,902 girls in Year 7. RESULTS: EDI scores were found to vary by race, age, socioeonomic status, and body weight of respondents. Black girls scored different from white girls on all EDI subscales. Scores on all but two subscales (Body Dissatisfaction, Drive for Thinness) decreased significantly with increasing age. Significant inverse associations were found between maximum parental education and all EDI subscales except Body Dissatisfaction and Perfectionism. Elevated body weight was associated significantly with Body Dissatisfaction, Drive for Thinness, Bulimia, Interoceptive Awareness, and Ineffectiveness. DISCUSSION: Our results illustrate the importance of taking into consideration the potentially confounding role of demographic characteristics and body weight when comparing different race or ethnic groups on the EDI.
INTRODUCTION: Previous studies have suggested that African-American (AA) ethnicity is a risk factor for rejection and graft loss after kidney transplantation. However, little data is available regarding outcomes after simultaneous kidney pancreas transplantation (SKPT) in AA recipients. The objective of this study was to compare the outcomes of SKPT in AA patients to matched Caucasian patients as controls. METHODS: From January 1996 to September 1999, we performed 79 SKPTs, including 10 in AA recipients. Ten Caucasian controls were selected and matched for age, gender, weight, timing and technique of transplantation, and immunosuppressive regimen. Clinical outcomes were collected and compared between the two groups. RESULTS: The two groups were well matched for donor and recipient demographic, immunologic and transplant characteristics, including 2 patients in each group with type 2 diabetes. All patients received tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids, and about half in each group received antibody induction therapy. Patient survival was 100% in both groups with a mean follow-up of 18 months (range 6 47). Kidney and pancreas graft survival rates were both 80% in the AA and 100% in the Caucasian groups, respectively (p = 0.14). All but one kidney (in the AA group) and all pancreas grafts experienced immediate function. There were two immunologic kidney and two immunologic pancreas graft losses in the AA group. No grafts were lost due to technical problems. The mean length of initial hospital stay was 16 d in the AA group compared to 10 d in the Caucasian group (p = 0.07). The AA group had a slight increase in the number of readmissions (mean 2.2 AA vs. 1.6 Caucasian, p = 0.08). The incidence of biopsy-proven pancreas acute rejection was significantly higher in the AA group (50%) compared to the Caucasian group (10%) (p = 0.05). The incidence of either kidney or pancreas acute rejection was also higher in the AA group (60% AA vs. 20% Caucasian, p = 0.06). TAC levels were comparable at specific times after transplantation, al-though there was a trend toward higher doses of TAC in the AA group to achieve therapeutic levels. The incidences of relaparotomy (30% AA vs. 20% Caucasian) and major infection (40% AA vs. 60% Caucasian) were similar between groups. Renal and pancreas allograft functions were comparable between groups at specific times after transplantation. CONCLUSIONS: These results suggest that SKPT in AA recipients may be associated with a higher incidence of rejection and immunologic graft loss compared to matched Caucasian controls.
BACKGROUND: Infections are the major life-threatening complication of burn injury and occur with the greatest frequency in children. Knowledge of their occurrence and management, however, is extrapolated from studies in adults. We performed a prospective study of infectious complications in burned children. OBJECTIVE: To delineate epidemiology, risk factors and microbiology of infections in burned children where burn care and surgical interventions are optimal. METHODS: Children hospitalized for burns were entered into prospective study. Characteristics of the burn injury were assessed, and active surveillance for infections was performed. RESULTS: Seventy patients were entered [mean age, 42 months; mean total body surface area (TBSA), burn 15%]. Twenty-seven percent of patients developed 39 infections: 13 involved the burn wound (burn wound sepsis, 6; graft loss, 5; and cellulitis, 2); 13 were catheter-associated septicemia; 13 involved other sites (i.e. pneumonia, 4; urinary tract infection, 3; bacteremia, 2; endocarditis, 1; myocardial abscess, 1; toxin-mediated syndrome, 1; and otitis media, 1). Twenty-three infections were caused by a single organism, 9 infections by more than 1 organism and in 7 infections defined by CDC criteria no organism was recovered. Organisms causing infection were: Staphylococcus aureus, 19; Candida albicans, 4; Pseudomonas aeruginosa, 4; coagulase-negative Staphylococcus, 4; Enterococcus sp., 3; Escherichia coli, 1; Klebsiella oxytoca, 1; Serratia marcescens, 1; Streptococcus pneumoniae, 1; Streptococcus pyogenes, 1; Aspergillus fumigatus, 1; and Candida parapsilosis, 1. Burn mechanism (flame and inhalation), extent (TBSA >30%) and depth (full thickness) were risk factors for infection; young age and site of burn were not. CONCLUSION: The most common infections occurring in burn children are burn wound infections and catheter-associated septicemia. Characteristics of burn injury predict risk of infection. Children with flame and inhalation injury, TBSA burned >30% and full thickness burns are at high risk of infectious complications.
Hong Kong is a well developed city in the center of an endemic region for hepatitis A. The age at which hepatitis A occurs has shifted from childhood and adolescence to adults like many western countries. There is a high chance of outbreaks with the introduction of infection from neighbouring countries. Reducing the susceptibility of a population by vaccination can eliminate the diseases but updated sero-epidemiological data is needed to analyse the level of natural immunity, and identify those susceptible to infection for preventive measures. This study conducted amongst secondary school children seeks to identify those who are at risk and to obtain data on the present sero-prevalence of anti-HAV. Overall prevalence of anti-HAV in this age group was 7% increasing with age. Analysed by multiple regression model, those students living in mainland China over 3 years had odds ratio of 31.6 (95% c. i. 17.4-57.3) compared with those born in Hong Kong. Students with a father in a skilled occupation and an education level of secondary school or above, and both parents with secondary education or above, had an odds ratio of 0.22 (95% c.i. 0.07-0.7) and 0.35 (95% c.i. 0. 17-0.72) associated with presence of anti-HAV, respectively. Improved socio-economic state exposes higher proportion of the population at risk. Immunisation is worthwhile to be considered for the adolescents in Hong Kong. Prevaccination screening is cost effective only for those adolescents who are most likely to have natural immunity.