Biomedical subjects

A Humar

Publications and source records attributed to A Humar.

At least 19 recordsLinked to original sources

PubMed2003

Differentiation and quantitation of human herpesviruses 6A, 6B and 7 by real-time PCR.

The beta-herpesviruses cause considerable morbidity in immunocompromised individuals, such as transplant patients. Most notably within this group is human cytomegalovirus, although HHV-6 and -7 are a growing concern. Identifying HHV-6 and -7 as the cause of post-transplant illness can be challenging due to high seroprevalence and latency properties associated with these human herpesviruses. We have developed a sensitive and specific real-time PCR assay, which can differentiate reliably and quantify HHV-6A, -6B and -7. Using two sets of hybridization probes specific for HHV-6A or -6B and HHV-7, the assay reliably differentiates the three viruses using melting curve analysis. The lower limit of detection for all three viruses was determined to be ten viral genomes. This real-time PCR assay will be useful for differentiation and quantitation of HHV-6A, -6B and -7, especially for monitoring transplant patients.

Cell Line↗

PubMed2002

Risk factors for slow graft function after kidney transplants: a multivariate analysis.

BACKGROUND: We previously defined an intermediate group of cadaver kidney transplant recipients who do not have immediate graft function (IGF), but do not have sufficient graft dysfunction to be classified as having delayed graft function (DGF). We showed that this group with slow graft function (SGF) had an increased risk of rejection and inferior long-term results vs. recipients with IGF. The aim of our current study was to determine risk factors for SGF, which have not been well defined (in contrast to risk factors for DGF). METHODS: Between January 1, 1984 and September 30, 1999, we performed 896 adult cadaver kidney transplants at the University of Minnesota. Recipients were analysed in three groups based on initial graft function: IGF [creatinine (Cr) < 3 mg/dL by post-operative day (POD) no. 5], SGF (Cr > 3 mg/dL on POD no. 5, but no need for dialysis), and DGF (need for dialysis in the first week post-transplant). A multivariate analysis looked specifically at risk factors for SGF, as compared with risk factors for DGF. Outcomes with regard to graft survival and acute rejection (AR) rates were determined for the three groups. RESULTS: Of the 896 recipients, 425 had IGF, 238 had SGF, and 233 had DGF. A multivariate analysis of risk factors for SGF showed donor age >50 yr (RR=3.3, p=0.0001) and kidney preservation time >24 h (RR=1.6, p=0.01) to be the most significant risk factors. A multivariate analysis of risk factors for DGF showed similar findings, although high panel-reactive antibodies (PRA) and donor Cr >1.7 mg/dL were also significant risk factors for DGF. Initial function of the graft significantly influenced the subsequent risk of AR: at 12 months post-transplant, the incidence of AR was 28% for those with IGF, 38% for those with SGF, and 44% for those with DGF (p=0.04 for SGF vs. DGF). Initial graft function also significantly influenced graft survival: the 5-yr death-censored graft survival rate was 89% for recipients with IGF, 72% for those with SGF, and 67% for those with DGF (p=0.01 for IGF vs. SGF; p=0.03 for SGF vs. DGF). CONCLUSIONS: SGF represents part of the spectrum of graft injury and post-transplant graft dysfunction. Risk factors for SGF are similar to those seen for DGF. Even mild to moderate graft dysfunction post-transplant can have a negative impact on long-term graft survival.

Female↗

PubMed2002

Low-virulence Citrobacter species encode resistance to multiple antimicrobials.

Citrobacter spp. are gram-negative commensal bacteria that infrequently cause serious nosocomial infections in compromised hosts. They are often resistant to cephalosporins due to overexpression of their chromosomal beta-lactamase. During a recent study of multidrug-resistant Enterobacteriaceae (MDRE) in solid-organ transplant patients, we found that almost half of patients colonized with MDRE carried one or more cefpodoxime-resistant Citrobacter freundii, Citrobacter braakii, or Citrobacter amalonaticus strains. Pulsed-field gel electrophoresis showed that 36 unique strains of Citrobacter were present among 32 patients. Genetic and phenotypic analysis of the resistance mechanisms of these bacteria showed that the extended-spectrum beta-lactamase (ESBL) SHV-5 or SHV-12 was encoded by 8 strains (26%) and expressed by 7 strains (19%). A number of strains were resistant to other drug classes, including aminoglycosides (28%), trimethoprim-sulfamethoxazole (31%), and fluoroquinolones (8%). PCR and DNA analysis of these multiresistant strains revealed the presence of class I integrons, including the first integrons reported for C. braakii and C. amalonaticus. The integrons encoded aminoglycoside resistance, trimethoprim resistance, or both. Despite the prevalence of MDR Citrobacter spp. in our solid-organ transplant patients, only a single infection with a colonizing strain was recorded over 18 months. Low-virulence Citrobacter spp., which can persist in the host for long periods, could influence pathogen evolution by accumulation of genes encoding resistance to multiple antimicrobial classes.

Citrobacter↗

PubMed2001

Are wound complications after a kidney transplant more common with modern immunosuppression?

BACKGROUND: The most common surgical complication after a kidney transplant is likely related to the wound. The purpose of this analysis was to determine the incidence of, and risk factors for, wound complications (e.g., infections, hernias) in kidney recipients and to assess whether newer immunosuppressive drugs increase the risk for such complications. METHODS: Between January 1, 1984 and September 30, 1998, we performed 2013 adult kidney transplants. Of these 2013 recipients, 97 (4.8%) developed either a superficial or a deep wound infection. Additionally, 73 (3.6%) recipients developed either a fascial dehiscence or a hernia of the wound. We used univariate and multivariate techniques to determine significant risk factors and outcomes. RESULTS: Mean time to development of a superficial infection (defined as located above the fascia) was 11.9 days posttransplant; to development of a deep infection (defined as located below the fascia), 39.2 days; and to development of a hernia or fascial dehiscence, 12.8 months. By multivariate analysis, the most significant risk factor for a superficial or deep wound infection was obesity (defined as body mass index>30 kg/m2) (RR=4.4, P=0.0001). Other significant risk factors were a urine leak posttransplant, any reoperation through the transplant incision, diabetes, and the use of mycophenolate mofetil (MMF) (vs. azathioprine) for maintenance immunosuppression (RR=2.43, P=0.0001). Significant risk factors for a hernia or fascial dehiscence were any reoperation through the transplant incision, increased recipient age, obesity, and the use of MMF (vs. azathioprine) for maintenance immunosuppression (RR=3.54, P=0.0004). Use of antibody induction and treatment for acute rejection were not significant risk factors for either infections or hernias. Death-censored graft survival was lower in recipients who developed a wound infection (vs. those who did not); it was not lower in recipients who developed an incisional hernia or facial dehiscence (vs. those who did not). CONCLUSIONS: Despite immunosuppression including chronic steroids, the incidence of wound infections, incisional hernias, and fascial dehiscence is low in kidney recipients. As with other types of surgery, the main risk factors for postoperative complications are obesity, reoperation, and increased age. However, in kidney recipients, use of MMF (vs. azathioprine) is an additional risk factor -one that potentially could be altered, especially in high-risk recipients.

Adult↗

PubMed2001

Epstein-Barr virus serology and posttransplant lymphoproliferative disease in lung transplantation.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is now a widely recognized complication of lung transplantation. In the current study, we present our experience with PTLD over a 15-year period, which includes the incidence rates in 242 lung allografts and the relative risk of developing PTLD in 146 patients with known pretransplantation Epstein-Barr virus (EBV) status. METHODS: Inpatient and outpatient charts of 300 consecutive lung transplant recipients between 1984 and 1999 were retrospectively reviewed. RESULTS: Twelve cases of PTLD were observed for a total incidence rate of 5.0%. Ten of these patients had pretransplantation EBV testing, and the consequent increase in relative risk for patients who were EBV negative was 6.8-fold. The mean time between organ transplantation and tissue diagnosis of PTLD was 17.6 months. Total 1-year survival rate from the time of diagnosis for the cohort was 58%, whereas 2-year survival rate was 50%. Median survival for the six patients who died was 4.5 months. CONCLUSIONS: These data suggest that although EBV seronegativity does carry a 6.8-fold increase in the relative risk of developing PTLD, long-term survival despite the development of PTLD can be achieved, and thus EBV seronegativity by itself should not be considered a contraindication to lung transplantation.

Adolescent↗

PubMed2001

Multicenter survey of daclizumab induction in simultaneous kidney-pancreas transplant recipients.

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.

Adult↗

PubMed2001

Non-nucleoside reverse transcriptase inhibitor failure impairs HIV-RNA responses to efavirenz-containing salvage antiretroviral therapy.

In a retrospective cohort study of salvage antiretroviral combination therapy including efavirenz, 60% of 51 patients were able to suppress HIV RNA by at least 1 log10 or to less than 50 copies/ml. A lack of the previous use of non-nucleoside reverse transcriptase inhibitors was the only factor predictive of response on multivariate analysis. No patient with a viral isolate with an increased IC50 to efavirenz by virtual phenotype had a virological response

Adult↗

PubMed2001

Kidney transplantation in young children: should there be a minimum age?

The optimal age for transplantation in children with end-stage renal disease remains controversial. Many centers have adopted a policy of waiting until such children reach a certain minimum age or weight, maintaining them on chronic dialysis until then. Their policy is based on historical data showing inferior graft survival in very young children. We feel that with proper donor selection and recipient care, comparable results can be achieved in very young age groups. We herein present our results with kidney transplantation in children <1 year old. Between 1 January 1984 and 31 December 1999, we performed 321 kidney transplants in children < or =13 years at the University of Minnesota. We analyzed our results in three age groups: <1 year (n=30), 1 through 4 years (n=122), and 5 through 13 years (n=169). We found no significant differences in patient or graft survival rates between the three groups. Almost all our infant (<1 year) recipients underwent primary transplants from living donors (LDs). However, even when we compared results only of primary LD transplants between the three groups, we found no significant differences. To date, all our infant recipients are alive and well, 24 (80%) with a functioning original graft. Causes of the 6 graft losses were chronic rejection (n=3), vascular thrombosis (n=2), and recurrent disease (n=1). Infants had significantly lower incidences of acute and chronic rejection compared with older recipients, but a tendency to higher incidences of delayed graft function and vascular thrombosis. Infants had significant increases in weight post transplant: the mean standard deviation score rose from -2.8 pre transplant to -0.2 by age 5 years and to +1.8 by age 10 years. The improvement in height was less marked: the mean standard deviation rose from -3.2 pre transplant to -1.6 by age 5 years and to -1.4 by age 10 years. Kidney transplant results in very young children can be comparable to those in older children. There need be no minimum age for performing a kidney transplant. The timing of the transplant should not be based on age or size alone.

Acute Disease↗

PubMed2001

Pancreas after kidney transplants.

BACKGROUND: For certain uremic diabetic patients, a sequential transplant of a kidney (usually from a living donor) followed by a cadaver pancreas has become an attractive alternative to a simultaneous transplant of both organs. The purpose of this study was to compare outcomes with simultaneous pancreas-kidney (SPK) versus pancreas after kidney (PAK) transplants to determine advantages and disadvantages of the two procedures. METHODS: Between January 1, 1994, and June 30, 2000, we performed 398 cadaver pancreas transplants at our center. Of these, 193 were SPK transplants and 205 were PAK transplants. We compared these two groups with regard to several endpoints, including patient and graft survival rates, surgical complications, acute rejection rates, waiting times, length of hospital stay, and quality of life. RESULTS: Overall, surgical complications were more common for SPK recipients. The total relaparotomy rate was 25.9% for SPK recipients versus 15.1% for PAK recipients (P = 0.006). Leaks, intraabdominal infections, and wound infections were all significantly more common in SPK recipients (P = 0.009, P = 0.05, and P = 0.01, respectively, versus PAK recipients). Short-term pancreas graft survival rates were similar between the two groups: at 1 year posttransplant, 78.0% for SPK recipients and 77.9% for PAK recipients (P = not significant). By 3 years, however, pancreas graft survival differed between the two groups (74.1% for SPK and 61.7% for PAK recipients), although this did not quite reach statistical significance (P = 0.15). This difference in graft survival seemed to be due to increased immunologic losses for PAK recipients: at 3 years posttransplant, the incidence of immunologic graft loss was 16.2% for PAK versus 5.2% for SPK recipients (P = 0.01). Kidney graft survival rates were, however, better for PAK recipients. At 3 years after their kidney transplant, kidney graft survival rates were 83.6% for SPK and 94.6% for PAK recipients (P = 0.001). The mean waiting time to receive the pancreas transplant was 244 days for SPK and 167 days for PAK recipients (P = 0.001). CONCLUSIONS: PAK transplants are a viable option for uremic diabetics. While long-term pancreas graft results are slightly inferior to SPK transplants, the advantages of PAK transplants include the possibility of a preemptive living donor kidney transplant, better long-term kidney graft survival, significantly decreased waiting times, and decreased surgical complication rates. Use of a living donor for the kidney transplant expands the donor pool. Improvements in immunosuppressive regimens will hopefully eliminate some of the difference in long-term pancreas graft survival between SPK and PAK transplants.

Adult↗

PubMed2001

Kidney retransplants after initial graft loss to vascular thrombosis.

BACKGROUND: Vascular thrombosis early after a kidney transplant is an infrequent but devastating complication. Often, no cause is found. These recipients are generally felt to be good candidates for a retransplant. However, their ideal care at the time of the retransplant and their outcomes have not been well documented. We studied outcomes in 16 retransplant recipients who had lost their first graft early posttransplant (< 1 month) to vascular thrombosis. METHODS: Of 2,003 kidney transplants between I January 1984 and 30 September 1998, we identified 32 recipients who had lost their first graft early posttransplant to vascular thrombosis. Of these 32 recipients, 16 were subsequently retransplanted and detailed chart reviews were done. RESULTS: Of the 16 retransplant recipients, 12 lost their first graft to renal vein thrombosis and 4 to renal artery thrombosis. Thrombosis generally occurred early (mean, 3.6 d). Five recipients underwent a complete hematologic workup to rule out a thrombophilic disorder before their retransplant: 4 had a positive result (presence of antiphospholipid antibodies, n = 3; increased homocysteine levels, n = 1). These 4 recipients, along with 1 other recipient who had a strong family history of thrombosis, underwent thrombosis prophylaxis at the time of their retransplant. Prophylaxis consisted of low-dose heparin for the first 3-5 d posttransplant, followed by acetylsalicylic acid or Coumadin. Of the 16 retransplant recipients, none developed thrombosis. Of the 5 who underwent thrombosis prophylaxis, none had significant bleeding complications. At a mean follow-up of 5.4 yr, 10 (63%) recipients have functioning grafts. Causes of graft loss in the remaining 6 recipients were death with function (n = 5, 31%) and acute rejection (n = 1.6%). Graft and patient survival rates after these 16 retransplants were equivalent to results after primary transplants. The incidence of acute and chronic rejection was also no different (p = ns). CONCLUSION: Vascular thrombosis in the absence of obvious technical factors should prompt a workup for a thrombophilic disorder before a retransplant. Recipients with an identified disorder should undergo prophylaxis at the time of the retransplant. Results in these retransplant recipients are equivalent to those seen in primary transplant recipients.

Chromatography, High Pressure Liquid↗

PubMed2001

Peri-operative cardiac morbidity in kidney transplant recipients: incidence and risk factors.

BACKGROUND: Renal transplant recipients are known to be at increased risk for developing cardiac disease. In both general and peripheral vascular surgery, pre-operative risk stratification (and intervention when indicated) has decreased the incidence of peri-operative cardiac complications. In this study, we set out to identify subsets of patients at high risk for peri-operative cardiac complications after a renal transplant. METHODS: We retrospectively reviewed the records of 2694 adult renal transplants performed at the University of Minnesota between January 1, 1985 and December 31, 1998. We determined the incidence of peri-operative (within 30 d post-transplant) cardiac complications, including myocardial infarction (MI). Risk factors for the development of these complications were determined by multivariate analysis. RESULTS: We found 163 peri-operative cardiac complications, for an overall incidence of 6.1%. Specific cardiac complications included MI (n=43, 1.6%), arrhythmia (n=74, 2.7%), angina (n=31, 1.2%), cardiac arrest (n=13, 0.5%), and congestive heart failure (n= 2, 0.1%). By multivariate analysis, significant risk factors for any cardiac complication were age> or =50 yr (relative risk (RR)=3.0, p=0.0001) and pre-transplant cardiac disease (RR=3.3, p=0.0001). Not significant were diabetes mellitus (DM), cadaver donor source, pre-transplant dialysis, a history of smoking, and hypertension. Significant risk factors for peri-operative MI were age> or =50 yr, pre-existing cardiac disease, and DM. Diabetic patients with pre-existing cardiac disease were at especially high risk for peri-operative cardiac events. CONCLUSIONS: Patients>50 yr and those with pre-existing cardiac disease, especially if diabetic, are at significantly increased risk for developing peri-operative cardiac complications after a renal transplant. Such patients require aggressive pre-operative investigations, which may include coronary angiography, to decrease the risk of post-transplant complications.

Adult↗

PubMed2001

Kidney and pancreas transplantation without a crossmatch in select circumstances--it can be done.

Given the constant flux in caseload and the number of personnel available in the OR, waiting for a final XM often prolongs organ preservation time (a room available at the time a XM is started is not available when the XM is completed). Longer preservation is associated with increased DGF and decreased graft survival. We have shown in a retrospective analysis that final XMs on 0% PRA recipients were always negative (Transplantation, 1999). We now describe a policy of: a) not doing screening XM and b) proceeding to the OR without a XM, in situations where the recipients's PRA has been documented to be 0% and when there have not been any interim transfusions (and the OR is ready before XM completion). Final XM is completed after the transplant. All patients send sera every 6 weeks for PRA (antiglobulin technique). If > o r=3 consecutive PRAs are 0%, no donor-specific screening XM is done prior to calling the patient in for tx (UNOS allocation algorithm used). If there have not been any interim transfusions, we have proceeded to tx prior to completion of the final XM. Between 1/1/98-12/31/99, we did 109 CAD kidney (K) and 79 simultaneous kidney pancreas (SPK) tx; 67 (61%) K and 56 (71%) SPK had 0% PRA. Of the 0% PRA, 25/67 (37%) K and 28/56 (50%) SPK had no pre-tx XM. For K with no XM, cold ischemia was shorter (13.2+/-0.2 vs. 18+/-0.9 hrs, p=0.01) and DGF less (12% vs. 24%, p=0.3); for SPK with no XM, cold ischemia was shorter (15.2+/-2 vs. 18+/-0.9 hrs, p=0.1); no diff in DGF. All post-XM were negative and there were no hyperacute rejections; there was no diff in acute rejection episodes. Actuarial 1 yr graft survival: no XM-K=87.5%, SKP=82%; Yes XM-K=88%, SKP=86% (NS). Our data suggests it is safe, in select circumstances, to proceed to the OR without a XM. Elimination of the screening XM for 0% PRA candidates saves money. Proceeding of the OR (if available) without a final XM shortens cold ischemia time.

Cadaver↗

PubMed2001

Rapid discontinuation of steroids in living donor kidney transplantation: a pilot study.

UNLABELLED: Steroids are associated with significant postoperative complications (hypertension, cosmetic changes, bone loss, hyperlipidemia, diabetes, and cataracts). Most develop early; in addition, late post-transplant steroid withdrawal in kidney transplant recipients has been associated with increased acute rejection (AR). To obviate these problems, we studied outcome of a protocol of rapid discontinuation of prednisone (RDS) (steroids stopped on POD6). Between November 1, 1999 and October 31, 2000, 51 adult living donor (LD) first transplant recipients (2 HLA-id, 28 non-id relative, 21 LURD) were immunosuppressed with thymoglobulin (1.25 mg/kg intraoperatively and then qdx4); prednisone (P) (500 mg methylprednisolone intraoperatively, 1 mg/kg x 1 day, 0.5 mg/kg x 2 days, 0.25 mg/kg x 2 days, then d/c); MMF, 1 g b.i.d.; and CSA, 4 mg/kg b.i.d. adjusted to achieve levels of 150-200 ng/mL (by HPLC). Exclusion criteria were delayed graft function or primary disease requiring P. Minimum follow-up was 5.5 months (range 5.5 to 17.5 months). Outcome was compared vs. previous cohorts of LD recipients immunosuppressed with P/AZA/CSA (n = 171) or P/MMF/CSA (n = 43) (both without antibody induction). RESULTS: For the RDS group, average CSA level (+/- S.E.) at 3 and 6 months was 190 +/- 12 and 180 +/- 9; avg. MMF dose, 1.7 +/- 0.1 g and 1.7 +/- 0.1 g. There was no significant difference in 6- and 12-month actuarial patient survival, graft survival and rejection-free graft survival between recipients on the RDS protocol vs. historical controls. For RDS recipients, actuarial 6- and 12-month rejection-free graft survival was 87%. Of the 51 RDS recipients, five (10%) have had AR (at 20 days, 1 month, 3 months, 3 months, and 3.5 months post-transplant). After treatment, all five were maintained on 5 mg P; there have been no second AR episodes. Two additional recipients were started on 5 mg P due to low white blood count (WBC) and low/no MMF. Of the 51 grafts, one has failed (death with function). Average serum Cr level (+/- S.E.) at 3 and 6 months for RDS recipients was 1.7 +/- 0.5 (NS vs. historical controls). CONCLUSION: For low-risk LD recipients, a kidney transplant with an RDS protocol does not increase risk of AR or graft loss. Future studies will need to be done to assess AR rates with an RDS protocol in cadaver transplant recipients and in recipients with delayed graft function.

Azathioprine↗

PubMed2001

Split liver transplantation for two adult recipients: an initial experience.

The shortage of cadaver donor livers has been most severe for adult patients. Split liver transplantation is one method to expand the donor pool, but to have a significant impact on the waiting list, it needs to be applied for 2 adult recipients. We split livers from 6 cadaver donors, and transplanted 12 adult recipients. All splits were performed in situ with transection through the midplane of the liver, resulting in a right lobe and a left lobe graft. Mean donor age was 19.7 years; mean donor weight was 79.1 kg. Mean recipient age was 41.5 years. Mean weight of right lobe recipients was 89 kg; left lobe recipients, 60 kg. All donors were hemodynamically stable and had normal liver function tests. Mean operative time for the procurement was 7.4 h. Average blood loss during the transection of the liver was 490 mL. Mean GW/ RW ratio for all recipients was 0.87%; right lobe recipients, 0.86%; and left lobe recipients, 0.88%. With mean follow-up of 9.3 months, patient and graft survival rates were both 83.3%. There were 2 deaths: 1 after hepatic artery thrombosis (HAT) and subsequent multiorgan failure; the other after HAT, a liver retransplant, and subsequent gram-negative sepsis. The remaining 10 recipients are doing well. We observed no cases of primary nonfunction. Other complications included bile leak and/or stenosis (n = 3), bleeding from the Roux loop (n = 1), bleeding after percutaneous biopsy (n = 1), and incisional hernia (n = 1). In conclusion, split liver transplantation, using 1 cadaver liver for 2 adult recipients, can be performed successfully. Crucial to success is proper donor and recipient selection.

Adolescent↗

PubMed2001

A randomised trial comparing cytomegalovirus antigenemia assay vs screening bronchoscopy for the early detection and prevention of disease in allogeneic bone marrow and peripheral blood stem cell transplant recipients.

Preemptive antiviral therapy is often employed for CMV prevention following allogeneic BMT. Two common strategies are a screening bronchoscopy for CMV post-BMT or regular CMV antigenemia testing with ganciclovir administration for a positive result. In a randomised trial, we prospectively compared the efficacy of these two preemptive strategies. Consecutive patients were randomised to either a bronchoscopy for CMV on day 35 post BMT or weekly CMV antigenemia testing. If the bronchoscopy was positive for CMV, patients received preemptive ganciclovir for 8-10 weeks. If the antigenemia was positive for CMV, patients received a minimum of 2 weeks of preemptive ganciclovir. The primary endpoint was the development of active CMV disease. One hundred and eighteen allogeneic BMT patients were enrolled (60 in the antigenemia arm and 58 in the bronchoscopy arm). The two groups were comparable with respect to baseline demographic data, underlying disease, conditioning regimen, and immunosuppression. Active CMV disease developed in 7/58 (12.1%) patients in the bronchoscopy arm vs 1/60 patients (1.7%) in the CMV antigenemia arm (P = 0.022). Based on the screening test, 13.8% of patients received preemptive ganciclovir in the bronchoscopy arm vs 48.3% of patients in the antigenemia arm (P < 0.001). There was no significant difference in the rate of graft-versus-host disease, bacteremia, invasive fungal infections or mortality between the two groups. Preemptive therapy based on regular CMV antigenemia monitoring is superior to screening bronchoscopy for the prevention of CMV disease after allogeneic BMT.

Adult↗

PubMed2001

Outcome of other organs recovered during in situ split-liver procurements.

Split-liver transplantation is becoming a useful technique to expand the donor pool. Whether the split should be performed in situ or ex situ is not clear. One potential disadvantage of in situ splits is that prolonged surgical time and increased blood loss may negatively affect the function of other solid organs (kidneys, pancreas, and heart) procured from the same donor. Therefore, we studied the function of other organs posttransplantation. Between September 1, 1999, and March 31, 2000, we performed six in situ splits at the University of Minnesota (Minneapolis, MN). These six splits yielded six right-lobe liver grafts and six left-lobe liver grafts, which were transplanted into 12 adult-size recipients. Other grafts obtained from these six donors were as follows: kidney (n = 11), heart (n = 4), lungs (n = 1), pancreas (n = 2), and kidney-pancreas (n = 1). We then analyzed posttransplantation function of these grafts and the postoperative course of transplant recipients. All six donors were hemodynamically stable at the time of procurement. Mean donor age was 19.7 years. Mean surgical time for the procurement was 7.4 hours, with an average blood loss of 490 mL during in situ splitting of the liver. The 12 liver grafts showed good initial function with no primary nonfunction. The other organs also showed good function. Of 11 kidney recipients, only 1 patient developed delayed graft function, which resolved within 4 days. In addition, 1 kidney was lost early because of severe acute rejection. For the 10 recipients with functioning kidneys, mean creatinine level at hospital discharge was 2.0 mg/dL, and mean creatinine level after an average 9-month follow-up was 1.3 mg/dL. Of the 4 heart transplant recipients, 3 patients had good graft function immediately posttransplantation, with an ejection fraction greater than 60%, minimal inotropic requirements, and no surgical complications. The fourth heart transplant recipient, a critically ill status 1 patient, had poor initial function and a prolonged intensive care unit stay. At hospital discharge, pancreas and pancreas-kidney transplant recipients were all insulin free, with good urine amylase levels, no surgical or infectious complications, and no evidence of significant pancreatitis posttransplantation. The kidney of the pancreas-kidney transplant recipient functioned immediately; creatinine level after 7 months of follow-up was 1.2 mg/dL. Despite increased surgical time and blood loss, in situ splitting of liver grafts can be accomplished in stable donors without significant negative effects on other organs.

Adolescent↗

PubMed2001

Lessons learned from more than 1,000 pancreas transplants at a single institution.

OBJECTIVE: To determine outcome in diabetic pancreas transplant recipients according to risk factors and the surgical techniques and immunosuppressive protocols that evolved during a 33-year period at a single institution. SUMMARY BACKGROUND DATA: Insulin-dependent diabetes mellitus is associated with a high incidence of management problems and secondary complications. Clinical pancreas transplantation began at the University of Minnesota in 1966, initially with a high failure rate, but outcome improved in parallel with other organ transplants. The authors retrospectively analyzed the factors associated with the increased success rate of pancreas transplants. METHODS: From December 16, 1966, to March 31, 2000, the authors performed 1,194 pancreas transplants (111 from living donors; 191 retransplants): 498 simultaneous pancreas-kidney (SPK) and 1 simultaneous pancreas-liver transplant; 404 pancreas after kidney (PAK) transplants; and 291 pancreas transplants alone (PTA). The analyses were divided into five eras: era 0, 1966 to 1973 (n = 14), historical; era 1, 1978 to 1986 (n = 148), transition to cyclosporine for immunosuppression, multiple duct management techniques, and only solitary (PAK and PTA) transplants; era 2, 1986 to 1994 (n = 461), all categories (SPK, PAK, and PTA), predominantly bladder drainage for graft duct management, and primarily triple therapy (cyclosporine, azathioprine, and prednisone) for maintenance immunosuppression; era 3, 1994 to 1998 (n = 286), tacrolimus and mycophenolate mofetil used; and era 4, 1998 to 2000 (n = 275), use of daclizumab for induction immunosuppression, primarily enteric drainage for SPK transplants, pretransplant immunosuppression in candidates awaiting PTA. RESULTS: Patient and primary cadaver pancreas graft functional (insulin-independence) survival rates at 1 year by category and era were as follows: SPK, era 2 (n = 214) versus eras 3 and 4 combined (n = 212), 85% and 64% versus 92% and 79%, respectively; PAK, era 1 (n = 36) versus 2 (n = 61) versus 3 (n = 84) versus 4 (n = 92), 86% and 17%, 98% and 59%, 98% and 76%, and 98% and 81%, respectively; in PTA, era 1 (n = 36) versus 2 (n = 72) versus 3 (n = 30) versus 4 (n = 40), 77% and 31%, 99% and 50%, 90% and 67%, and 100% and 88%, respectively. In eras 3 and 4 combined for primary cadaver SPK transplants, pancreas graft survival rates were significantly higher with bladder drainage (n = 136) than enteric drainage (n = 70), 82% versus 74% at 1 year (P =.03). Increasing recipient age had an adverse effect on outcome only in SPK recipients. Vascular disease was common (in eras 3 and 4, 27% of SPK recipients had a pretransplant myocardial infarction and 40% had a coronary artery bypass); those with no vascular disease had significantly higher patient and graft survival rates in the SPK and PAK categories. Living donor segmental pancreas transplants were associated with higher technically successful graft survival rates in each era, predominately solitary (PAK and PTA) in eras 1 and 2 and SPK in eras 3 and 4. Diabetic secondary complications were ameliorated in some recipients, and quality of life studies showed significant gains after the transplant in all recipient categories. CONCLUSIONS: Patient and graft survival rates have significantly improved over time as surgical techniques and immunosuppressive protocols have evolved. Eventually, islet transplants will replace pancreas transplants for suitable candidates, but currently pancreas transplants can be applied and should be an option at all stages of diabetes. Early transplants are preferable for labile diabetes, but even patients with advanced complications can benefit.

Adolescent↗

PubMed2001

2,500 living donor kidney transplants: a single-center experience.

OBJECTIVE: To review a single center's experience and outcome with living donor transplants. SUMMARY BACKGROUND DATA: Outcome after living donor transplants is better than after cadaver donor transplants. Since the inception of the authors' program, they have performed 2,540 living donor transplants. For the most recent cohort of recipients, improvements in patient care and immunosuppressive protocols have improved outcome. In this review, the authors analyzed outcome in relation to protocol. METHODS: The authors studied patient and graft survival by decade. For those transplanted in the 1990s, the impact of immunosuppressive protocol, donor source, diabetes, and preemptive transplantation was analyzed. The incidence of rejection, posttransplant steroid-related complications, and return to work was determined. Finally, multivariate analysis was used to study risk factors for worse 1-year graft survival and, for those with graft function at 1 year, to study risk factors for worse long-term survival. RESULTS: For each decade since 1960, outcome has improved after living donor transplants. Compared with patients transplanted in the 1960s, those transplanted in the 1990s have better 8-year actuarial patient and graft survival rates. Death with function and chronic rejection have continued to be a major cause of graft loss, whereas acute rejection has become a rare cause of graft loss. Cardiovascular deaths have become a more predominant cause of patient death; infection has decreased. Donor source (e.g., ideally HLA-identical sibling) continues to be important. For living donor transplants, rejection and graft survival rates are related to donor source. The authors show that patients who had preemptive transplants or less than 1 year of dialysis have better 5-year graft survival and more frequently return to full-time employment. Readmission and complications remain problems; of patients transplanted in the 1990s, only 36% never required readmission. Similarly, steroid-related complications remain common. The authors' multivariate analysis shows that the major risk factor for worse 1-year graft survival was delayed graft function. For recipients with 1-year graft survival, risk factors for worse long-term outcome were pretransplant smoking, pretransplant peripheral vascular disease, pretransplant dialysis for more than 1 year, one or more acute rejection episodes, and donor age older than 55. CONCLUSIONS: These data show that the outcome of living donor transplants has continued to improve. However, for living donors, donor source affects outcome. The authors also identify other major risk factors affecting both short- and long-term outcome.

Adolescent↗