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Biomedical subjects

Abhinav Humar

Publications and source records attributed to Abhinav Humar.

At least 19 recordsLinked to original sources
PubMed2006

A randomized trial of ganciclovir versus ganciclovir plus immune globulin for prophylaxis against Epstein-Barr virus related posttransplant lymphoproliferative disorder.

BACKGROUND: Transplant recipients who are Epstein-Barr virus (EBV)-seronegative and receive organs from seropositive donors (EBV D+/R-) are at increased risk for posttransplant lymphoproliferative disorder (PTLD) and may benefit from antiviral prophylaxis. We performed a multi-center trial assessing two different antiviral regimens and their effect on EBV replication. METHODS: EBV D+/R- solid organ transplant recipients were randomized to receive either ganciclovir and placebo or ganciclovir and immunoglobulin (IG) for 3 months. Following this, patients were unblinded and IG patients received additional IG therapy until 6 months. EBV viral loads were done at least monthly. RESULTS.: Thirty-four patients (25 pediatric, 9 adult) completed the protocol (16 placebo; 18 IG). The incidence of a detectable viral load within the first year posttransplant was 13/16 (81.3%) in the ganciclovir arm vs. 13/18 (72.2%) in the ganciclovir and IG arm (P=0.8). Time to first detectable viral load, and time to high-level viral load were not significantly different. By repeated measures ANOVA analysis, and by estimation of viral load AUC, no significant effect of randomization group was observed on EBV viral loads. PTLD developed in 3 (8.8%) patients (all in IG arm; P=0.23). CONCLUSIONS: No significant difference in EBV viral load suppression was observed when ganciclovir was compared with ganciclovir and IG in high-risk EBV D+/R- patients.

Adolescent↗
PubMed2006

Graft loss from recurrent glomerulonephritis is not increased with a rapid steroid discontinuation protocol.

BACKGROUND: The risk of recurrence of glomerulonephritis in kidney transplant recipients on a steroid-free maintenance immunosuppression protocol is unknown. METHODS: We studied the 4-year graft and patient survival in 105 adult kidney transplant recipients who received their transplant for glomerulonephritis (GN) and were treated with a protocol incorporating rapid discontinuation of prednisone for 5 days (group 1). We compared these outcomes to two control groups; 439 concurrent recipients who received a transplant for causes other than GN (group 2) and to 260 kidney transplant recipients who received an allograft for GN between 1994 and 1999 and were maintained on a steroid-based immunosuppressive protocol (group 3). RESULTS: The 4-year graft and patient survival were similar in the three groups. Acute rejection-free survival was also similar. Serial annual serum creatinine and estimated GFR were also comparable amongst the three groups. Two grafts were lost in group 1 from biopsy-proven recurrent GN and eight other subjects had evidence of histological recurrence at 11.2+/-11.9 months. Seven grafts were lost for recurrent disease in group 3 and 15 others had evidence of histological recurrence at 29.1+/-32.6 months. The mean time to graft loss from recurrence was 52+/-22 months. CONCLUSION: A regimen that utilizes rapid discontinuation of steroids conveys no added risk of graft loss from recurrent GN in the short term but longer follow-up is needed. A consideration should be made to discontinue corticosteroids in the potential recipients who are on them at the time of transplantation.

Adolescent↗
PubMed2005

Posttransplant lymphoproliferative disorder in pancreas transplantation: a single-center experience.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a rare, serious complication of transplantation. The characteristics and associations of this disease in pancreas recipients have not been extensively studied. METHODS: From January 1988 through December 2002, 787 pancreas and 569 kidney-pancreas transplants were performed at our institution. Eighteen pancreas recipients developed polymorphic PTLD or malignant lymphoma. Data on clinical course, organ involvement, molecular characteristics, and association with immunosuppression and recent cytomegalovirus (CMV) infection were compiled from the institutional transplant database. Patient survival was compared to recipients of liver and kidney transplants at the same center by using Kaplan-Meier analysis. RESULTS: The 5-year cumulative incidence of PTLD in simultaneous pancreas-kidney, pancreas after kidney, and pancreas transplant alone recipients was 2.5%, 1.2%, and 1.0%, respectively (P = 0.23). A noticeably, but not significantly, higher cumulative incidence was seen in the more recent era since 1995 (2.1% vs. 0.9%, P = 0.15). PTLD in pancreas recipients carried a worse prognosis than in liver or kidney for recipients B-cell, early-onset, and Epstein Barr virus-positive lesions. PTLD was more aggressive in pancreas recipients, with a higher stage at presentation and a trend to more bone marrow involvement. There appeared to be a tendency toward association with recent CMV infection. Since 1995, PTLD recipients have had a lower exposure to antilymphocyte preparations (25 +/- 5 vs. 10 +/- 0.8)(P < 0.05). CONCLUSIONS: PTLD in pancreas recipients remains a rare but aggressive disease, and carries a worse prognosis in comparison to other transplant recipients. These heavily immunosuppressed patients, who often face multiple transplants, may be at greater risk; CMV infection may play an antecedent role.

Adult↗
PubMed2005

Calcineurin inhibitor- and steroid-free immunosuppression in pancreas-kidney and solitary pancreas transplantation.

BACKGROUND: Calcineurin inhibitors and steroids are standard immunosuppressants in solid organ transplantation, but (long-term) side effects are harmful to the recipient and the graft. The authors present a novel strategy for posttransplant immunosuppression that combines a depleting antibody with an antimetabolite, avoiding calcineurin inhibitors and steroids. METHODS: In a prospective, nonrandomized, observational cohort study, 75 pancreas-kidney and solitary pancreas recipients received alemtuzumab (4 doses for induction and up to 12 doses within the first year) and mycophenolate mofetil (> or = 2 g/day) for induction and maintenance therapy. Minimum follow-up was 6 months. We compared the results with a historical group of 266 consecutive pancreas recipients on Thymoglobulin (induction) and tacrolimus (maintenance). RESULTS: Differences in patient and graft survival rates between the study and control groups at 6 months were not statistically significant. However, the incidence of a first reversible rejection episode was significantly higher for simultaneous pancreas-kidney recipients in the study (vs. control) group. We noted a trend toward higher modification of renal disease levels at 6 months posttransplant in the study (vs. control) groups. CONCLUSIONS: The combination of alemtuzumab and mycophenolate mofetil was associated with an acceptable rejection rate, a good safety profile, and good (graft and native) kidney function; it eliminated undesired calcineurin inhibitor- and steroid-related side effects. Longer follow-up is warranted before expanded application can be recommended.

Alemtuzumab↗
PubMed2005

Late anastomotic leaks in pancreas transplant recipients - clinical characteristics and predisposing factors.

BACKGROUND: Anastomotic leaks after pancreas transplants usually occur early in the postoperative course, but may also be seen late post-transplant. We studied such leaks to determine predisposing factors, methods of management, and outcomes. RESULTS: Between January 1, 1994 and December 31, 2002, a total of 25 pancreas transplant recipients at our institution experienced a late leak (defined as one occurring more than 3 months post-transplant). We excluded recipients with an early leak or with a leak seen immediately after an enteric conversion. The mean recipient age was 40.3 yr; mean donor age, 31.3 yr. The category of transplant was as follows: simultaneous pancreas-kidney (n = 5, 20%), pancreas after kidney (n = 10, 40%), and pancreas transplant alone (n = 10, 40%). At the time of their leak, most recipients (n = 23, 92%) had bladder-drained pancreas grafts; only two recipients (8%) had enteric-drained grafts. The mean time from transplant to the late leak was 20.5 months (range = 3.5-74 months). A direct predisposing event or risk factor occurring in the 6 wk preceding leak diagnosis was identified in 10 (40%) of the recipients. Such events or risk factors included a biopsy-proven episode of acute rejection (n = 4, 16%), a history of blunt abdominal trauma (n = 3, 12%), a recent episode of cytomegalovirus infection (n = 2, 8%), and obstructive uropathy from acute prostatitis (n = 1, 4%). Non-operative or conservative care (Foley catheter placement with or without percutaneous abdominal drains) was the initial treatment in 14 (56%) of the recipients. Such care was successful in nine (64%) of the 14 recipients; the other five (36%) required surgical repair after failure of conservative care at a mean of 10 d after Foley catheter placement. Of the 25 recipients, 11 underwent surgery as their initial leak treatment: repair in nine and pancreatectomy because of severe peritonitis in two. After appropriate management (conservative or operative) of the initial leak, five (20%) of the 25 recipients had a recurrent leak; the mean length of time from initial leak to recurrent leak was 5.6 months. All five recipients with a recurrent leak ultimately required surgery. CONCLUSIONS: Late anastomotic leaks are not uncommon; they may be more common with bladder-drained grafts. One-third of the recipients with a late leak had experienced some obvious preceding event that predisposed to the leak. For two-thirds of our stable recipients with bladder-drained grafts, non-operative treatment of the leak was successful.

Abdominal Injuries↗
PubMed2005

Outcomes of pancreas transplants for patients with type 2 diabetes mellitus.

BACKGROUND: The objective of this study was to examine how effectively pancreas transplants provide long-term glucose control in patients with type 2 diabetes mellitus (DM). We used guidelines from the American Diabetes Association (ADA) and the World Health Organization (WHO) to appropriately classify recipients with type 2 DM (vs. type 1 DM). RESULTS: From 1994 through 2002, a total of 17 patients with type 2 DM underwent a pancreas transplant at our center. Mean recipient age was 52.5 yr. The mean age at diabetes onset was 35.7 yr; mean duration, 16.8 yr. Most recipients had one or more secondary complications related to their diabetes: retinopathy (94%), neuropathy (76%), or nephropathy (65%). At the time of their transplant, three (18%) were on oral hypoglycemic agents alone and 14 (82%) were on insulin therapy. Of the 17 transplants, seven (41%) were a simultaneous pancreas-kidney transplant (SPK); four (24%), pancreas after kidney transplant (PAK); and six (35%), pancreas transplant alone (PTA). One recipient died during the perioperative period because of aspiration. The other 16 recipients became euglycemic post-transplant and had a functional graft at 1 yr post-transplant (patient and graft survival rates, 94%). Now, with a mean follow-up of 4.3 yr post-transplant, the patient survival rate is 71%. The four additional deaths were because of sepsis (n = 2), suicide (n = 1), and unknown cause (n = 1). All four of these recipients were insulin-independent at the time of death, although one was on an oral hypoglycemic agent. Of the 12 recipients currently alive, 11 remain euglycemic without requiring insulin therapy or oral hypoglycemic agents; one began insulin therapy 1.2 yr post-transplant (current daily dose, 60 units). CONCLUSION: These findings suggest that pancreas transplants can provide excellent glucose control in recipients with type 2 DM. All 16 (94%) of our recipients whose transplant was technically successful were rendered euglycemic. Long-term results were comparable with those seen in transplant recipients with type 1 DM.

Adult↗
PubMed2005

Successful re-use of liver allografts: three case reports and a review of the UNOS database.

The donor organ shortage has compelled transplant centers to use organs from non-traditional sources. One example is the re-use of a previously transplanted organ, such as a kidney or liver. We report three cases detailing the successful re-use of liver allografts. In all three cases, the index recipient was declared brain-dead very soon post-transplant, but was felt to have a well-functioning liver graft. Important points in these cases were to ensure that the liver graft was functioning well in the index recipient, that it appeared normal per biopsy examination, and that ischemic time was kept very short at the time of the second transplant. We queried the United Network for Organ Sharing (UNOS) database for similar cases, and found 11 such cases, which we briefly describe herein.

Adult↗
PubMed2005

Living donor and split-liver transplants in hepatitis C recipients: does liver regeneration increase the risk for recurrence?

Concern exists that partial liver transplants (either a living donor [LD] or deceased donor [DD] in hepatitis C virus (HCV)-positive recipients may be associated with an increased risk for recurrence. From 1999 to 2003, at our institution, 51 HCV-positive recipients underwent liver transplants: 32 whole-liver (WL) transplants, 12 LD transplants and 7 DD split transplants. Donor characteristics differed in that WL donors were older, and LD livers had lower ischemic times. Recipient characteristics were similar except that mean MELD scores in LD recipients were lower (p < 0.05). With a mean follow-up of 28.3 months, 46 (90%) recipients are alive: three died from HCV recurrent liver disease and two from tumor recurrence. Based on 1-year protocol biopsies, the incidence of histologic recurrence in the three groups is as follows: WL, 81%; LD, 50% and DD split, 86% (p = 0.06 for LD versus WL). The mean grade of inflammation on the biopsy specimens was: WL, 1.31; LD, 0.33 and DD split, 1.2 (p = 0.002 for LD versus WL; p = 0.03 for LD versus DD split). Mean stage of fibrosis was: WL, 0.96; LD, 0.22 and DD split, 0.60 (p = 0.07 for LD versus WL). Liver regeneration does not seem to affect hepatitis C recurrence as much, perhaps, as factors such as DD status, donor age and cold ischemic time.

Adult↗
PubMed2005

A comparison of surgical outcomes and quality of life surveys in right lobe vs. left lateral segment liver donors.

Concern remains regarding the possibly higher risk to living liver donors of the right lobe (RL), as compared with the left lateral segment (LLS). We studied outcomes and responses to quality of life (QOL) surveys in the two groups. From 1997 to 2004, we performed 49 living donor liver transplants (LDLTs): 33 RL and 16 LLS. Notable differences included a higher proportion of female and unrelated donors in the RL group. A significantly larger liver mass was resected in RL (vs. LLS) donors: 720 (vs. 310) g, p = 0.01; RL donors also had greater blood loss (398 vs. 240 mL, p = 0.04) and operative times (7.2 vs. 5.7 h, p = 0.05). However, those findings did not translate into significant differences in donor morbidity. The complication rate was 12.5% in LLS donors and 9.1% in RL donors (p = ns). Per a QOL survey at 6 months postdonation, no significant differences were noted in SF-12 scores for the two groups. Recovery times were somewhat longer for RL donors. Mean time off work was 61.0 days for RL donors and 32.4 days for LLS donors (p = 0.004). RL donation is associated with greater operative stress for donors, but not necessarily with a more complicated recovery or differences in QOL.

Adolescent↗
PubMed2005

A prospective randomized trial of steroid-free maintenance regimens in kidney transplant recipients--an interim analysis.

We compared three maintenance immunosuppressive regimens in a rapid discontinuation of prednisone protocol. From March 1, 2001, through December 31, 2003, 239 first and second kidney transplant recipients (166 LD; 73 DD) were randomized. All recipients were treated with Thymoglobulin; all received steroids intraoperatively and for 5 days postoperatively. Randomization was to cyclosporine-mycophenolate mofetil (n = 85); high-level tacrolimus (TAC) (8-12 ng/mL)-low-level sirolimus (SRL) (3-7 ng/mL) (n = 72); or low-level TAC (3-7 ng/mL)-high-level SRL (8-12 ng/mL) (n = 82). We found no difference at 24 months between groups in patient, graft, death-censored graft, or acute rejection-free graft survival, or in kidney function. Wound complications were more common in SRL-treated recipients (p = 0.02); we found no other differences between groups in complication rates. Our data suggest that excellent patient and graft survival and low rejection rates can be obtained using a variety of maintenance protocols without prednisone.

Antilymphocyte Serum↗
PubMed2005

Prednisone-free maintenance immunosuppression-a 5-year experience.

Concern persists that prednisone-free maintenance immunosuppression in kidney transplant recipients will be associated with an increase in late allograft dysfunction and graft loss. We herein report 5-year follow-up of a trial of prednisone-free maintenance immunosuppression. From October 1, 1999, through January 31, 2005, at our center, 589 kidney transplant recipients were treated with a protocol incorporating discontinuation of their prednisone on postoperative day 6. At 5 years, actuarial patient survival was 91%; graft survival, 84%; death-censored graft survival, 92%; acute rejection-free graft survival, 84% and chronic rejection-free graft survival, 87%. The mean serum creatinine level (+/-SD) at 1 year was 1.6 +/- 0.6; at 5 years, 1.7 +/- 0.8. In all, 86% of kidney recipients with functioning grafts remain prednisone-free as of April 30, 2005. As compared with historical controls, recipients on prednisone-free maintenance immunosuppression had a significantly lower rate of a number of complications, including cataracts (p < 0.001), posttransplant diabetes mellitus (p < 0.001), avascular necrosis (p = 0.001), and fractures (p = 0.004). We conclude that prednisone-related side effects can be minimized in a protocol incorporating prednisone-free maintenance immunosuppression. Five-year graft outcome remains good.

Anti-Infective Agents↗
PubMed2004

Rapid discontinuation of prednisone in higher-risk kidney transplant recipients.

Prednisone-minimization protocols have been successful in low-risk recipients. We report on the use of a protocol incorporating rapid discontinuation of prednisone in a cohort of kidney transplant recipients (n = 79) at increased immunologic risk. Our data suggests that such recipients should not be excluded from prednisone-minimization protocols.

Humans↗
PubMed2004

Technical failures after pancreas transplants: why grafts fail and the risk factors--a multivariate analysis.

BACKGROUND: Technical failure (TF) rates remain high after pancreas transplants; while rates have decreased over the last decade, more than 10% of all pancreas grafts continue to be lost due to technical reasons. We performed a multivariate analysis to determine causes and risk factors for TF of pancreas grafts. RESULTS: Between 1994 and 2003, 937 pancreas transplants were performed at our center in the following transplant categories: simultaneous pancreas-kidney (SPK) (n=327), pancreas after kidney (PAK) (n=399), and pancreas transplant alone (PTA) (n=211). Of these, 123 (13.1%) grafts were lost due to technical reasons (thrombosis, leaks, infections). TF rates were higher for SPK (15.3%) versus PAK (12.2%) or PTA (11.4%), though this was not statistically significant. Thrombosis accounted for 52.0% of all TFs. Other causes were infections (18.7%), pancreatitis (20.3%), leaks (6.5%), and bleeding (2.4%). Thrombosis was the most common cause for TF in all three transplant categories. By multivariate analysis, the following were significant risk factors for TF of the graft: recipient body mass index (BMI) >30 kg/m (relative risk [RR]=2.42, P=0.0003), preservation time >24 hr (1.87, P=0.04), cause of donor death other than trauma (RR=1.58, P=0.04), enteric versus bladder drainage (1.68, P=0.06), and donor BMI >30 kg/m (1.66, P=0.06). Not significant were donor or recipient age, a retransplant, and the category of transplant. CONCLUSIONS: TFs remain significant after pancreas transplants. In SPK recipients, TF represents the most common cause of pancreas graft loss. For isolated pancreas transplants, TF is second only to rejection as a cause of graft loss. Increased preservation times and donor or recipient obesity seem to be risk factors. Minimizing these risks factors would be important to try to decrease TF.

Adult↗
PubMed2004

Liver regeneration after adult living donor and deceased donor split-liver transplants.

As the number of living donor (LD) and deceased donor (DD) split-liver transplants (SLTs) have increased over the last 5 years, so too has the interest in liver regeneration after such partial-liver transplants. We looked at liver regeneration, as measured by computed tomography (CT) volumetrics, to see if there were significant differences among LDs, right-lobe LD recipients, and SLT recipients. We measured liver volume at 3 months postoperatively by using CT, and we compared the result to the patient's ideal liver volume (ILV), which was calculated using a standard equation. The study group consisted of 70 adult patients who either had donated their right lobe for LD transplants (n = 24) or had undergone a partial-liver transplant (right-lobe LD transplants, n = 24; right-lobe SLTs, n = 11; left-lobe SLTs, n = 11). DD (vs. LDs) were younger (P < 0.01), were heavier (P = 0.06), and had longer ischemic times (P < 0.01). At 3 months postoperatively, LDs had attained 78.6% of their ILV, less than the percentage for right-lobe LD recipients (103.9%; P = 0.0002), right-lobe SLT recipients (113.6%; P = 0.01), and left-lobe SLT recipients (119.7%; P = 0.0006). When liver size at the third postoperative month was compared with the liver size immediately postoperatively, LDs had a 1.85-fold increase. This was smaller than the increase seen in right-lobe LD recipients (2.08-fold), right-lobe SLT recipients (2.17-fold), and left-lobe SLT recipients (2.52-fold). In conclusion, liver regeneration, as measured by CT volume, seems to be greatest in SLT recipients. LD recipients seem to have greater liver growth than their donors. The reason for this remains unclear.

Adult↗
PubMed2004

Regionwide sharing for status 1 liver patients--beneficial impact on waiting time and pre- and posttransplant survival.

On August 21, 1999, Region 7 of the United Network for Organ Sharing (UNOS) adopted a policy of regionwide sharing of cadaver livers for UNOS Status 1 recipients. We examined what impact this policy had at our center on their waiting times, waiting list mortality, and outcomes. From January 1, 1995, through December 31, 2002, our center listed 39 patients for an emergent (Status 1) transplant, according to the current criteria for Status 1 listing: patients (adult and pediatric) with fulminant hepatic failure (FHF), hepatic artery thrombosis, or primary nonfunction early after a liver transplant, or critically ill pediatric patients with chronic liver disease. These 39 candidates were analyzed in 2 groups: those listed before regionwide sharing (Group I, n = 19) and those listed after (Group II, n = 20). Patient characteristics did not differ significantly between the 2 groups, including mean donor and recipient age, proportion of pediatric patients, and type of graft used (i.e., living or deceased donor, segmental or whole-organ). FHF was the most common cause of liver failure in both groups-74% versus 70% (P = ns). The next most common cause in both groups was hepatic artery thrombosis, followed by primary nonfunction. Most transplants used deceased donors; however, 2 of the transplants in Group I versus only 1 in Group II used living donors. Waiting list mortality (the patient death rate before a transplant could take place) was 32% in Group I versus only 5% in Group II (P =.03). The mean number of days on the waiting list was also substantially lower in Group II (2.9 days) than in Group I, (5.8 days) (P =.04). For patients who underwent a transplant, graft and patient survival rates at 6 months posttransplant were 69.2% in Group I versus 89.5% in Group II (P =.03). In conclusion, the introduction of regionwide sharing seems to have been of benefit for Status 1 patients at our center. They have a significantly lower risk of dying while waiting for a transplant and undergo one in a much shorter period of time.

Adult↗