Publications by authors named "Wendy J Grant"

31 Publications

Viral enteritis in intestinal transplant recipients.

Transpl Infect Dis 2020 Apr 29;22(2):e13248. Epub 2020 Jan 29.

Transplant Surgery Division, University of Nebraska Medical Center, Omaha, Nebraska.

Intestinal transplant recipients (ITR) are at high risk for infections due to the high level of immunosuppression required to prevent rejection. There are limited data regarding viral enteritis post-intestinal transplantation. We retrospectively reviewed ITR transplanted between January 2008 and December 2016. Descriptive statistics, including mean (standard deviation) and median (range), were performed. Sixty-one (43.9%) of the 139 transplanted patients had viral enteritis: 26% norovirus, 25% adenovirus, and 9% each rotavirus and sapovirus. The median age of pediatric patients was 1.6 years (0.4-16.9) and for adults 36.3 years (27.1-48.2). Fifty-seven (58%) of 99 pediatric ITR had viral enteritis compared to 4 (10%) of 40 adult ITR. Median time-to-clinical resolution of enteritis for all patients was 5 days (1-92). Standard of care therapies administered: anti-motility agents (10%), anti-emetics agents (14%), and intravenous fluids (42%). There was a higher incidence of viral enteritis in pediatric compared to adults ITR. The majority of viral enteritis episodes resolved within 1 week and were treated with supportive therapy.
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http://dx.doi.org/10.1111/tid.13248DOI Listing
April 2020

Failure of abdominal wall closure after intestinal transplantation: Identifying high-risk recipients.

Clin Transplant 2019 11 23;33(11):e13713. Epub 2019 Oct 23.

Division of Transplant, Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA.

Open abdomen and fascial dehiscence after intestinal transplantation increase morbidity. This study aims to identify recipient and donor factors associated with failure to achieve sustained primary closure (failed-SPC) of the abdomen after intestinal transplant. We conducted a single-center retrospective study of 96 intestinal transplants between 2013 and 2018. Thirty-eight (40%) were adult patients, and 58 were pediatric patients. Median age at transplantation was 36.0 and 5.8 years, respectively. Failed-SPC occurred in 31 (32%) patients. Identified risk factors of failed-SPC included preexisting enterocutaneous fistula (OR: 6.8, CI: 2.4-19.6, P = .0003), isolated intestinal graft (OR: 3.4, CI: 1.24-9.47, P = .02), male sex in adults (OR: 3.93, CI: 1.43-10.8, P = .009), and age over four years (OR: 6.22, CI: 1.7-22.7, P = .004). There was no association with primary diagnosis and prior transplant with failed-SPC. Donor-to-recipient size ratios did not predict failed-SPC. There was an association between failed-SPC and extended median hospital stay (100 vs 57 days, P = .007) and increased time to enteral autonomy in pediatric patients. There is a relationship between failed-SPC and a higher rate of laparotomy (OR: 21.4, CI: 2.78-178.2, P = .0003) and fistula formation posttransplant (OR: 11.4, CI: 2.83-45.84, P = .0005) in pediatric patients. Given inferior outcomes with failed-SPC, high-risk recipients require careful evaluation.
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http://dx.doi.org/10.1111/ctr.13713DOI Listing
November 2019

Including colon in intestinal transplantation: a focus on post-transplant renal function - a retrospective study.

Transpl Int 2020 Feb 10;33(2):142-148. Epub 2019 Oct 10.

Division of Transplant, Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA.

Intestinal transplant recipients experience a high rate of renal complications secondary to dehydration due to increased ostomy output. It is hypothesized that inclusion of donor colon in the intestinal allograft may improve renal function in patients without functional native colon by improving fluid absorption. A single-center retrospective study of intestinal transplant recipients compared outcomes of patients receiving en bloc colon as part an intestinal allograft (ICTx), and those not receiving colon (CCNTx), as well as a control group of intestinal transplant recipients with functional native colon (ITx). Forty-seven patients (ICTx n = 17, CCNTx n = 15, ITx n = 15) were studied. One-year post-transplant renal function, as measured by change in glomerular filtration rate (GFR) and blood urea nitrogen (BUN) from baseline, was superior in ICTx (mean delta-GFR of -1.31 and delta-BUN of -1.46) compared to CCNTx (-6.54 and 17.54, P = 0.05 and P = 0.17, respectively) and similar to the ITx controls (0.55 and 2.09). Recipients of donor colon experienced a higher rate of ileostomy reversal when compared to CCNTx (62.5% vs. 20%, P = 0.0008), which was similar to the ITx controls (60%). These findings support the inclusion of en bloc donor colon in the intestinal allograft for recipients without functional native colon.
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http://dx.doi.org/10.1111/tri.13523DOI Listing
February 2020

Prophylactic cholecystectomy in short bowel syndrome: Is it being utilized?

Am J Surg 2018 07 27;216(1):73-77. Epub 2018 Apr 27.

University of Nebraska Medical Center, Omaha, NE, USA.

Introduction: Cholelithiasis is common in patients with short bowel syndrome (SBS). Prophylactic cholecystectomy (PC) of the non-diseased gallbladder has been recommended in SBS patients when laparotomy is being undertaken for other reasons. Our aim was to determine if PC is being utilized.

Methods: 500 adults with SBS were seen over a 25 year period. 215 undergoing cholecystectomy prior to SBS were excluded, leaving 285 patients for evaluation.

Results: 151 (53%) SBS patients underwent a subsequent laparotomy. 77 underwent cholecystectomy for cholelithiasis at the 1st opportunity. 27 patients underwent a PC at the 1st opportunity. 47 patients did not undergo PC at the 1st opportunity. 17 (36%) of these 47 patients subsequently developed cholelithiasis with 7 undergoing cholecystectomy. Age, gender, diagnosis and initial BMI and need for longterm parenteral nutrition were similar in patients who had PC or did not. PC patients were more likely to have intestinal remnant length <60 cm (59% vs 21%, p < .05).

Conclusions: Overall 10% of SBS patients underwent PC. However, only 36% of eligible patients undergoing laparotomy had a PC.
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http://dx.doi.org/10.1016/j.amjsurg.2018.04.002DOI Listing
July 2018

Invasive pneumococcal infections in pediatric liver-small bowel-pancreas transplant recipients.

Pediatr Transplant 2018 05 13;22(3):e13165. Epub 2018 Feb 13.

Pediatric Gastroenterology, Hepatology and Nutrition, University of Nebraska Medical Center, Omaha, NE, USA.

Children undergoing LSBPTx are at increased risk of IPI due to splenectomy. We aimed to describe the clinical features and outcomes of IPI in pediatric LSBPTx recipients. Between 2008 and 2016, 122 LSBPTx children at our center were retrospectively reviewed. Nine patients had 12 episodes of IPI; the median age at first infection was 3.5 years (range: 1.5-7.1 years). The median time from transplant to first infection was 3 years (range: 0.8-5.8 years). Clinical presentation included as follows: pneumonia (n = 1), bacteremia/sepsis (n = 7), pneumonia with sepsis (n = 1), meningitis with sepsis (n = 2), pneumonia and meningitis with sepsis (n = 1). The overall risk for IPI was 7.4% or 0.9% per year. The mortality rate was 22%. Seven (78%) children had received at least one dose of PCV13, four (44%) patients had received 23-valent pneumococcal polysaccharide vaccine prior to IPI. All patients were on oral penicillin prophylaxis. In conclusion, despite partial or complete pneumococcal immunization and reported antimicrobial prophylaxis, IPI in LSBPTx children can have a fatal outcome. Routine monitoring of pneumococcal serotype antibodies to determine the timing for revaccination might be warranted to ensure protective immunity in these transplant recipients.
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http://dx.doi.org/10.1111/petr.13165DOI Listing
May 2018

Predictors of persistent diarrhea in norovirus enteritis after solid organ transplantation.

Clin Transplant 2016 11 6;30(11):1488-1493. Epub 2016 Oct 6.

Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA.

Solid organ transplant (SOT) recipients may develop protracted diarrheal illness from norovirus. We performed a retrospective chart review between January 2010 and April 2014 to identify predictors of persistent diarrhea in transplant recipients with norovirus enteritis. A total of 152 SOT recipients with mean age of 31.5 years (SD 23.1) were included: 43.4% male, 34.2% pediatric patients. Allograft types were abdominal 136 (89.5%) (kidney [39.5%], liver-small bowel [23%], other [27%]) and thoracic 16 (10.5%). The median time to diagnosis of first norovirus enteritis episode from date of transplantation was 1.7 (0.3-5.3) years. At time of presentation, diarrhea was present in 141 (93%). Thirty percent had persistent diarrhea at 2 weeks. Hospitalization was required for treatment in 121 (80%) of episodes with the mean length of stay of 10±15.2 days. Most (91%) infections were due to norovirus genogroup II, and gastrointestinal coinfections were seen in 23 (19%) norovirus enteritis episodes. Nausea at time of diagnosis (P=.002) and cytomegalovirus (CMV) infection in the preceding 90 days (P=.036) were identified as independent risk factors for persistent diarrhea using univariate and multivariable logistic regression. Our study shows that nausea on presentation and prior CMV infection were associated with persistent diarrhea in patients with norovirus enteritis.
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http://dx.doi.org/10.1111/ctr.12844DOI Listing
November 2016

Cholecystectomy and Liver Disease in Short Bowel Syndrome.

J Gastrointest Surg 2016 Feb 26;20(2):322-7. Epub 2015 Oct 26.

Department of Surgery, University of Nebraska Medical Center, 983280 Nebraska Medical Center, Omaha, NE, 68198-3280, USA.

Background: Recently, an association has been proposed between cholecystectomy and various liver diseases. Our aim was to determine whether cholecystectomy in short bowel patients influences the risk of liver disease.

Methods: We reviewed 422 adults: 182 underwent cholecystectomy prior to short bowel, 102 after developing short bowel, and 138 patients still had the gallbladder in place.

Results: Compared to pre and post short bowel, gallbladder patients were significantly less likely to have obesity (18 % and 21 % vs 9 %), central line infections (59 % and 69 % vs 46 %), intestine <60 cm (30 % and 39 % vs 26 %), and require parenteral nutrition >1 year (72 % and 77 % vs 64 %). The incidence of fatty liver was similar (31, 26, and 25 %). Fibrosis/cirrhosis was less common in the gallbladder group (26 % and 36 % vs 16 %). Frequency of end-stage liver disease was similar (15, 22, and 11 %). On multivariate analysis, cholecystectomy, parenteral nutrition >1 year, line infection, and intestine <60 cm were predictors of fibrosis/cirrhosis. Parenteral nutrition >1 year, line infection, and intestine <60 cm were predictors of end-stage liver disease.

Conclusions: Cholecystectomy does not appear to increase the incidence of liver disease in short bowel patients overall. Fibrosis/cirrhosis occurs significantly less frequently in patients with an intact gallbladder.
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http://dx.doi.org/10.1007/s11605-015-3008-8DOI Listing
February 2016

Risk of Intestinal Malignancy in Patients With Short Bowel Syndrome.

JPEN J Parenter Enteral Nutr 2017 05 29;41(4):562-565. Epub 2015 Sep 29.

1 Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska.

Background: Postresection intestinal adaptation is an augmented self-renewal process that might increase the risk of malignant transformation in the intestine. Furthermore, patients with short bowel syndrome (SBS) have other characteristics that might increase this risk. Our aim was to determine the incidence of new intestinal malignancy in SBS patients.

Methods: We reviewed the records of 500 adult SBS patients identified from 1982-2013. There were 199 men and 301 women ranging in age from 19-91 years. Follow-up from the time of diagnosis of SBS ranged from 12-484 months. A total of 186 (37%) patients were followed >5 years.

Results: The cause of SBS was postoperative in 35% of patients, malignancy/radiation in 19%, mesenteric vascular disease in 17%, Crohn's disease in 16%, and other in 13%. Twenty-eight (6%) patients received growth stimulatory medications. Fifteen percent of patients had a prior total colectomy. Twenty-eight (6%) patients underwent intestinal transplantation, and 115 (23%) patients had a previous abdominal malignancy, including colorectal cancer in 43 patients. Thirty-six (7%) received radiation therapy. Recurrent colon cancer was found in 2 patients, one at a stoma and the other with lung metastases. New colon cancer was found in 1 patient (0.2%), a 62-year-old woman with long-standing Crohn's disease.

Conclusion: The incidence of colon cancer in this heterogenous group of patients with SBS was similar to that of the normal population. This suggests that the risk of developing a new colon cancer in patients with SBS is not increased.
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http://dx.doi.org/10.1177/0148607115609587DOI Listing
May 2017

Combined heart and liver transplantation against positive cross-match for patient with hypoplastic left heart syndrome.

Transplantation 2014 Dec;98(12):e100-2

1 Division of Cardiology University of Nebraska Medical Center Omaha, NE 2 Division of Cardiovascular and Thoracic Surgery University of Nebraska Medical Center Omaha, NE 3 Division of Pathology and Microbiology University of Nebraska Medical Center Omaha, NE 4 Division of Surgery University of Nebraska Medical Center Omaha, NE 5 Address correspondence to: Eugenia Raichlin, M.D., University of Nebraska Medical Center, Omaha, NE 68198-2265.

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http://dx.doi.org/10.1097/TP.0000000000000542DOI Listing
December 2014

The sum is greater than its parts: clinical evaluations and grade inflation in the surgery clerkship.

Am J Surg 2015 Apr 22;209(4):760-4. Epub 2015 Jan 22.

Department of Surgery, University of Nebraska Medical Center, 983280 Nebraska Medical Center, Omaha, NE 68198-3280, USA. Electronic address:

Background: This study examines grading component distributions to determine whether alterations in clinical grade determination reduce skew and improve predictive capability of the clinical evaluation.

Methods: Rotation evaluations, examination scores, and final grades were collected for third-year medical students over a 2-year period. Conditional logistic regression and ordinary least squares regression models were run using SAS 9.3.

Results: Conditional logistic regression demonstrated significant association between global clinical score and final grade and between average clinical evaluation score and final grade. Inclusion of shelf score into either model demonstrated increase in overall final grade.

Conclusions: Regressions using global and average clinical evaluation score indicate that average score is a better fit for a norm-based grading system. Arguably, the Shelf measures clinical knowledge more objectively than clinical evaluation, but both were significant. Clinical evaluation is prone to inflation because of its subjective nature; conceivably, inflation leads to the decreased correlation with shelf score.
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http://dx.doi.org/10.1016/j.amjsurg.2014.10.023DOI Listing
April 2015

Impact of anti-thymocyte globulin during immunosuppression induction in patients with hepatitis C after liver transplantation.

Dig Dis Sci 2014 Nov 28;59(11):2804-12. Epub 2014 May 28.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 W Markham St #567, Little Rock, AR, 72205, USA,

Background: Induction immunosuppression with anti-thymocyte globulin (ATG) provides potential benefits after liver transplantation (LT). However, its use in patients with LT and hepatitis C (HCV) is controversial.

Aim: To evaluate the 1- and 2-year patient survival and HCV recurrence rate in patients receiving ATG during the induction phase of immunosuppression (IPI) after LT.

Methods: A total of 49 patients undergoing their first LT for HCV were randomized to receive ATG during IPI. Patient survival and HCV recurrence were determined at 1 and 2 years. The frequency of acute cellular rejection (ACR), infections, and neoplasms was also evaluated.

Results: Twenty-six patients were randomized to receive ATG (Arm-1) and 23 to standard induction therapy (Arm-2). Those given ATG had lower HCV recurrence (26.9 vs 73.9 %, p = 0.001). The 1- and 2-year patient survival rates were similar for both arms (p = 0.33). Infections occurred in 46.1 % subjects in Arm-1 and 34.7 % in Arm-2 (p = 0.562). There was a greater proportion of fungal infections in Arm-1 (19.2 vs 0 %, p = 0.032).

Conclusions: ATG during the IPI was associated with lower frequency of recurrence of HCV in patients undergoing LT. This, however, did not affect the 1- and 2-year survival and the frequency of ACR, infections, or neoplasms.
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http://dx.doi.org/10.1007/s10620-014-3215-2DOI Listing
November 2014

Pre-resection gastric bypass reduces post-resection body mass index but not liver disease in short bowel syndrome.

Am J Surg 2014 Jun 4;207(6):942-8. Epub 2014 Jan 4.

Department of Surgery, University of Nebraska Medical Center Omaha, Omaha, NE, USA.

Background: Obese patients developing short bowel syndrome (SBS) maintain a higher body mass index (BMI) and have increased risk of hepatobiliary complications. Our aim was to determine the effect of pre-resection gastric bypass (GBP) on SBS outcome.

Methods: We reviewed 136 adults with SBS: 69 patients with initial BMI < 35 were controls; 43 patients with BMI > 35 were the obese group; and 24 patients had undergone GBP before SBS.

Results: BMI at 1, 2, and 5 years was similar in control and GBP groups, whereas obese patients had a persistently increased BMI. Eight (33%) of the GBP patients had a pre-resection BMI > 35, but post-SBS BMI was similar to those <35. Obese patients were more likely to wean off PN (47% vs 20% control and 12% GBP, P < .05). Radiographic fatty liver tended to be higher in the GBP group (54% vs 19% control and 35% obese). End-stage liver disease occurred more frequently in obese and GBP patients (30% and 33% vs 13%, P < .05).

Conclusions: Pre-resection GBP prevents the nutritional benefits of obesity but does not eliminate the increased risk of hepatobiliary disease in obese SBS patients. This occurs independent of pre-SBS BMI suggesting the importance of GBP itself or history of obesity rather than weight loss.
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http://dx.doi.org/10.1016/j.amjsurg.2013.10.019DOI Listing
June 2014

Intestinal transplantation in children with multiple intestinal atresias and immunodeficiency.

Pediatr Transplant 2014 Mar 28;18(2):190-6. Epub 2013 Dec 28.

Department of Pediatric Gastroenterology, Children's Mercy Hospital, Kansas City, MO, USA.

GVHD has been reported in 8-10% of children after small bowel transplant (SBTx). Immunodeficient children may be predisposed to aggressive, steroid-resistant GVHD. There exists a unique association of immunodeficiency in children with MIA (MIAI). We report on our SBTx experience in patients with the diagnosis of MIAI, their high incidence of GVHD, and the possible role of stem cell transplantation in these patients. We performed a review of records from children that underwent SBTx or that we evaluated for SBTx at our institution. We focused on the diagnoses of atresia, multiple intestinal atresia, immunodeficiency, and GVHD in our patient population. Children with MIAI are likely to experience severe GVHD following SBTx. MIAI correlated with a 100% incidence of GVHD in these patients. Of the five patients with MIAI that underwent SBTx, three succumbed to severe GVHD within 1-6 months after SBTx. One patient received stem cell transplant prior to SBTx and did not develop severe GVHD, but died from influenza nine months after SBTx. Our unique patient survives long-term, with engraftment of donor γ δ T cells. He has mild, persistent chronic GVHD. Atresia is a common referral diagnosis for SBTx. Patients with multiple atresias, especially MIAI, are at significant risk for the complication of GVHD following SBTx. We recommend careful immunologic assessment and antecedent stem cell transplant in children with MIAI prior to SBTx.
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http://dx.doi.org/10.1111/petr.12211DOI Listing
March 2014

Serial transverse enteroplasty allows children with short bowel to wean from parenteral nutrition.

J Pediatr 2014 Jan 1;164(1):93-8. Epub 2013 Oct 1.

Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE.

Objective: To analyze the effects of serial transverse enteroplasty (STEP) on parenteral and enteral calories in children with short bowel syndrome, and examine short- and long-term complications.

Study Design: A retrospective analysis of prospectively-collected data from a large single center cohort of patients undergoing STEP procedure was analyzed. Baseline demographic and clinical information, operative data, and short- and long-term complications were recorded. Detailed growth and nutritional data were obtained for 6 months prior and 12 months following STEP procedure.

Results: Sixty-eight procedures were performed in 51 patients over a 68-month period. Median bowel length at first STEP was 51 cm with a median length gain of 54%. Repeat STEP patients had longer initial length (77 cm) and reduced length gain (20%). Operative times and blood loss were low, with few complications. Parenteral calorie requirement was stable or rising for 6 months prior to STEP, but decreased to median <20 kCal/kg/d at 1 year postop. Longer length gains were associated with higher risk of stricture formation. Seven children were transplanted, and 60% of nontransplanted children were enterally independent, with the remainder making ongoing progress; 48/51 children are alive at a median of 39 months follow-up.

Conclusions: STEP is shown to be safe, well tolerated, and to have definitive benefit in reducing parenteral calorie requirements over the first year following the procedure. It has an important role in achieving enteral independence in children with short bowel syndrome.
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http://dx.doi.org/10.1016/j.jpeds.2013.08.039DOI Listing
January 2014

Successful rehabilitation in pediatric ultrashort small bowel syndrome.

J Pediatr 2013 Nov 15;163(5):1361-6. Epub 2013 Jul 15.

Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE. Electronic address:

Objective: To examine treatment outcomes in pediatric patients with ultrashort small bowel (USSB) syndrome in an intestinal rehabilitation program (IRP).

Study Design: We reviewed IRP records for 2001-2011 and identified 28 children with USSB (≤ 20 cm of small bowel). We performed univariate analysis using the Fisher exact test and Wilcoxon rank-sum test to compare characteristics of children who achieved parenteral nutrition (PN) independence with intact native bowel and those who did not. Growth, nutritional status, and hepatic laboratory test results were compared from the time of enrollment to the most recent values using the Wilcoxon signed-rank test.

Results: Of the 28 patients identified, 27 (96%) survived. Almost one-half (48%) of these survivors achieved PN independence with their native bowel. The successfully rehabilitated patients were more likely to have an intact colon and ileocecal valve (P = .01). Significant improvements in PN kcal/kg, total bilirubin, and height and weight z-scores were seen in all patients, but serum hepatic transaminase levels did not improve in the nonrehabilitated patients.

Conclusion: Enrollment in an IRP provides an excellent probability of survival for children with USSB. The presence of an intact ileocecal valve and colon are positively associated with rehabilitation in this population, but are not requisite. Approximately one-half of patients with USSB can achieve rehabilitation, with a median time to PN independence of less than 2 years. The USSB population can attain reduced PN dependence, improvement of PN-associated liver disease, and enhanced growth with the aid of an IRP.
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http://dx.doi.org/10.1016/j.jpeds.2013.05.062DOI Listing
November 2013

Early onset, EBV(-) PTLD in pediatric liver-small bowel transplantation recipients: a spectrum of plasma cell neoplasms with favorable prognosis.

Blood 2013 Feb 18;121(8):1377-83. Epub 2012 Dec 18.

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.

EBV(-) posttransplantation lymphoproliferative disorders (PTLDs) are rare compared with EBV(+) PTLDs, occur later after transplantation, and have a poor response to treatment. Few studies have reported EBV(-) PTLD in pediatric solid-organ transplantation recipients. We describe 5 cases of EBV(-) PTLD in recipients of combined liver and small bowel allografts ranging in age from 16 months to 7 years. EBV(-) PTLD developed 9-22 months (median, 15) after transplantation. Morphologically, the lesions ranged from atypical plasma cell hyperplasia (a term not currently included in the World Health Organization classification) to plasmacytoma like. In all cases, in situ hybridization for EBV was negative, and molecular studies demonstrated clonal IgH gene rearrangements. Protein electrophoresis showed multiple clonal paraproteins in 4 of 5 cases. In 2 cases with a donor-recipient sex mismatch, FISH cytogenetics demonstrated that the plasma cells were of mixed donor/recipient origin. One patient died before therapy. Four patients were treated with high-dose dexamethasone, and 1 patient subsequently required thalidomide. All 4 remain in remission 75-128 months (median, 86) after diagnosis. In contrast to reports of EBV(-) PTLD in adults, these plasma cell lesions occurred early after transplantation and resolved completely after minimal treatment.
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http://dx.doi.org/10.1182/blood-2012-06-438549DOI Listing
February 2013

Histologic analysis of chronic rejection in small bowel transplantation: mucosal and vascular alterations.

Transplantation 2013 Jan;95(2):378-82

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA.

Background: Chronic rejection is a significant barrier to small bowel allograft survival. Although chronic rejection primarily involves vessels of the submucosa, serosa, and mesentery, some mucosal alterations have been suggested to be correlative.

Methods: We retrospectively investigated explanted small bowel allografts for clinical characteristics and histological alterations in the mucosa, submucosa, and serosa.

Results: Crypt epithelial mucin loss, submucosal fibrosis, and length of time to explant were all statistically associated with chronic rejection. Medium-sized and large-sized vessels of the serosa and mesentery preferentially demonstrated histologic changes of chronic rejection.

Conclusion: These results further define chronic vascular rejection and the relationship between the mucosal changes and chronic rejection.
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http://dx.doi.org/10.1097/TP.0b013e318270f370DOI Listing
January 2013

Preresection obesity increases the risk of hepatobiliary complications in short bowel syndrome.

Nutrients 2012 Sep 26;4(10):1358-66. Epub 2012 Sep 26.

The University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE 68198, USA.

Patients developing the short bowel syndrome (SBS) are at risk for hepatobiliary disease, as are morbidly obese individuals. We hypothesized that morbidly obese SBS individuals would be at increased risk for developing hepatobiliary complications. We reviewed 79 patients with SBS, 53 patients with initial body mass index (BMI) < 35 were controls. Twenty-six patients with initial BMI > 35 were the obese group. Obese patients were more likely to be weaned off parenteral nutrition (PN) (58% vs. 21%). Pre-resection BMI was significantly lower in controls (26 vs. 41). BMI at 1, 2, and 5 years was decreased in controls but persistently increased in obese patients. Obese patients were more likely to undergo cholecystectomy prior to SBS (42% vs. 32%) and after SBS (80% vs. 39%, p < 0.05). Fatty liver was more frequent in the obese group prior to SBS (23% vs. 0%, p < 0.05) but was similar to controls after SBS (23% vs. 15%). Fibrosis (8% vs. 13%) and cirrhosis/portal hypertension (19% vs. 21%) were similar in obese and control groups. Overall, end stage liver disease (ESLD) was similar in obese and control groups (19% vs. 11%) but was significantly higher in obese patients receiving PN (45% vs. 14%, p < 0.05). Obese patients developing SBS are at increased risk of developing hepatobiliary complications. ESLD was similar in the two groups overall but occurs more frequently in obese patients maintained on chronic PN.
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http://dx.doi.org/10.3390/nu4101358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496999PMC
September 2012

Hepatic fibrosis persists and progresses despite biochemical improvement in children treated with intravenous fish oil emulsion.

J Pediatr Gastroenterol Nutr 2013 Apr;56(4):364-9

Department of Surgery, University of Nebraska Medical Center, 983285 Nebraska Medical Center, Omaha, NE 68198–3285, USA.

Objectives: Intestinal failure-associated liver disease (IFALD) is a multifactorial process, which can culminate in cirrhosis and need for transplantation. Fish oil-based lipid emulsions (FOE) reportedly reverse hyperbilirubinemia, but there are little data on their effect on the histopathology of IFALD.

Methods: We blindly examined sequential liver biopsy data on 6 children receiving FOE, with scoring of cholestasis, inflammation, fibrosis, and ductal proliferation based on standardized systems. This information was correlated with biochemical and clinical data to determine any possible relations between biologic and histologic improvement.

Results: The median gestational age was 35 weeks, median birth weight 2064 g, and common most reason for intestinal loss was gastroschisis (5/6 children). Median intestinal length was 26 cm beyond the ligament of Treitz and most children had roughly 2 of 3 of their colonic length. It was observed that although hyperbilirubinemia reversed and hepatic synthetic function was preserved across timepoints, fibrosis was persistent in 2 cases, progressive in 3 cases, and regressed in only 1. It remained severe (grade 2 or higher) in 5 of 6 children at last biopsy. Histologic findings of cholestasis improved in all patients and inflammation improved in 5 of 6 children. There were mixed effects on ductal proliferation and steatosis.

Conclusions: In children treated with FOE, reversal of hyperbilirubinemia is not reflected by a similar histologic regression of fibrosis at the timepoints studied. Children with IFALD should have active ongoing treatment and be considered for early referral to an Intestinal Failure Program even with a normalized bilirubin.
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http://dx.doi.org/10.1097/MPG.0b013e31827e208cDOI Listing
April 2013

Risk of cytomegalovirus disease in high-risk liver transplant recipients on valganciclovir prophylaxis: a systematic review and meta-analysis.

Liver Transpl 2012 Dec;18(12):1440-7

Divisions of Infectious Diseases,University of Nebraska Medical Center, Omaha, NE 68198, USA.

Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of their high incidence of CMV disease with this drug. However, surveys have shown its common off-label use for CMV prophylaxis in liver transplant recipients. We aimed to evaluate the risk of CMV disease with VGC prophylaxis in liver transplant recipients. All studies that evaluated liver transplant recipients and used VGC (900 or 450 mg daily) for the prevention of CMV disease were included. Five controlled studies (n = 483) were pooled with a random effects model; five single-arm studies (n = 380) were pooled for the prevalence rate of CMV disease. The risk of CMV disease with VGC versus ganciclovir was 1.81 [95% confidence interval (CI) = 1.00-3.29, P = 0.05, I(2) = 0%]. For high-risk (donor-positive/recipient-negative) patients, the risk of CMV disease was 1.96 (95% CI = 1.05-3.67, P = 0.035, I(2) = 0%). The risk of CMV disease remained significant with 900 mg of VGC daily (P = 0.04) but not with 450 mg of VGC daily (P = 0.76). The risk of leukopenia with VGC was 1.87 (95% CI = 1.03-3.37, P = 0.04, I(2) = 0%). In single-arm trials, the overall CMV disease rate was 12% (95% CI = 9%-16%, P < 0.001), and the rate for high-risk patients was 20% (95% CI = 10%-38%, P = 0.002). In conclusion, 900 mg of VGC daily may not be safe as CMV prophylaxis in high-risk liver transplant recipients because of the significant 2-fold increase in the risk of CMV disease and the 1.9-fold increase in the risk of leukopenia. Alternative CMV prophylaxis should be used for liver transplant recipients.
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http://dx.doi.org/10.1002/lt.23530DOI Listing
December 2012

Massive small bowel resection during pregnancy causing short bowel syndrome.

Am Surg 2011 Dec;77(12):1589-92

Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska 68198-3280, USA.

Massive small bowel infarction in pregnancy is rare but has devastating complications. Diagnosis is difficult because pregnancy masks the symptoms. Our aim was to assess risk factors and outcomes of massive resection associated with pregnancy. We conducted a review of nine patients with short bowel syndrome (SBS) secondary to massive bowel resection during pregnancy. The most common cause of bowel resection was midgut volvulus in seven patients. Four of these also had malrotation. Three others had previous abdominal operations, including gastric bypass. The two remaining patients had vascular insufficiency. Five of the nine patients presented after a cesarean delivery. There were three fetal deaths. Resulting small bowel length was less than 60 cm in all but one patient. All patients required parenteral nutrition (PN). Seven patients developed significant complications related to SBS and long-term PN. Four patients underwent transplantation. Massive small bowel resection during pregnancy is a devastating complication, which requires a high degree of suspicion to diagnose. Most patients have risk factors, which include previous surgery, congenital malrotation, and a hypercoagulable state. Surviving patients usually need long-term PN or transplantation.
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December 2011

Is there a role for oral human immunoglobulin in the treatment for norovirus enteritis in immunocompromised patients?

Pediatr Transplant 2011 Nov 23;15(7):718-21. Epub 2011 Aug 23.

Division of Infectious Diseases, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5400, USA.

No treatment for NVE is available. Immunocompromised patients with NVE treated with OHIG (12 cases) were retrospectively identified and matched 1:1 by age and gender with immunocompromised patients with NVE not treated with OHIG (12 controls). Chi-squared test, t-test, bivariate conditional linear regression analyses, and Kaplan-Meier curve were performed. A total of 58.3% patients were small bowel transplant (SBT) recipients. Although not statistically significant, cases compared with controls were more likely to have had induction therapy (p = 0.25, OR = 65.3), higher peak tacrolimus levels (p = 0.43, OR = 1.04), SBT (p = 0.30, OR = 65.3), prior NVE (p = 0.42, OR = 2.0), TPN support (p = 0.42 OR = 2.0), and decrease in immunosuppression (p = 0.14, OR = 5.0). Treatment with OHIG favored resolution of diarrhea (p = 0.078, OR = 65.3) and decreased stool output seven days after treatment compared with controls (mean difference 11.95 mL/kg/day, p = 0.09). OHIG did not impact total time to resolution of diarrhea (mean 12.08 vs. 11.91 days; p = 0.63), length of hospital stay (p = 0.31, OR = 1.05), or cost of hospitalization (p = 0.32, OR = 1.0). We show a potential role of OHIG treatment for NVE. Resolution of diarrhea and decreased stool output were observed at seven days; no benefit was found for length of hospital stay or hospital cost.
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http://dx.doi.org/10.1111/j.1399-3046.2011.01556.xDOI Listing
November 2011

Stool calprotectin monitoring after small intestine transplantation.

Transplantation 2011 May;91(10):1166-71

Section of Transplantation, Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198-3285, USA.

Background: Small intestine transplantation is the only life-saving therapy available for patients with intestinal failure and life-threatening complications of parenteral nutrition, but it is still plagued by high levels of early acute rejection. The ability to diagnose rejection noninvasively, ideally before pathologic manifestations, would be a major advance in the care of intestinal transplant patients.

Methods: We measured calprotectin levels in 732 stool samples collected, analyzed over from 72 patients having undergone 74 total transplants, and correlated them with clinical indications, ostomy output, and pathologic findings.

Results: We found that overall patients with rejection have higher mean levels of stool calprotectin than those without, but because of significant interpatient variability, defining an effective general "cutoff" for the test is difficult. Each patient, in effect, has to act as their own control. Patients experiencing rejection episodes have greater fluctuations in calprotectin levels than those without, suggesting increased "reactivity" within the graft. Our most frequent clinical indicator for biopsy, an increase in ostomy output, had no real relationship to the discovery of rejection.

Conclusion: Although more frequent prospective sampling could perhaps demonstrate an advantage in early indication of rejection, based on these data, routine stool calprotectin monitoring is not strongly supported.
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http://dx.doi.org/10.1097/TP.0b013e318215e709DOI Listing
May 2011

Left lobe adult-to-adult living donor liver transplantation: small grafts and hemiportocaval shunts in the prevention of small-for-size syndrome.

Liver Transpl 2010 May;16(5):649-57

Division of Transplantation, Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Adult-to-adult living donor liver transplantation (AA-LDLT) has better outcomes when a graft weight to recipient weight ratio (GW/RW) > 0.8 is selected. A smaller GW/RW may result in small-for-size syndrome (SFSS). Portal inflow modulation seems to effectively prevent SFSS. Donor right hepatectomy is associated with greater morbidity and mortality than left hepatectomy. In an attempt to shift the risk away from the donor, we postulated that left lobe grafts with a GW/RW < 0.8 could be safely used with the construction of a hemiportocaval shunt (HPCS). We combined data from 2 centers and selected suitable left lobe living donor/recipient pairs. Since January 2005, 21 patients underwent AA-LDLT with left lobe grafts. Sixteen patients underwent the creation of an HPCS between the right portal vein and the inferior vena cava. The portocaval gradient (portal pressure - central venous pressure) was measured before the unclamping of the shunt and 10 minutes after unclamping. The median actual graft weight was 413 g (range = 350-670 g), and the median GW/RW was 0.67 (range = 0.5-1.0). The portocaval gradient was reduced from a median of 18 to 5 mmHg. Patient survival and graft survival at 1 year were 87% and 81%, respectively. SFSS developed in 1 patient, who required retransplantation. Two patients died at 3 and 10 months from a bile leak and fungal sepsis, respectively. The median recipient bilirubin level and INR were 1.7 mg/dL and 1.1, respectively, at 4 weeks post-transplant. One donor had a bile leak (cut surface). This is the first US series of small left lobe AA-LDLT demonstrating that the transplantation of small grafts with modulation of the portal inflow by the creation of an HPCS may prevent the development of SFSS while at the same time providing adequate liver volume. As it matures, this technique has the potential for widespread application and could positively effect donor safety, the donor pool, and waiting list times.
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http://dx.doi.org/10.1002/lt.22043DOI Listing
May 2010

Plasma nitrite and nitrate levels as a noninvasive marker of pathology after human small bowel transplantation.

Transplantation 2010 Feb;89(3):307-11

Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198-3285, USA.

Introduction: Small bowel transplantation provides a potentially life-saving treatment of severe intestinal failure. Lack of a noninvasive marker of disease makes diagnosis of rejection dependent on frequent endoscopy and biopsy. We hypothesized that increased plasma nitrite and nitrate (NOx) levels measured after small bowel transplant would be associated with abnormal final pathology.

Methods: We measured total plasma NOx levels (the stable end products of the L-arginine/nitric oxide biosynthetic pathway) in 120 prospectively collected samples taken from 27 patients after small bowel transplantation. We used immunohistochemistry to detect inducible nitric oxide synthetase expression in 19 tissue biopsies from 9 patients.

Results: We found NOx concentrations to be statistically different between pathologic categories (e.g., normal, mild, moderate, and severe rejections, nonspecific enteritis), although there was sufficient overlap to prompt caution clinically. After establishing from the dataset a "normal" plasma NOx level of 50 microM, we found that combined assessment of plasma NOx levels and clinical suspicion of pathology could accurately predict which patients were histologically normal and those requiring further evaluation with endoscopy and biopsy.

Conclusions: We conclude that serum NOx levels are significantly associated with small bowel pathology after transplant, although not specifically enough with rejection to be relied on for clinical discrimination.
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http://dx.doi.org/10.1097/TP.0b013e3181c9b5c4DOI Listing
February 2010

Randomized trial of single-dose versus divided-dose rabbit anti-thymocyte globulin induction in renal transplantation: an interim report.

Transplantation 2008 May;85(10):1391-9

Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198-3285, USA.

Background: The optimal dosing protocol for rabbit anti-thymocyte globulin (rATG) induction in renal transplantation has not been determined, but evidence exists that rATG infusion before renal allograft reperfusion improves early graft function. Infusing a large rATG dose over a short interval has not previously been evaluated for its effect on renal function and allograft nephropathy in a prospective, randomized comparison against conventional rATG induction.

Methods: Between April 20, 2004 and December 26, 2007 we enrolled renal transplant patients into a prospective, randomized, nonblinded trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment=160) followed after 6 months by calcineurin-inhibitor withdrawal. Primary endpoints are renal function by calculated glomerular filtration rate (GFR) and chronic allograft nephropathy at protocol biopsy. We now present the early GFR data of all 160 patients and safety and efficacy data of the first 142 patients with 6 months follow up and before calcineurin inhibitor withdrawal (average follow up=23.3+/-11.6 months).

Results: There were no differences between groups in rATG-related adverse events, patient and graft survival, acute rejection, or chronic allograft nephropathy rate at 6 months. Calculated DeltaGFR (POD 1-4) was significantly better in the single-dose group (P=0.02), with a trend toward improved renal function from months 2 to 6 in recipients of deceased donor kidneys (P=0.08).

Conclusions: This study demonstrates that administering 6 mg/kg of rATG over 24 hr is safe and is associated with improved early renal function compared with administering rATG in alternate-day doses.
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http://dx.doi.org/10.1097/TP.0b013e3181722fadDOI Listing
May 2008

Mild donor liver steatosis has no impact on hepatitis C virus fibrosis progression following liver transplantation.

Liver Int 2007 Aug;27(6):758-63

Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198-3285, USA.

Background: This study examines the impact of donor liver macrovesicular steatosis on recurrence of hepatitis C virus (HCV) disease after liver transplantation.

Methods: Between 1998 and 2004, 113 patients underwent liver transplantation for HCV-related cirrhosis. Time to histologic recurrence (fibrosis score >or=2) was the primary endpoint of the study. Recurrence was graded according to the system of Ludwig and Batts. A Cox's proportional hazard regression model was used to analyse the association between donor liver steatosis and HCV recurrence.

Results: Recurrence-free survival for patients who received steatotic grafts was 82% and 47% at 1 and 4 years, respectively, and 81% and 52% for patients who received a non-steatotic liver. Donor macrovesicular steatosis (5-45%) was found to have no impact on HCV recurrence (P=0.47). Donor age (P=0.02) and cold ischaemia time (P=0.01) were found to increase the relative risk of HCV recurrence. The estimated risk of HCV recurrence increased by 23% for every 10-year increase in donor age. Similarly the risk of recurrence increased by 13% for every 1-h increase in cold ischaemia time.

Conclusion: Mild-moderate donor liver macrovesicular steatosis has no impact on HCV recurrence after liver transplantation for HCV-related cirrhosis. Cold ischaemia time and donor age increased the likelihood of HCV recurrence.
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http://dx.doi.org/10.1111/j.1478-3231.2007.01490.xDOI Listing
August 2007

Isolated liver transplantation in infants with end-stage liver disease due to short bowel syndrome.

Liver Transpl 2006 Jul;12(7):1062-6

Department of Surgery, Section of Organ Transplantation, University of Nebraska Medical Center, Omaha, NE 68918-3285, USA.

Infants with short bowel syndrome (SBS) and associated liver failure are often referred for combined liver/intestinal transplantation. We speculated that in some young children, nutritional autonomy would be possible with restoration of normal liver function. Features we believed to predict nutritional autonomy include history of at least 50% enteral tolerance, age less than 2 yr, and no underlying intestinal disease. This report documents our experience with liver transplantation alone in children with liver failure associated with SBS. Twenty-three children with SBS and end-stage liver disease, considered to have good prognostic features for eventual full enteral adaptation, underwent isolated liver transplantation. Median age was 11 months (range, 6.5 to 48 months). Median pretransplant weight was 7.4 kg (range, 5.2 to 15 kg). All had growth retardation and advanced liver disease. Bowel length ranged from 25 to 100 cm. Twenty-three children underwent 28 isolated liver transplants. There were 14 whole livers and 14 partial grafts (five living donors). Seventeen patients are alive at a median follow-up of 57 months (range, 6 to 121 months). Actuarial patient and graft survival rates at 1 yr are 82% and 75% and at 5 yr are 72% and 60%, respectively. Four deaths resulted from sepsis, all within 4 months of transplantation, and 1 death resulted from progressive liver failure. Two allografts developed chronic rejection; both children were successfully retransplanted with isolated livers. Of 17 surviving patients, three require supplemental intravenous support; the remaining 14 have achieved enteral autonomy, at a median of 3 months (range, 1 to 72 months) after transplantation. Linear growth is maintained and, in many, catch-up growth is evident. Median change in z score for height is 0.57 (range, -4.47 to 2.68), and median change in z score for weight is 0.42 (range, -1.65 to 3.05). In conclusion, Isolated liver transplantation in children with liver failure as a result of SBS, who have favorable prognostic features for full enteral adaptation, is feasible with satisfactory long-term survival.
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http://dx.doi.org/10.1002/lt.20763DOI Listing
July 2006

Portosystemic shunts in children: a 15-year experience.

J Am Coll Surg 2004 Aug;199(2):179-85

Division of Transplantation, Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198-3285, USA.

Background: The role of portosystemic shunt (PSS) in children with portal hypertension has changed because of acceptance of liver transplantation and endoscopic hemostasis. We report our experience with PSS, mainly the distal splenorenal shunt, to define its role in the management of variceal bleeding.

Study Design: From 1987 to 2002, 20 children with variceal bleeding after endoscopic therapy underwent PSS. Patient and database records were reviewed.

Results: There were 14 boys and 6 girls; mean age was 11 years (range 3 to 18 years). Seventeen distal splenorenal and three mesocaval venous interposition shunts were performed. There was no operative mortality, 19 patients were alive at a median followup of 31 months (range 4 to 168 months) without evidence of recurrent gastrointestinal bleeding. One patient underwent transplantation 2 years after PSS and 1 patient died of hepatic failure while awaiting transplantation. The cause of portal hypertension was portal vein thrombosis (n = 13), biliary atresia (n = 3), congenital hepatic fibrosis (n = 2), hepatitis C cirrhosis (n = 1), and Budd-Chiari syndrome (n = 1). Eighteen children were Child-Turcotte-Pugh class A and the remaining two were class B. One patient had two episodes of hematemesis after PSS. Two patients had worsening ascites. One patient had mild encephalopathy and one patient had shunt stenosis requiring angioplasty.

Conclusions: PSS is a safe and durable therapy for pediatric patients with portal hypertension. Liver transplantation should be reserved for children with poor synthetic function associated with variceal bleeding. PSS may also serve as a bridge to transplantation in patients with preserved hepatic function. PSS, in particular the distal splenorenal shunt, has produced excellent results. This experience challenges the need for alternative forms of portal decompression.
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http://dx.doi.org/10.1016/j.jamcollsurg.2004.03.024DOI Listing
August 2004

West Nile virus-associated encephalitis in recipients of renal and pancreas transplants: case series and literature review.

Clin Infect Dis 2004 May 14;38(9):1257-60. Epub 2004 Apr 14.

Department of Surgery, Nebraska Medical Center, Omaha, NE 68198-3285, USA.

Although West Nile fever is mild in the vast majority of infected persons, there is growing evidence that the disease may be more severe in the immunocompromised population. We describe 3 recipients of kidney or pancreas transplants who developed West Nile fever, 2 of whom had meningoencephalitis. As is the norm when treating serious infections in transplant recipients, a reduction of immunosuppression was pursued for these patients. Despite the severe nature of the disease in 2 patients, all recovered from the disease. The time course of neurologic recovery in the 2 patients with meningoencephalitis is highlighted. We also review the literature on West Nile fever in organ transplant recipients. In areas where West Nile virus is endemic, one must have a high index of suspicion for the illness when dealing with fever in transplant recipients.
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http://dx.doi.org/10.1086/383325DOI Listing
May 2004