Publications by authors named "David F Mercer"

49 Publications

Glucocorticoids Improve Enteral Feeding Tolerance in Pediatric Short Bowel Syndrome with Chronic Intestinal Inflammation.

J Pediatr Gastroenterol Nutr 2021 Jan 28. Epub 2021 Jan 28.

College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska Department of Clinical Nutrition, University of Nebraska Medical Center, Omaha, Nebraska Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska.

Objectives: A group of short bowel syndrome (SBS) patients developed chronic intestinal inflammation while struggling weaning off parenteral nutrition (PN). They did not respond to standard management of SBS and food allergy. We treated them with glucocorticoids and described the outcome.

Methods: Our study is a retrospective descriptive study. We reviewed records from the intestinal rehabilitation program from 2006 to 2017. We identified 15 patients whose lab values, pathology results, and clinic notes were reviewed.

Results: We had more patients (n = 10) with diagnosis of gastroschisis, and more female patients (n = 9). Seven patients weaned off PN with median treatment duration of 5 months, five of which remained on budesonide for significant period of time (median: 7.5 months). One of these 7 patients relapsed, as the patient resumed glucocorticoids due to recurrence of chronic intestinal inflammation. Six of 15 children had significant eosinophils in their initial biopsy, 5 of these children weaned off PN while one's GI bleeding stopped. Four patients were not able to decrease PN calorie. Two of these patients'GI bleeding stopped, the other two had normalized histology.

Conclusions: For SBS children with histologically confirmed chronic intestinal inflammation, glucocorticoids may help promote enteral feeding tolerance. Glucocorticoids regimen should be chosen individually. Patients are more likely to respond if initial histology has significant eosinophilic infiltration. Patients may need to remain on glucocorticoids for over six months.
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http://dx.doi.org/10.1097/MPG.0000000000003058DOI Listing
January 2021

Safety Findings in Pediatric Patients During Long-Term Treatment With Teduglutide for Short-Bowel Syndrome-Associated Intestinal Failure: Pooled Analysis of 4 Clinical Studies.

JPEN J Parenter Enteral Nutr 2020 Dec 10. Epub 2020 Dec 10.

Shire Human Genetic Therapies, Inc, a Takeda company, Cambridge, Massachusetts, USA.

Background: This analysis assessed combined safety data from 4 clinical studies of teduglutide in pediatric patients with short-bowel syndrome-associated intestinal failure (SBS-IF).

Methods: Safety data from teduglutide-treated patients in 4 clinical trials were pooled. The completed 12-week and 24-week phase 3 core studies (NCT01952080/EudraCT 2013-004588-30 and NCT02682381/EudraCT 2015-002252-27) enrolled children aged 1-17 years with SBS-IF. Patients could elect to enroll in ongoing open-label extensions (NCT02949362/EudraCT 2016-000863-17 and NCT02954458/EudraCT 2016-000849-30). Interim data from ongoing studies were included.

Results: Safety data are reported for 89 pediatric patients treated with teduglutide for a median (range) of 51.7 (5.0-94.7) weeks. Adverse events (AEs) were reported in all patients; the most common were vomiting (51.7%), pyrexia (43.8%), upper respiratory tract infection (41.6%), and cough (33.7%). Thirty-five patients (39.3%) had AEs considered related to teduglutide treatment; abdominal pain and vomiting were most frequent (5.6% each). Three serious AEs in 3 patients (3.4%) were considered related to teduglutide treatment: ileus, d-lactic acidosis, and gastrointestinal obstruction due to hard stools. All 3 events resolved. One cecal polyp was detected, which was not biopsied or found on repeat colonoscopy. No cases of neoplasia occurred.

Conclusion: Based on integrated data from 4 clinical studies, including long-term follow-up for ≤161 weeks, teduglutide had a safety profile consistent with the individual core pediatric studies and as expected for pediatric patients with SBS-IF who never received teduglutide. The most frequent AEs reflected treatment with teduglutide, complications of the underlying disease, and typical childhood illnesses.
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http://dx.doi.org/10.1002/jpen.2061DOI Listing
December 2020

Repeat serial transverse enteroplasty leads to reduction in parenteral nutrition in children with short bowel syndrome.

J Pediatr Surg 2020 Jul 10. Epub 2020 Jul 10.

Department of Pediatrics, University of Nebraska Medical Center, 983285 Nebraska Medical Center, Omaha, NE, USA 68198-3285.

Background/purpose: Following a serial transverse enteroplasty (STEP) procedure some children develop redilation of the small intestine leading to impaired enteral tolerance and inability to wean parenteral nutrition (PN). The benefit of a second STEP procedure (2STEP) has been controversial.

Methods: We performed a retrospective review of our experience (2008-2018) performing 2STEP, with comparative analysis of nutritional outcomes pre- and postsurgery.

Results: During this period 2STEP was performed in 23 patients (13 F:10 M) at a median (25%-75%) age of 2.2 (1.2-3.6) years. Median intestinal length was 68 (40-105) cm before and 85 (40-128) cm after 2STEP. Leading up to 2STEP, PN provided almost 75% of estimated calorie needs. By 24 weeks following 2STEP drops in mean PN percent approached statistical significance (p = 0.07) and at most recent follow up the mean PN percentage was statistically better than at the time of operation or 4 weeks prior to 2STEP, and was nearly significant compared with 12 weeks (p = 0.07) and 24 weeks (p = 0.06) prior. Thirteen children were completely off parenteral support.

Conclusion: When small intestine redilation occurs following a STEP procedure and where PN cannot otherwise be weaned we believe these data support performing a 2STEP. We cannot predict preoperatively which children will ultimately benefit.

Level Of Evidence: 3 (retrospective comparative study).
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http://dx.doi.org/10.1016/j.jpedsurg.2020.06.045DOI Listing
July 2020

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

Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome: A 24-Week, Phase III Study.

JPEN J Parenter Enteral Nutr 2020 05 8;44(4):621-631. Epub 2019 Sep 8.

Shire Human Genetic Therapies, Inc, Cambridge, Massachusetts, USA.

Background: This study evaluated the safety and efficacy of teduglutide in pediatric patients with short bowel syndrome-associated intestinal failure (SBS-IF).

Methods: A 24-week, phase III trial with 2 randomized, double-blind teduglutide dose groups and a nonblinded standard of care (SOC) arm was used; patients received 0.025 mg/kg or 0.05 mg/kg teduglutide once daily. Safety end points included treatment-emergent adverse events (TEAEs) and growth parameters. The primary efficacy/pharmacodynamic end point was the number of patients who achieved a ≥20% reduction in parenteral support (PS) from baseline at week 24.

Results: All 59 enrolled patients completed the study (0.025 mg/kg, n = 24; 0.05 mg/kg, n = 26; SOC, n = 9). Baseline demographics and disease characteristics were comparable among groups. TEAEs were reported by 98% and 100% of patients in the teduglutide and SOC groups, respectively. The most common TEAEs in the teduglutide-treated groups were pyrexia and vomiting. The primary end point was achieved by 13 (54.2%), 18 (69.2%), and 1 (11.1%) patients who received 0.025 mg/kg teduglutide, 0.05 mg/kg teduglutide, and SOC, respectively (P < 0.05 vs SOC). Both 0.025-mg/kg and 0.05-mg/kg teduglutide groups showed clinically significant reductions in PS volume (P < 0.05 vs SOC), PS calories, days per week and hours per day of PS infusions, and increases in enteral nutrition and plasma citrulline at week 24 compared with baseline. Two (8.3%, 0.025 mg/kg teduglutide) and 3 patients (11.5%, 0.05 mg/kg teduglutide) achieved enteral autonomy.

Conclusion: The safety profile of teduglutide was similar to that reported previously in children and adults. Treatment with teduglutide was associated with significant reductions in PS for pediatric patients with SBS-IF over 24 weeks.
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http://dx.doi.org/10.1002/jpen.1690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318247PMC
May 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

Demethylase JMJD6 as a New Regulator of Interferon Signaling: Effects of HCV and Ethanol Metabolism.

Cell Mol Gastroenterol Hepatol 2018 16;5(2):101-112. Epub 2017 Oct 16.

Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska.

Background & Aims: Alcohol-induced progression of hepatitis C virus (HCV) infection is related to dysfunction of innate immunity in hepatocytes. Endogenously produced interferon (IFN)α induces activation of interferon-stimulated genes (ISGs) via triggering of the Janus kinase-signal transducer and activator of transcription 1 (STAT1) pathway. This activation requires protein methyltransferase 1-regulated arginine methylation of STAT1. Here, we aimed to study whether STAT1 methylation also depended on the levels of demethylase jumonji domain-containing 6 protein (JMJD6) and whether ethanol and HCV affect JMJD6 expression in hepatocytes.

Methods: Huh7.5-CYP (RLW) cells and hepatocytes were exposed to acetaldehyde-generating system (AGS) and 50 mmol/L ethanol, respectively. JMJD6 messenger RNA and protein expression were measured by real-time polymerase chain reaction and Western blot. IFNα-activated cells either overexpressing JMJD6 or with knocked-down JMJD6 expression were tested for STAT1 methylation, ISG activation, and HCV RNA. In vivo studies have been performed on C57Bl/6 mice (expressing HCV structural proteins or not) or chimeric mice with humanized livers fed control or ethanol diets.

Results: AGS exposure to cells up-regulated JMJD6 expression in RLW cells. These results were corroborated by ethanol treatment of primary hepatocytes. The promethylating agent betaine reversed the effects of AGS/ethanol. Similar results were obtained in vivo, when mice were fed control/ethanol with and without betaine supplementation. Overexpression of JMJD6 suppressed STAT1 methylation, IFNα-induced ISG activation, and increased HCV-RNA levels. In contrast, JMJD6 silencing enhanced STAT1 methylation, ISG stimulation by IFNα, and attenuated HCV-RNA expression in Huh7.5 cells.

Conclusions: We conclude that arginine methylation of STAT1 is suppressed by JMJD6. Both HCV and acetaldehyde increase JMJD6 levels, thereby impairing STAT1 methylation and innate immunity protection in hepatocytes exposed to the virus and/or alcohol.
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http://dx.doi.org/10.1016/j.jcmgh.2017.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904050PMC
October 2017

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

Empirical Study on the Impact of a Tactical Biosurveillance Information Visualization on Users' Situational Awareness.

Mil Med 2017 03;182(S1):322-329

Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, 42nd and Emily Street, Omaha, NE 68198-4375.

Decisions on antibiotic-resistant infection (ARI) prevention in dynamic health care settings should be agile and target the right process at the right time. Health information technologies can aid the recognition of high-risk situations for ARI transmission and timely facilitate operators' situational awareness (SA) in various military and civilian health care locations or transport platforms. High SA is one of the significant predictors of better performance. The objective of this study was to evaluate the impact of the developed health information visualization (VIZ) on the users' SA regarding situations when risks of ARI transmission and exposure are high. The enrolled 19 subjects assessed the proposed VIZ artifacts representing 1 scenario, compared the VIZ effectiveness against the currently employed local methods, and reported their SA (perception and comprehension) with the use of a pre- and post-self-rating questionnaire. The results showed that the VIZ significantly increased SA in the study subjects and revealed the importance of communicating the risk of exposure to ARIs. The VIZ enabled the participants to quickly acknowledge the high-risk individuals (super-spreaders), locations (hot spots), and biosafety (deficient infection prevention). The study concluded that SA-oriented technologies may be promising for promoting better infection prevention practices.
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http://dx.doi.org/10.7205/MILMED-D-16-00143DOI Listing
March 2017

Epidemiological investigation of Candida species causing bloodstream infection in paediatric small bowel transplant recipients.

Mycoses 2017 Jun 31;60(6):366-374. Epub 2017 Jan 31.

Department of Food Science & Technology, University of Nebraska-Lincoln, Lincoln, NE, USA.

Small bowel transplantation (SBT) can be a life-saving medical procedure. However, these recipients experience high risk of bloodstream infections caused by Candida. This research aims to characterise the SBT recipient gut microbiota over time following transplantation and investigate the epidemiology of candidaemia in seven paediatric patients. Candida species from the recipients' ileum and bloodstream were identified by internal transcribed spacer sequence and distinguished to strain by multilocus sequence typing and randomly amplified polymorphic DNA. Antifungal susceptibility of bloodstream isolates was determined against nine antifungals. Twenty-two ileostomy samples harboured at least one Candida species. Fungaemia were caused by Candida parapsilosis, Candida albicans, Candida glabrata, Candida orthopsilosis and Candida pelliculosa. All but three bloodstream isolates showed susceptibility to all the antifungals tested. One C. glabrata isolate showed multidrug resistance to itraconazole, amphotericin B and posaconazole and intermediate resistance to caspofungin. Results are congruent with both endogenous (C. albicans, C. glabrata) and exogenous (C. parapsilosis) infections; results also suggest two patients were infected by the same strain of C. parapsilosis. Continuing to work towards a better understanding of sources of infection-particularly the exogenous sources-would lead to targeted prevention strategies.
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http://dx.doi.org/10.1111/myc.12603DOI Listing
June 2017

Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome.

J Pediatr 2017 02 15;181:102-111.e5. Epub 2016 Nov 15.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Objective: To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF).

Study Design: This 12-week, open-label study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0.05 mg/kg/d [n = 15]) or received standard of care (SOC, n = 5). Descriptive summary statistics were used.

Results: All patients experienced ≥1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related treatment-emergent adverse events occurred. Between baseline and week 12, prescribed PN volume and calories (kcal/kg/d) changed by a median of -41% and -45%, respectively, with 0.025 mg/kg/d teduglutide and by -25% and -52% with 0.05 mg/kg/d teduglutide. In contrast, PN volume and calories changed by 0% and -6%, respectively, with 0.0125 mg/kg/d teduglutide and by 0% and -1% with SOC. Per patient diary data, EN volume increased by a median of 22%, 32%, and 40% in the 0.0125, 0.025, and 0.05 mg/kg/d cohorts, respectively, and by 11% with SOC. Four patients achieved independence from PN, 3 in the 0.05 mg/kg/d cohort and 1 in the 0.025 mg/kg/d cohort. Study limitations included its short-term, open-label design, and small sample size.

Conclusions: Teduglutide was well tolerated in pediatric patients with SBS-IF. Teduglutide 0.025 or 0.05 mg/kg/d was associated with trends toward reductions in PN requirements and advancements in EN feeding in children with SBS-IF.

Trial Registration: ClinicalTrials.gov:NCT01952080; EudraCT: 2013-004588-30.
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http://dx.doi.org/10.1016/j.jpeds.2016.10.027DOI Listing
February 2017

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

Nutrition and small bowel transplantation.

Nutr Clin Pract 2014 Oct;29(5):615-20

Division of Transplantation, Department of Surgery, University of Nebraska Medical Center, 983285 Nebraska Medical Center, Omaha, NE 68198-3285, USA. Email:

Intestinal transplantation is indicated for patients with intractable intestinal failure, especially when life-threatening complications of parenteral nutrition (PN) occur. The rates of 1- and 5-year graft survival range from 65%–80% and 40%–50% across differing age ranges, with adult recipients generally performing better. Despite nutrition being so central to intestinal transplantation, there are little published literature and essentially no data from clinical trials. In this review, we critically examine published manuscripts in an attempt to draw common themes between various transplant programs, covering experimental physiologic data, published nutrition protocols, and common postoperative management issues. We conclude that the well-established intestinal graft in a healthy state absorbs key nutrients adequately to wean off PN and that the wide variation in practice across different programs suggests that different approaches can equally lead to success.
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http://dx.doi.org/10.1177/0884533614539354DOI Listing
October 2014

Cidofovir in pediatric solid organ transplant recipients: University of Nebraska experience.

Pediatr Infect Dis J 2015 Jan;34(1):47-51

From the *Transplant Infectious Diseases Program; †Transplant Surgery Division; ‡Department of Biostatistics, University of Nebraska Medical Center; §Department of Pharmaceutical and Nutrition Care, Nebraska Medical Center Omaha, NE; and ¶Nephrology Division, University of Nebraska Medical Center, Omaha, NE.

Background: Clinical experience with cidofovir in pediatric solid organ transplantation is limited. We assessed the effect of cidofovir use on renal function in pediatric solid organ transplant recipients.

Methods: Wilcoxon signed-rank tests were used to determine if changes in renal function were significant, Wilcoxon rank-sum tests to test the association between changes in glomerular filtration rate and potential confounding factors, and MacNemar tests to compare the proportions of patients at different time points.

Results: We included 25 patients with a mean age of 4.2 years (SD 4.6). More patients were receiving renal replacement therapy while being treated with cidofovir compared with baseline (24% vs. 4%; P = 0.03). For patients not receiving renal replacement therapy, there was no evidence of a significant median change in glomerular filtration rate from baseline to 1 month after cidofovir treatment (P = 0.32) or to the end of cidofovir treatment (P = 0.23) or in creatinine from baseline to the end of cidofovir therapy (P = 0.2). There was a marginal decreased median change in creatinine from baseline to 1 month after cidofovir treatment (P = 0.06). Fewer patients had proteinuria (72.2% vs. 27.8%; P = 0.02) and hematuria (22.2% vs. 0%) after cidofovir treatment.

Conclusion: In our pediatric transplant cohort, cidofovir did not significantly change renal function reflected by creatinine, glomerular filtration rate, hematuria or proteinuria, but a significant number of patients required renal replacement therapy because of fluid overload.
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http://dx.doi.org/10.1097/INF.0000000000000487DOI Listing
January 2015

Ethanol affects hepatitis C pathogenesis: humanized SCID Alb-uPA mouse model.

Biochem Biophys Res Commun 2014 Jul 19;450(1):773-6. Epub 2014 Jun 19.

Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68105, USA.

Alcohol consumption exacerbates the course of hepatitis C viral (HCV) infection, worsens outcomes and contributes to the development of chronic infection that exhibits low anti-viral treatment efficiency. The lack of suitable in vivo models makes HCV-ethanol studies very difficult. Here, we examine whether chimeric SCID Alb-uPA mice transplanted with human hepatocytes and infected with HCV develop worsening pathology when fed ethanol. After 5 weeks of feeding, such mice fed chow+water (control) or chow+20% ethanol in water (EtOH) diets mice developed oxidative stress, decreased proteasome activity and increased steatosis. Importantly, HCV(+) mice in the control group cleared HCV RNA after 5 weeks, while the infection persisted in EtOH-fed mice at the same or even higher levels compared with pre-feeding HCV RNA. We conclude that in chimeric SCID Alb-uPA mice, EtOH exposure causes the complex biochemical and histological changes typical for alcoholic liver injury. In addition, ethanol feeding delays the clearance of HCV RNA thereby generating persistent infection and promoting liver injury. Overall, this model is appropriate for conducting HCV-ethanol studies.
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http://dx.doi.org/10.1016/j.bbrc.2014.06.048DOI Listing
July 2014

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

Human hepatocytes and hematolymphoid dual reconstitution in treosulfan-conditioned uPA-NOG mice.

Am J Pathol 2014 Jan 6;184(1):101-9. Epub 2013 Nov 6.

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska; Liver Unit, Nebraska/Western Iowa Healthcare System, Omaha, Nebraska. Electronic address:

Human-specific HIV-1 and hepatitis co-infections significantly affect patient management and call for new therapeutic options. Small xenotransplantation models with human hepatocytes and hematolymphoid tissue should facilitate antiviral/antiretroviral drug trials. However, experience with mouse strains tested for dual reconstitution is limited, with technical difficulties such as risky manipulations with newborns and high mortality rates due to metabolic abnormalities. The best animal strains for hepatocyte transplantation are not optimal for human hematopoietic stem cell (HSC) engraftment, and vice versa. We evaluated a new strain of highly immunodeficient nonobese diabetic/Shi-scid (severe combined immunodeficiency)/IL-2Rγc(null) (NOG) mice that carry two copies of the mouse albumin promoter-driven urokinase-type plasminogen activator transgene for dual reconstitution with human liver and immune cells. Three approaches for dual reconstitution were evaluated: i) freshly isolated fetal hepatoblasts were injected intrasplenically, followed by transplantation of cryopreserved HSCs obtained from the same tissue samples 1 month later after treosulfan conditioning; ii) treosulfan conditioning is followed by intrasplenic simultaneous transplantation of fetal hepatoblasts and HSCs; and iii) transplantation of mature hepatocytes is followed by mismatched HSCs. The long-term dual reconstitution was achieved on urokinase-type plasminogen activator-NOG mice with mature hepatocytes (not fetal hepatoblasts) and HSCs. Even major histocompatibility complex mismatched transplantation was sustained without any evidence of hepatocyte rejection by the human immune system.
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http://dx.doi.org/10.1016/j.ajpath.2013.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873481PMC
January 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

An international survey of cytomegalovirus prevention and treatment practices in intestinal transplantation.

Transplantation 2014 Jan;97(1):78-82

1 Transplant Infectious Diseases Program, University of Nebraska Medical Center, Omaha, NE. 2 Transplant Surgery Division, University of Nebraska Medical Center, Omaha, NE. 3 Transplant Surgery, Cleveland Clinic, Cleveland, OH. 4 Biostatistics Department, University of Nebraska Medical Center, Omaha, NE. 5 Address correspondence to: Diana F. Florescu, M.D., Transplant Infectious Diseases Program, University of Nebraska Medical Center, 985400 Nebraska Medical Center, Omaha, NE 68198.

Background: Practice variation regarding cytomegalovirus (CMV) prevention and treatment across intestinal transplantation (IT) programs is unknown.

Methods: An electronic survey was sent to IT programs registered with the Intestinal Transplant Association. Proportions were analyzed for categorical variables; means and SDs were analyzed for continuous variables.

Results: Seventy-seven percent of IT programs responded to the survey. For CMV D+/R- recipients, 39.1% programs used universal prophylaxis (UP), 8.7% preemptive strategy (PE), and 52.2% hybrid strategy. For CMV R+ recipients, 45.8% programs used UP, 12.5% PE, 37.1% hybrid strategy, and 4.2% none. For CMV D-/R- recipients, 39.1% programs used UP, 21.7% PE, 26.1% hybrid strategy, and 13% none. Frequency of monitoring for PE was weekly 71.4% of programs, every 2 weeks 21.4%, and monthly 7.1%. For CMV viremia, syndrome and disease, the most common first-line agents used were ganciclovir (100% and 96.2%) and valganciclovir (23.1%) and the second-line agent was foscarnet (73.1% and 84.6%). Immunoglobulins were administered in 65.4% of the programs for pneumonia (69.2%), meningoencephalitis (50%), enteritis (46.2%), colitis (38.5%), syndrome (42.3%), viremia (30.8%), and resistant/refractory infections (11.5%).

Conclusions: Prophylaxis and hybrid strategy were the most commonly used. Treatment practices were consistent and mainly involved ganciclovir as first-line agent and foscarnet as second-line agent. The use of immunoglobulins appeared to be more common than in other allografts.
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http://dx.doi.org/10.1097/TP.0b013e3182a6baa2DOI 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

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

Fish oil emulsions in the management of intestinal failure-associated liver disease.

Authors:
David F Mercer

J Clin Gastroenterol 2012 Nov-Dec;46(10):823-7

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

The role of parenteral lipid emulsions in the treatment of intestinal failure-associated liver disease (IFALD) is both topical and controversial. There is strong evidence supporting plant-based (soy, olive) lipid emulsions as a key cause for IFALD, especially in neonates. As a result, alternate lipid formulations, most notably fish oil emulsions (FOE) have come into widespread use despite somewhat limited clinical data on their overall benefit and potential long-term consequences. This review examines putative mechanisms of action of FOE in reversing cholestasis associated with IFALD, and critically reviews published clinical studies of the use of FOE in pediatric patients with IFALD. From these works, it appears the mechanism of action of FOE is most likely related to the reduction of serum phytosterols associated with plant-based lipid emulsions rather than a specific positive benefit of the fish oils themselves. Although the use of FOE seems to correlate with a reduction in cholestasis, their actual individual benefit is not established, and data on long-term outcomes and safety are not yet available.
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http://dx.doi.org/10.1097/MCG.0b013e318261836dDOI 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

Respiratory syncytial virus lower respiratory tract infection in a pediatric liver transplant recipient treated with oral ribavirin.

Pediatr Transplant 2012 Dec 26;16(8):E348-51. Epub 2012 Apr 26.

Department of Pharmaceutical and Nutrition Care, The Nebraska Medical Center, Omaha, NE 68198-1090, USA.

The mainstay of therapy for RSV disease is supportive care, although aerosolized ribavirin has been used to treat infants and young children with severe lower respiratory tract infections. Aerosolized ribavirin has adverse effects, high cost and teratogenic potential. We report the case of a pediatric liver transplant recipient diagnosed with lower respiratory RSV infection, who was successfully treated with oral ribavirin.
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http://dx.doi.org/10.1111/j.1399-3046.2012.01700.xDOI Listing
December 2012

Bloodstream infections during the first year after pediatric small bowel transplantation.

Pediatr Infect Dis J 2012 Jul;31(7):700-4

Infectious Diseases Section, Biostatistics Department, University of Nebraska Medical Center, Omaha, NE 68198-5400, USA.

Background: Little information regarding bloodstream infections (BSIs) in small bowel transplantation has been published.

Methods: We reviewed the medical records of 98 pediatric patients who underwent small bowel transplantation. Patients' characteristics were analyzed with Wilcoxon rank-sum, χ or Fisher's exact tests. We estimated the overall survival by the Kaplan-Meier method and compared survival distributions between groups with the log-rank test.

Results: Sixty-eight patients developed ≥1episode of BSIs (total of 146 episodes), and 69.1% of the first infections were diagnosed in the 3 months post-transplantation. The most common sources of infection were as follows: central venous catheters (49.3%) and intra-abdominal infections (32.9%). Central venous catheters were present in 86.3%, and total parenteral nutrition within 7 days before infection was administered in 72.6% of episodes. Gram-positive bacteria (96 isolates) were more frequently isolated than Gram-negative bacteria (52 isolates), with Enterococcus spp. being the most commonly identified (48 isolates), followed by coagulase-negative Staphylococcus (40 isolates). Patients with infections were younger than those without (median 1.4 versus 2.1 years, P=0.02). Four grafts were lost after transplantation in patients with BSIs and 2 in patients without BSIs (P = 0.99). One-year survival rate for patients without BSIs was 86.7% (95% confidence interval: 68.3%-94.8%) versus 72.1% in patients with BSIs (95% confidence interval: 59.8%-81.2%). Overall time to death was shorter in patients with BSIs than in patients without BSIs (P=0.056).

Conclusions: Almost 70% of small bowel transplantation recipients developed BSIs, mainly in the early months after transplantation. BSIs were mainly from a central venous catheter or intra-abdominal source. Enterococcus spp were the most frequently isolated organisms. Patients with BSIs had worse survival than patients with BSIs.
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http://dx.doi.org/10.1097/INF.0b013e318256f9c3DOI Listing
July 2012