Publications by authors named "Samuel Kocoshis"

38 Publications

Operational tolerance after pediatric composite liver-pancreas-intestine transplantation following severe graft-versus-host disease.

Pediatr Transplant 2021 Jun 14:e14069. Epub 2021 Jun 14.

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

Background: While operational tolerance has been previously described in isolated intestinal transplant, reports of this phenomenon in combined liver-intestine transplant are lacking.

Case Description: We detail a unique case of a patient who received a composite allograft including liver, pancreas, and small bowel due to short gut syndrome secondary to gastroschisis complicated by volvulus. The indication for transplantation was permanent dependence on total parenteral nutrition, end-stage liver disease, recurrent sepsis, and persistent stomal variceal hemorrhage. The patient developed severe graft-versus-host disease with grade 3 skin involvement, ophthalmic, and pulmonary involvement with 53% donor T-cell chimerism. She required aggressive therapy including high-dose methylprednisolone, rituximab, cyclophosphamide, and alemtuzumab. Due to infection concerns following depletion of her lymphocytes, immunosuppression was discontinued with close surveillance of her allograft. Nearly 10 years later, the patient has continued off all immunosuppression without evidence of rejection or graft dysfunction and demonstrates immunocompetence with normal functional immune assays and development of appropriate live vaccination titers.

Conclusion: This report of operational tolerance following pediatric composite liver-pancreas-intestine transplantation provides evidence that the complex immunologic balance in intestinal transplantation may on rare occasions favor immunosuppression reduction or even discontinuation. Future trials of immunosuppression minimization in this population may be warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.14069DOI Listing
June 2021

50 Years Ago in TheJournalofPediatrics: You Are What You Eat: "tu sei quello che mangi".

J Pediatr 2021 May;232:132

Department of Pediatrics, University of Cincinnati College of Medicine, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital Medical Center, Cincinnati, Ohio.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2021.01.036DOI Listing
May 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jpen.2061DOI Listing
December 2020

"Even When the Wound Is Healed, the Scar Remains".

J Pediatr 2021 03 24;230:11-12. Epub 2020 Nov 24.

University of Cincinnati College of Medicine, Intestinal Care Center and Intestinal Transplantation, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2020.11.027DOI Listing
March 2021

Evaluation of a change in cytomegalovirus prevention strategy following pediatric solid organ transplantation.

Transpl Infect Dis 2020 Apr 30;22(2):e13232. Epub 2019 Dec 30.

Department of Pediatrics, Cincinnati Children's Medical Center, Cincinnati, Ohio.

Background: An optimal cytomegalovirus (CMV) prevention strategy following solid organ transplantation (SOT) remains uncertain. This study reports on the rates of CMV events following a change in a local prevention guideline involving increased surveillance, earlier transition to oral valganciclovir, and decreased CMV-immunoglobulin use.

Methods: A retrospective cohort study utilizing historical controls evaluated the rates of CMV invasive disease pre- and post-intervention among pediatric heart, liver, and kidney recipients. Outcomes were recorded for the 4 years pre- and post-intervention, 9/2009-10/2017. Logistic regression was used to estimate the risk of a CMV event.

Results: There was no difference in the rates of CMV invasive disease between the two study groups (P = 1). An increase in the detection of CMV events occurred (P = .04), predominantly asymptomatic CMV infection. This increase was independently associated with increased surveillance testing among high-risk heart and liver recipients, aOR 1.08 (1.06-1.12). Surprisingly, 28.9% of CMV events occurred during antiviral prophylaxis.

Conclusions: Modification of the local CMV prevention guideline did not result in an increase in CMV invasive disease. CMV events occurred while on prophylaxis, highlighting a potential difference from adult solid organ transplant (SOT) and emphasizing the potential need for monitoring on prophylaxis in the pediatric population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tid.13232DOI Listing
April 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jpen.1690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318247PMC
May 2020

Evidence-Based Strategies and Recommendations for Preservation of Central Venous Access in Children.

JPEN J Parenter Enteral Nutr 2019 07 21;43(5):591-614. Epub 2019 Apr 21.

VANGUARD, Venous Access (VANGUARD) Task Force, Society of Interventional Radiology (SIR), Pittsburgh, Pennsylvania, USA.

Children with chronic illness often require prolonged or repeated venous access. They remain at high risk for venous catheter-related complications (high-risk patients), which largely derive from elective decisions during catheter insertion and continuing care. These complications result in progressive loss of the venous capital (patent and compliant venous pathways) necessary for delivery of life-preserving therapies. A nonstandardized, episodic, isolated approach to venous care in these high-need, high-cost patients is too often the norm, imposing a disproportionate burden on affected persons and escalating costs. This state-of-the-art review identifies known failure points in the current systems of venous care, details the elements of an individualized plan of care, and emphasizes a patient-centered, multidisciplinary, collaborative, and evidence-based approach to care in these vulnerable populations. These guidelines are intended to enable every practitioner in every practice to deliver better care and better outcomes to these patients through awareness of critical issues, anticipatory attention to meaningful components of care, and appropriate consultation or referral when necessary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jpen.1591DOI Listing
July 2019

Esophageal dysmotility: An intrinsic feature of megacystis, microcolon, hypoperistalsis syndrome (MMIHS).

J Pediatr Surg 2019 Jul 7;54(7):1303-1307. Epub 2018 Sep 7.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, The Ohio State University College of Medicine and Nationwide Children's Hospital.

Objectives: Megacystis-microcolon-hypoperistalsis syndrome (MMIHS) also called Berdon's Syndrome, is a smooth muscle myopathy that results in an enlarged bladder, microcolon, and small bowel hypoperistalsis. In our series of six patients with this disorder, all had disordered swallowing. Therefore, we prospectively characterized esophageal structure and function in all.

Methods: Diagnoses had been established by contrast radiography, small bowel manometry, and urodynamic studies. To investigate the esophagus, we endoscoped and biopsied the esophagus of each patient on multiple occasions. All patients also underwent water soluble contrast esophagography and esophageal manometry.

Results: Upon careful questioning, all patients had swallowing dysfunction, and the majority of their enteral intake was via gastrostomy or gastrojejunostomy. All took some oral alimentation, but eating was slow and none could aliment themselves completely by the oral route, receiving 50% or less of their calories by mouth. Four had megaesophagus whereas the esophagus of the two youngest was of normal caliber. All had eosinophilic esophagitis and/or esophageal Candidiasis from time to time, but successful treatment of these findings failed to improve their symptoms. Manometry revealed normal lower esophageal sphincter (LES) resting tone and normal LES relaxation, but for all, peristalsis was absent in the esophageal body.

Conclusions: This series expands the spectrum of findings in MMIHS, to include a primary motility disorder of the esophageal body. As patients age, the esophageal caliber appears to increase. Successful treatment of neither esophageal eosinophilia nor Candidiasis is effective in ameliorating the motility disorder. If our findings are confirmed in more patients with MMIHS, this disorder should be renamed, megacystis-microcolon-intestinal-and esophageal hypoperistalsis syndrome.

Type Of Study: Prognosis study, Level IV (case series).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpedsurg.2018.08.051DOI Listing
July 2019

Unusual Etiology for Subacute Terminal Ileitis in a 5-Year-Old Boy.

Gastroenterology 2019 02 18;156(3):556-557. Epub 2018 Sep 18.

Pediatric Gastroenterology, Hepatology, and Nutrition, and Pediatric Surgery, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2018.09.032DOI Listing
February 2019

Serum Unconjugated Bile Acids and Small Bowel Bacterial Overgrowth in Pediatric Intestinal Failure: A Pilot Study.

JPEN J Parenter Enteral Nutr 2019 02 23;43(2):263-270. Epub 2018 Jul 23.

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

Background: We determined qualitative and quantitative serum unconjugated bile acid (SUBA) levels among children with history of intestinal failure (IF) and suspected small bowel bacterial overgrowth (SBBO).

Methods: This was a single-center, case-control pilot study conducted at Cincinnati Children's Hospital Medical Center. Children with history of IF and suspected SBBO were enrolled as subjects. Age-matched children without IF or suspected SBBO served as controls. All participants underwent small bowel fluid sampling for microbial culture analysis. Additionally, serum fractionated and total bile acids were measured by liquid chromatography-mass spectrometry at enrollment and following treatment for SBBO.

Results: SUBA concentrations were elevated in IF subjects (median 1.16 μM, range 0.43-10.65 μM) compared with controls (median 0.10 μM, range 0.05-0.18 μM, P = 0.001). Among SUBA, chenodeoxycholic acid (CDCA) was significantly elevated in subjects (median 0.8 μM, range 0-7.08 μM) compared with controls (median 0 μM, range 0-0.03 μM, P = 0.012). When controls were excluded from analysis, IF subjects with positive aspirates for SBBO demonstrated higher concentration of CDCA (median 7.36 μM, range 1.1-8.28 μM) compared with IF subjects with negative aspirates (median 0.18 μM, range 0-1.06 μM, P = 0.017). Treatment for SBBO did not alter SUBA concentration.

Conclusions: SUBA concentrations are elevated in children with history of IF and presumed SBBO compared with non-IF controls. CDCA was more prevalent in IF subjects with positive aspirates for SBBO compared with IF subjects with negative aspirates. The determination of SUBA concentration may be a useful surrogate to small bowel fluid aspiration in the diagnosis of SBBO in children with history of IF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jpen.1316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344318PMC
February 2019

Chronic Central Venous Access: From Research Consensus Panel to National Multistakeholder Initiative.

J Vasc Interv Radiol 2018 04 15;29(4):461-469. Epub 2018 Feb 15.

Division of Vascular and Interventional Radiology, Department of Radiology, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvir.2017.12.009DOI Listing
April 2018

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2016.10.027DOI Listing
February 2017

"Twin" Biliary Trees in a Patient With Heterotaxy Syndrome.

J Pediatr Gastroenterol Nutr 2018 06;66(6):e158

Division of Gastroenterology, Hepatology, and Nutrition.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000001370DOI Listing
June 2018

A Procedural and Educational Experience Following Creation of an Advanced Pediatric Endoscopy Service.

J Pediatr Gastroenterol Nutr 2017 04;64(4):e96-e99

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

Advanced endoscopic procedures occur infrequently enough in pediatric patients to preclude effective maintenance of competence among all pediatric gastroenterologists. A recent study suggests that fellows are largely unable to achieve the prescribed case volume recommended to achieve competence. We sought to describe the procedural and educational experience following the creation of an advanced pediatric endoscopy service in response to declining confidence among practice members regarding advanced procedures. We found most advanced endoscopy cases (90%) were accomplished during routine business hours with little seasonal variation. Esophageal dilations occurred far more than all other procedures provided by this service. Control of nonvariceal bleeding, feeding tube placement, enteroscopy, and needle knife therapy, among others, were performed exclusively but relatively infrequently by members of this advanced endoscopy service. Fellows were present for many cases, although they participated in relatively few. We conclude that the creation of an advanced endoscopy service permits distillation of rare but technically demanding cases to few providers, ensuring maintenance of skills, although the role of fellows remains in question.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000001290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5156590PMC
April 2017

Ethanol Lock Efficacy and Associated Complications in Children With Intestinal Failure.

JPEN J Parenter Enteral Nutr 2016 08 23;40(6):815-9. Epub 2015 Feb 23.

Division of Gastroenterology, Hepatology and Nutrition.

Background: Prophylactic ethanol lock therapy (ELT) reduces central line-associated bloodstream infections (CLA-BSIs) in children with intestinal failure (IF). However, the risk of associated complications is unclear. We aim to describe our experience with prophylactic ethanol locks in a cohort of patients with IF.

Materials And Methods: Thirty patients on ELT from 2010-2013 were identified by review of our intestinal rehabilitation registry. Patient demographics, CLA-BSI events, and line complications were extracted. Comparisons in infection and complication rates when on and off ELT were made using a Poisson mixed-effect regression model.

Results: CLA-BSIs when on and off ELT were 3.1 and 5.5 per 1000 catheter days, respectively (P <015). Overall complication rates were similar in both groups. In those patients who experienced a complication, the complication rates on ELT compared with time off ELT were significantly lower (P <003). Line perforation or breakage rates declined significantly when on ELT, from 1.8 to 1.53 per 1000 catheter days (P <006). Line occlusion rates also decreased on ELT, from 0.6 to 0.3 per 1000 catheter days (P =056). Infecting organisms were not different on and off ELT, and patients experienced a similar number of polymicrobial infections on or off therapy. Klebsiella pneumoniae was the most common infecting organism in both groups.

Conclusions: Ethanol lock therapy use reduces both CLA-BSI and central line complication rates in children with IF. These results underscore the safety and efficacy of ELT use in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0148607115574745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816678PMC
August 2016

Incidence of bloodstream infections in small bowel transplant recipients receiving selective decontamination of the digestive tract: A single-center experience.

Pediatr Transplant 2015 Nov 2;19(7):722-9. Epub 2015 Sep 2.

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

Pediatric patients undergoing small bowel transplantation are susceptible to postoperative CLABSI. SDD directed against enteric microbes is a strategy for reducing CLABSI. We hypothesized that SDD reduces the frequency of CLABSI, infections outside the bloodstream, and allograft rejection during the first 30 days following transplant. A retrospective chart review of 38 pediatric small bowel transplant recipients at CCHMC from 2003 to 2011 was conducted. SDD antimicrobials were oral colistin, tobramycin, and amphotericin B. The incidence of CLABSI, infections outside the bloodstream, and rejection episodes were compared between study periods. The incidence of CLABSI did not differ between study periods (6.9 CLABSI vs. 4.6 CLABSI per 1000 catheter days; p = 0.727), but gram positives and Candida predominated in the first 30 days. Incidence of bacterial infections outside the bloodstream did not differ (p = 0.227). Rejection occurred more frequently during the first month following transplant (p = 0.302). SDD does not alter the incidence of CLABSI, bacterial infections outside the bloodstream, or allograft rejection in the immediate 30 days post-transplantation. However, SDD does influence CLABSI organism types (favoring gram positives and Candida) and Candidal infections outside the bloodstream.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.12583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837460PMC
November 2015

Limited surgical resection for graft salvage following recovery from complicated exfoliative rejection in pediatric intestinal recipients.

Pediatr Transplant 2015 Nov 31;19(7):E170-6. Epub 2015 Jul 31.

Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Complications of ER contribute significantly to morbidity and mortality following intestinal transplantation. The surgical management of three pediatric patients who experienced complications of late ER after composite LSB transplantation is described, highlighting the potential for allograft salvage after limited surgical resection. A retrospective case series was compiled. Data collected included time to ER from transplant, medical management of ER, complications, and surgical management of ER complications. All patients had undergone composite LSB transplantation between one and two yr of age. Time to ER after transplantation was 9.5-26.5 months. ER complications included ileal allograft stricture, intramural hematoma with perforation of jejunal allograft, and massive GI hemorrhage secondary to focal ulceration and pseudopolyp formation. With evidence of mucosal regeneration, all three patients underwent limited segmental allograft resection. Two patients continue to maintain satisfactory allograft function 39-44 months following operation. The third patient retained adequate allograft function until he developed PTLD, subsequently dying from disseminated Adenovirus infection 51 months after resection. Severe disruption of intestinal allograft integrity in ER can lend itself to medically refractory complications. Prompt recognition and surgical correction of complications can play a crucial role in allograft salvage and patient survival after ER.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.12563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361159PMC
November 2015

Predictors of Enteral Autonomy in Children with Intestinal Failure: A Multicenter Cohort Study.

J Pediatr 2015 Jul 25;167(1):29-34.e1. Epub 2015 Apr 25.

Boston Children's Hospital, Boston, MA. Electronic address:

Objectives: In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional characteristics associated with enteral autonomy.

Study Design: A multicenter, retrospective cohort analysis from the Pediatric Intestinal Failure Consortium was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with dependence on parenteral nutrition (PN) >60 days. Enteral autonomy was defined as PN discontinuation >3 months.

Results: A total of 272 infants were followed for a median (IQR) of 33.5 (16.2-51.5) months. Enteral autonomy was achieved in 118 (43%); 36 (13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified necrotizing enterocolitis (NEC; OR 2.42, 95% CI 1.33-4.47), care at an IF site without an associated intestinal transplantation program (OR 2.73, 95% CI 1.56-4.78), and an intact ileocecal valve (OR 2.80, 95% CI 1.63-4.83) as independent risk factors for enteral autonomy. A second model (n = 144) that included only patients with intraoperatively measured residual small bowel length found NEC (OR 3.44, 95% CI 1.36-8.71), care at a nonintestinal transplantation center (OR 6.56, 95% CI 2.53-16.98), and residual small bowel length (OR 1.04 cm, 95% CI 1.02-1.06 cm) to be independently associated with enteral autonomy.

Conclusions: A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ileocecal valve, and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2015.03.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485931PMC
July 2015

Increased Anti-Flagellin and Anti-Lipopolysaccharide Immunoglobulins in Pediatric Intestinal Failure: Associations With Fever and Central Line-Associated Bloodstream Infections.

JPEN J Parenter Enteral Nutr 2015 Jul 4;39(5):562-8. Epub 2014 Jun 4.

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

Background: Central line-associated bloodstream infections (CLABSIs) pose a significant challenge in the lives of patients with intestinal failure (IF). We hypothesized that plasma immunoglobulins against flagellin (FLiC) and lipopolysaccharide (LPS) would be able to differentiate CLABSIs from nonbacterial febrile episodes and that levels would increase with infection and decline following appropriate antibiotic treatment.

Materials And Methods: Patients with IF, due to short bowel syndrome, between the ages of 3 months and 4 years of age, were recruited at Cincinnati Children's Hospital Medical Center. Anti-FLiC and anti-LPS plasma antibody levels were measured in 13 children with IF at baseline, during febrile events, and also following treatment with antibiotics. These were also measured in 11 healthy children without IF who were recruited as controls.

Results: Plasma anti-FLiC IgA levels increased during febrile episodes in all patients with IF (baseline mean of 1.10 vs febrile episode mean of 1.32 optical density units, respectively; P = .046). Neither plasma anti-FLiC nor anti-LPS IgA or IgG levels distinguished CLABSI from nonbacterial febrile episodes compared with baseline levels. Compared with controls, patients with IF had significantly higher plasma levels of anti-FLiC and anti-LPS IgA at baseline.

Conclusion: Plasma anti-FLiC IgA antibody levels rise during febrile episodes but do not differentiate between nonbacterial febrile illnesses and CLABSIs in pediatric IF. However, the upregulation of these antibodies in IF suggests the baseline systemic presence of Gram-negative bacterial products.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0148607114537073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623326PMC
July 2015

Multiple micronutrient deficiencies among patients with intestinal failure during and after transition to enteral nutrition.

J Pediatr 2013 Dec 24;163(6):1692-6. Epub 2013 Aug 24.

Intestinal Rehabilitation Program, Intestinal Care Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Nigeria Teaching Hospital, Ituku/Ozalla, Enugu, Nigeria. Electronic address:

Objectives: To determine the prevalence of deficiencies of specific micronutrients (iron, zinc, magnesium, phosphorus, selenium, copper, folate, and vitamins A, D, E, and B12) in children with intestinal failure (IF), and to identify risk factors associated with developing these deficiencies.

Study Design: This study was a retrospective review of prospectively collected data from 178 children with IF managed by the Intestinal Care Center of Cincinnati Children's Hospital Medical Center between August 1, 2007, and July 31, 2012. Transition to full enteral nutrition (FEN) was defined as the period during which the patient received between 20% and 100% of estimated required nutrition enterally. FEN was defined as the patient's ability to tolerate 100% estimated required nutrition enterally for >2 weeks.

Results: Necrotizing enterocolitis was the most common cause of IF (27.5%). Iron was the most common micronutrient deficiency identified both during (83.9%) and after (61%) successful transition to FEN, with a significant reduction in the percentage of patients with iron deficiency between these 2 periods (P = .003). Predictors of micronutrient deficiency after successful transition to FEN included birth weight (P = .03), weight percentile (P = .02), height percentile (P = .04), and duration of parenteral nutrition (PN) (P = .013). After multivariate adjustments, only duration of PN remained statistically significant (P = .03).

Conclusion: Micronutrient deficiencies persist in patients with IF during and after transition to FEN. These data support the need for routine monitoring and supplementation of these patients, especially those on prolonged PN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2013.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842410PMC
December 2013

Micronutrient deficiencies in pediatric and young adult intestinal transplant patients.

Pediatr Transplant 2013 Nov 6;17(7):638-45. Epub 2013 Aug 6.

Intestinal Care Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Paediatrics, University of Nigeria Teaching Hospital, Enugu, Nigeria; Division of Gastroenterology, Hepatology and Nutrition, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Intestinal transplant recipients are at risk of micronutrient deficiency due to the slow process of post-transplant adaptation. Another contributing factor is calcineurin inhibitor-induced renal tubular dysfunction. Patients are typically supplemented with micronutrients during PN; however, the risk of deficiency may persist even after a successful transition to FEN. The goal was to determine the prevalence of, and associated risk factors for, iron, zinc, magnesium, phosphorus, selenium, copper, folate, and vitamins A, D, E, and B12 deficiency in pediatric intestinal transplant recipients after successful transition to FEN. A retrospective review of prospectively collected data from children who underwent intestinal transplantation at Cincinnati Children's Hospital Medical Center was done. Deficiencies of various micronutrients were defined using the hospital reference values. Twenty-one intestinal transplant recipients, aged one to 23 yr, who were successfully transitioned to FEN were included in the study. The prevalence of micronutrient deficiency was 95.2%. The common deficient micronutrients were iron (94.7%) and magnesium (90.5%). Age ≤ 10 yr (p = 0.002) and tube feeding (p = 0.02) were significant risk factors for micronutrient deficiencies. Pediatric intestinal transplant recipients have a high risk of micronutrient and mineral deficiencies. These deficiencies were more common among younger patients and those who received jejunal feeding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.12132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795992PMC
November 2013

Encephalopathy in a patient with short bowel syndrome: case report and discussion of the pathophysiology.

JPEN J Parenter Enteral Nutr 2014 May 26;38(4):518-20. Epub 2013 Jul 26.

Division of Gastroenterology, Hepatology and Nutrition.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0148607113496819DOI Listing
May 2014

Nutrition management of infants with surgical short bowel syndrome and intestinal failure.

Nutr Clin Pract 2013 Aug 12;28(4):421-8. Epub 2013 Jun 12.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 2010, Cincinnati, OH 45229, USA.

Appropriate nutrition recommendations are important for the successful management of the infant with an injured gastrointestinal tract postsurgery who is at risk for intestinal failure. Management strategies that can be used to augment successful adaptation and prevent liver disease are summarized in this review. These include appropriate postoperative fluid and electrolyte management, modification of parenteral nutrition to minimize intestinal failure-associated liver disease, early and aggressive enteral feeding advancement, the use of hormonal and trophic agents, prevention of central line-associated bloodstream infections using ethanol lock, appropriate treatment, and prevention of pathologic small bowel bacterial overgrowth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0884533613491787DOI Listing
August 2013

Vitamin D deficiency and low bone mineral density in pediatric and young adult intestinal failure.

J Pediatr Gastroenterol Nutr 2013 Sep;57(3):372-6

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

Objectives: The aim of the present study was to determine the prevalence and predisposing factors for vitamin D deficiency and low bone mineral density (BMD) in patients with intestinal failure (IF).

Methods: A retrospective review of patients with IF managed at the Cincinnati Children's Hospital Medical Center. IF was defined as history of parenteral nutrition (PN) >30 days. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25 (OH) D) <20 ng/dL. Reduced BMD was defined using dual x-ray absorptiometry z score ≤-2. A binary logistic regression model was used to test for association of significant risk factors and the outcome variables after univariate analyses.

Results: One hundred and twenty-three patients with median age of 4 years (range 3-22 years) were evaluated. Forty-nine (39.8%) patients had at least a documented serum 25 (OH) D deficiency during the study interval, whereas 10 of 80 patients (12.5%) with dual x-ray absorptiometry scans completed had a low BMD z score. Age at study entry was associated with both 25 (OH) D deficiency (P = 0.01) and low BMD z score (P = 0.03). Exclusive PN at study entry was associated with reduced bone mass (P = 0.03). There was no significant association between vitamin D deficiency and low BMD z score (P = 0.31).

Conclusions: The risk of 25 (OH) D deficiency and low BMD z score increases with age among patients with IF. Strategies for monitoring and preventing abnormal bone health in older children receiving exclusive PN need to be developed and evaluated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0b013e31829c10ebDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757114PMC
September 2013

Physiology of the small intestine after resection and transplant.

Curr Opin Gastroenterol 2013 Mar;29(2):153-8

The Department of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.

Purpose Of Review: Recent studies have evaluated intestinal physiology following bowel resection; understanding changes in small bowel physiology after intestinal transplantation has received less attention. In this review, we will examine recent studies focused on changes in intestinal physiology following resection and intestinal transplantation.

Recent Findings: Absorption, immunity, and motility are fundamental components of small bowel physiology. Absorption after resection or transplantation is mediated by adaptation and enterocyte function. After resection, adaptation results in increased villus height and crypt depth. Hepatocyte growth factor and epidermal growth factors cause enterocyte hypertrophy and hyperplasia, allowing greater peptide uptake. Little is known about intestinal adaptation after transplant, but enteral autonomy is attainable. Immunity in small bowel after transplantation relies on a balance of innate and adaptive immune responses in the presence of the luminal microbiota. Intraepithelial lymphocytes are decreased following small bowel resection. After small bowel transplant, the number and the ratio of intraepithelial lymphocytes to enterocytes, as well as changes in the microbiota, can be used to identify rejection. After intestinal transplant, immune-mediated dysmotility is common. Perioperative infliximab in addition to tacrolimus may decrease the inflammation that contributes to dysmotility.

Summary: As intestinal transplantation becomes more successful, understanding how absorption, immunity, and motility changes will allow for optimization of bowel function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MOG.0b013e32835c9c9dDOI Listing
March 2013

Natural history of pediatric intestinal failure: initial report from the Pediatric Intestinal Failure Consortium.

J Pediatr 2012 Oct 11;161(4):723-8.e2. Epub 2012 May 11.

Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA.

Objective: To characterize the natural history of intestinal failure (IF) among 14 pediatric centers during the intestinal transplantation era.

Study Design: The Pediatric Intestinal Failure Consortium performed a retrospective analysis of clinical and outcome data for a multicenter cohort of infants with IF. Entry criteria included infants <12 months receiving parenteral nutrition (PN) for >60 continuous days. Enteral autonomy was defined as discontinuation of PN for >3 consecutive months. Values are presented as median (25th, 75th percentiles) or as number (%).

Results: 272 infants with a gestational age of 34 weeks (30, 36) and birth weight of 2.1 kg (1.2, 2.7) were followed for 25.7 months (11.2, 40.9). Residual small bowel length in 144 patients was 41 cm (25.0, 65.5). Diagnoses were necrotizing enterocolitis (71, 26%), gastroschisis (44, 16%), atresia (27, 10%), volvulus (24, 9%), combinations of these diagnoses (46, 17%), aganglionosis (11, 4%), and other single or multiple diagnoses (48, 18%). Prescribed medications included oral antibiotics (207, 76%), H2 blockers (187, 69%), and proton pump inhibitors (156, 57%). Enteral feeding approaches varied among centers; 19% of the cohort received human milk. The cohort experienced 8.9 new catheter-related blood stream infections per 1000 catheter days. The cumulative incidences for enteral autonomy, death, and intestinal transplantation were 47%, 27%, and 26%, respectively. Enteral autonomy continued into the fifth year after study entry.

Conclusions: Children with IF endure significant mortality and morbidity. Enteral autonomy may require years to achieve. Improved medical, nutritional, and surgical management may reduce time on PN, mortality, and need for transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2012.03.062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419777PMC
October 2012

The Morton's fork of total parenteral nutrition administration.

J Pediatr 2012 Mar 3;160(3):361-2. Epub 2011 Dec 3.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2011.10.013DOI Listing
March 2012

Incidence of acute and chronic graft-versus-host disease and donor T-cell chimerism after small bowel or combined organ transplantation.

J Pediatr Surg 2011 Sep;46(9):1732-8

Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital and Medical Center, Cincinnati, OH 45229, USA.

Purpose: Graft-versus-host disease (GVHD) after organ transplantation is a rare but life-threatening complication with very high mortality.

Methods: A retrospective review was performed of all patients undergoing small bowel or combined organ transplantation at a single institution during 2003 to 2009. Patients with donor T-cell chimerism were analyzed in detail for development of GVHD.

Results: Thirty-two patients were included in the study. Of 32 patients, 11 (34%) had donor T-cell chimerism (range, 0%-53%) studies performed; 7 (64%) of those 11 patients demonstrated clinical features of GVHD. All patients who demonstrated GVHD had detectable donor T-cell chimerism. All patients with GVHD presented with skin involvement. Graft-versus-host disease responded to increased immune suppression therapy. Mortality was 43% (3/7) among patients with GVHD and was caused by multiorgan failure and sepsis in all cases.

Conclusion: Acute and chronic GVHD were observed frequently after combined solid organ transplantation and were associated with significant mortality and morbidity. Alloreactive donor T cells cotransplanted with the organ likely play a role in the pathophysiology because levels of donor-derived T-cell chimerism correlated with the clinical course of GVHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpedsurg.2011.04.016DOI Listing
September 2011

sTREM-1 and LBP in central venous catheter-associated bloodstream infections in pediatric intestinal failure.

J Pediatr Gastroenterol Nutr 2011 Dec;53(6):627-33

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

Objective: Central venous catheter-associated bloodstream infections (CVC-BSIs) are a major cause of morbidity and mortality in the pediatric intestinal failure (IF) population. We assessed plasma lipopolysaccharide-binding protein (LBP) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as biomarkers for CVC-BSI. We hypothesized that sTREM-1 and LBP rise with BSI and decline following treatment, and that baseline LBP is higher in the IF population than in controls.

Patients And Methods: Patients younger than 4 years were recruited from the IF registry at Cincinnati Children's Hospital. LBP and sTREM-1 levels were measured on 22 patients with IF at baseline, 17 patients with IF with BSIs, and 11 healthy controls.

Results: Mean sTREM-1 level (pg/mL) and LBP level (μg/mL) rose with CVC-BSI over baseline (115.0 ± 51.2 vs 85.9 ± 27.6, P = 0.011 and 79.8 ± 45.4 vs 20.5 ± 11.3, P < 0.001, respectively) and declined following antibiotic therapy (115.0 ± 51.2 vs 77.9 ± 29.8, P = 0.003 and 79.8 ± 45.4 vs 26.2 ± 10.8, P < 0.001, respectively). Receiver operating characteristic curves showed that neither sTREM-1 nor LBP is sufficient to predict bacteremia versus fever without bacteremia (area under these curves = 0.57 and 0.82, respectively). Baseline LBP was higher in hospitalized patients than in outpatients (27.5 ± 8.7 vs 13.5 ± 9.2, P = 0.002), patients with previous BSIs versus those without (23.5 ± 10.4 vs 10.1 ± 8.3, P = 0.016), and those listed for transplantation versus those not listed (29.6 ± 9.8 vs 16.2 ± 9.5, P = 0.033).

Conclusions: sTREM-1 and LBP rise with CVC-BSI in IF and decline after treatment; however, neither distinguishes infection from nonbacteremic febrile episodes. Baseline LBP may be a marker of disease severity in IF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0b013e3182294fccDOI Listing
December 2011

Medical management of pediatric intestinal failure.

Semin Pediatr Surg 2010 Feb;19(1):20-6

University of Cincinnati College of Medicine, Nutrition and Intestinal Transplantation, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.

The outcome for children with congenital enteropathies or massive surgical resections has improved significantly over the past two decades. Advances in understanding of the pathophysiology of intractable diarrhea and of the mutations causing many of the congenital enteropathies have enabled initiation of preventive measures for intractable diarrhea, and have enabled clinicians to provide focused treatment of immune-mediated congenital diarrheal illnesses. Children with surgical short bowel syndrome also face an improved outcome because of improvements in the composition of parenteral nutrition (TPN) and in enteral alimentation strategies. It is now recognized that, through adaptation, small intestinal surface area and absorptive function may improve over time to facilitate emancipation from parenteral nutrition. Beyond provision of enteral nutrition, ancillary therapies such as judicious use of acid suppression, antibiotics, prokinetic agents, and soluble fiber seem to accelerate the rate of adaptation in young children. In the future, trophic hormones such as epidermal growth factor (EGF) or glucagon-like peptide 2 (GLP-2) may become routine members of the therapeutic armamentarium for surgical short bowel syndrome, thus further improving outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.sempedsurg.2009.11.003DOI Listing
February 2010