Peace Nkechinyere Dike

All Publications

• Incidence and risk factors for chronic rejection in pediatric liver transplantation. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Dike, P. N., Schady, D., Himes, R., Goss, J. A., Guffey, D., Cerminara, D., Mysore, K. R. 2024

  Abstract

  Chronic rejection (CR) is a progressive immunological injury that frequently leads to long-term liver allograft dysfunction and loss. Although CR remains an important indication for re-transplantation, as transplant immunosuppression has evolved, its prevalence in adults undergoing liver transplantation (LT) has declined. However, the incidence and factors that lead to CR in pediatric LT are poorly defined. Therefore, we sought to systematically measure CR's incidence and assess both the risk factors for developing CR and outcomes in a large cohort of pediatric LT recipients. In this single center study, we retrospectively analyzed and compared relevant recipient characteristics, surgical details, immunosuppression, graft, and patient survival in the CR and control groups over a 17-year period. After a median time of 1.9 years post-LT, 19/356 LT recipients (5.3%) developed CR in our cohort. Post-transplant lymphoproliferative disorder (p=0.01), infections (p=0.02), autoimmune liver diseases (HR 7.3, p=<0.01), Black race (HR11.5, p=0.01) and two or more episodes of acute cellular rejection (HR 5.1, p=<0.01) were associated with CR development. The re-transplantation rate among CR cases was 15.8% at a median follow-up time of 4.1 years. Overall, patient survival was lower in the CR group (78.9%) versus controls (91.1%). While CR incidence in our pediatric cohort was lower than previously reported rates of ˃12%, the CR group had a higher graft failure rate that required re-transplantation and lower overall patient survival. Thus, identifying risk factors may warrant specialized immunosuppression protocols and closer post-transplantation monitoring to reduce the risk of morbidity and mortality from CR.

  View details for DOI 10.1097/LVT.0000000000000488

  View details for PubMedID 39311848

• Bile acids differentially regulate longitudinal smooth muscle contractility in everted mouse ileum. FASEB bioAdvances Dike, P. N., Soni, K. G., Chang, D. S., Preidis, G. A. 2024; 6 (7): 200-206

  Abstract

  Bile acids regulate gastrointestinal motility by mechanisms that are poorly understood. Standard isolated tissue bath assays might not recapitulate in vivo physiology if contractile responses to certain bile acids require direct application to the intestinal mucosa. We sought to determine the feasibility of quantifying longitudinal smooth muscle contractile responses to bile acids from intact segments of everted mouse ileum. Ileum from adult female C57BL/6J mice was isolated, gently everted over a notched metal rod, and mounted in tissue baths. Individual bile acids and agonists of bile acid receptors were added to the baths, and longitudinal smooth muscle contractile responses were quantified by isometric force transduction. Ursodeoxycholic acid robustly increased contractile responses in a dose-dependent manner. Deoxycholic acid stimulated contractility at low doses but inhibited contractility at high doses. Chenodeoxycholic acid, glycocholic acid, and lithocholic acid did not alter contractility. The dose-dependent increase in contractility resulting from the application of ursodeoxycholic acid was recapitulated by INT-777, an agonist of the Takeda G protein-coupled receptor 5 (TGR5), and by cevimeline, a muscarinic acetylcholine receptor agonist. Agonists to the nuclear receptors farnesoid X receptor, glucocorticoid receptor, pregnane X receptor, vitamin D receptor, and to the plasma membrane epidermal growth factor receptor did not modify baseline contractile patterns. These results demonstrate that gentle eversion of intact mouse ileum facilitates the quantification of longitudinal smooth muscle contractile responses to individual bile acids. Prokinetic effects of ursodeoxycholic acid and low-dose deoxycholic acid are replicated by agonists to TGR5 and muscarinic acetylcholine receptors.

  View details for DOI 10.1096/fba.2024-00044

  View details for PubMedID 38974116

  View details for PubMedCentralID PMC11226990

• The Multidisciplinary Pediatric Liver Transplant. Current problems in surgery Ruan, W., Galvan, N. T., Dike, P., Koci, M., Faraone, M., Fuller, K., Koomaraie, S., Cerminara, D., Fishman, D. S., Deray, K. V., Munoz, F., Schackman, J., Leung, D., Akcan-Arikan, A., Virk, M., Lam, F. W., Chau, A., Desai, M. S., Hernandez, J. A., Goss, J. A. 2023; 60 (11): 101377

  View details for DOI 10.1016/j.cpsurg.2023.101377

  View details for PubMedID 37993242

• Beyond Varices: Complications of Cirrhotic Portal Hypertension in Pediatrics. Seminars in liver disease Banc-Husu, A. M., Shiau, H., Dike, P., Shneider, B. L. 2022

  Abstract

  Complications of cirrhotic portal hypertension (PHTN) in children are broad and include clinical manifestations ranging from variceal hemorrhage, hepatic encephalopathy (HE), ascites, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS) to less common conditions such as hepatopulmonary syndrome, portopulmonary hypertension, and cirrhotic cardiomyopathy. The approaches to the diagnosis and management of these complications have become standard of practice in adults with cirrhosis with many guidance statements available. However, there is limited literature on the diagnosis and management of these complications of PHTN in children with much of the current guidance available focused on variceal hemorrhage. The aim of this review is to summarize the current literature in adults who experience these complications of cirrhotic PHTN beyond variceal hemorrhage and present the available literature in children, with a focus on diagnosis, management, and liver transplant decision making in children with cirrhosis who develop ascites, SBP, HRS, HE, and cardiopulmonary complications.

  View details for DOI 10.1055/s-0042-1759613

  View details for PubMedID 36572031

• Addressing Racism in Pediatric Liver Transplantation: A Moral Imperative. The Journal of pediatrics Ebel, N. H., Dike, P. N., Hsu, E. K. 2022

  View details for DOI 10.1016/j.jpeds.2022.04.046

  View details for PubMedID 35504347

• Variability of Care and Access to Transplantation for Children with Biliary Atresia Who Need a Liver Replacement JOURNAL OF CLINICAL MEDICINE de Goyet, J., Illhardt, T., Chardot, C., Dike, P. N., Baumann, U., Brandt, K., Wildhaber, B. E., Pakarinen, M., di Francesco, F., Sturm, E., Cornet, M., Lemoine, C., Pfister, E., Calinescu, A. M., Hukkinen, M., Harpavat, S., Tuzzolino, F., Superina, R. 2022; 11 (8)

  Abstract

  Biliary atresia (BA) is the commonest single etiology indication for liver replacement in children. As timely access to liver transplantation (LT) remains challenging for small BA children (with prolonged waiting time being associated with clinical deterioration leading to both preventable pre- and post-transplant morbidity and mortality), the care pathway of BA children in need of LT was analyzed-from diagnosis to LT-with particular attention to referral patterns, timing of referral, waiting list dynamics and need for medical assistance before LT.International multicentric retrospective study. Intent-to-transplant study analyzing BA children who had indication for LT early in life (aged < 3 years at the time of assessment), over the last 5 years (2016-2020). Clinical and laboratory data of 219 BA children were collected from 8 transplant centers (6 in Europe and 2 in USA).39 patients underwent primary transplants. Children who underwent Kasai in a specialist -but not transplant- center were older at time of referral and at transplant. At assessment for LT, the vast majority of children already were experiencing complication of cirrhosis, and the majority of children needed medical assistance (nutritional support, hospitalization, transfusion of albumin or blood) while waiting for transplantation. Severe worsening of the clinical condition led to the need for requesting a priority status (i.e., Peld Score exception or similar) for timely graft allocation for 76 children, overall (35%).As LT currently results in BA patient survival exceeding 95% in many expert LT centers, the paradigm for BA management optimization and survival have currently shifted to the pre-LT management. The creation of networks dedicated to the timely referral to a pediatric transplant center and possibly centralization of care should be considered, in combination with implementing all different graft type surgeries in specialist centers (including split and living donor LTs) to achieve timely LT in this vulnerable population.

  View details for DOI 10.3390/jcm11082142

  View details for Web of Science ID 000786181800001

  View details for PubMedID 35456234

  View details for PubMedCentralID PMC9032543

• A Rare Case of Pediatric Amyloidosis Presenting as Upper Gastrointestinal Bleeding JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION Dike, P. N., Pereira, M. M., Kaufman, G. P., Patel, K., Schady, D., Vogel, A. M., van Buren, K. L., Fishman, D. S. 2022; 74 (3): E73

  View details for DOI 10.1097/MPG.0000000000003310

  View details for Web of Science ID 000761954400002

  View details for PubMedID 34560726

• Recent advances in the use of ultrasound and related techniques in diagnosing and predicting outcomes in biliary atresia CURRENT OPINION IN PEDIATRICS Dike, P. N., Mahmood, N., Harpavat, S. 2021; 33 (5): 515-520

  Abstract

  Biliary atresia (BA) is the leading cause of chronic liver disease and the most common indication for pediatric liver transplantation. The use of ultrasound (US) and related techniques continues to evolve to help diagnose BA as well as potentially to help predict outcomes after treatment with the Kasai portoenterostomy (KP).There are no US findings that are definitive for BA; however, signs which are consistent with BA include gallbladder abnormalities, the triangular cord sign, presence of hepatic subcapsular flow, and hilar lymphadenopathy. Elastography techniques to measure liver stiffness may also increase the diagnostic accuracy of detecting BA, particularly in older infants or without other US findings. In addition, both US and elastography are still being studied as potential methods to predict outcomes after KP such as the development of portal hypertension and the need for liver transplant.US findings in the diagnosis of BA are well characterized. Future studies will help determine the utility of elastography in diagnosing BA, as well as both US and elastography in monitoring and predicting disease outcomes after KP.

  View details for DOI 10.1097/MOP.0000000000001048

  View details for Web of Science ID 000693362000009

  View details for PubMedID 34369411

  View details for PubMedCentralID PMC8615294

• Early-life malnutrition causes gastrointestinal dysmotility that is sexually dimorphic NEUROGASTROENTEROLOGY AND MOTILITY Soni, K. G., Dike, P. N., Suh, J., Halder, T., Edwards, P. T., Foong, J. P., Conner, M. E., Preidis, G. A. 2020; 32 (12): e13936

  Abstract

  Slow gastrointestinal (GI) transit occurs in moderate-to-severe malnutrition. Mechanisms underlying malnutrition-associated dysmotility remain unknown, partially due to lack of animal models. This study sought to characterize GI dysmotility in mouse models of malnutrition.Neonatal mice were malnourished by timed maternal separation. Alternatively, low-protein, low-fat diet was administered to dams, with malnourished neonates tested at two weeks or weaned to the same chow and tested as young adults. We determined total GI transit time by carmine red gavage, colonic motility by rectal bead latency, and both gastric emptying and small bowel motility with fluorescein isothiocyanate-conjugated dextran. We assessed histology with light microscopy, ex vivo contractility and permeability with force-transduction and Ussing chamber studies, and gut microbiota composition by 16S rDNA sequencing.Both models of neonatal malnutrition and young adult malnourished males but not females exhibited moderate growth faltering, stunting, and grossly abnormal stomachs. Progression of fluorescent dye was impaired in both neonatal models of malnutrition, whereas gastric emptying was delayed only in maternally separated pups and malnourished young adult females. Malnourished young adult males but not females had atrophic GI mucosa, exaggerated intestinal contractile responses, and increased gut barrier permeability. These sex-specific abnormalities were associated with altered gut microbial communities.Multiple models of early-life malnutrition exhibit delayed upper GI transit. Malnutrition affects young adult males more profoundly than females. These models will facilitate future studies to identify mechanisms underlying malnutrition-induced pathophysiology and sex-specific regulatory effects.

  View details for DOI 10.1111/nmo.13936

  View details for Web of Science ID 000545517300001

  View details for PubMedID 33021011

  View details for PubMedCentralID PMC7688589