Ke-You (Yoyo) Zhang

All Publications

• Unlocking the promise of mesenchymal stem cells and extracorporeal photopheresis to address rejection and graft failure in intestinal transplant recipients. Human immunology Levitte, S., Nilkant, R., Jensen, A. R., Zhang, K. Y. 2024; 85 (6): 111160

  Abstract

  In patients with irreversible intestinal failure, intestinal transplant has become a standard treatment option. Graft failure secondary to acute or chronic cellular rejection continues to be a significant challenge following transplant. Even with optimal immune suppression, some patients continue to struggle with refractory rejection. Both extracorporeal photopheresis (ECP) and extracellular vesicles derived from mesenchymal stem cells (EVs) have been used to treat refractory rejection following intestinal transplantation, although their use remains limited and consistent treatment protocols are lacking.Intestinal transplant recipients who received ECP only or ECP and EVs as rescue therapy for acute cellular rejection or chronic inflammation between 2016 and 2022 were included in this single-center retrospective analysis. Baseline demographics, pre- and post-treatment histopathology, endoscopic and biochemical findings, and long-term transplant outcomes were analyzed.Three patients (two pediatric and one adult) with acute steroid- and biologic-refractory rejection were treated with ECP and/or EVs, as was one patient (pediatric) with chronic graft rejection and inflammation. Patients received twice weekly ECP for 4 weeks and once weekly thereafter. EVs were administered in three doses each separated by 72 h. Immunosuppression at the time of treatment initiation included high-dose tacrolimus and sirolimus. Histologic resolution of rejection was achieved in all patients over 12-16 weeks. Steroids were weaned to low-dose or withdrawn in every patient within 4 weeks of ECP/EV treatment. C-reactive protein decreased from an average of 14.75 to 1.6 mg/dL post-treatment and fecal calprotectin decreased from average 800 mg/g to 31 mg/g. Donor-induced cytotoxic T cell populations were quantified for two of the patients with acute rejection, and in both cases decreased dramatically following treatment. There were no complications associated with either treatment.Both ECP and EVs present novel opportunities to address graft rejection and inflammation in bowel transplant recipients. More work will be needed to define the optimal therapeutic parameters for each treatment modality.

  View details for DOI 10.1016/j.humimm.2024.111160

  View details for PubMedID 39471538

• Pediatric Combined Heart-liver Transplantation: A Single-center Long-term Experience. Transplantation direct Levitte, S., Nilkant, R., Chen, S., Beadles, A., Lee, J., Bonham, C. A., Rosenthal, D., Gallo, A., Hollander, S., Esquivel, C., Ma, M., Zhang, K. Y. 2024; 10 (9): e1696

  Abstract

  Combined heart liver transplant (CHLT) continues to gain attention as a surgical treatment for patients with end-stage heart and liver disease but remains rare. We present our institutional longitudinal experience with up to 14 y of follow-up, focused on long-term outcomes in CHLT recipients.We conducted a single-institutional, retrospective review from January 1, 2010, to December 31, 2023, including 7 patients ages 7-17 y who underwent CHLT.Most patients were surgically palliated via Fontan procedure pretransplant (n = 6), and all had evidence of advanced fibrosis or cirrhosis before transplant. The 30-d mortality was 14.3% (n = 1, multiorgan failure). During the follow-up period, 1 patient developed acute heart rejection which required treatment and 2 developed acute liver rejection. In all cases, rejection was successfully treated. Two patients developed acute heart rejection which did not require treatment (grade 1R). No patients developed chronic or refractory rejection. No patients developed allograft coronary artery vasculopathy.CHLT remains a rarely performed treatment for pediatric patients with end-stage heart and liver disease, but our long-term data suggest that this treatment strategy should be considered more frequently.

  View details for DOI 10.1097/TXD.0000000000001696

  View details for PubMedID 39165490

  View details for PubMedCentralID PMC11335332

• Precision Delivery of Therapeutics to the Intestine: A Case Series of Superselective Steroid Administration in Pediatric Intestinal Transplant Recipients. Transplantation Levitte, S., Guevara-Tique, A. A., Ganguly, A., Syed, A., Gugig, R., Zhang, K. Y., Bonham, C. A., Thakor, A. S. 2024; 108 (8): e202-e203

  View details for DOI 10.1097/TP.0000000000005053

  View details for PubMedID 39042371

• Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute rejection in pediatric and adult bowel transplant AMERICAN JOURNAL OF TRANSPLANTATION Levitte, S., Zhang, K., Guevara-Tique, A. A., Ganguly, A., Dulken, B. W., Nilkant, R., Rigmaiden, M., Kumari, R., Khlifi, K., Thakor, A. S., Bonham, C. A. 2024; 24 (4): 693-696

  View details for DOI 10.1016/j.ajt.2023.10.019

  View details for Web of Science ID 001217324600001

• Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute rejection in pediatric and adult bowel transplant. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Levitte, S., Zhang, K. Y., Guevara-Tique, A. A., Ganguly, A., Dulken, B. W., Nilkant, R., Rigmaiden, M., Kumari, R., Khlifi, K., Thakor, A. S., Bonham, C. A. 2023

  Abstract

  Mesenchymal stem cells are under investigation as a novel therapy to treat solid organ transplant rejection. However, significant hurdles have limited their use in humans. Mesenchymal stem cell-derived extracellular vesicles address many of these shortcomings but have not been investigated clinically. Here we report our experience treating two patients with graft rejection and inflammation following bowel transplant using mesenchymal stem cell-derived extracellular vesicles.

  View details for DOI 10.1016/j.ajt.2023.10.019

  View details for PubMedID 39491097

• Temporal Analysis of Inflammatory Bowel Disease and Pancreatitis Co-Occurrence in Children and Adults in the United States. Clinical and translational gastroenterology Zhang, K. Y., Siddiqi, I., Saad, M., Balabanis, T., Dehghan, M. S., Nasr, A., Tolj, V., Habtezion, A., Park, K. T., Abu-El-Haija, M., Sellers, Z. M. 2023

  Abstract

  Pancreatitis in inflammatory bowel disease has been attributed to peripancreatic intestinal disease and/or drug-induced pancreatic toxicity. We used large cohort analyses to define inflammatory bowel disease and pancreatitis temporal co-occurrence with a detailed descriptive analysis to gain greater insight into the pathophysiological relationship between these two diseases.Truven Health MarketScan private insurance claims from 141,017,841 patients (<65 years-old) and 7,457,709 patients from four academic hospitals were analyzed. We calculated prevalence of Crohn's disease or ulcerative colitis with acute or chronic pancreatitis and performed temporal and descriptive analyses.Of 516,724 inflammatory bowel disease patients, 12,109 individuals (2.3%) had pancreatitis. Acute pancreatitis was 2-6x more prevalent than chronic pancreatitis. In adults, acute pancreatitis occurred equally among Crohn's disease and ulcerative colitis (1.8-2.2% vs. 1.6-2.1%, respectively), whereas in children, acute pancreatitis was more frequent in ulcerative colitis (2.3-3.4% vs. 1.5-1.8%, respectively). The highest proportion of pancreatitis (21.7-44.7%) was at/near the time of inflammatory bowel disease diagnosis. Of these, 22.1-39.3% were on steroids at the time of pancreatitis. Individuals with chronic pancreatitis or recurrent pancreatitis hospitalizations had increased risk of a future inflammatory bowel disease diagnosis (odds ratio=1.52 or 1.72, respectively).Pancreatitis in inflammatory bowel disease may not simply be a drug adverse event but may also involve local and/or systemic processes that negatively impact the pancreas. Our analysis of pancreatitis before, during, and after inflammatory bowel disease diagnosis suggests a bi-directional pathophysiologic relationship between inflammatory bowel disease and pancreatitis, with potentially more complexity than previously appreciated.

  View details for DOI 10.14309/ctg.0000000000000628

  View details for PubMedID 37556391

• Extracorporeal Photopheresis for Refractory Rejection in Intestinal Transplantation Zhang, K., Kumari, R., Bonham, C. LIPPINCOTT WILLIAMS & WILKINS. 2023: 29

  View details for DOI 10.1097/01.tp.0000945660.23307.c7

  View details for Web of Science ID 001023645700047

• Mesenchymal stem cell-derived exosomes for the treatment of acute rejection in pediatric and adult bowel transplant Zhang, K., Kumari, R., Lightner, A., Gallo, A., Bonham, C., Esquivel, C. LIPPINCOTT WILLIAMS & WILKINS. 2023: 38

  View details for DOI 10.1097/01.tp.0000945716.40222.b5

  View details for Web of Science ID 001023645700061

• MELD 3.0 for adolescent liver transplant candidates. Hepatology (Baltimore, Md.) Kwong, A. J., Zhang, K. Y., Ebel, N., Mannalithara, A., Kim, W. R. 2023

  Abstract

  Adolescents constitute a unique waitlist cohort that is distinct from younger children. MELD 3.0, which was developed in an adult population of liver transplant candidates, is planned to replace MELD-Na in the current liver allocation system for both adult and adolescents aged 12-17. We evaluated the predictive performance of MELD-Na, MELD 3.0, and PELD, for 90-day waitlist mortality risk among adolescent liver transplant registrants.New waitlist registrations for primary liver transplant among individuals aged 12-17 and aged 18-25 for comparison were identified using OPTN data from Nov 17 2004 to Dec 31 2021. The predictive performance of the current and proposed MELD and PELD scores was assessed using the Harrell's concordance (c) statistic.There were 1,238 eligible listings for adolescents aged 12-17, and 1,740 young adults aged 18-25. In the adolescent group, 90-day survival was 97.8%, compared to 95.9% in those aged 18-25 (log-rank p = 0.005), with no significant differences when stratified by sex or indication. Among adolescents, increasing MELD 3.0 was associated with an increased hazard of mortality (HR 1.27, 95% CI 1.18-1.37), and the c-statistic for 90-day waitlist survival using MELD 3.0 was 0.893, compared with 0.871 using MELD-Na, and 0.852 using PELD.The discriminative ability of MELD 3.0 to rank adolescents according to the risk of death within 90 days was robust. Although MELD 3.0 was initially developed and validated in adults, MELD 3.0 may also improve the prediction of waitlist mortality in adolescents and better represent their urgency for liver transplant.

  View details for DOI 10.1097/HEP.0000000000000352

  View details for PubMedID 36943091

• MELD 3.0 PREDICTS WAITLIST MORTALITY RISK IN ADOLESCENT LIVER TRANSPLANT REGISTRANTS Kwong, A. J., Zhang, K., Ebel, N., Mannalithara, A., Kim, W. WILEY. 2022: S17-S18

  View details for Web of Science ID 000870796600018

• Superior Mesenteric Artery Syndrome in an Adolescent With Anorexia and Suspected Pancreatitis. JPGN reports Hsu, D., Zhang, K. Y., Rubesova, E., Bruzoni, M., Khavari, N., Goyal, A. 2022; 3 (2): e194

  View details for DOI 10.1097/PG9.0000000000000194

  View details for PubMedID 37168901

  View details for PubMedCentralID PMC10158292

• Towards identifying predictors of pediatric heart only versus combined heart liver transplantation Zhang, K., Chen, S., Syed, A., Gallo, A., Esquivel, C., Bonham, A., Hollander, S. A., Ma, M., Han, J., Ebel, N. H. WILEY. 2022

  View details for Web of Science ID 000783167500071

• A Unified Treatment Algorithm and Admission Order Set for Pediatric Acute Pancreatitis JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION Sellers, Z. M., Dike, C., Zhang, K., Giefer, M. J., Uc, A., Abu-El-Haija, M. 2019; 68 (6): E109–E111

  View details for DOI 10.1097/MPG.0000000000002341

  View details for Web of Science ID 000480695000008

• A Unified Treatment Algorithm and Admission Order Set for Pediatric Acute Pancreatitis. Journal of pediatric gastroenterology and nutrition Sellers, Z. M., Dike, C., Zhang, K., Giefer, M. J., Uc, A., Abu-El-Haija, M. 2019

  View details for PubMedID 30921257

• Procalcitonin as a Predictive Marker for Bacteremia in Children With a Central Line and Fever. Hospital pediatrics Damman, J. n., Arias, P. n., Kerner, J. n., Zhang, K. Y., Dehghan, M. n., Krishnan, G. n., Nespor, C. n., Bensen, R. n., Park, K. T. 2019

  Abstract

  Unnecessary use of antibiotics is an increasing problem. In this study, we sought to determine the diagnostic accuracy of procalcitonin in predicting bacteremia in children with a central line and fever, and we sought to determine optimal cutoff values to maximize sensitivity and specificity. This is the largest study to date in which procalcitonin is examined as a predictive marker of bacteremia in pediatric patients with a central line and fever.We conducted a retrospective cohort study of children aged 0 to 23 years with a central line and fever of 38°C who had procalcitonin and blood cultures drawn before initiation of antibiotics and had no other identified bacterial infection. Patients were also prospectively monitored via a custom-built electronic medical record dashboard for eligibility.There were 523 patients and >2500 procalcitonin values reviewed for eligibility. Of these, 169 (47%) patients and 335 blood cultures with procalcitonin were included. There were 94 (28%) positive bacterial blood cultures and 241 (72%) negative bacterial blood cultures. In bacteremic cultures, the mean procalcitonin level was 9.96 ± 15.96 ng/mL, and the median procalcitonin level was 4.85 ng/mL (interquartile range 18.5). In nonbacteremic cultures, the mean procalcitonin level was 1.23 ± 10.37 ng/mL, and the median procalcitonin level was 0.3 ng/mL (interquartile range 0.7). A receiver operating characteristic analysis indicated a procalcitonin level of ≥0.6 ng/mL as the best cutoff point that produced a sensitivity of 85.6% and a specificity of 65.7% (area under the curve 0.85).Procalcitonin is a sensitive biomarker in predicting bacteremia in children with a central line and fever.

  View details for PubMedID 31097470

• Nationwide Trends in Acute and Chronic Pancreatitis Among Privately Insured Children and Non-Elderly Adults in the United States, 2007-2014 GASTROENTEROLOGY Sellers, Z. M., MacIsaac, D., Yu, H., Dehghan, M., Zhang, K., Bensen, R., Wong, J. J., Kin, C., Park, K. T. 2018; 155 (2): 469-+

  View details for DOI 10.1053/j.gastro.2018.04.013

  View details for Web of Science ID 000440023400042

• Nationwide Trends in Acute and Chronic Pancreatitis Among Privately Insured Children and Non-Elderly Adults in the United States, 2007-2014. Gastroenterology Sellers, Z. M., MacIsaac, D. n., Yu, H. n., Dehghan, M. n., Zhang, K. Y., Bensen, R. n., Wong, J. J., Kin, C. n., Park, K. T. 2018

  Abstract

  Epidemiologic analyses of acute and chronic pancreatitis (AP and CP) provide insight into causes and strategies for prevention, and affect allocation of resources to its study and treatment. We sought to determine current and accurate incidences of AP and CP, along with the prevalence of CP, in children and adults in the United States.We collected data from the Truven MarketScan Research Databases of commercial inpatient and outpatient insurance claims in the United States from 2007 through 2014 (patients 0-64 years old). We calculated the incidences of AP and CP, and prevalence of CP, based on International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. Children were defined as 18 years or younger and adults as 19 to 64 years old.The incidence of pediatric AP was stable from 2007 through 2014, remaining at 12.3/100,000 persons in 2014. Meanwhile the incidence for adult AP decreased from 123.7/100,000 persons in 2007 to 111.2/100,000 persons in 2014. The incidence of CP decreased over time in children (2.2/100,000 persons in 2007 to 1.9/100,000 persons in 2014) and adults (31.7/100,000 persons in 2007 to 24.7/100,000 persons in 2014). The prevalence of pediatric and adult CP was 5.8/100,000 persons and 91.9/100,000 persons, respectively in 2014. Incidences of AP and CP increased with age; we found little change in incidence during the first decade of life, but linear increases starting in the second decade.We performed a comprehensive epidemiologic analysis of privately insured non-elderly adults and children with AP and CP in the United States. Changes in gallstone formation, smoking, and alcohol consumption, along with advances in pancreatitis management, may be responsible for the stabilization and even decrease in the incidences of AP and CP.

  View details for PubMedID 29660323

• Plasmapheresis for Hypertriglyceridemia-Induced Acute Pancreatitis in a Child A Case Report and Brief Review of the Literature PANCREAS Zhang, K., Cox, K. L., Sellers, Z. M. 2017; 46 (7): E58–E59

  View details for PubMedID 28697142