Jeffrey Yu

All Publications

• Case Report: Life-threatening Kasabach-Merritt phenomenon in a 2-month-old child. Frontiers in pediatrics Wong Grossman, A. V., Forero, J. P., Yu, J. S., Gilbert, M. M., Anand, K. J. 2025; 13: 1690450

  Abstract

  We present a rare case of a 2-month-old girl, born at term, who was admitted to the pediatric intensive care unit for fussiness, increasing abdominal distension, and intermittent diarrhea for one week. She was found to be hypertensive, coagulopathic, and suffering from unrelenting ascites. Over the course of the following month, her symptoms became life-threatening, and she was intubated, sedated, and paralyzed. She underwent multiple diagnostic and therapeutic procedures, including exploratory laparotomy, MRI, colonoscopy, and multiple peritoneal drains. After several weeks, the medical teams reached a consensus diagnosis of a rare and complex vascular anomaly characterized by a life-threatening Kasabach-Merritt Phenomenon (KMP). KMP is known to occur in association with several anomalies, including kaposiform hemangioendothelioma and kaposiform lymphangiomatosis. Life-saving therapies were initiated, including methylprednisolone and sirolimus. The patient was ultimately discharged and sent home with her parents. To our knowledge, this is the only reported case describing this constellation of symptoms in a critically ill infant. Multidisciplinary cooperation was key in saving the patient's life. Critical care providers should consider vascular anomalies in patients with similar presentations.

  View details for DOI 10.3389/fped.2025.1690450

  View details for PubMedID 41244261

  View details for PubMedCentralID PMC12615453

• Methadone-based Multimodal Analgesia Provides the Best-in-class Acute Surgical Pain Control and Functional Outcomes With Lower Opioid Use Following Major Posterior Fusion Surgery in Adolescents With Idiopathic Scoliosis PEDIATRIC QUALITY & SAFETY Ye, J., Myung, K., Packiasabapathy, S., Yu, J. S., Jacobson, J. E., Whittaker, S. C., Castelluccio, P., Jackson, M., Sadhasivam, S. 2020; 5 (4): e336

  Abstract

  Posterior spinal fusion for idiopathic scoliosis is extremely painful, with no superior single analgesic modality. We introduced a methadone-based multimodal analgesia protocol, aiming to decrease the length of hospital stay (LOS), improve pain control, and decrease the need for additional opioids.We analyzed 122 idiopathic scoliosis patients with posterior instrumented spinal fusion. They were matched by age, sex, surgeon, and the number of levels fused before and after the implementation of the new protocol. This analysis included 61 controls (intrathecal morphine, gabapentin, intravenous opioids, and adjuncts) and 61 patients on the new protocol (scheduled methadone, methocarbamol, ketorolac/ibuprofen, acetaminophen, and oxycodone with intravenous opioids as needed). The primary outcome was LOS. Secondary outcomes included pain scores, total opioid use (morphine milligram equivalents), time to a first bowel movement, and postdischarge phone calls.New protocol patients were discharged earlier (median LOS, 2 days) compared with control patients (3 days; P < 0.001). Total inpatient morphine consumption was lower in the protocol group (P < 0.001). Pain scores were higher in the protocol group on the day of surgery, similar on postoperative day (POD) 1, and lower by POD 2 (P = 0.01). The new protocol also reduced the median time to first bowel movement (P < 0.001), and the number of postdischarge pain-related phone calls (P < 0.006).Methadone-based multimodal analgesia resulted in significantly lower LOS compared with the conventional regimen. It also provided improved pain control, reduced total opioid consumption, and early bowel movement compared with the control group.

  View details for DOI 10.1097/pq9.0000000000000336

  View details for Web of Science ID 000714176300018

  View details for PubMedID 32766507

  View details for PubMedCentralID PMC7392616

• Adjuvant lidocaine to a propofol-ketamine-based sedation regimen for bone marrow aspirates and biopsy in the pediatric population EUROPEAN JOURNAL OF PEDIATRICS Yu, J. S., Louer, R., Lutfi, R., Abu-Sultaneh, S., Yabrodi, M., Zee-Cheng, J., Abulebda, K. 2021; 180 (1): 73-80

  Abstract

  Pediatric patients with hematological malignancies repeatedly undergo painful bone marrow aspirates and biopsies (BMABs) in routine care. No standard sedation regimen has been established. This study evaluated the addition of injected local lidocaine to a propofol-ketamine sedation for BMAB and its effects on propofol dosing, safety, and efficacy. A retrospective analysis of children undergoing BMAB with propofol-ketamine with (PK+L) and without (PK-only) the injection of local lidocaine. Patients were matched through propensity probability scores. To measure efficacy, dosing, procedure length, and recovery time were evaluated. To assess safety, adverse and serious events were recorded. As an indirect measurement of analgesia, changes in heart rate and blood pressure were analyzed. Of the 420 encounters included, 188 matched pairs (376 patients) were analyzed. Patient demographics were comparable. The median dose of propofol was not significantly different between both groups. The incidence of adverse events was similar. There were no significant differences in the changes in heart rate and blood pressure with sedation between groups.Conclusion: This study suggests that the addition of local lidocaine injection to a propofol-ketamine sedation for BMAB pediatric patients does not affect the propofol dose, safety, or efficacy properties of the regimen. What is Known: •Although propofol is commonly used, there is no standard sedation regimen for pediatric patients undergoing bone marrow aspiration and biopsy. •Local lidocaine is used in analgesia in the adults undergoing the same procedure. What is New: •Local lidocaine adjuvant to propofol-ketamine sedation does not affect propofol dosing, the safety of efficacy properties of the regimen in the pediatric population.

  View details for DOI 10.1007/s00431-020-03713-5

  View details for Web of Science ID 000541092400001

  View details for PubMedID 32556505

  View details for PubMedCentralID 6287759

• Diagnostic and Prognostic Plasma Biomarkers for Idiopathic Pneumonia Syndrome after Hematopoietic Cell Transplantation BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Seo, S., Yu, J., Jenkins, I. C., Leisenring, W. M., Steven-Ayers, T., Kuypers, J. M., Huang, M., Jerome, K. R., Boeckh, M., Paczesny, S. 2018; 24 (4): 678-686

  Abstract

  Idiopathic pneumonia syndrome (IPS) is a noninfectious pulmonary complication after hematopoietic cell transplantation (HCT) and is difficult to diagnose. In 41 patients with IPS, we evaluated 6 candidate proteins in plasma samples at day 7 post-HCT and at onset of IPS to identify potential diagnostic or prognostic biomarkers for IPS. Samples at similar times from 162 HCT recipients without documented infections and 37 HCT recipients with respiratory viral pneumonia served as controls. In multivariable models, a combination of Stimulation-2 (ST2; odds ratio [OR], 2.8; P < .001) and IL-6 (OR, 1.4; P = .025) was the best panel for distinguishing IPS at diagnosis from unaffected controls, whereas tumor necrosis factor receptor 1 (TNFR1; OR, 2.9; P = .002) was the best marker when comparing patients with IPS and viral pneumonia. The areas under the curve of the receiver operating characteristic (ROC) curves for discriminating between IPS and unaffected controls at day 7 post-HCT were .8 for ST2, .75 for IL-6, and .68 for TNFR1. Using estimated sensitivity and specificity values from cutoffs determined with the ROC analysis (cutoff level: ST2, 21 ng/mL; IL-6, 61 pg/mL; TNFR1, 3421 pg/mL), we calculated positive predictive values (PPV) for a range of estimated population prevalence values of IPS. Among the 3 markers, ST2 showed the highest PPV for IPS occurrence. Based on an assumed prevalence of 8%, a positive ST2 test increased likelihood of IPS to 50%. We conclude that a prospective validation study is warranted to determine whether a plasma biomarker panel can aid the noninvasive diagnosis and prognosis of IPS.

  View details for DOI 10.1016/j.bbmt.2017.11.039

  View details for Web of Science ID 000430640800007

  View details for PubMedID 29223372

  View details for PubMedCentralID PMC5902640

• Plasma biomarkers of risk for death in a multicenter phase 3 trial with uniform transplant characteristics post-allogeneic HCT BLOOD Abu Zaid, M., Wu, J., Wu, C., Logan, B. R., Yu, J., Cutler, C., Antin, J. H., Paczesny, S., Choi, S. 2017; 129 (2): 162-170

  Abstract

  A phase 3 clinical trial (BMT CTN 0402) comparing tacrolimus/sirolimus (Tac/Sir) vs tacrolimus/methotrexate (Tac/Mtx) as graft-versus-host disease (GVHD) prophylaxis after matched-related allogeneic hematopoietic cell transplantation (HCT) recently showed no difference between study arms in acute GVHD-free survival. Within this setting of a prospective, multicenter study with uniform GVHD prophylaxis, conditioning regimen, and donor source, we explored the correlation of 10 previously identified biomarkers with clinical outcomes after allogeneic HCT. We measured biomarkers from plasma samples collected in 211 patients using enzyme-linked immunosorbent assay (Tac/Sir = 104, Tac/Mtx = 107). High suppression of tumorigenicity-2 (ST2) and T-cell immunoglobulin mucin-3 (TIM3) at day 28 correlated with 2-year nonrelapse mortality in multivariate analysis (P = .0050, P = .0075, respectively) and in a proportional hazards model with time-dependent covariates (adjusted hazard ratio: 2.43 [1.49-3.95], P = .0038 and 4.87 [2.53-9.34], P < .0001, respectively). High ST2 and TIM3 correlated with overall survival. Chemokine (C-X-C motif) ligand 9 (CXCL9) levels above the median were associated with chronic GVHD compared with levels below the median in a time-dependent proportional hazard analysis (P = .0069). Low L-Ficolin was associated with hepatic veno-occlusive disease (P = .0053, AUC = 0.80). We confirmed the correlation of plasma-derived proteins, previously assessed in single-center cohorts, with clinical outcomes after allogeneic HCT within this prospective, multicenter study.

  View details for DOI 10.1182/blood-2016-08-735324

  View details for Web of Science ID 000396528200012

  View details for PubMedID 27827824

  View details for PubMedCentralID PMC5234220

• Proteomic Characterization Reveals That MMP-3 Correlates With Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Cell and Lung Transplantation AMERICAN JOURNAL OF TRANSPLANTATION Liu, X., Yue, Z., Yu, J., Daguindau, E., Kushekhar, K., Zhang, Q., Ogata, Y., Gafken, P. R., Inamoto, Y., Gracon, A., Wilkes, D. S., Hansen, J. A., Lee, S. J., Chen, J. Y., Paczesny, S. 2016; 16 (8): 2342–51

  Abstract

  Improved diagnostic methods are needed for bronchiolitis obliterans syndrome (BOS), a serious complication after allogeneic hematopoietic cell transplantation (HCT) and lung transplantation. For protein candidate discovery, we compared plasma pools from HCT transplantation recipients with BOS at onset (n = 12), pulmonary infection (n = 16), chronic graft-versus-host disease without pulmonary involvement (n = 15) and no chronic complications after HCT (n = 15). Pools were labeled with different tags (isobaric tags for relative and absolute quantification), and two software tools identified differentially expressed proteins (≥1.5-fold change). Candidate proteins were further selected using a six-step computational biology approach. The diagnostic value of the lead candidate, matrix metalloproteinase 3 (MMP3), was evaluated by enzyme-linked immunosorbent assay in plasma of a verification cohort (n = 112) with and without BOS following HCT (n = 76) or lung transplantation (n = 36). MMP3 plasma concentrations differed significantly between patients with and without BOS (area under the receiver operating characteristic curve 0.77). Consequently, MMP3 represents a potential noninvasive blood test for diagnosis of BOS.

  View details for DOI 10.1111/ajt.13750

  View details for Web of Science ID 000380026900015

  View details for PubMedID 26887344

  View details for PubMedCentralID PMC4956556

• Biomarker Panel for Chronic Graft-Versus-Host Disease JOURNAL OF CLINICAL ONCOLOGY Yu, J., Storer, B. E., Kushekhar, K., Abu Zaid, M., Zhang, Q., Gafken, P. R., Ogata, Y., Martin, P. J., Flowers, M. E., Hansen, J. A., Arora, M., Cutler, C., Jagasia, M., Pidala, J., Hamilton, B. K., Chen, G. L., Pusic, I., Lee, S. J., Paczesny, S. 2016; 34 (22): 2583-U57

  Abstract

  To identify diagnostic and prognostic markers of chronic graft-versus-host disease (cGVHD), the major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT).Using a quantitative proteomics approach, we compared pooled plasma samples obtained at matched time points after HCT (median, 103 days) from 35 patients with cGVHD and 18 without cGVHD (data are available via ProteomeXchange with identifier PXD002762). Of 105 proteins showing at least a 1.25-fold difference in expression, 22 were selected on the basis of involvement in relevant pathways and enzyme-linked immunosorbent assay availability. Chemokine (C-X-C motif) ligand 9 (CXCL9) and suppression of tumorigenicity 2 (ST2) also were measured on the basis of previously determined associations with GVHD. Concentrations of the four lead biomarkers were measured at or after diagnosis in plasma from two independent verification cohorts (n = 391) to determine their association with cGVHD. Their prognostic ability when measured at approximately day +100 after HCT was evaluated in plasma of a second verification cohort (n = 172).Of 24 proteins measured in the first verification cohort, nine proteins were associated with cGVHD, and only four (ST2, CXCL9, matrix metalloproteinase 3, and osteopontin) were necessary to compose a four-biomarker panel with an area under the receiver operating characteristic curve (AUC) of 0.89 and significant correlation with cGVHD diagnosis, cGVHD severity, and nonrelapse mortality. In a second verification cohort, this panel distinguished patients with cGVHD (AUC, 0.75), and finally, the panel measured at day +100 could predict cGVHD occurring within the next 3 months with an AUC of 0.67 and 0.79 without and with known clinical risk factors, respectively.We conclude that the biomarker panel measured at diagnosis or day +100 after HCT may allow patient stratification according to risk of cGVHD.

  View details for DOI 10.1200/JCO.2015.65.9615

  View details for Web of Science ID 000382465300006

  View details for PubMedID 27217465

  View details for PubMedCentralID PMC5012688

• Biomarkers for Idiopathic Pneumonia Syndrome (IPS) after Hematopoietic Cell Transplantation (HCT): Comparison with Viral Infectious Pneumonia Seo, S., Yu, J., Jenkins, I. C., Stevens-Ayers, T. L., Kuypers, J. M., Huang, M., Leisenring, W. M., Jerome, K. R., Boeckh, M. J., Paczesny, S. ELSEVIER SCIENCE INC. 2016: S73-S74

  View details for DOI 10.1016/j.bbmt.2015.11.366

  View details for Web of Science ID 000370910300078

• Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Akil, A., Zhang, Q., Mumaw, C. L., Raiker, N., Yu, J., de Mendizabal, N., Haneline, L. S., Robertson, K. A., Skiles, J., Diaz-Ricart, M., Carreras, E., Renbarger, J., Hanash, S., Bies, R. R., Paczesny, S. 2015; 21 (10): 1739-1745

  Abstract

  Reliable, noninvasive methods for diagnosing and prognosing sinusoidal obstruction syndrome (SOS) early after hematopoietic cell transplantation (HCT) are needed. We used a quantitative mass spectrometry-based proteomics approach to identify candidate biomarkers of SOS by comparing plasma pooled from 20 patients with and 20 patients without SOS. Of 494 proteins quantified, we selected 6 proteins (L-Ficolin, vascular cell adhesion molecule-1 [VCAM1], tissue inhibitor of metalloproteinase-1, von Willebrand factor, intercellular adhesion molecule-1, and CD97) based on a differential heavy/light isotope ratio of at least 2 fold, information from the literature, and immunoassay availability. Next, we evaluated the diagnostic potential of these 6 proteins and 5 selected from the literature (suppression of tumorigenicity-2 [ST2], angiopoietin-2 (ANG2), hyaluronic acid [HA], thrombomodulin, and plasminogen activator inhibitor-1) in samples from 80 patients. The results demonstrate that together ST2, ANG2, L-Ficolin, HA, and VCAM1 compose a biomarker panel for diagnosis of SOS. L-Ficolin, HA, and VCAM1 also stratified patients at risk for SOS as early as the day of HCT. Prognostic Bayesian modeling for SOS onset based on L-Ficolin, HA, and VCAM1 levels on the day of HCT and clinical characteristics showed >80% correct prognosis of SOS onset. These biomarkers may provide opportunities for preemptive intervention to minimize SOS incidence and/or severity.

  View details for DOI 10.1016/j.bbmt.2015.07.004

  View details for Web of Science ID 000361781100008

  View details for PubMedID 26172478

  View details for PubMedCentralID PMC4568166