Browsing by Author "Martin, Paul J."

Now showing 1 - 7 of 7
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    Association of Plasma CD163 Concentration with De Novo–Onset Chronic Graft-versus-Host Disease
    (Elsevier, 2017) Inamoto, Yoshihiro; Martin, Paul J.; Paczesny, Sophie; Tabellini, Laura; Momin, Amin A.; Mumaw, Christen L.; Flowers, Mary E. D.; Lee, Stephanie J.; Carpenter, Paul A.; Storer, Barry E.; Hanash, Samir; Hansen, John A.; Department of Pediatrics, IU School of Medicine
    Chronic graft-versus-host disease (GVHD) is the leading cause of long-term morbidity and mortality after allogeneic hematopoietic cell transplantation. To identify prognostic plasma proteins associated with de novo– or quiescent-onset chronic GVHD (cGVHD), we performed a discovery and validation proteomic study. The total study cohort included 167 consecutive patients who had no clinical evidence of GVHD under minimum glucocorticoid administration and had available plasma samples obtained at 80 ± 14 days after transplantation. We first used high-throughput mass spectrometry to screen pooled plasma using 20 cases with subsequent cGVHD and 20 controls without it, and we identified 20 candidate proteins. We then measured 12 of the 20 candidate proteins by ELISA on the same individual samples and identified 4 proteins for further verification (LGALS3BP, CD5L, CD163, and TXN for de novo onset, and LGALS3BP and CD5L for quiescent onset). The verification cohort included 127 remaining patients. The cumulative incidence of de novo–onset cGVHD was higher in patients with higher plasma soluble CD163 concentrations at day 80 than those with lower concentrations (75% versus 40%, P = .018). The cumulative incidence of de novo– or quiescent-onset cGVHD did not differ statistically according to concentrations of the 3 other proteins at day 80. CD163 is a macrophage scavenger receptor and is elevated in oxidative conditions. These results suggest that monocyte or macrophage activation or increased oxidative stress may contribute to the pathogenesis of cGVHD.
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    The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease
    (Elsevier, 2017-02) Cooke, Kenneth R.; Luznik, Leo; Sarantopoulos, Stefanie; Hakim, Frances T.; Jagasia, Madan; Fowler, Daniel H.; van den Brink, Marcel R. M.; Hansen, John A.; Parkman, Robertson; Miklos, David B.; Martin, Paul J.; Paczesny, Sophie; Vogelsang, Georgia; Pavletic, Steven; Ritz, Jerome; Schultz, Kirk R.; Blazar, Bruce R.; Department of Pediatrics, School of Medicine
    Chronic graft-versus-host disease (GVHD) is the leading cause of late, nonrelapse mortality and disability in allogeneic hematopoietic cell transplantation recipients and a major obstacle to improving outcomes. The biology of chronic GVHD remains enigmatic, but understanding the underpinnings of the immunologic mechanisms responsible for the initiation and progression of disease is fundamental to developing effective prevention and treatment strategies. The goals of this task force review are as follows: • Summarize the current state of the science regarding pathogenic mechanisms of chronic GVHD and critical knowledge gaps. • Develop working hypotheses/overriding concepts for chronic GVHD development. • Define the usefulness of current preclinical models to test working hypotheses and ultimately discover and develop new therapeutic strategies. • Identify shortcomings of preclinical models, and define criteria for the creation of additional models to address these limitations. This document is intended as a review of our understanding of chronic GVHD biology and therapies resulting from preclinical studies, and as a platform for developing innovative clinical strategies to prevent and treat chronic GVHD.
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    Biomarker Panel for Chronic Graft-Versus-Host Disease
    (American Society of Clinical Oncology, 2016-08-01) Yu, Jeffrey; Storer, Barry E.; Kushekhar, Kushi; Zaid, Mohammad Abu; Zhang, Qing; Gafken, Philip R.; Ogata, Yuko; Martin, Paul J.; Flowers, Mary E.; Hansen, John A.; Arora, Mukta; Cutler, Corey; Jagasia, Madan; Pidala, Joseph; Hamilton, Betty K.; Chen, George L.; Pusic, Iskra; Lee, Stephanie J.; Paczesny, Sophie; Medicine, School of Medicine
    PURPOSE: 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). PATIENTS AND METHODS: 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). RESULTS: 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. CONCLUSION: We conclude that the biomarker panel measured at diagnosis or day +100 after HCT may allow patient stratification according to risk of cGVHD.
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    Educating Radiologists for Self-governance
    (Elsevier, 2018-04) Gunderman, Richard B.; Martin, Paul J.; Radiology and Imaging Sciences, School of Medicine
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    The impact of members of the Society of University Surgeons on the scholarship of American surgery
    (Elsevier, 2016-07) Valsangkar, Nakul P.; Kays, Joshua K.; Feliciano, David V.; Martin, Paul J.; Parett, Jordan S.; Joshi, Mugdha M.; Zimmers, Teresa A.; Koniaris, Leonidas G.; Department of Surgery, IU School of Medicine
    Background A core objective of the Society of University Surgeons (SUS) is research focused: to “advance the art and science of surgery through original investigation.” This study sought to determine the current impact of the SUS on academic surgical productivity. Methods Individual faculty data for numbers of publications, citations, and National Institute of Health (NIH) funding history were collected for 4,015 surgical faculty at the top 55 NIH-funded departments of surgery using SCOPUS and the NIH Research Portfolio Online Reporting Tools. SUS membership was determined from membership registry data. Results Overall, 502 surgical faculty (12.5%) were SUS members with 92.7% holding positions of associate or full professor (versus 59% of nonmembers). Median publications (P) and citations (C) among SUS members were P: 112, C: 2,460 versus P: 29, C: 467 for nonmembers (P < .001). Academic productivity was considerably higher by rank for SUS members than for nonmembers: associate professors (P: 61 vs 36, C: 1,199 vs 591, P < .001) and full professors (P: 141 vs 81, C: 3,537 vs 1,856, P < .001). Among full professors, SUS members had much higher rates of NIH funding than did nonmembers (52.6% vs 26%, P < .05) and specifically for R01, P01, and U01 awards (37% vs 17.7%, P < .01). SUS members were 2 times more likely to serve in divisional leadership or chair positions (23.5% vs 10.2%, P < .05). Conclusion SUS society members are a highly productive academic group. These data support the premise that the SUS is meeting its research mission and identify its members as very academically productive contributors to research and scholarship in American surgery and medicine.
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    MR imaging findings in a neonate with COVID -19 associated encephalitis
    (Elsevier, 2021) Martin, Paul J.; Felker, Marcia; Radhakrishnan, Rupa; Radiology and Imaging Sciences, School of Medicine
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    Obligation for transparency regarding treating physician credentials at academic health centres
    (BMJ, 2018) Martin, Paul J.; Skill, N. James; Koniaris, Leoniadas G.; Surgery, School of Medicine
    Academic health centres have historically treated patients with the most complex of diseases, served as training grounds to teach the next generations of physicians and fostered an innovative environment for research and discovery. The physicians who hold faculty positions at these institutions have long understood how these key academic goals are critical to serve their patient community effectively. Recent healthcare reforms, however, have led many academic health centres to recruit physicians without these same academic expectations and to partner with non-faculty physicians at other health systems. There has been limited transparency in regard to the expertise among the physicians and the academic faculty within these larger entities. Such lack of transparency may lead to confusion among patients regarding the qualifications of who is actually treating them. This could threaten the ethical principles of patient autonomy, benevolence and non-maleficence as patients risk making uninformed decisions that might lead to poorer outcomes. Furthermore, this lack of transparency unjustly devalues the achievements of physician faculty members as well as potentially the university they represent. In this paper, it is suggested that academic health centres have an obligation to foster total transparency regarding what if any role a physician has at a university or medical school when university or other academic monikers are used at a hospital.