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James Ferrara

Publications and source records attributed to James Ferrara.

4 recordsLinked to original sources
PubMed2026

REG3α is a Predictive Biomarker of Complicated Disease from Preclinical through Established Crohn's Disease.

BACKGROUND: Regenerating islet-derived 3-alpha (REG3&#x3b1;) is a serum biomarker in patients with graft-versus-host disease (GVHD) linked to 6-month mortality. REG3&#x3b1; is produced by intestinal Paneth cells, which are implicated in Crohn's disease (CD) pathophysiology. OBJECTIVE: To assess associations between serum REG3&#x3b1; and progressive CD DESIGN: Serum REG3&#x3b1; was measured in two cross-sectional (M: Mount Sinai, L: Leuven) and a pre-diagnostic cohort (P: PREDICTS) with serial samples up to 10 years before CD diagnosis. Tissue REG3&#x3b1; expression was assessed via bulk RNA sequencing from paired ileal and colonic biopsies. Serum REG3&#x3b1; and tissue REG3&#x3b1; were associated with CD progression (hospitalization, surgery, steroid course, or new advanced therapy). Single-cell RNA sequencing data explored associations between REG3&#x3b1; expression, Paneth cell phenotypes, and CD. RESULTS: In 394 patients, high serum REG3&#x3b1; associated with CD progression, independent of C-reactive protein and endoscopic activity (M: HR 1.9 (95%CI 1.3-2.8); L: HR 2.9 (95%CI 1.9-4.6), both p<0.001). The association persisted in patients with mild or inactive CD. In the pre-diagnostic cohort, high serum REG3&#x3b1; predicted the development of CD, particularly complicated (B2/3) and surgical presentations, up to 10 years before diagnosis (P). Analysis of REG3&#x3b1; expression and Paneth cell transcriptomes suggested that CD is associated with loss of regenerative Paneth cell populations and enrichment in REG3&#x3b1;-expressing populations, suggesting a mechanism through which changes in serum REG3&#x3b1; associate with complicated CD. CONCLUSION: Serum REG3&#x3b1; holds potential as a non-invasive, prognostic biomarker in CD, independent of disease activity. High serum REG3&#x3b1;, even years before diagnosis, is linked to a complicated disease course.

Crohn&#x2019;s Disease↗
PubMed2006

Toward biomarkers for chronic graft-versus-host disease: National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: III. Biomarker Working Group Report.

Biology-based markers that can be used to confirm the diagnosis of chronic graft-versus-host disease (GVHD) or monitor progression of the disease could help in the evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biologic or pathogenic process, a pharmacologic response to a therapeutic intervention, or a surrogate end point intended to substitute for a clinical end point. The following applications of biomarkers could be useful in chronic GVHD clinical trials or management: (1) predicting response to therapy; (2) measuring disease activity and distinguishing irreversible damage from continued disease activity; (3) predicting the risk of developing chronic GVHD; (4) diagnosing chronic GVHD: (5) predicting the prognosis of chronic GVHD; (6) evaluating the balance between GVHD and graft-versus-leukemia effects (graft-versus-leukemia or GVT); and (7) serving as a surrogate end point for therapeutic response. Such biomarkers can be identified by either hypothesis-driven testing or by high-throughput discovery-based methods. To date, no validated biomarkers have been established for chronic GVHD, although several candidate biomarkers have been identified from limited hypothesis-driven studies. Both approaches have merit and should be pursued. The consistent treatment and standardized documentation needed to support biomarker studies are most likely to be satisfied in prospective clinical trials.

Biomarkers↗
PubMed2005

Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation.

The syndrome of microangiopathic hemolysis associated with renal failure, neurologic impairment, or both is a recognized complication of hematopoietic stem cell transplantation. This entity is often called hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP), yet it is clear that the pathophysiology of transplant-associated HUS/TTP is different from that of classic HUS or TTP. Furthermore, the incidence of this syndrome varies from 0.5% to 76% in different transplant series, primarily because of the lack of a uniform definition. The toxicity committee of the Blood and Marrow Transplant Clinical Trials Network has reviewed the current literature on transplant-related HUS/TTP and recommends that it be henceforth renamed posttransplantation thrombotic microangiopathy (TMA). An operational definition for TMA based on the presence of microangiopathic hemolysis and renal and/or neurologic dysfunction is proposed. The primary intervention after diagnosis of TMA should be withdrawal of calcineurin inhibitors. Plasma exchange, although frequently used in this condition, has not been proven to be effective. In the absence of definitive trials, plasma exchange cannot be considered a standard of care for TMA. It is hoped that these positions will improve the identification and reporting of this devastating complication after hematopoietic stem cell transplantation and facilitate future clinical studies for its prevention and treatment.

Clinical Trials as Topic↗