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Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotyping.
Sci Rep
January 2025
Department of Dermatology, University of Maryland School of Medicine, 419 West Redwood Street, Suite 235, Baltimore, MD, 21201, USA.
Erythroderma is a severe and heterogeneous inflammatory skin condition with little guidance on the approach to management in cases of unknown etiology. To guide therapeutic selection, we sought to create an immunophenotyping platform able to identify aberrant cell populations and cytokines in subtypes of erythroderma. We performed high-parameter flow cytometry on peripheral blood mononuclear cells (PBMCs) and whole blood of a patient with refractory idiopathic erythroderma, erythrodermic patients with Sézary syndrome and pityriasis rubra pilaris, and healthy controls.
View Article and Find Full Text PDFEnabling next-generation engineered TCR-T therapies based on high-throughput TCR discovery from diagnostic tumor biopsies.
Nat Commun
January 2025
Neogene Therapeutics, A member of the AstraZeneca Group, Amsterdam, The Netherlands.
Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate tumor regression, including complete and durable responses, in a range of solid cancers, most notably in melanoma. However, its wider application and efficacy has been restricted by the limited accessibility, proliferative capacity and effector function of tumor-specific TIL. Here, we develop a platform for the efficient identification of tumor-specific TCR genes from diagnostic tumor biopsies, including core-needle biopsies frozen in a non-viable format, to enable engineered T cell therapy.
View Article and Find Full Text PDFRefractory pyoderma gangrenosum-like ulcerations in granulomatosis with polyangiitis treated successfully with rituximab.
BMJ Case Rep
January 2025
Dermatology, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
Granulomatosis with polyangiitis (GPA) is a small-to-medium vessel vasculitis that can affect the skin, respiratory tract, kidneys and other organs. A rare cutaneous manifestation of GPA is pyoderma gangrenosum (PG)-like ulcerations, which can have debilitating and disfiguring consequences. We report the case of a man in his 40s with refractory PG-like ulcerations secondary to GPA, not responsive to conventional immunosuppression, who was successfully treated with rituximab.
View Article and Find Full Text PDFModeling, synthesis and cell-based evaluation of pyridine-substituted analogs of CD3254 and fluorinated analogs of CBt-PMN as novel therapeutics.
Bioorg Med Chem
January 2025
School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, 4701 W. Thunderbird Road, Glendale, AZ 85308, USA. Electronic address:
Six pyridine analogs of (E)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)-4-hydroxyphenyl)acrylic acid-or CD3254 (11)-in addition to two novel analogs of 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-benzo[d][1,2,3]triazole-5-carboxylic acid (CBt-PMN or 23) were prepared and evaluated for selective retinoid-X-receptor (RXR) agonism alongside bexarotene (1), an FDA-approved drug for cutaneous T-cell lymphoma (CTCL). Treatment with 1 often elicits side-effects by disrupting or provoking other RXR-dependent nuclear receptors and cellular pathways. All analogs were assessed through modeling for their ability to bind RXR and then evaluated in human colon and kidney cells employing an RXR-RXR mammalian-2-hybrid (M2H) system and in an RXRE-controlled transcriptional assay.
View Article and Find Full Text PDFThe Topographic Map of the Midfoot: Implication for Improving Safety of Dorsal Approach of Midfoot Surgeries.
J Am Acad Orthop Surg Glob Res Rev
January 2025
From the Department of Anatomy, School of Medicine, Marmara University, Basibuyuk Yolu, Maltepe, Istanbul, Turkey (Dr. Ismailoglu, Dr. Sehirli, and Dr. Ayingen); the Department of Anatomy, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, Turkey (Dr. Bayramoglu and Dr. Savasan); and the Department of Orthopedic Surgery, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, Turkey (Dr. Kocaoglu).
Purpose: The surgical approach for midfoot injuries classically requires dual dorsal incision and identification of the neurovascular structures that are susceptible to injury during the surgery. The aim of this study was to map the topographic anatomy of the dorsum of the foot along with tarsal joints for the dorsal approach of midfoot surgery that would facilitate the surgery and minimize the risk of neurovascular injuries for surgeons who specially focus on foot and ankle injuries.
Methods: The dorsum of the foot was evaluated in 12 feet injected with latex containing a red colorant to visualize the arterial vessels.
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