Publications by authors named "Aaron R Mangold"
Background: Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of interferon gamma (IFN)-γ, a cytokine implicated in the pathogenesis of LP.
Methods: In this phase II trial, twelve patients with cutaneous LP received baricitinib 2 mg daily for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre- and post-treatment samples.
Background: Combination immune checkpoint blockade targeting PD-1 and CTLA-4 leads to high response rates and improved survival in advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM).
Objectives: To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a real-world, diverse population of ALM.
Article Synopsis
- Drug repurposing offers a cost-effective strategy for developing therapies for rare diseases, which often face challenges in traditional drug development.
- This study used a new drug identification and repurposing pipeline to discover molecular drivers and potential therapies for psoriasis, leading to the identification of both known and novel disease mechanisms.
- The approach was further applied to necrobiosis lipoidica, revealing important disease drivers and potential treatments, demonstrating a high success rate in matching drugs to identified molecular targets.
Article Synopsis
- The study compares the effectiveness of home-based vs. office-based phototherapy for psoriasis, highlighting that while office therapy is cost-effective, it’s often hard to access compared to the more patient-preferred home therapy, which lacks sufficient clinical data, especially for those with darker skin.
- Conducted across 42 dermatology practices in the US, the trial involved 783 participants aged 12 and older with psoriasis, who were randomly assigned to either home or office phototherapy for 12 weeks, followed by another 12 weeks of observation.
- Results showed that home phototherapy led to better skin clearance and quality of life improvements, with 32.8% of participants achieving clear skin compared to
Purpose: Low-dose total skin electron beam therapy (TSEBT) is a proven treatment for managing cutaneous T-cell lymphoma (CTCL) and Sezary syndrome with skin burden. We performed a retrospective comparison of response rates and time to progression for patients receiving low-dose TSEBT based on dose per fractionation, total dose, and stage.
Methods And Materials: One hundred and ten patients with CTCL and Sezary syndrome were treated with 135 courses of low-dose (400-1500 cGy) TSEBT or subtotal skin electron therapy at multiple centers of a single institution between August 2003 and June 2023.
Article Synopsis
- Total skin electron beam therapy (TSEBT) is a common treatment for cutaneous T-cell lymphoma (CTCL) but can cause unnecessary side effects; a new method called subtotal skin electron beam therapy (STSEBT) uses a shield to protect healthy skin.
- A study reviewed 32 CTCL patients, with 7 receiving STSEBT and 25 receiving TSEBT, showing a median response rate of 96% and comparable effectiveness between the two methods after a follow-up of about 465 days.
- The findings suggest that STSEBT offers similar treatment benefits while potentially reducing toxicity for CTCL patients with less severe disease compared to traditional TSEBT.
Article Synopsis
- Bullous pemphigoid (BP) is a rare autoimmune skin disease causing significant suffering and reduced quality of life, currently managed with corticosteroids and immunosuppressants that have unwanted side effects.
- A clinical trial named LIBERTY-BP ADEPT is underway to investigate the effectiveness and safety of dupilumab, a drug that targets type 2 inflammation, in treating adults with moderate-to-severe BP.
- The trial includes a 52-week treatment period for 98 adults, focusing on achieving steroid-free remission and other key outcomes such as itch reduction and disease severity over time.
Article Synopsis
- The COVID-19 pandemic accelerated the adoption of telemedicine in dermatology, prompting an analysis of its effectiveness within the Mayo Clinic system from January 2020 to January 2021.
- A total of 13,181 televisits were conducted with an average patient age of 34.1 years, and most appointments utilized live video conferencing, though about 30% concluded with a single visit.
- Results indicated that older patients were more likely to need follow-ups after initial visits, particularly with asynchronous methods, suggesting that live video might be more efficient for some patient encounters.
Challenges in identifying tumor-rejecting neoantigens limit the efficacy of neoantigen vaccines to treat cancers, including cutaneous squamous cell carcinoma (cSCC). A minority of human cSCC tumors shared neoantigens, supporting the need for personalized vaccines. Using a UV-induced mouse cSCC model which recapitulated the mutational signature and driver mutations found in human disease, we found that CD8 T cells constrain cSCC.
View Article and Find Full Text PDFPatching whole slide images (WSIs) is an important task in computational pathology. While most of them are designed to classify or detect the presence of pathological lesions in a WSI, the confounding role and redundant nature of normal histology are generally overlooked. In this paper, we propose and validate the concept of an "atlas of normal tissue" solely using samples of WSIs obtained from normal biopsies.
View Article and Find Full Text PDFBACKGROUND: Hidradenitis suppurativa (HS) is a debilitating, inflammatory skin disease with limited treatment options and partially understood pathophysiology. Using an umbrella trial design, three kinase inhibitor immunomodulators with different mechanisms of action were evaluated. METHODS: This phase 2a, double-blind, parallel-group trial enrolled adults with moderate to severe HS who were then randomly assigned (1:1:1:1) to once-daily brepocitinib 45 mg (a JAK1/TYK2 inhibitor), zimlovisertib 400 mg (an IRAK4 inhibitor), ropsacitinib 400 mg (a TYK2 inhibitor), or matching placebo for 16 weeks.
View Article and Find Full Text PDFBackground: Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of interferon (IFN)-γ, a cytokine implicated in the pathogenesis of LP.
Methods: In this phase II trial, twelve patients with cutaneous LP received baricitinib 2 mg daily for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre-and post-treatment samples.
Background: Immunotherapies have changed the landscape of late-stage melanoma; however, data evaluating timely access to immunotherapy are lacking.
Methods: A retrospective cohort study utilizing the National Cancer Database was conducted. Stage III and IV melanoma cases diagnosed between 2011 and 2018 that received systemic treatment with either immunotherapy or chemotherapy were included.
Article Synopsis
- Necrobiosis lipoidica (NL) is a rare skin condition characterized by collagen degeneration, and existing treatment options have been poorly researched, highlighting the need for better understanding and options.
- This review looks at various treatment approaches for NL, including phototherapy, topical corticosteroids, and newer treatments like JAK inhibitors, based on a literature search from 2016 to 2022 that analyzed 60 articles involving 274 patients.
- The findings suggest that photodynamic therapy showed the most significant improvement in patients, but due to the limited quality of evidence, more rigorous randomized controlled trials are needed for a clearer understanding of treatment effectiveness.
Article Synopsis
- Patients can be sensitized to multiple allergens simultaneously, making it important to identify these "copositivity groups" for better contact avoidance.
- A study analyzed data from 5943 patients at the Mayo Clinic to determine copositivity rates among 80 allergens, using hierarchical clustering to reveal distinct groups.
- Results showed that many identified copositivity groups matched previous findings, while new associations were also discovered, enhancing understanding of how different allergens may relate to each other.
Article Synopsis
- Subtotal skin electron beam therapy can help patients with cutaneous lymphoma by focusing radiation on large skin areas while protecting others that have had prior treatment or are cosmetically sensitive.* -
- A customizable shield was developed using acrylic blocks mounted on a steel frame to tailor the treatment and was tested for its effectiveness in shielding patients during therapy.* -
- The shield proved to be user-friendly and effective, reducing electron transmission and maintaining safety without increasing x-ray exposure, making it suitable for personalized treatment in over 30 patients.*