Publications by authors named "Satveer Mahil"

Article Synopsis
  • The study investigates the complex relationship between immune-mediated diseases (IMIDs), like psoriasis, and cardiovascular diseases (CVDs), such as coronary artery disease (CAD) and stroke, focusing on genetic factors.
  • It employs Mendelian randomization to analyze data from large genome-wide association studies (GWAS) to establish potential causative links between psoriasis and these cardiovascular conditions.
  • The analysis encompasses nearly 3.4 million individuals, providing insights into how genetic predictors of CAD and stroke may influence the risk of developing psoriasis and nine other IMIDs.
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The routine use of targeted systemic immunomodulatory therapies has transformed outcomes for people with severe psoriasis, with skin clearance (clinical remission) rates up to 60% at 1 year of biologic treatment. However, psoriasis may recur following drug withdrawal, and as a result, patients tend to continue receiving costly treatment indefinitely. Here, we review research into the "inflammatory memory" in resolved psoriasis skin and the potential mechanisms leading to psoriasis recurrence following drug withdrawal.

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Article Synopsis
  • More severe forms of atopic dermatitis and psoriasis significantly impact quality of life, lead to higher healthcare costs, and are linked to other health issues; addressing these problems early can help lessen the burden.
  • The BIOMAP consortium is a large-scale research initiative that compiles clinical and molecular data from various studies to improve the understanding of disease severity and identify reliable biomarkers.
  • The consortium emphasizes the importance of using consistent definitions for disease severity and considers various factors when analyzing data to ensure that findings are relevant to both patients and healthcare practitioners.
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Background: Biologic therapies have led to increasing numbers of patients with psoriasis who have clear or nearly clear skin. It is current practice to continue biologic therapy indefinitely in these patients, which contributes to a substantial long-term drug and healthcare burden. 'As needed' biologic therapy in psoriasis may address this; however, our understanding of patient and clinician perceptions of this strategy is limited.

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Biologic therapies targeting the IL-23/IL-17 axis have transformed the treatment of psoriasis. However, the early mechanisms of action of these drugs remain poorly understood. Here, we perform longitudinal single-cell RNA-sequencing in affected individuals receiving IL-23 inhibitor therapy.

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Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci.

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Article Synopsis
  • Skin diseases affect a lot of people, about one-third of everyone in the world, and can be hard to manage in healthcare.
  • Deep learning technology can help doctors by analyzing skin images to find and diagnose various skin conditions, but most studies focus mainly on skin cancer rather than the many other skin issues.
  • Although deep learning shows promise in accurately identifying common skin diseases like acne and eczema, many studies have flaws and more research is needed to make it truly helpful in real-life situations.
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Recent advances in atopic dermatitis (AD) present the condition as a heterogeneous disease of distinct endotypes across ethnic groups. AD in people with skin of colour may appear psoriasiform, lichenoid, scaly or papular, with a violaceous colour and there is a higher prevalence of post-inflammatory dyspigmentation compared with affected individuals of White ethnicity. These differences in clinical presentation may limit the use of AD assessment tools in people with skin of colour, leading to the potential for misdiagnosis and underestimation of severity, particularly in relation to assessment of erythema.

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Atopic dermatitis (AD) is a global condition that has a rising prevalence in developing countries such as those within South-east Asia and Latin America. Recent research represents the condition as a heterogeneous disease of distinct endotypes among different ethnic groups. Variation between ethnic groups in physiological measures such as transepidermal water loss, ceramide/+, skin sensitivity, alongside pathological barrier and immune system dysfunction processes, may ultimately lead to the distinct phenotypes seen clinically.

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Article Synopsis
  • Adalimumab therapeutic drug monitoring (TDM) was successfully integrated into a national psoriasis service, aiming to improve treatment responses by evaluating serum drug concentrations.
  • Out of 229 patients, 74% received TDM, with significant clinical improvement noted in nonresponders who adjusted their medication based on TDM results.
  • The study highlights that tailored implementation strategies and regular assessments can help translate biomarker research into practical applications in patient care.
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Article Synopsis
  • Targeted biologic therapies, such as adalimumab, can provoke the creation of antidrug antibodies (ADA), leading to treatment failures in immune-mediated diseases.
  • This study focused on identifying genetic variations that make certain patients more likely to develop ADA against adalimumab, particularly in psoriasis patients on their first treatment course.
  • The researchers found specific genetic markers in the major histocompatibility complex (MHC) that correlate with resistance to ADA development, suggesting that these markers play a key role in the effectiveness of biologic therapies.
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Objectives: To investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).

Methods: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death.

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Background: Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic.

Objectives: To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence.

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Purpose Of Review: SARS-CoV-2 has had a devastating global effect, with vaccinations being paramount in the public health strategy against COVID-19. Vaccinations have uncoupled infection from adverse COVID-19 outcomes worldwide. While immune-modifying therapies are effective for the management of skin diseases such as psoriasis and atopic dermatitis, these medications also impair protective immune responses.

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Background: Responses to the systemic treatments commonly used to treat psoriasis vary. Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost-effective healthcare.

Objectives: To perform a scoping review to identify and catalogue candidate biomarkers of systemic treatment response in psoriasis for the translational research community.

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Background: Palmoplantar pustulosis (PPP) is a severe inflammatory skin disorder characterized by eruptions of painful, neutrophil-filled pustules on the palms and soles. Although PPP has a profound effect on quality of life, it remains poorly understood and notoriously difficult to treat.

Objective: We sought to investigate the immune pathways that underlie the pathogenesis of PPP.

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Background: Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice.

Objectives: To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community.

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Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide.

Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics.

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Background: COVID-19 vaccines have robust immunogenicity in the general population. However, data for individuals with immune-mediated inflammatory diseases who are taking immunosuppressants remains scarce. Our previously published cohort study showed that methotrexate, but not targeted biologics, impaired functional humoral immunity to a single dose of COVID-19 vaccine BNT162b2 (Pfizer-BioNTech), whereas cellular responses were similar.

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