Solihull Hospital is an acute general hospital in Solihull, West Midlands, England. It is managed by University Hospitals Birmingham NHS Foundation Trust.
Abstract Background There are no licensed treatments for patients with mild-to-moderate patchy alopecia areata (AA). Objectives To evaluate the efficacy, safety and dose-response of STS01, a novel nanoparticle controlled-release, topical formulation of dithranol/Prosilic. Methods In a phase 2, double-blind study, adult patients with mild-to-moderate AA (guideline ≥10% to ≤50% of scalp hair loss) were randomly assigned to STS01 at doses of 0.25%, 0.5%, 1%, 2% or placebo, daily for 6 months. The primary endpoints included the proportion of patients achieving a ≥30% improvement in Severity of Alopecia Tool (SALT) score, and percentage change from baseline in SALT score. This minimum level of improvement is generally accepted as an indicator of the population likely to progress to complete regrowth Results A total of 155 patients were randomized and treated (placebo, n=32; STS01 groups, n=30–31). STS01 1% met the primary efficacy endpoint of ≥30% SALT score improvement compared to placebo: 75.9% (95% CI, 60.3–91.4%) vs 36.7% (95% CI, 19.4–53.9%) at 6 months; p=0.0037. The least squares (LS) mean percentage change in SALT score from baseline to end-of-treatment showed a clear dose response relationship; STS01 0.5% was the minimally effective dose and 2% the maximum tolerated dose, and there was a statistically significant improvement in the STS01 1% group (−55.0% vs +0.6% with placebo; p<0.01). Significant improvements (p<0.05) in LS mean percentage changes from baseline in SALT scores were demonstrated in the STS01 1% group at 2 months (−28.6% vs 12.8%), 4 months (−57.2% vs 1.5%), and 6 months (−67.0% vs 0.6%). Clinical Global Impression-improvement was reported in 72.0% of patients with STS01 1% vs 41.7% with placebo (p<0.05). The most commonly reported treatment-emergent adverse events were skin irritation reactions, but were mostly mild (STS01: 56.7%–71.0%; placebo: 21.9%) or moderate (STS01:13.3%–35.5%; placebo: 0%) and manageable by reduced frequency of application. There were 15 skin-related discontinuations with STS01 (12.2%) and 2 (6.3%) with placebo. Conclusions STS01 demonstrated a clear dose response, with STS01 1% dose optimally more effective than placebo for hair regrowth with minimal tolerance concerns in mild-to-moderate patchy AA. Skin irritation reactions were generally manageable and there were no new safety signals. Further characterisation of the STS01 1% dose is planned in a phase 3 study. Lay summary Alopecia areata (AA) is a specific form of hair loss that occurs when the immune system attacks hair follicles causing hair to fall out. It usually starts in small, round patches. AA is a distressing condition that has many negative psychological and social effects. While there are new treatments for people with severe AA, there are still few treatments for mild/moderate patchy AA. Dithranol is a treatment that has been used for AA. In a simple cream form it purposely irritates the skin to stimulate hair regrowth, but this also stains skin, hair and fabrics. In this study, we tested a more advanced form of dithranol, called STS01 targeting the immune system without causing irritation. STS01 has been specifically designed as a new type of cream, to reduce the irritation and staining but also improve immune response. Overall, 155 UK adults with mild/moderate patchy AA took part – one group of people were given cream that had no STS01 (placebo) and the other groups were given similar creams that contained different amounts of STS01. We found that more participants using STS01 had hair regrowth than those using the placebo cream. Skin irritation reactions were mostly mild or moderate. Unlike previous dithranol creams, STS01 does not need to be washed off after 30 minutes, making it more convenient. Staining of the skin occurred in very few participants. Hair regrowth was better with higher doses of STS01, but the 1% dose had fewer skin irritation reactions than the 2% dose. The 1% STS01 dose will now be tested in a larger number of people with AA to further confirm these promising results. What is already known about this topic? There are no licensed treatments for patients with mild to moderate patchy alopecia areata (AA), the most common form of this auto-immune condition. Topical dithranol is recommended on British Association of Dermatology guidelines as an irritant treatment for AA. However, these standard preparations have administration issues due to rapid oxidation, skin irritation, and staining. STS01 is a novel nanoparticle controlled-release once-daily topical formulation of dithranol specifically targeting down regulation of the auto-immune response and reducing administration issues What does this study add? This phase 2, placebo-controlled trial showed clinically relevant improvements in hair regrowth with all measures assessed. STS01 was generally well-tolerated with no serious adverse events; skin reactions were mostly of mild or moderate intensity. STS01 represents a convenient and effective approach to the treatment of mild to moderate AA. Graphical abstract
Abstract By the Industrial Revolution, Manchester had become the capital of cotton manufacture in the UK. During the 18th century, technological innovations like the ‘spinning mule’ enabled a production boom. Operating this machinery exposed workers to the lubricant mineral oils, which splashed onto clothing and seeped into the skin. The scrotum was particularly vulnerable. Reports of the high incidence of scrotal epitheliomas (squamous cell carcinoma) in textile workers first appeared in 1887, but it took almost 40 years for it to be recognized as an occupational disease following a 1926 Home Office enquiry. Mule spinners’ cancer developed in stages. Initially keratotic plaques appeared. With continued exposure, transformation into invasive squamous cell carcinoma occurred, with metastasis to the inguinal nodes being common. Leitch estimated that 20% of scrotal cancers causing death occurred in mule spinners. Southam put the incidence of the disease at 2.5 per 1000 workers annually, and Brockbank reported at least 64 cases and 21 deaths between 1923 and 1939. After the initial enquiry there was some debate over the aetiology; Savatard, a Manchester dermatologist, suggested underlying ichthyosis as a causative factor. A consensus eventually developed that prolonged exposure to mineral oils was the principal factor, with shale oil being the primary carcinogen. Recommendations from the enquiry included installing splash guards to the machinery and education of workers on skin lesions, alongside regular medical examinations. Research into noncarcinogenic oil substitutes was considered; however, determined use of personal protective equipment became the norm. Mule spinners’ cancer offers a snapshot of industrial occupational health in an era without regulation. By highlighting the risk of occupational carcinogenesis, it laid a foundation for modern occupational dermatology, underscoring the need for legislation to limit preventable deaths. It is an example of how chronic inflammation and epidermal damage, combined with harmful environmental factors, can drive malignant transformation.
Pulsed field ablation (PFA) of atrial fibrillation (AF) using a pentaspline multi-electrode catheter is commonly performed under fluoroscopic guidance. No data exist on the integration of this catheter within a three-dimensional electroanatomical mapping (3D-EAM) system for left atrial voltage and activation mapping, posterior wall isolation (PWI), or redo ablation. To assess the feasibility of impedance-based mapping using the single-shot pentaspline PFA catheter itself within an open architectural EAM system, and identify advantages and limitations of this approach over fluoroscopy only. In this prospective series, impedance-based 3D-EAM within an open architectural EAM system was performed using the pentaspline PFA catheter itself. Cases involved real-time visualisation of the guidewire tip and PFA catheter within the 3D-EAM system. In certain cases, additional 3D-EAM was performed with a grid-style high-density mapping catheter for comparison. We studied 22 patients (45% female, mean age 63±13 years, 55% paroxysmal AF, 27% redo procedures). Five patients underwent concomitant high-density mapping, and six received PWI. Mapping increased procedural times (mean 108 mins, vs. 68 mins in fluoroscopy-only controls), without reducing fluoroscopy times. We identified three lessons: (1) The approach helped identify sleeves of incomplete pulmonary vein isolation (PVI) after index applications (Figure 1); (2) Mapping with the PFA catheter appeared concordant with the grid-style mapping catheter (Figure 2); (3) The technique facilitated robust PWI and helped identify inadvertent partial PWI. The cost-effectiveness of this approach requires formal assessment (additional equipment cost of £912 over fluoroscopy-only). 3D-EAM with a pentaspline PFA catheter is feasible, with potential advantages over fluoroscopic-only guidance or mapping with an additional high-density mapping catheter. This approach requires further workflow optimisation to minimise procedure duration, along with analysis of cost-effectiveness.Figure 1 Figure 2
