Negar Mahmoudi, Shahriar Sharifi, Dmitry Leshchiner, Sachi Horibata, Zijin Lin, Noor Ghazali, Mohammad-Ali Shahbazi, Ayushi Priyam, Richard J Williams, Irena Pastar, Lisa Gould, Simon Matoori, David Nisbet, Morteza Mahmoudi
{"title":"Tailored Bioengineering and Nanomedicine Strategies for Sex-Specific Healing of Chronic Wounds.","authors":"Negar Mahmoudi, Shahriar Sharifi, Dmitry Leshchiner, Sachi Horibata, Zijin Lin, Noor Ghazali, Mohammad-Ali Shahbazi, Ayushi Priyam, Richard J Williams, Irena Pastar, Lisa Gould, Simon Matoori, David Nisbet, Morteza Mahmoudi","doi":"10.1093/bjd/ljae457","DOIUrl":"https://doi.org/10.1093/bjd/ljae457","url":null,"abstract":"<p><p>Chronic wounds, defined by their prolonged healing process, significantly impair patient quality of life and impose a hefty financial burden on healthcare systems worldwide. Sex/gender-specific mechanisms regulate inflammation and infection, angiogenesis, matrix synthesis, and cell recruitment contribute to cutaneous wound healing, but remain largely understudied. This review is aimed to spotlight the innovative realm of bioengineering and nanomedicine, which is at the helm of revolutionizing complex chronic wound care. It underscores the significance of integrating patient sex into the development and (pre)clinical testing of these avant-garde treatment modalities, in order to enhance healing prospects for both women and men. Moreover, we explore the representation of both sexes in clinical trials of bioengineered and nanomedicine products. Finally, we examine the primary reasons for the historical neglect in translating sex-specific wound healing research into clinical practice and propose strategic solutions. By tackling these issues, the article advocates for advanced treatment frameworks that could significantly improve healing outcomes for individuals of all sexes, thereby optimizing both efficacy and inclusivity in chronic wound management.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Duc Binh Phan, Hugo Jourdain, Miguel Angel Descalzo-Gallego, Alicia González-Quesada, Mahmoud Zureik, Raquel Rivera-Díaz, Antonio Sahuquillo-Torralba, Mark Lunt, Ignacio Garcia-Doval, Emilie Sbidian, Richard B Warren, Zenas Z N Yiu
{"title":"Drug Survival and Safety of Biosimilars Compared with Originator Adalimumab for Psoriasis: A Multinational Cohort Study.","authors":"Duc Binh Phan, Hugo Jourdain, Miguel Angel Descalzo-Gallego, Alicia González-Quesada, Mahmoud Zureik, Raquel Rivera-Díaz, Antonio Sahuquillo-Torralba, Mark Lunt, Ignacio Garcia-Doval, Emilie Sbidian, Richard B Warren, Zenas Z N Yiu","doi":"10.1093/bjd/ljae454","DOIUrl":"https://doi.org/10.1093/bjd/ljae454","url":null,"abstract":"<p><strong>Background: </strong>The lack of evidence under routine clinical settings limited the widespread adoption of adalimumab biosimilars for psoriasis treatment.</p><p><strong>Objective: </strong>This study compared the drug survival and safety of adalimumab biosimilars to Humira for psoriasis treatment.</p><p><strong>Methods: </strong>We conducted a prevalent new-user cohort study using data from the French National Health Data System (SNDS), the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), and the Spanish Registry of Systemic Therapy in Psoriasis (BIOBADADERM). Adalimumab-naïve patients initiating adalimumab biosimilars (new users) were compared with Humira new users. Patients switching from Humira to biosimilars (switchers) were compared with those who continued Humira treatment. Patients were matched 1:1 based on previous adalimumab exposure time to create equal-sized cohorts of biosimilar and Humira users. Co-primary outcomes included drug discontinuation and serious adverse events (SAEs). Hazard ratios (HR) were calculated using Cox proportional hazard models. Meta-analyses using random effect models were performed to combine results from 3 databases.</p><p><strong>Results: </strong>7387 biosimilar new users and 3654 switchers were matched and compared with Humira users. No differences in all-cause discontinuation were found between biosimilars and Humira new users (HR: 0.99, 95% CI: 0.94-1.04). Switching from Humira to biosimilars was associated with a higher discontinuation rate compared to remaining on Humira (HR: 1.35, 95% CI: 1.19-1.52). Similar results were observed for discontinuation due to ineffectiveness or adverse events. Risks of SAEs were similar between biosimilar new users and Humira new users (Incidence rate ratio IRR: 0.91, 95% CI: 0.80-1.05) or between switchers and continuous Humira users (IRR: 0.92, 95% CI: 0.83-1.01).</p><p><strong>Conclusion: </strong>Adalimumab biosimilars can be considered viable alternatives to Humira for new patients with comparable effectiveness and safety. However, due to the higher likelihood of discontinuation, patients who switch from Humira to biosimilars may require closer monitoring and support.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xing Xiong, Nicole Cesarato, Yasmina Gossmann, Maria Wehner, Sheetal Kumar, Holger Thiele, Stephanie Demuth, Vinzenz Oji, Matthias Geyer, Henning Hamm, F Buket Basmanav, Regina C Betz
{"title":"A nonsense variant in KRT31 is associated with autosomal dominant monilethrix.","authors":"Xing Xiong, Nicole Cesarato, Yasmina Gossmann, Maria Wehner, Sheetal Kumar, Holger Thiele, Stephanie Demuth, Vinzenz Oji, Matthias Geyer, Henning Hamm, F Buket Basmanav, Regina C Betz","doi":"10.1093/bjd/ljae298","DOIUrl":"10.1093/bjd/ljae298","url":null,"abstract":"<p><strong>Background: </strong>Monilethrix is a rare hereditary hair disorder that is characterized by a beaded hair shaft structure and increased hair fragility. Patients may also present with keratosis pilaris and nail changes. Research has identified three genes responsible for autosomal dominant monilethrix (KRT81, KRT83, KRT86) and one responsible for the autosomal recessive form (DSG4).</p><p><strong>Objectives: </strong>To investigate the genetic basis of autosomal dominant monilethrix in families with no pathogenic variants in any of the known monilethrix genes, and to understand the mechanistic basis of variant pathogenicity using a cellular model.</p><p><strong>Methods: </strong>Nine affected individuals from four unrelated families were included. A clinical diagnosis of monilethrix was assigned based on clinical examination and/or trichoscopy. Exome sequencing was performed in six individuals to identify pathogenic variants; Sanger sequencing was used for co-segregation and haplotype analyses. Cell culture experiments [immunoblotting, immunofluorescence and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analyses] were used to confirm variant pathogenicity, to determine the expression and subcellular localization of proteins, and to identify possible nonsense-mediated mRNA decay.</p><p><strong>Results: </strong>In six affected individuals with clinically suggested monilethrix, exome sequencing led to the identification of the nonsense variant c.1081G>T; p.(Glu361*) in KRT31, which was subsequently identified in other affected members of these families by Sanger sequencing. This variant led to the abolition of both the last three amino acids of the 2B subdomain and the complete C-terminal tail domain of keratin 31. Immunoblotting demonstrated that when co-expressed with its binding partner keratin 85, the truncated keratin 31 was still expressed, albeit less abundantly than the wildtype protein. Immunofluorescence revealed that p.(Glu361*) keratin 31 had an altered cytoskeletal localization and formed vesicular-like structures in the cell cytoplasm near the cell membrane. RT-qPCR analysis did not generate evidence for nonsense-mediated decay of the mutant transcript.</p><p><strong>Conclusions: </strong>This study is the first to identify pathogenic variants in KRT31 as a cause of autosomal dominant monilethrix. This highlights the importance of hair keratin proteins in hair biology, and will increase the molecular diagnostic yield for rare ectodermal phenotypes of hair and nail tissues.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"979-987"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inflammatory dermatoses and an era of new diagnostic dermatopathology.","authors":"John A McGrath, Chao-Kai Hsu","doi":"10.1093/bjd/ljae306","DOIUrl":"10.1093/bjd/ljae306","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"855-856"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring sex- and site-specific differences in melanoma.","authors":"Alan C Geller, Alexander J Stratigos","doi":"10.1093/bjd/ljae345","DOIUrl":"10.1093/bjd/ljae345","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"860"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Helen Alexander, Rayka Malek, David Prieto-Merino, Elizaveta Gribaleva, Manisha Baden, Paula Beattie, Sara Brown, Tim Burton, Shona Cameron, Bola Coker, Michael J Cork, Ross Hearn, John R Ingram, Alan D Irvine, Graham A Johnston, Alice Lambert, Mark Lunt, Irene Man, Louise Newell, Graham Ogg, Prakash Patel, Mandy Wan, Richard B Warren, Richard Woolf, Zenas Z N Yiu, Nick Reynolds, Michael R Ardern-Jones, Carsten Flohr
{"title":"A prospective observational cohort study comparing the treatment effectiveness and safety of ciclosporin, dupilumab and methotrexate in adult and paediatric patients with atopic dermatitis: results from the UK-Irish A-STAR register.","authors":"Helen Alexander, Rayka Malek, David Prieto-Merino, Elizaveta Gribaleva, Manisha Baden, Paula Beattie, Sara Brown, Tim Burton, Shona Cameron, Bola Coker, Michael J Cork, Ross Hearn, John R Ingram, Alan D Irvine, Graham A Johnston, Alice Lambert, Mark Lunt, Irene Man, Louise Newell, Graham Ogg, Prakash Patel, Mandy Wan, Richard B Warren, Richard Woolf, Zenas Z N Yiu, Nick Reynolds, Michael R Ardern-Jones, Carsten Flohr","doi":"10.1093/bjd/ljae287","DOIUrl":"10.1093/bjd/ljae287","url":null,"abstract":"<p><strong>Background: </strong>The main conventional systemic treatments for atopic dermatitis (AD) are methotrexate (MTX) and ciclosporin (CyA). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomized controlled trials or real-world studies comparing these agents directly. Network meta-analyses provide indirect comparative efficacy and safety data and have shown strong evidence for dupilumab and CyA.</p><p><strong>Objectives: </strong>To compare the real-world clinical effectiveness and safety of CyA, dupilumab and MTX in AD.</p><p><strong>Methods: </strong>We compared the effectiveness and safety of these systemic agents in a prospective observational cohort study of adult and paediatric patients recruited into the UK-Irish Atopic eczema Systemic TherApy Register (A-STAR). Treatment effectiveness measures included Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and children's DLQI (cDLQI). The minimum duration of treatment was 28 days and follow-up was 12 months. Adjusted Cox-regression analysis was used to compare the hazard ratios of achieving EASI-50, EASI-75 and EASI-90 over time, and linear mixed-effects models were used to estimate changes in efficacy scores. Treatment safety was assessed by examining adverse events (AEs) at follow-up visits.</p><p><strong>Results: </strong>We included 488 patients (311 adults and 177 children/adolescents) on dupilumab (n = 282), MTX (n = 149) or CyA (n = 57). CyA and MTX were primarily used as the first-line treatment, while dupilumab was mainly a second-line systemic treatment as per UK National Institute of Clinical and Care Excellence (NICE) recommendations. EASI-50, EASI-75 and EASI-90 were achieved more rapidly in the dupilumab and CyA groups compared with MTX. After adjustment for previous severity, the reduction in EASI, POEM, PP-NRS and DLQI was greater for patients treated with dupilumab compared with MTX. In patients with severe disease the reduction in EASI, POEM and PP-NRS was even greater with CyA. The incidence rates of AEs were similar across groups (734, 654 and 594 per 10 000 person-month on CyA, dupilumab and MTX, respectively).</p><p><strong>Conclusions: </strong>This real-world comparison of CyA, dupilumab and MTX in AD suggests that dupilumab is consistently more effective than MTX and that CyA is most effective in very severe disease within 1 year of follow-up.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"988-999"},"PeriodicalIF":11.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"VEXAS syndrome was in front of us for decades.","authors":"Nicolas Giachetti, Valentin Lacombe","doi":"10.1093/bjd/ljae309","DOIUrl":"10.1093/bjd/ljae309","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"1022-1023"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Paternal exposure: two patients' perspectives in an evolving landscape of therapeutics. Can we now provide reassurance?","authors":"Bhaskar Narayan, Leila Asfour","doi":"10.1093/bjd/ljae319","DOIUrl":"10.1093/bjd/ljae319","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"1008-1009"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}