bluuebunny/crossref_metadata_2025 huggingface dataset:
The Second Fusion/Fusing the Fusions
Authors: Strawson Galen
Published: June 2024

Chapter 6 argues for Stoff ist Kraft, the view that there are no metaphysically fundamental distinctions to be made between the phenomena of force, energy, power, causation, physical law, and natural necessity. Some of these terms have genuinely different uses, but this does not support any sort of metaphysical separatism with respect to their fundamental being. The chapter then argues, with Nietzsche, for a further identity: there is no fundamental distinction between a thing and its power/force/energy features. To think otherwise is to succumb to a separatist, staticist conception of stuff: a thing’s power features must also be reckoned to be among its intrinsic qualities and so (by the argument of Chapter 5) as part of its total qualitiedness—with which it is identical. So too a thing’s behaviour is as much part of its fundamental being as anything about it that can’t be counted as its behaviour.
Effectiveness of non-pharmacological interventions delivered at home for urinary and faecal incontinence with homebound older people: systematic review of randomised controlled trials
Authors: Buck Jackie , Fromings Hill Julia , Collins Rachael , Booth Joanne , Fleming Jane
Published: June 2024

Introduction

Incontinence is a common, distressing condition, most prevalent in older people. There is an unmet need for effective interventions to support continence. This review focuses on non-pharmacological interventions to reduce incontinence among homebound older people. Aim: to identify interventions with potential to be delivered by care workers, nurses or family members in a person’s home.

Methods

Multiple databases were searched until 15 September 2023 for randomised controlled trials reporting home-based interventions for incontinence for older people (≥65 years) living at home. Two reviewers independently screened titles, abstracts and papers against inclusion criteria, then assessed for the Risk of Bias (RoB2). A third reviewer resolved the discrepancies. Primary data were extracted and synthesised.

Results

A full-text review of 81 papers identified seven eligible papers (1996–2022, all USA), including n = 636 participants (561 women and 75 men). Two studies focusing on multicomponent behavioural interventions showed benefit, as did one study of transcutaneous tibial nerve stimulation self-administered through electrode-embedded socks. Three, which included cognitively impaired people, reported improvement with toileting assistance programmes, but the effects were not all significant. Results were inconclusive from a study examining the effects of fluid intake adjustments. Interventions were delivered by nurses, three in collaboration with family caregivers. No faecal incontinence interventions met the criteria.

Conclusion

There is scant evidence for continence supporting interventions delivered in older people’s own homes. With an ageing population often reliant on family or social care workers well-placed to support continence promotion and policy drives for services to support older people remaining at home, this evidence gap needs addressing.
Advancing research: a commentary on the untapped potential of acceptance and commitment therapy in alcohol use disorder treatment
Authors: Garel Nicolas , Brodsky Kimberly L , Ostacher Michael J
Published: June 2024

Alcohol use disorder poses a significant global health threat, with profound consequences for individuals, families, and communities, necessitating continued exploration of novel treatment approaches. Acceptance and Commitment Therapy, an evidence-based approach for various mental health disorders, offers promise in addressing alcohol use disorder as well, but controlled trials are lacking, highlighting a crucial gap in research.
A search for food extracts inhibiting ferroptosis using immortalized mouse embryonic fibroblasts derived from xCT knockout mice
Authors: Mori Yasushi , Abe Tsukumo , Masaya Nami , Igarashi Kiharu , Sato Hideyo , Kobayashi Sho
Published: June 2024

Depleting glutathione by xCT inhibition induces iron-dependent ferroptotic cell death, which is suppressed by lipophilic antioxidants. We screened food extracts with xCTKO-MEFs, identifying garlic extracts as particularly potent in inhibiting ferroptosis among the food extracts examined in this study. xCTKO-MEFs can serve as a convenient tool for identifying food extracts that are effective in inhibiting ferroptosis.
Transfer learning of condition-specific perturbation in gene interactions improves drug response prediction
Authors: Bang Dongmin , Koo Bonil , Kim Sun
Published: June 2024

Drug response is conventionally measured at the cell level, often quantified by metrics like IC50. However, to gain a deeper understanding of drug response, cellular outcomes need to be understood in terms of pathway perturbation. This perspective leads us to recognize a challenge posed by the gap between two widely used large-scale databases, LINCS L1000 and GDSC, measuring drug response at different levels—L1000 captures information at the gene expression level, while GDSC operates at the cell line level. Our study aims to bridge this gap by integrating the two databases through transfer learning, focusing on condition-specific perturbations in gene interactions from L1000 to interpret drug response integrating both gene and cell levels in GDSC. This transfer learning strategy involves pretraining on the transcriptomic-level L1000 dataset, with parameter-frozen fine-tuning to cell line-level drug response. Our novel condition-specific gene–gene attention (CSG2A) mechanism dynamically learns gene interactions specific to input conditions, guided by both data and biological network priors. The CSG2A network, equipped with transfer learning strategy, achieves state-of-the-art performance in cell line-level drug response prediction. In two case studies, well-known mechanisms of drugs are well represented in both the learned gene–gene attention and the predicted transcriptomic profiles. This alignment supports the modeling power in terms of interpretability and biological relevance. Furthermore, our model’s unique capacity to capture drug response in terms of both pathway perturbation and cell viability extends predictions to the patient level using TCGA data, demonstrating its expressive power obtained from both gene and cell levels.

Availability and implementation

The source code for the CSG2A network is available at https://github.com/eugenebang/CSG2A.
ISMB 2024 Proceedings
Authors: Milenković Tijana , Ponty Yann
Published: June 2024

This editorial describes the selection process and the collection of articles selected for presentation for the Proceedings Track of the ISMB 2024 conference.
METTL14 mediates nerve growth factor-stimulated testosterone synthesis in porcine theca cells
Authors: Luo Yuxin , Zhao Yun , Zhang Boqi , Chen Tong , Chen Xue , Shen Caomeihui , He Guitian , Cao Maosheng , Chen Lu , Wang Yueying , Wang Nan , Zong Jinxin , Zhou Xu , Li Chunjin
Published: June 2024

Ovarian theca cells produce testosterone, which acts as a vital precursor substance for synthesizing estrogens during follicular development. Nerve growth factor (NGF) has been shown to participate in reproductive physiology, specifically to follicular development and ovulation. There is currently no available data on the impact of NGF on testosterone synthesis in porcine theca cells. Furthermore, m6A modification is the most common internal modification in eukaryotic mRNAs that are closely associated with female gametogenesis, follicle development, ovulation, and other related processes. It is also uncertain whether the three main enzymes associated with m6A, such as Writers, Erasers, and Readers, play a role in this process. The present study, with an in vitro culture model, investigated the effect of NGF on testosterone synthesis in porcine theca cells and the role of Writers-METTL14 in this process. It was found that NGF activates the PI3K/AKT signaling pathway through METTL14, which regulates testosterone synthesis in porcine theca cells. This study will help to further elucidate the mechanisms by which NGF regulates follicular development and provide new therapeutic targets for ovary-related diseases in female animals.

Summary Sentence 

The present study investigated the effect of NGF on testosterone synthesis in porcine theca cells. It was found that NGF activates the PI3K/AKT signaling pathway through METTL14, which regulates testosterone synthesis in porcine theca cells.
CPC10 A curious case of recurrent melanomas and field change confined to the left thigh over 25 years
Authors: Hussain Khawar , Chung Jenny , Goss Charlotte , Fernandez Carolina , Dave Siddarth , Weir Justin , Craythorne Emma , Fearfield Louise
Published: June 2024

A 52-year-old woman presented in 1999 with an atypical erythematous plaque on her left thigh containing a flesh-coloured nodule surrounded by four pink scaly papules. She had no significant past medical, drug or family history. Excision of the nodule revealed an amelanotic malignant melanoma (MM) of Breslow thickness (BT) 1 mm. Biopsies of the four surrounding lesions confirmed satellite MM in one, with no radiological evidence of metastases. She received adjuvant interferon therapy for 1 year. Repeat imaging was normal. Eighteen years later, she developed a new pigmented lesion on her left thigh confirmed as MM (0.9 mm BT), with three further erythematous plaques on the left thigh reported as (i) proximal left-thigh MM (1.08 mm BT), (ii) middle-left-thigh amelanotic MM (0.6 mm BT) and (iii) left-thigh MM (1.7 mm BT). Wide local excision (WLE) failed to obtain histological clearance of (i) and (iii), with mildly dysplastic naevus and melanoma in situ (MiS), respectively, at the peripheral margins. Reflective confocal microscopy (RCM) was used to guide further surgery, with continued incompletely excised MiS and field change at the margins. Eighteen months later she presented with another MiS and MM (0.5 mm BT) on the left thigh. Imiquimod 5% once daily for 8 weeks to the affected area was instigated to treat any residual in situ component. BRAF, CDKN2A, CDK4 and BAP1 showed no pathological variants, and xeroderma pigmentosum testing was negative. Six months later a further MM (1.2 mm BT) on the left thigh was treated with WLE and skin graft. Sentinel lymph node biopsy was deemed not possible due to previous multiple surgical excisions. Ultrasound groin scan and whole-body FDG-PET computed tomography showed no occult metastases. Several months later, another MM (0.5 mm BT) was excised at the edge of the graft site. Residual dysplastic lentiginous proliferation at the edge with no MM was reported on the 1-cm WLE. This represents a complex case with recurrent MM, often indistinguishable from primary MM histologically. Widespread dysplastic field change evidenced by involvement at the edges of the WLEs and the RCM images was also challenging. RCM can be a noninvasive adjunct in identification of superficial skin tumours. Adjuvant interferon therapy for high-risk MM has demonstrated an increase in disease-free survival (Petrella T, Verma S, Spithoff K et al. Adjuvant interferon therapy for patients at high risk for recurrent melanoma: an updated systemic review and practice guideline. Clin Oncol 2012; 24: 413–23). This may have contributed to the 18-year delay between her first and second melanomas, as well as her complex, recurrent presentations and ongoing local confinement of the MM to the left thigh with lack of disease progression.
P006 Tumour necrosis factor-α-induced lupus panniculitis: one case report and literature review
Authors: Grechin Cristina , Doheny Jane , Pilson Keith , Howard Donough , Roche Muireann
Published: June 2024

The anti-tumour necrosis factor (TNF)-α therapies have revolutionized the management of multiple chronic inflammatory diseases. However, a wide range of adverse events have been reported over the years (Durand A, Goussot J, Thiolat D et al. Anti-tumour necrosis factor α-induced lupus erythematosus panniculitis. J Eur Acad Dermatol Venereol 2017; 3: e307–48). Lupus erythematosus panniculitis (LEP) is a rare variant of cutaneous lupus erythematosus (1–3% of cutaneous lupus erythematosus), with just two reports of cases potentially triggered by anti-TNF-α therapies (Durand et al.; and Lee H, Kim DS, Chung DY. Adalimumab-induced lupus panniculitis. Letter to the editor. Lupus 2014 ; 23: 1443–4). We report a case of a 62-year-old woman with rheumatoid arthritis treated with etanercept, who previously had not responded to multiple therapies including methotrexate, sulfasalazine and adalimumab. She presented with an 18-month history of a rash on her left upper arm that developed 6 months after initiation of adalimumab. Despite a switch to etanercept, the rash continued to evolve. Examination revealed several discrete telangiectatic plaques on the left upper arm with marked subcutaneous atrophy, clinically suspicious for lupus panniculitis. A similar area was found on the right upper arm. Two punch biopsies for haematoxylin and eosin staining were performed. Histology revealed a thin epidermis with a slightly thickened basement membrane, chronic inflammation at the dermoepidermal junction with lymphocyte exocytosis, transdermal perivascular chronic inflammation and mild lymphoplasmacytic lobular inflammation within the subcutis consistent with lupus panniculitis. Following a switch by her rheumatologist to certolizumab pegol for active rheumatoid arthritis, she had an episode of acute lupus panniculitis requiring hospitalization. A trial of hydroxychloroquine (5 mg kg−1 real bodyweight) and mepacrine in conjunction with potent topical steroids failed to control her panniculitis. Her anti-TNF-α therapies were suspected as a potential cause. Certolizumab was changed to a Janus kinase inhibitor (baricitinib), and dapsone was added to the current treatment. A considerable clinical improvement was noticed. Moreover, her LEP has been in remission for 18 months without any flares. Our literature review highlights only two case of lupus panniculitis induced by anti-TNF-α agents. Lee et al. published a case of adalimumab-induced LEP for first time in 2014, followed by Durand et al., who reported the second case of LEP after 24 months of TNF-α treatment. Interestingly, both patients were female and had known rheumatoid arthritis. In conclusion, our case report and literature review highlights that anti-TNF-α therapies can induce lupus panniculitis, especially in the cohort of patients with rheumatoid arthritis. Is there any relation between these two diseases or is it just a coincidence? Further research in this field is required.
P035 Quantifying the mutation burden of a therapeutic course of narrowband ultraviolet B (UVB) to help inform on the carcinogenicity of narrowband UVB
Authors: Coltart George , Fowler Joanna , Sood Roshan , Lai Chester , Nadarajah Noeline , Jones Philip , Healy Eugene
Published: June 2024

Narrowband ultraviolet B (NB-UVB) is recommended by NICE as a treatment for chronic plaque and guttate psoriasis that cannot be controlled with topical therapies. However, ultraviolet radiation is a carcinogen that causes DNA mutations in the skin, and in some cases results in skin cancer development. To date, there have been no studies determining how many mutations develop in human skin as a result of a therapeutic course of NB-UVB, and therefore we investigated the mutation burden of NB-UVB in the current study. Although whole-exome or whole-genome sequencing and target-enriched sequencing can detect mutations in large clones of mutated skin cells, these approaches do not detect mutations occurring only in single skin cells, hence we used a novel type of sequencing called Nanorate sequencing (which can identify mutations occurring in just a single molecule of DNA) in this study. We obtained 6-mm punch biopsies of normal skin (buttock and/or forearm) before and after a course of UV from patients (n = 16) undergoing NB-UVB treatment for psoriasis. Epidermis was microdissected from the dermis and the epidermal DNA was sequenced using nanorate sequencing. DNA from venous blood underwent whole-genome sequencing as germline control for accurate identification of mutations in the epidermal samples. The numbers of DNA mutations were compared between the skin samples taken before and after NB-UVB in order to quantify the mutation burden attributable to the course of NB-UVB. Minimal erythema doses ranged from 0.3 to 0.9 J cm−2 and the total dose received during the course of NB-UVB ranged from 14.8 to 133 J cm−2. There was a significant rise in the number of mutations in buttock and forearm skin due to the NB-UVB treatment, with median increases in single-base substitutions per megabase of 1.09 SBS/Mb (P = 0.001) and 3.77 SBS/Mb (P = 0.0098) in buttock and forearm epidermis, respectively. The change in number of mutations secondary to NB-UVB treatment was predominately due to UV signatures SBS7a and SBS7b, with the DBS1 (CC>TT mutations) double-base substitution signature also identified in buttock and forearm skin samples. Comparison of the increase in mutation burden from NB-UVB with the mutation burden in keratinocyte cancers indicated that, for more susceptible patients, a course of NB-UVB therapy contributed as much as one-sixteenth of the total mutational burden of a cutaneous squamous cell cancer.
P049 Best foot forward: awareness of melanoma of the foot among podiatrists
Authors: Nolan Brian , O’Connor Cathal , Murphy Michelle
Published: June 2024

Melanoma of the foot can masquerade as ulcerative conditions, congealed blood and trauma. Thus, even for experienced clinicians, diagnosis can prove challenging. There is a paucity of evidence about the role that podiatrists, who are routinely exposed to patients’ lower limbs, play in melanoma detection. The aim of this study was to assess the awareness and knowledge of melanoma among podiatrists, and to investigate whether podiatrists examine and assess suspicious pigmented lesions of the foot. An anonymous 18-question survey was designed assessing podiatrists’ knowledge of melanoma of the lower limb, and exposure to suspicious pigmented lesions. Ethical approval was granted by the local research ethics committee. This survey investigated the frequency of examination of suspicious pigmented lesions, insight into what constitutes a suspicious pigmented lesion, actions taken upon detection of such lesions, and suggestions for helping to improve early detection of melanoma. The survey was distributed anonymously by the national podiatrists’ association to 400 registered members over a 3-month period. The survey generated 247 responses (62% response rate, n = 400). Most podiatrists (81%) had over 20 years’ experience, and saw an average of 30 patients weekly. Over two-thirds (68%, n = 167) had been asked to examine suspicious pigmented lesions on the lower limb, of whom almost two-thirds (61%, n = 102) reported being frequently asked to examine suspicious pigmented lesions. Over two-thirds of podiatrists (71%, n = 175) reported identifying a lesion that they felt could represent melanoma, of whom 79% advised presentation to the general practitioner (GP), 8% advised dermatology review, 6% took photographs for skin-mapping, 6% contacted the patient’s GP directly, and one took a biopsy. Most (81.9%) did not receive subsequent feedback from the patients or GP. Just over a third (34.4%, n = 83) reported not feeling comfortable contacting a GP surgery directly to refer a patient, while 55.8% (n = 135) did not feel comfortable discussing sunscreen and photoprotection with patients. Most (81.7%, n = 196) did not feel they received satisfactory undergraduate education in melanoma. Suggestions for improving early detection of melanoma of the foot among podiatrists included enhanced undergraduate training, a clear referral pathway for podiatrists, and feedback from their referrals to GP or dermatologists. There is a concerning gap between the reported frequency of suspicious pigmented lesions in podiatry practice and the lack of formal training in melanoma detection and assessment. Improved training, clearer referral guidelines, and enhanced interprofessional communication strategies may improve early detection of melanoma of the foot among podiatrists.
P055 A randomized single-blinded prospective study to compare simulated daylight photodynamic therapy with natural daylight photodynamic therapy for the treatment of multiple actinic keratoses
Authors: Drumm Ciara , Morgan Imelda , Kavanagh Ann , Gill Danielle , Buckley Julia , Reade Matthew , Loughman Eamon , McCavana Jackie , Ryan Aisling , Moriarty Blaithin , Lally Aoife
Published: June 2024

Actinic keratoses (AKs) are considered precursor lesions of cutaneous squamous cell carcinoma, with a reported conversion rate of 3–16%. Photodynamic therapy (PDT) is a widely approved therapy for AKs. Conventional PDT (c-PDT) using red light is limited by pain and a small treatment field. Daylight PDT (d-PDT), an approved alternative, is limited by geographical location and weather conditions. Simulated daylight PDT (sd-PDT) with light-emitting diode (LED) light sources is now commercially available due to robust evidence that these devices are effective, but the devices are limited by cost (∼€30 000). We hypothesized that sd-PDT with a 4000 K white-light LED floodlight, costing €961, is equally as effective and well tolerated as d-PDT in the treatment of AKs across treatment fields of up to 55 cm2 on the scalp. Twenty-two men with a mean age of 74.5 years (SD 7.0) and multiple scalp AKs were enrolled in this prospective, randomized, single-blinded study, which employed a split-scalp design to compare the effectiveness and adverse events of d-PDT and sd-PDT. Block randomization was used to determine which side of the scalp would be treated with d-PDT. Each patient received four treatments in total, two d-PDT and two sd-PDT, each a week apart. The AKs were counted, graded, mapped and photographed at baseline, at blinded 1- and 3-month reviews and at unblinded 6-, 9- and 12-month reviews. The primary endpoint was mean lesion-specific clearance, defined as the mean number and percentage of cleared AKs per treatment field at 3 months. At baseline, the mean (SD) number of AKs per field was 44 (17.4) for the d-PDT group and 45.5 (17.8) for the sd-PDT group (P = 0.4). The mean lesion-specific clearance (percentage reduction) in AKs per field was 35.3 (71.5%) for d-PDT and 35.0 (75.1%) for sd-PDT at 1 month (P > 0.99), 33.6 (66.4%) for d-PDT and 30.3 (61.6%) for sd-PDT at 3 months (P = 0.6). Both d-PDT and sd-PDT were effective, with a significant reduction in AKs from baseline at 1 and 3 months (P < 0.01). Pain was reported by 15 patients with d-PDT and 12 with sd-PDT (median maximum score out of 100, 3.5 vs. 4.5; P = 0.6). Erythema was observed in 17 after d-PDT and 15 after sd-PDT. On a scale of 0 (intolerable) to 10 (very tolerable), patients rated d-PDT as 10 and sd-PDT as 9.8 (P = 0.08). We conclude that sd-PDT with a 4000 K white-light LED floodlight is equally as effective and well tolerated as d-PDT and is an affordable treatment option not limited by pain, small treatment field, geographical location or weather conditions.
P059 Cutaneous sarcomas: a 5-year review of treatment outcomes and literature
Authors: Chung Jenny , Macedo Chrystalla , Sinha Rishika
Published: June 2024

Cutaneous sarcomas comprise 5% of skin cancers yet carry great morbidity and mortality. They include atypical fibroxanthoma (AFX), pleomorphic dermal sarcoma (PDS), leiomyosarcoma (LMS), dermatofibrosarcoma protuberans (DFSP) and angiosarcoma (AS) (Stoneham S, Hunter A, Raahimi M et al. Cutaneous sarcoma: a review and practical approach to management. Clin Exp Dermatol 2023; 48: 866–72). Standardized agreed national guidelines for the management of these rare tumours are lacking, and we rely on guidance from sarcoma specialists (Dangoor A, Seddon B, Gerrand C et al. UK guidelines for the management of soft tissue sarcomas. Clin Sarcoma Res 2016; 6: 20). However, these tumours are lower grade, and do not carry the same local and metastatic recurrence risk as noncutaneous sarcomas. The aim of this study at a tertiary UK centre was to review the treatment and follow-up outcomes of patients with sarcoma managed locally. All patients with biopsy-proven cutaneous sarcomas discussed at our skin cancer multidisciplinary team (MDT) from March 2020 to January 2024 were retrospectively reviewed. Patient demographics, and histology were gathered along with the treatments offered, recurrence and follow-up outcome. All patients were restaged using the American Joint Committee on Cancer soft tissue sarcoma criteria. In total 40 patients met the criteria; their mean age at diagnosis was 70 years (range 24–91) and 25% were immunosuppressed. The cohort was followed up for an average of 11.3 weeks (range 1–36). The diagnoses included PDS (35%), AFX (20%), LMS (20%), DFSP (15%) and AS (5%); all but one had T1 or T2 disease. Overall, 97% of patients received surgery first line, with a clearance rate of 85% (29 of 34). Two patients had recurrence: one with PDS, requiring further surgery, and one with AS, who was managed at a sarcoma unit. There were no metastases reported or deaths due to disease. Most patients (80%) remain in clinical remission. Appropriate imaging and follow-up recommendations were made in most cases, according to their diagnosis. In summary, many of the patients with cutaneous sarcoma in the study had superficial disease. Despite our conservative surgical margins offered and a short duration of follow-up, we observed a 5% recurrence rate with no metastases. This study highlights the importance of an MDT approach to cutaneous sarcomas, which helps draw expertise from different specialties. Our lower recurrence rate and metastases compared with literature suggests that patients with cutaneous sarcoma could be safely managed in local skin cancer MDTs. We propose national guidance to help similar skin cancer MDTs and clinicians to standardize and reduce variation in care, as well as to provide an evidence base on which to recommend monitoring of this rare group of tumours.
P061 Squamoid eccrine ductal carcinomas: challenges in diagnosis and management
Authors: Cunliffe Amy , Elsheikh Somaia , Odedra Sunita , Varma Sandeep
Published: June 2024

Squamoid eccrine ductal carcinomas (SEDCs) are rare adnexal carcinomas displaying both squamous and duct differentiation. We wish to remind clinicians of these recently described cancers, which can have aggressive behaviour (van der Horst MPJ, Garcia-Herrera A, Markiewicz D et al. Squamoid eccrine ductal carcinoma. Am J Surg Pathol 2016; 40: 755–60). We identified five cases in our department: four female patients and one male. All lesions developed on the face, in patients aged 69–83 years. The majority developed over one to several years, apart from one rapidly growing lesion, and measured between 5 and 40 mm. Clinical examination suggested squamous cell carcinoma (SCC) in two cases and basal cell carcinoma in three cases due to features such as puckering, rolled borders, telangiectasia, shine, ulceration and crust. Punch biopsies were performed in all five lesions; however, histological diagnosis of SEDC was suggested in only two. One of these patients underwent Mohs micrographic surgery (MMS), which successfully cleared the lesion after two stages. The second patient, diagnosed on biopsy, had a large 30-mm lesion with invasion into the lacrimal sac and left nasal bone. The patient opted for palliative radiotherapy rather than extensive surgery and subsequently developed a left-cheek metastasis and symptoms suggestive of metastatic disease. Three of our cases were diagnosed after wide local excision (WLE) based on the histological and immunological features. The punch biopsies had suggested either SCC or adenosquamous/adnexal infiltrative carcinoma. One of these patients required adjuvant radiotherapy due to perineural involvement (< 0.1 mm). The other two cases were incompletely excised on WLE and the patients were offered further surgery or radiotherapy. Histologically these lesions were poorly defined infiltrative neoplasms consisting of atypical squamoid cells extending into the deep dermis or subcutaneous tissue with ductal differentiation, pronounced cytological atypia and associated desmoplastic stroma. Tumour thickness measured 3–10.3 mm. Immunohistochemistry was positive for CK7, AE1/AE3, CK5/6, p63, CAM5.2, carcinoembryonic antigen and epithelial membrane antigen. These five cases highlight the challenges faced in the diagnosis of SEDC for both the dermatologist and the dermatopathologist. MMS is recommended (Lim MM, Macdonald JA. Squamoid eccrine ductal carcinoma: treatment and outcomes. Am J Dermatopathol 2022; 44: 249–53) and lesions misdiagnosed as SCC may receive less effective treatment; our three patients who underwent WLE have required further interventions. We also report one patient with locally aggressive and likely metastatic disease. Patients with SEDC benefit from early diagnosis, MMS and close follow-up to reduce the risk of recurrence and improve patient outcomes.
P063 Understanding the landscape of Kaposi sarcoma hospitalizations in the USA: demographic associations stratified by AIDS/HIV status
Authors: Mendoza Roy , Espinoza Norma , Saoub Jessica , Kieron Leslie , Ge Shaokui
Published: June 2024

Kaposi sarcoma (KS), a low-grade vascular tumour associated with human herpesvirus 8 (KSHV/HHV8), has demonstrated a notable increase among Black men despite an overall decreasing trend in the USA. Given the lack of information regarding the national rates of KS in the USA, this study aims to characterize the national inpatient burden of individuals affected by KS, exploring demographic disparities on a broader scale. We queried the National Inpatient Sample (NIS), a subset of the Healthcare Cost and Utilization Project database containing US hospital discharge data, from 2016 to 2019 to identify all patients aged ≥ 18 years with a diagnosis of KS. We used the data to estimate the national representation and KS-relevant hospital admissions compared with the national civilian population. Stratifying by HIV/AIDS status (AIDS-related KS vs. non-AIDS-related KS), we examined the demographic associations of inpatients with KS using a Wald χ2-test. We determined the incidence rate ratios of admission for KS-related concerns using a Poisson regression model. All statistical analyses were performed with SAS 9.4 (SAS Institute Inc., Cary, NC, USA). In total, 12 246 patients with KS were estimated from the NIS. Overall, the inpatients with KS were predominantly male (91.1%), Black (41.4%) and in the 18–44-year age group (47.7%). AIDS-related KS constituted the majority of patients with KS (10 065, 82.2%), predominantly affecting Black individuals (45.7%) compared with patients classified as White, Hispanic and other (30.2%, 17.6% and 6.5%, respectively). Male patients were more often affected, at a 16 : 1 male-to-female ratio, the largest recorded thus far. Black patients with AIDS had a significantly higher risk of hospitalization. Non-AIDS-related KS comprised 17.8% of cases, primarily among White (51.4%) and male (77.5%) patients, and those aged 65–84 years (49.3%). Despite the differences by KS type, Black patients and those aged ≥ 85 years with non-AIDS-related KS still faced a heightened risk of hospitalization. This study underscores the distinct demographic patterns of inpatients with KS by HIV/AIDS status. For AIDS-related KS, focused efforts are required for Black individuals – addressing their elevated risk, initiating early therapeutic intervention, and promoting adherence to antiretroviral therapy. In cases of non-AIDS-related KS, attention must be given to the older age groups, especially those with a history of immunosuppression. These findings advocate for specialized dermatological strategies considering demographic nuances, contributing to more effective and targeted care for patients with KS.
P090 A randomized study to compare the efficacy of topical tofacitinib vs. topical tacrolimus in treatment of patients with unstable vitiligo
Authors: Mehta Hitaishi , Bishnoi Anuradha , Vinay K , Kumaran Sendhil , Parsad Davinder
Published: June 2024

Topical tacrolimus 0.1% is a widely accepted treatment for localized vitiligo. However, emerging Janus kinase inhibitors like tofacitinib show promise. Existing evidence for topical tofacitinib largely comes from open-label, uncontrolled studies and case reports, often in combination with other therapies. This prospective, 16-week, single-blinded, split-body study evaluated the efficacy and tolerability of topical tofacitinib 2% ointment vs. topical tacrolimus 0.1% ointment applied twice daily in a cohort of 25 patients with limited vitiligo. Participants aged ≥ 5 years with a diagnosis of nonsegmental vitiligo, limited to ≤ 10% body surface area, and at least two symmetrical vitiligo patches that had been active in last 12 months were included. After informed consent was obtained, vitiliginous patches on either side of the body were randomized to receive either topical tofacitinib or topical tacrolimus. The total duration of therapy was 16 weeks, and patients were followed up every 4 weeks. The primary outcome was Vitiligo Noticeability Scale (VNS) of two symmetrical target patches at week 16 as reported by patients, with a VNS of 4 (‘a lot less noticeable’) or 5 (‘no longer noticeable’) considered as treatment success. Secondary outcomes included clinician-reported percentage repigmentation, time to attainment of treatment success and incidence of adverse effects. The study cohort, comprising 25 patients analysed for 50 vitiligo patches, had a mean age of 22.4 years (range 5–59). The topical tofacitinib group achieved a VNS of 4 or 5 (considered treatment success) in 14 patients (56%), compared with 11 (44%) in the tacrolimus group (P = 0.40). Clinicians observed significant repigmentation exceeding 75% in 15 patients within the tofacitinib group and 13 patients within the tacrolimus group (P = 0.57). The mean (SD) time to attain treatment success was 12.4 (3.8) weeks for tacrolimus and 10.0 (4.4) weeks for tofacitinib. Strikingly, tofacitinib demonstrated treatment success as early as 4 weeks in three patients, whereas no such rapid success was observed in the tacrolimus group. Adverse effects, predominantly mild, included transient erythema (n = 1) and burning sensations (n = 5) with tacrolimus, while tofacitinib led to application-site pain and pruritus in one patient each (P = 0.12). Limitations of our study include the small sample size, short treatment duration and single-blinded study design. In summation, this study unveils the efficacy of both topical tofacitinib and tacrolimus in repigmenting vitiligo lesions. Tofacitinib exhibits a higher, though statistically nonsignificant, treatment success rate and a swifter onset of repigmentation, indicating its potential as a robust therapeutic option for limited vitiligo.
P093 Bespoke omalizumab prescribing in chronic spontaneous urticaria
Authors: Vandormael Isabelle , Font Daniela Mock , Carne Emily , Kamath Sandeep
Published: June 2024

Chronic spontaneous urticaria (CSU) represents the most common form of chronic urticaria and is estimated to affect 0.5–1% of the worldwide population. This condition has an underestimated but significant impact on the quality of life of patients. It represents a high socioeconomic burden to healthcare systems due to its chronic nature and the challenges currently faced in its treatment. Omalizumab is the only IgE-targeted biologic currently approved for patients with CSU who have persistent symptoms despite high-dose antihistamines. The licensed dose for omalizumab is 300 mg every 4 weeks and it is currently recommended for 6 months; however, it is estimated that approximately 30% of patients do not respond to this standardized regimen and there is currently no clear guidance on managing this cohort of patients. This study provides an overview of our clinical practice when prescribing omalizumab for the management of CSU and further evidence of the efficacy of a personalized dosing regimen. We report on 36 patients started on omalizumab during the year 2022 from five separate dermatology centres. Data were collected retrospectively from pharmacy records using data spreadsheets. Twenty-seven patients were given omalizumab for the first time, while nine patients were on their second course. Dosing and treatment intervals were adjusted according to disease activity using the Urticaria Activity Score (UAS7). Eleven patients received personalized dosing, with their dose titrated up or down based on symptom control. Three patients required updosing to 450 mg 4-weekly, one patient was given 600 mg 4-weekly, one patient had their dose titrated down to 150 mg monthly, and six patients remained on 300 mg 4-weekly beyond 6 months. Our results suggest that 30.5% of patients would have had to discontinue treatment and consider switching to ciclosporin had personalized dosing not been considered. Immunosuppression comes with its challenges, with significant adverse events, rigorous blood monitoring and more frequent hospital reviews all contributing to the ever-increasing financial burden on the NHS. Omalizumab, in comparison, is better tolerated and carries a much better safety profile. This study also supports findings from a proportion of patients will require longer treatment courses, as a reduction in UAS7 scores may occur beyond the fourth dose. Overall, 25% of patients were on their second course of treatment at the time of analysis, suggesting a lack of remission at 6 months and the need for more guidance on longer-term treatment.
P099 Use of roflumilast in erosive oral inflammatory conditions
Authors: Botrugno Rachel , Rajlawat Bijaya , Finn Daniel , Yesudian Paul Devakar
Published: June 2024

Roflumilast is a phosphodiesterase type 4 (PDE4) inhibitor commonly used in respiratory medicine to manage chronic obstructive lung disease. Recently, there have been case reports of its effectiveness in oral mucosal conditions. We review five patients with different erosive mucosal lesions who responded to this medication. All patients were commenced on 250 μg daily, increasing to 500 μg if indicated. Case 1 is a 57-year-old woman who presented to the dermatology/oral medicine (DOM) clinic with long-standing recurrent aphthous stomatitis from her late teens. Treatment with colchicine and dapsone in combination was ineffective. Roflumilast was added and colchicine was stopped following a positive response. Case 2 is a 78-year-old woman seen in DOM in 2021 with erosive oral lichen planus. She did not respond to oral hydroxychloroquine, mycophenolate mofetil, azathioprine and multiple tapering courses of systemic steroids. Roflumilast was commenced recently, and the patient has not reported any flares since. Case 3 is a 26-year-old man with recurrent erythema multiforme predominantly involving the oral mucosa with erosive changes. He was treated with dapsone, prophylactic valaciclovir, and multiple courses of tapering prednisolone. Response was noted but breakthrough flares continued to occur. Roflumilast was commenced 6 months ago with no flares noted since. Case 4 is a 67-year-old woman who presented to dermatology in 2022 with severe oral erosive lichen planus of 4 years’ duration. Treatment with courses of oral prednisolone, hydroxychloroquine and acitretin were ineffective. Roflumilast was introduced, with excellent remission of all the erosions for the last 7 months. Case 5 is a 34-year-old woman who presented to DOM in August 2021 with recurrent deep, severe aphthous stomatitis. She was previously prescribed mycophenolate mofetil and reducing oral systemic steroids by dermatology for severe pyoderma gangrenosum; however, it did not help the oral ulcers. Hydroxychloroquine, colchicine and azathioprine were ineffective for the aphthous stomatitis. Roflumilast was commenced, resulting in clearance of the oral ulcers. Roflumilast acts by inhibiting PDE4, which in turn increases cyclic adenosine monophosphate, and this causes inflammatory modulators such as interleukins and tumour necrosis factor-α to be downregulated. These inflammatory mediators play a role in oral erosive conditions such as oral lichen planus and recurrent aphthous stomatitis. PDE4 inhibitors, including roflumilast and apremilast, have shown promising results in managing oral ulceration in patients with Behçet disease and aphthous ulcers. We advocate the use of roflumilast for oral erosive conditions when standard systemic agents are ineffective or cause side-effects.
BC02 Role of platelet-rich plasma in atrophic acne scars along with microneedling and subcision
Authors: Bhargava Shashank
Published: June 2024

Atrophic acne scarring is one of the most common sequel of acne vulgaris. The objective of this study was to evaluate the role of platelet-rich plasma (PRP) as adjunctive therapy to a combined subcision and needling treatment in severe (grade 4) atrophic acne scarring. In total 78 patients with grade 4 atrophic acne scars were randomly divided into two groups with 39 patients each: group A underwent three sessions of subcision and microneedling, while group B had three treatments of subcision, needling, and topical application of PRP. The sessions were repeated every 4 weeks. Scar grading was assessed 6 months following the final session. The participant’s assessment of treatment response was also considered. Scar improvement by ≥ 50% was reported significantly more often by patients in group B than in group A (P = 0.025). There were 11 patients from group B who improved by two grades, in comparison with only three from group A. The physician’s evaluation of improvement correlated with the patients’ own assessments: 50% of patients in group A and 67% in group B showed improvement of 25–49% and 50–74%, respectively. The mean duration of downtime was shorter among patients in group B than in group (21.1 vs. 32.9 h, respectively). Icepick scars showed the least improvement when compared with other variants of atrophic scars. In conclusion, PRP definitely works as an adjuvant modality to treat atrophic acne scars.
BC06 A systematic review of social media and Melanotan, the ‘Barbie drug’
Authors: O’Mahony Sarah , Connolly Archie , Collins Aoibhin , Alhunay Talal , Edgar Katie , Hynes Madeline , Tobin Anne Marie
Published: June 2024

Melanotan, a term referring to both Melanotan I (MT1) and Melanotan II (MT2), is a synthetic analogue of the endogenous hormone, α-melanocyte-stimulating hormone (α-MSH). Although the compound is unregulated and unlicensed, it is commonly exploited for its ability to produce a sunless tan. Melanotan has recently regained notoriety through social media platforms such as TikTok, a video-sharing online platform. The substance gained traction on TikTok, where the hormone is known as the ‘vacation peptide’. MT2 is an illicit substance sold on websites such as www.trutan.net, in gyms and in aesthetic clinics. The ‘Barbie drug’, MT2 promises to suppress appetite and thus induce weight loss, increase libido and produce an artificial tan that does not wash off. Recent increases in social media use have demonstrated positive correlations with body dissatisfaction. As a result, one can see how, in a world where social media has been demonstrated to cultivate body dissatisfaction, a seemingly quick-fix solution may prove attractive. MT2 is injected subcutaneously or administered intranasally via nasal sprays to produce increased skin pigmentation in the user via stimulation of melanocytes. From baking in the sun, to messy applications of temporary tans, and the now declining popularity of sunbed use, this new method of achieving a darker complexion surfaced incidentally. Initially researched for their photoprotective properties and their potential to reduce skin cancer, these synthetic hormones were found to have the desirable effects that are now sought after by self-proclaimed Instagram ‘influencers’ and fitness models. Despite being structurally different compounds, both are α-MSH analogues; α-MSH is a nonselective full agonist that targets melanocortin receptors. MT1 and MT2, in turn, act as relatively nonspecific agonists at melanocortin receptors. MT1 is more structurally like α-MSH and maintains its high affinity for the melanocortin 1 receptor (MCR1), while MT2 has an increased affinity for melanocortin 4 receptors (MCR4). This explains the increased pigmentation effects of both analogues, while MT2 also has additional sexual effects due to the role of MCR4 in sexual behaviour and erectile function. This systematic review aims to explore the impact of social media on Melanotan consumer perception through qualitative analysis. Four relevant studies were included in this systematic review. The results revealed that social media is a driving force in unlicensed Melanotan sales. Additionally, it was made clear that very few social media posts show Melanotan in a negative light, despite its deleterious adverse effects. From a perspective of safety, the results of this study outline a need for increased awareness of the negative aspects of Melanotan throughout social media platforms.
PD02 Sunscreen database app
Authors: Parkin Donna , Kayamkhani Surayyakhanam , Ayer Jean
Published: June 2024

Sunscreens play a pivotal role in the effective management of photodermatoses by safeguarding the skin against harmful ultraviolet radiation, thereby mitigating the onset or exacerbation of symptoms. However, complications arise when individuals develop allergies to sunscreen filters and other formula constituents. Navigating the process of finding a suitable sunscreen that offers adequate protection without triggering adverse reactions can often be challenging. Careful scrutiny of product labels is vital for individuals with known allergies. However, deciphering ingredient information can be difficult due to the small print size and complex chemical names. To address this, we present the development of an innovative sunscreen database designed to help healthcare professionals to identify appropriate sunscreens for patients with sunscreen allergies in a clinical setting. The Sunscreen database has been developed using Power Apps. The application has two interfaces, one for administrators and one for guest users. Administrators are granted access to add, edit and delete sunscreens and ingredients in the existing dataset. Various data fields are provided, including the sunscreen name, sun protection factor, star rating, ingredients, ultraviolet filters, formulation date, and company details. The home page displays a table of all sunscreens we have populated the database with. Filter and search options using simple drop-down menus provide a customized list of sunscreens, facilitating easy access to sunscreen information and quick and accurate decision making. The app allows groups to be assigned to ingredients with several names, which keeps the ingredient list simple. Moreover, if an ingredient from a group is selected for filtering out of the sunscreen dataset, all the remaining ingredients in that group will be automatically selected as well. This saves time and effort that would otherwise be spent manually selecting each individual ingredient in a group. Currently, the app can only be used by clinicians within the Northern Care Alliance, as the current system is set up for data integrity and security. External use may be permitted, but at this early stage, access must be granted from the IT department and their email added as a guest into the trust network. The aim of this project is to provide clinicians with a tool that generates printable, personalized recommendations for this patient group, especially for those who have confirmed allergies following formal patch testing. By providing patients with an allergen-free list of sunscreens, the app empowers them to make informed choices about the sunscreen products they use.