tbuckley/cabot-search huggingface dataset:
Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial
Authors: Hedyeh Ebrahimi, Nazli Dizman, Luis Meza, Jasnoor Malhotra, Xiaochen Li, Tanya Dorff, Paul Frankel, Marian Llamas-Quitiquit, Joann Hsu, Zeynep B. Zengin, Marice Alcantara, Daniela Castro, Benjamin Mercier, Neal Chawla, Alex Chehrazi-Raffle, Regina Barragan-Carrillo, Salvador Jaime-Casas, Ameish Govindarajan, John Gillece, Jeffrey Trent, Peter P. Lee, Thomas P. Parks, Motomichi Takahashi, Atsushi Hayashi, Marcin Kortylewski, J. Gregory Caporaso, Keehoon Lee, Abhishek Tripathi, Sumanta K. Pal
Journal: Nature Medicine (2024)

Supplementation with CBM588, a bifidogenic live bacterial product, has been associated with improved clinical outcomes in persons with metastatic renal cell carcinoma (mRCC) receiving nivolumab and ipilimumab. However, its effect on those receiving tyrosine kinase inhibitor-based combinations is unknown. In this open-label, randomized, investigator-initiated, phase 1 study, 30 participants with locally advanced or mRCC with histological confirmation of clear cell, papillary or sarcomatoid component were randomized in a 2:1 fashion to receive cabozantinib (an inhibitor of vascular endothelial growth factor receptor, MET and AXL) and nivolumab (anti-programmed cell death protein 1) with or without CBM588 as first-line treatment. Metagenomic sequencing was performed on stool samples to characterize their gut microbiome at baseline and 13 weeks into treatment. The primary endpoint was a change in the relative abundance of Bifidobacterium spp.; secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and toxicity profile. The primary endpoint of the study was not met and the addition of CBM588 to cabozantinib and nivolumab did not result in a difference in the relative abundance of Bifidobacterium spp. or alpha diversity (as measured by the Shannon index). However, ORR was significantly higher in participants treated with CBM588 compared to those in the control arm (14 of 19, 74% versus 2 of 10, 20%; P = 0.01). PFS at 6 months was 84% (16 of 19) and 60% (6 of 10) in the experimental and control arms, respectively. No significant difference in toxicity profile was seen between the study arms. Our results provide a preliminary signal of improved clinical activity with CBM588 in treatment-naive participants with mRCC receiving cabozantinib and nivolumab. Further investigation is needed to confirm these findings and better characterize the underlying mechanism driving this effect.ClinicalTrials.gov identifier: NCT05122546.
CPC13 BRAF mutated and morphologically Spitz naevi and tumours: a series of four cases
Authors: Maged Daruish, Helen Goodyear, Julie Lemahieu, Saleem Taibjee
Journal: British Journal of Dermatology (2024)

Abstract The current World Health Organization classification of skin tumours (5th edition) indicates that melanocytic tumours of the Spitz pathway can be defined by mutually exclusive oncogenic drivers, including HRAS-activating mutations or kinase fusions. Accordingly, the term ‘spitzoid’ has been suggested for tumours that show morphological features of Spitz tumours but lack these defining molecular aberrations. Such neoplasms harbouring BRAF or NRAS mutations include a subtype of melanomas with confirmed risk of local recurrence and metastasis. In contrast, a recent study described a subset of Spitz-looking neoplasms with BRAF mutations and insufficient criteria for melanoma (Zhao J, Benton S, Zhang B et al. Benign and intermediate-grade melanocytic tumours with BRAF mutations and Spitzoid morphology. Am J Surg Pathol 2022; 46: 476–85). The term BRAF mutated and morphologically spitzoid naevi/tumours (BAMS) was proposed for such lesions. We present a series of four cases of BAMS. The patients ranged in age from 3 to 40 years; three were male and one was female. The clinical history varied from new growing moles to change within long-standing lesions, congenital in one instance. One lesion was submitted with the query of halo naevus. Anatomical sites included the abdomen, pubis, right buttock and left upper back. In one of our cases the clinical appearance, including starburst pattern on dermoscopy, was very suggestive of a pigmented Spitz naevus. All cases showed a predominantly epithelioid cytomorphology with accompanying melanophages. The cytoplasmic pigment was prominent in three cases. Three of the neoplasms were compound, with evidence of maturation with depth. The case described clinically as a changing congenital lesion had a mild degree of cytological atypia, a single superficial mitosis and focal PReferentially expressed Antigen in MElanoma positivity. In this case there was bridging of nests and lamellar fibroplasia, indicating overlapping features with Clark dysplastic naevus. Three cases had Kamino bodies. Immunostaining for BRAF V600E was positive in all cases. Overall, the histological findings in our cohort are in concordance with those reported by Zhao et al. Interestingly, BRAF mutations were also identified in another study of ‘Spitz naevi’, likely representing BAMS (Fullen DR, Poynter JN, Lowe L et al. BRAF and NRAS mutations in spitzoid melanocytic lesions. Mod Pathol 2006; 19: 1324–32). Further studies are necessary to characterize the BAMS group, including long-term follow-up. Recognition of this group of tumours is important to avoid melanoma overdiagnosis in the advent of ancillary immunohistochemistry and molecular testing in determining melanocytic lineage in day-to-day practice.
Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer
Authors: Linda Bojmar, Constantinos P. Zambirinis, Jonathan M. Hernandez, Jayasree Chakraborty, Lee Shaashua, Junbum Kim, Kofi Ennu Johnson, Samer Hanna, Gokce Askan, Jonas Burman, Hiranmayi Ravichandran, Jian Zheng, Joshua S. Jolissaint, Rami Srouji, Yi Song, Ankur Choubey, Han Sang Kim, Michele Cioffi, Elke van Beek, Carlie Sigel, Jose Jessurun, Paulina Velasco Riestra, Hakon Blomstrand, Carolin Jönsson, Anette Jönsson, Pernille Lauritzen, Weston Buehring, Yonathan Ararso, Dylanne Hernandez, Jessica P. Vinagolu-Baur, Madison Friedman, Caroline Glidden, Laetitia Firmenich, Grace Lieberman, Dianna L. Mejia, Naaz Nasar, Anders P. Mutvei, Doru M. Paul, Yaron Bram, Bruno Costa-Silva, Olca Basturk, Nancy Boudreau, Haiying Zhang, Irina R. Matei, Ayuko Hoshino, David Kelsen, Irit Sagi, Avigdor Scherz, Ruth Scherz-Shouval, Yosef Yarden, Moshe Oren, Mikala Egeblad, Jason S. Lewis, Kayvan Keshari, Paul M. Grandgenett, Michael A. Hollingsworth, Vinagolu K. Rajasekhar, John H. Healey, Bergthor Björnsson, Diane M. Simeone, David A. Tuveson, Christine A. Iacobuzio-Donahue, Jaqueline Bromberg, C. Theresa Vincent, Eileen M. O’Reilly, Ronald P. DeMatteo, Vinod P. Balachandran, Michael I. D’Angelica, T. Peter Kingham, Peter J. Allen, Amber L. Simpson, Olivier Elemento, Per Sandström, Robert E. Schwartz, William R. Jarnagin, David Lyden
Journal: Nature Medicine (2024)
PA08 Extensive congenital epidermal skin loss with sparing of the palms, soles and head: strikingly similar appearances in four patients with neonatal herpes simplex infection
Authors: Emily Vaughan, Pablo Lopez Balboa, Anna Martinez, Jane Ravenscroft
Journal: British Journal of Dermatology (2024)

Abstract We present a case series of four preterm neonates from two tertiary centres in the UK. All presented at birth with 90% epidermal skin loss. In all four neonates, there was a strikingly similar presentation, with skin spared on the palms, soles, and areas on either the face or scalp. Three of the neonates tested positive for herpes simplex virus (HSV) type 1 and one tested positive for HSV type 2 on skin swabs taken soon after birth. None of the mothers gave a history of genital HSV infection. In the past, this pattern of skin loss has been attributed to severe congenital erosive and vesicular dermatosis, with a differential diagnosis of aplasia cutis or epidermolysis bullosa. HSV has been recognized in a few cases but there is limited literature available discussing widespread skin loss secondary to HSV infection. In utero HSV is rare in neonates and accounts for 5% of all neonatal herpes infections. Intrauterine HSV has an increased risk of preterm labour and has been reported to occur in asymptomatic mothers with no history of genital herpes. HSV contracted in utero commonly presents with cutaneous lesions in the context of an unwell neonate and carries a high risk of eye involvement, mouth disease and neurological complications such as encephalitis, meningitis and neurodisability. Babies with this suspected diagnosis need urgent skin swabs for viral polymerase chain reaction and bacterial culture. Early treatment with high-dose intravenous antivirals prior to swab results is essential. Full neonatal intensive care support is needed, as well as analgesia, gentle handling and antibiotics. Neonates are best managed in a tertiary neonatal intensive care setting with input from the national epidermolysis bullosa team, due to the extensive nature of the skin loss. Two of our cases healed with severe reticulated scarring and contractures, requiring multiple procedures and extensive physiotherapy. The other two did not survive the neonatal period despite early diagnosis and a multidisciplinary approach. Management of HSV in future pregnancies must be discussed with the obstetric team. This is the first case series describing a characteristic pattern of severe skin loss among neonates with congenital HSV. We recommend early recognition and empirical treatment of HSV, while swabs are awaited.
PA15 Paediatric lupus vulgaris masquerading as an unusual facial lesion: a diagnostic dilemma
Authors: Ashima R Chandran
Journal: British Journal of Dermatology (2024)

Abstract We present a rare case of lupus vulgaris in a 9-year-old boy with an asymptomatic raised lesion on the left cheek, initially posing a diagnostic challenge due to its atypical presentation. Clinical and investigative findings were analysed, including the patient’s medical history, physical examination, routine investigations, Mantoux test, differential diagnoses, histopathological examination and response to treatment. The patient presented with a progressively enlarging, single, well-defined erythematous plaque (1 × 1 cm) on the left cheek over 2 months. Notably, a bacille Calmette–Guérin scar was present, and routine investigations, including chest X-ray, were normal. The Mantoux test yielded a positive result (18 mm). Differential diagnoses considered were borderline tuberculoid Hansen disease, lupus vulgaris, sarcoidosis, and granuloma annulare. Histopathological examination revealed mild flattening of the epidermis with elongated rete ridges, accompanied by numerous epithelioid granulomas in the dermis and epidermal junction, surrounded by inflammatory infiltrate. A 20% acid-fast bacilli (AFB) staining for Mycobacterium tuberculosis was positive. However, sputum smear for AFB was negative. The final diagnosis was lupus vulgaris, a rare form of cutaneous tuberculosis. This case highlights the importance of considering lupus vulgaris in the differential diagnosis of facial lesions, even in paediatric patients. The positive Mantoux test and histopathological findings supported the diagnosis, emphasizing the need for a multidisciplinary approach in challenging cases. Treatment involved a 6-month course of category 1 antitubercular therapy. This case underscores the significance of early diagnosis and prompt initiation of appropriate therapy to prevent complications and ensure a favourable outcome. This report contributes to the limited literature on lupus vulgaris in paediatric patients, emphasizing the necessity of vigilance among dermatologists in recognizing atypical presentations of cutaneous tuberculosis, particularly in regions with a high prevalence of tuberculosis.
PA06 A cross-sectional study to evaluate the clinical and allergenic differences between intrinsic and extrinsic forms of atopic dermatitis
Authors: Divya Garg, Rahul Mahajan, Vinod Kumar Sharma, Dipankar De, Sanjeev Handa
Journal: British Journal of Dermatology (2024)

Abstract Atopic dermatitis (AD) is now recognized as a condition comprising various endotypes, rather than being a homogeneous disease. One of these distinctions lies in the intrinsic and extrinsic forms of AD, which are pathogenetically different but exhibit subtle clinical differences. Limited knowledge is available regarding the comparison of clinical features between the two endotypes in paediatric populations and individuals with skin of colour. The aim of this study was to compare the frequency of occurrence of different demographic parameters and clinical features of AD between intrinsic and extrinsic AD. Consecutive children with AD, all under the age of 18 years, were enrolled. A comprehensive examination of their medical history and clinical assessment was conducted. Serum IgE levels were utilized to distinguish between extrinsic AD (characterized by high IgE) and intrinsic AD (associated with normal IgE levels). Additionally, assessments for food-allergen-specific IgE (with seven food allergens) and skin prick tests were performed. Out of the 200 children who were recruited, 181 (90.5%) had high IgE levels. The group with extrinsic AD showed a positive association with a personal history of atopy (P = 0.005), involvement of the dorsum of the hands and feet (P = 0.01), orbital darkening (P = 0.01), and prurigo-like lesions (P = 0.02). Conversely, the group with intrinsic AD exhibited a significant association with the presence of ichthyosis (P = 0.01). A moderate correlation (correlation coefficient, r = 0.48) between Scoring Atopic Dermatitis and IgE was observed, which was statistically significant (P &amp;lt; 0.001). According to the radioallergosorbent test, the most common food allergen was wheat (46.4%), followed by peanut (39.7%). In skin prick tests, the most common allergens were house dust mites, specifically Dermatophagoides pteronyssinus (52.4%) and Dermatophagoides farina (38.1%), followed by wheat dust (23.8%), whole egg (19%) and Blomia mites (19%). However, no significant association was found between either endotype and allergen testing. The findings highlight the clinical differences, disease course and associated factors between these subtypes, which can aid in accurate diagnosis, management, and personalized care for individuals with AD.
Finotonlimab with chemotherapy in recurrent or metastatic head and neck cancer: a randomized phase 3 trial
Authors: Yuankai Shi, Wei Guo, Wei Wang, Yunteng Wu, Meiyu Fang, Xiaoming Huang, Ping Han, Qingyuan Zhang, Pin Dong, Xiaohong Zhou, Hanwei Peng, Chunhong Hu, Xiaopin Chen, Shurong Zhang, Zhiwei Chang, Xiaojiang Li, Yuhai Ding, Song Qu, Shanghua Jing, Songnan Zhang, Lin Gui, Yan Sun, Lin Wang, Yanyan Liu, Hui Wu, Guoqing Li, Zhichao Fu, Jianhua Shi, Hao Jiang, Yuansong Bai, Jiuwei Cui, Yulong Zheng, Wei Cui, Xiaojing Jia, Limin Zhai, Qingqing Cai, Deming Xiong, Yunong Wu, Junning Cao, Rong Wu, Guangyuan Hu, Liang Peng, Liangzhi Xie, Wenlin Gai, Yan Wang, Yuehua Su
Journal: Nature Medicine (2024)
PA19 The importance of a paediatric biopsy service in dermatology departments: a service evaluation
Authors: Helena Wells, Raakhee Ramesh
Journal: British Journal of Dermatology (2024)

Abstract Access to paediatric skin biopsy services in dermatology departments varies widely. A timely skin biopsy can result in a quicker diagnosis for the family and child and hence swifter management, which is crucial for a paediatric dermatology service to run efficiently. Some services may be reliant upon assistance from other specialists, such as the plastic surgeon, to perform these procedures, which are sometimes preformed unnecessarily under a general anaesthetic. This can complicate the patient pathway, resulting in breaks in continuity of care and delays to investigations. Overall, there is a paucity of published data on skin biopsies in children, particularly on the indications and spectrum of diagnoses. We performed a service evaluation of our paediatric biopsy service at a busy district general hospital, to understand the role and importance of this service. We have a total of four paediatric dermatologists, who have regular clinics and theatre lists. We collected data retrospectively on paediatric biopsies performed between April 2020 and March 2023 (a 35-month period). Nearly all patients attending for a biopsy had clinical images taken. In total 71 biopsies were performed on children during this timeframe. Most patients were aged between 11 and 15 years (61%), with 7% aged 16–18 years, and the remainder aged &amp;lt; 10 years (32%). There was an even sex distribution, with 35 male patients and 36 female patients. A variety of procedures were performed, with punch biopsies (30%) and excision biopsies (24%) being the most common type. Regarding the body site, 17% of procedures were performed on the head and neck, and 8% on the scalp. In total, 41% were performed on the limbs, and 32% on the torso or abdomen. The biopsies were categorized as lesional or inflammatory. Forty-six biopsies (65%) were performed for lesions, of which pyogenic granuloma was the most common cause (15%), alongside spitz naevus (11%). Twenty-five biopsies (35%) were performed for inflammatory conditions, including folliculitis decalvans (1%), ichthyosis (1%), lymphangioma circumscriptum (1%) and confluent and reticulated papillomatosis (1%), alongside many other pathologies. Of lesional biopsies, 37 (80%) had the correct diagnosis listed prior to the procedure and 9 (20%) were incorrect. Of the inflammatory pathologies, 17 (68%) were correct, and 8 (32%) incorrect. This demonstrates the importance of the biopsy in identifying the diagnosis. Our data demonstrate the importance of a paediatric dermatology biopsy service offered at all sites where paediatric dermatology is undertaken, to aid in the diagnosis and management of paediatric patients in a timely fashion.
PA27 Expanding the phenotype of congenital erosive and vesicular dermatosis
Authors: Lindy Moxham, Sarah Felton, Joseph Lam
Journal: British Journal of Dermatology (2024)

Abstract Congenital erosive and vesicular dermatosis (CEVD) is a rare condition that typically presents at birth with erosions and vesicles (Cohen B, Esterly N, Nelson P. Congenital erosive and vesicular dermatosis healing with reticulated and supple scarring. Arch Dermatol 1985; 121: 361–7). Lesions heal with distinctive reticulate and supple scarring and can involve &amp;gt; 75% of the skin surface (Tlougan BE, Paller AM, Schaffer JV et al. Congenital erosive and vesicular dermatosis with reticulated supple scarring: unifying clinical features. J Am Acad Dermatol 2013; 69: 909–15). The pathogenesis of CEVD is unknown, although hypotheses include intrauterine infection, amniotic adhesions, or a developmental defect in skin healing. Histopathological findings early in the disease process can include epidermal necrosis, subepidermal vesiculation and an eroded epidermis. Older lesions demonstrate scar formation, decreased hair follicles, and absent eccrine glands. Historically, CEVD has been described as preferentially affecting the trunk and limbs, with sparing of the face and volar surfaces. Patients with CEVD have been reported to have higher prevalence of premature birth, neurodevelopmental abnormalities, nail abnormalities, tongue atrophy or sores, alopecia, and cardiac defects. Here, we highlight two patients with presumed CEVD with atypical features. Patient A presented at 13 months with a history of linear erosions and vesiculation over their scalp, forehead and posterior left flank. The lesions were present at birth and healed with reticulate scarring with no further flares. Patient B presented at 11 months with a history of stellate scarring over the lower abdomen, with noncontiguous involvement of the right and left axillae, scalp, and right forehead. The lesions were also present at birth and were initially more erythematous and developed milia-like cysts. The cysts resolved, leaving reticulate and supple scarring. Of note, patient B had no erosions or vesicles. At the time of assessment, both children were otherwise healthy and developing normally. These cases add to evidence that CEVD is neither facial nor scalp sparing, as commonly described, and can be more localized than previously thought, but affect noncontiguous sites. Case B also demonstrates that, despite the name, CEVD can present without erosions, and instead with milia-like cysts. The cases also demonstrate that CEVD can occur in the absence of other congenital abnormalities; outcomes for children with the condition are then more favourable. Both families were provided with reassurance that although the scarring would not disappear completely, and can be of cosmetic concern, CEVD is a nonprogressive condition and thus no specific treatment is indicated.
PA20 Follicular Becker naevus: an unusual presentation
Authors: Lucy Mackie, Dimalee Herath, Jessie Felton
Journal: British Journal of Dermatology (2024)

Abstract A 16-year-old girl presented with an asymptomatic hyperpigmented patch on the left chest, growing with her since the age of 7 years. Her medical history was unremarkable. Examination revealed a 9 × 5-cm lesion extending from the left areola to the left shoulder and one-third of the way round the midback. Dermoscopy revealed discrete &amp;lt; 5-mm dark-brown perifollicular macules, with some areas coalescing towards the back. Mild hyperkeratosis was present, with no hypertrichosis. This was diagnosed as a follicular Becker naevus, which is a novel variant not previously described in the UK. Becker naevus, also known as Becker melanosis and Becker pigmentary haematoma, was first described in 1949 by Samuel William Becker. It is a relatively common benign late-onset epidermal naevus, with proliferation of the epidermis, melanocytes and hair follicles. Occasionally it forms part of an epidermal naevus syndrome, known as Becker naevus syndrome. Traditionally, pigment networks in Becker naevus are described as even, but since 2020 seven follicular cases have been described in Kuwait, India and China. Six of the seven patients were male, all had skin of colour, and they were between the ages of 16 and 37 years. None had Becker naevus syndrome. There have been recent breakthroughs in understanding of the aetiology of Becker naevus. Cai et al. demonstrated postzygotic mutations in the ACTB gene (Cai ED, Sun BK, Chiang A et al. Postzygotic mutations in beta-actin are associated with Becker’s nevus and Becker’s nevus syndrome. J Invest Dermatol 2017; 137: 1795–8). There could be heterogeneity in mutations playing a role in the development of follicular lesions. Other recent advances include in the role of hormones. It has long been known that there is androgen dependence, but Sheng et al. have shown that oestrogen and progesterone receptors are also overexpressed in lesional skin and hair follicles (Sheng P, Cheng YL, Cai CC et al. Overexpression of androgen, oestrogen and progesterone receptors in skin lesions of Becker’s naevus. Acta Derm Venereol 2018; 98: 867–72). These advances raise interesting questions for genetics, pigmentation and hair research. Lesions are benign but the appearance can lead to psychological distress, affecting confidence and choice of clothing. Our patient was referred for cosmetic camouflage. Knowledge of this unusual diagnosis is important for being able to reassure patients and treat them appropriately.