bluuebunny/crossref_metadata_2025_split huggingface dataset:
O05 Management of acute desloughing of the oesophageal lining in patients with dystrophic epidermolysis bullosa: a case series of six paediatric patients
Authors: Bageta Maria , Balboa Pablo Lopez , Yerlett Natalie , Rybak Anna , Petrof Gabriela , Martinez Anna 
Published: August 2023

Abstract
Dystrophic epidermolysis bullosa (DEB) is a subtype of inherited skin disorders characterized by skin and mucosal fragility due to collagen VII (COL7A1) gene mutations. Desloughing of the lining of the oesophagus has not been reported before. We retrospectively reviewed the hospital electronic patient records between 2008 and 2021 with regard to acute treatment and long-term management. Six patients with recessive DEB (RDEB) severe (n = 4), RDEB intermediate (n = 1) and dominant DEB (DDEB) were identified. The mean age at the time of the episode was 29.6 months. Most of the patients (n = 5) suffered from severe gastro-oesophageal reflux at the time of onset. Clinically, they presented with a coughing episode (n = 6), haematemesis (n = 6), vomiting (n = 6) and choking (n = 3) with a piece of mucosae coughed up. Four patients recovered with medical management including immediate hospitalization, no oral intake (nil by mouth, NBM), pain relief and optimization of the dose of proton-pump inhibitors. Due to severe persistent dysphagia, two patients required gastrostomy insertions for feeding; one also required a Nissen's fundoplication due to severe reflux. One patient had an aspiration pneumonia. Desloughing of varying lengths of segments of the oesophagus is an emergency. The lining coughed up needs to be cut at the mouth not pulled and the emergency services called immediately. On arrival, an urgent assessment and chest X-ray should be performed to rule out any signs of perforation. The patient should be kept NBM with intravenous fluids and pain relief. Expert multidisciplinary care is needed to manage this rare but extremely serious condition.
O06 Novel multispectral imaging vs. clinical assessment to assess disease activity in paediatric morphoea
Authors: O’Connor Cathal , McCarthy Siobhan , McCauliffe Michael , Bennett Mary 
Published: August 2023

Abstract
The assessment of disease activity in paediatric morphoea is challenging. Clinical examination and the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) are subjective. Thermography is the monitoring tool of choice but has a high rate of false-positive results, with low specificity. Multispectral imaging (measuring depth, volume, haemoglobin and melanin) may provide a noninvasive objective assessment of disease activity. The aim of this study was to compare activity assessment with multispectral imaging vs. clinical assessment in children with morphoea. 3D images of site-matched affected and unaffected skin were obtained using a handheld portable Antera 3D camera (Miravex Ltd). Analysis of depth, volume, haemoglobin and melanin was performed using the Antera Clinical Studies software. Objective and subjective clinical assessment was performed using LoSCAT and Children's Dermatology Life Quality Index (CDLQI). To date, 17 children (age range 7–18 years) have been recruited. Two-thirds (65%) had linear morphoea and 58% were treated with systemic agents (pulsed methylprednisolone, methotrexate, mycophenolate mofetil, abatacept). Average LoSCAT scores were 20.6 (range 5–73), and average CDLQI scores were 3.7 (range 0–14). The average haemoglobin gradient between affected and unaffected skin was 0.3 in children with active disease and 0.08 in those who had persistent disease remission (P &lt; 0.0001). The sensitivity of multispectral imaging in paediatric morphoea is 90% with specificity of 100%, giving a positive predictive value of 100%, and a negative predictive value of 95%. Multispectral imaging of affected skin may aid activity detection in paediatric morphoea and is particularly useful in darkly pigmented skin.
O10 Cohort study of paradoxical psoriasis in an adolescent population receiving anti-tumour necrosis factor-α for inflammatory bowel disease in a large teaching hospital with specialist dermatology and paediatric gastroenterology services
Authors: Shareef Narin , Price Josephina , Ferguson Leila , Abdul-Wahab Alya 
Published: August 2023

Abstract
Paradoxical psoriasis is well recognized in adults receiving anti-tumour necrosis factor-(TNF)-α therapy for inflammatory bowel disease (IBD) [Bucalo A, Rega F, Zangrilli A et al. Paradoxical psoriasis induced by anti-TNFα treatment: evaluation of disease-specific clinical genetic markers. Int J Mol Sci 2020; 21: 7873. https://doi.org/10.3390/ijms21217873]. Biologics are increasingly being initiated earlier in the treatment ladder for IBD in the paediatric population, who are also vulnerable to paradoxical psoriasis. This observational study aimed to describe the clinical features and management in this group, as there are limited data on how paradoxical psoriasis differs in children. Eight patients with paradoxical psoriasis were referred between 2019 and 2022: five females and three males; age range 12–19 years (mean 15.4 years). They all had Crohn disease and were receiving infliximab (7/8 patients) or adalimumab (1/8). The onset of symptoms following anti-TNF-α initiation was 3 months to 3 years (mean 12.75 months). Involvement included scalp (7), flexural areas (3), trunk (4) limb (3) and face (1). In adults, palmoplantar and pustular forms were commonly reported whereas our cohort demonstrated eczematous forms requiring antibacterial agents, rarely seen in adults. Management included switching from infliximab to ustekinumab in three patients; and the addition of methotrexate (two). Topical treatments alone were sufficient in three patients. There were florid presentations in our cohort and the scalp was predominantly affected (7/8). Five of eight patients required a switch of their anti-TNF-α therapy or an additional systemic treatment. It is crucial for physicians to be aware of this phenomenon and work collaboratively to recognize this early to optimize patients’ symptoms and quality of life [Bucalo et al.].
P07 Quality improvement project of acute referrals to the on-call dermatology service
Authors: Jayaprakash Sindoora , Millette Dijon , Khan Farishta 
Published: August 2023

Abstract
With dermatology services now integrating neural networks and artificial intelligence into departments, the importance of technology to streamline services has been timely in light of the increased influx of referrals needing remote reviews from both community and secondary care. We performed a department quality improvement project to compare referrals made to the on-call dermatology service, Dudley Group NHS trust, during September 2019 and September 2020 against the ‘COVID-19: Clinical guidelines for the management of dermatology patients remotely’. Data were collected from telephone, paper and email referrals made in September 2019 and 2020. Referral data including patient demographics, nature and urgency of referrals, diagnosis, availability of medical photography and follow-up arrangements was collated on a Microsoft Excel Proforma. Of 74 total referrals (35 in 2019; 39 in 2020), hospital referrals in September 2020 (92%, n = 36) largely outweighed GP referrals (8%, n = 3). Urgent referrals made by hospital departments rose from 17% (n = 5 of 29) in September 2019 to 53% (n = 19 of 36) in September 2020. Medical photography, often essential for triage and diagnosis, was available only at the time of referral in 8.6% (n = 3) of cases in 2019 and 48.7% (n = 19) in 2020. The rise may be explained by an increased dependence on remote services. With current pressures placing greater demand on resources, there is a need for online referral systems. Moving away from emails, letters and phone calls ensures a less user-dependent interface. Medical photography can be implemented as an integral feature of referral. Online systems facilitate triage and remote management in keeping with dermatological guidelines.
P20 Job syndrome: hyper IgE syndrome in a young girl with an acneiform rash
Authors: Hefferon Tom , Byrne Berbie , Leahy Marion , Murphy Annette 
Published: August 2023

Abstract
Hyper IgE syndrome (HIES1) is a rare, autosomal dominant, primary immunodeficiency characterized by eczema, recurrent staphylococcal skin infections, pneumonia, increased serum IgE and eosinophilia. It is caused by a heterozygous mutation in the STAT3 gene on chromosome 17q21 with variable expressivity. Nonimmunological findings including characteristic facies, hyperextensibility, long-bone fractures, aneurysms, craniosynostosis and dental abnormalities. We present the case of an 11-year-old girl referred to dermatology with an acneiform facial rash. Examination was consistent with papulo-pustular scarring acne of the face and back. Her history was also significant for recurrent MSSA bacterial lymphadenitis requiring incision and drainage over the proceeding 3 years. Her past medical history was significant for the development of moderate-severity infantile acne at 2 weeks of age, mild childhood eczema, recurrent childhood otitis media Staphylococcus infections resulting in grommet insertion, primary tooth retention requiring extraction and a fractured wrist at age 9 years. Because of the burden of infection the patient was referred to immunology in Crumlin. Investigations revealed mild neutropenia, marginally elevated IgA and IgM, normal eosinophils, marginally elevated IgE, normal lymphocyte subsets, intact complement pathways and normal oxidative burst test. Next-generation sequencing was significant for STAT3 gene mutation consistent with HIES. As there is no family history this likely represents a de novo mutation. The patient is currently on prophylactic azithromycin and low-dose isotretinoin with good effect. This case represents a patient with both immunological and nonimmunological features of HIES1, marginally elevated IgE, absence of eosinophils and negative family history.
P22 Life-threatening bleeding is a serious potential complication of ulcerated congenital haemangiomas: three case reports
Authors: Alenezi Hadi , Solman Lea 
Published: August 2023

Abstract
Congenital haemangiomas (CH) are rare vascular tumours that can be complicated by high-output heart failure (HOHF), transient thrombocytopaenia and ulceration. We present three patients who had life-threatening bleeding from the ulcerated CH, which was fatal for one of the patients. The first patient was born with a large CH of his left thigh, causing thrombocytopaenia and HOHF, requiring ventilation. He was discharged home after 3 weeks, but subsequently developed an ulceration and had a profuse bleeding following a dressing change at home. He required admission to PICU and ventilation support. The second patient was born with a large segmental CH of his right scalp with two ulcerated areas, without HOHF or thrombocytopaenia. He developed a massive bleeding from the ulcerated area at 6 weeks of age, was admitted to PICU with cardiac arrest, but died a few hours later due to multiorgan failure. The third patient was born at 29 weeks’ gestation with a large CH of her right thigh which was ulcerated. She had a profuse arterial bleeding after the dressing was removed in the hospital, requiring emergency surgery and admission to PICU. Although it is a rare complication, neonates/infants with ulcerated CH are at risk for severe, life-threatening arterial bleeding. If an ulceration is present, it needs to be protected with a suitable dressing, until it heals completely. Parents need to be educated on appropriate dressing changing technique, have the support of local tissue viability nurses and learn basic CPR techniques should arterial bleeding occur and necessitate CPR.
Failure of scabies treatment: a systematic review and meta-analysis
Authors: Mbuagbaw Lawrence , Sadeghirad Behnam , Morgan Rebecca L , Mertz Dominik , Motaghi Shahrzad , Ghadimi Maryam , Babatunde Ifeoluwa , Zani Babalwa , Pasumarthi Tejanth , Derby McKenzie , Kothapudi Venkata N , Palmer Nicole R , Aebischer Anton , Harder Thomas , Reichert Felix 
Published: August 2023

Abstract

Background
Treatment failure is considered to be an important factor in relation to the increase in scabies incidence over the last decade. However, the regional and temporal differences, in addition to the predictors of therapy failure, are unclear.

Objectives
We aimed to conduct a systematic review of the prevalence of treatment failure in patients with scabies and investigation of associated factors.

Methods
We searched MEDLINE, EMBASE, CINAHL, Web of Science, Scopus, Global Health and the Cochrane Central Register of Controlled Trials from inception to August 2021 for randomized and quasi-randomized trials, in addition to observational studies that enrolled children or adults diagnosed with confirmed or clinical scabies treated with permethrin, ivermectin, crotamiton, benzyl benzoate, malathion, sulfur or lindane, and measured treatment failure or factors associated with treatment failure. We performed a random effects meta-analysis for all outcomes reported by at least two studies.

Results
A total of 147 studies were eligible for inclusion in the systematic review. The overall prevalence of treatment failure was 15.2% [95% confidence interval (CI) 12.9–17.6; I2 = 95.3%, moderate-certainty evidence] with regional differences between World Health Organization regions (P = 0.003) being highest in the Western Pacific region (26.9%, 95% CI 14.5–41.2). Oral ivermectin (11.8%, 95% CI 8.4–15.4), topical ivermectin (9.3%, 95% CI 5.1–14.3) and permethrin (10.8%, 95% CI 7.5–14.5) had relatively lower failure prevalence compared with the overall prevalence. Failure prevalence was lower in patients treated with two doses of oral ivermectin (7.1%, 95% CI 3.1–12.3) compared with those treated with one dose (15.2%, 95% CI 10.8–20.2; P = 0.021). Overall and permethrin treatment failure prevalence in the included studies (1983–2021) increased by 0.27% and 0.58% per year, respectively. Only three studies conducted a multivariable risk factor analysis; no studies assessed resistance.

Conclusions
A second dose of ivermectin showed lower failure prevalence than single-dose ivermectin, which should be considered in all guidelines. The increase in treatment failure over time hints at decreasing mite susceptibility for several drugs, but reasons for failure are rarely assessed. Ideally, scabicide susceptibility testing should be implemented in future studies.
SUN1 facilitates CHMP7 nuclear influx and injury cascades in sporadic amyotrophic lateral sclerosis
Authors: Baskerville Victoria , Rapuri Sampath , Mehlhop Emma , Coyne Alyssa N 
Published: August 2023

AbstractWe have recently identified the aberrant nuclear accumulation of the ESCRT-III protein CHMP7 as an initiating event that leads to a significant injury to the nuclear pore complex (NPC) characterized by the reduction of specific nucleoporins from the neuronal NPC in sporadic amyotrophic lateral sclerosis (sALS) and C9orf72 ALS/frontotemporal dementia (FTD)-induced pluripotent stem cell-derived neurons (iPSNs), a phenomenon also observed in post-mortem patient tissues. Importantly, this NPC injury is sufficient to contribute to TDP-43 dysfunction and mislocalization, a common pathological hallmark of neurodegenerative diseases. However, the molecular mechanisms and events that give rise to increased nuclear translocation and/or retention of CHMP7 to initiate this pathophysiological cascade remain largely unknown. Here, using an iPSN model of sALS, we demonstrate that impaired NPC permeability barrier integrity and interactions with the LINC complex protein SUN1 facilitate CHMP7 nuclear localization and the subsequent ‘activation’ of NPC injury cascades. Collectively, our data provide mechanistic insights in the pathophysiological underpinnings of ALS/FTD and highlight SUN1 as a potent contributor to and modifier of CHMP7-mediated toxicity in sALS pathogenesis.
Depression and HIV: a scoping review in search of neuroimmune biomarkers
Authors: Mudra Rakshasa-Loots Arish 
Published: August 2023

Abstract
People with HIV are at increased risk for depression, though the neurobiological mechanisms underlying this are unclear. In the last decade, there has been a substantial rise in interest in the contribution of (neuro)inflammation to depression, coupled with rapid advancements in the resolution and sensitivity of biomarker assays such as Luminex, single molecular array and newly developed positron emission tomography radioligands. Numerous pre-clinical and clinical studies have recently leveraged these next-generation immunoassays to identify biomarkers that may be associated with HIV and depression (separately), though few studies have explored these biomarkers in co-occurring HIV and depression. Using a systematic search, we detected 33 publications involving a cumulative N = 10 590 participants which tested for associations between depressive symptoms and 55 biomarkers of inflammation and related processes in participants living with HIV. Formal meta-analyses were not possible as statistical reporting in the field was highly variable; future studies must fully report test statistics and effect size estimates. The majority of included studies were carried out in the United States, with samples that were primarily older and primarily men. Substantial further work is necessary to diversify the geographical, age, and sex distribution of samples in the field. This review finds that alterations in concentrations of certain biomarkers of neuroinflammation (interleukin-6, tumour necrosis factor-α, neopterin) may influence the association between HIV and depression. Equally, the chemokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) or the metabolic index kynurenine:tryptophan (Kyn:Trp), which have been the focus of several studies, do not appear to be associated with depressive symptoms amongst people living with HIV, as all (MCP-1) or most (IL-8 and Kyn:Trp) available studies of these biomarkers reported non-significant associations. We propose a biomarker-driven hypothesis of the neuroimmunometabolic mechanisms that may precipitate the increased risk of depression among people with HIV. Chronically activated microglia, which trigger key neuroinflammatory cascades shown to be upregulated in people with HIV, may be the central link connecting HIV infection in the central nervous system with depressive symptoms. Findings from this review may inform research design in future studies of HIV-associated depression and enable concerted efforts towards biomarker discovery.
Cost-effectiveness of Low-complexity Screening Tests in Community-based Case-finding for Tuberculosis
Authors: Brümmer Lukas E , Thompson Ryan R , Malhotra Akash , Shrestha Sourya , Kendall Emily A , Andrews Jason R , Phillips Patrick , Nahid Payam , Cattamanchi Adithya , Marx Florian M , Denkinger Claudia M , Dowdy David W 
Published: August 2023

Abstract

Introduction
In high-burden settings, low-complexity screening tests for tuberculosis (TB) could expand the reach of community-based case-finding efforts. The potential costs and cost-effectiveness of approaches incorporating these tests are poorly understood.

Methods
We developed a microsimulation model assessing 3 approaches to community-based case-finding in hypothetical populations (India-, South Africa-, The Philippines-, Uganda-, and Vietnam-like settings) with TB prevalence 4 times that of national estimates: (1) screening with a point-of-care C-reactive protein (CRP) test, (2) screening with a more sensitive “Hypothetical Screening test” (95% sensitive for Xpert Ultra-positive TB, 70% specificity; equipment/labor costs similar to Xpert Ultra, but using a $2 cartridge) followed by sputum Xpert Ultra if positive, or (3) testing all individuals with sputum Xpert Ultra. Costs are expressed in 2023 US dollars and include treatment costs.

Results
Universal Xpert Ultra was estimated to cost a mean $4.0 million (95% uncertainty range: $3.5 to $4.6 million) and avert 3200 (2600 to 3900) TB-related disability-adjusted life years (DALYs) per 100 000 people screened ($670 [The Philippines] to $2000 [Vietnam] per DALY averted). CRP was projected to cost $550 (The Philippines) to $1500 (Vietnam) per DALY averted but with 44% fewer DALYs averted. The Hypothetical Screening test showed minimal benefit compared to universal Xpert Ultra, but if specificity were improved to 95% and per-test cost to $4.5 (all-inclusive), this strategy could cost $390 (The Philippines) to $940 (Vietnam) per DALY averted.

Conclusions
Screening tests can meaningfully improve the cost-effectiveness of community-based case-finding for TB but only if they are sensitive, specific, and inexpensive.
Doxorubicin-induced cardiovascular toxicity: a longitudinal evaluation of functional and molecular markers
Authors: Bosman Matthias , Krüger Dustin , Van Assche Charles , Boen Hanne , Neutel Cédric , Favere Kasper , Franssen Constantijn , Martinet Wim , Roth Lynn , De Meyer Guido R Y , Cillero-Pastor Berta , Delrue Leen , Heggermont Ward , Van Craenenbroeck Emeline M , Guns Pieter-Jan 
Published: August 2023

Abstract

Aims
Apart from cardiotoxicity, the chemotherapeutic doxorubicin (DOX) induces vascular toxicity, represented by arterial stiffness and endothelial dysfunction. Both parameters are of interest for cardiovascular risk stratification as they are independent predictors of future cardiovascular events in the general population. However, the time course of DOX-induced cardiovascular toxicity remains unclear. Moreover, current biomarkers for cardiovascular toxicity prove insufficient. Here, we longitudinally evaluated functional and molecular markers of DOX-induced cardiovascular toxicity in a murine model. Molecular markers were further validated in patient plasma.

Methods and results
DOX (4 mg/kg) or saline (vehicle) was administered intra-peritoneally to young, male mice weekly for 6 weeks. In vivo cardiovascular function and ex vivo arterial stiffness and vascular reactivity were evaluated at baseline, during DOX therapy (Weeks 2 and 4) and after therapy cessation (Weeks 6, 9, and 15). Left ventricular ejection fraction (LVEF) declined from Week 4 in the DOX group. DOX increased arterial stiffness in vivo and ex vivo at Week 2, which reverted thereafter. Importantly, DOX-induced arterial stiffness preceded reduced LVEF. Further, DOX impaired endothelium-dependent vasodilation at Weeks 2 and 6, which recovered at Weeks 9 and 15. Conversely, contraction with phenylephrine was consistently higher in the DOX-treated group. Furthermore, proteomic analysis on aortic tissue identified increased thrombospondin-1 (THBS1) and alpha-1-antichymotrypsin (SERPINA3) at Weeks 2 and 6. Up-regulated THBS1 and SERPINA3 persisted during follow-up. Finally, THBS1 and SERPINA3 were quantified in plasma of patients. Cancer survivors with anthracycline-induced cardiotoxicity (AICT; LVEF &lt; 50%) showed elevated THBS1 and SERPINA3 levels compared with age-matched control patients (LVEF ≥ 60%).

Conclusions
DOX increased arterial stiffness and impaired endothelial function, which both preceded reduced LVEF. Vascular dysfunction restored after DOX therapy cessation, whereas cardiac dysfunction persisted. Further, we identified SERPINA3 and THBS1 as promising biomarkers of DOX-induced cardiovascular toxicity, which were confirmed in AICT patients.