Comparison of humans versus mobile phone-powered artificial intelligence for the diagnosis and management of pigmented skin cancer in secondary care: a multicentre, prospective, diagnostic, clinical trial.

BACKGROUND: Diagnosis of skin cancer requires medical expertise, which is scarce. Mobile phone-powered artificial intelligence (AI) could aid diagnosis, but it is unclear how this technology performs in a clinical scenario. Our primary aim was to test in the clinic whether there was equivalence between AI algorithms and clinicians for the diagnosis and management of pigmented skin lesions. METHODS: In this multicentre, prospective, diagnostic, clinical trial, we included specialist and novice clinicians and patients from two tertiary referral centres in Australia and Austria. Specialists had a specialist medical qualification related to diagnosing and managing pigmented skin lesions, whereas novices were dermatology junior doctors or registrars in trainee positions who had experience in examining and managing these lesions. Eligible patients were aged 18-99 years and had a modified Fitzpatrick I-III skin type; those in the diagnostic trial were undergoing routine excision or biopsy of one or more suspicious pigmented skin lesions bigger than 3 mm in the longest diameter, and those in the management trial had baseline total-body photographs taken within 1-4 years. We used two mobile phone-powered AI instruments incorporating a simple optical attachment: a new 7-class AI algorithm and the International Skin Imaging Collaboration (ISIC) AI algorithm, which was previously tested in a large online reader study. The reference standard for excised lesions in the diagnostic trial was histopathological examination; in the management trial, the reference standard was a descending hierarchy based on histopathological examination, comparison of baseline total-body photographs, digital monitoring, and telediagnosis. The main outcome of this study was to compare the accuracy of expert and novice diagnostic and management decisions with the two AI instruments. Possible decisions in the management trial were dismissal, biopsy, or 3-month monitoring. Decisions to monitor were considered equivalent to dismissal (scenario A) or biopsy of malignant lesions (scenario B). The trial was registered at the Australian New Zealand Clinical Trials Registry ACTRN12620000695909 (Universal trial number U1111-1251-8995). FINDINGS: The diagnostic study included 172 suspicious pigmented lesions (84 malignant) from 124 patients and the management study included 5696 pigmented lesions (18 malignant) from the whole body of 66 high-risk patients. The diagnoses of the 7-class AI algorithm were equivalent to the specialists' diagnoses (absolute accuracy difference 1·2% [95% CI -6·9 to 9·2]) and significantly superior to the novices' ones (21·5% [13·1 to 30·0]). The diagnoses of the ISIC AI algorithm were significantly inferior to the specialists' diagnoses (-11·6% [-20·3 to -3·0]) but significantly superior to the novices' ones (8·7% [-0·5 to 18·0]). The best 7-class management AI was significantly inferior to specialists' management (absolute accuracy difference in correct management decision -0·5% [95% CI -0·7 to -0·2] in scenario A and -0·4% [-0·8 to -0·05] in scenario B). Compared with the novices' management, the 7-class management AI was significantly inferior (-0·4% [-0·6 to -0·2]) in scenario A but significantly superior (0·4% [0·0 to 0·9]) in scenario B. INTERPRETATION: The mobile phone-powered AI technology is simple, practical, and accurate for the diagnosis of suspicious pigmented skin cancer in patients presenting to a specialist setting, although its usage for management decisions requires more careful execution. An AI algorithm that was superior in experimental studies was significantly inferior to specialists in a real-world scenario, suggesting that caution is needed when extrapolating results of experimental studies to clinical practice. FUNDING: MetaOptima Technology.

Diagnostic difficulties in pediatric annular dermatoses.

The polymorphic presentation of annular dermatoses in the pediatric population renders them a diagnostic challenge to the clinician. They include various distinct disease entities that can be vaguely categorized according to the age of onset. Herein, we report on a young girl with clinical characteristics of Wells' syndrome, while histological findings favored the diagnosis of annular erythema of infancy (AEI). Although morphological and histological similarities do exist, AEI and eosinophilic annular erythema (EAE) of childhood are considered as distinct entities in the literature. Wells' syndrome (WS) is an eosinophilic dermatosis and histologically characterized by eosinophilic dermal infiltration with the hallmark feature of "flame figures." Based on this case, we discuss and review the differential diagnoses of annular dermatoses in children.

Hypopyon sign as an unusual complication of varicella infection in a girl with atopic dermatitis.

Varicella-zoster virus (VZV) infection, also known as chickenpox, is a common childhood affliction. Generalized small itchy single-standing vesicles on erythematous skin are typical. Both cutaneous and systemic complications of the VZV infection may commonly occur. A three-year-old girl with a previous history of mild atopic dermatitis presented in our Pediatric Dermatology Clinic in poor general condition, with a skin rash predominantly consisting of generalized large blisters with hypopyon sign and erosions. On a closer look, scattered erythematous papules and vesicles were also visible. A positive Tzanck smear from an intact pinhead-sized vesicle and VZV PCR confirmed the clinical diagnosis of chickenpox. Cultures from hypopyon material revealed Staphylococcus aureus superinfection. We report an exceptional, not-yet described complication of chickenpox with hypopyon-forming superinfection in an atopic child. In addition, our case nicely underscores the necessity of early VZV vaccination, which has been available and recommended now for more than 10 years in pediatric vaccination programs to avoid severe complications.

Long-term sirolimus treatment in blue rubber bleb nevus syndrome: Case report and review of the literature.

Blue rubber bleb nevus syndrome is a rare vascular syndrome characterized by continuous eruption of vascular nodules in the skin, mucous membranes, and solid organs due to somatic activating mutations of the angiopoietin receptor TEK gene. It may be complicated by acute life-threatening hemorrhage and localized intravascular coagulation. We report an 11-year-old girl with complicated blue rubber bleb nevus syndrome treated with sirolimus since the age of 2. We review the literature on sirolimus therapy for children with blue rubber bleb nevus syndrome.

Ustekinumab treatment in severe atopic dermatitis: Down-regulation of T-helper 2/22 expression.

BACKGROUND: It has recently been suggested that patients with moderate to severe atopic dermatitis (AD) may profit from anti-interleukin (IL)-12/-23 p40 therapy. OBJECTIVE: We sought to assess the immunologic effects of ustekinumab treatment on AD skin and to correlate them with the clinical efficacy of this drug. METHODS: We investigated the course of 3 patients with severe AD who were administered 45 mg of subcutaneous ustekinumab over a period of 16 weeks. Clinical scores and skin biopsy specimens, taken at baseline and at week 8, were used to assess changes in disease severity. RESULTS: All patients showed a gradual improvement of the disease, achieving a 50% reduction in the Eczema Area and Severity Index score by week 16. Immunohistology of skin biopsy specimens revealed a significant decrease in the degree of epidermal hyperplasia/proliferation and the number of infiltrating dermal T cells, dendritic cells, and mast cells after treatment. Using quantitative real-time polymerase chain reaction of lesional skin, we found a clear reduction of T-helper 2-/22-associated molecules after therapy. LIMITATIONS: The small number of patients (n = 3) limits efficacy analysis and warrants prospective placebo-controlled studies in larger patient cohorts. CONCLUSION: Blocking IL-12/-23 p40 could be beneficial for a subgroup of patients with severely infiltrated AD.

Acne inversa complicated by Actinomyces neuii.

INTRODUCTION: Acne inversa (AI) is a chronic and recurrent inflammatory skin disease. It occurs in intertriginous areas of the skin and causes pain, drainage, malodor and scar formation. While supposedly caused by an autoimmune reaction, bacterial superinfection is a secondary event in the disease process. METHODS: A unique case of a 43-year-old male patient suffering from a recurring AI lesion in the left axilla was retrospectively analysed. RESULTS: A swab revealed Actinomyces neuii as the only agent growing in the lesion. The patient was then treated with Amoxicillin/Clavulanic Acid 3 × 1 g until he was cleared for surgical excision. The intraoperative swab was negative for A. neuii. Antibiotics were prescribed for another 4 weeks and the patient has remained relapse free for more than 12 months now. CONCLUSION: Primary cutaneous Actinomycosis is a rare entity and the combination of AI and Actinomycosis has never been reported before. Failure to detect superinfections of AI lesions with slow-growing pathogens like Actinomyces spp. might contribute to high recurrence rates after immunosuppressive therapy of AI. The present case underlines the potentially multifactorial pathogenesis of the disease and the importance of considering and treating potential infections before initiating immunosuppressive regimens for AI patients.

Autoantibody Levels and Clinical Disease Severity in Patients with Pemphigus: Comparison of Aggregated Anti-desmoglein ELISA Values and Indirect Immunofluorescence Titres.

Detecting serum-autoantibodies by anti-Desmoglein-1 (anti-Dsg1) and anti-Dsg3 ELISAs as well as indirect immunofluorescence (IIF) are established complementary methods to diagnose pemphigus. Whether autoantibody levels also reflect clinical disease activity is still a matter of debate, as head-to-head comparisons of ELISA values and IIF titres with clinical activity over a longer treatment period are scarce. In our retrospective study, we compared aggregated repetitive intra-patient ELISA values and IIF titres with grades of clinical disease (1 = remission, 2 = moderate activity, 3 = exacerbation) in 47 patients suffering from pemphigus vulgaris (PV, n = 36) and pemphigus foliaceus (PF, n=11). We found that anti-Dsg1 ELISA values in PF and mucocutaneous PV as well as anti-Dsg3 ELISA values in PV best reflect disease activity. IIF titres, by contrast, did not show a significant association with disease severity. From these data we conclude that ELISA index values can be a valuable tool to monitor disease in patients with pemphigus, whereas IIF titres reflect clinical activity only insufficiently.

Immunofluorescent distribution of postribosomal particles during oogenesis and early development of an insect (Dysdercus intermedius, Heteroptera, Pyrrhoc.).

During previtellogenesis, the oocytes of the telotrophic meroistic ovary ofDysdercus are provided with ribosomes and ribonucleoprotein (RNP) particles by the nurse cells. At the end of vitellogenesis, the oocyte itself becomes active as shown by autoradiography. The proteins synthesized by the oocyte are stored in cytoplasmic postribosomal particles which are preformed by the tropharium. The proteins of these particles were separated by SDS polyacrylamide gels and their endogenous oocyte proteins revealed by fluorography. The synthesis, transport, and storage of the postribosomal particles are demonstrated by indirect immunofluorescence. The young oocytes of previtellogenic follicles show a diffuse distribution of these particles. In late vitellogenesis, fluorescence becomes more and more concentrated in spots throughout a distinct region in the middle part of the oocyte. Thus, in freshly laid eggs, the periplasm is free of fluorescence. During migration of the cleavage nuclei the postribosomal particles were shifted into the cortex. Fluorescence is then most intense in the periplasmic region. During blastoderm formation, however, fluorescence decreases.

[Endogenous synthesis of short-lived messenger-RNA-species in oocytes ofDysdercus intermedius Dist. after termination of vitellogenesis]. / Endogene Synthese kurzlebiger Messenger-RNS in der Oocyte vonDysdercus intermedius Dist. nach Abschluß der Vitellogenese.

Non-ribosomal RNA is synthesized in oocytes of the telotrophicmeroistic ovary ofDysdercus intermedius Dist. during late oogenesis, 4-14 h before they become mature eggs. RNA is labelled "in vivo" by radioactive RNA precursors from a nucleotide pool which is established in the ooplasm prior to chorion-formation.RNA synthesized by late oocytes is characterized by a high turnover rate and appears first as a high molecular weight precursor which is converted during a few hours to smaller non-ribosomal RNA species of 30-5 S. In newly-laid eggs RNA molecules synthesized by the oocyte are no longer present. Their degradation products can be found within the nucleotide fraction. Thus, in contrast to RNA synthesized by trophocytes and stored in eggs in a stable form, endogeneously-formed RNA is not conserved for use in embryogenesis.Endogeneous RNA of oocytes is found to have a high content of poly(A)-segments. Fifty-seven percent of these are hybridizable with poly(U) immobilised on glassfiber filters. A few hours before the maturation of eggs, shortlived RNA synthesized by the oocyte is found in association with polysomes. By incubation of such polysomes in an "in vitro" protein-synthesizing system, polypeptides are formed which show a characteristic banding pattern after separation on SDS-polyacrylamide gels. The apparent molecular weights for the 4 main proteins are 65.000, 48.000, 44.000, and 40.000. There is no evidence for identity of any one of these proteins with a chorion protein.Some of the heterogeneous population of RNA molecules synthesized by late oocytes are characterized by a short lifetime, a relatively high content of poly(A) and the ability to activate protein synthesis "in vivo" or "in vitro", thus suggesting a function like that of mRNA.