A Deep Learning Approach for Histopathological Diagnosis of Onychomycosis: Not Inferior to Analogue Diagnosis by Histopathologists.

Onychomycosis is common. Diagnosis can be confirmed by various methods; a commonly used method is the histological examination of nail clippings. A deep learning system was developed and its diagnostic accuracy compared with that of human experts. A dataset with annotations for fungal elements was used to train an artificial intelligence (AI) model. In a second dataset (n=199) the diagnostic accuracy of the AI was compared with that of dermatopathologists. The results show a non-inferiority of the deep learning system to that of analogue diagnosis (non-inferiority margin 5%) with respect to specificity and the area under the receiver operating characteristic curve (AUC). The AI achieved an AUC of 0.981. One limitation of this system is the need for a large number of training images. The AI had difficulty recognizing spores and confused serum or aggregated bacteria with fungal elements. Use of this deep learning system in dermatopathology routine might help to diagnose onychomycosis more efficiently.

Screening for biomarkers of spermatogonia within the human testis: a whole genome approach.

BACKGROUND: A key step in studying the biology of spermatogonia is to determine their global gene expression profile. However, disassociation of these cells from the testis may alter their profile to a considerable degree. To characterize the molecular phenotype of human spermatogonia, including spermatogonial stem cells (SSCs), within their cognate microenvironment, a rare subtype of human defective spermatogenesis was exploited in which spermatogonia were the only germ cell type. METHODS: The global expression profile of these samples was assessed on the Affymetrix microarray platform and compared with tissues showing homogeneous Sertoli-cell-only appearance; selected genes were validated by quantitative real-time PCR and immunohistochemistry on disparate sample sets. RESULTS: Highly significant differences in gene expression levels correlated with the appearance of spermatogonia, including 239 best candidates of human spermatogonially expressed genes. Specifically, fibroblast growth factor receptor 3 (FGFR3), desmoglein 2 (DSG2), E3 ubiquitin ligase c-CBL (casitas B-cell lymphoma), cancer/testis antigen NY-ESO-1 (CTAG1A/B), undifferentiated embryonic cell transcription factor 1 (UTF1) and synaptosomal-associated protein, 91 kDa homolog (SNAP91) were shown to represent specific biomarkers of human spermatogonia. CONCLUSIONS: These biomarkers, specifically the surface markers FGFR3 and DSG2, may facilitate the isolation and enrichment of human stem and/or progenitor spermatogonia and thus lay a foundation for studies of long-term maintenance of human SSCs/progenitor cells, spermatogonial self-renewal, clonal expansion and differentiation.

A prospective, rater-blind, randomized comparison of the effectiveness and tolerability of Belotero ® Basic versus Restylane ® for correction of nasolabial folds.

The aim of this prospective, rater-blind, randomized, intra-individual, 4-week study was to compare the effectiveness and safety of two hyaluronic acid dermal fillers, Belotero® Basic (monophasic) and Restylane® (biphasic), for correction of nasolabial folds (NLF). Twenty subjects with bilateral, symmetrical NLF were randomized to receive a single injection of Belotero® Basic and Restylane® in a split-face design. The primary endpoint measured intra-individual differences of treatment effects in mean depth and evenness of the NLF target area relative to its edges, from baseline to Week 4, as evaluated by the Phase-shift Rapid In-vivo Measurement of Skin (PRIMOS) system. Assessments were undertaken at Visit 2 (baseline) and Visit 3 (study endpoint). Treatment with Belotero® Basic resulted in a significantly greater improvement in evenness compared with Restylane® at Week 4 (mean intra-individual difference between treatments in PRIMOS measurement: -37.6 µm; 95% CI: -65.4; -9.9). Subject-rated secondary endpoints demonstrated numerical differences in favour of Belotero® Basic when compared with Restylane®. Both dermal fillers were equally well tolerated, as 85% (Belotero® Basic group) and 80% (Restylane® group) rated the tolerability of both treatments as "good" to "very good".

The multi-step process of human skin carcinogenesis: a role for p53, cyclin D1, hTERT, p16, and TSP-1.

As proposed by Hanahan and Weinberg (2000. Cell 100, 57-70) carcinogenesis requires crucial events such as (i) genomic instability, (ii) cell cycle deregulation, (iii) induction of a telomere length maintenance mechanism, and (iv) an angiogenic switch. By comparing the expression of p53, cyclin D1, p16, hTERT, and TSP-1 in spontaneously regressing keratoacanthoma (KA) as a paradigm of early neoplasia, with malignant invasive cutaneous squamous cell carcinoma (SCC) as a paradigm of advanced tumour development, we are now able to assign the changes in the expression of these proteins to specific stages and allocate them to defined roles in the multi-step process of skin carcinogenesis. We show that mutational inactivation of the p53 gene, and with that the onset of genomic instability is the earliest event. Individual p53-positive cells are already seen in "normal" skin, and 3/5 actinic keratoses (AKs), 5/22 KAs, and 13/23 SCCs contain p53-positive patches. Cell cycle deregulation was indicated by the overexpression of the cell cycle regulator cyclin D1, as well as by the loss of the cell cycle inhibitor p16. Interestingly, overexpression of cyclin D1 - observed in 80% of KAs and SCCs, respectively - showed a cell cycle-independent function in HaCaT cell transplants on nude mice. Cyclin D1 overexpression was associated with a massive inflammatory response, finally leading to tissue destruction. Loss of the cell cycle inhibitor p16, on the other hand, correlated with SCCs. Thus, it is tempting to suggest that overexpression of cyclin D1 is an early change that in addition to growth stimulation leads to an altered epithelial-mesenchymal interaction, while functional p16 is able to control this deregulated growth and needs to be eliminated for malignant progression. Another requirement for uncontrolled growth is the inhibition of telomere erosion by up-regulating telomerase activity. As measured by hTERT protein expression, all of the KAs and SCCs studied were positive, with a similar distribution of the protein in both groups and an expression pattern resembling that of normal epidermis. Thus, telomerase may not need to be increased significantly in skin carcinomas. Finally, we show that the angiogenesis inhibitor TSP-1 is strongly expressed in most KAs, and mainly by the tumour cells, while in SCCs the generally weak expression is restricted to the tumour-stroma. Furthermore, we provide evidence that the loss of a copy of chromosome 15 is responsible for reduced TSP-1 expression and thereby this aberration contributes to tumour vascularisation (i.e. the angiogenic switch) required for malignant growth.

[Aesthetic dermatology]. / Asthetische Dermatologie.

In addition to treating neoplastic disease, inflammatory skin disorders and allergies Aesthetic Dermatology has grown to become an important issue in the field of dermatology. Aesthetic Dermatology puts medicine in a field of tension between medical necessities and patients' wishes. Aesthetic issues are most relevant to dermatology because skin is not only a functional organ like heart, liver and kidneys, but a medium also of visual and tactile communication. The desire for beauty and youth is thus often expressed by patients and customers seeking advice on the improvement of their appearance and looks. Aesthetic medicine means a great challenge to the dermatologist because request and reality must be brought together and ethic thoughts kept in mind. Modern medicine with its new approaches to molecular biology and biophysical technologies (e.g. laser technology) has opened up many new therapeutic possibilities for dermatologists that were largely unimaginable until recently. Aesthetic dermatology has enriched dermatology and will not become a burden if we succeed with integrating aesthetic issues into medical strategies in a sensitive, evidence-based and critical fashion.

Refining criteria for diagnosis of cutaneous infections caused by herpes viruses through correlation of morphology with molecular pathology.

BACKGROUND: Infections of the skin by herpes viruses do not always present themselves in typical fashion. Early diagnosis, however, is crucial for appropriate treatment. Polymerase chain reaction (PCR) allows diagnosis and differential diagnosis of herpes virus infections, but the method is not yet available in large parts of the world, where diagnosis is made based on morphology alone. AIM: To refine criteria for the diagnosis of herpes virus infections of the skin by way of correlation of clinical and histopathologic findings with results of PCR studies. METHODS: We studied 75 clinically diagnosed patients of "zoster," "varicella," and "herpes simplex", to correlate clinical and histopathological findings with results of PCR studies on paraffin embedded biopsy specimens. RESULTS: Clinical suspicion of infection by herpes viruses was confirmed by histopathology in 37% of the cases and by PCR studies in 65% of the cases. Zoster was frequently misdiagnosed as infection with herpes simplex viruses (30%). When diagnostic signs of herpes virus infection were encountered histopathologically, PCR confirmed the diagnosis in 94%. By way of correlation with results of PCR studies, initial lesions of herpes virus infections could be identified to have a distinctive histopathological pattern. Herpetic folliculitis appeared to be a rather common finding in zoster, it occurring in 28% of the cases. CONCLUSION: We conclude that correlation of clinical and histopathological features with results of PCR studies on one and the same paraffin embedded specimen permits identification of characteristic morphologic patterns and helps to refine criteria for diagnosis both clinically and histopathologically.