Diagnose und Therapie aktinischer Keratosen: Diagnosis and therapy of actinic keratosis.

Actinic keratosis (AK) is considered a chronic and recurring in situ skin neoplasia, with a possible transformation into invasive squamous cell carcinoma (SCC). Among others, predominant risk factors for development of AK are UV-light exposure and immunosuppression. Basal epidermal keratinocyte atypia (AK I) and proliferation (PRO Score) seem to drive malignant turnover, rather than clinical appearance of AK (Olsen I-III). Due to the invasiveness of punch biopsy, those histological criteria are not regularly assessed. Non-invasive imaging techniques, such as optical coherence tomography (OCT), reflectance confocal microscopy (RCM) and line-field confocal OCT (LC-OCT) are helpful to distinguish complex cases of AK, Bowen's disease and SCC. Moreover, LC-OCT can visualize the epidermis and the papillary dermis at cellular resolution, allowing real-time PRO Score assessment. The decision-making for implementation of therapy is still based on clinical risk factors, ranging from lesion- to field-targeted and ablative to non-ablative regimes, but in approximately 85% of the cases a recurrence of AK can be observed after a 1-year follow-up. The possible beneficial use of imaging techniques for a non-invasive follow-up of AK to detect recurrence or invasive progression early on should be subject to critical evaluation in further studies.

Diagnosis and therapy of actinic keratosis.

Actinic keratosis (AK) is considered a chronic and recurring in situ skin neoplasia, with a possible transformation into invasive squamous cell carcinoma (SCC). Among others, predominant risk factors for development of AK are UV-light exposure and immunosuppression. Basal epidermal keratinocyte atypia (AK I) and proliferation (PRO score) seem to drive malignant transformation, rather than clinical appearance of AK (Olsen I-III). Due to the invasiveness of punch biopsy, those histological criteria are not regularly assessed. Non-invasive imaging techniques, such as optical coherence tomography (OCT), reflectance confocal microscopy (RCM) and line-field confocal OCT (LC-OCT) are helpful to distinguish complex cases of AK, Bowen's disease, and SCC. Moreover, LC-OCT can visualize the epidermis and the papillary dermis at cellular resolution, allowing real-time PRO score assessment. The decision-making for implementation of therapy is still based on clinical risk factors, ranging from lesion- to field-targeted and ablative to non-ablative regimens, but in approximately 85% of the cases a recurrence of AK can be observed after a 1-year follow-up. The possible beneficial use of imaging techniques for a non-invasive follow-up of AK to detect recurrence or invasive progression early on should be subject to critical evaluation in further studies.

Differences in the annotation between facial images and videos for training an artificial intelligence for skin type determination.

BACKGROUND: The Grand-AID research project, consisting of GRANDEL-The Beautyness Company, the dermatology department of Augsburg University Hospital and the Chair of IT Infrastructure for Translational Medical Research at Augsburg University, is currently researching the development of a digital skin consultation tool that uses artificial intelligence (AI) to analyze the user's skin and ultimately perform a personalized skin analysis and a customized skin care routine. Training the AI requires annotation of various skin features on facial images. The central question is whether videos are better suited than static images for assessing dynamic parameters such as wrinkles and elasticity. For this purpose, a pilot study was carried out in which the annotations on images and videos were compared. MATERIALS AND METHODS: Standardized image sequences as well as a video with facial expressions were taken from 25 healthy volunteers. Four raters with dermatological expertise annotated eight features (wrinkles, redness, shine, pores, pigmentation spots, dark circles, skin sagging, and blemished skin) with a semi-quantitative and a linear scale in a cross-over design to evaluate differences between the image modalities and between the raters. RESULTS: In the videos, most parameters tended to be assessed with higher scores than in the images, and in some cases significantly. Furthermore, there were significant differences between the raters. CONCLUSION: The present study shows significant differences between the two evaluation methods using image or video analysis. In addition, the evaluation of the skin analysis depends on subjective criteria. Therefore, when training the AI, we recommend regular training of the annotating individuals and cross-validation of the annotation.

Artificial intelligence-based PRO score assessment in actinic keratoses from LC-OCT imaging using Convolutional Neural Networks.

BACKGROUND AND OBJECTIVES: The histological PRO score (I-III) helps to assess the malignant potential of actinic keratoses (AK) by grading the dermal-epidermal junction (DEJ) undulation. Line-field confocal optical coherence tomography (LC-OCT) provides non-invasive real-time PRO score quantification. From LC-OCT imaging data, training of an artificial intelligence (AI), using Convolutional Neural Networks (CNNs) for automated PRO score quantification of AK in vivo may be achieved. PATIENTS AND METHODS: CNNs were trained to segment LC-OCT images of healthy skin and AK. PRO score models were developed in accordance with the histopathological gold standard and trained on a subset of 237 LC-OCT AK images and tested on 76 images, comparing AI-computed PRO score to the imaging experts' visual consensus. RESULTS: Significant agreement was found in 57/76 (75%) cases. AI-automated grading correlated best with the visual score for PRO II (84.8%) vs. PRO III (69.2%) vs. PRO I (66.6%). Misinterpretation occurred in 25% of the cases mostly due to shadowing of the DEJ and disruptive features such as hair follicles. CONCLUSIONS: The findings suggest that CNNs are helpful for automated PRO score quantification in LC-OCT images. This may provide the clinician with a feasible tool for PRO score assessment in the follow-up of AK.

Innovation in Actinic Keratosis Assessment: Artificial Intelligence-Based Approach to LC-OCT PRO Score Evaluation.

Actinic keratosis (AK) is a common skin cancer in situ that can progress to invasive SCC. Line-field confocal optical coherence tomography (LC-OCT) has emerged as a non-invasive imaging technique that can aid in diagnosis. Recently, machine-learning algorithms have been developed that can automatically assess the PRO score of AKs based on the dermo-epidermal junction's (DEJ's) protrusion on LC-OCT images. A dataset of 19.898 LC-OCT images from 80 histologically confirmed AK lesions was used to test the performance of a previous validated artificial intelligence (AI)-based LC-OCT assessment algorithm. AI-based PRO score assessment was compared to the imaging experts' visual score. Additionally, undulation of the DEJ, the number of protrusions detected within the image, and the maximum depth of the protrusions were computed. Our results show that AI-automated PRO grading is highly comparable to the visual score, with an agreement of 71.3% for the lesions evaluated. Furthermore, this AI-based assessment was significantly faster than the regular visual PRO score assessment. The results confirm our previous findings of the pilot study in a larger cohort that the AI-based grading of LC-OCT images is a reliable and fast tool to optimize the efficiency of visual PRO score grading. This technology has the potential to improve the accuracy and speed of AK diagnosis and may lead to better clinical outcomes for patients.

Temporomandibular Joint Fibrocartilage Contains CD105 Positive Mouse Mesenchymal Stem/Progenitor Cells with Increased Chondrogenic Potential.

Objective: A specific type of mesenchymal stem/progenitor cells (MSPCs), CD105+ is reported to aid in cartilage regeneration through TGF-ß/Smad2-signalling. The purpose of this study was to identify and characterize CD105+ MSPCs in temporomandibular joint (TMJ) cartilage. Materials and Methods: MSPCs were isolated from mouse TMJ condyle explants and evaluated for their clonogenicity and pluripotential abilities. MSPC were examined for CD105 antigen using immunohistochemistry and flow cytometry. Results: Immunohistochemistry revealed presence of CD105+ MSPCs in the proliferative zone of condyle's cartilage. Only 0.2% of isolated MSPCs exhibited CD105, along with the stem cell surface markers CD44 and Sca-1. In CD105+ MSPCs, intracellular immunostaining revealed significantly higher (p < 0.05) protein levels of collagen type 1, 2, proteoglycan 4. Ability for chondrogenic differentiation was found to be significantly higher (p < 0.05) after 4 weeks compared to CD105- cells, using alcian blue staining. CD105+ cells were found to resemble an early MSPC subgroup with significantly higher gene expression of biglycan, proteoglycan 4, collagen type 2, Gli2, Sox5 (p < 0.001) and Sox9 (p < 0.05). In contrast, significantly lower levels of Runx2 (p < 0.05), Osterix, Trps1, Col10a1 (p < 0.01), Ihh (p < 0.001) related to chondrocyte senescence and commitment to osteogenic lineage, were observed compared to CD105- cells. Conclusion: The study showed the existence of a CD105+ MSPC subgroup within TMJ fibrocartilage that may be activated to aid in fibrocartilage repair.

Implementation of a dermatoscopy curriculum during residency at Augsburg University Hospital in Germany.

BACKGROUND AND OBJECTIVES: To date, there is no structured program for dermatoscopy training during residency in Germany. Whether and how much dermatoscopy training is acquired is left to the initiative of each resident, although dermatoscopy is one of the core competencies of dermatological training and daily practice. The aim of the study was to establish a structured dermatoscopy curriculum during residency at the University Hospital Augsburg. PATIENTS AND METHODS: An online platform with dermatoscopy modules was created, accessible regardless of time and place. Practical skills were acquired under the personal guidance of a dermatoscopy expert. Participants were tested on their level of knowledge before and after completing the modules. Test scores on management decisions and correct dermatoscopic diagnosis were analyzed. RESULTS: Results of 28 participants showed improvements in management decisions from pre- to posttest (74.0% vs. 89.4%) and in dermatoscopic accuracy (65.0% vs. 85.6%). Pre- vs. posttest differences in test score (7.05/10 vs. 8.94/10 points) and correct diagnosis were significant (p < 0.001). CONCLUSIONS: The dermatoscopy curriculum increases the number of correct management decisions and dermatoscopy diagnoses. This will result in more skin cancers being detected, and fewer benign lesions being excised. The curriculum can be offered to other dermatology training centers and medical professionals.

Optical coherence tomography-guided Nd:YAG laser treatment and follow-up of basal cell carcinoma.

OBJECTIVES: Basal cell carcinoma (BCC) is the most common skin tumor with an annually increasing incidence. Standard care requires several visits for diagnosis and treatment. Optical coherence tomography (OCT) as a diagnostic tool increases the sensitivity (95%) and specificity (77%) of the diagnosis of BCC. Although laser therapy is not the standard of care, the long-pulsed 1064 nm Nd:YAG laser seems to be a promising option. However, data are scarce. The published papers had a short follow-up (FU) time and used to some extent inferior methods to detect complete tumor clearance. To address this research gap, this study evaluates the efficiency of laser treatment by FU OCT. We pursue a patient-focused approach and combine OCT with Nd:YAG laser treatment in one procedure. MATERIALS AND METHODS: The study was conducted as a prospective, single-center trial that recruited biopsy-confirmed or OCT-proven BCC with a tumor thickness of less than 1.2 mm. Patients underwent two or three repeated sessions with the Nd:YAG laser (5-6 mm spot, fluence of 120-140 J/cm2 , pulse duration of 8-10 milliseconds). Each BCC was assessed at baseline, and 3 and 12 months after laser treatment by clinical image, dermoscopy, and OCT. Incomplete tumor clearance (ITC) was defined as a clearly detectable BCC on the OCT image or a biopsy-confirmed BCC in the treated area. RESULTS: Forty-five patients completed the 12-month FU (46.7% women; median age of 74.0 [52-88] years) with a total number of 78 BCC lesions. At baseline, all patients had their BCC diagnosed by OCT (tumor thickness of 0.6 [0.4; 0.8] mm), 15.4% lesions were additionally diagnosed by histopathology. The most common subtype of BCC was superficial (48.7%), followed by nodular (47.4%) and infiltrative (3.8%). ITC rate after the treatment using Nd:YAG laser was 30.8% (95% CI: 20.8%-42.2%) (24/78) after 3 months and 7.4% (95% CI: 2.1%-17.9%) (4/54) after 12 months. ITC was not associated with histological subtype, tumor thickness, or location. If ITC was detected, the lesion was treated again. Out of 19 lesions with at least one additional laser treatment, 7 lesions (36.8%) suffered from incomplete tumor removal. In 46.7% of the treated lesions, the cosmetic outcome was rated as moderate or severe scarring after 12 months. CONCLUSION: Our results demonstrate that the ITC rate of BCC treated with the Nd:YAG laser is much higher (up to one-third) than reported, although the laser settings were identical to prior studies. This is especially evident at the 3-month FU. In addition, we witnessed a larger number of side effects and a worse cosmetic outcome compared to previous studies.

Chondrogenic differentiation of mouse CD105+ stem/progenitor cells on amino-group-functionalized biosilica-hydrogel scaffolds.

OBJECTIVES: Mesenchymal stem/progenitor cells (MSPCs) are critical for tissue regeneration. Moreover, the CD105 antigen identifies early MSPCs with increased chondrogenic differentiation ability. We hypothesized that amine-(NH2)-functionalized biosilica incorporating hydrogel scaffolds, seeded with mCoSPCs105+ would contribute to creating tissue-engineered scaffolds, capable of de novo cartilage synthesis. MATERIALS AND METHODS: Scaffolds were characterized by water uptake, lysozyme degradation, axial compression, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Differentiation stimulus of scaffold functionalization was evaluated using Alcian blue staining. Cartilage-forming abilities of mCoSPCs105+ were evaluated using Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. RESULTS: Biosilica particle incorporation into scaffolds resulted in increased water uptake capacity and compression force withstanding abilities. Amine-(NH2)-group functionalization of biosilica led to significantly increased stem cell differentiation potential, by Alcian blue staining, in the first 3 weeks. Scaffold attachment and viable cell proliferation were observed for 6 weeks under chondrogenic differentiation. Downregulation of Runx2, an increase of Col10a1, Ihh, and maintenance of Sox9, was seen under these culture conditions. mCoSPCs105+ gene expression pattern was defined by the significant upregulation of Col1a1, Col2a1, Prg4, and Agc-1 over 6 weeks of incubation compared to the unsorted control. Immunostaining of cell-seeded scaffolds revealed significantly higher secretion of proteins relevant to cartilage extracellular matrix. CONCLUSION: The preselecting of CD105+ phenotype in MSPCs may enhance tissue regeneration of fibrocartilage and biosilica nanoparticles may be a beneficial additive in tissue engineering of scaffolds.

Increased Osteogenic Activity of Dynamic Cultured Composite Bone Scaffolds: Characterization and In Vitro Study.

PURPOSE: The purpose of this study was to develop and characterize beta-tricalcium phosphate (ß-TCP)/polycaprolactone (PCL) scaffolds, with 2 different ratios (50/50% and 65/35%), using 3-dimensionally (3D) printed dissolvable molds, and to evaluate cellular growth and osteogenic differentiation of both groups seeded with porcine bone marrow stem cells (pBMSCs) under dynamic culture in vitro. MATERIALS AND METHODS: Two different groups of scaffolds were produced: group 1 (n = 40) with a ratio (wt%) of 50/50% and group 2 (n = 40) with 65/35% of ß-TCP/PCL. Physicochemical, morphological, and mechanical characterization of the scaffolds were performed. Scaffolds were seeded with pBMSCs and differentiated osteogenically in dynamic culture. Cell density, distribution, and viability were assessed. Osteogenic differentiation was examined through alkaline phosphatase (ALP) staining, immunofluorescence, and photospectrometry. RESULTS: Osteogenic differentiated constructs showed homogenous and viable cell distribution. Cell density was significantly higher (P < .05) for 65/35% scaffolds at 10 days postseeding, whereas at 6 weeks, cell number equalized for both groups. ALP activity increased over time and was significantly higher (P < .05) for 65/35% scaffolds at 14 days postseeding. CONCLUSIONS: The mechanical properties of the developed 65/35% scaffolds were within the range of natural trabecular bone. Moreover, the 65/35% scaffolds showed biological advantages, such as higher cell growth and higher ALP activity.