Hair is a defining feature of mammals and has critical functions, including protection, production of sebum, apocrine sweat and pheromones, social and sexual interactions, thermoregulation, and provision of stem cells for skin homeostasis, regeneration, and repair. The hair follicle (HF) is considered a “mini-organ,” consisting of intricate and well-organized structures which originate from HF stem and progenitor cells. Dermal papilla cells are the main components of the mesenchymal compartments in the hair bulb and are instrumental in generating signals to regulate the behavior of neighboring epithelial cells during the hair cycle. Mesenchymal-epithelial interactions within the dermal papilla niche drive HF embryonic development as well as the postnatal hair growth and regeneration cycle. This review summarizes the current understanding of HF development, repair, and regeneration, with special focus on cell signaling pathways governing these processes. In particular, we discuss emerging paradigms of molecular signaling governing the dermal papilla-epithelial cellular interactions during hair growth and maintenance and the recent progress made towards tissue engineering of human hair follicles.

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Immune checkpoint inhibitors (ICI) represent a new therapeutic approach in recurrent and metastatic head and neck squamous cell carcinoma (HNSCC). The patient selection for the PD-1/PD-L1 inhibitor therapy is based on the degree of PD-L1 expression in immunohistochemistry reflected by manually determined PD-L1 scores. However, manual scoring shows variability between different investigators and is influenced by cognitive and visual traps and could therefore negatively influence treatment decisions. Automated PD-L1 scoring could facilitate reliable and reproducible results. Our novel approach uses three neural networks sequentially applied for fully automated PD-L1 scoring of all three established PD-L1 scores: tumor proportion score (TPS), combined positive score (CPS) and tumor-infiltrating immune cell score (ICS). Our approach was validated using WSIs of HNSCC cases and compared with manual PD-L1 scoring by human investigators. The inter-rater correlation (ICC) between human and machine was very similar to the human-human correlation. The ICC was slightly higher between human-machine compared to human-human for the CPS and ICS, but a slightly lower for the TPS. Our study provides deeper insights into automated PD-L1 scoring by neural networks and its limitations. This may serve as a basis to improve ICI patient selection in the future.

Objective: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and severe skin and mucosal reactions that are associated with high mortality. Despite the severity, an evidence-based treatment protocol for SJS/TEN is still lacking. Method: In this systematic review and meta-analysis, the PubMed database was searched using the following terms: [Stevens–Johnson syndrome] OR [toxic epidermal necrolysis] AND [therapy] OR [treatment] over a 20-year period (1999–2019) in the German and English language. All clinical studies reporting on the treatment of SJS/TEN were included, and epidemiological and diagnostic aspects of treatment were analysed. A meta-analysis was conducted on all comparative clinical studies that met the inclusion criteria. Results: A total of 88 studies met the inclusion criteria, reporting outcomes in 2647 patients. Treatment was either supportive or used systemic corticosteroid, intravenous immunoglobulin, plasmapheresis, cyclosporine, thalidomide or cyclophosphamide therapy. The meta-analysis included 16 (18%) studies, reporting outcomes in 976 (37%) patients. Systemic glucocorticoids showed a survival benefit for SJS/TEN patients in all analyses compared with other forms of treatment. Cyclosporine treatment also showed promising results, despite being used in a small cohort of patients. No beneficial effects on mortality could be demonstrated for intravenous immunoglobulins. Conclusion: Glucocorticoids and cyclosporine may be tentatively recommended as the most promising immunomodulatory therapies for SJS/TEN, but these results should be investigated in future prospective controlled trials.

Background The impact of additional soft tissue resection on recurrence of oral squamous cell carcinoma (OSCC) remains controversial. The study aim was to compare recurrence between patients with secondary tumor‐free resection margins after intraoperative additional resection (STF‐RM) and patients with primary tumor‐free resection margins without additional resection (PTF‐RM). Methods Forty‐five patients with STF‐RM were matched with patients with PTF‐RM according to Union for International Cancer Control stage, tumor location, and treatment modality and compared for local, regional, and distant recurrence. Results Patients with STF‐RM showed lower local and distant control rates compared to patients with PTF‐RM (66.2% vs. 82.8%; p = 0.045 and 86.3% vs. 100.0%; p = 0.021). STF‐RM was the only predictor of local recurrence accounting for tumor (T) status, nodal (N) status, tumor grade, margin distance, and extracapsular extension (hazard ratio 4.21 [95% confidence interval 1.26–14.04]; p = 0.019). Conclusions STF‐RM have an adverse impact on local and distant recurrence of OSCC.

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VEGF signaling regulated by the vascular endothelial growth factor receptor 2 (VEGFR2) plays a decisive role in tumor angiogenesis, initiation and progression in several tumors including HNSCC. However, the impact of HPV-status on the expression of VEGFR2 in OPSCC has not yet been investigated, although HPV oncoproteins E6 and E7 induce VEGF-expression. In a series of 56 OPSCC with known HPV-status, VEGFR2 expression patterns were analyzed both in blood vessels from tumor-free and tumor-containing regions and within tumor cells by immunohistochemistry using densitometry. Differences in subcellular colocalization of VEGFR2 with endothelial, tumor and stem cell markers were determined by double-immunofluorescence imaging. Immunohistochemical results were correlated with clinicopathological data. HPV-infection induces significant downregulation of VEGFR2 in cancer cells compared to HPV-negative tumor cells (p = 0.012). However, with respect to blood vessel supply, the intensity of VEGFR2 staining differed only in HPV-positive OPSCC and was upregulated in the blood vessels of tumor-containing regions (p < 0.0001). These results may suggest different routes of VEGFR2 signaling depending on the HPV-status of the OPSCC. While in HPV-positive OPSCC, VEGFR2 might be associated with increased angiogenesis, in HPV-negative tumors, an autocrine loop might regulate tumor cell survival and invasion.

Background Although nearly one-third of the world’s disease burden requires surgical care, only a small proportion of digital health applications are directly used in the surgical field. In the coming decades, the application of augmented reality (AR) with a new generation of optical-see-through head-mounted displays (OST-HMDs) like the HoloLens (Microsoft Corp) has the potential to bring digital health into the surgical field. However, for the application to be performed on a living person, proof of performance must first be provided due to regulatory requirements. In this regard, cadaver studies could provide initial evidence. Objective The goal of the research was to develop an open-source system for AR-based surgery on human cadavers using freely available technologies. Methods We tested our system using an easy-to-understand scenario in which fractured zygomatic arches of the face had to be repositioned with visual and auditory feedback to the investigators using a HoloLens. Results were verified with postoperative imaging and assessed in a blinded fashion by 2 investigators. The developed system and scenario were qualitatively evaluated by consensus interview and individual questionnaires. Results The development and implementation of our system was feasible and could be realized in the course of a cadaver study. The AR system was found helpful by the investigators for spatial perception in addition to the combination of visual as well as auditory feedback. The surgical end point could be determined metrically as well as by assessment. Conclusions The development and application of an AR-based surgical system using freely available technologies to perform OST-HMD–guided surgical procedures in cadavers is feasible. Cadaver studies are suitable for OST-HMD–guided interventions to measure a surgical end point and provide an initial data foundation for future clinical trials. The availability of free systems for researchers could be helpful for a possible translation process from digital health to AR-based surgery using OST-HMDs in the operating theater via cadaver studies.