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Simple Summary: This study investigates the prognostic value of C-reactive protein (CRP) kinetics in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M-HNSCC) treated with checkpoint inhibitors (CPI). We analyzed data from 44 patients treated between 2018 and 2023, applying two existing CRP classifications and developing a new one. While the existing classifications did not correlate with overall survival (OS), our novel CRP kinetic classification showed a significant association with OS (p = 0.05). Multivariate analysis identified our CRP classification (p = 0.007) and the outcome of the first re-staging (p = 0.002) as independent prognostic factors. These findings suggest that our new CRP kinetic classification could serve as a valuable prognostic marker for R/M-HNSCC patients undergoing CPI therapy, though further validation with larger patient cohorts is needed. Introduction The kinetic of C-reactive protein (CRP) in the early phase of therapy with checkpoint inhibitors (CPI) and its prognostic value has already been investigated in several tumor entities. In particular, flare dynamics have been described as a positive prognostic parameter. The aim of this retrospective study is to examine the extent to which such an application can also be transferred to patients with recurrent or metastatic squamous cell carcinoma of the head and neck region (R/M-HNSCC). Material and Methods All patients treated with CPI for R/M-HNSCC at our clinic between 2018 and 2023 were included (n = 44). Demographic, clinical, histopathologic and laboratory data were extracted from the digital patient records and statistically analyzed. We then examined the CRP kinetic using two previously published classifications and proposed a new classification ourselves. Subsequently, correlation analyses were performed with the overall survival (OS) of the patients. Results Of the two CRP kinetic classifications previously published, only one showed a correlation with the result of the first re-staging, and neither showed a correlation with the OS of R/M-HNSCC patients. Our new CRP kinetic classification showed a significant association with OS in R/M-HNSCC patients (p = 0.05). In a multivariate analysis, our CRP kinetic classification (p = 0.007) and the outcome of the first re-staging (p = 0.002) were significant independent factors for OS. Discussion Our novel CRP kinetic classification significantly correlates with OS in R/M-HNSCC patients, indicating a potential prognostic marker. Existing classifications from other cancer entities showed limited prognostic significance, emphasizing the need for tailored markers. For validation, however, testing on larger R/M-HNSCC patient collectives is necessary. [ABSTRACT FROM AUTHOR]

Tissue engineering (TE) techniques offer solutions for tissue regeneration but require large quantities of cells. For microtia patients, TE methods represent a unique opportunity for therapies with low donor-site morbidity and reliance on the surgeon's individual expertise. Microtia-derived chondrocytes and perichondrocytes are considered a valuable cell source for autologous reconstruction of the pinna. The aim of this study was to investigate the suitability of perichondrocytes from microtia patients for autologous reconstruction in comparison to healthy perichondrocytes and microtia chondrocytes. Perichondrocytes were isolated via two different methods: explant culture and enzymatic digestion. The isolated cells were analyzed in vitro for their chondrogenic cell properties. We examined migration activity, colony-forming ability, expression of mesenchymal stem cell markers, and gene expression profile. We found that microtic perichondrocytes exhibit similar chondrogenic properties compared to chondrocytes in vitro. We investigated the behavior in three-dimensional cell cultures (spheroids and scaffold-based 3D cell cultures) and assessed the expression of cartilage-specific proteins via immunohistochemistry, e.g., collagen II, which was detected in all samples. Our results show that perichondrocytes from microtia patients are comparable to healthy perichondrocytes and chondrocytes in terms of chondrogenic cell properties and could therefore be a promising cell source for auricular reconstruction. [ABSTRACT FROM AUTHOR]

Microtia is a congenital condition of abnormal development of the outer ear. Tissue engineering of the ear is an alternative treatment option for microtia patients. However, for this approach, the identification of high regenerative cartilage progenitor cells is of vital importance. Raman analysis provides a novel, non-invasive, label-free diagnostic tool to detect distinctive biochemical features of single cells or tissues. Using micro-Raman spectroscopy, we were able to distinguish and characterize the particular molecular fingerprints of differentiated chondrocytes and perichondrocytes and their respective progenitors isolated from healthy individuals and microtia patients. We found that microtia chondrocytes exhibited lower lipid concentrations in comparison to healthy cells, thus indicating the importance of fat storage. Moreover, we suggest that collagen is a useful biomarker for distinguishing between populations obtained from the cartilage and perichondrium because of the higher spectral contributions of collagen in the chondrocytes compared to perichondrocytes from healthy individuals and microtia patients. Our results represent a contribution to the identification of cell markers that may allow the selection of specific cell populations for cartilage tissue engineering. Moreover, the observed differences between microtia and healthy cells are essential for gaining better knowledge of the cause of microtia. It can be useful for designing novel treatment options based on further investigations of the discovered biochemical substrate alterations. [ABSTRACT FROM AUTHOR]

Sudden onset of anosmia is a phenomenon often associated with developing COVID-19 disease and has even been described as an initial isolated symptom in individual cases. In this case-control study, we investigated the feasibility of this condition as a suitable screening test in a population at risk. We performed a prospective study with a total of 313 subjects with suspected SARS-CoV-2 infection. In parallel to routine PCR analysis, a modified commercial scent test was performed to objectify the presence of potential anosmia as a predictor of SARS-CoV-2 positivity. Furthermore, a structured interview assessment of the participants was conducted. A total of 12.1% of the study participants had molecular genetic detection of SARS-CoV-2 infection in the nasopharyngeal swab. It could be demonstrated that these subjects had a significantly weaker olfactory identification performance of the scents. Further analysis of the collected data from the scent test and medical history via random forest (Boruta) algorithm showed that no improvement of the prediction power was achieved by this design. The assay investigated in this study may be suitable for screening general olfactory function. For the screening of COVID-19, it seems to be affected by too many external and internal biases and requires too elaborate and selective pre-test screening. [ABSTRACT FROM AUTHOR]

Background: Various symptoms have been associated with COVID-19, but little is known about the impacts of COVID-19 on the sensory system, risk factors, and the duration of symptoms. This study assesses olfactory, gustatory, hearing, and vestibular systems after COVID-19. Methods: This cross-sectional, single-center study involved 50 patients one to six months after COVID-19 and reports their patient records and the extent, onset, and duration of olfactory, gustatory, hearing, and balance disorders using questionnaires during and after COVID-19. Sensory symptoms were objectively studied using the following clinical tests after COVID-19 Sniffin' Sticks, taste tests, tone/speech audiometry, and video head impulse test. Results: Post-COVID-19-patients were suffering from olfactory and gustatory impairment for up to six months. According to the Dizziness Handicap Inventory, balance disorders were less noticed: Overall, about 40% of the patients during COVID-19 and nearly all patients recovered within six months. After COVID-19, clinical tests revealed that 75% were suffering from hyposomnia/anosmia, and 20% of all patients reported mild hypogeusia for up to six months. Vestibular disorders and hearing impairment rarely/did not occur. Females were significantly more affected by sensory impairments than males. Conclusions: COVID-19 particularly caused olfactory and gustatory impairment; balance disorders were present too; vestibular and auditory symptoms were negligible. [ABSTRACT FROM AUTHOR]

Head and Neck Cancers (HNCs) have highly immunosuppressive properties. Small extracellular vesicles (sEVs), including exosomes, nanosized mediators of intercellular communication in the blood, carry immunosuppressive proteins and effectively inhibit anti-tumor immune responses in HNCs. This study evaluates immunosuppressive markers on sEVs from 40 HNC patients at different disease stages and 3- and 6-month follow-up after surgery and/or chemoradiotherapy. As controls, sEVs from normal donors (NDs) are examined. Immunoregulatory surface markers on sEVs were detected as relative fluorescence intensity (RFI) using on-bead flow cytometry, and their expression levels were monitored in the early and late stages of HNC and during follow-up. In parallel, the sEV-mediated apoptosis of CD8+ Jurkat cells was assessed. Together with TGF-β1 and PD-L1 abundance, total sEV proteins are elevated with disease progression. In contrast, total sEV protein, including TGF-β1, PD-1 and PD-L1, decrease upon therapy response during follow-up. Overall survival analysis implies that high sEV PD-1/PD-L1 content is an unfavorable prognostic marker in HNC. Consistently, the sEV-mediated induction of apoptosis in CD8+ T cells correlates with the disease activity and therapy response. These findings indicate that a combination of immunoregulatory marker profiles should be preferred over a single marker to monitor disease progression and therapy response in HNC. [ABSTRACT FROM AUTHOR]

Background: Head and neck squamous cell carcinomas (HNSCC) are phenotypically and molecularly heterogeneous and frequently develop therapy resistance. Reliable patient-derived 3D tumor models are urgently needed to further study the complex pathogenesis of these tumors and to overcome treatment failure. Methods: We developed a three-dimensional organotypic co-culture (3D-OTC) model for HNSCC that maintains the architecture and cell composition of the individual tumor. A dermal equivalent (DE), composed of healthy human-derived fibroblasts and viscose fibers, served as a scaffold for the patient sample. DEs were co-cultivated with 13 vital HNSCC explants (non-human papillomavirus (HPV) driven, n = 7; HPV-driven, n = 6). Fractionated irradiation was applied to 5 samples (non-HPV-driven, n = 2; HPV-driven n = 3). To evaluate expression of ki-67, cleaved caspase-3, pan-cytokeratin, p16INK4a, CD45, ∝smooth muscle actin and vimentin over time, immunohistochemistry and immunofluorescence staining were performed Patient checkup data were collected for up to 32 months after first diagnosis. Results: All non-HPV-driven 3D-OTCs encompassed proliferative cancer cells during cultivation for up to 21 days. Proliferation indices of primaries and 3D-OTCs were comparable and consistent over time. Overall, tumor explants displayed heterogeneous growth patterns (i.e., invasive, expansive, silent). Cancer-associated fibroblasts and leukocytes could be detected for up to 21 days. HPV DNA was detectable in both primary and 3D-OTCs (day 14) of HPV-driven tumors. However, p16INK4a expression levels were varying. Morphological alterations and radioresistant tumor cells were detected in 3D-OTC after fractionated irradiation in HPV-driven and non-driven samples. Conclusions: Our 3D-OTC model for HNSCC supports cancer cell survival and proliferation in their original microenvironment. The model enables investigation of invasive cancer growth and might, in the future, serve as a platform to perform sensitivity testing upon treatment to predict therapy response. [ABSTRACT FROM AUTHOR]