C-Reactive Protein Kinetic as a Potential Predictive and Prognostic Factor during Treatment with Checkpoint Inhibitors in R/M-HNSCC.

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.

Nivolumab as a Promising Treatment Option for Metastatic Salivary Duct Carcinoma.

Salivary duct carcinomas (SDC) of the parotid gland are rarely occurring highly malignant tumors. A 65-year-old man presented with a preauricular mass. After surgical treatment and histologic examination, the findings were interpreted as a squamous cell carcinoma (SCC) metastasis of the parotid gland deriving from a cancer of unknown primary DD primary SCC of the parotid gland. Adjuvant platinum-based radiochemotherapy was administered in domo. However, re-staging revealed multiple size-progressive pulmonary round lesions. After resection and histological examination of a pulmonary mass and in synopsis with the primary tumor, the initial diagnosis of SCC was revised to SDC of the parotid gland. With positive HER-2 status, off-label trastuzumab/docetaxel was initiated in an individual healing attempt, during which the pulmonary metastases showed clear progression. Consequently, the patient received immunotherapy with nivolumab according to his negative PD-L1 status. After 57 cycles of nivolumab, the patient presents with partial remission and in good condition. We report, for the first time, a robust response of metastatic SDC to checkpoint inhibition with nivolumab without additional radiotherapy.

Risk factors for immune-related adverse effects during CPI therapy in patients with head and neck malignancies - a single center study.

Introduction: Checkpoint inhibitors, such as PD1 inhibitors, represent an important pillar in the therapy of advanced malignancies of the head and neck region. The most relevant complications are immune-related adverse effects (irAEs), which represent an immense burden for patients. Currently, no sufficient stratification measures are available to identify patients at increased risk of irAEs. The aim of this retrospective study was to examine whether demographic, histopathological, clinical, or laboratory values at the start of CPI therapy represent a risk factor for the later occurrence of autoimmune complications. Material and methods: Data from 35 patients between 2018 and 2021 who received therapy with nivolumab or pembrolizumab for head and neck malignancy were analyzed and assessed for any associations with the subsequent occurrence of irAEs. Results: IrAE developed in 37% of patients, with pneumonitis being the most common form (14%). Pneumonitis was found in patients with an average significantly lower T-stage of primary tumors. An increase in basophilic leukocytes was found in patients with dermatitis later in the course. When thyroiditis developed later, the patients had a higher CPS score and lower monocyte levels. Discussion: Even though individual laboratory values at the beginning of therapy might show a statistical association with the later occurrence of irAEs, neither demographic, histopathological, nor laboratory chemistry values seem to be able to generate a sound and reliable risk profile for this type of complication. Therefore, patients need to be educated and sensitized to irAEs, and regular screening for irAEs should be carried out.

Plasma-derived small extracellular vesicles unleash the angiogenic potential in head and neck cancer patients.

BACKGROUND: In Head and neck cancer (HNC) angiogenesis is essential for tumor progression and metastasis. Small extracellular vesicles (sEVs) from HNC cell lines alter endothelial cell (EC) functions towards a pro-angiogenic phenotype. However, the role of plasma sEVs retrieved from HNC patients in this process is not clear so far. METHODS: Plasma sEVs were isolated on size exclusion chromatography columns from 32 HNC patients (early-stage UICC I/II: 8, advanced-stage UICC III/IV: 24), 12 patients with no evident disease after therapy (NED) and 16 healthy donors (HD). Briefly, sEVs were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), BCA protein assays and Western blots. Levels of angiogenesis-associated proteins were determined using antibody arrays. The interaction of fluorescently-labeled sEVs with human umbilical vein ECs was visualized by confocal microscopy. The functional effect of sEVs on tubulogenesis, migration, proliferation and apoptosis of ECs was assessed. RESULTS: The internalization of sEVs by ECs was visualized using confocal microscopy. Based on antibody arrays, all plasma sEVs were enriched in anti-angiogenic proteins. HNC sEVs contained more pro-angiogenic MMP-9 and anti-angiogenic proteins (Serpin F1) than HD sEVs. Interestingly, a strong inhibition of EC function was observed for sEVs from early-stage HNC, NED and HD. In contrast, sEVs from advanced-stage HNC showed a significantly increased tubulogenesis, migration and proliferation and induced less apoptosis in ECs than sEVs from HD. CONCLUSIONS: In general, plasma sEVs carry a predominantly anti-angiogenic protein cargo and suppress the angiogenic properties of ECs, while sEVs from (advanced-stage) HNC patients induce angiogenesis compared to HD sEVs. Thus, tumor-derived sEVs within the plasma of HNC patients might shift the angiogenic switch towards angiogenesis.

The effects of COVID-19 on the vestibular system.

Introduction: The symptoms and severity of SARS-CoV-2 infection vary greatly across the spectrum, from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome and even death. Dizziness is a frequently reported symptom of SARS-CoV-2 viral infection. However, the extent to which this symptom results from the effect of SARS-CoV-2 on the vestibular system remains unclear. Materials and methods: In the present single-center, prospective cohort study, patients with a previous SARS-CoV-2 infection underwent a vestibular assessment consisting of the Dizziness Handicap Inventory to assess dizziness during and after infection, a clinical examination, the video head impulse test, and the subjective visual vertical test. When the subjective visual vertical test result was abnormal, vestibular-evoked myogenic potentials were performed. Vestibular testing results were compared to pre-existing normative data of healthy controls. In addition, we performed a retrospective data analysis of patients admitted to hospital presenting with acute symptoms of dizziness who were also diagnosed with acute SARS-CoV-2 infection. Results: A total of 50 participants have been enrolled. During and after the SARS-CoV-2 infection, women were significantly more likely than men to suffer from dizziness. A significantly reduced semicircular canal or otolith function was not observed in either women or men. Acute SARS-CoV-2 infection was diagnosed in nine patients who presented to the emergency room with acute vestibular syndrome. Six of the patients exhibited acute unilateral peripheral vestibulopathy upon diagnosis. A different patient was diagnosed with vestibular migraine, and two individuals had a posterior inferior cerebellar artery infarct revealed by magnetic resonance imaging. Discussion/conclusion: Overall, a persisting structural affection of the vestibular system by SARS-CoV-2 seems to be unlikely and could not be confirmed by vHIT, SVV, and VEMPS in our study. It seems possible but unlikely that SARS-CoV-2 induces acute vestibulopathy. Nevertheless, dizziness is a common symptom in patients with COVID-19, which should be taken and worked through seriously.

Anosmia Testing as Early Detection of SARS-CoV-2 Positivity; A Prospective Study under Screening Conditions.

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.

Targeted Treatment of HPV16-positive and -negative SCC Cells With Small Molecule Tyrosine Kinase Inhibitors and Everolimus Affects MMP2 and MMP14 Expression.

BACKGROUND/AIM: The rise of targeted therapies in the treatment of head and neck squamous cell carcinoma (HNSCC) has considerably widened the treatment range. Matrix metalloproteinases (MMPs) are key regulators of the tumor development of many cancer entities, which makes them a promising target for new treatment options. We examined the expression patterns of MMP2 and MMP14 in human papillomavirus (HPV)-positive and -negative SCC lines after treatment with small molecule tyrosine kinase inhibitors (TKIs) and a mechanistic target of rapamycin (mTOR) inhibitor in vitro. MATERIALS AND METHODS: Cells of two human HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) were incubated with 20 µmol/l of erlotinib, gefitinib, nilotinib, dasatinib, or everolimus for 24-96 h. Cell proliferation was assessed by proliferation assay and the protein concentrations of MMP2 and MMP14 by sandwich enzyme-linked immunosorbent assay. For statistical analysis, the results were compared with those of untreated SCC cells. RESULTS: MMP2 and MMP14 were expressed in all three tested cell lines; expression levels were highest in the UMSCC-14C cell line. The tested TKIs significantly (p<0.05) reduced MMP2 expression in the UMSCC-14C cell line. In the HPV-positive cell line, the drugs led to an increase in MMP2 and MMP14 expression. CONCLUSION: Dysregulations in MMP signaling are involved in tumorigenesis and metastasis of HNSCCs; MMP2 has been noted as a potential biomarker. The expression of MMP2 and MMP14 is influenced effectively by small molecule TKIs and everolimus. Based on our data, future research should concentrate on a better understanding of the interplay between tumor microenvironment and tumor cells in vitro and in vivo.

Prognostic Factors for the Therapeutic Performance of Cisplatin in Head and Neck Malignancies.

Introduction: For squamous cell carcinoma of the head and neck (HNSCC), cisplatin is used as primary or adjuvant (radio)chemotherapy. In terms of dosage, two main regimens are used, weekly 40mg/m2 or 3-weekly 100mg/m2. For an optimal outcome, the highest possible cumulative total dose of cisplatin is aimed for. The selection of the scheme is patient-specific, but the factors for the selection of the optimal scheme have not yet been conclusively researched. The aim of this study was to find correlations between initial laboratory values and the cumulative total dose of cisplatin, as well as any correlations between early laboratory values or their dynamics and later laboratory values or their dynamics to provide support in the selection of the chemo regimen. Material and Methods: In this retrospective study, the clinical data and laboratory values, namely glomerular filtration rate (GFR), hemoglobin, albumin, leucocyte, erythrocyte and platelet count, over the course of time of 79 patients with HNSCC who had received chemotherapy with cisplatin in our clinic between 2018 and 2021 were evaluated. Results: Patients on 3-weekly regimens achieved a higher mean cumulative total dose of cisplatin than patients on weekly regimens (214.18 ± 65.95 vs 183.33 ± 65.2 mg/m2). Significant positive correlations were seen for total cumulative dose of cisplatin with initial GFR (p=0.001, Pearson's r=0.364), initial hemoglobin (p=0.035, r=0.237), initial erythrocyte (p=0.002, r=0.337), and initial albumin (p=0.002, r=0.337). There were no significant correlations for initial leucocyte or platelets. Regarding the dynamics of the laboratory values under the first chemo administration, no correlation was found with later laboratory values or dynamics. Discussion and Conclusion: As in other prospective studies, our retrospective analysis found a higher cumulative total dose in the 3-weekly regimen. As this seems to correlate positively with patient outcome, superiority of the 3-weekly regimen over the weekly regimen can be assumed. Functioning organ systems, especially of the bone marrow and kidneys, are associated with an increased cumulative total dose and can therefore be regarded as predictive factors. Regular monitoring of laboratory values is nevertheless essential throughout the entire course of chemotherapy.

Post-COVID-19 Impairment of the Senses of Smell, Taste, Hearing, and Balance.

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.

[Professional teamwork and communication in the operating room-A narrative review]. / Professionelle Teamarbeit und Kommunikation im Operationssaal ­ Eine narrative Übersicht.

BACKGROUND: A team in the operating room (OR) is a hierarchically structured, gender-mixed group of people belonging to different professional categories. Disparities in the objectives of the different team members under economic pressure to perform, are sources of potential conflict in the daily work routine. This may have a negative impact on patient safety and commercial efficiency of hospital management. OBJECTIVE: The aim of this summary is to sensitize the reader to the complex of problems in daily life in the OR and to increase awareness of possible approaches to solve the difficulties in an OR. Problem solutions might be approached by improvement of communication and team building. METHODS: Narrative review of current literature and expert recommendations by a literature search in PubMed and Medline; keywords included teamwork, communication, operating room, team building. RESULTS AND CONCLUSION: Communication and teamwork in the OR are of immense importance for patient safety and the economic development of a hospital. Improvements in communication structure, among other things due to the implementation of a team time out and moderation from outside (OR manager) offer solutions to avoid conflicts in everyday clinical practice.