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.
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.
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.
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.
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.
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.
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.
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.
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/m
or 3-weekly ...100mg/m
. 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.
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.
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/m
). 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.
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.
During the COVID-19 pandemic, adverse neurological effects have been described. In addition to unspecific neurological symptoms, cranial nerve deficits have appeared as part of SARS-CoV-2 infection. ...In this case report, we describe a 74-year-old patient who developed bilateral paralysis of the vocal cords some weeks following his dismissal in stable condition after COVID-19 pneumonia. After ruling out central lesions, peripheral tumors, and other possible causes, therapy was initiated with methylprednisolone, inhalations, and oxygen. The patient showed no improvement, so laterofixation after Lichtenberger was performed. The dyspnea worsened after several weeks, so a laser posterior cordectomy was performed with satisfactory outcome.
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.
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.
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.
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.
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.
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.
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.
COVID-19 particularly caused olfactory and gustatory impairment; balance disorders were present too; vestibular and auditory symptoms were negligible.
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.
Aim
To investigate the usability of querying subjective impairments of the sense of smell and taste in order to improve pre‐test probability in testing for SARS‐CoV‐2. To achieve this, exploring the ...prevalence of these restrictions in the COVID‐19‐negative population, as well as nasal co‐symptoms.
Design
A cross‐sectional study was carried out as part of the secondary prophylaxis, following the STROBE guidelines of the EQUATOR network.
Methods
In total, 1,734 employees of retirement and nursing homes were tested for COVID‐19 and asked for subjective reduction or loss in the sense of smell and taste, furthermore about nasal co‐symptoms such as nasal obstruction and rhinorrhoea.
Results
All employees tested negative for COVID‐19. Subjective hyposmia and hypogeusia rarely occurred and were usually accompanied by other nasal symptoms such as nasal obstruction. Querying subjective hyposmia/anosmia or hypogeusia/ageusia appears to be a useful anamnestic instrument for the clinical assessment of the probability of SARS‐CoV‐2 infection.
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.
Despite extensive research into new treatment options, the prognosis for head and neck squamous cell carcinoma remains poor. Platelet-derived growth factor (PDGF) is up-regulated in HNSCC and ...expression levels decrease after surgery, suggesting its role in tumour development. The influence of HPV on the PDGF/PDGF receptor (PDGFR) pathway remains unclear. In this study, we investigated the effect of small-molecule tyrosine kinase inhibitors (TKIs) on the expression of PDGF and its receptor in vitro using squamous cancer cell lines with different human papillomavirus 16 (HPV16) status.
Two human HPV16-negative cell lines (UMSCC-11A/-14C) and one HPV16-positive cell line (CERV196) were used. Tumour cells were incubated with 20 μmol/l of TKIs nilotinib, dasatinib, afatinib, gefitinib and erlotinib for 24-96 h. Cell proliferation was assessed via proliferation assay and protein concentrations of PDGF-AA and BB and PDGFRα and -β via sandwich enzyme-linked immunosorbent assay. For statistical analysis, the results were compared with those from an untreated negative control.
PDGF-AA/BB and PDGFRα/-β were detected in all three tested cell lines. The addition of TKI led to a significant (p<0.05) decrease of PDGF/PDGFR at different time points and cell lines. The strongest effects were seen for the expression of PDGF-AA, which was consistently inhibited by most drugs. The effects of the TKI were independent of the HPV status.
Proteins of this pathway can effectively be inhibited by small molecule TKIs. PDGF-AA seems to be a promising target for future studies with selective TKIs.
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