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1.
Artigo em Inglês | MEDLINE | ID: mdl-38750174

RESUMO

BACKGROUND: Highflow nasal cannula oxygen (HFNO) is known to be used for noninvasive oxygenation in intensive care patients but it has rarely been used in airway management for elective surgery of the upper aerodigestive tract. OBJECTIVES: HFNO offers opportunities of a tubeless oxygenation system which is easy to handle and not limited only on surgery of the endolarynx. METHODS: We evaluated this method for oxygenation during brief interventional procedures of the larynx and pharynx in 92 adult patients for safety and intraoperative complications. The need of secondary endotracheal intubation and limiting comorbidities as pulmonal and cardiac diseases were documented. RESULTS: HFNO showed a good safety profile concerning saturation and hypercapnia. Oxygen desaturation below 90% occurred only in 5 patients, mask ventilation led to quick recovery except in one patient who was secondary intubated. A significant influence of the body mass index on the minimal O2 saturation was shown (p < 0,001) so that a possible limitation of the method exists here. Comorbidities were grouped into the ASA classification. There was a significant difference between ASA I/II and ASA III patients in terms of minimum O2saturation. CONCLUSION: We conclude that HFNO may hold great promise for changing ventilator technique in general anesthesia, particularly in short elective laryngeal and pharyngeal surgery. Safety and feasibility were proven in this study.

2.
Bioengineering (Basel) ; 11(2)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38391673

RESUMO

Different studies suggest an impact of biofilms on carcinogenic lesion formation in varying human tissues. However, the mechanisms of cancer formation are difficult to examine in vivo as well as in vitro. Cell culture approaches, in most cases, are unable to keep a bacterial steady state without any overgrowth. In our approach, we aimed to develop an immunocompetent 3D tissue model which can mitigate bacterial outgrowth. We established a three-dimensional (3D) co-culture of human primary fibroblasts with pre-differentiated THP-1-derived macrophages on an SIS-muc scaffold which was derived by decellularisation of a porcine intestine. After establishment, we exposed the tissue models to define the biofilms of the Pseudomonas spec. and Staphylococcus spec. cultivated on implant mesh material. After 3 days of incubation, the cell culture medium in models with M0 and M2 pre-differentiated macrophages presented a noticeable turbidity, while models with M1 macrophages presented no noticeable bacterial growth. These results were validated by optical density measurements and a streak test. Immunohistology and immunofluorescent staining of the tissue presented a positive impact of the M1 macrophages on the structural integrity of the tissue model. Furthermore, multiplex ELISA highlighted the increased release of inflammatory cytokines for all the three model types, suggesting the immunocompetence of the developed model. Overall, in this proof-of-principle study, we were able to mitigate bacterial overgrowth and prepared a first step for the development of more complex 3D tissue models to understand the impact of biofilms on carcinogenic lesion formation.

3.
Cancers (Basel) ; 15(22)2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-38001610

RESUMO

Drug resistance is a common cause of therapy failure in head and neck squamous cell carcinoma (HNSCC). One approach to tackling it is by targeting fundamental cellular processes, such as translation. The eukaryotic translation initiation factor 2α (EIF2α) is a key player in canonical translation initiation and integrates diverse stress signals; when phosphorylated, it curbs global protein synthesis. This study evaluates EIF2α expression and phosphorylation in HNSCC. A small-molecule inhibitor of EIF2α dephosphorylation, salubrinal, was tested in vitro, followed by viability assays, flow cytometry, and immunoblot analyses. Patient-derived 3D tumor spheres (PD3DS) were cultured with salubrinal and their viability assessed. Lastly, salubrinal was evaluated with standard-of-care chemotherapeutics. Our analysis of RNA and proteomics data shows elevated EIF2α expression in HNSCC. Immunohistochemical staining reveals increasing EIF2α abundance from premalignant lesions to invasive and metastatic carcinoma. In immunoblots from intraoperative samples, EIF2α expression and steady-state phosphorylation are higher in HNSCC than in neighboring normal tissue. Inhibition of EIF2α dephosphorylation decreases HNSCC cell viability and clonogenic survival and impairs the G1/S transition. Salubrinal also decreases the viability of PD3DS and acts synergistically with cisplatin, 5-fluorouracil, bleomycin, and proteasome inhibitors. Our results indicate that pharmacological inhibition of EIF2α dephosphorylation is a potential therapeutic strategy for HNSCC.

4.
BMC Cancer ; 23(1): 1054, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919644

RESUMO

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is the only subgroup of head neck cancer that presents with an increased incidence. Gender-specific studies in other cancer entities have revealed differences in treatment response and prognosis. However, only limited data in OPSCC according to gender and human papillomavirus (HPV) status exist. Therefore, we aimed to investigate sex-specific differences in OPSCC and how these may be distributed in relation to HPV and other risk factors. METHODS: This retrospective, bicentric study included 1629 patients with OPSCC diagnosed between 1992 and 2020. We formed subgroups based on TNM status, American Joint Cancer Committee 8th edition (AJCC8), HPV status, treatment modality (surgery (± radio(chemo)therapy (RCT) vs. definitive RCT) and patient-related risk factors and investigated gender differences and their impact on patients survival via descriptive-,uni- and multivariate analysis. RESULTS: With the exception of alcohol abuse, no significant differences were found in risk factors between men and women. Females presented with better OS than males in the subgroup T1-2, N + , independent of risk factors (p = 0.008). Males demonstrated significant stratification through all AJCC8 stages (all p < 0.050). In contrast, women were lacking significance between stage II and III (p = 0.992). With regard to therapy (surgery (± R(C)T) - vs. definitive RCT) women treated with surgery had better OS than men in the whole cohort (p = 0.008). Similar results were detected in the HPV-negative OPSCC sub-cohort (p = 0.042) and in high-risk groups (AJCC8 stage III and IV with M0, p = 0.003). CONCLUSION: Sex-specific differences in OPSCC represent a health disparity, particularly according to staging and treatment, which need to be addressed in future studies.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Masculino , Humanos , Feminino , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Estudos de Coortes , Neoplasias Orofaríngeas/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias de Cabeça e Pescoço/patologia , Prognóstico , Papillomavirus Humano , Papillomaviridae
5.
Sci Data ; 10(1): 733, 2023 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-37865668

RESUMO

The endoscopic examination of subepithelial vascular patterns within the vocal fold is crucial for clinicians seeking to distinguish between benign lesions and laryngeal cancer. Among innovative techniques, Contact Endoscopy combined with Narrow Band Imaging (CE-NBI) offers real-time visualization of these vascular structures. Despite the advent of CE-NBI, concerns have arisen regarding the subjective interpretation of its images. As a result, several computer-based solutions have been developed to address this issue. This study introduces the CE-NBI data set, the first publicly accessible data set that features enhanced and magnified visualizations of subepithelial blood vessels within the vocal fold. This data set encompasses 11144 images from 210 adult patients with pathological vocal fold conditions, where CE-NBI images are annotated using three distinct label categories. The data set has proven invaluable for numerous clinical assessments geared toward diagnosing laryngeal cancer using Optical Biopsy. Furthermore, given its versatility for various image analysis tasks, we have devised and implemented diverse image classification scenarios using Machine Learning (ML) approaches to address critical clinical challenges in assessing laryngeal lesions.


Assuntos
Neoplasias Laríngeas , Laringoscopia , Laringe , Adulto , Humanos , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/patologia , Laringe/diagnóstico por imagem , Imagem de Banda Estreita , Prega Vocal/diagnóstico por imagem
6.
NPJ Digit Med ; 6(1): 152, 2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37598255

RESUMO

Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell cancer (OPSCC) represents an OPSCC subgroup with an overall good prognosis with a rising incidence in Western countries. Multiple lines of evidence suggest that HPV-associated tumors are not a homogeneous tumor entity, underlining the need for accurate prognostic biomarkers. In this retrospective, multi-institutional study involving 906 patients from four centers and one database, we developed a deep learning algorithm (OPSCCnet), to analyze standard H&E stains for the calculation of a patient-level score associated with prognosis, comparing it to combined HPV-DNA and p16-status. When comparing OPSCCnet to HPV-status, the algorithm showed a good overall performance with a mean area under the receiver operator curve (AUROC) = 0.83 (95% CI = 0.77-0.9) for the test cohort (n = 639), which could be increased to AUROC = 0.88 by filtering cases using a fixed threshold on the variance of the probability of the HPV-positive class - a potential surrogate marker of HPV-heterogeneity. OPSCCnet could be used as a screening tool, outperforming gold standard HPV testing (OPSCCnet: five-year survival rate: 96% [95% CI = 90-100%]; HPV testing: five-year survival rate: 80% [95% CI = 71-90%]). This could be confirmed using a multivariate analysis of a three-tier threshold (OPSCCnet: high HR = 0.15 [95% CI = 0.05-0.44], intermediate HR = 0.58 [95% CI = 0.34-0.98] p = 0.043, Cox proportional hazards model, n = 211; HPV testing: HR = 0.29 [95% CI = 0.15-0.54] p < 0.001, Cox proportional hazards model, n = 211). Collectively, our findings indicate that by analyzing standard gigapixel hematoxylin and eosin (H&E) histological whole-slide images, OPSCCnet demonstrated superior performance over p16/HPV-DNA testing in various clinical scenarios, particularly in accurately stratifying these patients.

7.
Cancers (Basel) ; 15(7)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37046829

RESUMO

BACKGROUND: Human papillomavirus (HPV) status is the most important predictor of survival in oropharyngeal squamous cell carcinoma (OPSCC). In patients with cervical lymph node metastases of squamous cell carcinoma of unknown origin (CUPHNSCC), much less is known. METHODS: We assessed a consecutive cohort of CUPHNSCC diagnosed from 2000-2018 for HPV DNA, mRNA, p16INK4a (p16) expression, and risk factors to identify prognostic classification markers. RESULTS: In 32/103 (31%) CUPHNSCC, p16 was overexpressed, and high-risk HPV DNA was detected in 18/32 (56.3%). This was mostly consistent with mRNA detection. In recursive partitioning analysis, CUPHNSCC patients were classified into three risk groups according to performance status (ECOG) and p16. Principal component analysis suggests a negative correlation of p16, HPV DNA, and gender in relation to ECOG, as well as a correlation between N stage, extranodal extension, and tobacco/alcohol consumption. CONCLUSIONS: Despite obvious differences, CUPHNSCC shares similarities in risk profile with OPSCC. However, the detection of p16 alone appears to be more suitable for the classification of CUPHNSCC than for OPSCC and, in combination with ECOG, allows stratification into three risk groups. In the future, additional factors besides p16 and ECOG may become important in larger studies or cases with special risk profiles.

9.
Laryngorhinootologie ; 102(7): 512-520, 2023 07.
Artigo em Alemão | MEDLINE | ID: mdl-36543220

RESUMO

OBJECTIVE: Salivary gland carcinomas are rare and heterogeneous. More than 20 subtypes are recognized and risk factors are diverse. The aim of this work was to evaluate the subtype and other risk factors in a monocentric population from more than four decades. MATERIAL AND METHODS: 205 cases (diagnosis period 1972-2014) were retrospectively collected and analyzed with regard to the distribution of risk factors and their influence on overall survival (OS). RESULTS: 19/24 (79.2%) of the subtypes listed in the WHO classification occurred rarely in the cohort (< 5%). 10/24 (41.7%) of all subtypes were never diagnosed. With a total of 145/205 cases (70.7%), squamous cell carcinoma (PEC), adenocarcinoma (AdenoCa), acinar cell carcinoma (AcinarCa), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) were by far the most common subtypes. Risk factors are significantly different in these groups (e.g., lymphogenic metastasis and degree of differentiation in AdenoCa and age, T and UICC stage in PEC). The 5-year overall survival of all patients was 66.9% and differed significantly within the most common subtypes. An independent impact on overall survival was detectable for patient age (p<0.001), and T- (p=0.003) and N-stage (p=0.046) in multivariate analysis. CONCLUSIONS: Most subtypes occurred markedly rarely or not at all within decades. The most common diagnoses differ with respect to risk factors as well as OS and 3 risk groups can be defined based on histology. In conclusion, considering TNM alone is insufficient for prognosis estimation in salivary gland carcinoma.


Assuntos
Adenocarcinoma , Carcinoma Adenoide Cístico , Neoplasias das Glândulas Salivares , Humanos , Estudos Retrospectivos , Incidência , Neoplasias das Glândulas Salivares/patologia , Carcinoma Adenoide Cístico/epidemiologia , Carcinoma Adenoide Cístico/patologia , Prognóstico , Glândulas Salivares
10.
HNO ; 71(1): 28-34, 2023 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-36264298

RESUMO

Patients presenting with laryngotracheal trauma can be in a life-threatening situation. Early recognition of the severity of the injury and, if necessary, surgical intervention within the first 24-48 h increases the chance of achieving a good functional late result. Preservation or restoration of voice and swallowing function is the long-term therapeutic goal. Precise assessment of the extent of the injury can be achieved using a combination of computed tomography and flexible laryngotracheoscopy. Symptoms often do not reflect the extent of the injury, which can vary from endolaryngeal hemorrhage to complete laryngotracheal separation. Conservative treatment consists of observation with symptomatic therapy. On the other hand, surgery may include endolaryngeal repair and/or transcervical reconstruction; securing the airways is of utmost importance.


Assuntos
Laringe , Lesões do Pescoço , Voz , Ferimentos não Penetrantes , Ferimentos Penetrantes , Humanos , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/cirurgia , Laringe/diagnóstico por imagem , Laringe/cirurgia , Ferimentos Penetrantes/diagnóstico por imagem , Ferimentos Penetrantes/cirurgia , Lesões do Pescoço/cirurgia
11.
Diagnostics (Basel) ; 12(9)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36140467

RESUMO

(1) Background: Computed tomography (CT) is considered mandatory for assessing the extent of pathologies in the paranasal sinuses (PNS) in chronic rhinosinusitis (CRS). However, there are few evidence-based data on the value of ultrasound (US) in CRS. This multicenter approach aimed to compare diagnostic imaging modalities in relation to findings during surgery. (2) Methods: 127 patients with CRS were included in this prospective multicenter study. Patients received preoperative US and CT scans. The sensitivity and specificity of CT and US were extrapolated from intraoperative data. (3) Results: CT scans showed the highest sensitivity (97%) and specificity (67%) in assessing CRS. Sensitivities of B-scan US were significantly lower regarding the maxillary sinus (88%), the ethmoid sinus (53%), and the frontal sinus (45%). The highest overall sensitivity was observed for assessing the pathology of the maxillary sinus. (4) Conclusions: We observed high accuracy with CT, confirming its importance in preoperative imaging in CRS. Despite the high US expertise of all investigators and a standardized examination protocol, the validity of CT was significantly higher than US. Ultrasound of the PNS sinuses is applicable in everyday clinical practice but lacks diagnostic accuracy. Nevertheless, it might serve as a complementary hands-on screening tool to directly correlate the clinical findings in patients with PNS disease.

12.
Eur J Vasc Endovasc Surg ; 64(4): 407-415, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35963514

RESUMO

OBJECTIVE: New onset aspirin resistance during surgery, known as peri-operative aspirin resistance, is observed in up to 30% of vascular surgery patients and is associated with post-operative myocardial damage; questioning aspirin effectiveness towards peri-operative cardiovascular events. The objective of this study was to prospectively evaluate whether peri-operative aspirin resistance in vascular surgery is associated with an adverse cardiovascular outcome. METHODS: Based on a sample size calculation, 194 adult elective vascular or endovascular surgery patients receiving aspirin were analysed in this prospective, single centred, non-interventional cohort study. Platelet function was measured before surgery, one hour after incision, four hours post-operatively, and on the morning of the first and second post-operative days using the Multiplate analyser. The primary outcome was myocardial injury after non-cardiac surgery (MINS). Secondary outcomes included major bleeding, admission to intensive care unit, length of hospital stay, and major adverse cardiac and cerebrovascular events. Subgroup analyses were performed for patients with different cardiovascular risk and for patients who underwent endovascular surgery. RESULTS: Peri-operative aspirin resistance was observed in 27.8% of patients but was not associated with MINS (27.8% vs. 32.1%, aspirin resistance vs. no aspirin resistance, OR 0.812, 95% CI 0.406 - 1.624, p = .56) or with any of the secondary endpoints (all p > .050). In nine of the 10 subgroup analyses, aspirin resistance was not associated with a difference in MINS rate. However, in patients with a low cardiovascular risk profile (RCRI 0-2), MINS occurred more frequently in patients without aspirin resistance (p = .049). CONCLUSION: This study confirmed previous reports demonstrating that peri-operative aspirin resistance is common in patients undergoing vascular or endovascular surgery. However, in patients who continue aspirin throughout the peri-operative period, aspirin resistance is a phenomenon, which does not appear to be related to MINS. Measuring peri-operative platelet function using the Multiplate analyser with the intention to identify and potentially prevent or treat peri-operative aspirin resistance seems to be dispensable.

13.
Comput Biol Med ; 143: 105243, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35139455

RESUMO

BACKGROUND: The larynx of the human respiratory tract plays a vital role in breathing and voice production. Both can be influenced by functional and/or morphological changes of the larynx, e.g., immobility of one or both vocal folds (VF). The immobile VF can become stationary in different positions such as the median, paramedian, intermediate or lateral position. The impact of unilateral vocal fold immobility (UVFI) on inhalation is the focus of this study. METHODS: Transient numerical simulations of the inhalation process in patient-specific airways are performed. Five configurations are considered: paramedian and intermediate VF positions on the left and right, and healthy. Large eddy simulations are used to describe the complex laryngeal turbulent flow. Airway resistance, power loss, and spectral entropy are calculated to quantify the work of inspiration and evaluate flow regimes. RESULTS: The laryngeal jet intensity and flow disturbance increase with the severity of immobility. In comparison to the healthy configuration, UVFI with right/left intermediate and right/left paramedian VF position increases the airway resistance over the oropharynx to the trachea by 69%/58% and 310%/285%, respectively. When the entire respiratory system is considered, an increase of up to 48% is estimated. Spectral entropy increases of up to 2.5 times indicate higher turbulence levels due to UVFI. CONCLUSIONS: Surgery of immobile VF aims to improve glottis closure. However, this can have a negative impact on breathing efficiency. To that end, this study provides initial insights into the conflicting objectives of open versus closed VFs.

14.
Laryngorhinootologie ; 101(2): 156-175, 2022 02.
Artigo em Alemão | MEDLINE | ID: mdl-35098514

RESUMO

Transcervical sonography has become an integral part of the diagnostic spectrum of otorhinolaryngology, as evidenced by its firm inclusion in continuing education catalogs and guidelines. For these reasons, the user should be aware of a basic understanding of ultrasound physics and of technical innovations. A standardized examination scheme with structured reporting and documentation is an elementary prerequisite to meet the daily clinical challenges and to be able to answer specific questions. In this educational article, we span from an introduction to structured examination techniques to a clinical update on sonography of the cephalic glands and cervical lymph nodes.


Assuntos
Neoplasias de Cabeça e Pescoço , Pescoço , Cabeça , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Pescoço/diagnóstico por imagem , Ultrassonografia
15.
Acta Radiol ; 63(2): 166-175, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33541089

RESUMO

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a common cancer. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) is a widely used imaging modality in HNSCC. PURPOSE: To provide evident data about associations between 18F-FDG PET and histopathology in HNSCC. MATERIAL AND METHODS: The MEDLINE database was screened for associations between maximum standard uptake values (SUVmax) derived from 18F-FDG PET and histopathological features in HNSCC up to May 2020. Only papers containing correlation coefficients between SUVmax and histopathology were acquired. Overall, 23 publications were collected. RESULTS: The following correlations were calculated: KI 67: 12 studies (345 patients), pooled correlation coefficient (PCC): 0.23 (95% confidence interval [CI] 0.06-0.40); hypoxia-inducible factor-1α: eight studies (240 patients), PCC: 0.24 (95% CI 0.06-0.42); microvessel density: three studies (64 patients), PCC: 0.33 (95% CI 0.02-0.65); vascular endothelial growth factor: two studies (59 cases), PCC: 0.27 (95% CI 0.02-0.51); tumor suppressor protein p53: four studies (159 patients), PCC: 0.05 (95% CI -0.41 to 0.51); epidermal growth factor receptor: two studies (124 patients), PCC: 0.21 (95% CI 0.05-0.37); tumor cell count: three studies (67 patients), PCC: 0.18 (95% CI -0.06 to 0.42); tumor cell apoptosis: two studies (40 patients), PCC: 0.07 (95% CI = -0.85 to 0.99); B-cell lymphoma-2 protein: two studies (118 patients); PCC: 0.04 (95% CI -0.65 to 0.74); glucose-transporter 1: 10 studies (317 patients), PCC: 0.20 (95% CI 0.10-0.30). CONCLUSION: SUVmax derived from 18F-FDG PET cannot reflect relevant histopathological features in HNSCC.


Assuntos
Biomarcadores Tumorais , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Tomografia por Emissão de Pósitrons/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Apoptose , Proteínas Reguladoras de Apoptose/análise , Proliferação de Células , Receptores ErbB/análise , Genes p53 , Transportador de Glucose Tipo 1/análise , Humanos , Antígeno Ki-67/análise , Microcirculação , Proteínas Repressoras/análise
16.
Sensors (Basel) ; 21(23)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34884166

RESUMO

(1) Background: Contact Endoscopy (CE) and Narrow Band Imaging (NBI) are optical imaging modalities that can provide enhanced and magnified visualization of the superficial vascular networks in the laryngeal mucosa. The similarity of vascular structures between benign and malignant lesions causes a challenge in the visual assessment of CE-NBI images. The main objective of this study is to use Deep Convolutional Neural Networks (DCNN) for the automatic classification of CE-NBI images into benign and malignant groups with minimal human intervention. (2) Methods: A pretrained Res-Net50 model combined with the cut-off-layer technique was selected as the DCNN architecture. A dataset of 8181 CE-NBI images was used during the fine-tuning process in three experiments where several models were generated and validated. The accuracy, sensitivity, and specificity were calculated as the performance metrics in each validation and testing scenario. (3) Results: Out of a total of 72 trained and tested models in all experiments, Model 5 showed high performance. This model is considerably smaller than the full ResNet50 architecture and achieved the testing accuracy of 0.835 on the unseen data during the last experiment. (4) Conclusion: The proposed fine-tuned ResNet50 model showed a high performance to classify CE-NBI images into the benign and malignant groups and has the potential to be part of an assisted system for automatic laryngeal cancer detection.


Assuntos
Neoplasias Laríngeas , Laringe , Endoscopia , Humanos , Neoplasias Laríngeas/diagnóstico por imagem , Imagem de Banda Estreita , Redes Neurais de Computação
17.
Oncoimmunology ; 10(1): 1938475, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34178430

RESUMO

The monoclonal antibody against CTLA-4, Ipilimumab, is a first-in-class immune-checkpoint inhibitor approved for treatment of advanced melanoma in adults but not extensively studied in children. In light of the fact that the immune response early in life differs from that of adults, we have applied a human in vitro model stimulating CD4+ T-cells from neonates, children (1-5 years), and adults antigen-specifically with Staphylococcus aureus (S. aureus) for assessment of CTLA-4 blockade early in life. We show that T-cell proliferation as well as frequencies of antigen-specific T-cells (CD40L+CD4+) were enhanced in neonatal T-cells upon CTLA-4 blockade showing a larger variance within the group (F-test p < .0001). Using machine learning algorithm Random Forest, adult and neonatal T-cell responses can be unambiguously categorized (F1 score-0.75) on the basis of their cytokine (co-)expression. Blockade of CTLA-4 enhanced frequencies of IL-8, IFNγ, and IL-10 producers among CD40L+ T-cells. Of note, antigen-specific T-cells from neonates displayed higher cytokine coproduction at baseline, while T-cells from children caught up to neonates, and adults to baseline of children upon CTLA-4 blockade. These findings reveal that in neonatal T-cells blockade of CTLA-4 mainly unleashes the antigen-specific capacity by increasing the numbers of responding T-cells, whereas in children and adults it promotes the coexpression of cytokines by individual T-cells. Thus, CTLA-4 blockade boosts antitumor immunity through different mechanisms depending on the patients' age. These data implicate a strong impact of the developmental stage of the T-cell compartment on the effects of immune-checkpoint therapy.


Assuntos
Antígeno CTLA-4/antagonistas & inibidores , Inibidores de Checkpoint Imunológico , Adulto , Pré-Escolar , Humanos , Imunoterapia , Lactente , Recém-Nascido , Staphylococcus aureus , Linfócitos T
18.
Laryngorhinootologie ; 100(6): 483-498, 2021 06.
Artigo em Alemão | MEDLINE | ID: mdl-34062579

RESUMO

Sonography of the head and neck area plays a major role in both outpatient and inpatient ear, nose and throat medicine. Transcervical ultrasound is an important imaging method, especially in lymph node and tumor diagnostics. Its advantage is the ubiquitous availability and the excellent combinability with endoscopy and palpation. Despite decades of experience with sonography in the head and neck area, in contrast to the transcutaneous application, the transoral or endosonographic approach has so far not been widely used. Here it is often not due to the technical capabilities of the examiner, but rather to the unusual approach within the scope of the investigation. In this context, endosonography may be used primarily in tumor diagnostics in order to establish a complete sonographic examination from in- and outside.


Assuntos
Endossonografia , Neoplasias de Cabeça e Pescoço , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática , Pescoço , Ultrassonografia
19.
Diagnostics (Basel) ; 11(3)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802625

RESUMO

BACKGROUND: Feature extraction is an essential part of a Computer-Aided Diagnosis (CAD) system. It is usually preceded by a pre-processing step and followed by image classification. Usually, a large number of features is needed to end up with the desired classification results. In this work, we propose a novel approach for texture feature extraction. This method was tested on larynx Contact Endoscopy (CE)-Narrow Band Imaging (NBI) image classification to provide more objective information for otolaryngologists regarding the stage of the laryngeal cancer. METHODS: The main idea of the proposed methods is to represent an image as a hilly surface, where different paths can be identified between a starting and an ending point. Each of these paths can be thought of as a Tour de France stage profile where a cyclist needs to perform a specific effort to arrive at the finish line. Several paths can be generated in an image where different cyclists produce an average cyclist effort representing important textural characteristics of the image. Energy and power as two Cyclist Effort Features (CyEfF) were extracted using this concept. The performance of the proposed features was evaluated for the classification of 2701 CE-NBI images into benign and malignant lesions using four supervised classifiers and subsequently compared with the performance of 24 Geometrical Features (GF) and 13 Entropy Features (EF). RESULTS: The CyEfF features showed maximum classification accuracy of 0.882 and improved the GF classification accuracy by 3 to 12 percent. Moreover, CyEfF features were ranked as the top 10 features along with some features from GF set in two feature ranking methods. CONCLUSION: The results prove that CyEfF with only two features can describe the textural characterization of CE-NBI images and can be part of the CAD system in combination with GF for laryngeal cancer diagnosis.

20.
Eur Arch Otorhinolaryngol ; 278(10): 3801-3811, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33320296

RESUMO

PURPOSE: It is still in question whether head oscillation damping during walking forms a part of the vestibular function. The anatomical pathway from the vestibular system to the neck muscles via the medial vestibulospinal tract (MVST) is well known but there is a lack of knowledge of the exact influence and modulation of each other in daily life activities. METHODS: (I) We fixed a head-neck unit of a human cadaver specimen in a steal frame to determine the required pitch-torque for a horizontal head position. The mean value of the acquired pitch-torque was 0.54 Nm. (II) On a motorized treadmill we acquired kinematic data of the head, the sternum and both feet by wireless 3D IMUs for seven asymptomatic volunteers. Subsequently three randomized task conditions were performed. Condition 1 was walking without any irritation. Condition 2 imitated a sacculus irritation using a standardized cVEMP signal. The third condition used an electric neck muscle-irritation (TENS). The data were analyzed by the simulation environment software OpenSim 4.0. RESULTS: 8 neck muscle pairs were identified. By performing three different conditions we observed some highly significant deviations of the neck muscle peak torques. Analysing Euler angles, we found during walking a LARP and RALP head pendulum, which also was strongly perturbated. CONCLUSION: Particularly the pitch-down head oscillation damping is the most challenging one for neck muscles, especially under biomechanical concerns. Mainly via MVST motor activity of neck muscles  might be modulated by vestibular motor signals. Two simultaneous proprioceptor effects might optimize head oscillation damping. One might be a proprioceptive feedback loop to the vestibular nucleus. Another might trigger the cervicocollic reflex (CCR).


Assuntos
Músculos do Pescoço , Vestíbulo do Labirinto , Cabeça , Humanos , Projetos Piloto , Caminhada
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