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1.
Laryngorhinootologie ; 103(5): 371-382, 2024 May.
Artículo en Alemán | MEDLINE | ID: mdl-38697084

RESUMEN

In CUP syndrome (CUP = cancer of unknown primary) there are 1 or more metastases of a primary tumor that cannot be localized despite extensive diagnostics. CUP syndrome accounts for 5% of all human malignancies, making it one of the 10 most common forms of cancer. In addition to inflammatory lymph node enlargement and benign changes such as cervical cysts, lymph node metastases are among the most common cervical masses. Cervical CUP syndrome is a histologically confirmed cervical lymph node metastasis with an unknown primary tumor. In addition to anamnesis, clinical examination and histological confirmation, diagnostics include radiological imaging using PET-CT and panendoscopy with histological primary tumor search. Treatment options include surgical therapy with neck dissection and chemoradiotherapy.


Asunto(s)
Metástasis Linfática , Neoplasias Primarias Desconocidas , Humanos , Neoplasias Primarias Desconocidas/terapia , Neoplasias Primarias Desconocidas/diagnóstico , Neoplasias Primarias Desconocidas/patología , Metástasis Linfática/patología , Disección del Cuello , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/patología , Síndrome , Terapia Combinada , Tomografía Computarizada por Tomografía de Emisión de Positrones , Diagnóstico Diferencial , Quimioradioterapia
2.
Biomed Hub ; 9(1): 9-15, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38322041

RESUMEN

Introduction: A 2½ D point cloud registration method was developed to generate digital twins of different tissue shapes and resection cavities by applying a machine learning (ML) approach. This demonstrates the feasibility of quantifying soft tissue shifts. Methods: An ML model was trained using simulated surface scan data obtained from tumor resections in a pig head cadaver model. It hereby uses 438 2½ D scans of the tissue surface. Tissue shift was induced by a temperature change from 7.91 ± 4.1°C to 36.37 ± 1.28°C. Results: Digital twins were generated from various branched and compact resection cavities (RCs) and cut tissues (CT). A temperature increase induced a tissue shift with a significant volume increase of 6 mL and 2 mL in branched and compact RCs, respectively (p = 0.0443; 0.0157). The volumes of branched and compact CT were decreased by 3 and 4 mL (p < 0.001). In the warm state, RC and CT no longer fit together because of the significant tissue deformation. Although not significant, the compact RC showed a greater tissue deformation of 1 µL than the branched RC with 0.5 µL induced by the temperature change (p = 0.7874). The branched and compact CT forms responded almost equally to changes in temperature (p = 0.1461). Conclusions: The simulation experiment of induced soft tissue deformation using digital twins based on 2½ D point cloud models proved that our method helps to quantify shape-dependent tissue shifts.

3.
Front Oncol ; 14: 1287178, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38420014

RESUMEN

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.

4.
Sci Rep ; 14(1): 946, 2024 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-38200037

RESUMEN

Small extracellular vesicles from saliva (SEVs) have high potential as biomarkers in Head and Neck cancer (HNC). However, there is no common consensus on the ideal method for their isolation. This study compared different ultracentrifugation (UC) methods (durations and + /- additional purification) with size exclusion chromatography (SEC) and investigated the potential of SEVs as diagnostic biomarkers and their biological activity on NK and CD8+ T cells. SEVs from 19 HNC patients and 8 healthy donors (HDs) were thoroughly characterized. Transmission electron microscopy confirmed the isolation of vesicles by all methods. The average size determined via nanoparticle-tracking analysis was smaller for SEVs isolated by SEC than UC. The highest particle-to-protein yield was achieved by UC (3 h + 3 h) (UCopt) and SEC. However, SEC yielded considerably fewer SEVs. Comparing the surface marker cargo, SEVs isolated by UCopt from HNC patients carried more PD-L1, FasL, and TGF-ß than SEVs from HDs. These levels correlated with tumor stage and HPV status. SEVs downregulated NKG2D expression on primary NK cells. HNC SEVs accelerated CD8+ T cell death compared to HD SEVs. This study suggests that UCopt is preferable when isolation of a high particle-to-protein load is required. Especially PD-L1 and FasL on SEVs hold substantial potential as diagnostic biomarkers.


Asunto(s)
Vesículas Extracelulares , Neoplasias de Cabeza y Cuello , Humanos , Saliva , Antígeno B7-H1 , Linfocitos T CD8-positivos , Biomarcadores
5.
Cancer Immunol Immunother ; 72(12): 4367-4383, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38019346

RESUMEN

Patients with HPV--localized head and neck cancer (HNC) show inferior outcomes after surgery and radiochemotherapy compared to HPV-associated cancers. The underlying mechanisms remain elusive, but differences in immune status and immune activity may be implicated. In this study, we analyzed immune profiles of CD8+ T cells and myeloid-derived suppressor cells (MDSC) in HPV+ versus HPV- disease.The overall frequency of CD8+ T cells was reduced in HNC versus healthy donors but substantially increased after curative therapy (surgery and/or radiochemotherapy). In HPV+ patients, this increase was associated with significant induction of peripheral blood CD8+/CD45RA-/CD62L- effector memory cells. The frequency of HPV-antigen-specific CD8+ cells was low even in patients with virally associated tumors and dropped to background levels after curative therapy. Pre-therapeutic counts of circulating monocytic MDSC, but not PMN-MDSC, were increased in patients with HPV- disease. This increase was accompanied by reduced fractions of terminally differentiated CD8+ effector cells. HPV- tumors showed reduced infiltrates of CD8+ and CD45RO+ immune cells compared with HPV+ tumors. Importantly, frequencies of tumor tissue-infiltrating PMN-MDSC were increased, while percentages of Granzyme B+ and Ki-67+ CD8 T cells were reduced in patients with HPV- disease.We report differences in frequencies and relative ratios of MDSC and effector T cells in HPV- HNC compared with more immunogenic HPV-associated disease. Our data provide new insight into the immunological profiles of these two tumor entities and may be utilized for more tailored immunotherapeutic approaches in the future.


Asunto(s)
Neoplasias de Cabeza y Cuello , Células Supresoras de Origen Mieloide , Infecciones por Papillomavirus , Humanos , Linfocitos T CD8-positivos , Infecciones por Papillomavirus/complicaciones , Neoplasias de Cabeza y Cuello/patología , Antígenos Comunes de Leucocito
6.
PLoS One ; 18(8): e0287081, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37556451

RESUMEN

Digital twins derived from 3D scanning data were developed to measure soft tissue deformation in head and neck surgery by an artificial intelligence approach. This framework was applied suggesting feasibility of soft tissue shift detection as a hitherto unsolved problem. In a pig head cadaver model 104 soft tissue resection had been performed. The surface of the removed soft tissue (RTP) and the corresponding resection cavity (RC) was scanned (N = 416) to train an artificial intelligence (AI) with two different 3D object detectors (HoloLens 2; ArtecEva). An artificial tissue shift (TS) was created by changing the tissue temperature from 7,91±4,1°C to 36,37±1,28°C. Digital twins of RTP and RC in cold and warm conditions had been generated and volumes were calculated based on 3D surface meshes. Significant differences in number of vertices created by the different 3D scanners (HoloLens2 51313 vs. ArtecEva 21694, p<0.0001) hence result in differences in volume measurement of the RTC (p = 0.0015). A significant TS could be induced by changing the temperature of the tissue of RC (p = 0.0027) and RTP (p = <0.0001). RC showed more correlation in TS by heating than RTP with a volume increase of 3.1 µl or 9.09% (p = 0.449). Cadaver models are suitable for training a machine learning model for deformable registration through creation of a digital twin. Despite different point cloud densities, HoloLens and ArtecEva provide only slightly different estimates of volume. This means that both devices can be used for the task.TS can be simulated and measured by temperature change, in which RC and RTP react differently. This corresponds to the clinical behaviour of tumour and resection cavity during surgeries, which could be used for frozen section management and a range of other clinical applications.


Asunto(s)
Inteligencia Artificial , Cabeza , Animales , Porcinos , Cabeza/cirugía , Cadáver
7.
Int J Oncol ; 63(3)2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37503786

RESUMEN

Although checkpoint inhibitors (CPI) have recently extended the treatment options and improved clinical response of advanced stage head and neck squamous cell carcinoma (HNSCC), treatment success remains unpredictable. Programmed cell death ligand­1 (PD­L1) is a key player in immunotherapy. Tumor cells, and exosomes derived therefrom, are carriers of PD­L1 and efficiently suppress immune responses. The aim of the present study was to analyze the influence of established therapies on PD­L1 expression of HNSCC cell lines and their exosomes. The HNSCC cell lines, UM­SCC­11B, UM­SCC­14C and UM­SCC­22C were treated with fractionated radiotherapy (RT; 5x2 Gy), cisplatin (CT) and cetuximab (Cetux) as monotherapy, or combined therapy, chemoradiotherapy (CRT; RT and CT) or radioimmunotherapy (RT and Cetux). The expression of PD­L1 and phosphorylated (p)ERK1/2 as a mediator of radioresistance were assessed using western blotting, immunohistochemistry and an ex vivo vital tissue culture model. Additionally, exosomes were isolated from concentrated supernatants of the (un­)treated HNSCC cell lines by size exclusion chromatography. Exosomal protein expression levels of PD­L1 were detected using western blotting and semi­quantitative levels were calculated. The functional impact of exosomes from the (un­)treated HNSCC cell lines on the proliferation (MTS assay) and apoptosis (Caspase 3/7 assay) of the untreated HNSCC cell lines were measured and compared. The HNSCC cell lines UM­SCC­11B and UM­SCC­22B showed strong expression of pERK1/2 and PD­L1, respectively. RT upregulated the PD­L1 expression in UM­SCC­11B and UM­SCC­14C and in exosomes from all three cell lines. CT alone induced PD­L1 expression in all cell lines. CRT induced the expression of PD­L1 in all HNSCC cell lines and exosomes from UM­SCC­14C and UM­SCC­22B. The data indicated a potential co­regulation of PD­L1 and activated ERK1/2, most evident in UM­SCC­14C. Exosomes from irradiated UM­SCC­14C cells protected the unirradiated cells from apoptosis by Caspase 3/7 downregulation. The present study suggested a tumor cell­mediated regulation of PD­L1 upon platinum­based CRT in HNSCC and in exosomes. A co­regulation of PD­L1 and MAPK signaling response was hypothesized.


Asunto(s)
Exosomas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Caspasa 3/metabolismo , Exosomas/metabolismo , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/metabolismo , Cetuximab/farmacología , Cisplatino/farmacología , Línea Celular Tumoral
8.
Mol Med ; 29(1): 69, 2023 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-37226100

RESUMEN

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.


Asunto(s)
Vesículas Extracelulares , Neoplasias de Cabeza y Cuello , Humanos , Anticuerpos , Apoptosis , Western Blotting
9.
Front Neurol ; 14: 1134540, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36970515

RESUMEN

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.

10.
Front Cell Dev Biol ; 10: 971596, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36072342

RESUMEN

Background: Head and neck squamous cell carcinomas (HNSCC) lack tumor-specific biomarkers. Exosomes from HNSCC patients carry immunomodulatory molecules, and correlate with clinical parameters. We compared miRNA profiles of plasma- and saliva-derived exosomes to reveal liquid biomarker candidates for HNSCC. Methods: Exosomes were isolated by differential ultracentrifugation from corresponding plasma and saliva samples from 11 HNSCC patients and five healthy donors (HD). Exosomal miRNA profiles, as determined by nCounter® SPRINT technology, were analyzed regarding their diagnostic and prognostic potential, correlated to clinical data and integrated into network analysis. Results: 119 miRNAs overlapped between plasma- and saliva-derived exosomes of HNSCC patients, from which 29 tumor-exclusive miRNAs, associated with TP53, TGFB1, PRDM1, FOX O 1 and CDH1 signaling, were selected. By intra-correlation of tumor-exclusive miRNAs from plasma and saliva, top 10 miRNA candidates with the strongest correlation emerged as diagnostic panels to discriminate cancer and healthy as well as potentially prognostic panels for disease-free survival (DFS). Further, exosomal miRNAs were differentially represented in human papillomavirus (HPV) positive and negative as well as low and high stage disease. Conclusion: A plasma- and a saliva-derived panel of tumor-exclusive exosomal miRNAs hold great potential as liquid biopsy for discrimination between cancer and healthy as well as HPV status and disease stage. Exosomal miRNAs from both biofluids represent a promising tool for future biomarker studies, emphasizing the possibility to substitute plasma by less-invasive saliva collection.

11.
Front Oncol ; 12: 778380, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35574347

RESUMEN

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.

12.
Viruses ; 14(5)2022 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-35632590

RESUMEN

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.


Asunto(s)
COVID-19 , Trastornos del Olfato , COVID-19/complicaciones , Estudios Transversales , Femenino , Audición , Humanos , Masculino , Trastornos del Olfato/complicaciones , Trastornos del Olfato/diagnóstico , Olfato , Gusto
13.
Ecol Appl ; 32(7): e2680, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35592909

RESUMEN

Retrospective comparison of predictive models that describe competing hypotheses regarding system function can shed light on regulatory mechanisms within the framework of adaptive resource management. We applied this approach to a 28-year study of red grouse (Lagopus lagopus scotica) in Scotland, with the aims of reducing uncertainty regarding important drivers of grouse population dynamics, and of evaluating the efficacy of using seasonal versus annual model assessments. We developed three sets of models that predicted pre-breeding and post-breeding grouse density, matching the timing of grouse counts on the ground. We updated conditions and management through time in the spirit of a real-time, adaptive management program and used a Bayesian model weight updating process to compare model predictions with empirical grouse densities. The first two model sets involved single annual updates from either pre-breeding or post-breeding counts; the third set was updated twice a year. Each model set comprised seven models representing increasingly complex hypotheses regarding potentially important drivers of grouse: the baseline model included weather and parasite effects on productivity, shooting losses and density-dependent overwinter survival; subsequent models incorporated the effect of habitat gain/loss (HAB), control of non-protected predators (NPP) and predation by protected hen harriers (Circus cyaneus, HH) and buzzards (Buteo buteo, BZ). The weight of evidence was consistent across model sets, settling within 10 years on the harrier (NPP + HH), buzzard (NPP + HH + BZ) and buzzard + habitat (NPP + HH + BZ + HAB) models, and downgrading the baseline + habitat, non-protected predator, and non-protected predator + habitat models. By the end of the study only the buzzard and buzzard + habitat models retained substantial weights, emphasizing the dynamical complexity of the system. Habitat inclusion failed to improve model predictions, implying that over the period of this study habitat quantity was unimportant in determining grouse abundance. Comparing annually and biannually assessed model sets, the main difference was in the baseline model, whose weight increased or remained stable when assessed annually, but collapsed when assessed biannually. Our adaptive modeling approach is suitable for many ecological situations in which a complex interplay of factors makes experimental manipulation difficult.


Asunto(s)
Falconiformes , Galliformes , Animales , Teorema de Bayes , Dinámica Poblacional , Conducta Predatoria , Estudios Retrospectivos
14.
Cells ; 11(5)2022 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-35269524

RESUMEN

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-ß1 and PD-L1 abundance, total sEV proteins are elevated with disease progression. In contrast, total sEV protein, including TGF-ß1, 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.


Asunto(s)
Vesículas Extracelulares , Neoplasias de Cabeza y Cuello , Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos , Progresión de la Enfermedad , Vesículas Extracelulares/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/terapia , Humanos , Inmunidad , Receptor de Muerte Celular Programada 1/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo
15.
Laryngorhinootologie ; 101(2): 138-146, 2022 02.
Artículo en Alemán | MEDLINE | ID: mdl-34010975

RESUMEN

BACKGROUND: Due to the limited compliance, the technically correct collection of a pooled nasopharyngeal swab is significantly more difficult in children. Especially during operations in the area of the upper respiratory tract, there is a significantly increased risk of infection with COVID-19 for everyone present in the operating room. The aim of the study is to analyze the validity of SARS-CoV-2 swabs taken preoperatively under suboptimal conditions. MATERIAL AND METHODS: Retrospective comparison of the PCR results of SARS-CoV-2 swaps taken preoperatively and intraoperatively from 62 children in the period from April to July 2020. Median age was 4.49 years. The PCR diagnosis was carried out one or two days preoperatively (in the case of emergency interventions on the same day) and again intraoperatively using a pooled nasopharyngeal swab. RESULTS: All 62 preoperatively taken swabs were negative. Deviating from the preoperative test result, one intraoperatively obtained swab was positive. CONCLUSIONS: Due to limited compliance, a correct preoperative swab technique (preanalytics) cannot always be assumed for children. Sufficient protective measures for everyone present in the operating room are therefore imperative. Intraoperative test should be considered if the preoperative test was performed under difficult conditions.


Asunto(s)
COVID-19 , SARS-CoV-2 , Niño , Preescolar , Humanos , Estudios Retrospectivos , Manejo de Especímenes
16.
Eur Arch Otorhinolaryngol ; 279(3): 1233-1242, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33830367

RESUMEN

PURPOSE: Numerous endeavors have been undertaken to preserve hearing in cochlear implant (CI) patients. Particularly, optimization of electrode array design aims at preservation of residual hearing (RH). This study examines whether a slim perimodiolar (PM) electrode array could bear the capability to preserve hearing. METHODS: A total of 47 patients underwent cochlear implantation receiving the PM electrode. (i) Patients with pure tone audiogram (PTA) thresholds better than 85 dB and/or hearing loss for Freiburg speech test numbers less than 60 dB and more than 50% maximum monosyllabic understanding were assigned to the RH group (n = 17), while all others belonged to the noRH group (n = 30). (ii) Another group implanted with a slim straight, lateral wall (LW) electrode was recruited for comparison. RESULTS: We compared 17 RH-30 noRH patients all receiving the PM electrode. RH in PM recipients decreased faster than in LW recipients. No significant differences were observed between both (RH v/s noRH) groups in NRT thresholds, Freiburg speech test and A§E® phonemes. Analogous satisfaction levels were indicated through the questionnaires in terms of sound quality, hearing in silence, noise and directional hearing in both groups. CONCLUSIONS: The results suggest that hearing preservation is influenced not only by electrode shape but various factors. This study opens an avenue for further investigations to elucidate and enumerate the causes for progressive hearing loss.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Sordera , Percepción del Habla , Adulto , Audiometría de Tonos Puros , Implantación Coclear/métodos , Sordera/cirugía , Audición , Humanos , Resultado del Tratamiento
17.
Anaesthesist ; 71(2): 141-147, 2022 02.
Artículo en Alemán | MEDLINE | ID: mdl-34448911

RESUMEN

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.


Asunto(s)
Quirófanos , Grupo de Atención al Paciente , Comunicación , Hospitales , Humanos , Seguridad del Paciente
18.
HNO ; 70(6): 436-444, 2022 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-34778901

RESUMEN

BACKGROUND: Accurate planning of operating times in surgical clinics is essential. Moreover, high-capacity utilization of operating rooms (ORs) is necessary for economic efficiency. OBJECTIVE: Most planning of operating times is performed by surgeons. Herein, surgeons' estimated times and the objective times for performing surgical procedures were compared to detect sources of error. MATERIALS AND METHODS: In a retrospective analysis, the durations of 1809 operations using general anesthesia (22 types of surgery) by 31 surgeons (12 specialists and 19 residents) were compared. Comparisons were analyzed by Mann-Whitney U­tests. RESULTS: The comparison of objective times of surgical action showed significant differences between specialists and residents in 6 of 15 types of surgeries. The post-processing times estimated by specialists deviated from the objective times in 2 out of 22 surgery types, while the post-processing times estimated by residents deviated in 7 of 15 types. Specialists misjudged the incision-to-suture times in 7 of 22 surgery types, and residents misjudged these times in 3 of 15 types. The preparation times estimated by specialists deviated from the objective times in 16 of 22 types of surgeries and in 7 of 15 types estimated by residents. CONCLUSION: A surgeon's routine must be carefully considered in order to estimate operating times. Specialists generally underestimated preparation and post-processing times and overestimated incision-to-suture times, whereas residents underestimated all three. Preparation and post-processing times must be considered in planning and, ideally, determined together with anesthesiologists and surgical assistants.


Asunto(s)
Quirófanos , Administración del Tiempo , Estudios Transversales , Procedimientos Quirúrgicos Otorrinolaringológicos , Estudios Retrospectivos
19.
Nurs Open ; 9(1): 175-180, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34599864

RESUMEN

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.


Asunto(s)
COVID-19 , Trastornos del Olfato , Estudios Transversales , Humanos , Casas de Salud , Trastornos del Olfato/diagnóstico , Trastornos del Olfato/epidemiología , Pandemias , Prevalencia , Jubilación , SARS-CoV-2 , Olfato , Gusto
20.
BMC Infect Dis ; 21(1): 612, 2021 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-34174816

RESUMEN

BACKGROUND: The unexpected outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused more than 49 million cases and an estimated 2,000,000 associated deaths worldwide. In Germany, there are currently more than 2,000,000 laboratory-confirmed coronavirus disease 2019 (COVID-19) cases including 51,800 deaths. However, regional differences also became apparent and with the second wave of infections, the detailed characterization of COVID-19 patients is crucial to early diagnosis and disruption of chains of infections. METHODS: Handing out detailed questionnaires to all individuals tested for COVID-19, we evaluated the clinical characteristics of negative and positive tested individuals. Expression of symptoms, symptom duration and association between predictor variables (i.e. age, gender) and a binary outcome (olfactory and gustatory dysfunction) were assessed. RESULTS: Overall, the most common symptoms among individuals who tested positive for SARS-CoV-2 were fatigue, headache, and cough. Olfactory and gustatory dysfunction were also reported by many SARS-CoV-2 negative individuals, more than 20% of SARS-CoV-2 negative tested individuals in our study reported olfactory and gustatory dysfunction. Independent of SARS-CoV-2 status, more females displayed symptoms of gustatory (29.8%, p = 0.0041) and olfactory dysfunction (22.9%, p = 0.0174) compared to men. CONCLUSIONS: Bringing early SARS-CoV-2 tests to the populations at risk must be a main focus for the upcoming months. The reliability of olfactory and gustatory dysfunction in COVID-19 negative tested individuals requires deeper investigation in the future.


Asunto(s)
COVID-19/epidemiología , COVID-19/virología , Trastornos del Olfato/epidemiología , Trastornos del Olfato/virología , Trastornos del Gusto/epidemiología , Trastornos del Gusto/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/fisiopatología , Tos/epidemiología , Diagnóstico Precoz , Fatiga/epidemiología , Femenino , Alemania/epidemiología , Cefalea/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Olfato/diagnóstico , Trastornos del Olfato/fisiopatología , Pandemias , Reproducibilidad de los Resultados , SARS-CoV-2/patogenicidad , Caracteres Sexuales , Olfato , Encuestas y Cuestionarios , Trastornos del Gusto/fisiopatología , Adulto Joven
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