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This study investigated sound localization abilities in patients with bilateral conductive and/or mixed hearing loss (BCHL) when listening with either one or two middle ear implants (MEIs). Sound localization was measured by asking patients to point as quickly and accurately as possible with a head-mounted LED in the perceived sound direction. Loudspeakers, positioned around the listener within a range of +73°/-73° in the horizontal plane, were not visible to the patients. Broadband (500 Hz-20 kHz) noise bursts (150 ms), roved over a 20-dB range in 10 dB steps was presented. MEIs stimulate the ipsilateral cochlea only and therefore the localization response was not affected by crosstalk. Sound localization was better with bilateral MEIs compared with the unilateral left and unilateral right conditions. Good sound localization performance was found in the bilaterally aided hearing condition in four patients. In two patients, localization abilities equaled normal hearing performance. Interestingly, in the unaided condition, when both devices were turned off, subjects could still localize the stimuli presented at the highest sound level. Comparison with data of patients implanted bilaterally with bone-conduction devices, demonstrated that localization abilities with MEIs were superior. The measurements demonstrate that patients with BCHL, using remnant binaural cues in the unaided condition, are able to process binaural cues when listening with bilateral MEIs. We conclude that implantation with two MEIs, each stimulating only the ipsilateral cochlea, without crosstalk to the contralateral cochlea, can result in good sound localization abilities, and that this topic needs further investigation.
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Estimulação Acústica , Perda Auditiva Condutiva , Perda Auditiva Condutiva-Neurossensorial Mista , Prótese Ossicular , Localização de Som , Humanos , Localização de Som/fisiologia , Feminino , Masculino , Pessoa de Meia-Idade , Perda Auditiva Condutiva/fisiopatologia , Perda Auditiva Condutiva/cirurgia , Perda Auditiva Condutiva/diagnóstico , Perda Auditiva Condutiva/reabilitação , Adulto , Perda Auditiva Condutiva-Neurossensorial Mista/fisiopatologia , Perda Auditiva Condutiva-Neurossensorial Mista/reabilitação , Perda Auditiva Condutiva-Neurossensorial Mista/cirurgia , Perda Auditiva Condutiva-Neurossensorial Mista/diagnóstico , Idoso , Perda Auditiva Bilateral/fisiopatologia , Perda Auditiva Bilateral/reabilitação , Perda Auditiva Bilateral/diagnóstico , Perda Auditiva Bilateral/cirurgia , Resultado do Tratamento , Desenho de Prótese , Sinais (Psicologia) , Adulto Jovem , Limiar Auditivo , Condução Óssea/fisiologiaRESUMO
Chronic Otitis Media (COM) is defined as long term inflammation and colonization with pathogenic bacteria due to a defect or retraction of the tympanic membrane. Surgical interventions are often augmented by antibiotic resistance development and therefore, off-label treatment using the natural drug 1,8-Cineol was carried out. All COM patients underwent antibiotic therapy and middle ear surgery and developed antibiotic resistances. Microbiological investigations from the auditory canal and stool samples were performed in correlation with the clinical course. Therapy of COM patients with 1,8-Cineol revealed a clear reduction of inflammatory microbes P. aeruginosa and Proteus mirabilis in ear samples as well as intestinal Prevotella copri, which was associated with an improved clinical outcome in certain individuals. The present off-label study revealed manifold anti-inflammatory effects of the natural monoterpene 1,8-Cineol in Otitis media patients. A better understanding of the underlying mechanisms will improve the current treatment options and possible forms of application of this natural drug.
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Otite Média , Otite Média/microbiologia , Otite Média/tratamento farmacológico , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Proteus mirabilis/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Microbiota/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , IdosoRESUMO
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) represents a common and heterogeneous malignancy of the oral cavity, pharynx and larynx. Surgery and radio(chemo)therapy are the standard treatment options and also have great influence on the composition of the tumor microenvironment and immune cell functions. However, the impact of radio(chemo)therapy on the distribution and characteristics of circulating monocyte subsets in HNSCC are not fully understood. METHODS: Expression patterns of adhesion molecules and chemokine receptors CD11a (integrin-α L; LFA-1), CD11b (integrin-α M; Mac-1), CD11c (integrin-α X), CX3CR1 (CX3CL1 receptor) and checkpoint molecule PD-L1 (programmed cell death ligand-1) were investigated upon radio(chemo)therapeutic treatment using flow cytometry. Furthermore, comprehensive analysis of plasma cytokines was performed before and after treatment using ELISA measurements. RESULTS: Our data reveal a partial recovery of circulating monocytes in HNSCC patients upon radio(chemo)therapeutic treatment, with differential effects of the individual therapy regimen. PD-L1 expression on non-classical monocytes significantly correlates with the individual plasma levels of chemokine CXCL11 (C-X-C motif chemokine 11). CONCLUSIONS: Further comprehensive investigations on larger patient cohorts are required to elucidate the meaningfulness of peripheral blood monocyte subsets and chemokine CXCL11 as potential bioliquid indicators in HNSCC with regard to therapy response and the individual immunological situation.
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Neoplasias de Cabeça e Pescoço , Monócitos , Humanos , Antígeno B7-H1 , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Quimiocina CXCL11 , Neoplasias de Cabeça e Pescoço/terapia , Microambiente TumoralRESUMO
BACKGROUND/AIM: Tobacco is a carcinogen that is closely associated with the occurrence of lung cancer and head and neck squamous cell carcinoma (HNSCC). The consumption of tobacco is also leading to alterations in different immune cell subtypes. However, the impact of different conventional and alternative smoking sources on human monocytes remains elusive. MATERIALS AND METHODS: In this study, we investigated the influence of aqueous extracts of different sources of smoking (cigarettes; heated tobacco product IQOS; e-cigarettes with and without nicotine; nicotine pouches) on different monocytic adhesion molecules, chemokine receptors and checkpoint molecule PD-L1 by flow cytometry. Cytokine expression patterns were evaluated using human cytokine arrays and the human monocyte leukemia cell line THP-1 as a model. RESULTS: Data revealed differential effects of the analyzed conventional and alternative smoking devices on monocyte adhesion molecules and cytokine secretion. The examined smoking devices can be assigned to two differential monocyte activation patterns. Monocytes stimulated with aqueous extracts of cigarettes, e-cigarette without nicotine, and heat not burn product IQOS revealed distinct alterations of surface markers and cytokines compared to the monocyte activation pattern in response to aqueous extracts of nicotine, nicotine pouches, and e-cigarette with nicotine. CONCLUSION: Our data indicate differential immunological consequences of different conventional and alternative smoking sources with and without nicotine. Further comprehensive analysis as well as in vivo investigations on peripheral blood monocyte subsets from smoking individuals using different smoking sources are required to better understand the impact on monocyte characteristics, especially with regard to the development of cancer.
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Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Humanos , Nicotina/farmacologia , Monócitos , Fumar , Moléculas de Adesão Celular , CitocinasRESUMO
BACKGROUND: Peripheral blood monocytes can be subdivided into different subsets based on the CD14/CD16 surface characteristics. Monocytes are a major source of cytokine secretion of pro-inflammatory immune responses, whereas CD16+ monocyte subsets can also contribute to persistent inflammation in the context of chronic diseases. However, the regulation and cellular characteristics of circulating monocyte subsets in patients with chronic otitis media (COM), one of the largest public health burdens, remains largely unknown. MATERIALS AND METHODS: In this study, we analyzed individual distributions of circulating monocyte subsets and associated protein expression levels of adhesion protein and chemokine receptors CD11a (integrin-α L; LFA-1), CD11b (integrin-α M; Mac-1), and CD11c (integrin-α X), CX3CR1 (CX3CL1 receptor), as well as checkpoint molecule PD-L1 (programmed cell death ligand-1), in a gender-balanced cohort of 14 patients with chronic otitis media using flow cytometry, especially in view of the therapeutic impact of the natural plant-derived monoterpene oxide 1,8-Cineol. Furthermore, using the human monocyte cell line THP-1 as a model, we investigated the influence of anti-inflammatory 1,8-Cineol on monocytic cytokine secretion patterns using human cytokine arrays and ELISA measurements. RESULTS: The data revealed significantly elevated expression levels of all analyzed adhesion molecules in certain monocyte subsets in COM patients; CX3CR1 was especially significantly down-regulated in response to 1,8-Cineol administration. Moreover, the data revealed significantly increased monocytic PD-L1 expression levels in circulating classical and intermediate monocyte subsets from COM patients compared to healthy donors, but also a significant decrease in PD-L1 in intermediate monocytes upon 1,8-Cineol therapy compared to the pre-treatment situation. Furthermore, the increased secretion of cytokine CXCL10 by THP-1 monocytes in response to LPS was found to be strongly attenuated by 1,8-Cineol. Plasma levels of CXCL10 were also significantly increased in COM patients, but no significant differences between the pre and post 1,8-Cineol situation were observed. CONCLUSIONS: The present study revealed new insights into the bioactive anti-inflammatory effects of 1,8-Cineol in terms of monocyte adhesion and immune regulation. Our data suggest the potential role of cytokine CXCL10 in COM development and maintenance, which is also involved in the activity of its concomitant disease, rheumatoid arthritis.
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Oxidative stress in patients suffering from obstructive sleep apnea syndrome (OSAS) is associated with a low-grade systemic inflammation, immune disturbance, and increased invasion of monocytes into the endothelium. Besides continuous positive airway pressure (PAP), hypoglossal nerve stimulation (HNS) has become a promising treatment option for patients with OSAS. We aimed to analyse the influence of HNS therapy on the cellular characteristics relevant for adhesion and immune regulation of circulating CD14/CD16 monocyte subsets. Whole blood flow cytometric measurements were performed to analyse the expression levels of different adhesion molecules and checkpoint molecule PD-L1 (programmed death-ligand 1) in connection with pro-inflammatory plasma cytokine IL-8 and the clinical values of BMI (body mass index), AHI (apnea-hypopnea index), ODI (oxygen desaturation index), and ESS (Epworth sleepiness scale) upon HNS treatment. Hypoglossal nerve stimulation treatment significantly improved the expression of adhesion molecule CD162 (P-selectin receptor) on non-classical monocytes and significantly downregulated the expression of PD-L1 on all three monocyte subsets. We conclude that the holistic improvement of different parameters such as the oxygenation of the peripheral blood, a reduced systemic inflammation, and the individual sleeping situation upon HNS respiratory support, leads to an improved immunologic situation.
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BACKGROUND AND OBJECTIVE: Data on enteral tube feeding in head and neck cancer (HNC) patients undergoing chemoradiotherapy vary considerably between German institutions. This survey aims to investigate the management of feeding tubes in an interdisciplinary context across Germany. MATERIALS AND METHODS: Between December 2022 and May 2023, 70 participants (42 radiation oncologists, 12 medical oncologists, 14 head and neck surgeons, and 2 physicians covering several specialties) responded to our web-based survey. In addition to the type of institution (university hospital, private practice, etc.), their age, and professional experience (in years), participants were asked several questions on the indication and institutional policy for tube placement and management (prophylactic/reactive nasogastric or gastrostomy tube). All questions were mandatory single- or multiple-choice questions, while additional comments were possible by email. RESULTS: Most participants were employed at a university hospital (nâ¯= 52; 74.3%) and came from a radiation oncology background (nâ¯= 42; 60%). Fifty-four contributors (77.1%) reported that no nutritional risk screening prior to chemoradiotherapy was routinely performed, and 71.4% (nâ¯= 50) stated that no standardized protocol was used at the institution to set the indication for tube placement. Generally, policies and methods of tube feeding vary considerably between the individual institutions and specialties. However, the majority (nâ¯= 56, 80%) recommended a prophylactic percutaneous enteral gastrostomy (PEG) tube to their patients before chemoradiotherapy. Still, there was no consistent trend regarding the approach for reactive tube feeding. CONCLUSION: The policies and methods of tube feeding vary considerably between the individual institutions and specialties in Germany. In the era of individualized medicine, uniform protocols are difficult to establish. However, a baseline nutritional risk screening could simplify decision-making in clinical practice.
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Quimiorradioterapia , Nutrição Enteral , Gastrostomia , Neoplasias de Cabeça e Pescoço , Intubação Gastrointestinal , Humanos , Alemanha , Neoplasias de Cabeça e Pescoço/terapia , Masculino , Inquéritos e Questionários , Padrões de Prática Médica/estatística & dados numéricos , Feminino , Pesquisas sobre Atenção à Saúde , Comunicação Interdisciplinar , Pessoa de Meia-Idade , Radio-OncologistasRESUMO
Obstructive sleep apnea syndrome (OSAS) and obesity go hand in hand in the majority of patients and both are associated with a systemic inflammation, immune disturbance and comorbidities such as cardiovascular disease. However, the unambiguous impact of OSAS and obesity on the individual inflammatory microenvironment and the immunological consequences of human monocytes has not been distinguished yet. Therefore, aim of this study was to investigate the impact of OSAS and obesity related factors on the inflammatory microenvironment by performing flow cytometric whole blood measurements of CD14/CD16 monocyte subsets in normal weight OSAS patients, patients with obesity but without OSAS, and patients with OSAS and obesity, compared to healthy donors. Moreover, explicitly OSAS and obesity related plasma levels of inflammatory mediators adiponectin, leptin, lipocalin and metalloproteinase-9 were determined and the influence of different OSAS and obesity related factors on cytokine secretion and expression of different adhesion molecules by THP-1 monocytes was analysed. Our data revealed a significant redistribution of circulating classical and intermediate monocytes in all three patient cohorts, but differential effects in terms of monocytic adhesion molecules CD11a, CD11b, CD11c, CX3CR1, CD29, CD49d, and plasma cytokine levels. These data were reflected by differential effects of OSAS and obesity related factors leptin, TNFα and hypoxia on THP-1 cytokine secretion patterns and expression of adhesion molecules CD11b and CD49d. In summary, our data revealed differential effects of OSAS and obesity, which underlines the need for a customized therapeutic regimen with respect to the individual weighting of these overlapping diseases.
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Leptina , Apneia Obstrutiva do Sono , Humanos , Monócitos/metabolismo , Obesidade/metabolismo , CitocinasRESUMO
Obesity is characterized by excessive body fat accumulation and comorbidities such as diabetes mellitus, cardiovascular disease, and obstructive sleep apnea syndrome (OSAS). Both obesity and OSAS are associated with immune disturbance, alterations of systemic inflammatory mediators, and immune cell recruitment to metabolic tissues. Chemokine CXCL10 is an important regulator of proinflammatory immune responses and is significantly increased in patients with severe obesity. This research project aims to investigate the impact of CXCL10 on human monocytes in patients with obesity. We studied the distribution of the CD14/CD16 monocyte subsets as well as their CX3CR1 expression patterns in whole-blood measurements from 92 patients with obesity and/or OSAS with regard to plasma CXCL10 values and individual clinical parameters. Furthermore, cytokine secretion by THP-1 monocytes in response to CXCL10 was analyzed. Data revealed significantly elevated plasma CXCL10 in patients with obesity with an additive effect of OSAS. CXCL10 was found to drive monocytic secretion of macrophage migration inhibitory factor via receptor protein CX3CR1, which significantly correlated with the individual body mass index. Our data show, for the first time, to our knowledge, that CX3CR1 is involved in alternative CXCL10 signaling in human monocytes in obesity-related inflammation. Obesity is a multifactorial disease, and further investigations regarding the complex interplay between obesity-related inflammatory mediators and systemic immune balances will help to better understand and improve the individual situation of our patients.
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Fatores Inibidores da Migração de Macrófagos , Apneia Obstrutiva do Sono , Humanos , Quimiocina CXCL10 , Receptor 1 de Quimiocina CX3C , Mediadores da Inflamação , Monócitos , ObesidadeRESUMO
HYPOTHESIS: The middle ear (ME) epithelium transforms because of changed immunomodulation during infection. INTRODUCTION: The epithelial cells of the tympanic cavity represent the first line of defense in the context of otitis media. They can convert from a typical mucosal site into a respiratory epithelium and vice versa. Our goal is to depict the specific immune response of epithelial cells after infection at the molecular level. METHODS: The investigations were carried out on healthy and inflamed ME tissue, removed during surgical interventions in mouse and human models, and in a human in-vitro cell model in human ME epithelial cell line. We determined the epithelial localization of the protein expression of Toll- and NOD-like immune receptors and their associated signaling molecules using immunohistochemistry. In addition, we examined growth behavior and gene expression due to direct stimulation and inhibition. RESULTS: We found clinically and immunobiologically confirmed transformation of the inflamed ME epithelium depending on their origin, as well as differences in the distribution of Toll-like receptors and nucleotide-binding oligomerization domain-like receptors in the epithelial cell lining. Dysregulated gene and protein expression of the inflammatory and apoptotic genes could be modulated by stimulation and inhibition in the epithelial cells. CONCLUSIONS: The local ME mucosal tissue is believed to modulate downstream immune activity after pathogen invasion via intrinsic cellular mechanism. Using translation approaches to target these molecular pathways may offer more reliable clinical resolution of otitis media in the future.
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Otite Média , Humanos , Camundongos , Animais , Orelha Média , Células Epiteliais , Fagocitose , ImunomodulaçãoRESUMO
BACKGROUND: Patients with obstructive or central sleep apnea are primarily treated with positive airway pressure treatment. There are novel implantable options targeting either obstructive sleep apnea using hypoglossal nerve stimulation (HNS) or central sleep apnea using phrenic nerve stimulation (PNS). METHODS: Patients with sleep apnea were implanted with both HNS and PNS devices, and their response to each therapy was monitored using home sleep tests as well as Epworth Sleepiness scale (ESS). RESULTS: We evaluated our concurrent neurostimulation approach in two patients. Both patients were implanted with two neuromodulation devices: The first case suffered from treatment emergent central sleep apnea after HNS activation for primarily obstructive sleep apnea (apnea-hypopnea index/AHI 54/h). The central portion resolved under PNS (AHI 23.7/h). The second case suffered from predominantly central sleep apnea (AHI 82/h). Here, the PNS device was implanted first, resulting in a subsequent reduction of the central portion. The residual obstructive sleep apnea was addressed using HNS (AHI 5.4/h). No interaction between the HNS and PNS systems was noticed in either of the two patients. CONCLUSIONS: In selected cases, a concurrent treatment with hypoglossal and phrenic nerve stimulation may lead to improvement of sleep apnea and patient satisfaction in a safe manner.
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BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous malignant disease of the oral cavity, pharynx, and larynx. HNSCC cells evade the host immune system through alterations in their immunogenicity, production of immunosuppressive mediators, and induction of immunomodulatory cell types. The immune status of solid HNSCC can be considered as hot, cold, or excluded for each patient individually, based on the distribution of tumor infiltrating immune cells. In this context immunotherapies based on the blockade of checkpoint molecules programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) have significantly improved therapeutic outcomes in different cancer types. In HNSCC, intra-tumoral expression levels of PD-L1 are used for decision making in checkpoint inhibitor treatment. The significance of PD-L1 as a prognostic indicator is still controversial because both PD-1 and PD-L1 are also expressed in different types of circulating immune cells and the interaction of systemic and intra-tumoral cell-type-specific expression patterns of checkpoint molecules PD-1/PD-L1 has not yet been fully unveiled. MATERIALS AND METHODS: Using immunohistochemical (IHC) staining and flow cytometry, we correlated the expression patterns of the checkpoint molecules PD1/PD-L1 in peripheral blood CD14/CD16 monocytes and CD4/CD8 T cells with intra-tumoral conditions in patients with head and neck cancer. RESULTS/CONCLUSION: Our data demonstrate significant connections between systemic and intra-tumoral PD-1/PD-L1 immune patterns, both of which may serve as promising combined biomarkers for treatment decisions in patients with head and neck cancer.
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Antígeno B7-H1 , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/metabolismoRESUMO
(1) Background: to report on the use of high-dose-rate (HDR) interventional radiotherapy (brachytherapy, IRT) as a salvage treatment for patients with regionally relapsed head and neck cancers. (2) Methods: A retrospective study of 60 patients treated with HDR-IRT for loco-regionally relapsed head and neck cancers at our institution (2016-2020). Treatment procedure, results, and related toxicities were collected. Local and overall survival outcomes were analyzed. (3) Results: The median follow-up was 22.4 months. Twenty-nine (48.3%) patients had locoregional recurrences with a median time of 28.9 months. The local-recurrence free-survival was 88.1% and 37.3% at 3 years and 5 years. At the last follow-up, 21 patients were alive and the median time to death was 24 months. The overall survival was 39.2% and 16.6% at 3 years and 5 years. Collectively, there were 28 events of grade ≥ 3 late toxicities recorded in 21 patients (35%). (4) Conclusions: Salvage HDR-IRT combined with surgery offers a second-line curative treatment option for regionally relapsed head and neck cancers with acceptable outcomes and toxicities.
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The monoterpene 1,8-Cineol is a natural plant-based therapeutic agent that is commonly applied to treat different inflammatory diseases due to its mucolytic, anti-microbial and anti-inflammatory properties. It has become increasingly clear in the recent years that 1,8-Cineol spreads almost everywhere in the human body after its oral administration, from the gut to the blood to the brain. Its anti-microbial potential and even its anti-viral effects have been observed to include numerous bacteria and fungi species. Many recent studies help to better understand the cellular and molecular immunological consequences of 1,8-Cineol treatment in inflammatory diseases and further provide information concerning the mechanistic modes of action in the regulation of distinct inflammatory biosynthetic pathways. This review aims to present a holistic and understandable overview of the different aspects of 1,8-Cineol in infections and inflammation.
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BACKGROUND/AIM: Immune checkpoint inhibitors have improved the treatment regimen for human cancers in recent years. Particularly, inhibitors of the checkpoint molecules PD-1/PD-L1 have emerged as promising therapeutic treatments by preventing T-cell anergy and exhaustion. However, the impact of different anti-PD-1/PD-L1 checkpoint inhibitors on human monocytes remains elusive. MATERIALS AND METHODS: In this study, using the human monocyte leukemia cell line THP-1 as a model, we investigated the influence of different therapeutic anti-PD-1/PD-L1 checkpoint inhibitors on monocytic adhesion molecule expression and cytokine secretion. THP-1 monocytes were treated with the anti-PD-1 checkpoint inhibitors Nivolumab and Pembrolizumab and anti-PD-L1 checkpoint inhibitors Atezolizumab and Durvalumab. Cytokine expression patterns were evaluated using cytokine arrays and enzyme-linked immunosorbent assays (ELISA) and analysis of adhesion molecules was addressed using flow cytometry. RESULTS: Our data show an overall moderate apoptosis induction upon checkpoint inhibitor treatment and significantly reduced expression levels of adhesion molecules CD29, CD49d, and CX3CR1 in response to anti-PD-1 treatment. Cytokine screening revealed overall decreased secretion levels of insulin-like growth factor binding protein 2 (IGFBP2), CD147 (basigin) and CD31 (PECAM-1) as well as elevated levels of interleukin 5 (IL-5) and interferon gamma (IFNγ) in response to checkpoint inhibitor treatment. CONCLUSION: Our data indicate differential effects of anti-PD-1/PD-L1 checkpoint inhibitors on THP-1 monocytes, both by specific anti-PD-1/PD-L1 binding and unspecific antibody IgG isotype recognition. Further investigations on peripheral blood monocyte subsets in terms of their expansion and function upon checkpoint inhibitor therapy are required to better understand the individual immunological balances in cancer patients in long-term observational studies.
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Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Monócitos , Nivolumabe , Citocinas , Antígeno B7-H1/metabolismoRESUMO
Exosomes play an important role in the individual immune regulation in patients with head and neck squamous cell carcinoma (HNSCC) as part of the tumor microenvironment. Patients with HNSCC with advanced tumor stages reveal significantly increased levels of plasma derived CD16+ (FcRIIIA) total exosomes as demonstrated in our previous study. Furthermore, increased individual abundances of peripheral blood CD16+ non-classical monocytes have been shown to correlate with increased monocytic programmed death ligand 1 (PD-L1) and CD4+ T cell disturbances in oropharyngeal cancer. However, the context of plasma derived CD16+ exosomes in patients with HNSCC and their role in the immune-regulation of circulating monocyte subsets has not been investigated so far. In the present study, exosomes were isolated from plasma samples of healthy donors and patients with HNSCC and evaluated for their morphology, size and protein composition using transmission electron microscopy, western blotting and bead-based flow cytometry. Monocyte subset abundances were analyzed in whole blood measurements in terms of the CD14/CD16 cell surface expression patterns, different monocytic adhesion molecules and checkpoint molecule PD-L1 using flow cytometry. Isolated exosomes were positive for the tetraspanins CD63 and CD9 as well as the endosomal marker TSG101, but negative for the non-exosomal marker glucose-regulated protein 94 and apolipoprotein ApoA1. Plasma derived CD16+ exosomes and exosome size distribution were significantly correlated with abundances of CD16+ non-classical monocytes and CD16+ intermediate monocytes, respectively. Furthermore, the data revealed significant correlations between CD16+ plasma derived exosomes and adhesion molecules CD29 (integrin ß1) and CX3CR1 on certain monocyte subsets. These data suggested that CD16 positive exosomes and exosome size distribution were potential surrogates to characterize the composition of monocyte subsets in patients with HNSCC. Overall, both CD16-positive exosomes and CD16-positive monocyte subsets are potential liquid biomarkers that could be used to characterize the individual immunological situation of patients with HNSCC.
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Obesity is a dramatically increasing disease, accompanied with comorbidities such as cardiovascular disease and obstructive sleep apnea syndrome (OSAS). Both obesity and OSAS per se are associated with systemic inflammation. However, the multifactorial impact of obesity, OSAS, and its concomitant diseases on the immunological characteristics of circulating monocytes has not yet been fully resolved. Monocyte subsets of 82 patients with obesity were analyzed in whole blood measurements in terms of the CD14/CD16 cell surface expression patterns and different monocytic adhesion molecules using flow cytometry. Plasma levels of adipokines adiponectin and leptin of all patients were evaluated and correlated with accompanying cellular and clinical values. Whole blood measurements revealed a significant overall redistribution of CD14/CD16 monocyte subsets in patients with obesity. Monocytic adhesion molecules CD11a, CD11b, and CX3CR1 were significantly elevated. The observed alterations significantly correlated with plasma leptin levels and diabetes status as crucial amplifying factors. The additive impact of obesity, diabetes, and OSAS on the immunological balance of peripheral blood monocytes requires a coordinated regimen in terms of therapeutic treatment, respiratory support, and weight loss to improve the systemic immunity in these patients.
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Diabetes Mellitus , Apneia Obstrutiva do Sono , Humanos , Leptina , Monócitos , Obesidade , Apneia Obstrutiva do Sono/terapiaRESUMO
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disease causing considerable disease burden. The anti-inflammatory monoterpene 1,8-Cineol is a natural plant-based therapeutic agent that is well established to treat chronic and acute airway diseases. Aim of this study was to investigate whether the herbal drug 1,8-Cineol reaches the nasal tissue via the gut and the blood stream upon its oral administration. A highly sensitive gas chromatography mass spectrometry-based method with stir bar sorptive extraction (SBSE) for sample preparation has been developed and validated for the extraction, detection and quantification of 1,8-Cineol in tissue samples of nasal polyps from 30 CRSwNP patients. Data revealed a highly sensitive detection of 1,8-Cineol in nasal tissue samples after 14 days of oral administration of 1,8-Cineol prior to surgical treatment. There was no significant correlation between the measured 1,8-Cineol concentrations and bodyweight or BMI values of the analyzed patients, respectively. Our data indicate a systemic distribution of 1,8-Cineol in the human body after its oral administration. Individual differences in terms of metabolic characteristics and have to be further investigated. The study increases our understanding of the systemic effects of 1,8-Cineol upon its therapeutic application and benefit in patients with CRSwNP.
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Magnoliopsida , Pólipos Nasais , Sinusite , Humanos , Eucaliptol , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas , Nariz , Doença CrônicaRESUMO
Patients with head and neck squamous cell carcinoma (HNSCC) continue to have a rather poor prognosis. Treatment-related comorbidities have negative impacts on their quality of life. TRIM21 is a cytosolic E3 ubiquitin ligase that was initially described as an autoantigen in autoimmune diseases and later associated with the intracellular antiviral response. Here, we investigated the role of TRIM21 as a biomarker candidate for HNSCC in predicting tumor progression and patient survival. We analyzed TRIM21 expression and its association with clinical-pathological parameters in our HNSCC cohort using immunohistochemistry. Our HNSCC cohort included samples from 419 patients consisting of primary tumors (n = 337), lymph node metastases (n = 156), recurrent tumors (n = 54) and distant metastases (n = 16). We found that cytoplasmic TRIM21 expression was associated with the infiltration of immune cells into primary tumors. In addition, TRIM21 expression was significantly higher in primary tumors than in lymph node metastases, and increased TRIM21 expression was correlated with shorter progression-free survival in HNSCC patients. These results suggest that TRIM21 could be a new biomarker for progression-free survival.
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Neoplasias de Cabeça e Pescoço , Humanos , Biomarcadores Tumorais/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Metástase Linfática , Recidiva Local de Neoplasia , Prognóstico , Intervalo Livre de Progressão , Qualidade de Vida , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
INTRODUCTION: Patients with otitis media (OM) encounter significant functional hearing impairment with conductive, or a combined hearing loss and long-term sequelae involving impaired speech/language development in children, reduced academic achievement and irreversible disorders of middle and inner ear requiring a long time therapy and/or multiple surgeries. In its persistent chronic form, Otitis media (COM) can often only be treated by undergoing ear surgery for hearing restoration. The persistent inflammatory reaction plays a major role, often caused by multi-resistant pathogens in the ear. Herein, we present outcomes of patients implanted with currently the only FDA approved active Middle Ear Implant Vibrant Soundbridge (VSB), suffering from persistent COM. METHODS: The study enrolled 42 patients, treated by performing middle ear (ME) surgery to different extents and implanted with the VSB to various structures in the ME. Included were 17 children and 25 adults that had recurrent and/or persisting OM and significant hearing loss. Preoperative and postoperative patients' audiometric data were evaluated and the benefit with VSB assessed using the Glasgow Benefit Inventory for adults and pediatric cohorts. The microbial spectrum of pathogens was assessed before and after surgery, exploring the colonization of the otopathogens, as well as the intestinal microbiome from individually burdened patients. RESULTS: The mean functional gain is 29.7 dB HL (range from 10 to 56.2 dB HL) with a significant improvement in speech intelligibility in quiet. Following VSB implantation, no significant differences in coupling were observed at low complication rates. Postoperatively patients showed significantly increased benefit with VSB compared to the untreated situation, including less otorrhea, pain, medical visits, and medication intake, with no recurrent OM and significant bacterial shift in otopathogens. The analysis of the intestinal microbiome displayed a high abundance of bacterial strains that might be linked to chronic and persistent inflammation. CONCLUSIONS: Functional ear surgery including rehabilitation with a VSB in patients suffering from COM present to be safe and effective. The successful acceptance accompanied by the improved audiological performance resulted in significant benefit with VSB, with a shift in the ear pathogens and altered microbiome and thus is a great opportunity to be treated.