Partial recovery of peripheral blood monocyte subsets in head and neck squamous cell carcinoma patients upon radio(chemo)therapy is associated with decreased plasma CXCL11.

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.

Is an oropharyngeal HPV infection more frequently detectable in women with a genital HPV infection?

PURPOSE: If not eliminated by the immune system and persisting over years, oropharyngeal high-risk HPV infection can lead to cancer development in the oropharynx. HPV infection is very commonly found in the genital region and can serve as an HPV reservoir. In this study, we investigate whether women with a genital HPV infection are at a higher risk of harboring an undetected oropharyngeal HPV infection via genital-oropharyngeal transmission. METHODS: Women presenting for routine gynecological checkups were included in this study. All participants received an HPV brush test from the genital region as well as from the oropharynx. Additionally, probable risk factors for an HPV infection were assessed in a structured questionnaire. RESULTS: 142 women were included in this study. The rate of oropharyngeal HPV infection was low with 2/142 (1,4%) women positive for a low-risk HPV genotype. In the genital brush test, 54/142 (38%) women were tested HPV positive of which 41/142 (29%) were positive for a high-risk HPV genotype. CONCLUSIONS: The rate of an oropharyngeal HPV detection in our population was low with 2/142 women harboring a low-risk HPV infection.

Middle Ear Implant Usage Restores Subjective Listening Effort toward Normal in Complex Acoustic Scenes.

INTRODUCTION: The amount of listening effort needed to understand speech in every-day life is an important outcome measure of the effectiveness of a hearing device. The main goal of this study was to assess subjective listening effort in patients implanted with an active middle ear implant Vibrant Soundbridge (VSB) with and without using their speech processor in complex acoustic scenarios. METHODS: Ten VSB users were measured using the adaptive categorical listening effort scaling (ACALES) method in four different acoustic scenarios, realized using a multichannel loudspeaker array. The four acoustic scenarios included both spatially simple and complex speech and noise arrangements that realistically simulated challenging every-day listening situations. Signal-to-noise ratios (SNRs) were adaptively varied during the measurement. Twelve normal-hearing (NH) listeners performed the same experiment as a control group. RESULTS: Listening effort was significantly reduced in all tested acoustic scenarios when participants used their VSB. When using the VSB, SNRs corresponding to mild-to-moderate listening effort were found not to be statistically different from SNRs found in the NH control group. SNRs corresponding to extreme listening effort of VSB users approached NH values, indicating partial restoration of listening effort. DISCUSSION AND CONCLUSIONS: Usage of the middle ear implant VSB was found to restore subjective listening effort to normal at high SNRs completely, and at lower SNRs partially. The remaining gap at low SNRs may be due to lower effectiveness of signal processing at high noise levels or due to the microphone location effect.

Hearing rehabilitation and microbial shift after middle ear surgery with Vibrant Soundbridge in patients with chronic otitis media.

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.

TRIM21 Expression as a Prognostic Biomarker for Progression-Free Survival in HNSCC.

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.

[Influence of directional microphones on listening effort in middle ear implant users]. / Einfluss von Richtmikrofonie auf die Höranstrengung bei Mittelohrimplantatträgern.

BACKGROUND AND OBJECTIVE: Besides speech intelligibility, subjective listening effort is an important outcome for the success of hearing devices and their signal processing. The aim of the present study was to determine subjective listening effort for speech in a noisy background in patients with the active middle ear implant Vibrant Soundbridge (VSB) for omnidirectional and directional microphone settings, with and without occlusion of the contralateral ear. MATERIAL AND METHODS: A total of 15 patients using a VSB were measured using the adaptive categorical listening effort scaling (ACALES) method in a ring of loudspeakers placed in an anechoic room. Different background noises from different directions and simultaneously presented sentences from the Oldenburg sentence test were combined in four different realistic acoustic scenes. RESULTS: The directional microphone program reduced median subjective listening effort only numerically compared to the omnidirectional microphone program in acoustic scenarios with diffuse noise and with low signal-to-noise ratios; however, this difference failed to reach statistical significance. When occluding the ear contralateral to the VSB, all investigated listening effort categories were measured at significantly higher signal-to-noise ratios than with access to both ears. CONCLUSION: Due to missing statistical significance in reduction of listening effort, this study delivered no recommendation for or against usage of the directional microphone program; however, reduced listening effort was shown for binaural listening in comparison to monaural listening. Therefore, patients should be encouraged to always listen with both ears for best results.

[Immunomodulation in Cholesteatoma]. / Immunmodulation im Cholesteatom.

INTRODUCTION: The etiopathogenesis of chronic otitis media epitympanalis/cholesteatoma and its proliferative destructive course with possible complications such as destruction of bony structures with hearing loss, vestibular dysfunction, facial nerve paralysis and intracranial complications are still unexplained. Surgery is still the way to go. New studies are increasingly looking at the innate immune system. METHODS: Our studies were carried out in a mouse model in WT mice and immundeficient KO-mice, as well as in cholesteatoma and healthy ear canal skin and middle ear tissue, which was removed during ear surgery. The expression analyses were carried out at the gene and protein level using TNF as the major target for therapy evaluation. By means of TUNEL staining and immunohistochemistry the level of apoptosis was evaluated. RESULTS: The uncontrolled undirected cholesteatoma growth shows an immunomodulatory profile with up and down-regulation of various gene networks, especially those involved in TNF downstream and upstream signaling pathways. TNF in cholesteatoma is modulated both inflammatorily and apoptotically and therefore is suitable as a possible therapeutic approach in various models. CONCLUSIONS: Cholesteatoma might be immunomodulatory regulated.

Transsphenoidal and infralabyrinthine approach of the petrous apex cholesterol granuloma.

Space-demanding or destructive changes in the petrous bone are often challenging differential diagnosis. Cholesterol granulomas of the petrous apex can clinically present in a combination of hearing loss, vertigo, tinnitus, chronic cephalgia, impairment of facial nerve function, neuralgic pain of the nervus trigeminus, or manifest diplopia by the nerve palsy of the nervus abducens. CT-morphologically cholesterol granulomas appear as soft-tissue density masses, which may display a discrete rim after intravenous administration of a contrast agent. The MRI, T1 as well as T2-weighted images show a strong signal in the area of the lesion. Depending on the individual anatomical conditions, the surgical access must be carefully chosen between transsphenoidal, transtemporal, infracochlear/-labyrinthine, or translabyrinthine. Here, we present the transsphenoidal and translabyrinthine access for the excision of cholesterol granulomas of the petrous apex. The different accesses are compared using a neuro-navigation-supported surgical technique with respect to its complications, drainage possibilities, outcomes, and recurrence of symptoms.

Systematic review to evaluate the safety, efficacy and economical outcomes of the Vibrant Soundbridge for the treatment of sensorineural hearing loss.

Introduced in the late 90s, the active middle ear implant Vibrant Soundbridge (VSB) is nowadays used for hearing rehabilitation in patients with mild to severe sensorineural hearing loss (SNHL) unable to tolerate conventional hearing aids. In experienced hands, the surgical implantation is fast done, safe and highly standardized. Here, we present a systematic review, after more than 15 years of application, to determine the efficacy/effectiveness and cost-effectiveness, as well as patient satisfaction with the VSB active middle ear implant in the treatment of mild to severe SNHL. A systematic search of electronic databases, investigating the safety and effectiveness of the VSB in SNHL plus medical condition resulted in a total of 1640 papers. After removing duplicates, unrelated articles, screening against inclusion criteria and after in-depth screening, the number decreased to 37 articles. 13 articles were further excluded due to insufficient outcome data. 24 studies remained to be systematically reviewed. Data was searched on safety, efficacy and economical outcomes with the VSB. Safety-oriented outcomes included complication/adverse event rates, damage to the middle/inner ear, revision surgery/explant rate/device failure and mortality. Efficacy outcomes were divided into audiological outcomes, including hearing thresholds, functional gain, speech perception in quiet and noise, speech recognition thresholds, real ear insertion gain and subjective outcomes determined by questionnaires and patient-oriented scales. Data related to quality of life (QALY, ICER) were considered under economical outcomes. The VSB turns out to be a highly reliable and a safe device which significantly improves perception of speech in noisy situations with a high sound quality. In addition, the subjective benefit of the VSB was found to be mostly significant in all studies. Finally, implantation with the VSB proved to be a cost-effective and justified health care intervention.

The transcriptome of a complete episode of acute otitis media.

BACKGROUND: Otitis media is the most common disease of childhood, and represents an important health challenge to the 10-15% of children who experience chronic/recurrent middle ear infections. The middle ear undergoes extensive modifications during otitis media, potentially involving changes in the expression of many genes. Expression profiling offers an opportunity to discover novel genes and pathways involved in this common childhood disease. The middle ears of 320 WBxB6 F1 hybrid mice were inoculated with non-typeable Haemophilus influenzae (NTHi) or PBS (sham control). Two independent samples were generated for each time point and condition, from initiation of infection to resolution. RNA was profiled on Affymetrix mouse 430 2.0 whole-genome microarrays. RESULTS: Approximately 8% of the sampled transcripts defined the signature of acute NTHi-induced otitis media across time. Hierarchical clustering of signal intensities revealed several temporal gene clusters. Network and pathway enrichment analysis of these clusters identified sets of genes involved in activation of the innate immune response, negative regulation of immune response, changes in epithelial and stromal cell markers, and the recruitment/function of neutrophils and macrophages. We also identified key transcriptional regulators related to events in otitis media, which likely determine the expression of these gene clusters. A list of otitis media susceptibility genes, derived from genome-wide association and candidate gene studies, was significantly enriched during the early induction phase and the middle re-modeling phase of otitis but not in the resolution phase. Our results further indicate that positive versus negative regulation of inflammatory processes occur with highly similar kinetics during otitis media, underscoring the importance of anti-inflammatory responses in controlling pathogenesis. CONCLUSIONS: The results characterize the global gene response during otitis media and identify key signaling and transcription factor networks that control the defense of the middle ear against infection. These networks deserve further attention, as dysregulated immune defense and inflammatory responses may contribute to recurrent or chronic otitis in children.

Glial cell line-derived neurotrophic factor (GDNF) induces neuritogenesis in the cochlear spiral ganglion via neural cell adhesion molecule (NCAM).

Glial cell line-derived neurotrophic factor (GDNF) increases survival and neurite extension of spiral ganglion neurons (SGNs), the primary neurons of the auditory system, via yet unknown signaling mechanisms. In other cell types, signaling is achieved by the GPI-linked GDNF family receptor α1 (GFRα1) via recruitment of transmembrane receptors: Ret (re-arranged during transformation) and/or NCAM (neural cell adhesion molecule). Here we show that GDNF enhances neuritogenesis in organotypic cultures of spiral ganglia from 5-day-old rats and mice. Addition of GFRα1-Fc increases this effect. GDNF/GFRα1-Fc stimulation activates intracellular PI3K/Akt and MEK/Erk signaling cascades as detected by Western blot analysis of cultures prepared from rats at postnatal days 5 (P5, before the onset of hearing) and 20 (P20, after the onset of hearing). Both cascades mediate GDNF stimulation of neuritogenesis, since application of the Akt inhibitor Wortmannin or the Erk inhibitor U0126 abolished GDNF/GFRα1-Fc stimulated neuritogenesis in P5 rats. Since cultures of P5 NCAM-deficient mice failed to respond by neuritogenesis to GDNF/GFRα1-Fc, we conclude that NCAM serves as a receptor for GDNF signaling responsible for neuritogenesis in early postnatal spiral ganglion.

The Merits of Bilateral Application of Middle Ear Implants in Patients With Bilateral Conductive and/or Mixed Hearing Loss.

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.

1,8-Cineol Attenuates Checkpoint Molecule PDL-1 and Adhesion Molecule CX3CR1 in Circulating Monocytes in Otitis Media Patients.

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.

Ultrasound visualization of augmentation rhinoplasty using diced cartilage framework: A pictorial study.

BACKGROUND: Diced cartilage (DC) plays an integral role in rhinoplasty, and its application is well established in nasal dorsal augmentation rhinoplasty as a diced cartilage framework (DCF). METHODS: Fifteen patients requiring nasal dorsal augmentation were included. Two different types of DCF were applied: DC wrapped in fascia lata or Lyomesh® and DC embedded in platelet-rich fibrin (PRF). Postoperative ultrasound follow-ups were performed at intervals of one month, three months, and one year after surgery using a high-frequency linear ultrasound transducer. The aim was to depict the viability of the DCF in vivo. RESULTS: DCF was successfully depicted using ultrasound imaging in all 15 patients. Ultrasound rendered DC as hypoechoic and inhomogeneous areas. Perifocal hypoechoic edema was detected, which significantly decreased by the one-year follow-up. During the one-year postoperative period, very little DC had decreased in diameter and the framework was fully intact, with no signs of migration. On high-frequency ultrasound, DC wrapped in fascia lata or Lyomesh® appeared as a hypoechoic and inhomogeneous area clearly limited by a thin hyperechoic envelope material, whereas DC embedded in PRF presented as a hypoechogenic area that spread laterally along the bone and nasal cartilage on both sides. Using color Doppler imaging, neovascularization of the DCF was identified in 7 of 15 patients at the postoperative examination. CONCLUSION: High-resolution ultrasound is an accurate, non-invasive imaging method appropriate for visualizing DCF in augmentation rhinoplasty. Additionally, it is possible to detect nascent neovascularization within grafts by using color Doppler imaging.

Anti-inflammatory response to 1,8-Cineol and associated microbial communities in Otitis media patients.

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.

PANEL 3: Otitis media animal models, cell culture, tissue regeneration & pathophysiology.

OBJECTIVE: To review and summarize recently published key articles on the topics of animal models, cell culture studies, tissue biomedical engineering and regeneration, and new models in relation to otitis media (OM). DATA SOURCE: Electronic databases: PubMed, National Library of Medicine, Ovid Medline. REVIEW METHODS: Key topics were assigned to the panel participants for identification and detailed evaluation. The PubMed reviews were focused on the period from June 2019 to June 2023, in any of the objective subject(s) or keywords listed above, noting the relevant references relating to these advances with a global overview and noting areas of recommendation(s). The final manuscript was prepared with input from all panel members. CONCLUSIONS: In conclusion, ex vivo and in vivo OM research models have seen great advancements in the past 4 years. From the usage of novel genetic and molecular tools to the refinement of in vivo inducible and spontaneous mouse models, to the introduction of a wide array of reliable middle ear epithelium (MEE) cell culture systems, the next five years are likely to experience exponential growth in OM pathophysiology discoveries. Moreover, advances in these systems will predictably facilitate rapid means for novel molecular therapeutic studies.

Immunomodulatory Response of the Middle Ear Epithelial Cells in Otitis Media.

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.

Modes of Action of 1,8-Cineol in Infections and Inflammation.

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.

Salvage High-Dose-Rate Interventional Radiotherapy (Brachytherapy) Combined with Surgery for Regionally Relapsed Head and Neck Cancers.

(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.

Determination of orally administered 1,8-Cineol in nasal polyp tissues from chronic rhinosinusitis patients using gas chromatography: mass spectrometry.

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.