Very regular high-frequency pulsation modes in young intermediate-mass stars.

Asteroseismology probes the internal structures of stars by using their natural pulsation frequencies1. It relies on identifying sequences of pulsation modes that can be compared with theoretical models, which has been done successfully for many classes of pulsators, including low-mass solar-type stars2, red giants3, high-mass stars4 and white dwarfs5. However, a large group of pulsating stars of intermediate mass-the so-called δ Scuti stars-have rich pulsation spectra for which systematic mode identification has not hitherto been possible6,7. This arises because only a seemingly random subset of possible modes are excited and because rapid rotation tends to spoil regular patterns8-10. Here we report the detection of remarkably regular sequences of high-frequency pulsation modes in 60 intermediate-mass main-sequence stars, which enables definitive mode identification. The space motions of some of these stars indicate that they are members of known associations of young stars, as confirmed by modelling of their pulsation spectra.

AllergoOncology: Biomarkers and refined classification for research in the allergy and glioma nexus-A joint EAACI-EANO position paper.

Epidemiological studies have explored the relationship between allergic diseases and cancer risk or prognosis in AllergoOncology. Some studies suggest an inverse association, but uncertainties remain, including in IgE-mediated diseases and glioma. Allergic disease stems from a Th2-biased immune response to allergens in predisposed atopic individuals. Allergic disorders vary in phenotype, genotype and endotype, affecting their pathophysiology. Beyond clinical manifestation and commonly used clinical markers, there is ongoing research to identify novel biomarkers for allergy diagnosis, monitoring, severity assessment and treatment. Gliomas, the most common and diverse brain tumours, have in parallel undergone changes in classification over time, with specific molecular biomarkers defining glioma subtypes. Gliomas exhibit a complex tumour-immune interphase and distinct immune microenvironment features. Immunotherapy and targeted therapy hold promise for primary brain tumour treatment, but require more specific and effective approaches. Animal studies indicate allergic airway inflammation may delay glioma progression. This collaborative European Academy of Allergy and Clinical Immunology (EAACI) and European Association of Neuro-Oncology (EANO) Position Paper summarizes recent advances and emerging biomarkers for refined allergy and adult-type diffuse glioma classification to inform future epidemiological and clinical studies. Future research is needed to enhance our understanding of immune-glioma interactions to ultimately improve patient prognosis and survival.

AllergoOncology: Danger signals in allergology and oncology: A European Academy of Allergy and Clinical Immunology (EAACI) Position Paper.

The immune system interacts with many nominal 'danger' signals, endogenous danger-associated (DAMP), exogenous pathogen (PAMP) and allergen (AAMP)-associated molecular patterns. The immune context under which these are received can promote or prevent immune activating or inflammatory mechanisms and may orchestrate diverse immune responses in allergy and cancer. Each can act either by favouring a respective pathology or by supporting the immune response to confer protective effects, depending on acuity or chronicity. In this Position Paper under the collective term danger signals or DAMPs, PAMPs and AAMPs, we consider their diverse roles in allergy and cancer and the connection between these in AllergoOncology. We focus on their interactions with different immune cells of the innate and adaptive immune system and how these promote immune responses with juxtaposing clinical outcomes in allergy and cancer. While danger signals present potential targets to overcome inflammatory responses in allergy, these may be reconsidered in relation to a history of allergy, chronic inflammation and autoimmunity linked to the risk of developing cancer, and with regard to clinical responses to anti-cancer immune and targeted therapies. Cross-disciplinary insights in AllergoOncology derived from dissecting clinical phenotypes of common danger signal pathways may improve allergy and cancer clinical outcomes.

[Allergo-oncology: what allergologists and oncologists can learn from each other : Regulatory T cells in allergy and cancer]. / Allergoonkologie: was Allergologen und Onkologen voneinander lernen können : Regulatorische T­Zellen bei Allergie und Krebserkrankungen.

BACKGROUND: The immune system has substantial involvement in the pathophysiology of allergies and cancer. The complexity of the immune system is well balanced in health, in so-called immune homeostasis. In many diseases, as in allergies and cancer, this balance is disturbed. The tolerance to foreign but harmless substances, such as tree or grass pollen, is no longer sufficiently given in allergic patients. In cancer patients, the immune system is tolerant to harmful tumor cells. Thus, allergies and cancer show an opposing pattern in terms of immune tolerance. The group of regulatory T cells occupies a central position here. OBJECTIVE: This article deals with the function of regulatory T cells in detail. This group of immune cells and its interaction with other involved immune cells and messenger signals in the pathophysiology and treatment of allergies and cancer are presented. METHODS: A review article was compiled based on the pertinent literature. RESULTS: The regulatory T cells of cancer patients are a mechanism of the so-called tumor escape phenomenon to hide from the immune system. The tumor uses danger signals, e.g., the HMGB1 protein, to mediate tolerance to the immune system through these cells and thus avoid elimination. In allergic patients, these cells are underrepresented and can be induced by a specific immunotherapy, in order to achieve tolerance to the allergens and thus a causal treatment. CONCLUSION: Regulatory T cells play an important role in the pathogenesis of cancer and allergies, and thus represent a therapeutic target.

AllergoOncology: Microbiota in allergy and cancer-A European Academy for Allergy and Clinical Immunology position paper.

The microbiota can play important roles in the development of human immunity and the establishment of immune homeostasis. Lifestyle factors including diet, hygiene, and exposure to viruses or bacteria, and medical interventions with antibiotics or anti-ulcer medications, regulate phylogenetic variability and the quality of cross talk between innate and adaptive immune cells via mucosal and skin epithelia. More recently, microbiota and their composition have been linked to protective effects for health. Imbalance, however, has been linked to immune-related diseases such as allergy and cancer, characterized by impaired, or exaggerated immune tolerance, respectively. In this AllergoOncology position paper, we focus on the increasing evidence defining the microbiota composition as a key determinant of immunity and immune tolerance, linked to the risk for the development of allergic and malignant diseases. We discuss novel insights into the role of microbiota in disease and patient responses to treatments in cancer and in allergy. These may highlight opportunities to improve patient outcomes with medical interventions supported through a restored microbiome.

Locoregional tumour evaluation of squamous cell carcinoma in the head and neck area: a comparison between MRI, PET/CT and integrated PET/MRI.

PURPOSE: To evaluate the accuracy of integrated (18)F-FDG PET/MR imaging for locoregional tumour evaluation compared to (18)F-FDG PET/CT and MR imaging in initial tumour and recurrence diagnosis in histopathologically confirmed head and neck squamous cell carcinoma (HNSCC). METHODS: (18)F-FDG PET/CT and integrated (18)F-FDG PET/MR imaging were performed for initial tumour staging or recurrence diagnosis in 25 patients with HNSCC. MR, fused (18)F-FDG PET/CT and fused (18)F-FDG PET/MR images were analysed by two independent readers in separate sessions in random order. In initial tumour staging, T and N staging was performed while individual lesions were analysed in patients with suspected cancer recurrence. In T and N staging, histopathological results after tumour resection served as the reference standard while histopathological sampling as well as cross-sectional and clinical follow-up were accepted in cancer recurrence diagnosis. The diagnostic accuracy of each modality was calculated separately for T and N staging as well as for tumour recurrence, and compared using McNemar's test. Values of p <0.017 were considered statistically significant after Bonferroni correction. RESULTS: In 12 patients undergoing (18)F-FDG PET/CT and (18)F-FDG PET/MR for initial tumour staging, T staging was accurate in 50 % with MRI, in 59 % with PET/CT and in 75 % with PET/MR while N staging was accurate in 75 % with MRI, in 77 % with PET/CT and in 71 % with PET/MR in relation to the reference standard. No significant differences were observed in T and N staging among the three modalities (p > 0.017). In 13 patients undergoing hybrid imaging for cancer recurrence diagnosis, diagnostic accuracy was 57 % with MRI and in 72 % with (18)F-FDG PET/CT and (18)F-FDG PET/MR, respectively. Again, no significant differences were found among the three modalities (p > 0.017). CONCLUSION: In this initial study, no significant differences were found among (18)F-FDG PET/MR, (18)F-FDG PET/CT and MRI in local tumour staging and cancer recurrence diagnosis.

Evaluation of the application of rhino-septal splints in endoscopic transsphenoidal skull base surgery.

The endoscopic transnasal route for the surgical removal of tumors in the sellar region is frequently associated with nasal complications such as synechiae or impaired nasal breathing. In this study, we investigated the impact of septal splints on avoiding surgery-related co-morbidities. 49 patients in whom endoscopic transnasal, transsphenoidal surgery for sellar tumors was performed between 2012 and 2014 were studied. In 30 of these, nasal septal splints were applied at the end of surgery to both sides of the septum and left in situ for 10 days (group 1), 19 patients received no splints (group 2). A standardized postsurgical follow-up investigation with endoscopic nasal examination, rhinomanometry and olfactory testing was performed on average 2 months postoperatively. Patients' subjective nose-related discomfort at follow-up was assessed descriptively using a set of standardized self-rating statements on nasal problems. Synechias occurred less likely with nasal septal splints (n = 15; 50 %) than without (n = 16; 84.2 %). Moreover, multiple synechiae were predominantly observed in the group without septal splints (n = 10 vs. n = 2). Rhinomanometry showed improved flow-V150-inspiration scores when splints were used (with significant differences between groups for the left nostril: p = 0.039 and p = 0.022, resp.). In accordance, impaired nasal breathing after surgery was reported more frequently by 76.9 % of patients without splints, but only 56 % of patients with splints. Our results provide support for the application of nasal septal splints when operating endoscopically on tumors in the sellar region to reduce postoperative synechias and to improve nasal breathing.

Until Death Do Us Part: Necrosis and Oxidation Promote the Tumor Microenvironment.

Tumor proliferation is concomitant with autophagy, limited apoptosis, and resultant necrosis. Necrosis is associated with the release of damage-associated molecular pattern molecules (DAMPs), which act as 'danger signals', recruiting inflammatory cells, inducing immune responses, and promoting wound healing. Most of the current treatment strategies for cancer (chemotherapy, radiation therapy, hormonal therapy) promote DAMP release following therapy-induced tumor death by necroptosis and necrosis. Myeloid cells (monocytes, dendritic cells (DCs), and granulocytes), as well as mesenchymal stromal cells (MSCs) belong to the early immigrants in response to unscheduled cell death, initiating and modulating the subsequent inflammatory response. Responding to DAMPs, MSCs, and DCs promote an immunosuppressive milieu, while eosinophils induce oxidative conditions limiting the biologic activity of DAMPs over time and distance. Regulatory T cells are strongly affected by pattern recognition receptor signaling in the tumor microenvironment and limit immune reactivity coordinately with myeloid-derived suppressor cells. Means to 'aerobically' oxidize DAMPs provide a novel strategy for limiting tumor progression. The present article summarizes our current understanding of the impact of necrosis on the tumor microenvironment and the influence of oxidative conditions found within this setting.

Eosinophil granulocytes in chronic inflammatory respiratory diseases and CRSwNP: Function, immunological basis, and clinical significance.

INTRODUCTION: Eosinophils play an important regulatory and immunomodulatory role in airway mucosa and have antiparasitic and antiviral properties as well as pro-inflammatory effects that may also cause persistence of inflammation with tissue remodeling. The number of eosinophils and the detection of specific mediators in biological samples from, e.g., blood, nasal secretions, and bronchial fluid can serve as biomarkers that reflect the underlying pathophysiology of certain diseases, predict treatment success, and detect therapy effects. MATERIALS AND METHODS: A literature search was conducted to determine the immunologic basis, mode of action, clinical significance, and available evidence for therapeutic approaches using eosinophil-targeted monoclonal antibodies by searching Medline, Pubmed, and the national and international trial database (ClinicalTrials.gov) and guideline registries as well as the Cochrane Library. Human studies published on the topic in the period up to and including 10/2023 were considered. RESULTS: Based on the international literature and previous experience, the results are summarized, and recommendations are given. CONCLUSION: The important role of eosinophils in immunological processes in the airway mucosa is comprehensively analyzed and can serve as a basis for current and future treatment approaches.

Monitoring mepolizumab treatment in chronic rhinosinusitis with nasal polyps (CRSwNP): Discontinue, change, continue therapy?

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL-5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy should be monitored, what follow-up documentation is necessary, and when it should be discontinued if necessary. MATERIALS AND METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries, and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals, and possible therapy breaks as well as discontinuation of therapy when using mepolizumab for the indication CRSwNP in the German healthcare system are given on the basis of a documentation sheet. CONCLUSION: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

HMGB1 conveys immunosuppressive characteristics on regulatory and conventional T cells.

OBJECTIVE: The high-mobility group box-1 protein (HMGB1) serves as the prototypic damage-associated molecular pattern molecule, interacting with a variety of defined pattern recognition receptors in the microenvironment of damaged or necrotic tissue. As regulatory T cells (T(reg)) play a crucial role in autoimmune diseases and tumor immune escape, the previously unexamined role of HMGB1 on the function of T(reg) is of great interest. METHODS: Human CD4(+)CD25(+)CD127(-) T(reg) and CD4(+)CD25(-)CD127(+) conventional T cells (T(con)) were phenotypically analyzed for their constitutive as well as HMGB1-modulated expression of Toll-like receptors (TLR) and the receptor for advanced glycation end products (RAGE). Furthermore, the influence of recombinant and complexed HMGB1 from necrotic cell supernatant on the function of T(reg) and T(con) was investigated. RESULTS: T(reg) express significantly higher levels of RAGE on the cell surface than T(con), while levels of TLR4 are similar. HMGB1 modulates T(reg) biology by inducing migration and prolonging survival. Furthermore, HMGB1 enhances IL-10 release and T(reg) suppressive capacity in a RAGE-dependent manner. In addition, HMGB1 directly suppresses IFNγ release of T(con) and inhibits their proliferation via TLR4. CONCLUSION: HMGB1 directly enhances immune inhibitory functions of T(reg) via RAGE-mediated mechanisms and limits the number and activity of T(con). HMGB1 effects on T(reg) may alter immune reactivity in the setting of chronic inflammatory states such as cancer.

Vascularised local and free flaps in anterior skull base reconstruction.

Lesions of the anterior skull base often require sufficient closure in order to prevent cerebrospinal fluid (CSF) leak, ascending infection and/or brain tissue prolapse. The transfer of devitalized autologous, allogenic or xenogeneic material is not always sufficient particularly not in larger defects or in the recurrent situation. Here the transfer of vascularised tissue seems to be more appropriate. The anterior skull base with various complex defects of 41 patients was reconstructed in an interdisciplinary setting by vascularised, autologous tissue transfer. Minor defects (<2.5 cm in max. diameter), generally occurring after extended endoscopic skull base approaches (n = 26, among those meningiomas, recurrent CSF fistulas, chordoma, chondroblastoma, metastasis, nasal fistula), were reconstructed by a local, vascularized pedicled mucosal flap of the lower turbinate (n = 3) or septum (n = 23). Patients with major defects (>2.5 cm in max. diameter, n = 15), comprising those with malignoma, meningoencephalocele, aneurysmatic bone cyst and trauma, were repaired by a "sandwich technique" with a combination of calvarian split and galea periosteum flap in 10 patients, in one case with a temporalis muscle flap, while in 4 further patients free vascularised radial forearm flaps were used for revision after multiple unsuccessful operations elsewhere. After a mean follow-up time of 30.5 months 38 of the 41 cases were successfully repaired with respect to prevention and treatment of CSF leakage or brain tissue prolapse, only 3 cases needed surgical revision. The reconstruction of the anterior skull base bearing complex lesions is feasible using vascularised, autologous local and also distal tissue transfer in a close interdisciplinary cooperation.

Human tumor-induced and naturally occurring Treg cells differentially affect NK cells activated by either IL-2 or target cells.

NK cells play a crucial role in the eradication of tumor cells. Naturally occurring (n) Treg cells and induced (i) Treg cells are two distinct Treg subsets. While the interaction of nTreg cells with NK cells has been investigated in the past, the role of tumor iTreg cells in the modulation of NK-cell function remains unclear. Tumor iTreg cells were generated from CD4(+) CD25(-) T cells in the presence of autologous immature DCs, head and neck cancer cells and IL-2, IL-10, and IL-15. The effect of iTreg cells and nTreg cells on the expression of NKG2D, NKp44, CD107a, and IFN-γ by NK cells, as well as NK tumor-cytolytic activity, were investigated. iTreg cells - similar to recombinant TGF-ß and nTreg cells - inhibited IL-2-induced activation of NK cells in the absence of target cell contact. Surprisingly, and in contrast to nTreg cells, iTreg cells enhanced NK-cell activity elicited by target cell contact. The cytolytic activity of NK cells activated by iTreg cells was mediated via perforin and FasL. We conclude that tumor iTreg cells inhibited IL-2-mediated NK-cell activity in the absence of target cells, whereas the tumoricidal activity of NK cells was enhanced by iTreg cells. Our data suggest a complex, previously not recognized, differential regulation of human NK activity by iTreg cells in the tumor microenvironment.

Epithelial immune regulation of inflammatory airway diseases: Chronic rhinosinusitis with nasal polyps (CRSwNP).

BACKGROUND: The epithelial immune regulation is an essential and protective feature of the barrier function of the mucous membranes of the airways. Damage to the epithelial barrier can result in chronic inflammatory diseases, such as chronic rhinosinusitis (CRS) or bronchial asthma. Thymic stromal lymphopoietin (TSLP) is a central regulator in the epithelial barrier function and is associated with type 2 (T2) and non-T2 inflammation. MATERIALS AND METHODS: The immunology of chronic rhinosinusitis with polyposis nasi (CRSwNP) was analyzed in a literature search, and the existing evidence was determined through searches in Medline, Pubmed as well as the national and international study and guideline registers and the Cochrane Library. Human studies or studies on human cells that were published between 2010 and 2020 and in which the immune mechanisms of TSLP in T2 and non-T2 inflammation were examined were considered. RESULTS: TSLP is an epithelial cytokine (alarmin) and a central regulator of the immune reaction, especially in the case of chronic airway inflammation. Induction of TSLP is implicated in the pathogenesis of many diseases like CRS and triggers a cascade of subsequent inflammatory reactions. CONCLUSION: Treatment with TSLP-blocking monoclonal antibodies could therefore open up interesting therapeutic options. The long-term safety and effectiveness of TSLP blockade has yet to be investigated.

Toll-like receptor 4 single-nucleotide polymorphisms Asp299Gly and Thr399Ile in head and neck squamous cell carcinomas.

BACKGROUND: Chronic inflammation plays an important role in head and neck squamous cell carcinomas (HNSCC). This study addresses the impact of two single nucleotide polymorphisms (SNP) Asp299Gly and Thr399Ile of the toll-like receptor (TLR) 4 gene on the clinical outcome while accounting for the influence of adjuvant systemic therapy in a large cohort of HNSCC patients. METHODS: Genotype analysis was done using DNA from tissue samples from 188 patients with HNSCC; TLR4 protein expression was assessed immunohistochemically in tissue microarrays. Classical survival models were used for statistical analyses. RESULTS: Ten percent of patients with HNSCC presented with the TLR4 299Gly and 17% with the TLR4 399Ile allele. Patients with the heterozygous genotype TLR4 Asp299Gly had a significantly reduced disease-free and overall survival. Also, patients with the heterozygous genotype TLR4 Thr399Ile had a reduced disease-free survival. Notably, these associations seem to be attributable to relatively poor therapy response as e.g. reflected in a significantly shorter DFS among HNSCC patients carrying the Asp299Gly variant and receiving adjuvant systemic therapy. CONCLUSION: According to this study, TLR4 299Gly und 399Ile alleles may serve as markers for prognosis of head and neck cancer in patients with adjuvant systemic therapy, particularly chemotherapy, and might indicate therapy resistance.

Human circulating CD4+CD25highFoxp3+ regulatory T cells kill autologous CD8+ but not CD4+ responder cells by Fas-mediated apoptosis.

Mechanisms utilized by human regulatory T cells (Treg) for elimination of effector cells may vary. We investigated the possibility that the mechanism of Treg suppression depends on Fas/FasL-mediated apoptosis of responder cells (RC). CD4(+)CD25(high)Foxp3(+) Treg and autologous CD4(+)CD25(-) and CD8(+)CD25(-) subsets of RC were isolated from blood of 25 cancer patients and 15 normal controls and cocultured in the presence of OKT3 and IL-2 (150 or 1000 IU/ml). Suppression of RC proliferation was measured in CFSE assays. RC and Treg apoptosis was monitored by 7-aminoactinomycin D staining in flow-based cytotoxicity assays. Treg from all subjects expressed CD95(+), but only Treg from cancer patients expressed CD95L. These Treg, when activated via TCR plus IL-2, up-regulated CD95 and CD95L expression (p < 0.001) and suppressed CD8(+) RC proliferation (p < 0.001) by inducing Fas-mediated apoptosis. However, Treg cocultured with CD4(+) RC suppressed proliferation independently of Fas/FasL. In cocultures, Treg were found to be resistant to apoptosis in the presence of 1000 IU/ml IL-2, but at lower IL-2 concentrations (150 IU/ml) they became susceptible to RC-induced death. Thus, Treg and RC can reciprocally regulate Treg survival, depending on IL-2 concentrations present in cocultures. This divergent IL-2-dependent resistance or sensitivity of Treg and RC to apoptosis is amplified in patients with cancer.

The Contribution of Galenics to Patients' Sensory Perception of Nasal Sprays After Nasal Surgery: Data from a Prospective Randomised, Controlled, Double-Blind, Crossover, Multicentre Study.

INTRODUCTION: Postoperative care after nasal surgery is commonly achieved with nasal sprays. The current study compared two decongesting, wound-healing nasal sprays in patients after nasal surgery in order to investigate their sensory perception. One of the sprays was a new galenic formulation (nasic® neo, Cassella-med GmbH & Co. KG). METHODS: According to the crossover design, patients who had undergone nasal surgery applied two different nasal sprays during two treatment periods of 4 days each, interrupted by a 3-day washout period. Sensory perception of the nasal sprays was assessed with the nasal spray sensoric scale. Throughout the study, nasal obstruction was evaluated by patients, and physical examinations, measurements of vital parameters and rhinoscopic examinations were carried out by investigators. Adverse events were documented during the entire study, and following treatment, patients judged the overall preference, efficacy and tolerability of both products. RESULTS: Overall, no significant differences in sum scores of the assessments of the nasal spray sensoric scale were observed between treatments. A significant period effect observed during the crossover study limited the overall analysis. Nevertheless, significantly more patients preferred the new galenics nasal spray compared to the comparator spray (57.1% vs. 34.7%; p = 0.031). Further, 10% more patients rated the efficacy of the new galenics as 'good' to 'very good' compared to the comparator. Importantly, a subgroup population of patients with more pronounced signs of inflammation present at screening evaluated the sensory perception of the new galenics as significantly better (p = 0.033) compared to the comparator. Within this subgroup, no period effect was observed. The application of both nasal sprays was shown to be safe and well-tolerated. CONCLUSION: The overall sensory perception of both nasal sprays was evaluated comparably well in patients after nasal surgery and overall the application of the new galenics nasal spray was preferred by significantly more patients compared to the comparator nasal spray. Patients with marked nasal abnormalities may have a greater benefit from the contribution of galenics as significant differences in the sensory evaluation by the nasal spray sensoric scale in favour of the new galenics product were shown for this subgroup. TRIAL REGISTRATION: The current study was registered in the EU Clinical Trials Register with the EudraCT No. 2019-004936-52.

Acute arterial hemorrhage following radiotherapy of oropharyngeal squamous cell carcinoma.

BACKGROUND AND PURPOSE: Vascular erosion is a rare but life-threatening complication after radiotherapy. The authors report on acute arterial bleeding and its therapy following radiotherapy of oropharyngeal tumors. PATIENTS AND METHODS: Ten patients with oropharyngeal squamous cell carcinoma of any stage developed foudroyant acute arterial hemorrhage 3-46 months (14.4 +/- 5.1 months) after primary (5/10) or adjuvant radio(chemo)therapy (R[C]T). RESULTS: All patients had a history of recurrent minor bleeding episodes and showed deep mucosal ulcerations also outside the primary tumor region. A life-threatening arterial hemorrhage appeared in the area of these mucosal defects in the pharyngeal region. Affected vessels were the common carotid artery as well as the internal and the external portion with branches like the ascending pharyngeal and superior thyroid arteries. Treatment consisted of emergency intubation or tracheotomy followed by exposure and package of the pharynx and surgical ligature and/or embolization. 6/10 patients (all hospitalized) survived the episode, however, lethal outcome in 4/10 patients (outpatients) was related to asphyxia as a result of blood aspiration or exsanguination. None of the patients revealed evidence of persistent or recurrent tumor disease as proven by biopsy/autopsy and imaging technique. CONCLUSION: Vascular erosion following primary or adjuvant R(C)T represents a rare and potentially life-threatening complication requiring immediate emergency treatment involving head and neck surgeons, anesthesiologists and neuroradiologists. For patients with oropharyngeal neoplasms treated by R(C)T and showing recurrent bleeding episodes and mucosal ulceration particularly after the acute treatment phase, hospitalization with prophylactic surgical ligature or embolization of affected arteries is recommended.

Randomised trial on performance, safety and clinical benefit of hyaluronic acid, hyaluronic acid plus dexpanthenol and isotonic saline nasal sprays in patients suffering from dry nose symptoms.

OBJECTIVE: Limited data exist on the clinical benefits of nasal applications for moistening the nasal mucosa. We therefore investigated the effects of hyaluronic acid, hyaluronic acid plus dexpanthenol and isotonic saline nasal sprays in patients suffering from dry nose symptoms in an otorhinolaryngological outpatient setting. METHODS: 240 patients were randomised into this prospective, three-armed clinical trial with two assessment points (baseline and 4 weeks later). Patients received either hyaluronic acid, hyaluronic acid plus dexpanthenol or isotonic saline nasal spray over a period of four weeks. Rhinitis Sicca Symptom Score (RSSS) was assessed as primary endpoint, and individual symptoms and tolerability of all treatments as secondary endpoints. Patient perceptions after first application of the allocated nasal spray were recorded using the Nasal Spray Sensory Scale. Treatment effects were analysed for each study arm first and subsequently compared against each other. RESULTS: RSSS (hyaluronic acid: mean difference = 8.90 [98.33% CI = 7.34/10.45]; hyaluronic acid plus dexpanthenol: mean difference = 8.42 [98.33% CI = 6.91/9.94]; isotonic saline: mean difference = 8.94 [98.33% CI = 7.33/10.54]), individual symptoms and Endoscopy Score improved significantly (p < 0.001) in all treatment arms. Tolerability was assessed as "flawless" in more than 85% of all treatments, which is reflected in overall high rankings in the Nasal Spray Sensory Scale. Perception of nasal moisturisation was reported to be significantly higher in patients receiving hyaluronic acid plus dexpanthenol as compared to patients receiving hyaluronic acid or isotonic saline. No further significant differences were observed between the three treatments. CONCLUSION: All three tested sprays (hyaluronic acid, hyaluronic acid plus dexpanthenol and isotonic saline) proved to be suitable treatments for patients suffering from dry nose symptoms. (DRKS-ID: DRKS00013357).